The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians – Poster Session (P001-P755) (2025)

Yiyang Ding¹, Yuhua Ru¹, Jinjin Zhu¹, Xi Zhang², Lin Liu³, Erlie Jiang⁴, He Huang⁵, Jishi Wang⁶, Jiong Hu⁷, Yanming Zhang⁸, Yajing Xu⁹, Mingzhen Yang¹⁰, Jia Chen ¹, Depei Wu¹

¹National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China, ²Xinqiao Hospital, Third Military Medical University, Chongqing, China, ³The First Affiliated Hospital of Chongqing Medical University, Chongqing, China, ⁴Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China, ⁵Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, ⁶Affiliated Hospital of Guizhou Medical University, Guiyang, China, ⁷Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ⁸Huai’an Hospital Affiliated to Xuzhou Medical College and Huai’an Second People’s Hospital, Huai’an, China, ⁹XiangYa Hospital, Central South University, Changsha, China, ¹⁰the First Affiliated Hospital of Anhui Medical University, Hefei, China

Background: In the absence of HLA-matched donor, HLA-haploidentical donor stem cell transplantation (haplo-SCT) and autologous SCT (ASCT) are both valid postremission therapy with well-documented effects in patients with favorable-and intermediate-risk acute myeloid leukemia (AML). Our previous retrospective study has suggested similar survival following ASCT compared to haplo-SCT for favorable- and intermediate-risk AML patients in the first complete remission (CR1). Hence, we designed a prospective, multi-center study to further confirm this conclusion.

Methods: A prospective study was conducted in 10 Chinese centers. The main inclusion criteria were: 1) adult patients >=18 years old; 2) diagnosis as AML with intermediate-risk according to ELN 2010 or 2017; 3) ASCT or haplo-SCT underwent between 2014-2019; 4) in CR1 and MRD negative before transplant. The Primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), cumulative incidence of relapse (CIR), treatment-related mortality (TRM), and graft-versus-host disease-free and relapse-free survival (GRFS).

Results: A total of 368 patients diagnosed with favorable-and intermediate-risk AML were included from 10 institutions between January 2014 and December 2019, in accordance with the European Leukemia Net criteria (Table 1). Of these, 184 patients underwent ASCT, and 184 underwent haplo-SCT. In the overall cohort analysis, the CIR in the ASCT group was offset by reduced TRM when compared with the haplo-SCT group, resulting in similar PFS (70.5% versus 74.9%, P = 0.880) and improved OS (83.0% versus 77.0%, P = 0.044). Furthermore, ASCT patients exhibited a higher GRFS (70.5% versus 57.4%, P<0.001) attributed to the absence of GVHD. The OS trend was accentuated in the favorable-risk cohort, while comparable OS was observed in the intermediate-risk cohort. Multivariate analyses indicated that haplo-SCT, advanced age, MLL-AF9 rearrangement, graft cell dosage, and hematopoietic engraftment time independently impacted outcomes.

Table 1. Patient Characteristics.

Conclusions: In conclusion, both ASCT and haplo-SCT proved to be viable approaches for the post-remission treatment of patients with favorable-and intermediate-risk AML. Notably, ASCT demonstrated superior outcomes in the favorable-risk cohort.

Clinical Trial Registry: Haplo-SCT vs ASCT With or Without Decitabine in AML CR1 - Full Text View - ClinicalTrials.gov (ClinicalTrails.gov Identifier: NCT02059720)

Disclosure: Nothing to declare

19: Acute Leukaemia

Gianluca Cavallaro ¹, Davide Lazzarotto², Chiara Pavoni¹, Francesca Valsecchi¹, Cristina Papayannidis³, Marco Cerrano⁴, Sabina Chiaretti⁵, Nicola Fracchiolla⁶, Fabio Giglio⁷, Michelina Dargenio⁸, Monia Lunghi⁹, Silvia Imbergamo¹⁰, Maria Ilaria Del Principe¹¹, Silvia Trappolini¹², Monica Fumagalli¹³, Patrizia Zappasodi¹⁴, Prassede Salutari¹⁵, Mario Delia¹⁶, Crescenza Pasciolla¹⁷, Federico Mosna¹⁸, Barbara Scappini¹⁹, Fabio Forghieri²⁰, Patrizia Chiusolo²¹, Cristina Skert²², Benedetta Cambò²³, Marzia Defina²⁴, Giuseppe Lanzarone²⁵, Mauro Endri²⁶, Massimiliano Bonifacio²⁷, Carla Mazzone²⁸, Lidia Santoro²⁹, Antonino Mulè³⁰, Valentina Mancini³¹, Paola Minetto³², Giorgia Battipaglia³³, Alessandro Cignetti³⁴, Lara Aprile³⁵, Robin Foà⁵, Anna Candoni^2,20, Federico Lussana^1,36

¹ASST Papa Giovanni XXIII, Bergamo, Italy, ²Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy, ³IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy, ⁴AOU Città della Salute e della Scienza – Presidio Molinette, Torino, Italy, ⁵Sapienza University, Roma, Italy, ⁶IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milano, Italy, ⁷IRCCS Ospedale San Raffaele, Milano, Italy, ⁸Ospedale Vito Fazzi, Lecce, Italy, ⁹University of Eastern Piedmont, Novara, Italy, ¹⁰Azienda Ospedale Università di Padova, Padova, Italy, ¹¹University of Rome Tor Vergata, Roma, Italy, ¹²Azienda Ospedaliero - Universitaria Ospedali Riuniti Umberto I, Ancona, Italy, ¹³Ospedale San Gerardo, Monza, Italy, ¹⁴Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, ¹⁵Azienda USL di Pescara, Pescara, Italy, ¹⁶Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Italy, ¹⁷IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy, ¹⁸Azienda Sanitaria dell’Alto Adige, Bolzano, Italy, ¹⁹Azienda Ospedaliera Universitaria Careggi, Firenze, Italy, ²⁰Azienda Ospedaliero Universitaria di Modena, Modena, Italy, ²¹Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy, ²²Ospedale dell’Angelo, Venezia, Italy, ²³University of Parma, Parma, Italy, ²⁴Azienda Ospedaliero Universitaria Senese, Siena, Italy, ²⁵A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy, ²⁶Ospedale Cà Foncello, Treviso, Italy, ²⁷Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy, ²⁸St. Eugenio Hospital, Roma, Italy, ²⁹Azienda Ospedaliera San Giuseppe Moscati, Avellino, Italy, ³⁰A.O. Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy, ³¹ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy, ³²IRCCS Ospedale Policlinico San Martino, Genova, Italy, ³³Azienda Ospedaliero-Universitaria Federico II, Napoli, Italy, ³⁴Azienda Ospedaliera Ordine Mauriziano, Torino, Italy, ³⁵Ospedale San Giuseppe Moscati, Taranto, Italy, ³⁶University of Milan, Milano, Italy

Background: The GIMEMA LAL 1913 was a pediatric-inspired and minimal residual disease (MRD)-oriented phase 2 chemotherapy protocol that included peg-asparaginase for the frontline treatment of adult Philadelphia-negative acute lymphoblastic leukemia (Ph- ALL) patients (Bassan et al, Blood Advances, 2023). This protocol represents the standard treatment for adult Ph- ALL in Italy. The outcome of patients treated with the same protocol in the real-life setting and who underwent an allogeneic stem cell transplant (SCT) was the aim of this study.

Methods: Within the framework of the Campus ALL network in Italy, we analyzed the post-transplant data of newly diagnosed adult Ph- ALL patients treated according to the LAL 1913 protocol and who underwent a SCT between August 2016 and January 2023 in 35 Italian centers. Patients in 1^st remission (CR1) were considered eligible for a SCT as consolidation based on the joint assessment of the disease risk profile at diagnosis (high white blood cell, immunophenotype or adverse cytogenetics/molecular biology) and post-consolidation MRD status. We also included relapsed patients in 2^nd CR (CR2). Endpoints were the 2-year overall survival (OS), disease-free survival (DFS), non-relapse mortality (NRM) and cumulative incidence of relapse (CIR). Outcomes were analyzed from the day of SCT.

Results: Among 322 consecutive newly diagnosed Ph- ALL, 201 patients who underwent a SCT were included in this analysis (Table 1). The median age at diagnosis was 38 years (18-66). Median follow-up was 28 months. Patients allografted in CR1 were associated with a significantly superior 2-year OS (77% vs 32%, p<0.001), DFS (67% vs 35%, p = 0.003) and CIR (24% vs 47%, p = 0.006) compared to patients transplanted in CR2. Pre-transplant MRD negativity was strongly associated with a superior OS (81% vs 50%, p<0.001), DFS (71% vs 44%, p = 0.003) and CIR (21% vs 43%, p = 0.006). MRD negativity also impacted favorably on the prognosis of patients transplanted in 2^nd CR in terms of OS and disease-free survival (Fig. 1). The outcome was similar between B- and T-lineage ALL, patients’ age (< or > 55 years) and baseline risk class. A myeloablative conditioning was adopted in 156 (79%) patients and total-body irradiation (TBI) in 125 (66%). There was no significant difference when using TBI 800 cGy vs TBI 1200 cGy and TBI-fludarabine vs TBI-alkylating agents. The use of ATG in sibling and unrelated donors did not affect CIR. The 2-year NRM was 11% and it was not significantly affected by pre- and post-transplant factors.

Table 1.

Figure 1: 2-years DFS

Conclusions: Our study on a series of patients treated with a modern therapeutic strategy confirms the higher risk of relapse in patients with pre-transplant MRD positivity. Given the availability of pre-transplant immunotherapies, all efforts should be made to eradicate MRD prior to undergoing the SCT, or with post-transplant pre-emptive treatment. An advantage in survival was observed when transplant was performed in CR1 compared to CR2, highlighting the importance of an early identification of high-risk patients candidate to transplant consolidation. Importantly, a significant improvement in NRM outcome was recorded.

Disclosure: Nothing to declare.

19: Acute Leukaemia

Ali Bazarbachi ¹, Jacques-Emmanuel Galimard², Myriam Labopin², Iman Abou Dalle¹, Jaime Sanz³, Huang He⁴, Jiri Mayer⁵, Carlos Solano⁶, Celestine Simand⁷, Laimonas Griskevicius⁸, Johan Maertens⁹, Maija Itäla-Remes¹⁰, Ain Kaare¹¹, Maria-Pilar Gallego-Hernanz¹², Gesine Bug¹³, Josep-Maria Ribera¹⁴, Alain Gadisseur¹⁵, Christoph Schmid¹⁶, Mi Kwon¹⁷, Xavier Poiré¹⁸, Paola Coccia¹⁹, Manuel Jurado Chacón²⁰, Frédéric Baron²¹, Eolia Brissot²², Arnon Nagler²³, Fabio Ciceri²⁴, Mohamad Mohty²⁵

¹American University of Beirut Medical Center, Beirut, Lebanon, ²EBMT Statistical Unit, Sorbonne University, Saint-Antoine Hospital, Paris, France, ³University Hospital La Fe, Valencia, Spain, ⁴First Affiliated Hospital of Zhejiang University School of Medicine, Kunming, China, ⁵University Hospital Brno, Brno, Czech Republic, ⁶Hospital Clínico Universitario. University of Valencia, Valencia, Spain, ⁷ICANS, Strasbourg, France, ⁸Hôpitaux Universitaires Strasbourg, Strasbourg, France, ⁹University Hospital Gasthuisberg, Leuven, Belgium, ¹⁰Turku University Hospital, Turku, Turkey, ¹¹Tartu University Hospital, Tartu, Estonia, ¹²Hopital La Miletrie, Poitiers, France, ¹³Goethe-Universitaet, Frankfurt Main, Germany, ¹⁴ICO-Hospital Universitari Germans Trias i Pujol, Josep Carreras Research Institute, Badalona, Spain, ¹⁵Antwerp University Hospital (UZA), Antwerp E, Belgium, ¹⁶University Hospital and Medical Faculty, University of Augsburg, Augsburg, Germany, ¹⁷Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain, ¹⁸Cliniques Universitaires St. Luc, Brussels, Belgium, ¹⁹Azienda Ospedali Riuniti di Ancona, Ancona, Italy, ²⁰Hospital Univ. Virgen de las Nieves, Granada, Grenada, ²¹University of Liege, Liege, Belgium, ²²Sorbonne University, Paris, France, ²³Hematology Division, Chaim Sheba Medical Center, Tel-Hashomer, Israel, ²⁴IRCCS Ospedale San Raffaele, Milano, Italy, ²⁵Sorbonne University, Saint-Antoine Hospital, Paris, France

Background: Acute myeloid leukemia (AML) is a very heterogeneous hematological malignancy, which includes numerous genetically defined subsets. In the context of allogeneic hematopoietic cell transplantation (allo-HCT), the frequency and prognostic value of different gene-gene interactions has not been studied and may differ from that of patients treated with chemotherapy alone.

Methods: This is a registry-based analysis from the EBMT with the approval of the EBMT Acute Leukemia Working Party. Adult patients aged more than 18 years with a diagnosis of AML who received an allo-HCT between 2013-2022, with an available genetic profile determined at diagnosis by next generation sequencing (NGS) were included.

Results: We identified 836 allografted AML patients who had NGS performed at diagnosis. Most of these patients had de novo AML (88%), with a median age of 53 years (range: 18-78 years). Karyotype was favorable in 7%, intermediate in 69% and adverse in 24% of patients. At transplant, 74% of patients were in first remission (CR1) and 13% in CR2. The most frequent detectable mutations by frequency were DNMT3A (33%), FLT3 (29%), NPM1 (29%), TET2 (28%), NRAS (23%), RUNX1 (22%), WT1 (22%), BCOR (19%), ASXL1 (17%), IDH2 (17%), IDH1 (15%), SRSF2 (13%), STAG2 (12%), CEBPA (11%), TP53 (10%), KRAS (10%), and PTPN11 (10%). By multiple correspondence analysis, two independent groups of co-occurring mutations were identified, the first group included DNMT3A, NPM1 and FLT3, the second group included ASXL1, SRSF2 and RUNX1. Outcome analysis was performed on the subset of 298 patients allografted in CR1 with available data for DNMT3A, NPM1, FLT3, ASXL1, SRSF2 and RUNX1. Most of these patients had de novo AML (90%), with a median age of 53 years (range: 19-75 years). Seventy percent had intermediate-risk cytogenetics, while 27% were adverse-risk. Median follow up was 2.5 years. When outcome analysis was performed according to the presence of single mutations, none of the six mutations significantly affected RI or LFS. The 2-year OS was positively affected by the presence of NPM1 mutation (78% vs 66%; p = 0.02) and FLT3 (79% vs 65%, p = 0.01) but not significantly affected by the other 4 mutations. When mutations were investigated in groups, the 2-year RI, LFS and OS were 24%, 70% and 78%, respectively, for patients with NPM1 mutation regardless of other co-mutations, 35%, 56% and 69% for patients with FLT3-ITD and/or DNMT3A mutation, wild type NPM1, regardless of other co-mutations, 17%, 70% and 74% for patients with RUNX1 and/or ASXL1 and/or SRSF2 mutation without FLT3-ITD and with wild type NPM1 and wild type DNMT3A, and 20%, 56% and 61% for patients with all six genes unmutated.

Conclusions: NGS at diagnosis can be extremely useful in risk stratification of AML patients undergoing allo-HSCT, potentially allowing adequate post-transplant interventions. Notably, the 2-year LFS of 70% for patients harboring RUNX1 and/or ASXL1 and/or SRSF2 mutation indicates that allo-HSCT can overcome the adverse risk associated with these somatic mutations at diagnosis.

Disclosure: Nothing to declare.

19: Acute Leukaemia

Yves Chalandon ¹, Raynier Devillier², Ariane Boumendil³, Stephanie Nguyen⁴, Claude-Eric Bulabois⁵, Patrice Ceballos⁶, Eolia Brissot⁷, Marie-Thérèse Rubio⁸, Hélène Labussière-Wallet⁹, Johan Maertens¹⁰, Patrice Chevallier¹¹, Natacha Maillard¹², Xavier Poiré¹³, Cristina Castilla-Llorente¹⁴, Yves Beguin¹⁵, Jérôme Cornillon¹⁶, Sébastien Maury¹⁷, Tony Marchand¹⁸, Etienne Daguindau¹⁹, Jacques-Olivier Bay²⁰, Pascal Turlure²¹, Amandine Charbonnier²², Anne-Lise Menard²³, Karin Bilger²⁴, Gaelle Guillerm²⁵, Sylvie François²⁶, Ali Bazarbachi²⁷, Sylvain Chantepie²⁸, Philippe Lewalle²⁹, Ambroise Marçais³⁰, Michael Loschi³¹, Malek Benakli³², Paul Chauvet³³, Edouard Forcade³⁴, Anne Huynh³⁵, Marie Robin³⁶, Stavroula Masouridi-Levrat¹

¹Hôpitaux Universitaire Genève (HUG) and Faculty of Medicine, Geneva, Switzerland, ²Institut Paoli-Calmettes, Marseille, France, ³SFGM-TC, Paris, France, ⁴Hôpital de la Pitié Salpêtrière, AP-HP, Paris, France, ⁵CHU Grenoble-Alpes, Grenoble, France, ⁶CHU de Montpellier, Montpellier, France, ⁷Hôpital Saint-Antoine, AP-HP, Paris, France, ⁸CHRU de Nancy-Brabois, Nancy, France, ⁹Hôpital Lyon Sud, Lyon, France, ¹⁰UZ Leuven, Leuven, Belgium, ¹¹CHU Nantes, Nantes, France, ¹²CHU Poitiers, Poitiers, France, ¹³Cliniques Universitaires Saint-Luc, Brussels, Belgium, ¹⁴Gustave Roussy Cancer Campus, Villejuif, France, ¹⁵CHU de Liège, Liège, Belgium, ¹⁶CHU St-Etienne, Saint-Etienne, France, ¹⁷Hôpital Henri-Mondor, AP-HP, Créteil, France, ¹⁸CHU Rennes, Rennes, France, ¹⁹CHU de Besançon, Besançon, France, ²⁰CHU de Clermont-Ferrand, Clermont-Ferrand, France, ²¹Limoges University Hospital, Limoges, France, ²²CHU Amiens, Amiens, France, ²³Centre Henri Becquerel, Rouen, France, ²⁴CHRU de Strasbourg, Strasbourg, France, ²⁵CHRU de Brest, Brest, France, ²⁶CHU Angers, Angers, France, ²⁷American University of Beirut, Beirut, Lebanon, ²⁸CHU de Caen, Caen, France, ²⁹Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet, Brussels, Belgium, ³⁰Hôpital Necker, AP-HP, Paris, France, ³¹CHU de Nice, Nice, France, ³²CPMC d’Alger, Alger, Algeria, ³³CHU de Lille, Université de Lille, Lille, France, ³⁴CHU Bordeaux, Bordeaux, France, ³⁵CHU Toulouse, Toulouse, France, ³⁶Hôpital Saint-Louis, AP-HP, Paris, France

Background: There are very scarce data regarding the outcome of elderly patients with ALL who received alloHSCT as consolidation therapy in CR. Thus, the optimal conditioning regimen still need to be determined. We here present the outcome of ALL patients older than 59 years from the SFGM-TC.

Methods: The primary outcome of this registry study was OS. Secondary outcomes were PFS, NRM, RI, aGvHD grade II-IV, cGvHD, engraftment and GRFS. Competing risks analyses were performed to analyze NRM, aGvHD grade II-IV, cGvHD and neutrophil engraftment. Univariable analyses were performed using the log-rang test for OS and PFS, while Gray’s test was used for CI. Multivariable analyses were performed using the Cox proportional hazards regression model including age, ALL subtype, time from diagnosis to alloHSCT, disease status at alloHSCT, donor to patient CMV status, donor to patient sex, ATG use, MAC, TBI use.

Results: A total of 316 patients ≥ 60 years old transplanted for ALL from 2012 to 2022 in 36 participating centers were included. Patient’s characteristics are described in Table 1.

With a median follow up of 34.5 months (IQR 29.5-38.8), 3-year OS was 46% (95% CI 40-53%) with disease status at transplant impacting negatively OS, 53% in CR1, 32% in CR2, 29% in advanced disease, p = 0.002 and ALL subtype, 59% in Ph+ ALL, 40% in Ph- ALL, 34% in T-ALL, 20% in other/NA, p<0.001.

3-year PFS was 41% (95% CI 35-48%) with disease status at transplant impacting negatively, 49% in CR1, 26% in CR2, 22% in advanced disease, p<0.001, ALL subtype, 51% in Ph+ ALL, 41% in Ph- ALL, 21% in T-ALL, 21% in other/NA, p<0.001, year of HSCT worse < 2018, p = 0.007, CMV -/- worse, p = 0.033, absence of TBI worse, p = 0.018. 3-year NRM was 23% (95% CI 18-28%). 3-year RI was 36% (95% CI 31-42%) with disease status at transplant impacting negatively, 29% in CR1, 50% in CR2, 56 in advanced disease, p = 0.0042, ALL subtype, 26% in Ph+ ALL, 43% in Ph- ALL, 57% in T-ALL, 42% in other/NA, p = 0.0064, year of HSCT worse < 2018, p = 0.0216, CMV -/- worse, p<0.001, absence of TBI worse, p = 0.0069, MRD worse, p = 0.0111. 3-year GRFS was 30% (95% CI 25-37%) with disease status at transplant impacting negatively, 35% in CR1, 22% in CR2, 23% in advanced disease, p = 0.029, ALL subtype, 37% in Ph+ ALL, 33% in Ph- ALL, 15% in T-ALL, 17% in other/NA, p = 0.0029, year of HSCT worse < 2018, p<0.001.

CI of aGVHD grade II-IV was 33% (95% CI 28-38%), grade III-IV 11% (95% CI 8-15%), cGVHD 35% (95% CI30-41%), extensive cGVHD 21% (95% CI 16-26%).

Multivariable analyses confirmed a worse OS and PFS for advanced disease, with a HR of 1.79 (95% CI 1.22-2.64), p = 0.00322 and ALL subtype with a HR for other than Ph+ ALL of 1.99 (95%CI 1.42-2.79).

Conclusions: This study suggests that alloHSCT is a reasonable option for elderly ALL patients without any impact of age but advanced disease and ALL subtype other than Ph+ ALL negatively influenced the outcome.

Disclosure: YC: Y.C. has received consulting fees for advisory board from MSD, Novartis, Incyte, BMS, Pfizer, Abbvie, Roche, Jazz, Gilead, Amgen, Astra-Zeneca, Servier; Travel support from MSD, Roche, Gilead, Amgen, Incyte, Abbvie, Janssen, Astra-Zeneca, Jazz, Sanofi all via the institution.

EF: EF received funding for congress participation from Alexion, Gilead, Jazz, MSD, Novartis; and also honoraria for boards and speaker bureau participation from Alexion, GSK, Novartis, Gilead, Astellas.

ML: honorari : Alexion, Astra Zeneca, BMS Celgene, Gilead, GSK, Jazz, Kartos, Medac, MSD, Novartis, Pfizer, Sanofi, Sobi, Telios

TM: Consulting fees : Servier, Jazz Pharmaceutical, Sobi, Astellas. Travel support from Servier, Jazz Pharmaceutical

AH : AH has received consulting fees advisory board from Jazz, Pfizer, Servier, Novartis, Astellas; Travel support from Medac, Jazz, Neovii all via the Institution.

All the others do not have any conflict of interest.

19: Acute Leukaemia

Sebastian Giebel ¹, Myriam Labopin², Ryszard Swoboda¹, Didier Blaise³, Ibrahim Yakoub-Agha⁴, Stephanie Nguyen⁵, Eva Maria Wagner-Drouet⁶, Cristina Castilla-Llorente⁷, Panagiotis Kottaridis⁸, Thomas Schroeder⁹, Renato Fanin¹⁰, Jakob Passweg¹¹, Jurjen Versluis¹², Charles Crawley¹³, Ludovic Gabellier¹⁴, Stephan Mielke¹⁵, Xavier Poiré¹⁶, Erfan Nur¹⁷, Carlos Pinho Vaz¹⁸, Matthias Eder¹⁹, Riccardo Saccardi²⁰, Peter Dreger²¹, Zinaida Peric²², Mohamad Mohty², Fabio Ciceri²³

¹Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland, ²EBMT Unit, Sorbonne Universités, UPMC University of Paris 06, INSERM, Centre de Recherche Saint-Antoine (CRSA), AP-HP, Saint Antoine Hospital, Paris, France, ³Programme de Transplantation & Therapie Cellulaire, Marseille, France, ⁴CHU de Lille, University of Lille, INSERM U1286, Infinite, Lille, France, ⁵Universite Paris IV, Hopital la Pitié-Salpêtrière, Paris, France, ⁶University Medical Center Mainz, Meinz, Germany, ⁷Gustave Roussy Cancer Campus, Villejuif, France, ⁸University College London Hospital, London, United Kingdom, ⁹University Hospital Essen, Essen, Germany, ¹⁰Azienda Ospedaliero Universitaria di Udine, Udine, Italy, ¹¹University Hospital | Basel, Basel, Switzerland, ¹²Erasmus University Medical Center Cancer Institute, Rotterdam, Netherlands, ¹³Addenbrookes Hospital Cambridge, Cambridge, United Kingdom, ¹⁴University Hospital of Montpellier, Montpellier, France, ¹⁵Karolinska University Hospital, Stockholm, Sweden, ¹⁶Cliniques Universitaires St. Luc, Brussels, Belgium, ¹⁷Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands, ¹⁸Inst. Português de Oncologia do Porto, Porto, Portugal, ¹⁹Hannover Medical School, Hannover, Germany, ²⁰Azienda Ospedaliera Universitaria Careggi, Firenze, Italy, ²¹University of Heidelberg, Heidelberg, Germany, ²²University Hospital Center Rijeka and School of Medicine, University of Rijeka, Rijeka, Croatia, ²³Ospedale San Raffaele s.r.l., Haematology and BMT, Milano, Italy

Background: Tyrosine kinase inhibitors (TKIs) with or without chemotherapy, followed by allogeneic hematopoietic cell transplantation (allo-HCT) are the standard of care for patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). In older patients, intensity of the conditioning regimens is frequently reduced, which may result in increased risk of relapse. However, introduction of alternative approaches using 2^nd or 3^rd generation TKIs in combination with blinatumomab may restrict the role of allo-HCT. The goal of this study was to evaluate results of recent allo-HCTs for patients aged ≥55 years, and to identify prognostic factors.

Methods: This was a retrospective analysis based on data from the EBMT registry, including 566 patients with Ph+ ALL treated with allo-HCT in first complete remission between the years 2016 and 2022.

Results: Median recipient age was 60 (range, 55-76) years. Allo-HCT was performed using either a matched sibling (n = 138, 24%), unrelated (n = 343, 61%) or haploidentical (n = 85, 15%) donor. Conditioning regimen was myeloablative in 47% of cases and based on total body irradiation (TBI) in 49% of patients. Status of measurable residual disease was reported as negative in 59.5% of patients.

The probability of overall survival (OS) and leukemia-free survival (LFS) at 2 years was 71% and 59.5%, respectively. The incidence of relapse (RI) and non-relapse mortality (NRM) was 18% and 22.5%, respectively. The rate of graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) was 50%. The incidence of grade 3-4 acute GVHD was 9% while that of extensive chronic GVHD it was 15%.

In univariate analysis the use of TBI-based as compared to chemotherapy-based regimens was associated with reduced RI (15% vs. 20.5%, p = 0.04), improved LFS (67% vs. 53%, p = 0.002) and OS (77% vs. 66%, p = 0.01), as well as a tendency toward reduced incidence of NRM (18% vs. 27%, p = 0.1). On the other hand, it was also associated with increased incidence of both overall and extensive chronic GVHD (46% vs. 27.5%, p = 0.001 and 21% vs. 10%, p = 0.001, respectively). In a multivariant model, the use of TBI was the only factor affecting outcomes, being associated with reduced risk of NRM (hazard ratio, [HR] = 0.46, p = 0.004), improved LFS (HR = 0.53, p<0.001) and OS (HR = 0.47, p<0.001) as well as increased risk of chronic GVHD (HR = 1.68, p = 0.009) and extensive chronic GVHD (HR = 1.84, p = 0.04).

Conclusions: Based on this large-scale analysis we conclude that results of allo-HCT for patients with Ph+ ALL aged ≥55 years in the last few years are very encouraging with approximately 60% LFS at 2 years. TBI-based conditioning appears preferable in this patient population. Our data can serve as reference for results of prospective trials.

Clinical Trial Registry: Not applicable

Disclosure: SG received honoraria from Angelini and Novartis

19: Acute Leukaemia

Thomas Schroeder ¹, Sarah Flossdorf¹, Caroline Pabst², Michael Stadler³, Johannes Schetelig⁴, Claudia Wehr⁵, Claudia Schuh⁶, Matthias Stelljes⁷, Elisa Sala⁸, Andreas Burchert⁹, Jennifer Kaivers¹, Christian Reinhardt¹, Nicolaus Kroeger¹⁰, Katharina Fleischhauer¹, Christina Rautenberg¹

¹University Hospital Essen, Essen, Germany, ²University Hospital Heidelberg, Heidelberg, Germany, ³MHH Hannover, Hannover, Germany, ⁴University Hospital Dresden, Dresden, Germany, ⁵University Hospital Freiburg, Freiburg, Germany, ⁶DRST, Ulm, Germany, ⁷University Hospital Muenster, Muenster, Germany, ⁸University Hospital Ulm, Ulm, Germany, ⁹University Hospital Marburg, Marburg, Germany, ¹⁰University Hospital Hamburg, Hamburg, Germany

Background: Somatic mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) are found in about 15% to 20% of patients with acute myeloid leukemia (AML). While the prognostic impact of these mutations is still controversial, IDH inhibitors have been developed and introduced as targeted treatment for patients with IDH-mutated AML. They are currently under investigation also as maintenance therapy after allogeneic transplantation (allo-SCT), although outcomes of IDH1- and IDH2-mutated (IDHmut) AML patients after allo-SCT have not been well described.

Methods: To address this, we retrospectively analyzed the outcome of IDHmut patients, who were allografted between 2014 and 2021, had available data collected within the German Registry for hematopoetic Stem Cell Transplantation and cellular therapy (DRST) and a follow-up of at least 6 months. Overall (OS) and event-free survival (EFS) were estimated by Kaplan–Meier method and logrank tests were applied for univariable comparisons. Relapse incidence and non-relapse mortality (NRM) were considered as competing risks and calculated using cumulative incidence (CI) estimates employing Gray test for univariable comparisons.

Results: Overall, 356 IDH-mutated AML patients (IDH1 n = 142 40%, IDH2 n = 214 60%) with a median age of 60 (18 to 76) received a first allo-SCT from a related (30%) or unrelated (70%) donor following myeloablative (50%) or reduced intensity (50%) conditioning. According to ELN 2016 genetic risk stratification 21% belonged to the favorable, 42% to intermediate and 27% to adverse category (missing 10%), with 71% of patients being in CR at transplant. Of 262 patients with available information 10 (4%) had received an IDH inhibitor outside clinical trials prior transplantation. After a median follow-up of 24 months, IDH1mut and IDH2mut patients had similar estimated 3-year probabilities of overall survival (78% vs 70%, p = .64). Non-relapse mortlity was comparable (10% vs 14%, p= .48). Three-year probabilities of relapse were numerically higher for IDH1mut compared with IHD2mut patients (34% vs 24%, p= .18) without reaching statistical significance, and concomitantly a numerically lower 3-year event-free survival (56% vs 62% respectively; p= .14).

Conclusions: Taken together, these data from a large multicenter cohort provide benchmarks for analysis and interpretation of results emerging from clinical trials evaluating maintenance IDH1 and IDH2 inhibitor therapy for AML patients after allo-SCT

Clinical Trial Registry: not applicable

Disclosure: Thomas Schroeder: Advisory Boards:BMS; lecture fees BMS, research funding: BMS

Elisa Sala: honoraria for consultancy or travel support from Gilead, Novartis, BMS, Jazz, Neovii, Therakos/Mallinckrodt, MSD, Priothera.

Johannes Schetelig: Advisory Boards: Abbvie, AstraZeneca, BeiGene, BMS, Janssen, and MSD und Lecture Fees: Astellas, AstraZeneca, BeiGene, BMS, Novartis, Eurocept, Medac and Janssen

Claudia Wehr: Travel support/honoraria from Takeda, Jazz Pharmaceuticals.

Christian Reinhardt: consulting and lecture fees from AbbVie, AstraZeneca, Roche, Janssen-Cilag, Novartis, Vertex and Merck. H.C.R. received research funding from Gilead and AstraZeneca. H.C.R. is a co-founder of CDL Therapeutics GmbH.

19: Acute Leukaemia

Mingming Zhang^1,2, Yongxian Hu^1,2, Peihua Lu^3,4, Liang Huang⁵, Shan Fu^1,2, Jingjing Feng^1,2, Ruimin Hong^1,2, Alex H. Chang⁶, He Huang ^1,2

¹Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, ²Liangzhu Laboratory, Hangzhou, China, ³Hebei Yanda Lu Daopei Hospital, Langfang, China, ⁴Lu Daopei Institute of Hematology, Beijing, China, ⁵Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, ⁶Shanghai YaKe Biotechnology, Shanghai, China

Background: CD19-targeted immunotherapy effectively induce remission in relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Patients who fail or relapse after CD19-targeted immunotherapy have an extremely poor prognosis, and immunotherapy targeting CD22 is one of the few possible therapeutic options, but there is currently limited data.

Methods: We conducted a multicenter, retrospective study of CD22-targeted immunotherapy for adult patients with r/r B-ALL who previously exposed to CD19-targeted immunotherapy. Primary objective was complete remission (CR) rate at 1 month.

Results: A total of 30 patients were included, and the median age was 32 (18-67) years old. Four (13.3%) patients were Ph-positive, 10 (33.3%) patients were primary refractory and 10 (33.3%) patients relapsed after allogeneic stem cell transplantation. Six (20.0%) patients were exposed to blinatumomab only, 20 (66.7%) patients were exposed to CD19 CAR-T cell therapy only, and 4 (13.3%) patients were exposed to both. 20 (66.7%) patients received CD22 CAR-T cell therapy, and 10 (33.3%) patients received inotuzumab ozogamicin. In the target expression analysis before CD22-targeted immunotherapy, all patients had CD22-positive expression except one patient was CD22-dim. As for the expression of CD19, 13 (43.3%) patients were CD19-positive, 12 (40.0%) patients were CD19-negative, and 5 (16.7%) patients were CD19-dim or partially expression. Totally 17 (56.7%) patients achieved CR at 1 month after CD22-targeted immunotherapy. The CR rate was 55.0% (11/20) in the CD22 CAR-T group, and 60.0% (6/10) in the inotuzumab ozogamicin group. There was no significant difference between the two groups (P = 0.79). The CR rate for patients exposed to both blinatumomab and CD19 CAR-T seemed to be low and was 25% (1/4). Other factors including primary refractory, post-transplantation relapse, and CD19 expression status had no effect on CR rate. Of the 17 patients who achieved CR, 10 had subsequent relapses, 2 lost to follow-up, 1 died of a post-CAR-T infection, and 1 died of complications of transplantation. As of December 15, 2023, excluding the 2 patients lost to follow-up, only 7 patients remained in MRD negative CR.

Conclusions: CD22-targeted immunotherapy is an effective treatment option for patients with r/r B-ALL who previously exposed to CD19-targeted immunotherapy. However, the relapse rate post CD22-targeted immunotherapy remains high. Therefore, new strategies are still needed to improve the prognosis of this group of patients.

Disclosure: Alex H. Chang is an employee of Shanghai YaKe Biotechnology Ltd., the other authors declare no conflict of interest.

19: Acute Leukaemia

Weihao Chen¹, Yeqian Zhao^1,2,3,4, Jimin Shi^1,2,3,4, Yi Luo^1,2,3,4, Jian Yu^1,2,3,4, Yamin Tan^5,6, Xiaoyu Lai^1,2,3,4, Lizhen Liu^1,2,3,4, Huarui Fu^1,2,3,4, Yishan Ye^1,2,3,4, Luxin Yang^1,2,3,4, Congxiao Zhang^1,2,3,4, He Huang^1,2,3,4, Yanmin Zhao ^1,2,3,4

¹Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, ²Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China, ³Institute of Hematology, Zhejiang University, Hangzhou, China, ⁴Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China, ⁵Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China, ⁶Institute of Cancer and Basic Medicine(IBMC), Chinese Academy of Sciences, Hangzhou, China

Background: Risk classification based on genetic aberrations plays a pivotal role in predicting prognosis and guiding treatment decisions in patients with acute myeloid leukemia (AML). In 2022, the European LeukemiaNet (ELN) issued an updated recommendations for diagnosis and risk classification, building upon the ELN2017 guidelines. While many studies have validated and compared the two versions of ELN risk classifications in chemotherapy cohorts, there remains a scarcity of research comparing the prognostic impact of ELN2017 and ELN2022 criteria in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: We conducted a retrospective study which compared the the prognostic impact between the 2017 and 2022 ELN risk classifications in a real-life cohort of de novo AML patients who underwent allo-HSCT (n = 641) in our center from January 2015 to January 2022. We enrolled patients who had sufficient clinical and genetic information available for ELN risk classification. Patients diagnosed with acute promyelocytic leukemia or whose who received a second transplantation were excluded. Gene mutations or fusion genes detection were performed using polymerase chain reaction before 2017 and next-generation sequencing after 2017.

Results: 623 patients were included in this retrospective study, with a median follow-up time of 2.8 years after allo-HSCT. The median age at allo-HSCT was 40 years (range 10-67). According to ELN2017 risk categories, 32% (n = 202) patients at diagnosis were classified into ELN2017 favorable group, 43% (n = 264) into ELN2017 intermediate group, and 25% (n = 157) into ELN2017 adverse group. In ELN2022, the classification was 32% (n = 202) in favorable, 45% (n = 277) in intermediate, and 23% (n = 144) in adverse group. Patients in adverse group had significantly lower RFS (relapse-free survival) and OS (overall survival) after allo-HSCT compared to those in favorable and intermediate group, regardless in ELN2017 or ELN2022. Nonetheless, RFS of ELN2022 intermediate patients was worse than favorable patients (68.8 vs 82.3%, P = 0.015), and we did not obverse this statistic difference in ELN2017. The c-statistic (area under the curves [AUC]) from ELN2022 for RFS after allo-HSCT was not obviously better compared to ELN2017 (AUC_ELN22 = 0.637 vs AUC_ELN17 = 0.616, P = 0.096). The univariate analysis indicated that adverse ELN classification, NR status at allo-HSCT, and CR patients with MRD positivity at allo-HSCT might be associated with worse RFS and OS after allo-HSCT. Therefore, we further refined the ELN2022 system into four categories by incorporating the remission and MRD status at allo-HSCT (favorable: ELN2022 favorable with MRD^neg, intermediate: ELN2022 favorable with MRD^pos and ELN2022 intermediate with MRD^neg, adverse: ELN2022 intermediate with MRD^pos and ELN2022 adverse with MRD^neg, and very adverse: NR patients at allo-HSCT and ELN2022 adverse with MRD^pos). The refined ELN risk classification showed that there was statistical significance between groups for RFS after allo-HSCT, and the AUC_{Refined ELN22} was significantly better than AUC_ELN22 (0.703 VS 0.637, P<0.001).

Table 1. Univariate analysis of clinical characteristics in RFS and OS

Conclusions: The updated ELN2022 risk classification did not demonstrate improved predictive performance for outcomes after allo-HSCT compared to ELN2017. We refined the stratification system into four groups by incorporating disease status at transplant, aiming to more accurately identify patients with different outcomes following allo-HSCT.

Disclosure: Nothing to declare

19: Acute Leukaemia

XiaoYu Zhang ¹, Yanhong Zhao¹, Rongli Zhang¹, Erlie Jiang¹

¹Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

Background: To investigate the efficacy and safety of an olverembatinib regimen in adult Ph/BCR-ABL1 + ALL patients with relapsed disease or persistent MRD prior to allo-HSCT.

Methods: We retrospectively enrolled Ph+ ALL patients with relapsed disease or persistent MRD who were treated with an olverembatinib-based regimen before bridging to HSCT between February 2022 and February 2023.

Results: Seventeen Ph+ ALL patients were treated with olverematinib because of disease recurrence (n = 3) and persistent molecular positivity (n = 14). BCR: ABL1 p190 and p210 fusions were found in nine and eight patients, respectively. Six patients harbored a T315I mutation. In all, 13 patients achieved CMR, and the overall CMR rate by PCR was 76.47%, whereas the MRD neg rate by flow cytometry was 100%. All patients successfully underwent bridging allo-HSCT. With a median follow-up time of 342 (60-509) days post-HSCT, the one-year overall survival rate and recurrence-free survival rate were 94.1±5.71% (95 % CI 83.6~100%) and 88.2±7.81% (95% CI 74.2~100%), respectively. Only one patient experienced extramedullary relapse on day 129. One patient died due to CNS complications.

Conclusions: The findings of this study suggest that in Ph+ ALL patients with disease recurrence and persistent MRD positivity, olverembatinib showed a profound molecular response rate and was well-tolerated in MRD clearance prior to allo-HSCT

Disclosure: The authors declare that they have no competing interests.

19: Acute Leukaemia

Olga Schutti¹, Lara Klauer^2,1, Tobias Baudrexler^2,1, Christoph Schmid³, Andreas Rank³, Joerg Schmohl⁴, Markus Hentrich⁵, Doris Kraemer⁶, Helga Schmetzer ¹

¹Klinikum Grosshadern, Ludwig-Maximilians-University, Working-Group Immune-Modulation, Munich, Germany, ²Contributed Equally, Munich, Germany, ³University Hospital of Augsburg, Augsburg, Germany, ⁴University Hospital of Tuebingen, Tuebingen, Germany, ⁵Red Cross Hospital of Munich, Munich, Germany, ⁶University Hospital of Oldenburg, Oldenburg, Germany

Background: Novel (immune) therapies are needed to stabilize remissions or the disease in AML. Leukemia derived dendritic cells (DCleu) can be generated ex vivo from AML patients’ blasts in whole blood using approved drugs (GM-CSF and PGE-1 (Kit-M)). After T cell enriched, mixed lymphocyte culture (MLC) with Kit-M pretreated (vs. untreated WB) antileukemically directed immune cells of the adaptive and innate immune system were already shown to be significantly increased.

Aims: To evaluate the use of leukemiaspecific assays intracellular cytokine production (INFy, TNFa) INCYT, degranulation (CD107a) DEG for a detailed quantification of leukemiaspecific cells in correlation with functional cytotoxicity and patients’ clinical data.

Methods: Whole blood (WB) samples were collected from 26 AML patients at first diagnosis, during persisting disease, or at relapse after allogeneic stem cell transplantation (SCT), and from 18 healthy volunteers. WB samples were treated with vs. without Kit-M to generate DC/DCleu. After MLC with Kit-M treated vs. untreated WB antigenspecific/ anti-leukemic effects were assessed through INCYT, DEG and a cytotoxicity fluorolysis assay. Quantification of cell subtypes was performed via flowcytometry.

Results: We generated significantly higher frequencies of (mature) DCleu without induction of blast proliferation in Kit-M treated vs. untreated samples. After MLC with Kit-M treated vs. untreated WB, frequencies of immunoreactive cells (e.g. non-naive T-cells, Tprol) as well as in INCYT/DEG ASSAYS leukemiaspecific adaptive - (e.g. B, T(memory)) or innate immune cells (e.g. NK, CIK) were significantly increased. The results of the intracellular production of INFy and TNFa were comparable. The cytotoxicity fluorolysis assay revealed a significantly enhanced blast lysis in Kit-M treated vs. untreated WB. Significant correlations could be shown between induced leukemiaspecific cells of several lines and improved blast lysis.

Conclusions: We successfully detected and quantified immunoreactive cells at a single-cell level using the functional assays (DEG, INCYT, and CTX) ex vivo, allowing us to evaluate the impact of Kit-M pretreated (DC/DCleu containing) WB on the provision of leukemia specific immune cells. Kit-M pretreatment (vs no pretreatment) was shown to significantly increase leukemia-specific IFNγ and TNFɑ producing, degranulating cells and to improve blast-cytotoxicity after MLC.

In vivo treatment of AML patients with Kit-M may lead to anti-leukemic effects and contribute to stabilize the disease or remissions. INCYT and DEG assays qualify to quantify potentially leukemia specific cells on a single cell level and to predict the clinical course of patients under treatment.

Disclosure: Conflict of interest: Modiblast Pharma GmbH (Oberhaching, Germany) holds the European Patent 15 801 987.7-1118 and US Patent 15-517627 ‘Use of immunomodulatory effective compositions for the immunotherapeutic treatment of patients suffering from myeloid leukemias’, with whom H.M.S. is involved with.

19: Acute Leukaemia

Anthony Stein ¹, Monzr Al Malki¹, Dongyun Yang¹, Joycelynne Palmer¹, Ni-Chun Tsai¹, Ibrahim Aldoss¹, Haris Ali¹, Ahmed Aribi¹, Andrew Artz¹, Savita Dandapani¹, Len Farol^1,2, Susanta Hui¹, An Liu¹, Ryotaro Nakamura¹, Vinod Pullarkat¹, Eric Radany¹, Amandeep Salhotra¹, James Sanchez¹, Ricardo Spielberger^1,2, Guido Marcucci¹, Stephen Forman¹, Jeffrey Wong¹

¹City of Hope, Duarte, United States, ²Southern California Permanente Medical Group, Los Angeles, United States

Background: We have conducted a phase 2 study of a conditioning regimen of total marrow and lymphoid irradiation (TMLI) at 2000cGy, together with post-transplant cyclophosphamide (PTCy) for patients with acute myeloid leukemia in first or second complete remission (CR). This approach employs PTCy to attenuate the risk of chronic graft-versus-host-disease (GVHD), while using escalated targeted radiation conditioning before allografting to offset the possible increased risk of relapse.

Methods: We evaluated to date the first 25 patients with a median follow-up of ≥1yr (Table) who enrolled between 2018–2023. Key criteria: ages 18–60, first or second CR, minimal residual disease negative by multi-color flow cytometry, and normal organ function. TMLI was administered on days -4 to 0 without addition of chemotherapy. The radiation dose for all patients (n = 25) was 2000cGy, delivered in 200cGy fractions twice daily. The radiation dose delivered to the liver and brain was kept at 1200cGy. Remaining organs were considered non-targeted. All patients received peripheral blood stem cells on day 0. Cyclophosphamide was given on days +3 and +4, 50mg/kg each day for GVHD prevention. Tacrolimus, 1mg continuous infusion adjusted to maintain levels from 5–10ng/mL, was given from day +5 to day +90, and G-CSF 5µg/kg daily was administered at day +5 until recovery of neutrophil counts.

Endpoints included toxicity, engraftment, overall survival (OS), non-relapse mortality (NRM), and GVHD/relapse-free survival (GRFS) at 1yr. Toxicities were defined according to the Bearman and CTCAE 4.03 scales, the latter for hematologic toxicity. A patient safety lead-in segment (n = 6) was conducted to ensure there were no unexpected toxicities. GRFS was defined as the absence of grade 3-4 acute GvHD, chronic GvHD requiring systemic treatment, relapse, or death (from any cause).

Results:

The median follow up was 47.1 months (range: 5.9-59.9) for surviving patients (n = 22). Bearman toxicity data are available for all patients. Among these patients, grade 2 toxicities were bladder toxicity and stomatitis. No grade 3-4 toxicities or toxicity-related deaths were observed. All patients engrafted. Median times to neutrophil and platelet recovery were 14 days (range: 13-32) and 20 days (range: 11-49), respectively.

Acute GVHD (aGVHD) developed in 2 patients (100-day Grade II-IV aGVHD: 8.0%, 95%CI: 1.3-22.9); of those, only 1 patient developed Grades III-IV (100-day Grade III-IV aGVHD: 4.0%, 95%CI: 0.3-17.4). Six patients developed chronic GVHD (2-year cGVHD rate: 27%, 95%CI: 11%-47%), which was mild in 5 patients and moderate/severe in 1 patient.

Two-year estimates of OS and leukemia-free survival were 89% (95%CI: 62-97) and 84% (95%CI: 62-94). Disease relapse at 2yrs was 16% (95%CI: 4.9-33). The estimate of NRM at 2yrs was 0%. Relapsed disease after transplant occurred in 5 patients, which led to 3 deaths from relapsed disease. The GRFS rate at 2yrs was 61% (95%CI: 37-78).

Conclusions: 1) This chemotherapy-free conditioning regimen, together with PTCy and tacrolimus, is safe and feasible, with no NRM. 2) All patients achieved engraftment. 3) Participants with ≥1yr follow-up have discontinued immunosuppressive therapy, reducing financial burden and leading to improved quality of life. The results to date suggest a favorable GRFS rate.

Clinical Trial Registry: clinicaltrials.gov, NCT#03467386

Disclosure: Anthony Stein: Sanofi: Current Employment, Current holder of stock options.

19: Acute Leukaemia

Alexandra Guelton ¹, Meriem El Ouafy¹, Romain Perouf¹, Naceur Charif¹, Simona Pagliuca¹, Marie-Thérèse Rubio¹, Natalia de Isla¹

¹University of Lorraine, Vandoeuvre-les-Nancy, France

Background: The acute myeloid leukemia (AML) is an hematological malignancy with a bad pronostic with an estimated survival of 50% at 1 year, and 27% at 5 years. The allogenic hematopoietic stem cells transplantation (allo-HSCT) is the only curative treatment of AML, marked by two major adverse effects: graft versus host disease and relapse. Although medullary microenvironment is composed of many cellular actors, mescenchymal stromal stem cells (MSC) constitute key players, both for their role in hematopoiesis and for their immunomodulatory capacities, particulary toward T cells. The aim of our work was to study the link between medullary microenvironment (MSC, cytokines…) in pre-transplantation, and the occurrence of GVHD.

Methods: We conducted a prospective, single-center study at the Nancy University Hospital, involving HSC allograft patients with AML. Inclusion criteria were: graft conditioning including a combination of fludarabine and busulfan, homogeneous graft-versus-host disease (GVHD) prophylaxis (anti-lymphocytic serum, cyclosporin and mycophenolate mofetil. Medullary MSC from bone marrow of patients before HSCT were isolated and cultured. MSC used as control provided from patients without AML, and were obtained after surgical hip arthroplasty. MSC were characterized based on the International Society of Cellular Therapie (ISCT) criteria as their adhesion to plastic, their surface phenotype (CD73 + , CD90+, HLA-DR−, CD45−, CD34−) and their self-renewal capacity.

Then, MSC senescence was studied thanks to β-galactosidase test coupled with EdU proliferation test (5-Methyl-2′-deoxycytidine), to distinguish senescents and proliferative cells, and avoid false positives. Moreover, proteins involved in cell senescence (p16, p21, p53, p38) were evaluated by Western-Blot. Then, many cytokines involved in cell senescence (IL10, IL6, IL1, IL13…) and in immune surveillance (CXCL14) were quantified by CBA and ELISA method. In parallel, MSC immunomodulatory properties were determined by coculture experiments between MSC and T cells from healthy donnors.

T statistical tests and Pearson correlation tests was performed thanks to GraphPad Prism. Principal component analysis (PCA) was performed thanks to XLSTAT.

Results: Our results showed that high levels of medullary MSC senescence from AML patients before HSCT, correlated with a decrease of MSC immunomodulatory properties toward T cells, was associated with the occurrence of GVHD, three months after HSCT. Moreover, a positive correlation between the level of medullary MSC senescence and the medullary concentration of CXCL14 was observed. Among the other cytokines studied, no correlation was shown between their concentration and medullary MSC senescence.

Conclusions: Our results showed that a pro inflammatory microenvironment before HSCT, characterized by the presence of senescent MSC with disturbed immunomodulatory properties, and the presence of CXCL14, would be favorable to the occurrence of GVHD after HSCT.

Disclosure: Nothing to declare

19: Acute Leukaemia

Naty López-Córdova ¹, Jessica Meza-Liviapoma¹, Jule Vasquez-Chavez¹, Claudio Flores-Flores², Shirley Quintana-Truyenque¹

¹Instituto Nacional de Enfermedades Neoplásicas (INEN), Lima, Peru, ²Universidad Peruana San Juan Bautista, Lima, Peru

Background: The Refined Disease Risk Index (R-DRI; 4 risk groups: low [LR], intermediate [IR], high [HR] and very high [V-HR]) is a score used to estimate overall survival after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in patients with haematological malignancies, however, both in its original version and in the R-DRI does not consider certain diagnoses, such as mixed-phenotype acute leukaemia (MPAL) and acute lymphoblastic lymphomas (LBL). These diagnoses constitute an important population since they have a very aggressive course and fatal outcomes in most cases. The objective of the study is to determine the correlation of overall survival in patients with MPAL and LBL after Allo-HSCT, in relation to R-DRI. These results will allow these patients to be assigned to one of the existing risk groups in order to have an estimate of their post HSCT prognosis.

Methods: We reviewed retrospectively the data of 166 patients who had an Allo-HSCT between 2012 and 2023 in the Bone Marrow Transplant (BMT) unit of the National Institute of Neoplastic Diseases (INEN). The information was extracted from the unit registry and was completed through the electronic medical records. Patients diagnosed and transplanted for MPAL and LBL were subjected to the analysis and their overall survival was evaluated, which was compared with the data of patients with acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Survival was estimated using the Kaplan-Meier method and comparisons were made using the Log-Rank test.

Results: The median age at HSCT was 26 years (range: 15 to 63), 84 patients were men (50.6%). 85 patients had ALL; 41, AML; 11, Chronic myeloid leukaemia (CML); 13, MPAL; and 16, others (Myelodysplastic syndrome: 8, LBL: 6, Hodgkin lymphoma: 1, aggressive T/NK cell leukaemia: 1). According to the R-DRI classification (does not include MPAL and LBL), 4.8% of patients were LR, 38.1% IR, 35.4% HR, and 21.8% V-HR. Median follow-up was 3.9 years and median overall survival (OS) was not reached for the entire cohort. According to R-DRI, the 4-year OS rate was 100% in LR, 57.4% in IR, 53.5% in HR, and 38.3% in V-HR, respectively. The 4-year OS in patients with MPAL was 76.9%, and in LBL 44.4%. The OS of patients with MPAL was superior to those with IR, presenting a significant difference in relation to the HR group (p = 0.015).

Conclusions: The OS of patients with MPAL is superior to those with IR, presenting a significant difference in relation to those with V-HR. These results suggest that there would be a group that is similar to that of IR, but with a better prognosis than that described in the R-DRI and that could give rise to a new “low-intermediate” group in which the MPAL could be included.

Disclosure: Nothing to declare.

19: Acute Leukaemia

Ben-Niklas Baermann¹, Paula Kessler ¹, Astrid Tautges², Paul Sebastian Jäger¹, Mustafa Kondakci³, Kathrin Nachtkamp¹, Sascha Dietrich¹, Guido Kobbe¹

¹Medical Faculty and University Hospital Düsseldorf, Düsseldorf, Germany, ²Office for general practice Dirk Röhlich, Trier, Germany, ³Lukas Hospital Solingen, Solingen, Germany

Background: Acute lymphoblastic leukemia (ALL) treatment landscape has dramatically changed within the last two decades. Especially tyrosine kinase inhibitors in Philadelphia positive (BCR-ABL) ALL as well as Blinatumomab, Inotuzumab and chimeric antigen receptor t-cell therapy for B-cell precursor ALL (B-ALL) were the most prominent pharmacologic milestones. Moreover the german multicenter ALL study group (GMALL) made strong efforts to improve conventional and transplant strategies to reduce non relapse mortality.

Methods: We retrospectively analyzed clinical outcome of 146 patients (61% male, 39% female, median age at transplant 36 years, range 17-74) with acute lymphoblastic leukemia (B-ALL 76%, T-ALL 24%) receiving allogeneic stem cell transplantation (alloHSCT) at the UKD, Heinrich Heine University of Düsseldorf between 1989 and 2022. Of Patients with B-ALL 33% were Philadelphia chromosome positive.

The majority of patients (92%) received myeloablative conditioning almost all containing total body irradiation (TBI) with at least 8 Gy. Matched related donors were used in 32%, 40% had matched unrelated donors and 27% mismatched or haploidentical donors. Median time from diagnosis to alloHSCT was 6 months (range 2-80). Haematologic remission could be achieved in 95% prior to transplant.

Results: Median follow up after alloHSCT was 5.6 years for surviving patients. Median overall survival (OS) from transplant for all patients was 2.8 years (95% CI 0.0-6.1 years). OS after two and five years were 51% (95% CI 43-59) and 47% (95% CI 39-55). For T-ALL median OS was not reached, for B-ALL median OS was 1.3 years (95% CI 0-2.9 years).

For patients with first diagnosis from 2000 to 2010, median OS from alloHSCT was 1.2 years, whereas after 2010 median OS is not reached with a significant difference between these subgroups (p<0.05). OS after two and five years for patients with first diagnosis after 2010 were 66 % (95% CI 55-78) and 64 % (95% CI 52-76). These findings can be reproduced for BCR-ABL positive as well as negative B-ALL subgroups but not for patients with T-ALL.

MRD persistence before alloHSCT was associated with significant worse OS even in haematologic complete remission (median OS 1.4 years vs. not reached, p < 0.05), not significantly differing for patients with first diagnosis before or after 2010.

Median OS after alloHSCT could not be improved by application of higher doses of TBI (12Gy vs. 8Gy, median OS 2.9 years vs. not reached, p = 0.5).

Conclusions: Prognosis of B-lineage acute lymphoblastic leukemia after alloHSCT significantly improved over time and reducing TBI toxicity by dose reduction did not negatively influence OS. Achieving MRD negativity before alloHSCT especially with new targeted therapies seems to play an important role. Nevertheless worse OS in patients with MRD persistence could not be overcome in recent years.

Disclosure: Ben-Niklas Baermann: Travel support: Medac, Kite-Gilead; Advisory Role or Speaker Honoraria: Kite-Gilead, Incyte

Paula Kessler: Nothing to declare.

Astrid Tautges: Nothing to declare

Paul Sebastian Jäger: Nothing to declare

Mustafa Kondakci: Nothing to declare

Sascha Dietrich: Nothing to declare

Kathrin Nachtkamp: Nothing to declare.

Guido Kobbe: Advisory Role or Speaker Honoraria: MSD, Pfizer, Amgen, Novartis, Gilead, BMS-Celgene, Abbvie, Biotest, Takeda, Eurocept; Financing of Scientific Research: BMS-Celgene, Amgen, Abbvie, Eurocept, Medac.

19: Acute Leukaemia

Mattia Algeri ¹, Michele Massa², Federica Galaverna², Daria Pagliara², Ilaria Pili², Francesca Del Bufalo², Marco Becilli², Emilia Boccieri², Roberto Carta², Francesco Quagliarella², Chiara Rosignoli², Carmen Dolores De Luca², Barbarella Lucarelli², Pietro Merli², Franco Locatelli³

¹IRCCS Bambino Gesù Children’s Hospital - Magna Graecia University, Rome - Catanzaro, Italy, ²IRCCS Bambino Gesù Children’s Hospital, Rome, Italy, ³IRCCS, Bambino Gesù Children’s Hospital, Catholic University of the Sacred Heart, Rome, Italy

Background: Blinatumomab, a CD3-CD19 bispecific T-cell engager, demonstrated high efficacy in inducing and consolidating remission in relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Available evidence suggests that r/r B-ALL patients have a better outcome if they received allogeneic hematopoietic stem cell transplantation (HSCT) after blinatumomab. However, the effect of blinatumomab on HSCT outcomes in children and young adults (YA) remains to be fully elucidated.

Methods: We retrospectively analyzed 78 children and YA with B-ALL who underwent allogeneic HSCT at our Institution, from February 2016 to June 2023, after receiving blinatumomab as last therapy before transplant either as part of reinduction/consolidation or as MRD-clearing strategy. Most patients (n = 55) received a single 28-day course. Median interval from blinatumomab discontinuation to HSCT was 23 days (IQR 19-31.75).

Median age at HSCT was 5 years (range 1-24). Patients received unmanipulated grafts from HLA-identical related (MFD, n = 13) or matched unrelated donors (MUD, n = 33), or αβT-cell depleted HSCT from HLA-haploidentical relatives (TCD-Haplo, n = 32) after TBI- (n = 72, 92.3%) or chemo-based myeloablative conditioning regimen (n = 6, 7.7%). All subjects were in complete remission (CR) at time of HSCT, associated with MRD-negativity (<10^-4) in 94% of cases. Thirty-one (39.7%) patients harbored at least one very high-risk (VHR) disease feature (Table 1). Further patient and transplant characteristics are reported in Table 1.

Results: All patients achieved sustained donor engraftment, median time to neutrophil and platelet recovery being 17 (IQR 14-19) and 15 (IQR 11-20) days, respectively. After a median follow-up of 26 months, disease-free survival (DFS) of the whole cohort was 74.2% (95%CI 63.3-85.1), overall survival (OS) 84.3% (95%CI 74.5-94.1) and non-relapse mortality (NRM) 2.6% (95%CI 0-6.2). Cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (aGvHD) was 17.9% (95%CI 9.08-26.6), with only two cases of grade III; CI of extensive chronic GvHD (cGvHD) was 4.6% (95%CI 0-9.7). No unexpected toxicities were observed. Patients aged ≤4 years had significantly lower DFS as compared to those aged 5-11 years or ≥12 years (45.6% 95%CI 20.1-71.1, 82% 95%CI 70-100 and 85.6% 95%CI 68.8-95.5, respectively, p = 0.02), due to a higher cumulative incidence of relapse (CIR 51.5% 95%CI 24-79.1, 18% 95%CI 4.9-31.1, 18.6 95%CI 8.6-28.9, respectively, p = 0.05). Neither the use a specific conditioning, nor MRD status and presence of VHR features influenced the probability of DFS. A trend toward better DFS was observed in CR1 patients (94.1%, 95%CI 82.95-100) versus CR2-3 (69.5%, 95CI 57-83.04, p = 0.18) and in those receiving unmanipulated matched grafts (80.1% 95%CI 64.6-95.6) versus TCD-Haplos (64.9%, 95%CI 48.2-81.5, p = 0.058).

Sixteen patients relapsed after HSCT, all with CD19-positive recurrence, after a median time of 9 months following transplantation (range 1-23). Of them, 10 received anti-CD19 CAR-T cells while 2 received inotuzumab, the 2-year OS after relapse being 52.7% (95%CI 27.1-78,3).

Conclusions: HSCT following blinatumomab in children/YA with r/r B-ALL is safe and highly effective, with remarkably low NRM (only 2 patients died for NRM) and absence of unexpected toxicities. These findings indicate that blinatumomab represents a suitable strategy to achieve long-term disease eradication and that it doesn’t preclude successful salvage with CAR-T cells in case of relapse.

Disclosure: Mattia Algeri: Vertex: Membership on an entity’s Board of Directors or advisory committees; Neovii: Speakers Bureau.

Pietro Merli: Sobi: Membership on an entity’s Board of Directors or advisory committees; Jazz: Membership on an entity’s Board of Directors or advisory committees; Miltenyi: Speakers Bureau; Amgen: Speakers Bureau.

Franco Locatelli: Miltenyi, Jazz Pharm, Medac, Sobi, Gilead, BluebirdBio: Speakers Bureau; Sanofi, Vertex: Membership on an entity’s Board of Directors or advisory committees; Bellicum, Amgen, Neovii, Novartis. Sanofi, SOBI, Vertex: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau

19: Acute Leukaemia

Kseniia Afanaseva¹, Ivan Moiseev ¹, Bella Ayubova¹, Elena Babenko¹, Ildar Barkhatov¹, Tatiana Gindina¹, Anna Smirnova¹, Olesya Smykova¹, Yulia Vlasova¹, Sergey Bondarenko¹, Alexander Kulagin¹

¹RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russian Federation

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) is a standard consolidation strategy for B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients with relapsed/refractory (r/r) disease and persistent minimal residual disease (MRD). Long-term outcomes of pharmacologic immunotherapy in r/r BCP-ALL is relatively modest, but MRD-negative patients have better prognosis, which was not directly compared to the results of allo-HCT in large studies.

Methods: The study included 101 BCP-ALL patients who achieved MRD-negative complete remission (CR) with two consecutive evaluations after either blinatumomab or inotuzumab ozogamicin treatment from November 2014 to September 2023 (Table 1). Median age was 22 years (range, 18 - 67 years). MRD response was assessed both by flow cytometry and molecular analysis for patients with known molecular markers. Median blinatumomab courses were 1 (range, 1-7), inotuzumab ozogamicin – 1 (range, 1-3). Consolidation with allo-HCT was performed in 62 patients, not performed in 39 patients within the frame of the routine clinical practice. Long-term outcomes after immunotherapy according to allo-HCT consolidation were estimated by landmark analysis.

Table 1. Patients’ characteristics of the study group

Results: Median follow-up time in the group of patients who received allo-HCT after immunotherapy was 55 months (range, 2-95), in immunotherapy without allo-HCT group – 56 months (range, 5 - 101) for those who survived by follow-up. Median time from achievement of MRD-negative CR to allo-HCT was 2 months (range, 2 - 27). Median time from achievement of MRD-negative CR to relapse was 12 months (range, 2 - 72) in immunotherapy followed by allo-HCT group and 13 months (range, 2 – 61) in immunotherapy without HCT group. In a landmark analysis of 5-year overall survival (OS) and relapse-free survival (RFS) by allo-HCT at 2 months after MRD-negative CR establishment no difference between outcomes in two groups was demonstrated: OS was 44,1% (95% CI 29,3 – 66,3) in allo-HCT group and 49,6% (95% CI 38,4 – 64,1) in immunotherapy without allo-HCT group, p = 0,19; RFS was 31% (95% CI 17,9 – 53,7) and 36,1% (95% CI 25,3 – 51,5), p = 0,25, respectively. Results were similar when assessed for 4-months (p = 0,46 for OS and p = 0,67 for RFS) and 6-months landmark points (p = 0,61 for OS and p = 0,83 for RFS). Subgroup univariate analysis showed no influence of any predictors (blinatumomab versus inotuzumab ozogamicin, high cytogenetic risk, extramedullary disease in relapse, MRD or relapse as an indication to immunotherapy, previous allo-HCT) for RFS in immunotherapy without subsequent allo-HCT group, while extramedullary disease in relapse and haploidentical donor increased risk of RFS after allo-HCT, which was confirmed in a multivariate model (HR 2,8 (95% CI 1,38 – 5,6), p = 0,004 and HR 2,3 (95% CI 1,06 – 4,9), p = 0,03).

Conclusions: The study demonstrated that responders to pharmacologic immunotherapy with r/r BCP-ALL with sustainable MRD-negative status have no benefit from all-HCT consolidation in the general group. Nonetheless, heterogeneity in allo-HCT outcomes indicates that further cooperative studies and consolidation of multicenter data is required to define the group which will benefit from allo-HCT in MRD-negative CR.

Disclosure: Nothing to declare

19: Acute Leukaemia

Evgeny Klyuchnikov¹, Anita Badbaran¹, Radwan Massoud ¹, Normann Steiner¹, Petra Freiberger¹, Franziska Modemann¹, Martin Schönrock¹, Sophia Cichutek¹, Walter Fiedler¹, Micha Peeck², Nico Gagelmann¹, Christine Wolschke¹, Francis Ayuk¹, Ulrike Bacher³, Nicolaus Kröger¹

¹University Cancer Center of Hamburg, Hamburg, Germany, ²Agaplesion Diakonie Clinic, Rotenburg, Germany, ³Bern University Hospital, Bern, Switzerland

Background: Patients (pts) with relapsed/refractory (R/R) AML experience poor remission rates and short durations of response. Combinations of BCL2 inhibition have proven to be synergistic with low intensity and intensive chemotherapy, leading to high remissions. In this monocentric study, we compared post-transplant outcomes in R/R AML pts who received low (azacitidine [AZA]) or intensive (FLAG-Ida) regimen combined with venetoclax [VEN] as “bridging” strategies before allogeneic stem cell transplantation (allo-SCT).

Methods: 90 pts (male, n = 53; median, 59 years [range, 19-75]) with R/R AML who received allo-SCT (related, n = 58) between 2019-2023 at the Department of Stem Cell Transplantation (University Medical Centre Hamburg) were included if they received VEN-based “bridging” strategies. The measurable residual disease (MRD) detection was performed by flow cytometry (“different from normal”; ELN guidelines). Primary endpoint was the difference in overall survival (OS) from allo-SCT. Secondary endpoints were differences in leukaemia-free survival (LFS), relapses and non-relapse mortality (NRM) from allo-SCT.

Results: The majority of allografts were performed after myeloablative conditioning (n = 57, 63%) with ATG as GvHD prophylaxis (n = 65, 72%). 62 pts underwent 1^st whereas 26 (29%) 2^nd and two 3^rd allo-SCT. At allo-SCT,62 pts (69%) were in complete remission (CR). Bridging therapy consisted of AZA-VEN (one or two cycles) in 41 pts or FLAG-Ida-VEN in 49 pts. Pre-transplant MRD data were available in 49 pts. The rate of MRD^negCR (16/27, 59% vs 11/27, 41%) and MRD^pos CR (16/22, 73% vs 6/22, 27%) was higher in the FLAG-Ida-VEN group. The rate of non-CR (17/28, 61% vs 11/28, 39%, p = 0.055) was higher in the AZA-VEN group.

During a median follow up of 13 months (2-140), there were 34 mortalities, 27 relapses and 13 NRM events. The 2-year OS (61%, 43-77% vs 46%, 29-64%, p = 0.089) and LFS (46%, 27-66% vs 39%, 24-52%, p = 0.045) were better in FLAG-Ida-VEN. The relapse and NRM rates were similar between two groups. Other factors, significant in univariate analysis included remission status and donor type. In the multivariate analysis, CR at allo-SCT had significant independent impact on OS (HR 0.17, 0.08-0.35, p<0.0001), LFS (HR 0.18, 0.1-0.35, p<0.0001) and relapses (HR 0.19, 0.08-0.43, p<0.0001).

In addition, we performed an analysis (n = 77) focusing on remission status augmented by MRD. The 1 y OS for MRD^neg CR, MRD^pos CR and pts with non-CR was 93% (77-98%), 63% (40-81%) and 30% (16-49%, p<0.001), respectively. The 1-y LFS for MRD^neg CR, MRD^pos CR and pts with non-CR was 92% (76-98%), 59% (37-78%) and 21% (11-51%, p<0.001), respectively. The relapse rate at 1 y for MRD^neg CR, MRD^pos CR and pts with non-CR was 9% (2-39%), 21% (8-44%) and 55% (36-72%, p<0.001), respectively. In multivariate analysis, MRD^posCR and non-CR had adverse impact on OS (HR 5.2, 1.1-24.4, p = 0.035; HR 11.5, 2.7-49.9, p = 0.001; Wald test, p = 0.002), LFS (HR 2.9, 0.9-9.2, p = 0.076; HR 8.6, 2.9-25, p<0.001; Wald test, p<0.001) and relapses (HR 2.6, 0.5-14.2, p = 0.24; HR 10.1, 2.5-39.8, p<0.001; Wald test, p<0.001) compared to MRD^negCR, respectively.

Conclusions: Intensive venetoclax-based “bridging” regimen with FLAG-Ida is associated with higher CR rates than AZA-VEN, leading to overall better outcomes.

Disclosure: Nothing to declare.

19: Acute Leukaemia

László Gopcsa ¹, Hajnalka Andrikovics¹, Alexandra Balogh¹, Anikó Barta¹, Judit Bogyó², Zoltán Csukly¹, Katalin Dobos¹, János Dolgos¹, Apor Hardi¹, János Fábián¹, Laura Giba-Kiss¹, József Harasztdombi¹, Kinga Kerner¹, Ágnes Király¹, Gergely Lakatos¹, Viktor Lakatos¹, Lilla Lengyel¹, Nóra Meggyesi¹, Noémi Németh¹, Melinda Paksi¹, Laura Regáli¹, Marienn Réti¹, János Sinkó¹, Bálint Szabó¹, Anikó Szilvási², Éva Torbágyi¹, Andrea Várkonyi¹, Nikolett Wohner¹, István Vályi-Nagy¹, Péter Reményi¹

¹Central Hospital of Southern-Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary, ²The Hungarian National Blood Transfusion Service, Budapest, Hungary

Background: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) represents a curative therapeutic option for the treatment of patients suffering from acute leukemia. Moreover, the incidence of severe acute and extensive chronic GVHD in the case of Haplo-HSCT has proven to be more favorable compared to the other donor types. Currently, Haplo-HSCT with post-transplantation cyclophosphamide (PTCY) GVHD prophylaxis is considered the “gold standard” procedure. However, a less common approach to performing Haplo-HSCT involves ex-vivo T-cell depletion, employing various methods, with the most recognized being the use of a graft produced through TCRαβ + CD19 double-negative depletion (TCDαβ + CD19). Experiencies with pediatric HSCT using haploidentical grafts generated through TCDαβ + CD19 have been notable for their compelling outcomes. There is limited clinical experience in adult HSCT practice with this method.

Methods: In our retrospective analysis, we compared the outcomes of Haplo-HSCT performed between 2015 and 2022 for AML using PTCY (N = 60) and TCDαβ + CD19 (N = 28).

Results: In the PTCY group, 37 males (62%) and 23 females (38%) were included, with a median age of 50.5 years, while in the TCDαβ + CD19 group, there were 15 males (54%) and 13 females (46%) with a median age of 50 years. Mostly myeloablative conditioning regimens were used in both groups, primarily involving Thiotepa-Busulfan-Fludarabine and Thiotepa-Treosulfan-Fludarabine. All patients in the PTCY group received PTCY+tacrolimus+MMF GVHD prophylaxis. In the TCDαβ + CD19 group, 64% of patients did not received post-graft immunosuppression, however, GVHD prophylaxis was administered in 36% of cases (18% with MMF, 11% with tacrolimus, and 7% with ruxolitinib). The incidence of acute GVHD in the PTCY and TCDαβ + CD19 groups was 39% and 25%, respectively, with severe cases being 7% and 4%. The majority of acute GVHD cases were grade 2 and responded well to steroid treatment. The incidence of chronic GVHD in the PTCY and TCDαβ + CD19 groups was 31% and 21%, respectively. The extensive chronic GVHD was similar in the two groups (14% versus 10,5%). The relapse rates were low in both groups: 13% and 11%. Prolonged poor graft function was observed in 22% of patients receiving PTCY. Non-relapse mortality (NRM) was identical in both groups: PTCY and TCDαβ + CD19 34% and 28%, respectively. The overall survival (OS), disease-free survival (DFS), and refined GVHD-free and relapse-free survival (rGRFS) were more favorable in the TCDαβ + CD19 group: 61% and 53%, 61% and 51%, 53% and 46%.

Conclusions: The presented results are unique in terms of comparing both PTCY and TCDαβ + CD19 methods within one center. The OS, DFS, and GRFS were favorable with the TCDαβ + CD19 method, but larger studies are necessary for confirmation. Unlike in ALL, the occurrence of rejection with the TCDαβ + CD19 method does not significantly impact long-term outcomes. Therefore, the use of TCDαβ + CD19 method in AML can be safely employed, resulting in faster engraftment, shorter hospital stays, and a clearly lower incidence of poor graft function. The relapse rate was low in both patient groups, indicating a significant graft-versus-leukemia effect. The incidence of severe acute GVHD was low. Moreover, the use of post-graft maintenance therapeutic strategies in AML can further enhance long-term patient survival.

Disclosure: Disclosure of conflict of interest: None.

19: Acute Leukaemia

Turot Mélanie ¹, Loschi Michael², Chantepie Sylvain³, Arnautou Pierre⁴, Poire Xavier⁵, Maillard Natacha⁶, Chalandon Yves⁷, El-Cheikh Jean⁸, Ceballos Patrice⁹, Devillier Raynier¹⁰, Alani Mustafa¹¹, Fatrara Thomas¹², Rubio Thérèse¹³, Daguindau Etienne¹⁴, Klemencie Marion¹⁵, Beauvais David¹⁶, Huynh Anne¹⁷, Marchand Tony¹⁸, Volpari Victoria¹⁹, Barette Lauren¹⁹, Pivert Cécile²⁰, Maury Sébastien²¹, Suarez Felipe²², Fuseau Charline²³, Lauron Sandrine²⁴, Uzunov Madalina²⁵, Castilla Cristina²⁶, Forcade Edouard²⁷, Bay Jacques-Olivier¹, Ravinet Aurélie¹

¹Clermont-Ferrand University Hospital, Clermont-Ferrand, France, ²Nice University Hospital, Nice, France, ³Basse-Normandie Institute of Hematology, Caen, France, ⁴Percy Army Training Hospital, Clamart, France, ⁵Saint-Luc University Clinic, Uclouvain Bruxelles Woluwe, Belgium, ⁶Poitiers University Hospital, Poitiers, France, ⁷Geneva University Hospitals, Geneva, Switzerland, ⁸AUB Medical Center, Beyrouth, Lebanon, ⁹Montpellier University Hospital, Montpellier, France, ¹⁰Paoli-Calmettes Institute, Marseille, France, ¹¹Henri Becquerel Center, Rouen, France, ¹²Saint-Etienne University Hospital, Saint-Etienne, France, ¹³Nancy Regional and University Hospital, Nancy, France, ¹⁴Besançon University Hospital, Besançon, France, ¹⁵Anger University Hospital, Anger, France, ¹⁶Lille University Hospital, Lille, France, ¹⁷Toulouse Cancer University Institute, Toulouse, France, ¹⁸Rennes University Hospital, Rennes, France, ¹⁹Grenoble Alpes University Hospital, Grenoble, France, ²⁰Public Assistance - Paris Hospitals, Paris, France, ²¹Henri-Mondor Hospital Public Assistance - Paris Hospitals, Créteil, France, ²²Necker Hospital Public Assistance - Paris Hospitals, Paris, France, ²³Strasbourg Europe Cancer Institute, Strasbourg, France, ²⁴Edouard Herriot Hospital-Lyon Civil Hospices, Lyon, France, ²⁵La Pitié Salpêtrière Hospital Public Assistance - Paris Hospitals, Paris, France, ²⁶Gustave Roussy, Villejuif, France, ²⁷Bordeaux University Hospital, Bordeaux, France

Background: Despite the recent therapeutic progress, between 30 to 40 % patients relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) for acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). While Azacitidine and Venetoclax (VenAza) combination has been approved in previously untreated patients with AML ineligible for intensive induction therapy, VenAza associated with donor lymphocyte infusion (DLI) is also considered post-transplant as salvage therapy. However, limited data are available regarding outcomes with this specific setting.

Methods: To evaluate efficiency and safety of VenAza with/without DLI in relapsed myeloid malignancies after alloHSCT, we retrospectively collected data from January 1, 2016 to September 1, 2022 in 29 centers from the Société Francophone de Greffe de Moelle et Thérapie Cellulaire (SFGM-TC). We included 173 patients aged 18 years or older treated with the association of VenAza as salvage therapy for AML or MDS after one or more alloHSCT. The data were extracted from the ProMISe database, an international registry coordinated in part by the SFGM-TC.

Results: The median follow up after the transplant was 14 months. Out of the 173 patients, 152 (87,86%) had an AML including 11 cases of secondary acute myeloid leukemia, and 21 (12,14%) had a MDS. The median age at transplant was 53,78 (17,9 – 74,86). DLI was administered to 43 patients (24,86%) who relapsed after alloHSCT.76 patients (44,19%) experienced a relapse within 6 months after alloHSCT (defined as “early relapse”) and 96 patients (55,8%) relapsed more than 6 months after alloHSCT (“late relapse”).117 patients were treated with VenAza after their 1st relapse,39 after their 2nd and 6 after 3 or more relapses. The median number of VenAza cycles per patient was 2 (1-13) (Table 1). The median overall survival time estimate was 18,99 months with a 1-year overall survival (OS) of 62,45% (95% CI 55,52 - 70,23%) and a 2-years OS of 40,32 % (95% CI 33,21 – 48,95%). The median survival was longer (p = 0,001) for patients who were treated by VenAza for a late relapse with a 2-years OS of 62,96% (95% CI 53,60 – 73,96%) and 7,17% (95% CI 2,58-19,89%) for early relapses. The OS and EFS (P<0,001) were better in the DLI group. In multivariate analysis, survival remains better in DLI group. (HR = 0,57 (95% CI 0,36 – 0,92)). A total of 82,75 % patients relapsed after post-transplant VenAza and 10,90 % had a complete remission. Additionally, 17 patients (10,43%) developed chronic graft-versus-host disease (GVHC) after alloHCST, including 6 patients after venAza. The main causes of death were relapse or progression of the original disease (61,81%) and infections (21,18%).

Table 1. Patients’ characteristics.

Conclusions: Notwithstanding the retrospective nature, the results suggest that VenAza is an acceptable salvage therapy after alloHSCT and that the addition of DLI appears to improve survival with superior OS and EFS compared with non-DLI group, according to univariate and multivariate analysis.

Disclosure: Yves Chalandon. has received consulting fees for advisory board from MSD, Novartis, Incyte, BMS, Pfizer, Abbvie, Roche, Jazz, Gilead, Amgen, Astra-Zeneca, Servier; Travel support from MSD, Roche, Gilead, Amgen, Incyte, Abbvie, Janssen, Astra-Zeneca, Jazz, Sanofi all via the institution.

19: Acute Leukaemia

Zhu Huili ¹, Cao Xingyu¹, Lu Yue¹, Zhang Jianping¹, Zhao Yanli¹, Liu Deyan¹, Xiong Min¹, Sun Ruijuan¹, Liu Hongxing¹, Wei Zhijie¹

¹Hebei Yanda Lu Daopei Hospital, Langfang, China

Background: Acute graft-versus-host disease (aGVHD) is a common complication following allogeneic hematopoietic stem cell transplantation. Currently, the reported incidence of moderate to severe aGVHD in domestic cases is 13%-47%, while the incidence of grade III/IV aGVHD after haploidentical transplantation ranges from 7.9% to 13.8%. This study aims to analyze whether the administration of Brentuximab vedotin after transplantation can reduce the incidence of aGVHD without increasing disease relapse rates and viral infections.

Methods: A retrospective analysis was conducted on 50 pediatric leukemia patients who underwent haploidentical hematopoietic stem cell transplantation at our hospital between June 2017 and July 2022. These patients received prophylactic treatment with Brentuximab vedotin (20mg) on day +1 and day +4 post-transplantation. The median age of the patients was 4.1 years (range: 0.6-16.0 years). Among the cases, 22 were acute lymphoblastic leukemia (ALL), and 28 were acute myeloid leukemia (AML). Before transplantation, 28 patients were in CR1, 14 in CR2, 2 in CR3, and 6 in NR. All patients received myeloablative conditioning regimens, with 33 receiving Bu/Cy, 15 receiving TBI/Cy, 1 receiving Bu/Flu, and 1 receiving TBI/Flu. The median follow-up time was 29.1 months (range: 3.1-70.1 months). Detailed patient data are presented in Table 1.

Results: All 50 patients achieved 100% engraftment of white blood cells, with a median time of 15 days (range: +10 to +21 days). Platelet engraftment occurred in a median time of 9 days (range: +5 to +78 days), except for one patient who did not achieve platelet engraftment. The incidence of aGVHD after transplantation was 44%, with 28% experiencing grade I-II and 16% experiencing grade III-IV aGVHD. The incidence of CMV viremia was 40%, while the incidence of EBV viremia was 8%. During the follow-up period, five patients experienced disease relapse. Seven patients died during the follow-up, including 4 with AML and 3 with ALL. The causes of death were disease relapse in 3 cases, infection in 2 cases, TMA in 1 case, and cGVHD in 1 case. The estimated 5-year overall survival (OS) and leukemia-free survival (LFS) rates were 86%, and the 5-year cumulative relapse rate was 10%. In comparison, a control group of 44 pediatric acute T-cell lymphoblastic leukemia patients who underwent haploidentical transplantation without prophylactic Brentuximab vedotin treatment between January 5, 2021, and June 30, 2022, were analyzed. In the control group, the incidence of aGVHD was 56.8% (P = 0.007), with 36.4% experiencing grade I-II and 20.4% experiencing grade III-IV aGVHD. The incidence of CMV viremia was 68.2% (P = 0.006), and the incidence of EBV viremia was 29.5% (P = 0.007). The relapse rate was 15.9%, and the mortality rate was 27.3%.

Conclusions: For pediatric acute leukemia haploidentical HSCT, the administration of Brentuximab vedotin (20mg) on days +1 and +4 after transplantation, in addition to conventional aGVHD prophylaxis (CsA+MMF+sMTX), significantly reduced the overall incidence of aGVHD and grade I-II aGVHD. Administering Brentuximab vedotin on days +1 and +4 did not increase the rates of CMV or EBV infection nor did it increase the risk of disease relapse.

Disclosure: Nothing to declare.

19: Acute Leukaemia

Jochen J. Frietsch ^1,2, Sarah Flossdorf^3,4, Ashrafossadat Ahmadian^3,4, Claudia Schuh³, Thomas Schroeder⁵, Igor-Wolfgang Blau⁶, Matthias Stelljes⁷, Nicolaus Kröger^3,8, Katharina Egger-Heidrich⁹, Matthias Eder¹⁰, Peter Dreger¹¹, Johanna Tischer¹², Eva Wagner-Drouet¹³, Rita Beier^14,15, Peter Bader¹⁶, Martin Sauer¹⁵, Barbara Meissner^14,15, Katharina Fleischhauer^3,17, Inken Hilgendorf²

¹Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany, ²Klinik für Innere Medizin II, Hämatologie und internistische Onkologie, Universitätsklinikum Jena, Jena, Germany, ³Deutsches Register für hämatopoetische Stammzelltransplantation und Zellherapie e.V., Ulm, Germany, ⁴Institut für Medizinische Informatik, Biometrie und Epidemiologie, Uniklinikum Essen, Essen, Germany, ⁵Klinik für Hämatologie und Stammzelltransplantation, Universitätsklinikum Essen, Essen, Germany, ⁶Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Campus Virchow-Klinikum, Berlin, Germany, ⁷Medizinische Klinik A, Hämatologie, Hämostaseologie, Onkologie und Pneumologie, Universitätsklinikum Münster, Münster, Germany, ⁸Klinik für Stammzelltransplantation, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany, ⁹Medizinische Klinik I, Universitätsklinikum Carl Gustav Carus, Dresden, Germany, ¹⁰Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany, ¹¹Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany, ¹²Medizinische Klinik und Poliklinik III, Klinikum der Ludwig-Maximilians-Universität München, München, Germany, ¹³III. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Germany, ¹⁴Pädiatrisches Register für Stammzelltransplantationen und Zelltherapien, Hannover, Germany, ¹⁵Klinik für Pädiatrische Hämatologie und Onkologie, Medizinische Hochschule Hannover, Hannover, Germany, ¹⁶Klinik für Kinder- und Jugendmedizin, Studienzentralen der Schwerpunkte Onkologie, Hämatologie und Hämostaseologie sowie Stammzelltransplantation, Immunologie und Intensivmedizin, Universitätsklinikum Frankfurt, Frankfurt, Germany, ¹⁷Institut für Zelltherapeutische Forschung, Universitätsklinikum Essen, Essen, Germany

Background: The survival after allogeneic hematopoietic SCT is influenced by the patients’ age, diagnosis, donor type and achieved remission. Nevertheless, with a 5-year overall survival (OS) probability of 53%, the outcome of young adults (YA) aged 18 to 39 years is sobering. We sought to provide more detail on outcome by focusing on acute leukemia (AL).

Methods: The German Registry for Hematopoietic Cell Transplantation and Cellular Therapy (DRST) and the German Pediatric Registry for Stem Cell Transplants and Cell Therapies (PRSZT) were screened for patients suffering from AL who received 1^st SCT between 2011 and 2019. OS rates were determined by Kaplan-Meier analysis and differences between were evaluated using Score-tests (corresponding to the log-rank test, computed when Hazards are not crossing). Gray’s test was applied to cumulative incidence of NRM using competing risk analysis. To separate relapse from progression, patients not being in complete remission at the time of SCT or within 100 days were excluded from competing risk analysis. A p-value of <0.05 was considered statistically significant.

Results: Altogether 11258 patients were included, with 573, 269, 2158, 4667 and 3591 in the age groups 0-12, 13-17, 18-39, 40-59 and 60-72 years at the time of SCT, respectively. 2424 (21.5%) suffered from acute lymphoblastic leukemia (ALL) and 8834 (78.5%) from acute myeloid leukemia (AML). The majority (89.6%, 10089) of the predominantly male (56.2%, 6331) patients received peripheral blood SCT from a related (28.4%, 3192) or an unrelated (71.6%, 8066) donor with varying degrees of histocompatibility. During the observation period, 4380 (38.9%) patients deceased.

The probability of 5-year OS decreased for AML with increasing patient age: 0-12: 69%; 13-17: 60%; 18-39: 57%; 40-59: 49%; and 60-72 years: 37% and for ALL: 0-12: 73%; 13-17: 71%; 18-39: 53%; 40-59: 51%; and 60-72 years: 37%. Statistically significant differences in the probability of 5-year OS were observed between related and unrelated donors for AML (48% vs. 46%, p = 0.0018), but not for ALL (52% vs. 57%). No statistically significant differences could be observed concerning gender for AML (♀ 49% vs. ♂ 45%, p = 0.0508) and ALL (♀ 57% vs. ♂ 55%).

The 5-year-NRM increased with patient age for both ALL (0-12: 7%; 13-17: 10%; 18-39: 19%; 40-59: 26% and 60-72: 30%; p<0.001) and AML (5%; 14%; 12%; 20% and 30%; p<0.001). The 5-year relapse rate in both entities was lower for 13-17 year old adolescents (AML/ALL 13-17: 26%/18%) than for the other age groups (0-12: 33%/28%, 18-39: 40%/31%, 40-59: 34%/28%, 60-72: 35%/32%).

Conclusions: In this preliminary large retrospective multicenter analysis we show that NRM increases with patient age which also negatively impacts OS. The heterogeneity of the cohort was taken into account by considering diseases separately and age in groups. As differences in patient outcome are being reflected by a distinct disease biology, further investigations are necessary to fully elucidate differences between AML and ALL in age-dependent survival. The increasing NRM with respect to age underlines the relevance of interdisciplinary collaboration between pediatricians and non-pediatricians for the improvement of aftercare concepts, especially for children, adolescents and YA.

Disclosure: IH is chairperson of the board of trustees of the German Foundation for Young Adults with Cancer, received research funding from the H.W. and J. Hector-Foundation and honoraria from AbbVie, Medac, Novartis and Takeda. JF received honoraria from Novartis. All other authors do not declare any conflicts of interest. The Cooperative German Transplant Study group is acknowledged for project development and support.

19: Acute Leukaemia

Ivan Moiseev ¹, Olga Epifanovskaya¹, Ksenia Afanasyeva¹, Anastasia Beynarovich¹, Dmitrii Zhogolev¹, Mikhail Kanunnikov¹, Yulia Rogacheva¹, Tatyana Rudakova¹, Nikita Volkov¹, Zhamshidbek Khudaiberdiev¹, Azamjon Meliboev¹, Yulia Vlasova¹, Elena Morozova¹, Sergei Bondarenko¹, Alexander Kulagin¹

¹RM Gorbacheva Research Institute, Pavlov University, Saint Petersburg, Russian Federation

Background: Efficacy of allogeneic hematopoietic stem cell transplantation (alloHCT) in disease progression of myeloid neoplasms resistant to chemotherapy or targeted therapy is low. Our group recently demonstrated an enhanced graft-versus-leukemia (GVL) effect when replacing cyclophosphamide with bendamustine in a graft-versus-host disease (GVHD) prophylaxis regimen (Moiseev IS et al., TCT, 2021), but there was significant toxicity from this regimen from a poorly controlled cytokine release syndrome (CRS). To reduce toxicity while preserving GVL, we conducted a pilot single-center study of graft-versus-host disease (GVHD) prevention with a combination of cyclophosphamide and bendamustine in refractory myeloid neoplasms.

Methods: Prospective single-center Phase I/II study (NCT04943757) enrolled 50 patients (table 1). Inclusion criteria were myeloid neoplasm, available hematopoietic cell donor, >5% clonal blasts at the start of conditioning, disease refractory to at least one course of induction therapy. Main exclusion criteria: absence of uncontrolled infection and severe concomitant co-morbidities. The protocol included the administration of bendamustine 50 mg/kg/day on days +3, + 4, cyclophosphamide 25 mg/kg/day on days +3, + 4 (PTBC), tacrolimus 0.03 mg/kg from day+5 to day+ 100 day and mycophenolate mofetil 30 mg/kg/day on days 5-35. Patients received FB2 or FB3 conditioning regimen according to their age and performance status.

Results: The cumulative engraftment rate was 86%. Only 1 patient died before engraftment assessment. The median time to recovery of white blood cells was 18 days (range 12-35), platelets - 14 days (range 9-104). Remission was achieved in 88% of patients, with 76% of patients negative for minimal residual disease (MRD). Overall survival (OS) was 33% (95%CI 19-48%), event-free survival (EF) - 21% (95%CI 10-35%). Non-relapse mortality (NRM) was 19% (95%CI 9-31%), cumulative relapse incidence was 60% (95%CI 43-74%). Toxicity included development of CRS in 30% of patients, including 2 patients with grade 4-5 CRS. The most common manifestation of CRS was fever, increased ferritin and abnormal liver function tests (24% of patients). The cumulative incidence of grade II-IV acute GVHD was 20% (95%CI 10-33%), grade III-IV – 18% (95%CI 7-31%), moderate and severe chronic GVHD - 18% (95%CI 8 -31%). Grade II-IV acute GVHD was observed predominantly in patients with CRS grades 2-5 (31% vs. 16%, p = 0.02). Survival subanalysis showed that unrelated or haploidentical donor transplantation was associated with better OS (40% vs 0%, p = 0.008). Unique tolerance mechanisms were revealed with a massive expansion of PD-1L positive monocytes by day +30 (17.7±10.9% of all nucleated cells [NC]) with a decline to 7.1±4.3% and 6.9±6.5% of NC by days +60 and +100 (p<0.001). The level of PD-1L granulocytes was also high: 13.2±10.9%, 8.1±9.4% and 9.0±9.0% of NC on days 30, 60 and 100 (p = 0.4). This was accompanied by rapid expansion of effector T-cells (p<0.001), effector memory T-cells (p<0.001), central memory T-cells (p<0.001), naive T-cells (p<0.0001) and CD197-positive activated T-cells (p<0.0001) early post-transplant. In several patients abnormally high levels of monocytes and lymphocytes persisted for 2 years after HCT.

Conclusions: We developed a promising alloHCT platform for refractory myeloid neoplasms with a unique immunological recovery profile.

Clinical Trial Registry: NCT04943757, clinicaltrials.gov

Disclosure: The study was supported by RSF grant №23-15-00327.

19: Acute Leukaemia

Francesca Biavasco ¹, Kristina Maas-Bauer¹, Jesus Duque-Afonso¹, Ralph Waesch¹, Michael Luebbert¹, Justus Duyster¹, Robert Zeiser¹, Juergen Finke¹, Claudia Wehr¹

¹University Hospital Freiburg, Freiburg, Germany

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) has become an accessible curative option in elderly patients with acute myeloid leukemia (AML) after development of reduced-intensity conditioning regimen and the introduction of hypomethylating agents (HMA) with venetoclax as induction therapy for elderly unfit patients. While a recent prospective randomised trial showed non-inferior efficacy and better tolerance of HMA over standard chemotherapy in elderly patients, only half of the studied cohort underwent allo-HCT and venetoclax was not included in the study (Luebbert et al., Lancet Haematol. 2023 Nov;10(11):e879-e889). Therefore, real-world data on outcomes of patients not eligible for intensive chemotherapy who received allo-HCT in the venetoclax era are needed.

Methods: We retrospectively analysed data of 106 adult AML patients who underwent allo-HCT without receiving intensive chemotherapy at our center between 2010 and 2023.

Results: Forty-two patients received HMA alone, 24 patients received HMA-venetoclax induction therapy, and 40 patients underwent allo-HCT without previous therapy (upfront) due to personalised clinical decision. Patients who received allo-HCT upfront were younger (median 59.1 years) than HMA (64.9 years) and HMA-venetoclax patients (70.9 years respectively, p<0.0001). The groups did not differ in Karnofsky performance status, ELN risk distribution and time from diagnosis to allo-HCT. Forty-three of the HMA treated (83%) and 15 of the HMA-venetoclax treated patients (62%) did not achieve CR before allo-HCT, resulting in a similar mean blast count before transplantation among groups (41.4 for upfront, 26.5 for HMA and 32.2 for HMA-venetoclax). With a median follow-up of 85.5, 75.4 and 18.9 months in upfront, HMA treated and HMA-venetoclax treated patients, the overall survival at median follow-up time (19 months) was 75.7%, 54.8% and 89.0% respectively, showing a better survival for patients treated with addition of BCL-2 inhibitor. Interestingly, the difference in survival was not reflected in marked difference of progression free survival, which was similar among groups (19-months progression free survival 77.8% upfront, 72.3% HMA and 73.9% HMA-venetoclax). Of note, overall survival benefits for HMA-venetoclax treated patients persisted in the subgroup of patients who did not reach a complete remission before transplant (19-months overall survival for HMA 51.5%, for HMA-venetoclax 82.3%). As expected though, the achievement of a complete remission before allo-HCT was associated with a better survival in both groups (19-months overall survival HMA CR 66.7%, HMA non-CR 51.5% vs. HMA-venetoclax CR 100%, HMA-venetoclax non-CR 82.3%).

Conclusions: These real-world retrospective data on the avoidance of intensive chemotherapy in pre-transplant setting suggest that HMA-venetoclax could be the best therapeutic option for patients with AML. Additionally, the advantage of HMA-venetoclax was independent from achieving CR, even though the achievement of CR is associated with better survival. Confirmatory data of prospective randomised trials are urgently needed to establish the best possible pre-transplant treatment for non-highly proliferating AML patients.

Disclosure: K. M-B is supported by a fellowship of the Faculty of Medicine, Freiburg University (Berta-Ottenstein-Programm) and by the Else-Kröner-Fresenius-Stiftung Nr: 2021_EKEA.131

R.W. received research fundings from Janssen, Sanofi, consultancy: from Amgen, BMS/Celgene, Janssen, Kite/Gilead, Novartis, Pfizer, Sanofi, Takeda, honoraria from Abbvie, Alexion/Astra Zeneca, Amgen, BMS/Celgene, Janssen, Kite/Gilead, Novartis, Pfizer, Sanofi, Takeda and travel support from Janssen, Kite/Gilead, Pfizer, BMS.

C.W. received honoraria/travel grant from Takeda and Jazz Pharmaceuticals.

19: Acute Leukaemia

Srividhya Senthil ¹, Abdul Moothedath¹, Archana Rauthan², Ioannis Peppas³, Sandeep Potluri⁴, Pamela Evans⁵, Valerie Broderick⁵, Sarah Lawson⁴, Emma Barrett⁶, Caroline Furness⁷, Kanchan Rao², Robert Wynn¹

¹Royal Manchester Children’s Hospital, Manchester, United Kingdom, ²Great Ormond Street Hospital, London, United Kingdom, ³Kings College Hospital NHS Foundation Trust, London, United Kingdom, ⁴Birmingham Children’s Hospital, Birmingham, United Kingdom, ⁵Royal Crumlin Hospital, Dublin, Ireland, ⁶Manchester University Foundation Trust, Manchester, United Kingdom, ⁷Royal Marsden Hospital, Manchester, United Kingdom

Background: Ciclosporin forms the major GVHD prophylaxis in allogeneic stem cell transplantation. It might be expected to reduce the beneficial graft-versus-leukemia [GVL] effect, and previous studies have reported a relationship between ciclosporin exposure and risk of post-transplant relapse in leukaemia. T cell replete Cord blood (TRCBT) HSCT might be considered the preferred donor cell source in AML with superior GVHD-free, Relapse-free survival (RFS). We report a multicentric experience of the relationship between ciclosporin exposure and time to relapse in a large cohort of paediatric AML patients receiving such a graft.

Methods: It is a retrospective study, data was collected from 5 paediatric transplant centers in the UK on the patients who had a TRCBT for HR AML between 2013 and 2023. Case records were analyzed to get patient, donor, transplant characteristics, GVHD prophylaxis, trough ciclosporin levels in the first 8 weeks and the transplant outcomes including GVHD and its treatment, relapse and transplant related mortality (TRM). The primary endpoint was time to disease relapse, and the relationship between this endpoint and ciclosporin AUC, use of additional immunosuppressive treatment (IST) and its total duration was investigated by Cox regression analysis.

Results:

The cohort included 108 patients, of whom 64 were MRD-positive pre-transplant, with a median follow up of 737.1 days (range: 24-3540 days). All were given ciclosporin and MMF as GVHD prophylaxis for a variable duration post-transplant according to each centers’ protocol. The severe aGVHD was treated with IST which included steroids in all with or without second agents.

The mortality rate was 40.7% of which nearly three-quarters occurred in the MRD-positive group. Overall, relapse formed the leading cause of death, causing 68.7% of the total deaths in MRD-positive group. It constituted only 41.6% of the deaths in the MRD negative group. The median time to relapse was 180 days (range: 32 to 949) and nearly a third occurred very early within 6 months. TRM was 13% and accounted for the most prominent cause of mortality in MRD-negative group. The GVHD related mortality was very low.

The RFS is significantly greater in MRD-negative group without severe aGVHD than in those without. By comparison, the RFS is significantly lower in the MRD-positive group without severe aGVHD than in those with it. The COX proportional hazards model using 95% CI confirmed a significant inverse relationship of AUC of Ciclosporin in the first 8 weeks on the time to relapse (p<0.02). However, it did not find any effect of IST or the duration of IST on time to relapse (p = 0.579 and p = 0.623 respectively).

Conclusions: This is the largest homogenous cohort of TRCBT in AML investigating the role of ciclosporin prophylaxis on relapse. It confirms the importance of GVL effect and its relation to GVHD in MRD-positive patients as RFS is significantly better in those who experience aGVHD. Most relapse is early and increased ciclosporin exposure in the first 2 months of HSCT reduces the time to relapse in AML. This study supports the development of novel protocols and alternative IS regimens during CBT in the highest risk AML.

Clinical Trial Registry: Not applicable

Disclosure: The authors have no conflict of interest.

19: Acute Leukaemia

Dmitrii Zhogolev¹, Bella Aybova¹, Anna Smirnova¹, Yulia Vlasova¹, Daria Chernyshova¹, Elena Babenko¹, Tatyana Gindina¹, Ildar Barkhatov¹, Elena Morozova¹, Ivan Moiseev ¹, Sergey Bondarenko¹, Alexander Kulagin¹

¹RM Gorbacheva Research Institute, St. Petersburg, Russian Federation

Background: For the majority of patients with acute myeloid leukemia (AML), allogeneic hematopoietic stem cell transplantation (alloHSCT) remains as the sole curative option. Recent advancements in transplant technologies, such as post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis, have enhanced the overall outcomes of alloHSCT. It is well-established that patients refractory to 2 induction courses, even with subsequent remission achievement, exhibit poorer outcomes after alloHSCT. However, the impact of refractoriness to the first induction course remains unclear, particularly within the context of PTCy.

Methods: A total of 260 adult patients with AML in first complete remission (CR1), who underwent alloHSCT at RM Gorbacheva Research Institute (CIC 725) from 2013 to 2022 were included in this retro- and prospective study. All participants received the “7 + 3” regimen as their initial induction therapy. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free survival (GRFS) were assessed using the Kaplan-Meier method and log-rank test. Multivariate analysis was conducted utilizing a Cox regression model. To estimate relapse incidence (RI) and non-relapse mortality (NRM) within a competing risk framework, cumulative incidence functions were applied.

Results: Achievement of CR1 occurred after 1 induction course in 158 patients, after 2 induction courses in 68 patients, and after more than 2 induction courses in 34 patients. Groups were balanced on key parameters, with the exception of a higher incidence of secondary AML in the non-refractory group (p = 0.026) and a higher prevalence of unfavorable cytogenetics in the 2 courses refractory group (p = 0.041) (Table 1).

Table 1. Patient, disease and transplant characteristics.

Median follow up after alloHSCT in survivors was 42.3 (3-108.5) months. Engraftment on d28 was attained in 86% (95%CI, 80-91), 90% (95%CI, 79-95), and 88% (95%CI, 70-96) in the non-refractory, refractory to 1, and refractory to 2 courses groups, respectively (p = 0.8). Three-year OS rates were 81.7% (95%CI, 75.7-88.1), 66.5% (95%CI, 55.6-79.5), and 60.1% (95%CI, 44.5-81.2) (p = 0.038), LFS – 78.6% (95%CI, 72.2-85.5), 66.8% (95%CI, 56-79.8), and 40.5% (95%CI, 25.3-64.8) (p<0.001), GRFS – 69.3% (95%CI, 62.2-77.2), 49.5% (95%CI, 38.6-63.6), and 36.5% (95%CI, 22.3-59.8) (p<0.001). The cumulative incidence of NRM at three years was 14% (95%CI, 8.7-19), 16% (95%CI, 8-26), and 19% (95%CI, 7.3-34) (p = 0.8), RI – 7.9% (95%CI, 4.1-13), 17% (95%CI, 9.1-28), and 41% (95%CI, 22-59) (p<0.001). There was no significant statistical difference in aGVHD grades 2-4 (p = 0.22) and grades 3-4 (p = 0.074), cGVHD grades 1-3 (p = 0.93) and grades 2-3 (p = 0.61) incidence.

In the multivariate analysis, failure to achieve remission after one “7 + 3” course was associated with lower OS (HR 1.97, p = 0.02) and GRFS (HR 1.96, p = 0.004) after alloHSCT, with a tendency for lower LFS (HR 1.72, p = 0.056). Age and refractoriness to 2 induction courses were also associated with lower OS, LFS, and GRFS.

Conclusions: This study highlights the failure to respond to one “7 + 3” course as a negative prognostic factor for both OS and GRFS after alloHSCT, when performed with PTCy. The findings underscore the necessity for novel treatment approaches to enhance survival outcomes in these patients. Additionally, there is a crucial need for improved strategies in patients with primary refractory AML and older patients.

Disclosure: Nothing to declare.

19: Acute Leukaemia

Eshrak Al-Shaibani ¹, Carol Chen¹, Igor Novitzky-Basso^1,2, Ivan Pasic^1,2, Auro Viswabandya^1,2, Rajat Kumar^1,2, Wilson Lam^1,2, Arjun Law^1,2, Armin Gerbitz^1,2, Jonas Mattson^1,2, Fotios V. Michelis^1,2, José-Mario Capo-chichi³, Dennis D. Kim^1,2

¹Hans Messner Allogeneic Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, Canada, ²University of Toronto, Toronto, Canada, ³University Health Network and University of Toronto, Toronto, Canada

Background: Post-allogenic hematopoietic cell transplantation (HCT) maintenance therapy with tyrosine kinase inhibitor (TKI) in Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) is expected to reduce the risk of relapse. However, clinical benefit from the post-HCT TKIs maintenance (PTM) in Ph+ALL remains still on debate due to conflicting results from the retrospective studies and lack of randomized controlled trial. Herein, we report the long-term outcomes of the patients who received PTM following allogeneic HCT versus not in Ph+ALL.

Methods: We have retrospectively reviewed 80 patients with Ph+ ALL underwent first HCT in complete remission at Princess Margaret Cancer Center from 2000 till 2022. Relapse was defined as morphologic recurrence of ≥5% blasts in bone marrow or by the presence of extramedullary disease. Overall (OS), graft-versus host disease (GVHD)/relapse-free (GRFS) and relapse-free survival (RFS) was calculated by the Kaplan-Meier method and analyzed using a log-rank test, respectively. Cumulative incidence of relapse (CIR), non-relapse mortality (NRM) and chronic GVHD (cGVHD) were calculated considering competing events and analyzed using Fine-Gray model.

Results: Patients’ and disease characteristic are summarized in Table 1. With a median follow-up duration of 26 months among survivors, 16 patients (20%) had progressed following HCT. Fifty-eight patients (72%) did not receive PTM while 22 (28%) patients received PTM. The median time to start PTM was 5.3 months (range; 2.6-9.2) with imatinib (n = 15), dasatinib (n = 5) or ponatinib (n = 4). ABL1 kinase-domain mutation (KDM) was detected in 8 patients: T315I (n = 2), F317L (n = 3), E255K (n = 1), Y253H (n = 1), Q252H (n = 1).

The analysis for OS, GRFS, RFS, NRM, cGVHD and CIR at 2 years showed improved outcomes in favor of PTM: OS, 81% vs 43.4% (p = 0.01); GRFS, 40% vs 5.3% (p = 0.003); RFS, 81% vs 43.4% (p = 0.02); NRM, 4.8% vs 45.8% (p = 0.003); cGVHD 27.7% vs 41.3% (p = 0.54); CIR, 14.3% vs 10.8% (p = 0.19).

Univariate analysis showed PTM improved OS (HR; 0.39 [0.19-0.85], P = 0.02), RFS (HR: 0.54 [0.29-0.99], P = 0.03), GRFS (HR: 0.41 [0.23-0.75], P = 0.004) and NRM (HR: 0.045 [0.003-0.20], P = 0.003). However, it was not associated with relapse risk (HR: 0.143 [0.03-0.33], P = 0.19).

Besides PTM, age >40 was associated with OS (HR: 2.08 [1.11-3.9], P = 0.02), RFS (HR: 1.85 [1.01-3.37], P = 0.05) and NRM (HR: 0.41 [0.27-0.55], P = 0.04). Time -dependent cGVHD found to be associated with improved OS (HR: 0.36 [0.16-0.78], P = 0.009), RFS (HR: 0.31 [0.14-0.68], P = 0.003) and CIR (HR: 0.1522 [0.04-0.54], P = 0.004). Detectable ABL-KDM at ant time prior-HCT increased risk of relapse (HR: 0.38 [0.07-0.69], P = 0.0005).

Multivariable analysis confirmed that PTM improved OS (HR; 0.28 [0.13-0.62], P = 0.02], RFS (HR: 0.32 [0.15- 0.68], P = 0.003), GRFS (HR: 0.41 [0.23-0.75], P = 0.004) and NRM (HR:0.18 [0.06-0.57], P = 0.003). cGVHD also found to improve OS (HR: 0.28 [0.13-0.64], P = 0.002), PFS (HR: 0.23 [0.10-0.51], P = 0.003) and decreased CIR (HR: 0.33 [0.09-1.14], P = 0.08).

Table 1: patients characteristics

Conclusions: PTM in Ph+ALL delivers a clinical benefit toward better OS, improved RFS, decreased NRM and better GRFS. However, it was not confirmed whether PTM can reduce the risk of relapse.

Disclosure: Nothing to declare

19: Acute Leukaemia

Matthieu Jestin¹, Sébastien Maury², Anne Huynh³, Edouard Forcade⁴, Ibrahim Yakoubagha⁵, Cristina Castilla-Llorente⁶, Jean-Baptiste Mear⁷, Urs Schanz⁸, Sylvain Chantepie⁹, Jakob Passweg¹⁰, Nathalie Contentin¹¹, Yves Chalandon¹², Nicole Raus¹³, Véronique Lheritier¹³, Natacha Maillard¹⁴, Marie-Thérèse Rubio¹⁵, Raynier Devillier¹⁶, Patrice Ceballos¹⁷, Sylvie François¹⁸, Stéphanie Nguyen-Quoc¹⁹, Patrice Chevallier²⁰, Hélène Labussière-Wallet¹³, Hervé Dombret¹, Nicolas Boissel¹, Nathalie Dhédin ¹

¹Hôpital Saint Louis, Paris, France, ²Hôpital Henri Mondor, Créteil, France, ³Institut universitaire du Cancer de Toulouse, Toulouse, France, ⁴CHU de Bordeaux, Bordeaux, France, ⁵CRHU Lille, Lille, France, ⁶Institut Gustave Roussy, Villejuif, France, ⁷CHU de Rennes, Rennes, France, ⁸Hôpital Universitaire de Zurich, Zurich, Switzerland, ⁹CHU de Caen, Caen, France, ¹⁰Hôpital Universitaire de Bâle, Bâle, Switzerland, ¹¹Centre Henri Becquerel, Rouen, France, ¹²Hôpitaux Universitaires de Génève, Génève, Switzerland, ¹³CHU de Lyon, Lyon, France, ¹⁴CHU de Poitiers, Poitiers, France, ¹⁵CHRU de Nancy, Nancy, France, ¹⁶Institut Paoli-Calmettes, Marseille, France, ¹⁷CHU de Montpellier, Montpellier, France, ¹⁸CHU d’Angers, Angers, France, ¹⁹Hôpital Pitié-Salpétrière, Paris, France, ²⁰CHU de Nantes, Nantes, France

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) stands as a cornerstone in managing high-risk (HR) Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) in the first complete remission (CR1). Whereas unrelated donor (UD) has become a standard option in absence of matched sibling donor (MSD), peripheral blood (PB) is mostly used despite a higher incidence of graft-versus-host disease (GVHD). The aim of this study was to evaluate the impact of donor and stem cell source in adults with HR Ph-negative ALL in CR1 prospectively included in the GRAALL-2003 and -2005 trials.

Methods: Between November 2003 and March 2014, 311 patients with HR Ph-negative ALL in CR1 were included in the GRAALL-2003/05 trials and received a HSCT from MSD or UD after a myeloablative conditioning (MAC) regimen. Cord blood (n = 17) or haploidentical transplant (n = 2) were excluded. The primary objective was to assess the impact of donor and stem cell source on acute grade III-IV or chronic extensive GVHD-free relapse-free survival (GRFS). Type of donor (MSD versus UD), use of anti-thymocyte globulin (ATG) and total body irradiation (TBI), stem cell source (PB versus bonne marrow (BM)) and age at transplant were included in univariate and multivariate analyses for GRFS, overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), incidence of aGVHD grade III-IV and of extensive cGVHD.

Results: Among the 311 patients, 100 had a T-ALL and 211 a Ph-negative BCP-ALL. Median age at transplant was 31.8 years (IQR, 29.7 – 34.5) with 60% of male. All received a MAC regimen, 293 (94%) a TBI-based, 14 (5%) a busulfan-based, and 4 another regimen. Transplant was performed from a MSD in 156 patients (50%) and from a 9/10 or 10/10 matched UD in 155 patients (50%). PB and BM were used in 105 patients (34%) and 206 patients (66%), respectively. ATG was part of the conditioning regimen in 58 patients (19%). In univariate and multivariate analysis for GFRS, after adjustment on age at transplant, use of ATG and TBI, and type of donor, stem cell source (PB vs BM) emerges as the sole variable significantly associated with GRFS (Table). Of note, the type of donor and the use of ATG did not show significant association with GRFS, and also lacked significant correlation with OS, EFS, CIR, TRM, cGVHD and aGVHD. In multivariate analysis using the same covariates, PB was significantly associated with an increased risk of NRM (SHR 2.03, 95%CI(1.19-3.48)), an increased incidence of cGVHD (SHR 3.20, 95%CI(1.79-5.76)) and a decreased CIR (SHR 0.51, 95%CI(0.27-0.96)), but did not correlate with OS and EFS. Interestingly, in sub-groups analysis, GRFS was significantly improved using BM versus PB from UD (HR 2.25, 95%CI(1.46-3.47)) whereas no impact of stem cell source was observed in transplant from MSD.

Conclusions: In adults with HR Ph-negative ALL in CR1, PB and BM are two acceptable options when a MSD is available. Despite the absence of impact of stem cell source on OS, the use of UD BM should be preferred over PB, since it improves long-term quality of life.

Clinical Trial Registry: NCT00327678

Disclosure: Nothing to declare.

19: Acute Leukaemia

Alessandro Bruno¹, Matteo Giovanni Carrabba¹, Simona Piemontese¹, Raffaella Greco¹, Sarah Marktel¹, Sara Mastaglio¹, Daniela Clerici¹, Francesca Farina¹, Elisa Diral¹, Luca Vago¹, Lorenzo Lazzari¹, Edoardo Campodonico¹, Giulia Furnari¹, Alessandro Criscimanna¹, Chiara Secco¹, Magda Marcatti¹, Consuelo Corti¹, Massimo Bernardi¹, Jacopo Peccatori¹, Fabio Ciceri^1,2, Maria Teresa Lupo-Stanghellini ¹

¹IRCCS Ospedale San Raffaele, Milan, Italy, ²Università Vita-Salute San Raffaele, Milan, Italy

Background: Acute myeloid leukemia (AML) is the most frequent indication for allogeneic hematopoietic stem cell transplant (allo-HSCT). The number of patients undergoing allo-HSCT for AML has steadily increased in the last decades, with improving outcomes. Both the incidence of disease relapse and treatment related mortality (TRM) decrease over time after transplant. While risk factors for disease relapse and TRM in the first years after allo-HSCT are well known, their correlation with long-term survivorship is unclear.

Methods: We retrospectively collected data of 456 consecutive patients (193 females and 263 males) with a diagnosis of AML who received a first allogeneic hematopoietic stem cell transplant in our centre between 2004 and 2019. Ninety-six patients had a matched related donor, 221 a mismatched related donor, 120 an unrelated donor and 19 underwent allo-HSCT from a cord blood unit. Sixty-four (14%) patients had secondary AML. Patients were included regardless of conditioning intensity and graft-versus-host disease (GvHD) prophylaxis. Two hundred and four patients (44%) received allo-HSCT in first complete remission (CR1), 62 patients (14%) in CR>1, and 190 patients (42%) in active disease (AD). Factors impacting on long-term survival after allo-HSCT were evaluated through a multivariate analysis using Cox proportional-hazards model in the whole cohort and subsequently in landmark analysis at 1, 2 and 3 years after allo-HSCT.

Results: Two-hundred and thirty-nine patients (52%) were alive 2 years after allo-HSCT, with a median follow-up of 5.1 years. In this subset, 51 patients died (21%) during subsequent follow-up: 31 of progressive disease (13%), 18 of treatment related complications (8%) and two due to unknown causes (1%), while 15 patients were lost at follow-up (6%). As expected, a better 5-years overall survival (OS) was observed in the overall cohort among patients in CR1 (63%) in comparison to patients in CR>1 (38%) or AD (25%). Nevertheless, in the landmark analysis the impact of disease status on long-term survival was progressively less meaningful: for example, for patients alive at 2 years landmark, the probability of being alive for 3 more years was 86% for patients in CR1, 72% for patients in CR>1 and 79% for patients in AD, with no statistically significant difference between CR>1 and AD. Similar results were found for progression free survival (PFS), TRM and relapse risk. Of note, better long-term outcomes in the overall cohort were associated with younger patient age, allo-HSCT performed after 2013 and using a female donor for a male recipient. Only being younger was still significantly associated with better outcomes in the various landmark analysis. Furthermore, our study confirmed that relapse is still the main cause of death even for long-term survivors: 13% of patients alive at 2 years eventually relapsed.

Conclusions: In conclusion, the negative impact on outcomes of a more advanced disease at allo-HSCT seems to decline progressively after transplant, fostering the importance of strategies that may enhance the anti-leukemic effect of allo-HSCT in the following first months and years.

Disclosure: Nothing to declare.

19: Acute Leukaemia

Gele Tong ¹, Yanli Zhao¹, Jianping Zhang¹, Min Xiong¹, Xingyu Cao¹, Deyan Liu¹, Ruijuan Sun¹, Zhijie Wei¹, Jiarui Zhou¹, Yue Lu¹

¹Hebei Yanda Lu Daopei Hospital, Langfang, China

Background: Acute myeloid leukemia (AML) patients with the TLS::ERG fusion gene tend to show poor outcomes to traditional chemotherapy. Allogeneic hematologic stem cell transplantation (allo-HSCT) may serve as a potential curative treatment, aiming to enhance the overall survival (OS). However, the long-term safety and efficacy of this treatment for these patients require further exploration.

Methods: A total of 30 AML patients with the TLS::ERG fusion gene were consecutively analyzed, who underwent allo-HSCT in our center between August 2012 and December 2022.

Results: The median age for these patients was 13(2-53) years, with 18 patients 18 years or younger. Before HSCT, the median disease course was 6(3-60) months. Of these patients, 17 (56%) had complex karyotypes, 10(30%) exhibited extramedullary disease, and 10(30%) had additional gene mutations. Prior to HSCT, the disease status was as follows: 18 patients in the first complete remission(CR1),6 in ≥CR2, and 6 in non-remission (NR). In 24 of morphologic CR patients, regular monitoring of TLS::ERG transcript levels before HSCT revealed that 10 patients were TLS::ERG negative, and 14 were TLS::ERG positive. Twenty-seven patients received intensified myeloablative conditioning regimens and the remaining 3 received standard regimens. The transplant donors were haploidentical (n = 23), matched unrelated (n = 5), and matched related (n = 2). In total, eight patients received celluar immutherapy to prophylaxis relapse after transplantation, of them 4 patients received received modified donor lymphocyte infusion (DLI) and another four received IFN-α.eight patients received TLS::ERG positive guided preemptive therapy after transplantation, of them 6 patients received received chemotherapy plus DLI and another two received IFN-α. The median follow-up time for the survivors was 42(12-86)months. The 5-year cumulative incidence of relapse (CIR), and 5-year leukemia-free survival (LFS) and overall survival(OS) after HSCT were 81.6%(95%CI:73.3-89.9),13.2%(95%CI:6.5-19.9), and 13.4%(95%CI:6.4-20.4%), respectively. Relapse occurred in 22 patients with a median relapsed time post-HSCT of 6(3-18) months, among whom 11 simultaneously merged with the extramedullary disease (EMD), among them, twenty patients died from relapse, one patient received therapy and achieved CR, the other one was in relapse status but still alive. Two patients died from treatment-related mortality(TRM). According to disease status (CR/TLS::ERG negative vs. CR/ TLS-ERG positive vs. NR) before allo-HSCT, no significant differences were observed in the 5-year CIR [83.1%(69.8-97.4%) vs. 71.4%(59.3-83.5) vs. 100%), p = 0.602], LFS[15.0%(2.2-27.8%) vs. 21.4%(10.4-32.4) vs 0%), p = 0.548], and OS[18.0%(2.9-33.1%) vs. 16.3%(5.8-26.8%) vs. 16.7%(1.5-31.9%), p = 0.568. Univariate analysis also showed that other factors did not affect the HSCT outcomes.

TABLE1 patient characteristics

Conclusions: The presence of TLS::ERG fusion gene in AML is strongly associated with complex karyotype and EMD. Although allo-HSCT is a promising treatment option, the prognosis remains poor due to a high early relapse rate, even in patients with negative TLS::ERG transcript levels before HSCT.

Disclosure: Nothing to declare.

19: Acute Leukaemia

Cuong An Do ¹, Anne-Claire Mamez¹, Amandine Pradier^1,2, Sarah Morin¹, Chiara Bernardi^1,2, Sarah Prati-Perdikis¹, Yan Beauverd¹, Thomas Longval¹, Maria Mappoura¹, Sarah Noetzlin¹, Laetitia Dubouchet¹, Evgenia Laspa¹, Marie Maulini¹, Thien-An Tran¹, Carmen de Ramon Ortiz¹, Stavroula Masouridi-Levrat¹, Federico Simonetta^1,2, Yves Chalandon^1,2, Federica Giannotti¹

¹Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland, ²Translational Research Center for Oncohematology, University of Geneva, Geneva, Switzerland

Background: Maintenance therapy after allogeneic hematopoietic stem cell transplantation (HSCT) aims to reduce relapse. Targeted maintenance is available for only about 25% of acute myeloid leukemia (AML). Studies employing hypomethylating agents for maintenance in patients without targetable mutations have shown conflicting results.

Methods: We retrospectively analyzed outcomes and tolerability of azacitidine as post-transplant maintenance in a cohort of 23 adult patients with FLT3neg AML, transplanted at our institution between March 2018 and September 2021. Azacitidine was started at hematological reconstitution from day 60 post-transplant, in patients without active GVHD, evidence of relapse or MRD + . It was administrated subcutaneously at 32.5-50 mg/m² for 5 days every 4 weeks for 2 years, if tolerated. Till May 2020, patients eligible for azacitidine maintenance were FLT3neg AML patients with MRD+ or active disease at transplant. Thereafter, we proposed azacytidine maintenance for all FLT3neg AML. Overall, 48 patients were screened: 25 did not start azacitidine due to MRD positivity (n = 7), relapse (n = 2), prolonged cytopenia (n = 7), GVHD (n = 5), death (n = 1), insurance refusal (n = 2) and physician choice (n = 1). Tolerability was evaluated by total number of cycles administrated, hematological toxicity, infections or other adverse events leading to withdrawal or delay of maintenance schedule.

Results: Median follow-up was 30 months (range 11-62). Among 23 patients, one had active disease and 10 were MRD+ before transplant. Median age at transplant was 57 years (range 39-74). Median time from transplant to azacitidine initiation was 102 days (range 66-244). The median number of cycles was 11 (range 1-25). Overall, 7 patients completed the 2-years schedule and 1 is still ongoing. Among these 8, one extended administration intervals to 6 weeks due to cytopenias occasionally requiring G-SCF, another developed recurrent grade 3 neutropenia at higher doses of azacitidine (50 mg/m²), rapidly resolved with G-CSF. One patient on ruxolitinib had grade 3 neutropenia requiring G-CSF once. None of these 3 patients developed infections related to hematological toxicity. Three patients stopped maintenance for mild adverse events (fatigue, myalgias and pruritis) after 11, 12 and 21 cycles, respectively. Among the remaining 12 patients, 3 permanently stopped maintenance due to GVHD (2 chronic moderate, 1 late acute grade 2) after a median of 2 cycles; 9 switched to pre-emptive or curative treatment due to MRD+ occurrence (n = 8) or relapse (n = 1), after a median of 3 cycles. Overall, 5 patients had GVHD or infections not related to azacitidine leading to temporary interruptions (>28 days) for a median time of 73 days (range 49-168). The probability of 2-years OS and PFS were 82.6% (95%CI 68.5%-99.6%) and 69.6% (95%CI 53.1%-91.2%), respectively. Overall, 7 patients died, 1 of lung cancer and 6 of relapse. The 2-years CI of relapse and NRM were 30%±9.85% and 0%±0% respectively.

Conclusions: In our cohort of AML patients lacking targetable mutations, prolonged post-transplant maintenance with azacitidine was relatively well tolerated and outcomes were encouraging. These data support azacitidine maintenance in AML when targeted therapy is not an option.

Disclosure: Y.C. has received consulting fees for advisory board from MSD, Novartis, Incyte, BMS, Pfizer, Abbvie, Roche, Jazz, Gilead, Amgen, Astra-Zeneca, Servier; Travel support from MSD, Roche, Gilead, Amgen, Incyte, Abbvie, Janssen, Astra-Zeneca, Jazz, Sanofi all via the institution.

F.S. has received institutional consulting fees from BMS/Celgene, Incyte, Kite/Gilead; Speaker fees from Kite/Gilead, Incyte; Travel support from Kite/Gilead, Novartis, AstraZeneca, Neovii, Janssen; Research funding from Kite/Gilead, Novartis, BMS/Celgene.

19: Acute Leukaemia

Elzbieta Patkowska¹, Anna Czyz², Alicja Sadowska-Klasa³, Andrzej Szczepaniak⁴, Lukasz Bolkun⁵, Marta Sobas², Michal Gorka⁶, Edyta Subocz⁷, Anna Koclega⁸, Renata Guzicka-Kazimierczak⁹, Jan Zaucha³, Lidia Gil⁴, Marta Libura⁶, Agnieszka Pluta¹⁰, Dorota Bartosinska¹¹, Ewa Lech-Maranda¹, Agnieszka Wierzbowska¹⁰, Sebastian Giebel¹², Barbara Nasilowska-Adamska ¹

¹Institute of Hematology and Transfusion Medicine, Warsaw, Poland, ²Wroclaw Medical University, Wroclaw, Poland, ³Gdansk Medical University, Gdansk, Poland, ⁴Poznan University of Medical Sciences, Poznan, Poland, ⁵Medical University of Bialystok, Bialystok, Poland, ⁶Warsaw Medical University, Warsaw, Poland, ⁷Independent Public Health Care Ministry of the Interior of Warmia and Mazury Oncology Center, Olsztyn, Poland, ⁸Medical University of Silesia, Katowice, Poland, ⁹Pomeranian Medical University, Szczecin, Poland, ¹⁰Medical University of Lodz, Lodz, Poland, ¹¹Centre of Postgraduate Medical Education, Warsaw, Poland, ¹²National Institute of Oncology, Gliwice, Poland

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) offers a potential survival benefit for patients with FLT3-positive acute myeloid leukemia (AML), particularly those harboring the FLT3-internal tandem duplication mutation (FLT3-ITDmut), which is associated with a poorer prognosis compared to point mutations in the tyrosine kinase domain (FLT3-TKDmut). Little is known about the impact of FLT3-TKDmut in the context of allo-HCT, especially with the use of FLT3 inhibitors. This study aims to analyze the outcomes of allo-HCT in FLT3-positive AML patients, considering the type of FLT3 mutation and post-transplant maintenance treatment.

Methods: This retrospective analysis includes FLT3-positive AML patients, encompassing FLT3-ITDmut and/or FLT3-TKDmut, who received intensive chemotherapy combined with midostaurin and underwent allo-HCT between 2017 and 2023.

Results: The study involved 88 patients, with a median age of 50.3 years (IQR 37.1-62.2), predominantly female (n = 58; 65.91%). FLT3-ITDmut was observed in 67 (76.1%) patients, FLT3-TKDmut in 15 (17%), and both mutations in 6 (6.8%) patients. All patients received intensive chemotherapy with midostaurin, initiated either after the first or second induction in 70 (80%) patients or after consolidation in 18 (20%) patients. The median follow-up period post allo-HCT was 15.7 months (IQR: 8.8-28.7). Allo-HCT was performed in the first complete remission (CR) in 68 (77%) patients, subsequent CR in 12 (13.63%) patients, or active disease in 8 (9%) patients. Most patients received myeloablative conditioning (MAC), including TBI-based MAC (n = 5; 5.6%), with grafts from matched related donors (MRD) (n = 24; 27%), matched unrelated donors (MUD) (n = 45; 51%), mismatched unrelated donors (mMUD) (n = 6; 6.8%), or family haploidentical donors (n = 13; 15%). The median overall survival (OS) post allo-HCT was 11 months, with a 2-year OS probability rate of 62%. Subgroup analysis of 60 patients who initiated midostaurin after the first or second induction and were tested for both FLT3 mutations showed a 2-year OS advantage for AML FLT3-TKDmut and AML FLT3-TKDmut co-occurring with FLT3-ITDmut patients compared to AML FLT3-ITDmut patients (rates: 81% vs 80% vs 67%, respectively), although this difference was not statistically significant (p = 0.289). Sorafenib was administered as maintenance treatment post allo-HCT to 22 (30%) of 73 AML FLT3-ITDmut patients. Univariate analysis of OS for the entire group identified age as the only significant prognostic factor, with better survival in patients under 60 years of age (HR = 0.44; 95% CI 0.2-0.93). In the FLT3-ITDmut subgroup, sorafenib maintenance (HR = 0.08; 95% CI 0.01-0.58), age under 60 years (HR 0.36; 95% CI 0.16-0.82) and male gender (HR 0.33; 95% CI 0.11-0.97) were prognostic factors associated with improved OS in univariate analysis. However, in the multivariate analysis of this subgroup, only sorafenib maintenance remained a favourable prognostic factor for improved OS (HR 0.11; 95% CI 0.01-0.89).

Conclusions: Allo-HCT emerges as an effective curative treatment option, providing satisfactory survival outcomes for both AML FLT3-ITDmut and FLT3-TKDmut patients. In the entire patient group, age stands out as the only significant prognostic factor for OS. However, among FLT3-ITDmut patients, post allo-HCT maintenance treatment with sorafenib remains the sole favorable prognostic factor for OS.

Disclosure: E. Patkowska: KCR- consultancy, Astellas Pharma, Servier, Amgen, Novartis - Honoraria.

19: Acute Leukaemia

Mimi Xu ^1,2,3, Yuqing Tu^1,2,3, Mengqi Xiang^1,2,3, Yi Fan^1,2,3, Xiang Zhang^1,2,3, Tiemei Song^1,2,3, Lian Bai⁴, Xiaoli Li⁵, Yang Xu^1,2,3, Yuejun Liu^1,2,3, Depei Wu^1,2,3

¹National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China, ²Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China, ³Key Laboratory of Stem Cells and Biomedical, Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Suzhou, China, ⁴Canglang of Suzhou Hospital, Suzhou, China, ⁵Soochow Hopes Hematonosis Hospital, Suzhou, China

Background: Several studies indicated that RAS mutations were associated with a poorer outcome in T cell acute lymphoblastic leukemia (T-ALL) patients. However, data regarding the clinical outcomes of adult RAS mutated T-ALL patients undergoing different consolidation treatment are limited. This study was conducted to analyze the clinical characteristics and prognosis of adult T-ALL patients with RAS mutations.

Methods: From January 2016 to December 2022, 137 newly diagnosed adult T-ALL patients were explored for activating RAS mutations in our center. We retrospectively analyzed the clinical characteristics of adult RAS mutated T-ALL patients and compare the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with chemotherapy in these patients. About statistical analysis, overall survival (OS) and event free survival (EFS) were estimated by the Kaplan-Meier method and the log-rank test. The cumulative incidence of relapse (CIR) was estimated using Gray’s test, with non-relapse morality considered a competing risk. The covariates with a P value < 0.2 in univariate analyses were used in the multivariate analyses (Fine-Gray model). A P value < 0.05 was considered statistically significant. Statistical analyses were carried out with SPSS 20.0 and R 4.3.0.

Results: KRAS and NRAS mutations were identified in four (2.9%) of 137 and 15 (11%) of 137 patients, respectively. Overall, 19 (13.9%) of 137 T-ALLs harbored activating RAS mutations, without any accompanying PTEN gene changes. The early precursor T (ETP) was the most common immunophenotype (68.4%), with chromosomal abnormalities accounting for 36.8%, and 3 cases of SET-NUP214 fusion gene positivity. The complete response (CR) rate in one course of treatment for 19 patients was 78.9%, and the total CR rate in two courses was 93.3%, one patient with continuous non-remission died on 5.7 months after diagnosis. The median follow-up of survivals was 26.2 months. The 3-year OS rate was (60±12)%, EFS rate was (41±12)%, and CIR was (61.6±1.9)%. Six patients who only received chemotherapy died within 2 years after diagnosis; The 3-year OS rate and EFS rate of 13 patients who underwent allo-HSCT as consolidation were (90.0±9.5)% and (62.3±15.2)%, respectively. Multivariate analyses revealed that achieved CR after first induction chemotherapy (P = 0.036, HR = 0.075, 95%CI: 0.007-0.849) and allo-HSCT (P = 0.008, HR = 0.031, 95%CI: 0.002-0.398) were independent good factors affecting CIR.

Table 1 Characteristics of 19 adult T-ALL patients with activating RAS mutations.

Conclusions: We concluded that RAS mutations were common in adult T-ALL without accompanying PTEN changes, and had more frequently an immature immunophenotype. Adult RAS mutated T-ALL patients had a high induction response rate, but were prone to relapse. Allo-HSCT might effectively reduce the recurrence rate and improve their survival.

Disclosure: Nothing to declare

19: Acute Leukaemia

Francesco Saraceni¹, Eliana Degrandi², Simona Piemontese³, Francesco Saglio⁴, Giorgia Battipaglia ⁵, Marta Lisa Battista⁶, Patrizia Chiusolo⁷, Jacopo Mariotti⁸, Stefania Bramanti⁸, Anna Grassi⁹, Fabio Benedetti¹⁰, Manuela Tumino¹¹, Giorgia Saporiti¹², Salvatore Leotta¹³, Sadia Falcioni¹⁴, Martina Chiarucci¹⁵, Gladis Bortoletto¹⁶, Elisabetta Terruzzi¹⁷, Annalisa Imovilli¹⁸, Carlo Borghero¹⁹, Eugenia Piras²⁰, Francesco Zallio²¹, Vincenzo Federico²², Irene Maria Cavattoni²³, Andrea Gilioli²⁴, Alessandra Picardi²⁵, Domenico Pastore²⁶, Anna Paola Iori²⁷, Valentina Giudice²⁸, Carmen Di Grazia²⁹, Luca Castagna³⁰, Michele Malagola³¹, Attilio Olivieri¹, Francesca Bonifazi³², Massimo Martino³³

¹Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy, ²GITMO Trial Office, Bologna, Italy, ³Ospedale S. Raffaele, Milano, Italy, ⁴CIttà della Salute e della Scienza, Torino, Italy, ⁵Università degli studi di Napoli Federico II, Napoli, Italy, ⁶Azienda sanitaria universitaria Friuli Centrale, Udine, Italy, ⁷Università Cattolica del Sacro Cuore, Roma, Italy, ⁸Istituto Humanitas, Rozzano - Milano, Milano, Italy, ⁹ASST Papa Giovanni XXIII, Bergamo, Italy, ¹⁰Ospedale Borgo Roma di Verona, Verona, Italy, ¹¹Azienda Ospedaliera di Padova, Padova, Italy, ¹²Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milano, Milano, Italy, ¹³Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele, Catania, Italy, ¹⁴AOC Ascoli Piceno, Ascoli Piceno, Italy, ¹⁵Azienda Ospedaliera Marche Nord, Pesaro, Italy, ¹⁶IRCCS Istituto Oncologico Veneto, Mestre, Italy, ¹⁷Azienda Ospedaliera San Gerardo, Monza, Italy, ¹⁸AUSL Reggio Emilia, Reggio Emilia, Italy, ¹⁹Ospedale S. Bortolo Vicenza, Vicenza, Italy, ²⁰Centro Trapianti Midollo Osseo, Università di Cagliari, Cagliari, Italy, ²¹Azienda Ospedaliera di Alessandria, Alessandria, Italy, ²²ASL Lecce, Lecce, Italy, ²³Ospedale Generale Regionale Bolzano, Bolzano, Italy, ²⁴Azienda Ospedaliero Universitaria di Modena, Modena, Italy, ²⁵Ospedale A. Cardarelli - Divisione di Ematologia, Napoli, Italy, ²⁶ASL Brindisi, Brindisi, Italy, ²⁷Università la Sapienza, Roma, Italy, ²⁸Università degli studi di Salerno, Salerno, Italy, ²⁹UO Ematologia e Terapie Cellulari. IRCCS Ospedale Policlinico San Martino, Genova, Italy, ³⁰Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello, Palermo, Italy, ³¹Università degli Studi di Brescia, Brescia, Italy, ³²IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy, ³³Azienda Ospedaliera “Bianchi-Melacrino-Morelli” di Reggio Calabria, Reggio Calabria, Italy

Background: Leukemia relapse remains the main cause of treatment failure in patients undergoing allogeneic stem cell transplant (allo-SCT) for acute myeloid leukemia (AML). There is currently no general agreement concerning management of patients at high risk of leukemia recurrence or with overt hematological relapse after allo-SCT.

Methods: We conducted the present survey with the aim to evaluate the current practice in Italy concerning prevention and treatment of AML relapse after allo-SCT. A questionnaire was sent to GITMO centers including specific questions on three main topic: maintenance, preemptive therapy and treatment of hematological relapse. Most of the agents discussed below currently represent off label prescriptions.

Results: In all, 34/60 (57%) of centers performing allo-SCT in Italy completed the questionnaire. 22/34 (65%) routinely employ maintenance strategies (in the absence of measurable residual disease (MRD) or mixed chimerism) after allo-SCT in patients considered at high risk of relapse basing on pre-transplant features (high risk according to ELN 2022 or presence of FLT3-ITD, positive MRD or active disease). Among institutions who deliver maintenance therapy after allo-SCT, in patients harbouring FLT3-ITD 86% administer FLT3 inhibitors (95% Sorafenib, 5% Gilteritinib). In the absence of FLT3-ITD 68% use hypometilating agents (87% azacitidine, 13% decitabine); 2 centers consider addition of venetoclax to hypometilating agents, while one institution prescribes venetoclax as single agent. Interestingly, 26% of institutions administer prophylactic DLI in high risk AML patients, in the absence of MRD relapse or mixed chimerism. With respect to preemptive therapy, the trigger to start treatment is represented by MRD relapse in all centers; 74% of institutions consider mixed chimerism as trigger to start preemptive therapy as well. In patient harbouring FLT3-ITD 82% of centers prescribe FLT3 inhibitors (48% sorafenib +/- azacitidine, 52% gilteritinib). In the absence of FLT3-ITD 62% of institutions use azacitidine (19% with the addition of venetoclax), one institution use venetoclax monotherapy, while 29% use DLI as single approach especially in case of mixed chimerism in the absence of MRD relapse. Nevertheless, 32/34 (94%) use DLI in addition to pharmacologic preemptive therapy.

In patients experiencing haematological relapse after transplant 76% of institutions perform NGS analysis at the time of relapse, while 50% look for HLA loss in case of relapse after haploidentical transplant. In patients harbouring FLT3-ITD 91% of centers treat AML relapse with gilteritinib. In fit patients, in the absence of FLT3-ITD, 44% employ conventional chemotherapy, while 56% consider as first option hypometilating agents (mostly azacitidine) in combination with venetoclax.

All institutions consider second allo-SCT after salvage treatment in patients who relapse after first transplant. 62% of centers perform second allo-SCT only in patients achieving CR2, while 38% regardless achievement of response to salvage. Finally, 97% of institutions prefer a different donor for second allo-SCT, if available.

Conclusions: Most Italian transplant institutions currently implement strategies to prevent AML relapse after allo-SCT, despite the lack of approved agents in this setting. In patients with haematological relapse a second allo-SCT remains a main option after salvage treatment with standard chemotherapy or hypometilating agents in combination with venetoclax.

Disclosure: Nothing to declare.

19: Acute Leukaemia

Sebastian Giebel ¹, Myriam Labopin², Frederic Baron³, Ali Bazarbachi⁴, Eolia Brissot⁵, Gesine Bug⁶, Jordi Esteve⁷, Norbert-Claude Gorin⁸, Francesco Lanza⁹, Arnon Nagler¹⁰, Annalisa Ruggeri¹¹, Jaime Sanz¹², Bipin Savani¹³, Christoph Schmid¹⁴, Roni Shouval¹⁵, Alexandros Spyridonidis¹⁶, Jurjen Versluis¹⁷, Zinaida Peric¹⁸, Mohamad Mohty⁵, Fabio Ciceri¹⁹

¹Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland, ²EBMT Unit, Sorbonne Universités, UPMC University of Paris 06, INSERM, Centre de Recherche Saint-Antoine (CRSA), AP-HP, Saint Antoine Hospital, Paris, France, ³GIGA-I3, University and CHU of Liège, Liège, Belgium, ⁴American University of Beirut Medical Center, Beirut, Lebanon, ⁵Sorbonne Universités, UPMC University of Paris 06, INSERM, Centre de Recherche Saint-Antoine (CRSA), AP-HP, Saint Antoine Hospital, Paris, France, ⁶University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany, ⁷Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain, ⁸European Society for Blood and Marrow Transplantation, Paris Office, Hopital Saint-Antoine, Paris, France, ⁹Romagna Transplant Network, Ravenna, Italy, ¹⁰Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, ¹¹IRCCS Bambino Gesù Children’s Hospital, Rome, Italy, ¹²Hospital Universitari i Politecnic La Fe. Instituto de Investigación Sanitaria La Fe, Valencia, Spain, ¹³Vanderbilt University Medical Center, Nashville, United States, ¹⁴Augsburg University Hospital, Augsburg, Germany, ¹⁵Memorial Sloan Kettering Cancer Center, New York, United States, ¹⁶University of Patras, Patras, Greece, ¹⁷Erasmus University Medical Center Cancer Institute, Rotterdam, Netherlands, ¹⁸University Hospital Center Rijeka and School of Medicine, University of Rijeka, Rijeka, Croatia, ¹⁹Ospedale San Raffaele s.r.l., Haematology and BMT, Milano, Italy

Background: Indications for hematopoietic cell transplantation (HCT) for adults with acute lymphoblastic leukemia (ALL) evolve over time and vary among countries. In our previous survey we reported continues increase of the number of allogeneic (allo)-HCT procedures between years 2001-2015 [Giebel S, et al., Ann Hematol 2019]. In recent years the role of HCT has been challenged by new protocols incorporating bispecific antibodies or immunotoxins in first-line treatment. The goal of this study was to assess general trends in the number of various types of HCTs performed between years 2010 and 2021 in Europe.

Methods: Data reported to the EBMT registry were used for this analysis. Altogether, 14389 first allogeneic (n = 13795) or autologous (auto-, n = 594) HCTs were performed in the period 2010-2021.

Results: The number of allo-HCTs analyzed in 2-year periods increased from 2074 for years 2010-2011 to 2428 between 2018-2019 (17% increase) and then dropped to 2282 for years 2020-2021 (6% decrease). Similar pattern was observed for the largest European countries (Germany, UK, France, Italy, Spain).

Comparing years 2020-2021 and 2010-2011, median recipient age increased from 37.3 to 41.1 (p<0.0001), the proportion of matched sibling donor transplants decreased from 39% to 24.2%, while the rate of unrelated donor and haploidentical donor transplants increased from 50.8% to 54.3% and 5.1% to 20.2%, respectively; the proportion of cord blood transplants decreased from 5.1% to 1.2% (p<0.0001) (Table). In respective periods the proportion of patients with Ph-negative B-ALL increased from 28.6% to 43.2%, for Ph-positive B-ALL it decreased from 38% to 32.7% while for T-ALL it dropped from 33.4% to 24.1% (p<0.0001). Most patients were treated in the first complete remission: 70.2% between years 2010-2011 and 70.9% between 2020-2021. The proportion of patients administered allo-HCT in active disease decreased from 10.5% to 4.7% in respective periods (p<0.0001). Peripheral blood was used as a source of stem cells for allo-HCT in 74.1% of patients between 2010-2011 and 90.3% of patients between 2020-2021. The use of post-transplant cyclophosphamide increased from 1.7% to 29.6% in respective periods (p<0.0001).

The total number of auto-HCTs was 130 between years 2010-2011 and 48 between 2020-2021 (63% decrease).

Conclusions: Results of our analysis indicate moderate increase of allo-HCT procedures for adults with ALL in the period 2010-2019 followed by a slight decrease between 2020-2021 that might be related to SARS-CoV-2 pandemic. The profile of allo-HCTs has changed over time with more frequent use of haploidentical donors, post-transplant cyclophosphamide – based immunosuppression and the use of peripheral blood as predominant source of stem cells. In recent years less patients have been treated with allo-HCT in active disease which may reflect higher efficacy of immunotherapy-based salvage regimens. Auto-HCT is rarely used for the treatment of adults with ALL.

Clinical Trial Registry: Not applicable

Disclosure: GB has received honoraria from Novartis, Jazz, BMS and Gilead and travel grants from Jazz, Gilead and Neovii

19: Acute Leukaemia

Veronika Válková ^1,2, Cyril Šálek^1,2, Antonín Vítek¹, Markéta Marková^1,2, Ludmila Nováková¹, Mariana Koubová¹, Michal Kolář¹, Barbora Čemusová¹, Hana Bartáková¹, Petr Cetkovský^1,2, Jan Vydra^1,2

¹Institute of Hematology and Blood Transfusion, Prague 2, Czech Republic, ²Faculty of Medicine of Charles University, Prague 2, Czech Republic

Background: Allogeneic stem cell transplantation (allo-SCT) may be curative for patients with high risk acute lymphoblastic leukemia (ALL). The aim of our analysis was to compare the results of allo-SCT in ALL over more than two decades and to identify the parameters that influence these results.

Methods: All patients (pts) older than 18 years who underwent allo-SCT at our center from March 1989 to July 2023 were included in the analysis. In total, there were 183 pts, median age 38 years (18-65, only 17% over 55 years), 116 (63%) were male, B-ALL-Ph pos 37%, T-ALL 17%, donors were MSD (26%), MUD (42%), MMUD (23%) and haplo (8%). The majority of grafts were PBPC (82%). Myeloablative conditioning (TBI based) received 158 (86%) pts, 62% of whom received Vep/12Gy TBI. A more detailed analysis in terms of GVHD and MRD was performed on a cohort of patients from 2007 (n = 136). At allo-SCT 105 pts (77%) were in CR1, 23 (17%) in CR2, 6% with active disease. In terms of MRD, 60 patients were negative and 59 positive before allo-SCT.

Results: With a median follow-up of 6.5 years (living pts), 5-year OS was 56% and EFS of 49%. The cumulative incidence of relapse and NRM was 30% and 27% respectively at 5 years. Acute GVHD grade 2-4 occurred in 23%, moderate/severe chronic GVHD in 11%. GRFS at 5 years was 42%. Relapse occurred in 23% of patients, at a median of 8 months. OS after relapse was 22% at 5 years (26% vs 19% in the last decade vs earlier, p= ns). In univariate analysis, significantly better outcomes in terms of OS were observed in the last decade (5y-OS 68%), optimal conditioning seems to be Vep/TBI, worse outcomes were observed in patients over 55 years. Survival was significantly better in pts reaching CR before allo-SCT, and also significantly better in MRD neg versus MRD pos pts (no difference between MRD neg CR1 or CR2), both before allo-SCT and at 3 months after allo-SCT. A multivariate Cox regression analysis confirmed the survival benefit for pts who reached MRD negativity before allo-SCT (p = 0.047) and for transplants from MSD (p = 0.02) or MUD (p = 0.02) over the other donors.

Conclusions: The outcomes of allo-SCT in ALL have improved significantly in the last decade, in our setting mainly due to the reduction of NRM. The role of novel therapies has been observed more in terms of of the possibility of achieving more CR (and even more MRD neg CR) before allo-SCT, rather than in the treatment of relapses after allo-SCT. Our results confirm the essential role of MRD monitoring during ALL treatment and in particular achieving MRD negativity before allo-SCT.

Disclosure: nothing to declare

19: Acute Leukaemia

Zijun Qian ^1,2, Lu Chen^1,2, Jie Zhang², Yuyuan Zheng¹, Chun Zhou^1,2, Haowen Xiao^1,2

¹Zhejiang University, Hangzhou, China, ²Sir Run Run Shaw Hospital, Hangzhou, China

Background: High expression level of protein tyrosine phosphatase non-receptor type 21 (PTPN21) has been detected in B-cell non-Hodgkin’s lymphoma and its mutations are associated with disease relapse in B-cell acute lymphoblastic leukemia (B-ALL) patients who received allo-HSCT. Recently, PTPN21 has been shown to be pivotal in maintaining cell mechanical properties and helps retain hematopoietic stem cells (HSCs) in the bone marrow niche through dephosphorylating the cytoskeleton-associated protein Septin1. However, the molecular structure and functions of PTPN21 have been less understood compared to other tyrosine phosphatases like PTP1 B. PTPN21 is a relatively large protein with two structured domains, FERM domain and the catalytic domain (PTP), and a long intrinsically disordered region in the middle. The mechanisms of regulation of PTPN21 phosphatase activity and the effect of mutations on its functions need to be explored.

Methods: We used protein purification and crystallization to determine structures of FERM^PTPN21, PTP^PTPN21 and a complex structure of the PTP and FERM domains. GST pulldown and MST titration as well as phosphatase assays and site direct mutagenesis were used to determine the interaction of PTP and FERM domains.

Results: Through biochemical assays, we found that PTPN21 FERM domain can interact with PTP domain, resulting in negatively regulating its phosphatase activity in vitro and in vivo. We further explored the structures of FERM^PTPN21, PTP^PTPN21 as well as a complex structure of the combination of PTP and FERM domains. The FERM-PTP complex structure allowed us to identify critical interface residues and mutations of these residues led to enhanced phosphatase activity of PTPN21 and induced activation of downstream ERK. More importantly, these mutations only activated ERK in the context of wild-typed PTP but not the catalytic inactive C1108S, indicating PTPN21’s phosphatase activity is indispensable.

Conclusions: We’ve demonstrated that PTPN21 catalytic domain PTP is autoinhibited by the FERM domain. Disruption of FERM-PTP interaction results in enhanced PTPN21 activity and activation of downstream MAPK signal pathway. Our work provides novel insights into understanding the role of PTPN21 in various cellular processes by discovering the molecular structure of the FERM and PTP domains of PTPN21. These findings are likely extendable to other FERM-containing tyrosine phosphatases like PTPN14 and PTPN3, which opens up new avenues for further mechanistic studies.

Disclosure: Nothing to declare.

19: Acute Leukaemia

Daire Quinn ¹, Anne Parker¹, Grant McQuaker¹, Anne-Louise Latif¹, David Irvine¹, Ailsa Holroyd¹, Dimitris Galopoulos¹, Andrew Clark¹

¹Queen Elizabeth University Hospital, Glasgow, United Kingdom

Background: Relapse following allogeneic stem cell transplant carries a poor prognosis. DLI has been used in this setting but is less effective if delayed or given in the context of haematological relapse.

Methods: Aliquots of DLI from the PBSC collection were stored prophylactically pre-transplant. The transplant dose was always protected and was never < 4x10⁶ CD34 cells/Kg. No DLI were stored if stem cell dose was lower than this threshold. Patients with relapsed acute leukaemia (AL) or MDS were detected early and treated with an effective salvage regimen followed by escalated doses of DLI, starting at 3x10⁵ CD3 cells/Kg (VUD) or 1x10⁶ CD3 cells/Kg (MRD). First dose DLI was given at 6-8 weeks post commencement of salvage treatment. Subsequent DLI doses (3x10⁶, 1x10⁷, 3x10⁷ CD3 cells/Kg) were delivered at 8-12 week intervals intercalated with salvage therapy. Maximum dose was 3x10⁷ CD3 cells/Kg (max cumulative dose 4.63 x10⁷ CD3 cells/Kg). Patients were excluded if they had rapidly progressive disease, BM blasts >50% or ECOG >2.

Results:

Between 2015 and 2022 thirty one patients were treated with DLI for relapsed AL (n = 19) or MDS (n = 12). Strikingly, only 4 of these interventions occurred before 2019. Before that time selecting patients with low disease burden and being able to acquire DLI in a rapid time frame was frequently not possible. After 2019 four factors facilitated effective DLI administration- Early disease relapse, detection using MRD combined with assessment of myeloid chimerism, newer agents to achieve remission responses and the ready availability of DLI.

In relapsed MDS all patients had recurrent cytopenias associated with: NGS abnormalities, increasing blast % or cytogenetic abnormalities. Myeloid chimerism ranged from 4-64% at diagnosis returning to 100% donor in all responding patients. In the AL group 10 were diagnosed by MRD methods and 9 had haematological relapse. Median Time to relapse was 10 months in AL and 19 months in MDS

In AL salvage treatment included FLAG, Dasatinib, Gemtuzumab, Ven/Aza, Gilteritininb, Blinatumomab, Inotuzumab, Azacitidine alone or no therapy while MDS patients all received Azacitidine for 4-12 cycles. Median number of DLI infusions was 3. Median total dose was 1.4x10⁷ CD3 cells/Kg in both groups. In responders the median total dose was 4.4x10⁷ CD3 cells/kg. Median FU post DLI was 20 and 30 months overall or for responders in AL and 19 and 22 months in MDS.

CR was achieved in 63% of acute leukaemia and 58% of MDS patients. Two leukaemic patients relapsed at 16 and 34 months. Responses were otherwise durable, 80% remained in CR at 3 years. Three additional MDS patients responded transiently. Acute GvHD occurred in 2 patients. Two patients have moderate chronic GvHD. One died of acute neurotoxicity. Two year DFS was 53% in AL and 42% in MDS.

Conclusions: Combining early detection of disease relapse, followed by treatment with novel therapies and consolidation with DLI provides effective salvage therapy. High levels of durable disease control are achieved and low rates of GvHD are seen resultant on DLI dose escalation. Prophylactic storage of DLI allows this approach and is cost effective.

Clinical Trial Registry: None

Disclosure: None

19: Acute Leukaemia

Ahmad Ibrahim ¹, Ahmad Khalil², Kamal Al Zahran³, Mohamad Hachem⁴, Pamela Sfeir⁵, Amin Abyad⁶, Jad Ibrahim⁷, Hussein Abou Abbas⁸, Ali Youssef⁸, Charbel Khalil², Tamima Jisr⁹

¹Makassed University Hospital, Middle East Institute of Health, University of Balamand and Lebanese University, Beirut, Lebanon, ²Middle East Institute of Health, Beirut, Lebanon, ³Middle East Institute of Health and Lebanese University, Beirut, Lebanon, ⁴Makassed University Hospital and Lebanese University, Beirut, Lebanon, ⁵University of Balamand, Beirut, Lebanon, ⁶Burjeel Medical City, Abu Dhabi, United Arab Emirates, ⁷American University of Beirut, Beirut, Lebanon, ⁸Makassed University Hospital, Beirut, Lebanon, ⁹Makassed University Hospital and Beirut Arab University, Beirut, Lebanon

Background: Haploidentical stem cell transplantation (HaploSCT) with thiotepa/busulfan/fludarabine (TBF) conditioning and post-transplant cyclophosphamide (PT-Cy) can achieve comparable outcomes for relapsed acute myeloblastic leukemia (AML) patients (pts) in complete remission (CR) to those of HLA-matched sibling or unrelated donor transplantation. However, a higher incidence of acute and chronic GVHD was reported with peripheral blood stem cell source (PBSC) compared to bone marrow (BM) in adult acute leukemia. In this study, we report the outcomes of adult pts (>18yo) with AML in second CR who underwent HaploSCT with unmanipulated BM source using TBF conditioning and PT-Cy.

Methods: This study is a retrospective analysis conducted between 2/2018 and 2/2023. The TBF-MAC included thiotepa IV 5mg/kg/d on d-7 and -6, IV busulfan 3.2mg/kg/d on d-4, -3, -2, and IV fludarabine 30mg/kg/d from d-5 to d-1. The TBF-RIC, for pts >60yo, involved reduced doses of thiotepa (5mg/kg on d-6) and busulfan (3.2mg/kg/d on d-3 and -2), with identical fludarabine doses. BM was infused on d0. The PT-Cy dose was 50mg/kg/d d + 3 and +4, followed on d + 5 by IV cyclosporine 3mg/kg/d, then tapered over 6 weeks after d + 60 if no GVHD. MMF was given at a dose of 15mg/kg every 12 hours d + 5 to d + 35. GCSF was started d + 5 until neutrophil recovery. Prophylaxis for VOD was ensured by ursodeoxycholic acid. Anti-microbial prophylaxis was given. Pts were monitored by PCR for CMV, EBV, HHV6 until d + 100, and for BK virus if indicated. Azacitidine was given as maintenance therapy after Haplo SCT for all pts, and sorafenib was given in case of FLT3 mutations.

Results: Thirty-two pts were included. Median age was 36yo (19-71). There were 17 females and 15 males. Twenty-four pts (75%) received TBF-MAC, and 8 (25%) TBF-RIC. Median number of nucleated cells infused was 5.2×10⁸ kg (4.1-6.7). All pts achieved neutrophil recovery within a median of 17d (14-31), and platelet recovery (>20 10⁹/L) within a median of 19d (10-42). All pts had full donor chimerism before d + 90. Seven pts (22%) developed grade II-IV aGVHD, including 2 (6%) with grade III–IV. Three pts (9%) developed non-severe cGVHD. Acute GVHD was refractory to steroids in 2 pts and was fatal in one. Fatal VOD occurred in 1 pt (3%). Eight pts (25%) had bacteremia, and 2 (6%) developed invasive fungal infections. Two pts (6%) developed fatal COVID-19. CMV reactivation, successfully treated with ganciclovir, occurred in 14 pts (44%). Seven pts (22%) died of infection, including 2 of COVID-19 and 5 of sepsis. Five pts (16%) relapsed within a median of 9 months (6-25) after Haplo SCT and died from AML between 1 and 6 months after relapse. Within a median follow-up of 22 months (1-68), 18 pts (56%) are still alive in CR with a median of 33 months (11-68). The 3y-OS and-DFS were 57% and 52%, respectively.

Conclusions: HaploSCT with BM source offers a curative therapy for adult AML pts in 2^nd CR with low risk of GVHD, and low incidence of relapse. However, infections remained the main cause of death.

Disclosure: Nothing to declare.

19: Acute Leukaemia

Dong Won Baek ¹, Jung Min Lee¹, Hyukjin Choi¹, Joon Ho Moon¹, Sang Kyun Sohn¹

¹Kyungpook National University Hospital, Daegu, Korea, Republic of

Background: With the introduction of tyrosine kinase inhibitors (TKI), survival outcomes of adult patients with Philadelphia chromosome positive (Ph-positive) acute lymphoblastic leukemia (ALL) has improved remarkably. Intensive chemotherapy plus TKI is still the standard approach to induce hematologic complete remission (CR) before allogeneic stem cell transplantation (allo-SCT). However, intensive chemotherapy before transplantation may have negative impacts on allo-SCT outcomes, including treatment-related mortality, worsening performance at the time of transplantation. In the current study, we compared the survival outcomes of intensive chemotherapy plus TKI and reduced intensity chemotherapy plus TKI in patients with newly diagnosed Ph-positive ALL. In addition, the clinical role of allo-SCT in the treatment of adult Ph-positive ALL was also evaluated.

Methods: We retrospectively analyzed data from 97 patients with newly diagnosed Ph-positive ALL who received intensive chemotherapy plus TKIs or reduced intensive chemotherapy plus TKIs over the past 10 years. Patients aged ≥ 20 years were included in this study. Patients who were in suitable condition for transplantation and had HLA matched donor underwent allo-SCT. Relapse-free survival (RFS) was determined from the date of diagnosis to the date of disease relapse or death from any cause. Overall survival (OS) was determined from the date of diagnosis to the date of death or last follow-up.

Results: In total, 97 patients were analyzed. Intensive chemotherapy was administered to 69 patients, and median age was 45 (range, 20-73) years old. Reduced intensity chemotherapy was administered to 28 patients, and their median age was 68.5 (range, 27-80) years old. In patients with intensive chemotherapy plus TKI, 55 patients (79.7%) achieved molecular CR after induction chemotherapy, and four patients (5.8%) died during induction therapy. In patients with reduced intensity chemotherapy plus TKI, 20 patients (71.4%) achieved molecular CR, while no one has died during induction therapy. In the intensive chemotherapy group, 46 patients (66.7%) underwent allo-SCT, and 20 patients showed disease relapse and three patients died after transplantation. In the reduced intensity chemotherapy group, 12 patients (42.9%) received allo-SCT, and four patients had relapsed disease and one died. In an analysis targeting only transplanted patients, there was no statistically significant difference in RFS and OS between patients who received intensive chemotherapy and patients with reduced intensity chemotherapy.

Conclusions: Reduced intensity chemotherapy decreased induction mortality compared to intensive chemotherapy. In addition, reduced intensity chemotherapy plus TKI was able to sufficiently induce molecular CR, and subsequent allo-SCT could improve long-term survivals.

Disclosure: The authors declare no conflict of interest.

19: Acute Leukaemia

Feng-ming Tien¹, Xavier Cheng-Hong Tsai ¹, Min-Yen Lo¹, Hsin-An Hou¹, Hwei-Fang Tien¹

¹National Taiwan University Hospital, Taipei, Taiwan, Province of China

Background: Acute myeloid leukemia (AML) with DNMT3A mutations is classified within intermediate-risk category according to ELN-2022 criteria. However, the impact of co-mutations on the transplant outcomes in this particular group remains to be explored.

Methods: A total of 148 patients (16.7%) with DNMT3A mutations were enrolled from a retrospective cohort of 887 AML patients homogeneously treated with intensive chemotherapy. Gene mutations were examined via targeted NGS, using the TruSight myeloid panel. Notably, none of the patients received oral azacitidine as maintenance therapy. Survival analysis modified according to Simon-Makuch method were used to compare outcomes between allogeneic stem cell transplantation (allo-HSCT) and postremission chemotherapy (PR-CT) in the first complete remission (CR1).

Results: The most frequent co-mutations in DNMT3A mutated patients were NPM1 (52.7%), FLT3-ITD (31.1%), and IDH2 (26.4%). 111 out of 148 (75%) patients achieved CR1. 68 patients received allo-HSCT: 30 with myeloablative conditioning, 38 with reduced intensity conditioning; 15 with a haploidentical donor, 23 with a matched sibling donor, 30 with a matched unrelated donor. Specifically, 30 patients received allo-HSCT at CR1, 11 at CR2, 27 at other disease statuses, resulting in a 5-year overall survival (OS) of 46%, 29%, 15%, respectively. For those with PR-CT without further transplant, the 5-year OS was 13%. Allo-HSCT in CR1 was associated with a better OS than PR-CT (median, not reached (NR) vs 15.3 months, P<0.0001).

Next we delved into the specific genetic subgroup within the DNMT3A mutated patients. In the NPM1-/FLT3-ITD- subgroup, the most frequent co-mutations were IDH2 (47.3%), ASXL1 (18.2%), NRAS (16.4%), IDH1 (16.4%). 37 out of 55 patients attained CR1. The relapse rate was 75% in those receiving PR-CT, and 50% in those receiving allo-HSCT in CR1. The lower relapse rate translate into a significantly better OS (median, 75.1 vs. 19.6 months, P = 0.015) and event-free survival (EFS)(median, 75.1 vs. 8.9 months, P = 0.001) in the allo-HSCT group.

In the NPM1 + /FLT3-ITD- subgroup, currently an ELN-2022 favorable-risk category, 39 out of 47 patients attained CR1. The relapse rate was 36.8% in those receiving PR-CT, and 0% in those receiving allo-HSCT in CR1. Allo-HSCT in CR1 was associated with a significantly better OS (median, NR vs. 98.2 months, P = 0.042) and EFS (median, NR vs. 18.7 months, P = 0.006). Lastly, in the IDH2 mutated subgroup, allo-HSCT in CR1 was associated with a significantly better EFS, while the OS remained similar.

Conclusions: The results indicated that NPM1-/FLT3-ITD- and NPM1 + /FLT3-ITD- subgroups in DNMT3A mutated AML benefit from allo-HSCT in CR1. Larger cohorts are warranted to validate these findings.

Disclosure: No relevant conflict of interest to declare.

19: Acute Leukaemia

Alexandros Rampotas ¹, Fotios Panitsas², Maximillian Brodermann¹, Sridhar Chaganti³, Styliani Bouziana⁴, Emma Nicholson⁵, Samantha Drummond⁶, Sharon Allen⁷, Andrew King⁷, Henry Crosland³, Anne-Louise Latif⁶, Daniele Avenoso⁴, Claire Roddie¹

¹University College London Hospital NHS Foundation Trust, London, United Kingdom, ²Laikon University Hospital, Athens, Greece, ³University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom, ⁴King’s College London Hospital NHS Foundation Trust, London, United Kingdom, ⁵The Royal Marsden NHS Foundation Trust, London, United Kingdom, ⁶Queen Elizabeth University Hospital, Glascow, United Kingdom, ⁷Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom

Background: Relapse following allogeneic hematopoietic stem cell transplantation (allo-HCT) in T-Acute Lymphoblastic Leukemia (T-ALL) poses a formidable clinical challenge. Diverse treatment modalities have been employed, showcasing variable efficacy. Notably, recent years have witnessed the emergence of novel therapeutic strategies for T-ALL such as Chimeric Antigen Receptor T-cells targeting CD7, CD5 and CXCR7 among others with a few phase I/II trials being underway. This study examines outcomes in relapsed T-ALL post allo-HCT, spanning the period from 2010 to 2022, across six major UK transplant centers. Our findings underscore the pressing need for innovative therapeutic interventions in this context, emphasizing the urgency for further research and the development of novel approaches to address the poor outcomes of relapsed T-ALL after transplantation.

Methods: Retrospectively, we compiled data from adult cases experiencing post-transplant relapse in T-ALL. Survival analysis, employing Kaplan-Meier methodology and log-rank tests, was conducted. Descriptive analysis was undertaken to assess baseline and disease characteristics. Approval for this project was obtained from the British Society of Blood and Marrow Transplantation. All data management adhered strictly to the principles outlined in the Declaration of Helsinki.

Results: Twenty-one patients with relapsed T-ALL post allo-HCT were identified, and 20 with sufficient data underwent analysis, with a median follow-up of 32.6 months. Baseline and disease characteristics are detailed in Table 1, Median age was 37 years, while high-risk features included a mediastinal mass in 4/20, early T-cell precursor leukemia in 7/19, high white cell count in 8/19, and CNS disease in 4/20. Relapse occurred at a median of 6 months post-transplant. Intensive chemotherapy, including FLAG-IDA (N = 1), Nelarabine (N = 2), Venetoclax and UKALL14 phase 2 (N = 1), Nelarabine and UKALL14 induction (N = 1), was employed in 5/20 patients, while the rest received non-intensive chemotherapy or palliative and supportive options. Donor Lymphocyte Infusions were not utilised for any patient. Out of 5 patients who received intensive chemotherapy, only 1 achieved CR and four patients went on to receive a second transplant. Among them, one succumbed to transplant complications, while three achieved CR. Two patients relapsed after 12 and 18 months, respectively, while one remains in remission at 26 months post-transplant. Median overall survival was 3.18 months (2-5).

Conclusions: The prognosis for post allo-HCT relapsed T-ALL is notably grim, with limited success observed in second transplant cases. Even within this context, outcomes remain disheartening. The anticipation for improved strategies is fervent, emphasizing the crucial need for innovative treatments. Ongoing investigations into CAR-T cell therapies, specifically CD7 and CXCR7, offer promising avenues. It is imperative that these novel approaches are actively incorporated into clinical practice, and patients are encouraged to participate in relevant trials. The urgency to explore and adopt these advanced therapeutic modalities underscores the commitment to enhancing outcomes for individuals grappling with relapsed T-ALL post allo-HCT.

Disclosure: Alex Rampotas received conference fees by Gilead. Claire Roddie declares Honoraria: Gilead Sciences Consulting or Advisory Role: Autolus, Kite/Gilead, Bristol Myers Squibb/Celgene Speakers’ Bureau: Novartis Pharmaceuticals UK Ltd, Gilead Sciences Travel, Accommodations, Expenses: Gilead Sciences, Autolus. Anna Louise Latif declares honoraria from Kite and Novartis. All other authors declare no conflicts of interest.

19: Acute Leukaemia

Sabrina Giammarco ¹, Elisabetta Metafuni¹, Maria Assunta Limongiello¹, Federica Sorá², Eugenio Galli¹, Filippo Frioni², John Marra², Patrizia Chiusolo², Simona Sica²

¹Fondazione Policlinico Universitario A. Gemelli, Rome, Italy, ²Universitá Cattolica del Sacro Cuore, Roma, Italy

Background: CPX-351 (VYXEOS®), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, was approved for the treatment of t-AML or AML-MRC, based on improved survival and remission and comparable safety versus 7 + 3 chemotherapy in a randomized trial in older adults.

The increased use of CPX 351, in association with reduced intensity conditioning regimen and new strategies of GvHD prophylaxis such as PTCY, allows to proceed with HSCT in older patients or previously heavily treated, improving outcomes.

Methods: To assess the feasibility of HSCT in patients with s-AML and t-AML treated with CPX-351, we collected clinical data on 27 consecutive patients submitted to HSCT at our center from February 2019 to October 2023. Then we compared data with 30 patients with AML submitted to HSCT, previously treated with 7 + 3 induction chemotherapy from January 2019 to April 2020.

Results: Of 49 patients treated with CPX-351 from February 2019, all 27 patients with indication to proceed with HSCT, underwent to transplant to consolidate the obtained response. There were 14 males and 13 female, with a median age of 62 yrs (range 43-69). They were all in complete remission except two. Median HCT-CI was 4 (range 0-7). Unrelated donors were the source in 18 patients, haploidentical donors in 8 pts, sibling donors in 1 patient. Stem cell source was peripheral blood in 23 pts, bone marrow in 3 pts and CBU in 1 patient. The median CD34+ cell dose was 4x10⁶/kg (range 0.1-12.779). The main conditioning regimen was the association of Thiotepa, Busulfan and Fludarabine, modulating the busulfan dose according to patient’s comorbidities and performance status, defined by HCT-CI. GVHD prophylaxis regimen was performed with cyclosporine, mycophenolic acid, and cyclophosphamide at day +3 and +5 after HSCT. Engraftment was reached in all patients except one patient who received CBU. Sepsis were identified in 14 patients out 27.

Seven patients developed acute GvHD, all with skin involvement (Stage 2-3); two patients also with gut involvement (Stage 3)and one patient with pulmonary involvement (severe).

1 years OS was 73%. Comparing the two populations, there was no difference in term of gender, disease status at transplant, donor type, donor sex, stem cell source, conditioning regimen, GVHD prophylaxis, sepsis occurrence and GVHD incidence. Significantly statistical difference was found in terms of median age (p = 0.0016), HCT-CI (p = 0.002) as expected, and in terms of median CD34+ stem cell infused, which were significantly higher in the younger comparison population (p = 0.04). (Table 1).

Conclusions: Our monocentric experience showed data in line with those reported in the literature. The growing use of CPX-351 appears to be a safe and effective bridge therapy for HSCT in patients with a poorer prognosis, reproducing outcomes similar to younger population.

Disclosure: No disclosure to declare

19: Acute Leukaemia

Tran-Der Tan ¹, Lun-Wei Chiou¹

¹Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan, Province of China

Background: The current standard treatment for fit newly diagnosed acute myeloid leukemia patients is idarubicin or daunorubicin plus cytarabine (3 + 7 regimen), followed by allogeneic hematopoietic stem cell transplantation. However, less than half of them could enter into allotransplant because of not remission or the occurrence of treatment-related morbidity or mortality. Venetoclax plus azacytidine or low-dose cytarabine could achieve a high CR rate in unfit or elderly patients in phase III trials.

Methods: We conducted a treatment protocol of venetoclax 100 mg and posaconazole 300 mg a day according to the pharmacokinetics plus a standard dose of cytarabine (100 mg/m2/d x 7 days) as the induction and consolidation therapy, followed by allogeneic hematopoietic stem cell transplantation for newly diagnosed transplant-eligible patients. And we compared the efficacy and outcome with our prior 3 + 7 induction followed by allo-transplant patients.

Results:

Between Mar 2019 and Dec 2023, we had 22 consecutive newly diagnosed transplant-eligible AML patients, including 8 therapy-related and 14 de novo AML. Eighteen underwent venetoclax plus standard-dose cytarabine, four underwent venetoclax plus azacitidine induction therapy, and twenty out of twenty-two were followed by allogeneic hematopoietic stem cell transplantation. CRc rate was 94.4% in our cohort and 90.9% in the adverse group of patients. Twenty of twenty-two of our patients were transitioned to allo-transplant, as compared with 46.9% in our previous 3 + 7 induction era between 2009 and 2018. Three-year overall survival was improved from 23% to 53% with the transplant patients’ median age from 43 to 52.8. The duration of neutropenia is similar but there was no significant severe watery diarrhea or oral mucositis in our present cohort as compared to the previous 3 + 7 group of patients.

Conclusions: Venetocla-based non-anthracycline induction therapy is feasible and has more propensity to allogeneic transplant in newly diagnosed AML patients and the pre-transplant CR rate and overall survival were improved as compared with conventional 3 + 7 induction, without more safety concerns.

Disclosure: No disclosure of conflict of interest.

19: Acute Leukaemia

Haixiao Zhang¹, Erlie Jiang ²

¹Peking Union Medical school, Tianjin, China, ²Peking Union Medical School, Tianjin, China

Background: Acute myeloid leukemia (AML) is a heterogeneous and aggressive disease caused by leukemia blasts. Bone marrow microenvironment (BMM) contributes to AML cell development. Myelofibrosis (MF) is characterized by excessive deposition of bone marrow reticulin fibrosis and other extracellular matrix proteins. MF of unknown etiology in hematological malignancies is acknowledged to be a reactive response to leukemic BMM.

AML with MF (AML-MF) is not recognized as an AML entity by the World Health Organization (WHO) classification system ^[6]. However, MF was approximately 30-72% at the time of diagnosis of AML and myelodysplastic syndromes (MDS), and 15% was marked reticulin fibrosis. Previous studies have shown that moderate to severe MF is a more advanced risk factor in patients with MDS ^[8-10]. Data pertaining to the AML-MF treatment and prognosis are very limited ^[11,12]. As far the only therapy to cure AML has been allogeneic hematopoietic stem cell transplantation (allo-HSCT). MF’s prognostic effect, which can be assessed by regular evaluation at diagnosis, in transplant AML patients is remains unknown.

Methods: To evaluate the prognostic impact of myelofibrosis (MF) on allogeneic hematological stem cell transplantation (allo-HSCT) outcomes in patients with acute myeloid leukemia (AML), we analyzed newly diagnosed patients with AML who received allo-HSCT in the National Longitudinal Cohort of Hematological Disease (NICHE, NCT04645199) from January 2014 to April 2023. Among the 532 patients, 255 (47.93%) patients were classified into the MF-0 group, 209 (39.29%) into the MF-1 group, and 68 (12.78%) into the MF-2-3 group at initial diagnosis according to the European consensus on the grading of MF.

Results: The MF-2-3 group showed poor overall survival, disease-free survival and cumulative incidence of relapse (CIR). Multivariate analyses showed that MF-2-3 (hazard ratio [HR] =2.17, P = 0.023) was an independent risk factor for CIR post-transplantation. Furthermore, MF delayed neutrophil and platelet engraftment and delayed B cell recovery post-transplantation. The MF-2-3 group had a higher cumulative incidence of acute graft-versus-host disease and a lower cumulative incidence of EBV-emia and CMV-emia post-transplantation than the MF-0 and MF-1 groups, however, the difference was not statistically significant.

Conclusions: These findings demonstrate the importance of MF in transplant outcomes and has attracted more attention to AML-MF.

Disclosure: none

19: Acute Leukaemia

Rihab Ouerghi¹, Nour Ben Abdeljelil ¹, Sabrine Mekni¹, Insaf Ben Yaiche¹, Ines Turki¹, Rim Dachraoui¹, Dorra Belloumi¹, Lamia Torjemane¹, Rimmel Kanoun¹, Saloua Ladeb¹, Tarek Ben Othman¹

¹Service d’Hématologie et de Greffe, Centre National de Greffe de Moelle Osseuse, Tunis, Tunisia

Background: Relapse remains the major cause of failure in adults with high-risk acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem-cell transplantation (AHSCT). The management of relapsed patients is a clinical challenge, especially in limited resource countries. The aim of our study was to evaluate the cumulative incidence of relapse (CIR) post AHSCT, identify predictive factors of relapse and evaluate the outcome and management of relapsed ALL in adult patients.

Methods: A retrospective study was conducted in adult patients who underwent AHSCT from HLA-identical sibling donors between November 2003 and December 2022. Conditioning regimens consisted of fractionated TBI (F-TBI) (3fractions/9.9Gy) with etoposide or cyclophosphamide or chemotherapy-based regimen (intravenous busulfan). GVHD prophylaxis consisted of cyclosporine and short course of methotrexate. Stem cell sources were bone marrow (BM) or peripheral blood stem cell.

Results: One hundred and five patients (69 males and 36 females) were included. Median age is 30 years (18-50 years): 60 B-ALL (57%) and 45 T-ALL (43%). Cytogenetic analysis was available for 83 patients: 33% of patients had high-risk cytogenetic abnormalities (25% had t(9,22) or positive BCR-ABL transcript). Before AHSCT, 86% of patients were transplanted in first complete remission (CR1). MRD was performed in 66% patients (MFC and/or molecular biology) and was positive in 55% of patients. The median time from diagnosis to AHSCT was 6 months (2-137m). Conditioning regimens were TBI-based in 60% of patients and 51% of patients received peripheral blood stem cell. CMV reactivation was observed in 41% of patients. The CI of acute GVHD (≥grade 2) and chronic GVHD were 32% and 50%, respectively. The CI of NRM was 17.6%. The 2-year CIR was 30% (medullary and combined relapse n = 26, extramedullary relapse n = 6, molecular relapse n = 4). The median time of relapse was 9 months (2-46m). Twenty-two patients were managed with palliative cares and 14 received salvage therapy (chemotherapy +/- radiotherapy n = 9, donor lymphocyte infusion n = 1, ITK only n = 4). A second CR was obtained in 8 patients and 3 patients underwent a second AHSCT. At last follow-up, 7 patients are alive. After a median follow up of 29 months (1-207m), the 2-year OS and EFS for the entire cohort and relapsed patients were 60% vs 31% and 53% vs 14%, respectively. At last follow-up, 49 patients (47 %) died. The main cause of death was relapse (n = 26; 53%). In univariate analysis, chemotherapy-based conditioning regimen was the only significant factor of CIR (p = 0.01).

Conclusions: The prognosis of adult patients relapsing after AHSCT is dismal. To reduce the risk of relapse TBI based conditioning regimen and immunotherapy should be considered when possible.

Disclosure: Nothing to declare

19: Acute Leukaemia

Iveta Oravcova^1,2, Zuzana Rusinakova¹, Eva Mikuskova¹, Miriam Ladicka¹, Ludmila Demitrovicova¹, Alica Slobodova¹, Vanda Mikudova¹, Jana Spanikova¹, Radka Vasickova¹, Denis Urban¹, Kristina Bandurova¹, Lubos Drgona^1,2, Silvia Cingelova ¹

¹National Cancer Institute, Bratislava, Slovakia, ²Faculty of Medicine Comenius University, Bratislava, Slovakia

Background: Obesity has been recognized as risk factor for many types of cancer and at the same time it is considered as an adverse prognostic factor associated with cancer survival. This study assessed the effect of body mass index (BMI) on transplantation outcomes in allogeneic hematopoietic cell transplantation (HCT) in AML and ALL recipients.

Methods: We retrospectively analyzed 98 adult AML and ALL patients who were followed up after alloSCT in National Cancer Institute in Slovakia between March 2013 and October 2023.

According to the World Health Organization (WHO) international BMI classification, patients were classified as obese when BMI was ≥ 30kg/m². We divided patients into 2-groups: BMI < 30kg/m² (non-obese patients) and BMI ≥ 30kg/m² (obese patients).

Results: At median follow up 22,3 (4,1-125,8) months, 98 patients entered the analysis (median age at alloSCT 49 years, 53 (54,5%) male). Median BMI value was 24,84 kg/m². We identified 80 patients with BMI < 30kg/m² (81,6%) and 18 (18,4%) with BMI ≥ 30kg/m². There was no difference in the prevalence of obesity between the genders (p = 0,299).

1 and 3- year overall survival (OS) for the BMI < 30kg/m² group was 68,6% (CI 95%; 58,1% - 79,0%) and 45,9% (CI 95%; 33,3% - 58,5%) with median OS 34,5 months (CI 95% 18,3-57,0); and for the obese group 32,5% (CI 95%; 9,4% - 55,6%) and 13,0% (CI 95%; 0,0% - 27,9%) with median OS 4,6 months (CI 95% 3,0-8,5). The difference between groups was statistically significant, HR 0,34 (95% CI 0,15-0,79); (p = 0,0002).

1 and 3- year relapse free survival (RFS) for the BMI < 30kg/m² group was 58,8% (CI 95%; 47,8% - 69,8%) and 41,2% (CI 95%; 29,1% - 53,4%) with median RFS 30,1 months (CI 95% 8,5-42,9); and for the obese group 20,7% (CI 95%; 0,4% - 41,1%) and 13,8% (CI 95%; 0% - 31,3%) with median RFS 3,5 months (CI 95% 1,9-4,4). The difference between groups was statistically significant, HR 0,39 (95% CI 0,18-0,87); (p = 0,001).

Obese patients have higher 12-months cumulative incidence of relapse rates than non-obese patients: 53,7% (CI 95%; 29,1%-99,3%) vs 29,5% (CI 95%; 20,5%-42,3%). There was no difference in non-relapse mortality between obese and non-obese patients.

Conclusions: Patients with BMI ≥30kg/m² had significantly lower one and three-year survival rates and higher cumulative incidence of relapses than those with BMI <30kg/m².

Disclosure: Nothing to declare.

19: Acute Leukaemia

Mimi Xu ^1,2,3, Yuqing Tu^1,2,3, Mengqi Xiang^1,2,3, Yi Fan^1,2,3, Xiang Zhang^1,2,3, Tiemei Song^1,2,3, Lian Bai⁴, Xiaoli Li⁵, Yang Xu^1,2,3, Yuejun Liu^1,2,3, Jia Chen^1,2,3, Depei Wu^1,2,3

¹National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China, ²Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China, ³Key Laboratory of Stem Cells and Biomedical, Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Suzhou, China, ⁴Canglang of Suzhou Hospital, Suzhou, China, ⁵Soochow Hopes Hematonosis Hospital, Suzhou, China

Background: Accumulating evidences indicated the effectiveness and importance of measurable residual disease (MRD) guided pre-emptive therapy in acute myeloid leukemia (AML) patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, limited data is available on the pre-emptive utility of venetoclax (VEN) for MRD positive in AML patients post-HSCT. This study was conducted to explore the efficiency and tolerability of VEN combined with hypomethylating agents (HMAs) based treatment for AML patients with MRD positive post-HSCT.

Methods: We collected retrospectively the data from 10 patients who underwent first allo-HSCT with high-risk AML between July 2020 and April 2022 and initiated VEN-based pre-emptive threapy for MRD positivity between March 2021 and July 2022 in our center for analysis. Patients who experienced haematological relapse before VEN-based pre-emptive treatment were excluded. The VEN combined with HMAs-based treatment regimen comprised 100 mg VEN daily on day 1 to day 21 and 15 mg/m² decitabine on day 1 to day 3 or 75mg/m2 azacytidine on day 1 to day 5 (or day 7). FLT3-ITD positive patients also added FLT3 inhibitor sorafenib (400mg scheduled for days 1 to 21). The primary endpoints of this study were MRD response, overall survival (OS) and event free survival (EFS). The secondary endpoints included adverse events (AEs), cumulative incidence of relapse (CIR) and nonrelapse mortality (NRM).

Results: 10 patients were included. The median age of the patients at the time of transplantation was 49 (range, 16-57)y. The rate of MRD response was 70.0% (7/10) and 71.4% (5/7) of whom achieved MRD response after first circle of VEN-based combination threapy. The median time from initiating VEN-based pre-emptive threapy to MRD response was 64 (10-175) d. For MRD response patients, two of whom appeared hematologic relapse on day 271 and 336 after MRD response respectively. Three patients had not achieved MRD response, 2 of whom experienced hematological relapse and 1 died from severe GVHD and transplantation associated thrombotic microangiopathy. During the study, we found no tumor lysis syndrome and severe AE for all patients. The median follow-up was 440.5 (88-872) d. 5 patients still had EFS and were alive with MRD negative CR at the time of last follow-up. Overall, the 1-y OS and EFS after VEN-based pre-emptive threapy were (80.0±12.6)% and (60.0±15.5)%, respectively. The cumulative incidence of relapse (CIR) at one years was (30.0±2.4)%, and nonrelapse mortality was (10.0±1.0)%.

Table 1 Patient characteristics

Conclusions: We conclude that VEN combined with HMAs-based regimen as pre-emptive treatment is efficient for patients with AML post-HSCT and with acceptable side effects.

Disclosure: Nothing to declare

19: Acute Leukaemia

Xiao Han¹, Qingxiao Song ¹, Kai Wan¹, Mengyun Zhang¹, Xue Liu¹, Hongju Yan¹, Cheng Zhang¹, Qin Wen¹, Xi Zhang¹

¹Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Chongqing, China

Background: Older or unfit patients with acute myeloid leukemia (AML) have a dismal prognosis. The combination of venetoclax with azacitidine had promising efficacy, but the minimal residual disease (MRD) negative rate is only 30-40%. In most cases measurable residual disease (MRD) positivity predicts hematologic relapse potentially allowing early therapeutic intervention.

Methods: This is a prospective, one-arm, multicenter, open clinical trial, Adults age ≥18 years with newly diagnosed AML ineligible for intensive chemotherapy were enrolled. Patients received induction treatment with venetoclax 100mg d1, 200mg d2, 400mg d3-28, azacytidine 75mg/m² d1-7, cytarabine 10mg/m² q12h d1-7. The primary observation was the remission rate (CR/CRi) and the negative rate of MRD.

Results: The baseline characteristics of 46 older or unfit patients who can evaluate the efficacy are presented in Table 1. Following the first course of Ven+AZA + LDAC treatment, the outcomes were as follows: 27 patients (58.7%) achieved complete remission (CR) with negative minimal residual disease (MRD), 14 patients (30.4%) achieved CR with positive MRD, 1 patients (2.2%) experienced partial remission (PR), and 4 patient (8.7%) did not achieve remission (NR). The overall response rate (ORR) was 91.3%. Subgroup analysis revealed that out of the 23 older patients, 16 (69.6%) achieved CR with negative MRD, 6 (26.1%) achieved CR with positive MRD. Among the 23 initially diagnosed unfit patients, 11 (47.8%) reached CR, with 8 (34.8%) showing negative MRD, 1 (4.3%) experiencing PR, and 3 (13.0%) not achieving remission. The median follow-up time was 8.3 months (range: 3-24.3 months), and the estimate median overall survival (OS) was 20.34 months. Subgroup analysis revealed that older patients had better survival outcomes compared to unfit patients, although the difference was not statistically significant. Among them, 9 patients had underwent allogeneic hematopoietic stem cell transplantation (HSCT), and 8 of the 9 HSCT patients were alive at the time of manuscript writing, One patient died because of SCT related thrombotic microangiopathy (TMA). This observation might be attributed to the limited sample size, indicating the necessity of gathering more data for comprehensive analysis. Safety: All the 23 older patients had neutropenia, which controlled after therapy, without severe infection and bleeding complications. 23 patients with unfit had severe complications such as severe infection, respiratory failure, or intracranial hemorrhage before treatment, but no treatment-related deaths occurred during the induction period.

Conclusions: The incidence of remission was higher among newly diagnosed older patients who received Ven+AZA + LDAC, especially CR with negative MRD. However, the remission rate of unfit AML patients has been improved compared to traditional chemotherapy, but the negative rate of MRD has not improved. Infection, chemotherapy-related mortality, and the tolerability were acceptable. At the same time, it would be contribute to provide transplant conditions for patients and prolong survival. However, it is necessary to further expand the sample size and extend the follow-up time to assess the long-term survival rate.

Clinical Trial Registry: ChiCTR2200063804

Disclosure: Nothing to declare.

19: Acute Leukaemia

Riccardo Boncompagni ¹, Chiara Camerini¹, Ilaria Cutini¹, Mirella Giordano¹, Antonella Gozzini¹, Chiara Nozzoli¹, Edoardo Simonetti¹, Riccardo Saccardi¹

¹BMT Unit, Careggi University Hospital, Firenze, Italy

Background: New drugs targeting acute leukaemia antigens or cellular survival/proliferation pathways are granting promising results in patients with relapsed and/or refractory acute leukaemia leading more patients to achieve a control of disease and access to allogenic hematopoietic stem cell transplantation (HSCT), the only potentially curative treatment. Here we investigated if target-therapy can confer a real-life survival advantage also in patients who relapse following HSCT, a population characterized from a very poor prognosis.

Methods: We retrospectively analysed data from patients affected by acute myeloid, mixed-phenotype, lymphoblastic leukaemia (AML, MPAL, ALL respectively) and blast crisis of chronic myeloid leukaemia (CB-CML) who performed allogeneic HSCT at Careggi University Hospital of Florence in the last 10 years. Primary endpoint of the current research was to compare overall survival (OS) and progression free survival (PFS) between patients treated or not with target therapy. Target therapy was administered based on availability at our institution.

Results: We found 288 HSCT performed for 275 patients. Indication for HSCT was AML for 196 (68%), ALL for 74 [24%; 25 (34%) with BCR/ABL mutation, 12 (16%) of T-lineage], CB-CML for 11 (4%) and MPAL for 10 (3%). Median age was 50 (19 – 69) and median comorbidity index (HCT-CI) was high (3; 0 – 9); however reduced intensity conditioning regimen was used only in 93 (32%). A significant number of AML was in active disease status at the time of HSCT (74, 38%), and molecular or cytofluorimetric minimal residual disease was detectable in more than half of the others (86 out of 122, 70%). Median OS was not reached, with 57% of patients alive with a 69 months median follow-up. Relapse incidence after HSCT was 36% (n = 100) and median PFS was reached at 18 months (95% confidence interval [CI]: 7 – 29). In the group who received a target therapy (n = 63) we observed both an OS (45 vs 7 months; p < 0,001) and PFS advantage (26 vs 2 months; p 0<,001). Donor lymphocytes infusions (DLI) was administered in 38% (n = 24) of target therapy group and conferred a further OS advantage (11 vs 42 months; p = 0,022). Finally, 3 out of 13 (23%) patients who performed a second HSCT after savage therapy with target therapy were alive and in complete remission at the time of their last follow-up.

Conclusions: Despite the low potency of monocentre retrospective study, our results support the hypothesis that new therapies for acute leukaemia are effective for patients who relapse following HSCT, and the possibility of combination of DLI and of a subsequent second HSCT may grant a longer survival in this very high-risk population.

Disclosure: We declare no potential conflict of interest.

19: Acute Leukaemia

Conor Browne ¹, Micheal Brennan¹, Mairead Ni Chonghaile¹, Sarah Maher¹, Greg Lee¹, Deirdre Waldron¹, Nicola Gardiner¹, Michelle Regan¹, Lorraine Brennan¹, Carmel Waldron¹, Catherine M. Flynn¹, Eibhlin Conneally¹, Patrick J. Hayden¹, Robert Henderson¹, Elisabeth Vandenberghe¹, Christopher L. Bacon¹

¹St James Hospital, Dublin 8, Ireland

Background: Adult acute lymphoblastic leukaemia (ALL) historically carries a poor prognosis with cure rates of less than 40%. Despite advances in therapeutics, allogeneic stem cell transplantation (AlloSCT) remains pivotal in the management of patients with high risk adult ALL.

Methods: The records of consecutive ALL patients receiving AlloSCT between 01/01/2013 and 31/12/2022 were retrieved from the St. James’ Hospital transplant-database and their electronic medical records. Progression free survival (PFS) and overall survival (OS) were estimated via the Kaplan-Meier method.

Results: 89 patients with ALL received AlloSCT. Clinical details are shown in Table-1. 74 (83%) had B-ALL with a median white cell count (WCC) of 30x10⁹/L (0.5-830) at diagnosis. 15 (17%) had T-ALL with a median WCC of 100x10⁹/L (4.9-470) at diagnosis.

38 patients (43%) had high-risk cytogenetics defined as having either a Philadelphia chromosome t(9;22)(q34;q11), N = 17 (9%), KMT2A rearrangement t(4;11)(q21;q23) N = 12 (13%), complex karyotype N = 2 (2%), low-hypodiploid N = 4 (4%) or near-triploid haplotype N = 3 (3%). 64 patients (72%) achieved complete remission (CR) post induction therapy. 13 (15%) had primary refractory disease and 16 (18%) in remission relapsed prior to transplant requiring re-induction. 73 (82%) were transplanted in CR1, 14 (16%) in CR2, 1 in CR3 and CR4.

The median time from diagnosis to transplant was 6 months (2-85). The median CD34 cell count infused was 3.32x10⁶/kg (0.67-5.7) with a median CD3 cell count of 3.08x10⁷/kg (1.21-52). The median days to neutrophil engraftment was 21 (10-34) and to platelet engraftment was 18 (9-96).

66 patients (74%) developed graft-versus-host-disease (GVHD); 63 (71%) acute-GVHD and 30 (34%) chronic-GVHD. Acute-GVHD occurred at a median of 30 days (13-298) post-transplant. 16 (18%) experienced Grade I, while 47 (53%) developed Grade II-IV acute-GVHD. Of those with acute-GVHD, 15 cases (24%) were steroid refractory requiring additional therapies including ruxolitinib, mycophenolate-mofetil, extracorporeal-photopheresis and ATG.

30 patients (34%) developed viral reactivation involving CMV, EBV or adenovirus. 5 patients had associated EBV post-transplant lymphoproliferative disorder.

9 patients (10%) received donor-lymphocyte infusions (DLI) at a median time of 12 months (4-33) post-transplant. 8 received pre-emptive DLI for mixed chimerism, 1 received therapeutic-DLI for relapsed disease. 3 patients developed acute-GVHD post-DLI. 7 cases (80%) achieved complete donor chimerism post-DLI.

The median duration of follow-up was 36 months (1-129). 18 patients (20%) relapsed at a median time of 8.5 months (1-63) post-transplant. Treatment strategies at relapse included blinatumomab, inotuzumab, Hyper-CVAD, nelarabine, TKIs, palliation and CAR-T therapy.

27 patients (30%) died during follow-up at a median time of 9 months (1-71) post-transplant; relapse-related mortality N = 11 (12%), transplant-related mortality (TRM) N = 14 (16%), lost to follow-up N = 2 (2%). Causes of TRM included GVHD (N = 3), veno-occlusive disease (N = 1), infection (N = 7), EBV-PTLD (N = 1), neurological complication (N = 1) and secondary malignancy (N = 1). The 100-day TRM rate was 6%.

The 5-year OS was estimated at 69% with a 5-year PFS of 62% as shown in Graph-1. OS or PFS didn’t differ significantly between those with acute-GVHD and those without (p = 0.7).

Table 1. Clinical Details

Conclusions: AlloSCT in high-risk patients is an effective strategy for the management of adult ALL with a 5 year OS of 69% in this cohort.

Disclosure: Nothing to declare.

19: Acute Leukaemia

Saveria Capria ¹, Silvia Maria Trisolini¹, Lorenzo Torrieri², Elena Amabile², Giovanni Marsili³, Alfonso Piciocchi³, Walter Barberi¹, Daniela Diverio¹, Daniela Carmini¹, Massimo Breccia², Maurizio Martelli², Clara Minotti¹

¹AOU Policlinico Umberto I, Rome, Italy, ²Sapienza University, Rome, Italy, ³GIMEMA Foundation, Rome, Italy

Background: The introduction of tyrosine kinase inhibitors (TKIs) in the treatment of FLT3-mutated AML has been a therapeutic breakthrough. However, prognosis remains challenging.

Methods: We retrospectively analyzed all patients with FLT3-mutated AML who were eligible for intensive therapy and treated at our institution since 1999, focusing on changes in management over time and the impact of TKI treatment.

Results: The cohort comprised 140 patients (68M/72F) with a median age of 51 years (14-73), 28 (21%) had WBC ≥100,000/µl at diagnosis and 38 were older than 60 years. The ITD/TKD ratio was 120/20 and 73 patients (52%) had NPM1 co-mutation.

Until 2018, 101/140 patients received the DCE regimen without TKI, while 39/140 patients diagnosed since 2018 received 3 + 7+midostaurin.

The overall CR rate was 64% (90/140), and 73% (53/73) in NPM1-mutant patients, regardless of TKI treatment during induction.

The CR rate was similar in both younger and older patients and was positively influenced by co-existing NPM1 mutation (p: 0.032) and WBC count <100,000/µl (p = 0.013) in univariate analysis. TKI administration during induction did not have a significant effect.

In a multivariate model adjusting for sex and age, only WBC count was confirmed to have an independent prognostic impact on response (OR 3.04 – CI 1.23-7.71 – p = 0.017).

Allogeneic transplantation was performed in 41/90 patients who achieved CR1 (22/60 no-TKI and 19/30 TKI), the transplantation rate between no-TKI and TKI patients is not statistically significant. Autologous transplantation was performed in 18 patients. No transplantation was performed in 31 patients.

The median probability of EFS at 3 and 6 years is comparable between autografted and allografted patients (1.1 vs. 1.6 years respectively – p = 0.9).

The cumulative incidence of 1-year non-relapse mortality was 0.00% for autologous and 28% (CI: 15-42) for allogeneic transplantation (p = 0.007), while the cumulative incidence of 1-year and 3-year relapse was 39% (CI: 17-61) vs. 15% (CI: 6.1-28) and 57% (CI: 30-77) vs. 21% (CI: 9.5-35), respectively (p = 0.004).

There was no statistical difference in outcome based on TKI administration at induction, although these data may be affected by the smaller number of patients in the TKI group.

Forty-three patients (34 no-TKI and 9 TKI) were refractory to induction. Twenty-five received salvage treatment (10 CHT + TKI, 4 single-agent TKI, 11 standard CHT). Of the 14 patients who received a TKI-containing regimen, 11 underwent allogeneic transplantation while none of the patients in the standard CHT group underwent transplantation. The 5-year OS of transplanted patients after salvage treatment is 51%.

Overall, 70/140 patients received stem cell transplantation, 18 autologous and 52 allogeneic (41 CR1 and 11 refractory). In 8/52 cases, preemptive TKI treatment was administered post-transplant due to FLT3 mutation recurrence in morphologic CR; all patients are alive at a median of 65 months (range 16-98) post-transplant and TKI treatment was discontinued after 2 years of continuous CR.

Conclusions: Allogeneic transplantation remains crucial in FLT3-mutated AML. However, several unanswered questions remain, such as how to optimize the use of different inhibitors to achieve the best pre-BMT response, and the potential impact of preemptive post-transplant therapy.

Disclosure: Nothing to declare.

19: Acute Leukaemia

A.S. Hartz¹, L. Li¹, H. Aslan¹, E. Pepeldjiyska¹, E. Rackl¹, T. Baudrexler¹, P. Bojko², J. Schmohl³, A. Rank⁴, C. Schmid⁴, H.M. Schmetzer ¹

¹Working-Group: Immune-Modulation, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany, ²Rotkreuzklinikum Munich, Munich, Germany, ³Department of Hematology and Oncology, Stuttgart, Germany, ⁴University Hospital of Augsburg, Augsburg, Germany

Background: Novel immunotherapies that overcome immunescape of acute myeloid leukemia (AML) cells are urgently needed. AML establishes a tolerant, immune-inert microenvironment e.g. by accumulating tolerogenic dendritic cells (tDCs). TDCs are dendritic cells and can be generally characterized by a modified cytokine production, ultimately leading to T-cell anergy. In this study we focused on tDCs expressing ILT-3, CTLA4, PD-1, IL3RA.

Leukemia-derived dendritic cells (DCleu) can be generated ex vivo directly from leukemic whole blood (WB) by using (clinically approved) GM-CSF and PGE-1 (Kit-M), leading to antileukemic immune responses after mixed lymphocyte culture enriched with patients’ T-cells (MLC).

Aims: To evaluate Kit-M on frequencies of DCleu or tDCs and on DC mediated (antileukemic) effects and to correlate results with patients’ clinical characteristics.

Methods: WB samples from 18 AML patients and 5 healthy WB samples were treated with vs without Kit-M to generate DC/DCleu and to quantify tDCs. After MLC, leukemia specific/antileukemic effects were assessed through the degranulation-, the intracellular IFNγ production- and the cytotoxicity fluorolysis assay. Quantification of cell subtypes was performed via flow cytometry.

Results: Treating leukemic WB with Kit-M vs control increased significantly frequencies of (mature) DCleu without induction of blast proliferation and significantly decreased frequencies of tDCs (DCs co-expressing ILT-3, CTLA4, PD-1 or IL3RA). After T-cell enriched MLC of Kit-M treated vs. not pretreated WB, frequencies of immunoreactive cells (e.g. non-naïve T-cells, CIK cells) were (significantly) increased, of regulatory T-cells (e.g. CD152 + T-cells) were (significantly) decreased, of activated T-cells (e.g. CD154 + T-cells) were increased and degranulating (CD107a + ) and intracellular IFNγ positive (e.g. CD107a+ non-naïve, - central memory, - non-naïve) T-cells were (significantly) increased. A cytotoxicity fluorolysis assay showed an improved blast lysis in Kit-M treated WB compared to control. We found negative correlations between frequencies of tDCs and improved blastolytic functionality and confirmed positive correlations between frequencies of DC/DCleu and improved blastolytic functionality. In patients with favourable (vs adverse) ELN risk stratification and response to chemotherapy (vs no response) lower frequencies of tDCs were found.

Conclusions: Kit-M treatment of leukemic WB was shown to induce DC/DCleu, to reduce tDCs and to induce leukemia-specific antileukemic immune cells after mixed lymphocyte culture. Reduction of tDCs correlated negatively with improved blastolytic functionality. Kit-M in vivo treatment could lead to an improved immune response and overcoming the immunosuppressive tumor environment in vivo.

Disclosure: Modiblast Pharma GmbH (Oberhaching, Germany) holds the European Patent 15 801 987.7-1118 and US Patent 15-517627 ‘Use of immunomodulatory effective compositions for the immunotherapeutic treatment of patients suffering from myeloid leukemias’, with whom H.M.S. is involved with.

19: Acute Leukaemia

Jiayu Huang¹, Luxiang Wang¹, Chuanhe Jiang¹, Zilu Zhang¹, Zengkai Pan¹, Ling Wang², Jieling Jiang², Jiong Hu², Jun Zhu³, Lijing Shen⁴, Suning Chen⁵, Yang Cao⁶, Xiaoxia Hu ¹

¹State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ²Shanghai Institute of Hematology, Blood and Marrow Transplantation Center, Collaborative Innovation Center of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ³GoBroad Medical Institute of Hematology (Shanghai Center), Liquan Hospital, Shanghai, China, ⁴Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ⁵National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China, ⁶Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Background: Allogeneic hematopoietic cell transplantation (allo-HSCT) is still a potentially curative therapy for high-risk B-lineage acute lymphoblastic leukemia (B-ALL). However, relapse is the major cause for transplant failure, especially within the first two years after allo-HSCT.

Methods: This multicenter, retrospective study was designed by the First Affiliated Hospital of Soochow University, Wuhan Tongji Hospital, Shanghai Renji Hospital, Shanghai Zhaxin Hospital and Shanghai Ruijin Hospital, to evaluate the efficacy and safety of blinatumomab as maintenance therapy after allo-HSCT in B-ALL patients. Consecutive patients diagnosed with B-ALL from November 2021 to April 2023 were screened, and the eligibility criteria were as followed: (1) aged ≥ 14 years; (2) patients were MRD-negative measured by flow cytometry with a sensitivity of 0.02%; (3) B-ALL with CD19 expression; (4) patients with complete medical information. The last follow-up was November 30, 2023. As pre-determined schedule, blinatumomab was administrated as a continuous infusion for 14-21 days.

Results: A total of 17 patients were retrospectively enrolled. The median age was 30-year old (range, 14-60). Before allo-HSCT, one patient was in relapse, four in second complete remission (CR) and the other patients (n = 12) in first CR. 76.5% patients (n = 13) were categorized as high-risk B-ALL according to NCCN 2023. 88.2% (n = 15) patients received graft from haploidentical donors. The median interval from transplant to the start of blinatumomab maintenance was 102 days (range, 42 to 227), with a median course of 1 (range, 1-6). Only four treatment courses were temporarily discontinued due to infection in the first cycle of blinatumomab maintenance, but the remaining thirty treatment courses were completed without interruptions. With a median follow-up of 269 days (range, 120-674), the 1-year overall survival (OS), event-free survival, relapse, and graft versus host disease (GVHD)-free and relapse-free survival for all patients were 69.1% (95% CI 44.2%-100%), 72.6% (95% CI 49.9%-100%),10.4% (95% CI 8.3-12.5%) and 72.9% (95% CI 50.3%-100%) respectively. One patient (P15) received one cycle of blinatumomab at 3-month after allo-HSCT, and relapsed at 8.5 months. Outcomes of patients based on different classification were shown in Table 1. Patients with negative MRD pre-HSCT had a superior OS as compared to those with positive MRD (not reached vs. 286 days P = 0.024). Two patients died of non-relapse causes related to blinatumomab, including transplant-associated thrombotic microangiopathy (n = 1) and blood stream infection (n = 1). The incidence of grade III-IV acute GVHD associated with blinatumomab was 2.9% (n = 1).

Table 1: Follow-up outcome of allo-HSCT patients based on MRD pre-allo-HSCT or R-DRI or NCCN 2023 risk