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2234 How Much Have Post-Transplant Outcomes Improved Since 2000 for Patients with Philadelphia-Positive Acute Lymphoblastic Leukemia in First Remission? a Study from the EBMT Acute Leukemia Working Party

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster I
Hematology Disease Topics & Pathways:
Biological therapies, Lymphoid Leukemias, ALL, Research, Clinical Research, health outcomes research, Diseases, Therapies, Lymphoid Malignancies, survivorship, Transplantation
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Ali Bazarbachi, MD, PhD1, Myriam Labopin2*, Iman Abou Dalle, MD3*, Ibrahim Yakoub-Agha, MD, PhD4*, Regis Peffault De Latour5*, Thomas Schroeder6*, Didier Blaise, MD, PhD7, Xavier Poire, MD8*, Marie Balsat, MD9*, Urpu Salmenniemi10*, Nicolaus Kröger, MD11*, Aleksandr Kulagin Sr.12*, Eva Wagner Drouet, MD13*, Depei Wu14, Eolia Brissot15*, Arnon Nagler, MD16, Sebastian Giebel17*, Fabio Ciceri18* and Mohamad Mohty, MD, PhD19

1American University of Beirut Dept. of Medicine, Beirut, Lebanon
2EBMT Statistical Unit, Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France
3Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut medical center, Beirut, Lebanon
4CHU de Lille, Université de Lille, INSERM U1286, Infinite, 59000, Lille, France
5Hôpital Saint-Louis,, Paris, France
6Department of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany
7Program of Transplant and cellular immunotherapy, Department of Hematology, Institut Paoli Calmettes, Marseille, France
8Section of hematology, Institut Roi Albert II, Cliniques Universitaires St-Luc, Brussels, Belgium
9Clinical Hematology Department, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France, Lyon, France
10Dept of Hematology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland
11University Hospital Eppendorf, Bone Marrow Transplantation Centre, Hamburg, Germany
12b. First State Pavlov Medical University of St. Petersburg, Raisa Gorbacheva Memorial Research Institute for Paediatric Oncology, Hematology, and Transplantation, St-Petersburg, Russia, St. Petersburg, RUS
13University Medicine Mainz, Mainz, Germany
14The First Affiliated Hospital of Soochow University, Suzhou, China
15Sorbonne Université Service d' Hématologie Clinique et Thérapie Cellulaire, Hospital Saint-Antoine, Centre de Recherche Saint-Antoine (CRSA), Paris, France
16Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel
17Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
18Unit of Hematology and Stem Cell Transplantation, Ospedale San Raffaele, University Vita-Salute San Raffaele, Milan, Italy
19Saint-Antoine Hospital, Sorbonne University, Paris, France


Allogeneic hematopoietic cell transplantation (allo-HCT) remains an important curative modality for patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) in first complete remission (CR1). Recent years have witnessed an improvement in transplant techniques and increased use of post-transplant pharmacological interventions aimed at reducing the risk of relapse. However, recent results using the combination of blinatumomab and second or third-generation tyrosine kinase inhibitors (TKI) have challenged the role of allo-HCT in CR1. To address these challenges, we assessed real-world changes over time in transplant characteristics and post-transplant outcomes in adult patients with Ph+ ALL in CR1, using a large dataset from the European Society for Blood and Marrow Transplantation (EBMT) registry.


We identified 3292 adult patients (45% female; median age 45 years, range 18-76) with Ph+ ALL allografted between 2001 and 2020 in CR1 from a matched sibling (38%), unrelated (54%) or haploidentical donor (8%). At transplant, 41% of patients were measurable disease (MRD) positive (pos). The comorbidity index (CI) was zero in 63% of patients with available data. Conditioning was myeloablative (MAC) in 77% of patients, and included total body irradiation (TBI) in 64% of patients. In vivo, T cell depletion (TCD) and peripheral blood stem cells (PBSC) were given to 52% and 86% of patients, respectively. Most patients (66%) and donors (55%) were cytomegalovirus (CMV) positive. Median follow-up for live patients was 56 months (interquartile range [IQR] 28-32).


We compared changes in patient and transplant characteristics over time in 245 patients transplanted in 2001-2005, 679 patients transplanted in 2006-2010, 1035 patients transplanted in 2011-2015, and 1333 patients transplanted in 2016-2020. Patients transplanted in recent years were older, were less likely to be MRDpos, and more likely to receive PBSC and TCD. The 3-year cumulative incidence of relapse (CIR) gradually and significantly decreased from 41% to 32%, 27%, and 19% over the 4 time periods (p=0.001), and non-relapse mortality (NRM) significantly decreased as well from 25% to 24%, 23% and 17% (p=0.001). The 3-year leukemia-free survival (LFS) and overall survival (OS) gradually and significantly improved over time from 34% to 44%, 50%, and 64% (p=0.001) and from 47% to 56%, 65%, and 75% (p=0.001), respectively. Finally, graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) improved from 26% to 34%, 37%, and 49% (p=0.001). In a Cox regression multivariate analysis (MVA), a progressive and significant improvement in all transplant outcomes was noted including reduced acute and chronic GVHD, reduced CIR and NRM, and increased LFS, OS, and GRFS. LFS was also negatively affected by older age, male gender of both patients and donors, MRDpos pretransplant, and the use of reduced intensity conditioning while positively affected by the use of TBI. OS was also positively affected by younger age, female gender of patients, matched sibling donor, TBI, and TCD. This improvement in post-transplant outcomes over time was observed both in MRDpos but also in MRD negative (neg) patients. In MRDneg patients, 3-year CIR decreased from 34% to 30%, 24%, and 17% (p=0.001) over the 4 time periods whereas LFS improved from 41% to 46%, 52%, and 66% (p=0.001). Similarly, in MRD-positive patients, CIR decreased from 48% to 34%, 32%, and 23% (p=0.001) over the 4 time periods whereas LFS improved from 27% to 42%, 47% and 60% (p=0.001).


In patients with Ph+ ALL, we observed an impressive improvement over time in post-transplant outcomes with decreased CIR and NRM and improved LFS, OS, and GRFS, both in MRDpos and MRDneg patients. These large-scale, real-world data can serve as a benchmark for future studies in this setting, including those testing the combination of TKI and blinatumomab as an alternative to transplant.

Disclosures: Yakoub-Agha: Novartis: Consultancy, Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support. Peffault De Latour: Jazz Pharmaceuticals: Honoraria. Salmenniemi: Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Immedia Pharma AB: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Viatris: Consultancy. Kröger: MSD: Honoraria; Neovii Biotech: Honoraria, Research Funding; Jazz: Honoraria; Takeda: Consultancy; BMS: Honoraria, Research Funding; Kite/Gilead: Honoraria; Novartis: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Pfizer: Honoraria; Sanofi: Honoraria. Giebel: Abbvie: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Servier: Honoraria, Speakers Bureau; Swixx: Honoraria, Speakers Bureau; Angelini: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Zentiva: Consultancy, Honoraria. Ciceri: ExCellThera: Other: Scientific Advisory Board . Mohty: JAZZ PHARMACEUTICALS: Honoraria, Research Funding.

*signifies non-member of ASH