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2193 Optimizing Haploidentical Transplant for Adults with Acute Lymphoblastic Leukemia: The Role of Donor and Graft Selection. a Study from the ALWP of the EBMT

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster I
Hematology Disease Topics & Pathways:
Research, Lymphoid Leukemias, ALL, Adult, Clinical Research, Diseases, Treatment Considerations, Registries, Lymphoid Malignancies, Study Population, Human
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Jaime Sanz1*, Allain-Thibeault Ferhat2*, Anna Maria Raiola3*, Didier Blaise, MD, PhD4, Mutlu Arat5*, Yener Koc6*, Malek Benakli, MD7*, Mi Kwon, MD, PhD8,9,10, Alexander Kulagin, MD, PhD11*, Matteo Parma, MD12*, Simona Sica, MD, PhD13,14*, Johanna Tischer, MD15*, Jiri Pavlu, MD, FRCPath, MRCP16, Nathalie Dhédin, MD17*, Giovanni Grillo18*, Nicolaus Kröger, MD Prof19*, Sebastian Giebel, MD, PhD20*, Simona Piemontese21*, Mohamad Mohty, MD, PhD22 and Fabio Ciceri, MD23,24*

1Hematology Department, Hospital Universitari i Politècnic La Fe, Departament de Medicina Universitat de Valencia, CIBERONC, Instituto Carlos III, Spain, VALENCIA, Spain
2EBMT Statistical Unit, Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France
3IRCCS Ospedale Policlinico San Martino, Genova, Italy, Genova, Italy
4Program of Transplant and cellular immunotherapy, Department of Hematology, Institut Paoli Calmettes, Marseille, France
5Demiroglu Bilim University Istanbul Florence Nightingale Hospital, Istanbul, Turkey
6Medicana International Hospital Istanbul, Istanbul, TUR
7Pierre and Marie Curie Center, Algiers, Algeria
8Health Research Institute Gregorio Marañón, Madrid, Spain
9Institute of Health Research Gregorio Marañon, Madrid, Spain
10General University Hospital Gregorio Marañón, Madrid, Spain
11RM Gorbacheva Research Institute, Pavlov University, Saint-Petersburg, Russian Federation
12Hematology Department, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
13Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Rome, Italy
14UNIVERSITA' CATTOLICA SACRO CUORE, ROME, ITA
15Ludwig-Maximilians-University (LMU) Hospital Munich -Campus Grosshadern, Department of Medicine III, Munich, -, DEU
16Centre for Haematology, Department of Immunology and Inflammation, Faculty of Medicine, Imperial College London, London, United Kingdom
17Service d'Hématologie Adolescents et Jeunes Adultes, Hôpital Saint-Louis, PARIS, France
18Department of Hematology and Stem Cell Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
19Department of Stem Cell Transplantation, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
20Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
21Hematology and Bone Marrow transplant Unit, San Raffaele Scientific Institute IRCCS, Milano, Milano, Italy
22Sorbonne University, Hôpital Saint-Antoine, and INSERM UMRs938, Paris, France
23Vita-Salute San Raffaele University, Milan, Italy
24Hematology and Bone Marrow Transplantation Unit, I.R.C.C.S. San Raffaele Scientific Institute, Milan, Italy

Introduction: Haploidentical (Haplo)-hematopoietic stem cell transplant (HSCT) activity has dramatically increased with the advent of post-transplant cyclophosphamide (PTCy). However, there is a paucity of information regarding outcomes of this procedure for patients with high-risk acute lymphoblastic leukemia (ALL).

Patients and Methods: We retrospectively analyzed patient, disease and transplant characteristics, with special focus on donor-related factors that may affect Haplo-HSCT outcomes in adults with ALL in first or second complete remission (CR1 or CR2) who received graft-versus-host disease (GVHD) prophylaxis with PTCy, registered in the EBMT database. The primary endpoint was GVHD-free and relapse-free survival (GRFS).

Results: Included were 933 patients with a median age of 37 years (range, 18-75), 702 (76%) had positive cytomegalovirus (CMV) serostatus and 635 (68%) were in CR1. B-cell ALL accounted for 740 (77%) patients of which 275 (29%) were Philadelphia chromosome positive. Conditioning was myeloablative in 753 (81%) and total body irradiation (TBI)-based in 369 (40%) transplants. Regarding donors, the median age was 36 years (range, 18-65), 355 (38%) were female of which 219 (23%) were donors for male recipients, 637 (70%) had positive CMV serostatus and 644 (69%) donated peripheral blood (PB). The 180-day cumulative incidence of acute GVHD grade II-IV and III-IV was 33% (95% CI 30-36) and 11% (95% CI 9-13), respectively, while the 2-year cumulative incidence of chronic and chronic extensive GVHD was 34% (95% CI 31-38) and 14% (95% CI 11-17), respectively. After a median follow-up of 26 months, the cumulative incidence of relapse and non-relapse mortality (NRM) and the probabilities of leukemia-free survival (LFS), overall survival (OS) and GRFS were 24% (95% CI 21-27), 20% (95% CI 17-23), 56% (95% CI 53-60), 64% (95% CI 61-68) and 42% (95% CI 38-46), respectively. Multivariable analysis identified certain risk factors with a detrimental impact on transplant outcomes. Regarding donor-related factors, the use of PB negatively affected GRFS (hazard ratio [HR] 1.3; 95% CI 1.03-1.64) and OS (HR 1.52; 95% CI 1.12-2.07). Additionally, older donor age (HR 1.14; 95% CI 1.02-1.28) and female donor to male recipient combination (HR 1.67; 95% CI 1.25-2.24) increased the risk of chronic GVHD. Patient-related factors such as positive CMV serostatus and older age, along with certain disease and transplant characteristics, such as CR2 and transplants conducted in earlier periods, adversely impacted GRFS, LFS, and OS by raising NRM in patient-related and relapse risk in disease and transplant-related factors.

Conclusion: Haplo-HSCT with PTCy is effective for patients with ALL in CR. Several modifiable donor-related factors significantly influenced transplant outcomes. Bone marrow grafts should be the preferred source of stem cells. Selecting younger donors and male donors for male recipients could further help in preventing GVHD.

Disclosures: Kwon: Sanofi: Honoraria; Gilead-Kite: Honoraria, Research Funding, Speakers Bureau; Jazz: Speakers Bureau; Pfizer: Speakers Bureau. Kröger: Novartis, BMS, Neovii, Kite/Gilead, Sanofi, Takada: Membership on an entity's Board of Directors or advisory committees; Novartis, Neovii, Kite/Gilead, Therakos, Alexion, Sanofi, Takeda: Other: Speaker honoraria; Novartis, DKMS: Research Funding; Provirex: Consultancy. Giebel: Kiadis Pharma, The Netherlands: Research Funding; Gilead/Kite: Research Funding, Speakers Bureau; Celgene/BMS, Janssen, Pfizer: Speakers Bureau; Immunicum/Mendes: Membership on an entity's Board of Directors or advisory committees; Miltenyi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Equity Ownership (Private company): Research Funding. Mohty: Stemline Menarini: Honoraria; Novartis: Honoraria; GSK: Honoraria; Takeda: Honoraria; Pfizer: Consultancy, Current holder of stock options in a privately-held company, Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria; Adaptive: Honoraria; MaaT Pharma: Current equity holder in publicly-traded company. Ciceri: ExCellThera: Membership on an entity's Board of Directors or advisory committees.

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