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
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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