Superior GVHD-Free, Relapse-Free Survival for Haploidentical Transplant With PTCy Than Matched Unrelated Donor for AML Patients Transplanted in Second Complete Remission
Researchers at the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation have found that haploidentical transplantation with posttransplant cyclophosphamide (PTCy) delivers superior graft-versus-host disease (GVHD) free, relapse free survival (GRFS) compared with matched unrelated donor transplantation for adults with acute myeloid leukemia (AML) in second complete remission. In a registry analysis of 3,878 first transplants performed between 2010 and 2022, haploidentical PTCy was associated with lower relapse and less chronic GVHD than matched unrelated donor grafts, translating to increased GRFS. When compared with matched sibling donors, haploidentical PTCy showed a trade-off of lower relapse but higher nonrelapse mortality, resulting in no significant difference in leukemia free survival or GRFS.
All patients were adults with AML in CR2 captured in the EBMT registry. The cohort included 803 haploidentical PTCy, 1,271 matched sibling, and 1,804 matched unrelated transplants. A larger share of the haploidentical group had intermediate or adverse ELN 2022 cytogenetics, 80.7 percent versus 79.6 percent for matched unrelated and 70.2 percent for matched sibling, underscoring real world selection toward higher risk biology. Outcomes were evaluated using univariate analyses and multivariable Cox regression. The primary comparative endpoints included relapse incidence, nonrelapse mortality, chronic GVHD, extensive chronic GVHD, leukemia free survival, and GRFS.
Key results favored haploidentical PTCy over matched unrelated donors; haploidentical PTCy reduced relapse incidence and lowered chronic GVHD, with an even larger reduction in extensive chronic GVHD, with these advantages producing superior GRFS versus matched unrelated donors. Compared to matched siblings, haploidentical PTCy reduced relapse risk while increasing nonrelapse mortality, yielding similar leukemia free survival and GRFS. Thus, haploidentical PTCy is a strong clinical option for AML in CR2 when the alternative is a matched unrelated donor, while decisions involving a matched sibling should weigh relapse control against nonrelapse mortality.
Reference:
Ye Y, Labopin M, Yakoub-Agha I, et al. Superior GVHD-Free, Relapse-Free Survival for Haploidentical Transplant With PTCy Than Matched Unrelated Donor for AML Patients Transplanted in Second Complete Remission: A Study From the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Am J Hematol. 2025;100(10):1760-1771.