Significance of Degree of HLA Disparity Using T-cell Replete Peripheral Blood Stem Cells From Haploidentical Donors With Posttransplantation Cyclophosphamide in AML in First Complete Hematologic Remission: A Study of the Acute Leukemia Working Party of the EBMT.

Abstract

Availability of haploidentical donors has broadened utilization of allogeneic hematopoietic cell transplantation (allo-HCT). Peripheral blood stem cells (PBSC) are being used with increased frequency in haploidentical allo-HCT. We evaluated extent of HLA disparity (2-3/8 versus 4/8 HLA antigen mismatches) on post-allograft outcomes when using T-cell replete PBSC from haploidentical donors for acute myeloid leukemia in first complete remission. Primary objectives entailed assessing cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD (any grade). A total of 645 patients received a haploidentical allo-HCT from a donor with either 2-3 of 8 HLA antigen mismatches (n = 180) or with 4 of 8 HLA antigen mismatches (n = 465). Presence of 2-3 of 8 versus 4 of 8 HLA mismatches did not affect the incidence of acute GVHD (grade 2-4) and chronic GVHD (any grade). Overall survival (OS), leukemia-free survival (LFS) relapse incidence (RI), nonrelapse mortality and the composite endpoint of GVHD-free relapse-free survival were also similar among the groups. Pertaining to HLA-B leader matching effect, our analysis did not discern any difference in aforementioned post-allograft outcomes for this variable. However, in univariate analysis, absence of an antigen mismatch in HLA-DPB1 showed a trend for better OS. Notwithstanding inherent limitations associated with registry data, our results did not show an advantage of selecting a haploidentical donor with 2-3 of 8 HLA antigen mismatches over one with 4 of 8 HLA antigen mismatches when using PBSC as the cell source. Adverse cytogenetics remains a major adverse determinant of inferior OS and LFS and a higher RI. Using reduced-intensity conditioning yielded worse OS and LFS.

• Authors: Mohamed A Kharfan-Dabaja, Myriam Labopin, Ernesto Ayala, Ali Bazarbachi, Didier Blaise, Jan Vydra, Stefania Bramanti, Maija Itälä-Remes, Christoph Schmid, Alessandro Busca, Edouard Forcade, Werner Rabitsch, Marco Zecca, Nicolaus Kröger, Claude-Eric Bulabois, Giovanni Grillo, Alessandro Rambaldi, Renato Fanin, Francesco Zallio, Nicola Di Renzo, Yener Koc, Yana Novis, Andrew McDonald, Concepcion Herrera Arroyo, Jaime Sanz, Arnon Nagler, Fabio Ciceri, Mohamad Mohty
• Journal: HemaSphere (Hemasphere) Vol. 7 Issue 7 Pg. e920 (Jul 2023) ISSN: 2572-9241 [Electronic] United States
• PMID: 37388926 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.