A1 Refereed original research article in a scientific journal

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




AuthorsKharfan-Dabaja MA, Labopin M, Ayala E, Bazarbachi A, Blaise D, Vydra J, Bramanti S, Itala-Remes M, Schmid C, Busca A, Forcade E, Rabitsch W, Zecca M, Kroger N, Bulabois CE, Grillo G, Rambaldi A, Fanin R, Zallio F, Di Renzo N, Koc Y, Novis Y, McDonald A, Arroyo CH, Sanz J, Nagler A, Ciceri F, Mohty M

PublisherLIPPINCOTT WILLIAMS & WILKINS

Publication year2023

JournalHemaSphere

Journal name in sourceHEMASPHERE

Journal acronymHEMASPHERE

Article number e920

Volume7

Issue7

Number of pages11

eISSN2572-9241

DOIhttps://doi.org/10.1097/HS9.0000000000000920(external)

Web address https://journals.lww.com/hemasphere/Fulltext/2023/07000/Significance_of_Degree_of_HLA_Disparity_Using.6.aspx(external)

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/180395439(external)


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.


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