HLA Factors versus Non-HLA Factors for Haploidentical Donor Selection

Authors

Rohtesh S Mehta
Kai Cao
Rima M Saliba
Gheath Al-Atrash
Amin M Alousi
Konstantinos Lontos
Curtis Marcoux
Yudith Carmazzi
Gabriela Rondon
Qaiser Bashir
Chitra M Hosing
Partow Kebriaei
Issa Khouri
David Marin
Yago Nieto
Betul Oran
Uday R Popat
Muzaffar H Qazilbash
Jeremy Ramdial
Katayoun Rezvani
Richard E Champlin
Elizabeth J Shpall

Publication Date

3-1-2023

Journal

Transplantation and Cellular Therapy

Abstract

When multiple haploidentical donors are available for transplantation, those of younger generations are generally selected over those of older generations. However, it is unclear who is the optimal donor when selecting candidates from within a generation, such as father versus mother, son versus daughter, or brother versus sister. Although traditionally male donors are favored over female donors, particularly for male recipients, and significant associations of individual HLA mis(matches) on outcomes are being increasingly recognized, the hierarchy of factors for donor selection is indeterminate. To assess whether HLA factors take precedence over non-HLA factors and to isolate the influence of specific characteristics on outcomes, we analyzed 412 patients stratified by donor relationship: child donor (son [n = 202] versus daughter [n = 96]), parent (father [n = 28] versus mother [n = 29]), and sibling (noninherited maternal [NIMA; n = 29] versus paternal [NIPA; n = 28] mismatched). Among siblings, NIMA mismatch was associated with a lower risk of acute graft-versus-host disease (aGVHD); B-leader mismatch was associated with high nonrelapse mortality (NRM), poor progression-free survival, and a trend toward poor overall survival (OS), whereas A-mismatch was associated with lower aGVHD. Among parent donors, the relationship did not impact any outcome; B-leader mismatch was associated with higher NRM and a trend toward poor OS, whereas A-mismatch was associated with lower NRM and improved progression-free survival and OS. Among child donors, no individual HLA mismatch was predictive of any outcome, and daughter donors were not associated with any adverse outcomes in multivariate analyses. Our data suggest that certain HLA factors may be more significant in some cases and should be given priority over simply selecting a donor based on relationship/sex.

Keywords

Child, Humans, Male, Female, Hematopoietic Stem Cell Transplantation, Donor Selection, Graft vs Host Disease, Tissue Donors, Mothers

Comments

Supplementary Materials

PMID: 36470579