TY - JOUR
T1 - HLA Factors versus Non-HLA Factors for Haploidentical Donor Selection
AU - Mehta, Rohtesh S.
AU - Cao, Kai
AU - Saliba, Rima M.
AU - Al-Atrash, Gheath
AU - Alousi, Amin M.
AU - Lontos, Konstantinos
AU - Marcoux, Curtis
AU - Carmazzi, Yudith
AU - Rondon, Gabriela
AU - Bashir, Qaiser
AU - Hosing, Chitra M.
AU - Kebriaei, Partow
AU - Khouri, Issa
AU - Marin, David
AU - Nieto, Yago
AU - Oran, Betul
AU - Popat, Uday R.
AU - Qazilbash, Muzaffar H.
AU - Ramdial, Jeremy
AU - Rezvani, Katayoun
AU - Champlin, Richard E.
AU - Shpall, Elizabeth J.
N1 - Publisher Copyright:
© 2022 The American Society for Transplantation and Cellular Therapy
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
KW - Donor age
KW - Donor sex
KW - Father versus mother
KW - HLA A-mismatch
KW - HLA B-leader mismatch
KW - HLA haploidentical donor
KW - Noninherited maternal antigen
KW - Noninherited paternal antigen
KW - Post-transplantation cyclophosphamide
KW - Sex mismatch
KW - Son versus daughter
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U2 - 10.1016/j.jtct.2022.11.027
DO - 10.1016/j.jtct.2022.11.027
M3 - Article
C2 - 36470579
AN - SCOPUS:85147421469
SN - 2666-6367
VL - 29
SP - 189
EP - 198
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 3
ER -