title: Effects of mismatching for minor histocompatibility antigens on clinical outcomes in HLA-matched, unrelated hematopoietic stem cell transplants.
abstract: Several studies in HLA-matched sibling hematopoietic stem cell transplantation (HSCT) have reported an association between mismatches in minor histocompatibility antigens (mHAg) and outcomes. We assessed whether single and multiple minor mHAg mismatches are associated with outcomes in 730 unrelated donor, HLA-A, B, C, DRB1, and DQB1 allele-matched hematopoietic stem cell transplants (HSCT) facilitated by the National Marrow Donor Program (NMDP) between 1996 and 2003. Patients had acute and chronic leukemia or myelodysplastic syndrome (MDS), received myeloablative conditioning regimens and calcineurin inhibitor-based graft-versus-host-disease (GVHD) prophylaxis, and most received bone marrow (BM; 85%). Donor and recipient DNA samples were genotyped for mHAg including: HA-1, HA-2, HA-3, HA-8, HB-1 and CD31(125/563). Primary outcomes included grades III-IV acute GVHD (aGVHD) and survival; secondary outcomes included chronic GVHD (cGVHD), engraftment, and relapse. Single disparities at HA-1, HA-2, HA-3, HA-8, and HB-1 were not significantly associated with any of the outcomes analyzed. In HLA-A2-positive individuals, single CD31(563) or multiple mHAg mismatches in the HVG vector were associated with lower risk of grades III-IV aGVHD. Based on these data, we conclude that mHAg incompatibility at HA-1, HA-2, HA-3, HA-8, HB-1, and CD31 has no detectable effect on the outcome of HLA matched unrelated donor HSCT.
authors.affiliation: National Marrow Donor Program, Minneapolis, MN 55413, USA. sspellma@nmdp.org
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Warden
authors.forename: Michael
authors.initials: M
authors.lastname: Haagenson
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Pietz
authors.forename: Els
authors.initials: E
authors.lastname: Goulmy
authors.forename: Edus H
authors.initials: EH
authors.lastname: Warren
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Ellis
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality; D019337:Hematologic Neoplasms / Q000401:mortality* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens; D015996:Survival Rate; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D015778:Minor Histocompatibility Antigens