TY - JOUR
T1 - Identification of a permissible HLA mismatch in hematopoietic stem cell transplantation
AU - Fernandez-Viña, Marcelo A.
AU - Wang, Tao
AU - Lee, Stephanie J.
AU - Haagenson, Michael
AU - Aljurf, Mahmoud
AU - Askar, Medhat
AU - Battiwalla, Minoo
AU - Baxter-Lowe, Lee Ann
AU - Gajewski, James
AU - Jakubowski, Ann A.
AU - Marino, Susana
AU - Oudshoorn, Machteld
AU - Marsh, Steven G.E.
AU - Petersdorf, Effie W.
AU - Schultz, Kirk
AU - Turner, E. Victoria
AU - Waller, Edmund K.
AU - Woolfrey, Ann
AU - Umejiego, John
AU - Spellman, Stephen R.
AU - Setterholm, Michelle
PY - 2014/2/20
Y1 - 2014/2/20
N2 - In subjects mismatched in the HLA alleles C*03:03/C*03:04 no allogeneic cytotoxic T-lymphocyte responses are detected in vitro. Hematopoietic stem cell transplantation (HSCT) with unrelated donors (UDs) showed no association between the HLA-C allele mismatches (CAMMs) and adverse outcomes; antigen mismatches at this and mismatches other HLA loci are deleterious. The absence of effect of the CAMM may have resulted from the predominance of the mismatch C*03:03/C*03:04. Patients with hematologic malignancies receiving UD HSCT matched in 8/8 and 7/8 HLA alleles were examined. Transplants mismatched in HLA-C antigens or mismatched in HLA-A, -B, or -DRB1 presented significant differences (P < .0001) in mortality (hazard ratio [HR] 5 1.37, 1.30), disease-free survival (HR 5 1.33, 1.27), treatment-related mortality (HR 5 1.54, 1.54), and grade 3-4 acute graft-versus-host disease (HR 5 1.49, 1.77) compared with the 8/8 group; transplants mismatched in other CAMMs had similar outcomes with HR ranging from 1.34 to 172 for these endpoints. The C*03:03/C*03:04 mismatched and the 8/8 matched groups had identical outcomes (HR ranging from 0.96-1.05). The previous finding that CAMMs do not associate with adverse outcomes is explained by the predominance (69%) of the mismatch C*03:03/03:04 in this group that is better tolerated than other HLA mismatches.
AB - In subjects mismatched in the HLA alleles C*03:03/C*03:04 no allogeneic cytotoxic T-lymphocyte responses are detected in vitro. Hematopoietic stem cell transplantation (HSCT) with unrelated donors (UDs) showed no association between the HLA-C allele mismatches (CAMMs) and adverse outcomes; antigen mismatches at this and mismatches other HLA loci are deleterious. The absence of effect of the CAMM may have resulted from the predominance of the mismatch C*03:03/C*03:04. Patients with hematologic malignancies receiving UD HSCT matched in 8/8 and 7/8 HLA alleles were examined. Transplants mismatched in HLA-C antigens or mismatched in HLA-A, -B, or -DRB1 presented significant differences (P < .0001) in mortality (hazard ratio [HR] 5 1.37, 1.30), disease-free survival (HR 5 1.33, 1.27), treatment-related mortality (HR 5 1.54, 1.54), and grade 3-4 acute graft-versus-host disease (HR 5 1.49, 1.77) compared with the 8/8 group; transplants mismatched in other CAMMs had similar outcomes with HR ranging from 1.34 to 172 for these endpoints. The C*03:03/C*03:04 mismatched and the 8/8 matched groups had identical outcomes (HR ranging from 0.96-1.05). The previous finding that CAMMs do not associate with adverse outcomes is explained by the predominance (69%) of the mismatch C*03:03/03:04 in this group that is better tolerated than other HLA mismatches.
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U2 - 10.1182/blood-2013-10-532671
DO - 10.1182/blood-2013-10-532671
M3 - Article
C2 - 24408320
AN - SCOPUS:84899151037
SN - 0006-4971
VL - 123
SP - 1270
EP - 1278
JO - Blood
JF - Blood
IS - 8
ER -