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Identification of a permissible HLA mismatch in hematopoietic stem cell transplantation

2014; Elsevier BV; Volume: 123; Issue: 8 Linguagem: Inglês

10.1182/blood-2013-10-532671

1528-0020

Marcelo Fernández-Viña, Tao Wang, Stephanie J. Lee, Michael Haagenson, Mahmoud Aljurf, Medhat Askar, Minoo Battiwalla, Lee-Ann Baxter-Lowe, James Gajewski, Ann A. Jakubowski, Susana R. Marino, Machteld Oudshoorn, Steven G. E. Marsh, Effie W. Petersdorf, Kirk R. Schultz, E. Victoria Turner, Edmund K. Waller, Ann E. Woolfrey, John Umejiego, Stephen R. Spellman, Michelle Setterholm,

Immune Cell Function and Interaction

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] = 1.37, 1.30), disease-free survival (HR = 1.33, 1.27), treatment-related mortality (HR = 1.54, 1.54), and grade 3-4 acute graft-versus-host disease (HR = 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.