HLA Haplotypes and Relapse After Hematopoietic Cell Transplantation.

Abstract

Recurrence of blood malignancy is the major cause of hematopoietic cell transplant failure. HLA class II molecules play a fundamental role in antitumor responses but the role of class II haplotypes is not known. HLA-DR, -DQ, -DM, and -DO allele variation was determined in 1,629 related haploidentical transplants to study the clinical significance of individual molecules and haplotypes. Outcome correlated with patient and donor variation for HLA-DRβ residue 86 (Gly/Val), HLA-DQ (G1/G2) heterodimers, and donor HLA-DM (DM11,11/nonDM11,11) molecules, and depended on patient-donor mismatching. Risks of relapse were lower for DRβ-86 GlyGly patients when the donor was GlyVal (hazard ratio [HR], 0.46 [95% CI, 0.30 to 0.68]; <i>P</i> < .001); GlyVal patients benefited from <i>HLA-DRB1</i>-matched donors, whereas no donor was superior to another for ValVal patients. G1G2 patients with G1G2-mismatched donors had lower relapse. Transplantation from donors with DMα residue 184 ArgHis was associated with higher risk of relapse (HR, 1.60 [95% CI, 1.09 to 2.36]; <i>P</i> = .02) relative to ArgArg. Relapse and mortality risks differed across HLA-DR-DQ-DM haplotypes. HLA class II haplotypes may be functional constituents of the transplantation barrier, and their consideration in patients and donors may improve the success of transplantation.