Effect of BLA class II gene disparity on clinical outcome in unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia: the US National Marrow Donor Program Experience

The clinical importance of HLA class II gene disparity in unrelated stem ce ll transplantation is not entirely known. The impact was evaluated of match ing donors and recipients for HLA-DR, HLA-DO, and HLA-DP genes on clinical outcome after stem cell transplantation for chronic myeloid leukemia (CML) performed between 1988 and 1997. HLA-DRB1, -DQA1, -DQB1, -DPA1, and -DPB1 a lleles were identified in 831 transplant pairs using a combination of seque nce-specific oligonucleotide probes, sequence-specific priming, and sequenc ing methods. Among the 831 pairs, 696 (84%) were HLA-A and -B serologically matched; of these, 565 (81%) were also matched for HLA-DRB1. HLA-DRB1 matc hing correlated with significantly improved survival (relative risk [RR], 1 .29 [95% confidence interval (CI), 1.02-1.64; P = .04]) independently of HL A-DQA1 or HLA-DQB1 (RR, 1.01 [95% CI, 0.81-1.26; P = .94]) and HLA-DPA1 or HLA-DPB1 (RR, 1.11 [95% CI, 0.84-1.48; P = .46]). Single-locus HLA-DQ or HL A-DP disparity was not associated with significantly poorer survival. For p atients who underwent transplantation in the first chronic phase (CIP) from HLA-A, B matched donors, the presence of DRB1 allele mismatching was indep endently associated with increased incidence of grades III-IV acute graft-v ersus-host disease (GVHD). No significant associations of class II allele m ismatching with risk for delayed engraftment or chronic GVHD disease were d etected. This study clearly demonstrates the Importance of precise matching of HLA-DRB1 alleles for successful transplantation. Furthermore, a good-ri sk population of patients whose transplantations were performed in the firs t CID of disease from HLA-A, B, DRB1 matched unrelated donors can be shown to have superior survival. (C) 2001 by The American Society of Hematology.