Abstract
Prior studies assessing the effects of HLA mismatching on outcomes of unrelated donor marrow transplantation (UBMT) have yielded conflicting results. Our previous study revealed that mismatching of HLA-A and -B antigens, and not of HLA-DRB1 antigen, was the most crucial risk factor for survival for patients with SAA who received UBMT (
Kojima S et al, Blood 100: 799, 2002
). Because only the data of HLA-A, -B, and DRB1 were available, the role of HLA-C and DQB1 mismatching was not clarified in that study. The current study aimed to evaluate the effects of HLA-C and DQB1 mismatching. From Feb 1993 to April 2003, 260 consecutive patients with acquired aplastic anemia (AA) received UBMT through the Japan Marrow Donor Program. We selected 79 recipient-donor pairs in which molecular analysis of HLA-A, -B, -C, -DRB1, and DQB1 were performed. Patient ages ranged from 3 to 46 years (median, 15 years). Various preconditioning regimens were used by individual centers. In 69 patients (87%), cyclosporine and methotrexate were used for the prophylaxis against GVHD. Of the 79 pairs, 26 (33%) were found to be matched at HLA-A, -B, -C, -DRB1, and DQB1; 18 (23%) were mismatched at a single HLA antigen (6 HLA-A or -B, 7 HLA-C, 5 HLA-DRB1 or HLA-DQB1); 31 (39%) were mismatched at two HLA antigens (5 HLA- and HLA-DQB1, 18 HLA-A or -B and HLA-C or -DRB1 or -DQB1, 8 HLA-C and HLA-DRB1 or -DQB1); and 9 (11%) were mismatched at 3 HLA antigens. Transplant-related toxicities such as graft failure, grade 3 to 4 acute GVHD, and chronic GVHD were found in 7/74, 14/70, and 16/59, respectively. In a univariate analysis, any single HLA mismatching including HLA-A, -B, or -C did not increase the incidence of acute GVHD. Of 79 patients, 44 survived. The 5-year survival rate did not differ between recipients transplanted from a full-matched donor (68.5%) and those from any single HLA mismatched donors (66.7 to 80.0%). In addition, the 5-year survival rate was not worse (62.5%) in patients transplanted from HLA-C and HLA-DRB1 or -DQB1 mismatched donors. However, the 5-year survival rate was significantly worse (38.9%) in recipients who transplanted from HLA-A or -B mismatched and -C or -DRB1 or -DQB1 mismatched donors and it was 0% in patients who were mismatched at 3 antigens. In a multivariate analysis, the relative risk for HLA-A or -B and -C or -DRB1 or -DQB1 mismatching was 4.24 (95% CI, 1.6–11.5) and for 3 antigen mismatching, it was 20.0 (95% CI, 5.6–71.6). The current JMDP study showed that mismatching of a single HLA antigen did not result in increased mortality. However, in patients with HLA-A or -B mismatching, additional mismatching at HLA-C, -DRB1, or -DQB1 had a significant adverse effect on survival. Matching of HLA-C and -DQB1 should be incorporated into algorithms for unrelated donor selection.Author notes
Corresponding author
2005, The American Society of Hematology
2005
