Serologically HLA-DR-mismatched unrelated donors might provide a valuable alternative in allogeneic transplantation: Experience from a single Japanese institution

To clarify the clinical significance of a serologic HLA-DR mismatch after unrelated-donor transplantation, we evaluated for hematologic malignancies 123 cases of unrelated bone marrow transplantation carried out in a single institution between 1995 and 2004. Of the patients in these cases, 12 were serologically mismatched at the single HLA-DR locus. Eighty-two patients who received HLA-matched transplantations were used as controls. Conditioning consisted of a conventional total body irradiation-based regimen or a fludarabine-based reduced-intensity regimen. Prophylaxis for graft-versus-host disease (GVHD) consisted of tacrolimus plus short-term methotrexate. Graft failure did not develop. With a median follow-up of 42 months (range, 11-99 months), rates of overall survival, nonrelapse mortality, and relapse at 4 years were 63%, 38%, and 0%, respectively, all of which were comparable with those after HLA-matched transplantation. The frequency of acute GVHD of grades II to IV was 75%, significantly higher than after HLA-matched transplantation (42%, P = .046), and there was a trend toward an increased incidence of acute GVHD of grades III to IV after serologically HLA-DR-mismatched unrelated transplantation (27% versus 10%, P = .093). Chronic GVHD developed in 4 of 11 evaluable patients, an incidence comparable with that after HLA-matched transplantation. In summary, serologically HLA-DR-mismatched unrelated transplantation is feasible and might be an acceptable alternative for the Japanese population, although the higher incidence of acute GVHD is notable.