The reported outcome of hematopoietic stem cell transplantation (HSCT) from HLA-mismatched family members has been inconsistent. The object of this study was to evaluate the true impact of HLAmismatch by using recent data from a homogenous population, excluding HSCT procedures that used graft manipulations, and by considering genotypic matching. Clinical data of 2947 patients who underwent allogeneic HSCT for leukemia or myelodysplastic syndrome were extracted from the database of the Japan Society for Hematopoietic Cell Transplantation. The main outcome measures were survival and the incidence of graft-versushost disease (GVHD). The presence of serologic HLA-mismatch, higher age, and high-risk disease were identified as independent risk factors for both shorter survival and the development of grade III to IV acute GVHD. The impact of HLAmismatch on survival was more relevant in standard-risk patients. These findings persisted when we used genotypic HLA matching. Survival after one-locusmismatched HSCT was equivalent to that after HLA-matched unrelated HSCT. We concluded that when a one-locusmismatched family donor is available for high-risk patients, immediate HSCT using this donor is warranted. In standard-risk patients, however, survival after onelocus-mismatched HSCT is significantly shorter than that after HLA-matched HSCT, and the indications for HSCT should be considered carefully. (Blood. 2003;102:1541-1547)

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Differentiation therapy with all-trans retinoic acid (ATRA) has marked a major advance and become the first choice drug in the treatment of acute promyelocytic leukemia (APL). However, patients who relapse from ATRA-induced complete remission (CR) have difficulty in obtaining a second CR with a second course of ATRA therapy alone. We tested the efficacy of a new synthetic retinoid, Am80, in APL that had relapsed from CR induced by ATRA in a prospective multicenter study. Am80 is approximately 10 times more potent than ATRA as an in vitro differentiation inducer, is more stable to light, heat, and oxidation than ATRA, has a low affinity for cellular retinoic acid binding protein, and does not bind to retinoic acid receptor-γ. Patients received Am80, 6 mg/m2, orally alone daily until CR. Of 24 evaluable patients, 14 (58%) achieved CR. The interval from the last ATRA therapy was not different between CR and failure cases. The clinical response was well correlated with the in vitro response to Am80 in patients examined. Adverse events included 1 retinoic acid syndrome, 1 hyperleukocytosis, 9 xerosis, 8 cheilitis, 16 hypertriglyceridemia, and 15 hypercholesterolemia, but generally milder than those of ATRA, which all patients had received previously. Am80 is effective in APL relapsed from ATRA-induced CR and deserves further trials, especially in combination with chemotherapy.