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Unrelated donor marrow transplantation for myelodysplastic syndromes: outcome analysis in 510 transplants facilitated by the National Marrow Donor Program.

Between April 1988 and July 1998, 510 patients with myelodysplastic syndromes (MDS) underwent unrelated donor bone marrow transplantation (BMT) facilitated by the National Marrow Donor Program. Median age was 38 years (range, <1-62 years). Several conditioning regimens and graft-versus-host disease (GVHD) prophylaxis methods were used, and T-cell depletion was used in 121 patients. Donors were serologically matched for HLA-A, -B, and -DRB1 antigens for 74% of patients. Of 437 patients evaluable for engraftment, 24 (5% cumulative incidence, with 95% confidence interval [CI] of 3%-7%) failed to engraft, and an additional 33 (8% cumulative incidence; 95% CI, 6%-10%) had late graft failure. Grades II to IV GVHD developed in 47% of patients (95% CI, 43%-49%), and limited and extensive chronic GVHD developed at 2 years in 27% (95% CI, 24%-30%). The incidence of relapse at 2 years was 14% (95% CI, 11%-17%). Greater relapse was independently associated with advanced MDS subtype and no acute GVHD. The estimated probability of disease-free survival (DFS) at 2 years was 29% (95% CI, 25%-33%). Improved DFS was independently associated with less advanced MDS subtype, higher cell dose, recipient cytomegalovirus (CMV) seronegativity, shorter interval from diagnosis to transplantation, and transplantation in recent years. Common causes of death were treatment-related complications accounting for 82% of fatalities. The 2-year cumulative incidence of treatment-related mortality (TRM) was 54% (95% CI, 53%-61%). Sixty-nine percent of TRM occurred within the first 100 days, and 93% occurred within the first year of transplantation. Higher TRM was independently associated with older recipient and donor age, HLA mismatch, and recipient CMV seropositivity. This study demonstrates that unrelated donor BMT cures a significant proportion of patients with MDS. TRM is the major problem limiting the success of unrelated donor BMT in MDS. The observations made in this study should facilitate the design of prospective trials aimed at improving the results of unrelated donor stem cell transplantation for MDS.