TRANSPLANTATION IN REMISSION IMPROVES THE DISEASE-FREE SURVIVAL OF PATIENTS WITH ADVANCED MYELODYSPLASTIC SYNDROMES TREATED WITH MYELOABLATIVE T CELL DEPLETED STEM CELL TRANSPLANTS FROM HLA IDENTICAL SIBLINGS

摘要

From 1985 to 2004, 49 patients with advanced MDS (≥5% blasts) or acute myeloid leukemia transformed from MDS underwent T cell depleted bone marrow or peripheral blood hematopoietic stem cell transplantation from HLA identical siblings following conditioning with a myeloablative regimen that included total body irradiation (44 patients) or busulfan (5 patients). Thirty-six patients received chemotherapy (3 low dose and 33 induction doses) before conditioning, and 13 patients did not receive any chemotherapy. Prior to transplant 22 of the 36 treated patients were in hematologic remission, 4 were in a second refractory cytopenia phase (26 responders), 8 had failed to achieve remission and 2 of the responders had progression or relapse of their MDS (10 failures). No posttransplant pharmacologic prophylaxis for GvHD was given. The median age was 48 years (range 13–61). Forty-five of the 49 patients engrafted, 2 had primary graft failure, and 2 died before engraftment. Only 3 patients developed acute GvHD (grades I and III) and 1 chronic GvHD. At 3 years posttransplant, the OS was 54% in the responders, 31% in the untreated group, and 0% in the failure group (p=0.0004). The DFS was 50%, 15% and 0% in each group respectively (p=0.0008). In multivariate analysis, disease status before cytoreduction remained highly correlated with DFS (p<0.001). The cumulative incidence (CI) of relapse at 2-years posttransplant for the responders was 23%, for the untreated group was 38% and for the failures was 50%. The CI of non-relapse mortality at 2-years posttransplant for the responders was 23%, for the untreated group was 38% and for the failures was 40%. All survivors achieved a KPS of ≥90. These results indicate that patients with advanced MDS who achieve and remain in remission or a second refractory cytopenia phase with chemotherapy before conditioning can achieve successful long term remissions following a myeloablative T cell depleted allogeneic HSCT.