Abstract

Posttransplant relapse is a major limitation to the success of allogeneic SCT in patients with advanced MDS (refractory anemia with excess blasts (RAEB I and II), refractory anemia in transformation (RAEB-t), and acute myeloid leukemia transformed from MDS). The use of induction chemotherapy prior to transplant to induce remission and thereby to reduce posttransplant relapse in these patients remains controversial. From 1985 to 2004, 47 patients with advanced MDS underwent bone marrow or peripheral blood SCT from HLA identical siblings after myeloablative conditioning with total body irradiation (TBI) and cyclophosphamide alone or in some combined with thiotepa, carboplatinum, diaziquone, or etoposide, or TBI combined with thiotepa and fludarabine. Thirty-six patients received low dose (3 patients) or full induction (33 patients) chemotherapy before conditioning, and 11 patients did not receive any chemotherapy. Prior to transplant, 22 of the 36 treated patients were in hematologic remission (CR) and 4 achieved a second refractory cytopenia phase (RCy2) for a total of 26 responders, and 10 had failed to respond to chemotherapy. Marrow grafts were depleted of T cells using soybean lectin agglutination and then sheep RBC-rosetting (n=32 patients). G-CSF-mobilized peripheral blood stem cell (PBSC) grafts underwent positive CD34 selection and T-cell depletion by sheep RBC-rosetting (n=10 patients). Five patients received a marrow graft followed by a PBSC allograft from the same donor because of low marrow cell dose. Rejection prophylaxis with anti-thymocyte globulin was used in 33 patients. No posttransplant pharmacologic prophylaxis for GvHD was given. The median age was 48 years (range 13–61). Forty-three of the 47 patients in this series engrafted, and 2 had primary graft failure. Two patients died before engraftment. Only 3 patients developed acute GvHD (grades 1 and 3) and 1 chronic GvHD. At 5 years posttransplant, the DFS was 44% for the patients in CR and RCy2 at time of transplant, but no patients in the untreated group or in the chemotherapy failure group survived (p=0.0004). The cumulative incidence (CI) of relapse at 2-years posttransplant for the responders was 27.0%, for the failures 50%, and for the untreated group 45%. The CI for non-relapse mortality at 2-years posttransplant was 19% for the responders, 40% for the failures, and 36% for the untreated patients. All survivors have achieved ≥KPS 90%. These results indicate that patients with advanced MDS who achieve remission or a second refractory anemia phase with chemotherapy before TCD allogeneic SCT can achieve successful long-term remisions. In contrast, the high incidence of posttransplant relapse mitigates against the use of TCD SCT in patients with advanced MDS with active disease (≥5% blasts) prior to transplant. Prospective multicenter randomized studies are needed to validate the value of pre-transplant chemotherapy in patients with advanced MDS undergoing allogeneic SCT.

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