Combination of Mycophenolate Mofetil with Cyclosporine A and Methotrexate as Gvhd Prophylaxis In Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract 1280

Graft-versus-host disease (GVHD) is the dominant complication limiting the efficacy and safety of hematopoietic stem cell transplantation (HSCT), especially from unrelated donors. The most widely used regimen of prophylaxis is the combination of cyclosporine A (CSA)and a short-course of methotrexate (MTX). But the patients receiving grafts from matched unrelated donors still have a 50–80% risk of clinical significant GVHD. Thus, more effective prophylaxis is needed. In this study, we try to evaluate the efficacy and safety of the new GVHD prophylaxis regimen combining mycophenolate mofetil (MMF) with CSA and MTX in unrelated donor allogeneic stem cell transplantation. Between November 1998 and June 2008, 153 patients with a variety of hematologic malignancies were enrolled. There were 102 males and 51 females, median age 26 (range, 8–52) years. Diagnoses were acute myeloid leukemia (n=54), acute lymphoblastic leukemia (n=47),myelodysplastic syndrome (n=8), multiple myeloma (n=1) and chronic myeloid leukemia (n=53). One hundred and eight patients had HLA compatible unrelated donors, 37 patients had single locus-mismatched unrelated donors and 8 patients had 2 loci-mismatched unrelated donors. GVHD prophylaxis consisted of CSA,MTX and MMF. CSA was started on day -7 with the initial dosage of 2.5mg/kg daily, and the dose was adjusted to maintain a whole blood steady-state level of 200–400ng/ml. The dose was tapered during the second to third month post-transplant depending on GVHD status. MTX was given at a dosage of 10mg on days+1, +3 and +6. MMF was administered at an oral dose of 500mg daily from day 0 to day +100. The cumulative incidence of grades II-IV aGVHD and grades III-IV aGVHD for all patients were 43.9% and 17.9% respectively for entire group. The cumulative incidence of grades II-IV aGVHD for patients who had HLA-matched donors and mismatched donors were 40.2% and 51.9% respectively (P=0.079). The cumulative incidence of grades III-IV aGVHD for patients who had HLA-matched donors and mismatched donors were 14.0% and 26.9% respectively (P=0.026). The cumulative incidence of cGVHD was 41.4%, with 19.3% extensive cGVHD. At 3 years, the incidence of relapse for entire group was 24.0%. The cumulative incidence of transplant-related mortality at 100 days and 3 years were 12.5% and 34.9%, respectively. The probabilities of overall survival at 2 years and 5 years were 59.2% and 50.2%, respectively. The probabilities of disease-free survival at 2 years and 5 years were 56.3% and 46.7%, respectively. From these results, we conclude that the combination of MMF with CSA and MTX is an effective prophylaxis regimen for acute and chronic GVHD in unrelated donor allogeneic stem cell transplantation without increasing the risk of relapse.