Mycophenolate mofetil and cyclosporine as graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation

Background Mycophenolate mofetil (MMF) is an inhibitor of purine nucleotide de novo synthesis leading to impaired proliferation of activated lymphocyt es, Studies in animals show a synergistic effect of MMF and cyclosporine (C sA) in preventing acute graft-versus-host disease (GVHD) after allogeneic b one marrow transplantation. We performed a pilot study evaluating the feasi bility of the combined application of MMF and CsA as GVHD prophylaxis after allogeneic blood stem cell transplantation. Toxicity and the bioavailabili ty of MMF in this setting were investigated. Methods. Fourteen patients who had received grafts from HLA-compatible sibl ings received 2 g of oral MMF from day 1 to 14 combined with intravenous Cs A at 4 mg/kg starting at day -1, Plasma levels of mycophenolic acid (MPA) a nd its glucoronide were measured by high-performance liquid chromatography. Fifteen patients treated with a combination of CsA and methotrexate at the same institution were referred to as the control group. Results. Trilineage engraftment was achieved in all study and control patie nts. Acute GVHD greater than or equal to grade II was observed in 46.5% and 60% of the study and control patients, respectively. No major differences in the rate of acute toxicities were detectable. The mean trough blood leve l of MPA in 10 patients was 0.28 mu g/ml, and 5.7 mu g/ml for MPA glucoroni de. Reduced peak levels of MPA indicate a reduced absorption rate of MMF in the early posttransplant phase. Conclusions. The combined administration of MMF and CsA was shown to be fea sible in patients after allogeneic blood stem cell transplantation. Because of the decreased bioavailability of MMF, dose-finding studies for an intra venous formulation are warranted.