Efficacy and safety of mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant recipient

Abstract

HE EFFICACY and safety of mycophenolate mofetil (MMF) in combination with CyA and Prednisolone for the treatment of acute and chronic GVHD (aGVHD and cGVHD respectively) after BMT and PBSCT from HLA mismatched and matched donors was evaluated in an open single center trial. Thirty patients, with aGVHD (n 5 21) and cGVHD (n 5 9) were treated with 2g MMF daily in addition to Cyclosporin A (CyA) and Prednisolone. The control group consisted of 21 patients with aGVHD (n 5 14) and cGVHD (n 5 7) treated with Predniosolone and CyA only. Acute GVHD prophylaxis consisted of a combination of MTX, CyA, and Prednisolone. Overall grade improvement of aGVHD was found in 15/21 (71%) patients treated with MMF and was significantly different compared to the control group. MMF therapy in the treatment of cGVHD lead to moderate improvement in 4 of 8 patients with limited cGVHD. The most common adverse hematologic events of MMF were leukopenia (n 5 6), anemia (n 5 4), and thrombocytopenia (n 5 5). Haematological adverse events were not severe and did not require the discontinuation of MMF. Similar to the study group, leukopenia was found in 4 of the 21 control patients, anemia in 1/21, and thrombocytopenia in 8/21 patients. In addition, 33% of the patients in the control group developed severe adverse effects due to Prednisolone therapy, which were not observed in the MMF group. In this preliminary study, we have shown that MMF can be used safely for the treatment of aGVHD. In addition, the MMF therapy resulted in a significant dose reduction of Prednisolone for the treatment of GVHD when compared to a control group of patients. Treatment for GvHD after allogeneic related and unrelated BMT is one of the most critical elements in the reduction of transplant related morbidity and mortality 1 . High incidence of aGVHD indicates that more effective therapy and prevention of this severe complication is needed. MMF is a potent, uncompetitive, reversible inhibitor of eucaryotic inosine monophosphate dehydrogenase and is successfully used in the prevention of acute rejection in renal allograft recipients. 2 However, very little is known about the effect of MMF in prevention or treatment of GVHD in experimental animals. 3 The aim of our study was to evaluate the safety and efficacy of MMF in the treatment of aGVHD and cGVHD in patients after allogeneic BMT. PATIENTS AND METHODS This study included 30 patients given a sibling transplant BM or PBSCT (n 5 12; four of which were HLA mismatched) as well as allogeneic MUD BM or PBSCT (n 5 18; three of which were HLA mismatched). Of these patients, 19 had AML, 7 had CML, and 4 had ALL. The conditioning regimens included TBI and CY in 24/30 patients. A BU/VP16 regimen was used in 3 patients. The control group included 21 patients given allogeneic familiar BM (n 5 8, 3 of which were HLA mismatched) or allogeneic MUD BM (n 5 13, 3 of which were HLA mismatched). As many variables as possible were matched between the control patients and the patients receiving MMF in the following order of priority: diagnosis, disease phase at transplant, patient age 6 5 years, and type of BMT. Of these patients, 7 had AML, 11 had CML, and 3 had ALL. The conditioning regimens in the control group of patients included TBI and CY in 17/21 patients. A BU/CY regimen was used in 2 patients, and a BU/VP16 regimen was used in 2 patients.