Mycophenolate mofetil (MMF) as therapy for refractory chronic GVHD (cGVHD)in children receiving bone marrow transplantation

Mycophenolate mofetil (MMF) is an alternative immunosuppressant which inhib its the proliferation of T and B lymphocytes, The purpose of the present st udy was to evaluate the safety and efficacy of MMF as salvage therapy for c hronic GVHD (cGVHD) in children receiving allogeneic bone marrow transplant ation. Fifteen children, 3-16 years of age, who had received grafts from HL A-compatible siblings (n = 8), partially matched related donors (n = 2) or matched unrelated donors (n = 5), developed extensive cGVHD which had prove d unresponsive to standard immunosuppressive therapy. Patients were treated with MMF at the dose of 15-40 mg/kg/day in combination with other immunosu ppressive therapy for a median of 4 months (range 1-15 months), The overall response rate (complete or partial response) was 60%, Thirteen percent had only minor responses, whereas 27% of patients had progressive disease. Bes t responses were seen in patients with GI tract (60% of complete responses) or mouth (33% of complete responses) cGVHD and skin involvement (43% of co mplete responses) that did not include sclerodermatous manifestations. Once MMF was started, improvements in the clinical manifestations of cGVHD allo wed a significant reduction of steroids in 45% of patients and discontinuat ion in 27% of cases. Six patients (40%) experienced adverse events, with ga strointestinal symptoms predominating. Five patients experienced opportunis tic infections. MMF was discontinued after 35-180 days in six patients for the following reasons: parents choice (n = 2), liver toxicity (n = 1), poor compliance (n = 2), and no response (n = 1). In conclusion, these prelimin ary results suggest that MMF in combination with other immunosuppressive ag ents may have a role to play in patients with cGVHD, Prospective clinical t rials are needed to establish exact indications for therapy and dosage sche duling.