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

Abstract

Summary:Mycophenolate mofetil (MMF) is an alternative immunosuppressant which inhibits the proliferation of T and B lymphocytes. The purpose of the present study was to evaluate the safety and efficacy of MMF as salvage therapy for chronic GVHD (cGVHD) in children receiving allogeneic bone marrow transplantation. Fifteen children, 3-16 years of age, who had received grafts from HLA-compatible siblings (n ‫؍‬ 8), partially matched related donors (n ‫؍‬ 2) or matched unrelated donors (n ‫؍‬ 5), developed extensive cGVHD which had proved unresponsive to standard immunosuppressive therapy. Patients were treated with MMF at the dose of 15-40 mg/kg/day in combination with other immunosuppressive 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. Best responses were seen in patients with GI tract (60% of complete responses) or mouth (33% of complete responses) cGVHD and skin involvement (43% of complete responses) that did not include sclerodermatous manifestations. Once MMF was started, improvements in the clinical manifestations of cGVHD allowed a significant reduction of steroids in 45% of patients and discontinuation in 27% of cases. Six patients (40%) experienced adverse events, with gastrointestinal symptoms predominating. Five patients experienced opportunistic 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 preliminary results suggest that MMF in combination with other immunosuppressive agents may have a role to play in patients with cGVHD. Prospective clinical trials are needed to establish exact indications for therapy and dosage scheduling. Bone Marrow Transplantation (2000) 25, 1067-1071.

Optimal management of chronic graft‐versus‐host disease in children

“…There was not an appreciable response in sclerotic skin manifestations. Most encouraging, almost half of the patients were able to have a significant corticosteroid reduction while on MMF (Busca et al, 2000).…”

“…In the Busca series mentioned above, adverse GI events including diarrhoea, nausea and vomiting were observed in five of the 15 patients (Busca et al, 2000). It has also been appreciated that MMF can cause a non-infectious enterocolitis in renal transplant recipients with symptoms of diarrhoea and pathology showing inflammation which is not dissimilar to GVHD pathology.…”

“…Interestingly, in a double-blind placebo controlled study, when MMF was added to standard therapy to newlydiagnosed patients with chronic GVHD, there was no evidence of benefit from adding MMF . Busca et al (2000) reported on the safety and efficacy of MMF when added as a salvage therapy, in 15 children with chronic GVHD. Seven of these patients had received alternative stem cell sources for transplant, and all had extensive chronic GVHD not responding to corticosteroids.…”

Mycophenolate mofetil for the treatment of acute and chronic GVHD is effective and well tolerated but induces a high risk of infectious complications: a series of 21 BM or PBSC transplant patients

“…18 This immunosuppressive agent might also be useful in the treatment of auto-immune diseases, such as diffuse proliferative lupus nephritis, in combination with prednisolone. 19 Preliminary clinical studies suggest that MMF might be an effective agent for prophylaxis of aGVHD 1,20,21 and/or treatment of acute 22,23 or chronic 14,22 GVHD after allogeneic BMT or PBSCT in adult patients or in children, 24 when administered alone or in combination with other immunosuppressive agents (CsA Ϯ prednisolone, 21,22 tacrolimus 14 ). However, few data are available.…”

Safety profile of mycophenolate mofetil: a response

“…2 In our study, adverse gastrointestinal events including diarrhea, nausea and vomiting were the most common clinically relevant side-effects, occurring in 30% (five out of 15) of the patients, whereas severe liver toxicity occurred in one case. Nevertheless, it should be emphasized that MMF was discontinued in only two patients (13%) due to the presence of adverse reactions.…”