Busca A, Saroglia E M, Lanino E, Manfredini L, Uderzo C, Nicolini B, Messina C, Rabusin M, Miniero R
Department of Pediatrics, University of Turin, Italy.
Bone Marrow Transplant. 2000 May;25(10):1067-71. doi: 10.1038/sj.bmt.1702410.
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).
霉酚酸酯（MMF）是一种抑制T和B淋巴细胞增殖的免疫抑制剂。本研究旨在评估MMF作为接受异基因骨髓移植儿童慢性移植物抗宿主病（cGVHD）挽救治疗的安全性和有效性。15名3至16岁的儿童接受了来自HLA匹配同胞（n = 8）、部分匹配的相关供者（n = 2）或匹配的无关供者（n = 5）的移植物，发生了广泛的cGVHD，且已证明对标准免疫抑制治疗无反应。患者接受MMF治疗，剂量为15 - 40mg/kg/天，并联合其他免疫抑制治疗，中位治疗时间为4个月（范围1 - 15个月）。总体缓解率（完全或部分缓解）为60%。13%的患者仅有轻微反应，而27%的患者病情进展。在胃肠道（60%的完全缓解）或口腔（33%的完全缓解）cGVHD以及不包括硬皮病表现的皮肤受累（43%的完全缓解）患者中观察到最佳反应。一旦开始使用MMF，cGVHD临床表现的改善使45%的患者能够显著减少类固醇用量，27%的患者能够停用类固醇。6名患者（40%）出现不良事件，以胃肠道症状为主。5名患者发生机会性感染。6名患者在35至180天后因以下原因停用MMF：家长选择（n = 2）、肝毒性（n = 1）、依从性差（n = 2）和无反应（n = 1）。总之，这些初步结果表明，MMF联合其他免疫抑制剂可能对cGVHD患者有效。需要进行前瞻性临床试验以确定确切的治疗指征和剂量方案。《骨髓移植》（2000年）
