Mycophenolate mofetil and cyclosporine as graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation
Mycophenolate mofetil and cyclosporine as graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation
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DOI：
10.1097/00007890-199902270-00001
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发表时间：
1999-02-27
期刊：
影响因子：
6.2
通讯作者：
Thiede, HM
中科院分区：
文献类型：
--
作者：
Bornhäuser, M;Schuler, U;Thiede, HM
背景霉酚酸酯（Mycophenolate mofetil，MMF）是一种嘌呤核苷酸从头合成抑制剂，可抑制活化淋巴细胞的增殖。动物实验表明，霉酚酸酯与环孢素A（cyclosporine，CsA）联合应用对异基因骨髓移植后急性移植物抗宿主病（acute graft-versus-host disease，GVHD）具有协同预防作用。我们进行了一项初步研究，评价霉酚酸酯和环孢素A联合应用预防异基因造血干细胞移植后GVHD的可行性。在这种情况下的毒性和霉酚酸酯的生物利用度进行了调查。对14例接受HLA相合同胞移植的患者，从第1天开始口服霉酚酸酯（MMF）2g，第14天开始静脉注射环孢素A（CsA）4 mg/kg。对照组15例，在同一机构接受CsA和甲氨蝶呤联合治疗。在所有研究和对照患者中均实现了三系移植。在研究和对照患者中分别观察到46.5%和60%的急性GVHD大于或等于II级。未检测到急性毒性发生率的重大差异。10例患者的MPA平均血药谷浓度为0.28 μ g/ml，MPA葡萄糖醛酸苷为5.7 μ g/ml。MPA峰值水平的降低表明移植后早期MMF的吸收率降低。异基因造血干细胞移植后患者应用霉酚酸酯和环孢素A联合用药是可行的。由于霉酚酸酯的生物利用度降低，需要对静脉制剂进行剂量探索研究。
Background Mycophenolate mofetil (MMF) is an inhibitor of purine nucleotide de novo synthesis leading to impaired proliferation of activated lymphocytes, Studies in animals show a synergistic effect of MMF and cyclosporine (CsA) in preventing acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. We performed a pilot study evaluating the feasibility of the combined application of MMF and CsA as GVHD prophylaxis after allogeneic blood stem cell transplantation. Toxicity and the bioavailability of MMF in this setting were investigated.Methods. Fourteen patients who had received grafts from HLA-compatible siblings received 2 g of oral MMF from day 1 to 14 combined with intravenous CsA at 4 mg/kg starting at day -1, Plasma levels of mycophenolic acid (MPA) and 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 patients. 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 level of MPA in 10 patients was 0.28 mu g/ml, and 5.7 mu g/ml for MPA glucoronide. 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 feasible in patients after allogeneic blood stem cell transplantation. Because of the decreased bioavailability of MMF, dose-finding studies for an intravenous formulation are warranted.