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霉酚酸脂联合环孢素和甲氨蝶呤预防外周血干细胞移植后急性移植物抗宿主病
作者姓名:Wang J  Song X  Zhang W  Tong S  Hou J  Chen L  Lou J  Li H  Ding X  Min B
作者单位:200433,上海第二军医大学长海医院血液科
基金项目:国家自然科学基金资助项目 (2 9870 710 ),上海市卫生系统百人计划基金资助项目(98BR0 2 9)
摘    要:目的 比较环孢素A(CsA)和短程甲氨蝶呤 (MTX)加或不加用短程霉酚酸脂 (MMF)预防急性移植物抗宿主病 (aGVHD)的效果。方法 人类白细胞抗原 (HLA)相合的异基因外周血造血干细胞移植 (allo PBSCT) 39例 ,常规环磷酰胺和全身照射为主进行预处理。GVHD预防分二组 :CsA +MTX组 2 6例 ,应用小剂量CsA(2mg·kg-1·d-1)和短程MTX(分别在移植后 1、3、6和 11d) ;MMF +CsA+MTX组 13例 ,在CsA和MTX基础上加用短程MMF 2g/d ,移植后口服 1~ 2 8d ,但MTX只在移植后1、3、6d应用。结果 两组患者移植后均顺利重建造血 ,中性粒细胞和血小板恢复时间的差异无显著意义 (P >0 0 5 ) ;MMF +CsA +MTX组aGVHD的发生率为 7 6 % ,未见II度以上aGVHD ,明显低于CsA+MTX组 (46 2 % ,P <0 0 5 ) ,CsA +MTX组II度以上aGVHD为 2 3 0 %。MMF +CsA +MTX组重度粘膜炎发生率 (15 4 % )亦明显低于CsA +MTX组 (30 8% )明显减少。结论 短程MMF联合CsA和短程MTX方案对allo PBSCT后的aGVHD的预防效果明显优于常规CsA和短程MTX ,其对慢性GVHD和移植后复发率的影响有待于进一步随访观察

关 键 词:霉酚酸酯  环孢素  甲氨蝶呤  外周血干细胞移植  急性移植物抗宿主病  免疫抑制剂
修稿时间:2001年8月13日

Combination of mycophenolate mofetil with cyclosporine A and methotrexate for the prophylaxes of acute graft versus host disease in allogeneic peripheral stem cell transplantation
Wang J,Song X,Zhang W,Tong S,Hou J,Chen L,Lou J,Li H,Ding X,Min B.Combination of mycophenolate mofetil with cyclosporine A and methotrexate for the prophylaxes of acute graft versus host disease in allogeneic peripheral stem cell transplantation[J].National Medical Journal of China,2002,82(8):507-510.
Authors:Wang Jianmin  Song Xianmin  Zhang Weiping  Tong Shupeng  Hou Jun  Chen Li  Lou Jingwei  Li Hongmei  Ding Xiaoqin  Min Bihe
Institution:Department of Hematology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Abstract:OBJECTIVE: To evaluate the efficacy of combination of mycophenolate mofetil (MMF) with cyclosporine (CsA) and methotrexate (MTX) on prophylaxes of acute graft-versus-host disease (GVHD) in HLA-matched allogeneic peripheral blood stem cell transplantation (allo-PBSCT). METHODS: Thirty-nine patients with acute leukemia (n = 21) and chronic myeloid leukemia (n = 17) and severe aplastic anemia (n = 1) were treated with allo-PBSCT from HLA matched siblings (n = 36) or unrelated donors (n = 3). Twenty-six patients were in CsA + MTX group. CsA was given at a dosage of 2 mg.kg(-1).d(-1) by continuous intravenous injection for 24 h, since on day(-1) and injection of CsA was changed to oral administration of CsA around day 18. CsA was tapered by 10% per week after day + 90. MTX was given at the dosage of 15 mg at day + 1, and 10 mg at day + 3, + 6 and + 11, respectively. Thirteen patients were included in MMF + CsA + MTX group with the same dosage of CsA and MTX as above but omitted at day + 11. MMF of 2 g/day was added orally from day + 1 to day + 28 post transplantation. RESULTS: All patients in both groups were successfully engrafted. The days of recovery of neutrophils and platelets were not significantly different between two groups (P > 0.05). The incidence of acute GVHD in MMF + CsA + MTX group (7.6%) was significantly lower than that in CsA/MTX group (46.2%, P < 0.05). Incidence of grade II approximately IV GVHD in MMF group was 0 while that in control group was 23.0%. The incidence of severe mucositis was lower in MMF group (15.4%) than in the control group (30.8%) (P < 0.05). CONCLUSION: The regimen of MMF + CsA + MTX for prevention of acute GVHD in allo-PBSCT is more efficient than that of CsA + MTX, without adversely affecting the engraftment and relapse rate.
Keywords:Hematopoietie  stem cell transplantation  Graft vs host disease  Immunosuppressive agents
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