CYCLOSPORINE, METHOTREXATE, AND PREDNISONE COMPARED WITH CYCLOSPORINE AND PREDNISONE FOR PROPHYLAXIS OF ACUTE GRAFT-VERSUS-HOST DISEASE
CYCLOSPORINE, METHOTREXATE, AND PREDNISONE COMPARED WITH CYCLOSPORINE AND PREDNISONE FOR PROPHYLAXIS OF ACUTE GRAFT-VERSUS-HOST DISEASE
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DOI：
10.1056/nejm199310213291703
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发表时间：
1993-10-21
影响因子：
158.5
通讯作者：
FORMAN, SJ
中科院分区：
文献类型：
--
作者：
CHAO, NJ;SCHMIDT, GM;FORMAN, SJ
背景异基因骨髓移植后的急性移植物抗宿主病（GVHD）仍然是一个严重的问题。在一项临床试验中，我们测试了环孢霉素和泼尼松联合甲氨蝶呤和不联合甲氨蝶呤预防GVHD的效果。150例急性白血病首次完全缓解、慢性粒细胞白血病首次慢性期或淋巴母细胞淋巴瘤首次完全缓解患者入组研究。所有患者均接受分次全身照射（1320 cGy）和依托泊苷（60 mg/kg体重）准备移植，并接受来自基因型组织相容性供体的骨髓。为了预防GVHD，他们被随机分配接受环孢素、甲氨蝶呤和泼尼松预防性治疗或环孢素和泼尼松联合甲氨蝶呤预防性治疗。所有患者在移植后均接受标准化的支持治疗，包括静脉注射丙种球蛋白。接受环孢素、甲氨蝶呤和泼尼松治疗的患者II级至IV级急性GVHD的发生率（9%）显著低于接受环孢素和泼尼松治疗的患者（23%，P = 0.02）。多因素回归分析显示，急性GVHD风险增加与血清肌酐浓度升高（P = 0.006）和单用环孢素和泼尼松治疗（P = 0.02）相关。急性GVHD发生率低与白血病或淋巴瘤复发率高无关。两个治疗组之间的3年无病生存率没有显著差异（三药方案为64%，两药方案为59%，P = 0.57）。环孢素、甲氨蝶呤和泼尼松联合用药在预防II级至IV级急性GVHD方面比环孢素和泼尼松联合用药（不含甲氨蝶呤）更有效。
Background. Acute graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation remains a serious problem. In a clinical trial, we tested the combination of cyclosporine and prednisone with and without methotrexate for the prevention of GVHD.Methods. One hundred fifty patients with either acute leukemia in first complete remission, chronic myelogenous leukemia in first chronic phase, or lymphoblastic lymphoma in first complete remission were enrolled in the study. All the patients were given fractionated total-body irradiation (1320 cGy) and etoposide (60 mg per kilogram of body weight) in preparation for transplantation, and received bone marrow from genotypically histocompatible donors. To prevent GVHD, they were randomly assigned to prophylactic treatment with either cyclosporine, methotrexate, and prednisone or cyclosporine and prednisone without methotrexate. All the patients received standardized supportive care after transplantation, including intravenous gamma globulin.Results. Patients receiving cyclosporine, methotrexate, and prednisone had a significantly lower incidence of acute GVHD of grades II to IV (9 percent) than those receiving cyclosporine and prednisone (23 percent, P = 0.02). Multivariate regression analysis demonstrated that an increased risk of acute GVHD was associated with an elevated serum creatinine concentration (P = 0.006) and treatment with cyclosporine and prednisone alone (P = 0.02). The lower incidence of acute GVHD was not associated with a higher rate of relapse of leukemia or lymphoma. There was no significant difference in disease-free survival at three years between the two treatment groups (64 percent with the three-drug regimen vs. 59 percent with the two-drug regimen, P = 0.57).Conclusions. The combination of cyclosporine, methotrexate, and prednisone was more effective in preventing acute GVHD of grades II to IV than was the combination of cyclosporine and prednisone without methotrexate.