Cyclophosphamide combined with antithymocyte globulin in preparation for allogeneic marrow transplants in patients with aplastic anemia.
Cyclophosphamide combined with antithymocyte globulin in preparation for allogeneic marrow transplants in patients with aplastic anemia.
复制标题
DOI：
10.1182/blood.v84.3.941.bloodjournal843941
复制
发表时间：
1994-08
期刊：
影响因子：
20.3
通讯作者：
R. Storb;R. Etzioni;C. Anasetti;F. Appelbaum;Buckner Cd;W. Bensinger;E. Bryant;R. Clift;H. Deeg-H
中科院分区：
文献类型：
--
作者：
R. Storb;R. Etzioni;C. Anasetti;F. Appelbaum;Buckner Cd;W. Bensinger;E. Bryant;R. Clift;H. Deeg-H
对于接受环磷酰胺(CY)治疗的再生障碍性贫血患者来说，移植排斥反应一直是骨髓移植后的一个问题。当患者除了骨髓外，还接受骨髓捐赠者的外周血液黄褐色涂层细胞时，排斥反应会减轻，但这一结果是以更多的慢性移植物抗宿主病(GVHD)为代价的。二次移植的结果表明，CY与抗胸腺细胞球蛋白(ATG)交替使用比单独使用CY更具免疫抑制作用。因此，本研究在39例再生障碍性贫血患者中探讨了不输血的CY和ATG，这些患者接受了来自HLA相合家庭成员的骨髓移植(38例兄弟姐妹，1例父亲)。我们希望将移植排斥反应和慢性移植物抗宿主病的风险降到最低，并提高存活率。患者年龄为2-52岁(中位数，24.5岁)；87%的患者以前接受过输血，41%的患者在移植前接受过免疫抑制药物的治疗。他们每天服用4剂CY(共200 mg/kg)和3剂ATG(共90 mg/kg)，然后进行人类白细胞抗原相合的骨髓移植。应用甲氨蝶呤和环孢素预防移植物抗宿主病。两名患者(5%)拒绝接受移植物，两人都成功地再次移植。急性(2级或3级)移植物抗宿主病占15%，慢性移植物抗宿主病占34%。3年的精算存活率为92%，与39例历史患者的72%的存活率相比，后者在年龄、排斥反应和GVHD的危险因素方面与当前患者匹配。CY/ATG是一种耐受性良好且有效的调节方案，用于再生障碍性贫血的骨髓移植，与甲氨蝶呤/环孢菌素预防GVHD相结合，可获得良好的存活率。
Graft rejection has been a problem after marrow grafts for patients with aplastic anemia who were conditioned with cyclophosphamide (CY). Rejection lessened when patients were given the marrow donor's peripheral blood buffy-coat cells in addition to the marrow, but this result was achieved at the price of more chronic graft-versus-host disease (GVHD). Results with second transplants suggested that CY alternating with antithymocyte globulin (ATG) was more immunosuppressive than CY alone. Therefore, the current study explored CY and ATG without buffy-coat cell transfusions in 39 patients with aplastic anemia given marrow transplants from HLA-identical family members (siblings in 38 cases, father in 1 case). We hoped both to minimize the risks of graft rejection and of chronic GVHD and to improve survival. Patients were 2 to 52 years of age (median, 24.5); 87% had received previous transfusions, and 41% had therapy with immunosuppressive agents before transplant. They were administered four daily doses of CY (total, 200 mg/kg) alternating with three doses of ATG (total, 90 mg/kg) followed by an HLA-identical marrow graft. Methotrexate and cyclosporine were administered to prevent GVHD. Two patients rejected their grafts (5%), and both were successfully retransplanted. Acute (grade 2 or 3) GVHD occurred in 15% and chronic GVHD in 34% of patients. The actuarial survival rate at 3 years was 92%, which compares favorably to the 72% survival rate in 39 historical patients who were matched with current patients for age and risk factors for rejection and GVHD. CY/ATG is a well-tolerated and effective conditioning program for marrow grafting in aplastic anemia that, when combined with GVHD prevention by methotrexate/cyclosporine, results in excellent survival.