Optimization of conditioning for marrow transplantation from unrelated donors for patients with aplastic anemia after failure of immunosuppressive therapy
Optimization of conditioning for marrow transplantation from unrelated donors for patients with aplastic anemia after failure of immunosuppressive therapy
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DOI：
10.1182/blood-2006-03-005041
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发表时间：
2006-09-01
期刊：
影响因子：
20.3
通讯作者：
Storer, Barry
中科院分区：
文献类型：
--
作者：
Deeg, H. Joachim;O'Donnell, Margaret;Storer, Barry
在87例免疫抑制治疗无效的再生障碍性贫血患者中，我们确定了当加入抗胸腺细胞球蛋白（ATG，30 mg/kg × 3）和环磷酰胺（CY，50 mg/kg × 4）以实现无关供体骨髓移植时所需的全身照射（TBI）的最小剂量。TBI以3 x 200 cGy开始，根据移植物失效或毒性以200 cGy的步骤递增或递减。患者年龄为1.3至53.5岁（中位数，18.6岁）。从诊断到移植的时间为3 ~ 328个月（中位数14.6个月）。62例患者的供者HLA-A、-B、-C、-DR和-DQ相同，25例患者在抗原或等位基因水平上1至3个HLA位点不相同。剂量限制性毒性为弥漫性肺损伤。最佳TBI剂量为1 × 200 cGy。9例患者不耐受ATG，并准备与CY + TBI。5%的患者发生移植物失败。中位随访7年，62例HLA相同移植受者中有38例（61%）存活，25例HLA不相同移植受者中有10例（40%）存活。在200 cGy TBI时观察到HLA相同移植物的最高存活率。因此，在接受多次输血的再生障碍性贫血患者中，低剂量TBI + CY + ATG预处理导致非相关移植的良好结局。
in 87 patients with aplastic anemia who failed to respond to immunosuppressive treatment, we determined the minimal dose of total body irradiation (TBI) required when added to antithymocyte globulin (ATG, 30 mg/kg x 3) plus cyclophosphamide (CY, 50 mg/kg x 4) to achieve engraftment of unrelated donor marrow. TBI was started at 3 x 200 cGy, to be escalated or deescalated in steps of 200 cGy depending on graft failure or toxicity. Patients were aged 1.3 to 53.5 years (median, 18.6 years). The interval from diagnosis to transplantation was 3 to 328 months (median, 14.6 months). Donors were HLA-A, -B, -C, -DR, and -DQ identical for 62 patients, and nonidentical for 1 to 3 HLA loci at the antigen or allele level for 25. The dose-limiting toxicity was diffuse pulmonary injury. The optimum TBI dose was 1 x 200 cGy. Nine patients did not tolerate ATG and were prepared with CY + TBI. Graft failure occurred in 5% of patients. With a median follow-up of 7 years, 38 (61%) of 62 HLA-identical, and 10 (40%) of 25 HLA-nonidentical transplant recipients are surviving. The highest survival rate with HLA-identical transplants was observed at 200 cGy TBI. Thus, low-dose TBI + CY + ATG conditioning resulted in excellent outcome of unrelated transplants in patients with aplastic anemia who had received multiple transfusions.