Radiation-free, alternative-donor HCT for Fanconi anemia patients: results from a prospective multi-institutional study
Radiation-free, alternative-donor HCT for Fanconi anemia patients: results from a prospective multi-institutional study
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DOI：
10.1182/blood-2016-09-743112
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发表时间：
2017-04-20
期刊：
影响因子：
20.3
通讯作者：
Boulad, Farid
中科院分区：
文献类型：
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作者：
Mehta, Parinda A.;Davies, Stella M.;Boulad, Farid
范可尼贫血（FA）是一种遗传性骨髓衰竭综合征，以染色体脆性、进行性骨髓衰竭和癌症易感性为特征。造血细胞移植（HCT）可以治疗fa相关的骨髓衰竭或白血病，但移植和移植物抗宿主病（GVHD）期间的辐射暴露都可能增加头颈部和性器官区域后期恶性肿瘤的风险。在这项研究中，我们测试了一种无辐射调理方案，使用t细胞耗尽的移植物来消除辐射暴露，并将移植的早期和晚期毒性降到最低。2009年6月至2014年5月，45例FA患者（中位年龄8.2岁，范围4.3-44岁）接受了HCT检查。制剂方案包括丁硫丹、环磷酰胺、氟达拉滨和兔抗胸腺细胞球蛋白。监测Busulfan水平以避免过量毒性。使用CliniMacs CD34柱（Miltenyi），所有移植物都是CD34选择/ t细胞耗尽。34例（75.6%）骨髓衰竭患者和11例（24.4%）骨髓增生异常综合征患者使用匹配的非亲属（n = 25, 55.5%）、错配的非亲属（n = 14, 31.1%）或错配的相关供者（n = 6, 13.4%）进行了HCT。包括髓系恶性肿瘤患者和接受错配相关/单倍同移植物的患者在内的整个队列的1年总体生存率和无病生存率分别为80%（+/- 6%）和77.7%(+/- 6.2%)（中位随访41个月）。所有幼童(
Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by chromosomal fragility, progressive marrow failure, and cancer predisposition. Hematopoietic cell transplantation (HCT) is curative for FA-related marrow failure or leukemia, but both radiation exposure during transplant and graft-versus-host disease (GVHD) may increase risk of later malignancies of the head and neck and anogenital area. In this study, we tested a radiation-free conditioning regimen with a T-cell-depleted graft to eliminate radiation exposure and minimize early and late toxicities of transplant. Forty-five patients (median age, 8.2 years; range 4.3-44) with FA underwent HCT between June 2009 and May 2014. The preparative regimen included busulfan, cyclophosphamide, fludarabine, and rabbit anti-thymocyte globulin. Busulfan levels were monitored to avoid excess toxicity. All grafts were CD34-selected/T-cell-depleted using the CliniMacs CD34 columns (Miltenyi). Thirty-four patients (75.6%) with marrow failure and 11 (24.4%) with myelodysplastic syndrome underwent HCT using matched unrelated (n = 25, 55.5%), mismatched unrelated (n = 14, 31.1%), or mismatched related donors (n = 6, 13.4%). One year probabilities of overall and disease-free survival for the entire cohort, including patients with myeloid malignancy and those receiving mismatched related/haploidentical grafts, were 80% (+/- 6%) and 77.7% (+/- 6.2%), respectively (median follow-up 41 months). All young children (