Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation
Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation
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DOI：
10.1182/blood-2015-10-672071
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发表时间：
2016-03-17
期刊：
影响因子：
20.3
通讯作者：
Martin, Paul J.
中科院分区：
文献类型：
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作者：
Mielcarek, Marco;Furlong, Terry;Martin, Paul J.
在移植来自HLA匹配的相关或无关供体的粒细胞集落刺激因子（G-CSF）动员的血细胞后1年，需要全身治疗的美国国立卫生研究院（NH-）定义的慢性移植物抗宿主病（GVHD）的累积发病率为35%。我们假设在G-CSF动员的血细胞移植后给予大剂量环磷酰胺将使慢性GVHD的累积1年发生率降低至15%或更低。2011年12月至2013年9月期间入组了43例高危恶性血液病患者（中位年龄43岁）。12例（28%）接受了相关供体的移植物，31例（72%）接受了无关供体的移植物。移植前预处理包括氟达拉滨和靶向白消安（n = 25）或全身照射（zI 2戈伊; n = 18）。在移植后第3天和第4天给予环磷酰胺50 mg/kg/天，然后从第5天开始给予环孢霉素。NIH定义的慢性GVHD的累积1年发生率为16%（95%置信区间，5-28%）。2-4级和3-4级急性GVHD的累积发生率估计值分别为77%和0%。2年时，非复发性死亡率和复发性恶性肿瘤的累积发生率估计分别为14%和17%，总生存率预计为70%。在随访一年的42例患者中，21例（50%）在移植后1年无复发，并且在没有全身免疫抑制的情况下存活。因此，清髓性移植前预处理可以在移植后安全地与高剂量环磷酰胺组合，并且可以显著降低与HLA匹配的动员血细胞移植物相关的慢性GVHD的风险。该试验在www.clinicaltrials.gov上注册为#NCT01427881。
The cumulative incidence of National Institutes of Health (NH-)-defined chronic graft versus -host disease (GVHD) requiring systemic treatment is 35% at 1 year after transplantation of granulocyte colony-stimulating factor (G-CSF) mobilized blood cells from HLA-matched related or unrelated donors. We hypothesized that high -dose cyclophosphamide given after G-CSF mobilized blood cell transplantation would reduce the cumulative 1-year incidence of chronic GVHD to 15% or less. Forty-three patients with high-risk hematologic malignancies (median age, 43 years) were enrolled between December 2011 and September 2013. Twelve (28%) received grafts from related donors, and 31 (72%) received grafts from unrelated donors. Pretransplant conditioning consisted of fludarabine and targeted busulfan (n = 25) or total body irradiation (zI2 Gy; n = 18). Cyclophosphamide was given at 50 mg/kg per day on days 3 and 4 after transplantation, followed by cyclosporine starting on day 5. The cumulative 1-year incidence of NIH-defined chronic GVHD was 16% (95% confidence interval, 5-28%). The cumulative incidence estimates of grades 2-4 and 3-4 acute GVHD were 77% and 0%, respectively. At 2 years, the cumulative incidence estimates of nonrelapse mortality and recurrent malignancy were 14% and 17%, respectively, and overall survival was projected at 70%. Of the 42 patients followed for year, 21 (50%) were relapse -free and alive without systemic immunosuppression at 1 year after transplantation. Thus, myeloablative pretransplant conditioning can be safely combined with high -dose cyclophosphamide after transplantation, and the risk of chronic GVHD associated with HLA-matched mobilized blood cell grafts can be substantially reduced. This trial was registered at www.clinicaltrials.gov as #NCT01427881.