Phase II Trial of Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide after Reduced-Intensity Busulfan/Fludarabine Conditioning for Hematological Malignancies
Phase II Trial of Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide after Reduced-Intensity Busulfan/Fludarabine Conditioning for Hematological Malignancies
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DOI：
10.1016/j.bbmt.2015.01.026
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发表时间：
2015-05-01
影响因子：
4.3
通讯作者：
Champlin, Richard E.
中科院分区：
文献类型：
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作者：
Alousi, Amin M.;Brammer, Jonathan E.;Champlin, Richard E.
据报道，与使用钙调神经磷酸酶抑制剂（CNI）和甲氨蝶呤（MTX）的历史预防相比，在消融性HLA匹配的骨髓（BM）移植后使用环磷酰胺（CY）预防移植物抗宿主病（GVHD）具有相当的急性GVHD发生率，慢性GVHD和感染明显减少。我们进行了一项II期试验，在骨髓或外周血（PB）移植后，从匹配的相关（MRD）或非相关供体（MUD）进行降低强度预处理（RIC）后，使用静脉注射白消安（曲线下面积为4000微摩尔分钟），氟达拉滨（40 mg/m2），持续4天，CV 50 mg/kg。MUD接受者接受抗胸腺细胞球蛋白（ATG）;然而，后来的修正案删除了ATG。49例患者接受了治疗（急性髓性白血病/骨髓增生异常综合征，82%）。中位年龄为62岁（范围：39 - 72岁）。15例患者接受了MRD（9 PB/6 BM）; 34例患者接受了MUD（2 PB/32 BM）。II至IV级急性GVHD、III至IV级急性GVHD和慢性GVHD的累积发生率分别为58%、22%和18%。一项配对队列分析比较了他克莫司/甲氨蝶呤预防GVHD的结局，结果显示CY后的急性GVHD II级至IV级发生率较高（46% vs 19%;风险比[HR]，2.8; P = 0.02），治疗相关死亡率较高（HR，3.3; P = 0.035），总生存率较低（HR，1.9; P = 0.04）。慢性GVHD和CMV再激活的发生率没有差异。这项研究表明，后CY不应该被用作唯一的GVHD预防后，从HLA匹配的供体RIC移植。(C)2015年美国血液和骨髓移植协会。
Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (CY) after ablative HLA-matched bone marrow (BM) transplantation has been reported to have comparable rates of acute GVHD with an apparent reduction in chronic GVHD and infections when compared to historical prophylaxis with a calcineurin-inhibitor (CNI) and methotrexate (MTX). We conducted a phase II trial of posttransplantation CY (post-CY) after reduced-intensity conditioning (RIC) using intravenous busulfan (area under the curve of 4000 micromolar minute), fludarabine (40 mg/m(2)) for 4 days, and CV 50 mg/kg on days +3 and +4 after BM or peripheral blood (PB) transplantations from matched related (MRD) or unrelated donors (MUD). MUD recipients received antithymocyte globulin (ATG); however, a later amendment removed ATG. Forty-nine patients were treated (acute myeloid leukemia/myelodysplastic syndrome, 82%). Median age was 62 years (range, 39 to 72). Fifteen patients received an MRD (9 PB/6 BM); 34 had a MUD (2 PB/32 BM). The cumulative incidence of grade II to IV acute GVHD, III to IV acute GVHD, and chronic GVHD was 58%, 22%, and 18%, respectively. A matched cohort analysis compared outcomes to tacrolimus/methotrexate GVHD prophylaxis and indicated higher rates of acute GVHD grade II to IV (46% versus 19%; hazard ratio [HR], 2.8; P = .02) and treatment-related mortality (HR, 3.3; P = .035) and worse overall survival (HR, 1.9; P = .04) with post-CY. The incidence of chronic GVHD and CMV reactivation did not differ. This study suggests that post-CY should not be used as sole GVHD prophylaxis after a RIC transplantation from HLA-matched donors. (C) 2015 American Society for Blood and Marrow Transplantation.