Allo-SCT conditioning for myelodysplastic syndrome and acute myeloid leukemia with clofarabine, cytarabine and ATG
Allo-SCT conditioning for myelodysplastic syndrome and acute myeloid leukemia with clofarabine, cytarabine and ATG
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DOI：
10.1038/bmt.2008.423
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发表时间：
2009-07-01
影响因子：
4.8
通讯作者：
Vij, R.
中科院分区：
文献类型：
--
作者：
Martin, M. G.;Uy, G. L.;Vij, R.
清髓性 Allo-SCT 的应用因其相关的发病率和死亡率而受到限制。降低强度的调理方案试图减少这些症状，但会增加疾病复发的风险。鉴于氯法拉滨和阿糖胞苷在骨髓增生异常综合征/急性髓系白血病（MDS/AML）中的活性证据，我们探索了一种基于此骨干的新型降低强度预处理方案。患者接受氯法拉滨 40 mg/m(2) 静脉注射。第-6至-2天，阿糖胞苷1 g/m(2) 静脉注射第-6至-2天，抗胸腺细胞球蛋白(ATG) 1 mg/kg，第-4天，2.5 mg/kg x 2天，第-3和-2天。七名患者入组。他们的中位年龄为 54 岁；其中 3 名患有 MDS，4 名患有 AML。中性粒细胞减少症的中位持续时间为 14 天，血小板减少症的中位持续时间为 22 天。毒性包括手足综合征（57%为2级）、丙氨酸转氨酶（ALT）升高（57%为3级）、天冬氨酸转氨酶（AST）升高（86%为3级）和高胆红素血症（29%为3-5级）。未观察到急性 GVHD。前 7 名患者中的 3 名在+15、+26 和 +32 天去世后，该试验的招募被停止。四名幸存患者中的三名复发，中位 TTP 为 152 天。该方案的免疫抑制作用不足以确保植入，并且与大量的发病率和死亡率相关。骨髓移植(2009) 44, 13-17; doi：10.1038/bmt.2008.423； 2009 年 1 月 12 日在线发布
The application of myeloablative Allo-SCT is limited by its associated morbidity and mortality. Reduced-intensity conditioning regimens attempt to diminish these, but are associated with a higher risk of disease relapse. Given the evidence of activity of clofarabine and cytarabine in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), we explored a novel reduced-intensity conditioning regimen based on this backbone. Patients received clofarabine 40 mg/m(2) i.v. on days -6 to -2, cytarabine 1 g/m(2) i.v. on days -6 to -2 and anti-thymocyte globulin (ATG) 1 mg/kg on day -4 and 2.5 mg/kg x 2 days on days -3 and -2. Seven patients were enrolled. Their median age was 54 years; three were with MDS and four with AML. The median duration of neutropenia was 14 days and that of thrombocytopenia was 22 days. Toxicities included hand-foot syndrome (57% grade 2), elevated alanine aminotransferase (ALT) (57% grade 3), elevated aspartate aminotransferase (AST) (86% grade 3) and hyperbilirubinemia (29% grade 3-5). No acute GVHD was observed. Enrollment to the trial was halted after three of the first seven patients expired on days +15, +26 and +32. Three of the four surviving patients have relapsed witha median TTP of 152 days. This regimen was not sufficiently immunosuppressive to ensure engraftment, and was associated with substantial morbidity and mortality. Bone Marrow Transplantation (2009) 44, 13-17; doi:10.1038/bmt.2008.423; published online 12 January 2009