A novel clofarabine bridge strategy facilitates allogeneic transplantation in patients with relapsed/refractory leukemia and high-risk myelodysplastic syndromes.
A novel clofarabine bridge strategy facilitates allogeneic transplantation in patients with relapsed/refractory leukemia and high-risk myelodysplastic syndromes.
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DOI：
10.1038/bmt.2013.79
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发表时间：
2013-11
影响因子：
4.8
通讯作者：
Stock, W.
中科院分区：
文献类型：
--
作者：
Locke, F.;Agarwal, R.;Kunnavakkam, R.;van Besien, K.;Larson, R. A.;Odenike, O.;Godley, L. A.;Liu, H.;Le Beau, M. M.;Gurbuxani, S.;Thirman, M. J.;Sipkins, D.;White, C.;Artz, A.;Stock, W.
复发/难治性白血病或晚期骨髓增生异常综合征（MDS）患者在异体造血细胞移植（HCT）后表现不佳。我们报告了前瞻性II期研究结果，29名患者给予氯法拉滨30mg /m2/天静脉注射× 5天，随后立即在细胞减少最低点进行HCT调节。共有15/29例患者（52%）根据预先定义的标准（细胞度< 20%，母细胞< 10%）出现细胞减少。骨髓细胞数量（P < 0.0001）和原细胞百分比（P = 0.03）降低。毒性是可以接受的，有短暂的高胆红素血症（48%）和gr3-4感染（10%）。总共有28/29进行了移植；27人接受ATG或阿仑单抗治疗。HCT后，180天无复发死亡率（NRM）为7%(95%置信区间（CI）： 1-21)，复发率为29% (95% CI: 13-46)， OS为71% (95% CI: 51-85)，与已发表的高风险患者数据相比有利。2年移植物抗宿主病发生率为40% (95% CI: 21-58)， 2年OS发生率为31% （95% CI: 14-48）。最低点疾病与HCT后较差的OS相关（HR = 1.22 / 10%骨髓母细胞，95% CI: 1.02-1.46）。对于AML/MDS患者，成功的细胞减少增加了PFS （330 vs 171天，P = 0.3）和OS （375 vs 195天，P = 0.31）。氯法拉滨作为HCT的桥梁可减轻疾病负担，耐受性良好，并允许高风险患者接受NRM可接受的HCT。晚期复发是常见的；因此，应采取其他战略。nct - 00724009。
Patients with relapsed/refractory leukemias or advanced myelodysplastic syndrome (MDS) fare poorly following allogeneic hematopoietic cell transplant (HCT). We report prospective phase II study results of 29 patients given clofarabine 30 mg/m2/day i.v. × 5 days followed immediately by HCT conditioning while at the cytopenic nadir. A total of 15/29 patients (52%) were cytoreduced according to pre-defined criteria (cellularity < 20% and blasts < 10%). Marrow cellularity (P < 0.0001) and blast% (P = 0.03) were reduced. Toxicities were acceptable, with transient hyperbilirubinemia (48%) and gr3–4 infections (10%). In all, 28/29 proceeded to transplant; 27 received ATG or alemtuzumab. Post HCT, 180 day non-relapse mortality (NRM) was 7% (95% confidence interval (CI): 1–21), relapse was 29% (95% CI: 13–46) and OS was 71% (95% CI: 51–85), comparing favorably to published data for high-risk patients. Two-year graft vs host disease incidence was 40% (95% CI: 21–58) and 2 year OS was 31% (95% CI: 14–48). Disease at the nadir correlated with inferior OS after HCT (HR = 1.22 for each 10% marrow blasts, 95% CI: 1.02–1.46). For AML/MDS patients, there was a suggestion that successful cytoreduction increased PFS (330 vs 171 days, P = 0.3) and OS (375 vs 195 days, P = 0.31). Clofarabine used as a bridge to HCT reduces disease burden, is well tolerated, and permits high-risk patients to undergo HCT with acceptable NRM. Late relapses are common; thus, additional strategies should be pursued. NCT-00724009.
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