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
1] Department of Blood and Marrow Transplant, H Lee Moffitt Cancer Center, Tampa, FL, USA [2] Department of Oncologic Sciences, University of South Florida, Tampa, FL, USA.
Bone Marrow Transplant. 2013 Nov;48(11):1437-43. doi: 10.1038/bmt.2013.79. Epub 2013 Jun 17.
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/m(2)/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.
复发/难治性白血病或晚期骨髓增生异常综合征（MDS）患者在异基因造血细胞移植（HCT）后预后较差。我们报告了一项前瞻性II期研究结果，29例患者接受氯法拉滨30mg/m²/天静脉注射×5天，在血细胞减少最低点时紧接着进行HCT预处理。根据预先定义的标准，共有15/29例患者（52%）实现了细胞减少（细胞密度<20%且原始细胞<10%）。骨髓细胞密度（P<0.0001）和原始细胞百分比（P=0.03）降低。毒性反应可接受，短暂性高胆红素血症发生率为48%，3-4级感染发生率为10%。总共28/29例患者继续进行移植；27例接受了抗胸腺细胞球蛋白或阿仑单抗。HCT后，180天非复发死亡率（NRM）为7%（95%置信区间（CI）：1-21），复发率为29%（95%CI：13-46），总生存率（OS）为71%（95%CI：51-85），与已发表的高危患者数据相比更具优势。两年移植物抗宿主病发生率为40%（95%CI：21-58），两年总生存率为31%（95%CI：14-48）。最低点时的疾病状态与HCT后的总生存率较差相关（每10%骨髓原始细胞的风险比（HR）=1.22，95%CI：1.02-1.46）。对于急性髓系白血病/骨髓增生异常综合征患者，有迹象表明成功的细胞减少可提高无进展生存期（330天对171天，P=0.3）和总生存期（375天对195天，P=0.31）。氯法拉滨用作HCT的桥梁可减轻疾病负担，耐受性良好，并使高危患者能够以可接受 的NRM进行HCT。晚期复发很常见；因此，应寻求其他策略。NCT-00724009。
