Homoharringtonine and low-dose cytarabine in the management of late chronic-phase chronic myelogenous leukemia
Homoharringtonine and low-dose cytarabine in the management of late chronic-phase chronic myelogenous leukemia
复制标题
DOI：
10.1200/jco.2000.18.20.3513
复制
发表时间：
2000-10-15
影响因子：
45.3
通讯作者：
O'Brien, S
中科院分区：
文献类型：
--
作者：
Kantarjian, HM;Talpaz, M;O'Brien, S
目的：评价汉三尖杉酯碱（HHT）和小剂量阿糖胞苷（ara-C）联合方案治疗干扰素α治疗失败的费城染色体（Ph）阳性慢性粒细胞白血病（CML）患者的疗效和毒性特征。患者和方法：治疗105名患者：慢性期100例（15例细胞遗传学克隆进化），加速期5例。他们的中位年龄为52岁;所有人都用IFN α治疗失败; 94%处于慢性晚期; 43%暴露于阿糖胞苷，11%暴露于HHT。患者接受HHT 2.5 mg/m2，每日连续输注5天，阿糖胞苷15 mg/m2，每日皮下注射2次，每4周5天。慢性期的100例患者的结果进行了比较，与以前的研究组73例HHT单独治疗。结果：总体而言，完全血液学反应（CML）率在慢性期为72%，细胞遗传学反应率为32%（主要反应，15%，完全反应，5%）。毒性是可接受的，主要与中度腹泻（3%）、头痛（3%）、心血管事件（3%）和骨髓抑制相关并发症（3%至14%）有关。中位随访期为25个月，估计4年生存率为55%。反应率是相同的HHT加阿糖胞苷与HHT单独，但生存期显着较长的组合后，占difficult在研究groups和多变量analysis.Conclusion：HHT和阿糖胞苷的组合方案是有效的，安全的慢性粒细胞白血病患者谁经历了治疗失败与IFN α和需要进行调查，与IFN α作为一线CML治疗的一部分。阿糖胞苷的加入并没有提高反应率，但可能提高了生存率，这可能是通过抑制与疾病转化相关的克隆。(C)2000年，美国临床肿瘤学会。
Purpose: To evaluate the efficacy and toxicity profiles of a combination regimen of hamoharringtonine (HHT) and low-dose cytarabine (ara-C) in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who had experienced treatment failure with interferon alfa (IFN alpha) therapy.Patients and Methods: One hundred five patients were treated: 100 in chronic phase (15 with cytogenetic clonal evolution) and five in accelerated phase. Their median age was 52 years; all had been treated unsuccessfully with IFN alpha; 94% were in late chronic phase; 43% held been exposed to ara-C and 11% had been exposed to HHT. Patients received HHT 2.5 mg/m(2) by continuous infusion daily for 5 days and ara-C 15 mg/m2 daily in two subcutaneous injections for 5 days every 4 weeks. The outcome of the 100 patients in chronic phase was compared with a previous study group of 73 patients treated with HHT alone.Results: Overall, the complete hematologic response (CHR) rate in chronic phase was 72%; the cytogenetic response rate was 32% (major response, 15%; complete response, 5%). Toxicities were acceptable, mostly related to moderate diarrhea (3%), headaches (3%), cardiovascular events (3%), and myelosuppression-associated complications (3% to 14%). With a median follow-up period of 25 months, the estimated 4-year survival rate wets 55%. Response rates were identical with HHT plus ara-C versus HHT alone, but the survival was significantly longer with the combination after accounting for diffrences in the study groups and by multivariate analysis.Conclusion: The combination regimen of HHT and ara-C is effective and safe in patients with CML who have experienced treatment failure with IFN alpha and needs to be investigated together with IFN alpha as part of front-line CML therapy. The addition of ara-C did not improve the response rates but may have improved survival, perhaps through suppression of clones related to disease transformation. (C) 2000 by American Society of Clinical Oncology.