Multicenter Independent Assessment of Outcomes in Chronic Myeloid Leukemia Patients Treated With Imatinib
Multicenter Independent Assessment of Outcomes in Chronic Myeloid Leukemia Patients Treated With Imatinib
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DOI：
10.1093/jnci/djr060
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发表时间：
2011-04-01
影响因子：
10.3
通讯作者：
Kim, Dong-Wook
中科院分区：
文献类型：
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作者：
Gambacorti-Passerini, Carlo;Antolini, Laura;Kim, Dong-Wook
伊马替尼可延缓慢性粒细胞白血病（CML）的发展。然而，现有的发病率和死亡率的信息主要是基于赞助的试验，而独立的长期领域的研究是缺乏的。患者和方法连续CML患者谁开始伊马替尼治疗2005年之前，谁在完全细胞遗传学缓解（CCyR）后2年（+/-3个月）有资格在独立的多中心伊马替尼长期（副作用）的研究（ILTE）招募。根据Kaplan-Meier方法估计首次严重和非严重不良事件的发生率以及CCyR损失，并与标准对数秩检验进行比较。用细胞遗传学和定量聚合酶链反应评价费城染色体阴性造血的获得。根据Kalbleisch-Prentice方法，估计与CML进展相关或无关的死亡累积发生率，考虑竞争风险。标准化发病率是根据特定性别和年龄组的人群发病率计算的。根据卡方（2）分布，通过精确方法计算置信区间。所有的统计检验是双侧的。结果共832例患者谁是治疗的中位数为5.8年。有139例记录的严重不良事件，其中19.4%与伊马替尼相关。在53%的患者中共观察到830起非严重不良事件; 560起（68%）与伊马替尼相关。最常见的是肌肉痉挛、虚弱、水肿、皮肤脆弱、腹泻、肌腱或韧带损伤。19例患者（2.3%）因药物相关毒性作用而停用伊马替尼。45例患者失去CCyR，发生率为1.4/100人-年。179例患者获得持久（> 1年）阴性费城染色体造血。观察到20例死亡，死亡发生率为4.8（标准化发病率= 0.7; 95%可信区间= 0.40 ~ 1.10，P = 0.08），只有6例（30%）与CML进展相关。结论在这项研究中，CML相关死亡在开始伊马替尼治疗后2年处于CCyR的CML患者中并不常见，存活率与一般人群无统计学显著差异。
Background Imatinib slows development of chronic myeloid leukemia (CML). However, available information on morbidity and mortality is largely based on sponsored trials, whereas independent long-term field studies are lacking.Patients and Methods Consecutive CML patients who started imatinib treatment before 2005 and who were in complete cytogenetic remission (CCyR) after 2 years (+/- 3 months) were eligible for enrollment in the independent multicenter Imatinib Long-Term (Side) Effects (ILTE) study. Incidence of the first serious and nonserious adverse events and loss of CCyR were estimated according to the Kaplan-Meier method and compared with the standard log-rank test. Attainment of negative Philadelphia chromosome hematopoiesis was assessed with cytogenetics and quantitative polymerase chain reaction. Cumulative incidence of death related or unrelated to CML progression was estimated, accounting for competing risks, according to the Kalbleisch-Prentice method. Standardized incidence ratios were calculated based on population rates specific for sex and age classes. Confidence intervals were calculated by the exact method based on the chi(2) distribution. All statistical tests were two-sided.Results A total of 832 patients who were treated for a median of 5.8 years were enrolled. There were 139 recorded serious adverse events, of which 19.4% were imatinib-related. A total of 830 nonserious adverse events were observed in 53% of patients; 560 (68%) were imatinib-related. The most frequent were muscle cramps, asthenia, edema, skin fragility, diarrhea, tendon, or ligament lesions. Nineteen patients (2.3%) discontinued imatinib because of drug-related toxic effects. Forty-five patients lost CCyR, at a rate of 1.4 per 100 person-years. Durable (> 1 year) negative Philadelphia chromosome hematopoiesis was attained by 179 patients. Twenty deaths were observed, with a 4.8% mortality incidence rate (standardized incidence ratio = 0.7; 95% confidence interval = 0.40 to 1.10, P = .08), with only six (30%) associated with CML progression.Conclusions In this study, CML-related deaths were uncommon in CML patients who were in CCyR 2 years after starting imatinib, and survival was not statistically significantly different from that of the general population.