Achieving deeper molecular response is associated with a better clinical outcome in chronic myeloid leukemia patients on imatinib front-line therapy
Achieving deeper molecular response is associated with a better clinical outcome in chronic myeloid leukemia patients on imatinib front-line therapy
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DOI：
10.3324/haematol.2013.095158
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发表时间：
2014-03-01
期刊：
影响因子：
10.1
通讯作者：
Mahon, Francois-Xavier
中科院分区：
文献类型：
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作者：
Etienne, Gabriel;Dulucq, Stephanie;Mahon, Francois-Xavier
伊马替尼持续治疗慢性粒细胞白血病患者可导致完全分子学缓解，允许停药而不复发。我们开始评估伊马替尼初治慢性期慢性粒细胞白血病患者完全分子学缓解的频率，以确定实现完全细胞遗传学缓解的患者完全分子学缓解的基线和治疗下预测因素，并评估完全分子学缓解是否与更好的结局相关。考虑纳入随机选择的接受伊马替尼一线治疗的患者（n=266）。确认完全分子学缓解，定义为MR4.5，BCR-ABL转录水平不可检测。中位随访时间为4.43年（范围0.79-10.8年）。65例患者（24%）在中位时间32.7个月内达到完全分子学缓解。诊断时无脾肿大、治疗前12个月达到完全细胞遗传学缓解以及完全细胞遗传学缓解后一年内主要分子学缓解可预测进一步达到完全分子学缓解。无论主要分子学缓解状态如何，达到完全分子学缓解的患者的无事件和无失败生存率均优于完全细胞遗传学缓解的患者（分别为95.2% vs. 64.7% vs. 27.7%，P=0.00124; 98.4% vs. 82.3% vs. 56%，P=0.0335）。3组的总生存期相同。除了完全细胞遗传学缓解和主要分子学缓解外，更深的分子学缓解与更好的无事件和无失败生存期相关，完全分子学缓解可提供最佳结局。
Sustained imatinib treatment in chronic myeloid leukemia patients can result in complete molecular response allowing discontinuation without relapse. We set out to evaluate the frequency of complete molecular response in imatinib de novo chronic phase chronic myeloid leukemia patients, to identify base-line and under-treatment predictive factors of complete molecular response in patients achieving complete cytogenetic response, and to assess if complete molecular response is associated with a better outcome. A random selection of patients on front-line imatinib therapy (n=266) were considered for inclusion. Complete molecular response was confirmed and defined as MR4.5 with undetectable BCR-ABL transcript levels. Median follow up was 4.43 years (range 0.79-10.8 years). Sixty-five patients (24%) achieved complete molecular response within a median time of 32.7 months. Absence of spleen enlargement at diagnosis, achieving complete cytogenetic response before 12 months of therapy, and major molecular response during the year following complete cytogenetic response was predictive of achieving further complete molecular response. Patients who achieved complete molecular response had better event-free and failure-free survivals than those with complete cytogenetic response irrespective of major molecular response status (95.2% vs. 64.7% vs. 27.7%, P=0.00124; 98.4% vs. 82.3% vs. 56%, P=0.0335), respectively. Overall survival was identical in the 3 groups. In addition to complete cytogenetic response and major molecular response, further deeper molecular response is associated with better event-free and failure-free survivals, and complete molecular response confers the best outcome.