Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate
Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate
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DOI：
10.1158/1078-0432.ccr-04-2139
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发表时间：
2005-05-01
影响因子：
11.5
通讯作者：
Kantarjian, H
中科院分区：
文献类型：
--
作者：
Cortes, J;Talpaz, M;Kantarjian, H
目的：确定接受伊马替尼治疗的慢性粒细胞白血病 (CIVIL) 患者的分子缓解和复发的临床意义。 实验设计：我们分析了 280 名使用伊马替尼实现完全细胞遗传学缓解的慢性期 CIVIL 患者的定量 PCR 结果（其中 117 名患者在 IFN-α 失败后，163 名之前未经治疗）。中位随访时间为 31 个月（范围为 3-52 个月）。结果：治疗开始前中位 BCR-ABL/ABL 比率为 39.44（范围为 0.252-170.53）。 174 例 (62%) 实现了主要分子反应（BCR-ABL/ABL 比率 < 0.05%），95 例（34%）的转录本变得无法检测到（完全分子反应）。通过多变量分析，只有高剂量伊马替尼治疗（P = 0.02）与主要分子反应的实现相关。 166 名获得主要分子缓解的患者中有 9 名 (5%) 失去了细胞遗传学缓解，而未获得这种缓解的 68 名患者中有 25 名 (37%) 失去了细胞遗传学缓解 (P < 0.0001)。治疗开始 12 个月后达到主要分子缓解的患者的完全细胞遗传学缓解持续时间明显优于其他患者。治疗 3 个月后转录水平降低 > 1 个对数，预示着 24 个月时实现主要分子反应的可能性提高。 BCR-ABL 转录物水平的增加仅在未达到主要分子反应的患者中预测细胞遗传学缓解的丧失。结论：实现主要分子反应，特别是在治疗的第一年内，可预测持久的细胞遗传学缓解，并且可能是 CML 治疗的未来目标。
Purpose:To determine the clinical significance of molecular response and relapse among patients with chronic myelogenous leukemia (CIVIL) treated with imatinib.Experimental Design: We analyzed the results of quantitative PCR in 280 patients with CIVIL in chronic phase who achieved complete cytogenetic remission with imatinib (117 after IFN-alpha failure and 163 previously untreated). Median follow-up was 31 months (range, 3-52 months).Results: Median BCR-ABL/ABL ratio before the start of therapy was 39.44 (range, 0.252-170.53). A major molecular response (BCR-ABL/ABL ratio < 0.05%) was achieved in 174 (62%), and transcripts became undetectable (complete molecular response) in 95 (34%). By multivariate analysis, only treatment with high-dose imatinib (P = 0.02) was associated with achievement of a major molecular response. Nine of 166 (5%) patients who achieved a major molecular response lost their cytogenetic remission, compared with 25 of 68 (37%) among those who did not achieve this response (P < 0.0001). Patients achieving a major molecular response 12 months after the start of therapy had significantly better complete cytogenetic remission duration than others. A > 1-log reduction in transcript levels after 3 months of therapy predicted for an improved probability of achieving a major molecular response at 24 months. Increasing levels of BCR-ABL transcripts predicted for a loss of cytogenetic remission only among patients who did not achieve a major molecular response.Conclusions: Achieving a major molecular response, particularly within the first year of therapy, is predictive of a durable cytogenetic remission and may be the future goal of therapy in CML.