Cortes Jorge, Talpaz Moshe, O'Brien Susan, Jones Dan, Luthra Rajyalakshmi, Shan Jenny, Giles Francis, Faderl Stefan, Verstovsek Srdan, Garcia-Manero Guillermo, Rios Mary B, Kantarjian Hagop
Departments of Leukemia, the University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Clin Cancer Res. 2005 May 1;11(9):3425-32. doi: 10.1158/1078-0432.CCR-04-2139.
To determine the clinical significance of molecular response and relapse among patients with chronic myelogenous leukemia (CML) treated with imatinib.
We analyzed the results of quantitative PCR in 280 patients with CML 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).
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.
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.
确定接受伊马替尼治疗的慢性髓性白血病（CML）患者分子反应和复发的临床意义。
我们分析了280例慢性期CML患者的定量PCR结果，这些患者接受伊马替尼治疗后达到了完全细胞遗传学缓解（117例为干扰素-α治疗失败后患者，163例为初治患者）。中位随访时间为31个月（范围3 - 52个月）。
治疗开始前BCR-ABL/ABL比值中位数为39.44（范围0.252 - 170.53）。174例（62%）患者达到主要分子反应（BCR-ABL/ABL比值<0.05%），95例（34%）患者转录本不可检测（完全分子反应）。多因素分析显示，仅高剂量伊马替尼治疗（P = 0.02）与达到主要分子反应相关。达到主要分子反应的166例患者中有9例（5%）失去了细胞遗传学缓解，而未达到该反应的68例患者中有25例（37%）失去缓解（P < 0.0001）。治疗开始12个月后达到主要分子反应的患者完全细胞遗传学缓解持续时间明显长于其他患者。治疗3个月后转录本水平降低>1个对数可预测24个月时达到主要分子反应的概率提高。仅在未达到主要分子反应的患者中，BCR-ABL转录本水平升高预示细胞遗传学缓解丧失。
达到主要分子反应，尤其是在治疗的第一年，预示着持久的细胞遗传学缓解，可能是CML治疗的未来目标。
