3个月时评估转录水平即可预测接受酪氨酸激酶抑制剂治疗的慢性粒细胞性白血病患者的结局
Purpose:
We studied BCR-ABL1 transcript levels in patients with chronic myeloid leukemia in chronic phase (CML-CP) at 3, 6, and 12months after starting imatinib to identify molecular milestones that would predict for overall survival (OS) and other outcomes more reliably than serial marrow cytogenetics.
Patients and Methods:
We analyzed 282 patients with CML-CP who received imatinib 400mg/d as first-line therapy followed by dasatinib or nilotinib if treatment with imatinib failed. We used a receiver operating characteristic curve to identify the cutoffs in transcript levels at 3, 6, and 12months that would best predict patient outcome. We validated our findings in an independent cohort of 95 patients treated elsewhere.
Results:
Patients with transcript levels of more than 9.84% (n=68) at 3months had significantly lower 8-year probabilities of OS (56.9% v 93.3%; P<.001), progression-free survival, cumulative incidence of complete cytogenetic response, and complete molecular response than those with higher transcript levels. Similarly, transcript levels of more than 1.67% (n=87) at 6months and more than 0.53% (n=93) at 12months identified high-risk patients. However, transcript levels at 3months were the most strongly predictive for the various outcomes. When we compared OS for the groups defined molecularly at 6 and 12months with the usual cytogenetic milestones, categorization by transcript numbers was the only independent predictor for OS (relative risk, 0.207; P<.001 and relative risk, 0.158; P<.001, respectively).
Conclusion:
A single measurement of BCR-ABL1 transcripts performed at 3months is the best way to identify patients destined to fare poorly, thereby allowing early clinical intervention.
来源: Eclips
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