低 OCT-1 活性的慢性期慢性髓性白血病患者随机分为高剂量伊马替尼组和标准剂量伊马替尼组，前者的缓解率更高，失败率更低。
Chronic phase chronic myeloid leukemia patients with low OCT-1 activity randomized to high-dose imatinib achieve better responses and have lower failure rates than those randomized to standard-dose imatinib.
机构信息
Department of Haematology, SA Pathology, RAH Campus, Adelaide, Australia.
出版信息
Haematologica. 2012 Jun;97(6):907-14. doi: 10.3324/haematol.2011.056457. Epub 2011 Dec 29.
BACKGROUND
The functional activity of the organic cation transporter 1 (OCT-1) protein (OCT-1 activity) is an excellent predictor of molecular response and progression-free survival in patients with newly diagnosed chronic phase chronic myeloid leukemia treated with imatinib as front-line therapy.
DESIGN AND METHODS
In this study the predictive value of OCT-1 activity in patients treated with imatinib 400 mg/day or 800 mg/day was evaluated in relation to trough imatinib plasma levels assessed in 100 patients enrolled in the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) trial.
RESULTS
The rate of major molecular responses by 24 months in patients on imatinib 400 mg/day was significantly higher in those with high OCT-1 activity than in those with low OCT-1 activity (low OCT-1 activity, 57% of patients; high OCT-1 activity, 100%; P < 0.001); the corresponding difference in patients treated with imatinib 800 mg/day did not reach statistical significance (low OCT-1 activity, 68%; high OCT-1 activity, 95%; P = 0.073). In addition, the combination of low trough imatinib levels (< 1200 ng/mL) and low OCT-1 activity defined a group of patients who had the lowest rates of major molecular response (47%) by 24 months compared to all other patients (81%, P = 0.009). These patients were also at the highest risk of failed imatinib therapy when compared to all other patients (P<0.001).
CONCLUSIONS
High-dose imatinib leads to superior molecular responses in patients with low OCT-1 activity. In this group trough imatinib levels may define a group with inferior outcomes. Among patients with high OCT-1 activity, neither higher imatinib dose nor monitoring imatinib trough levels was found to be of significant clinical value. Hence OCT-1 activity determined prior to the start of therapy in newly diagnosed CML patients provides a valuable prognostic tool to determine the optimal up-front dose of imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia.
背景
有机阳离子转运蛋白 1（OCT-1）蛋白的功能活性（OCT-1 活性）是新诊断的慢性期慢性髓性白血病患者接受伊马替尼一线治疗时预测分子反应和无进展生存期的极佳指标。
设计和方法
在这项研究中，我们评估了在接受伊马替尼 400mg/天或 800mg/天治疗的患者中，OCT-1 活性与酪氨酸激酶抑制剂优化和选择性（TOPS）试验中评估的 100 例患者的伊马替尼谷浓度之间的预测价值。
结果
接受伊马替尼 400mg/天治疗的患者在 24 个月时主要分子反应的发生率在高 OCT-1 活性患者中明显高于低 OCT-1 活性患者（低 OCT-1 活性患者，57%；高 OCT-1 活性患者，100%；P<0.001）；而在接受伊马替尼 800mg/天治疗的患者中，差异无统计学意义（低 OCT-1 活性患者，68%；高 OCT-1 活性患者，95%；P=0.073）。此外，低伊马替尼谷浓度（<1200ng/mL）和低 OCT-1 活性的组合定义了一组患者，这些患者在 24 个月时的主要分子反应率最低（47%），与所有其他患者相比（81%，P=0.009）。与所有其他患者相比，这些患者在伊马替尼治疗失败的风险也最高（P<0.001）。
结论
高剂量伊马替尼可使低 OCT-1 活性患者获得更好的分子反应。在这组患者中，伊马替尼谷浓度可能定义了一组预后较差的患者。在高 OCT-1 活性患者中，无论是更高的伊马替尼剂量还是监测伊马替尼谷浓度都没有显示出显著的临床价值。因此，在新诊断的 CML 患者开始治疗前确定 OCT-1 活性为新诊断的慢性期慢性髓性白血病患者确定伊马替尼的最佳起始剂量提供了有价值的预后工具。
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