伊马替尼治疗初发慢性髓性白血病慢性期患者获得分子学反应的临床预测模型

OBJECTIVE: To develop a scoring system to predict molecular responses in patients with chronic myeloid leukemia in the chronic phase（CML-CP）receiving initial imatinib therapy. METHODS: Data from consecutive adults with newly diagnosed CML-CP treated by initial imatinib was interrogated and subjects were distributed randomly into training and validation cohort, in a ratio of 2∶1. Fine-gray models were applied in the training cohort to identify co-variates of predictive value for major molecular response（MMR）and MR4. A predictive system was built using significant co-variates. The predictive system was then tested in the validation cohort and the area under the receiver-operator characteristic curve（AUROC）was used to estimate accuracy of the predictive system. RESULTS: 1 364 CML-CP subjects receiving initial imatinib were included in this study. Subjects were distributed randomly into training cohort（n＝909）and validation cohort（n＝455）. In the training cohort, the male gender, European Treatment and Outcome Study for CML（EUTOS）Long-Term Survival（ELTS）intermediate-risk, ELTS high-risk, high WBC（≥130×10(9)/L or 120×10(9)/L, MMR or MR4）and low HGB（<110 g/L）at diagnosis were significantly related with poor molecular responses and were given points based on their regression coefficients. For MMR, male gender, ELTS intermediate-risk and low HGB（<110 g/L）were given 1 point; ELTS high-risk and high WBC（≥130×10(9)/L）, 2 points. For MR4, male gender was given 1 point; ELTS intermediate-risk and low HGB（<110 g/L）were given 2 points; high WBC（≥120×10(9)/L）, 3 points; ELTS high-risk, 4 points. We divided all subjects into 3 risk subgroups according to the predictive system above. Cumulative incidence of achieving MMR and MR4 in 3 risk subgroups was significantly different in both training and validation cohort（all P values <0.001）. In the training and validation cohorts, the time-dependent AUROC ranges of MMR and MR4 predictive systems were 0.70-0.84 and 0.64-0.81, respectively. CONCLUSION: A scoring system combining gender, WBC, HGB level and ELTS risk was built to predict MMR and MR4 in CML-CP patients receiving initial imatinib therapy. This system had good discrimination and accuracy, which could help phsicians optimize the selsction of initial TKI-therapy.