Objectives: To explore the incidence and factors of severe leukopenia and/or thrombocytopenia in newly diagnosed patients with chronic myeloid leukemia (CML) to probe their impacts on cytogenetic and molecular responses, progression free survival (PFS) and overall survival (OS) . Methods: Data of newly diagnosed patients with CML in the chronic phase (CP) and/or accelerated phase (AP) were retrospectively collected and analyzed. Results: 855 CML patients [including 744 (87%) in the CP and 111 (13.0%) in the AP] were included in this study. 523 (61.2%) patients were male with a median age of 39 years (range, 14-87 years) . 749 (87.6%) patients received imatinib, 93 (10.9%) nilotinib, and 13 (1.5%) dasatinib, respectively as front-line therapy. At a median treatment of 1 month (range, 0.1-7.0 months) , 137 (16.0%) developed ≥grade 3 leukopenia and/or thrombocytopenia and recovered 0.6 month (range, 0.3-6.5 months) . Multivariate analysis showed that female gender (OR=1.5, 95%CI 1.0-2.2, P=0.033) , WBC ≥100×109/L (OR=1.9, 95%CI 1.3-2.8, P=0.001) , CP in Sokal high-risk (OR=2.2, 95%CI 1.2-3.9, P=0.005) , AP with ≥15% blast cells in blood or bone marrow (OR=5.1, 95%CI 1.9-13.3, P=0.001) were factors associated with higher incidence of ≥grade 3 leukopenia and/or thrombocytopenia. Severe leukopenia and/or thrombocytopenia with time of drug discontinuance >2 weeks was associated with lower probabilities of achieving complete cytogenetic (OR=0.4, 95%CI 0.3-0.6, P<0.001) , severe leukopenia and/or thrombocytopenia, no matter the time of drug discontinuance >2 weeks or ≤2 weeks, were associated with lower probabilities of achieving major molecular responses (OR=0.3, 95%CI 0.2-0.5, P<0.001; OR=0.7, 95%CI 0.5-1.0, P=0.036) and MR4.5 (OR=0.2, 95%CI 0.1-0.5, P=0.002; OR=0.7, 95%CI 0.4-1.1, P=0.110) ; however, those had no impacts on PFS and OS. Conclusions: Severe leukopenia and/or thrombocytopenia were common adverse events during TKI therapy. Female patients, WBC ≥100×109/L at diagnosed, CP in Sokal high-risk, CML-AP with ≥15% blast cells in blood or bone marrow were at high risk for higher incidence of severe leukopenia and/or thrombocytopenia. Those severe adverse events had impacts on lower cytogenetic and molecular response.
目的： 评估慢性髓性白血病（CML）初诊患者酪氨酸激酶抑制剂（TKI）一线治疗中严重的白细胞和（或）血小板减少的发生率、相关因素及其对治疗反应及生存的影响。 方法： 回顾性分析2001年1月至2018年1月诊治的初诊CML慢性期（CP）或加速期（AP）连续病例资料。 结果： 共收集855例患者的数据，其中523例（61.2%）为男性，中位年龄39（14~87）岁。CP患者744例（87.0%），AP患者111例（13.0%）。一线服用伊马替尼749例（87.6%），尼洛替尼93例（10.9%），达沙替尼13例（1.5%）。137例（16.0%）在中位1.0（0.1~7.0）个月时发生≥3级白细胞和（或）血小板减少，持续0.6（0.3~6.5）个月。多因素分析显示，女性（OR=1.5，95%CI 1.0~2.2，P=0.033）、诊断时WBC ≥100×109/L（OR=1.9，95%CI 1.3~2.8，P=0.001）、CP-Sokal高危（OR=2.2，95%CI 1.2~3.9，P=0.005）和原始细胞增多型AP（OR=5.1，95%CI 1.9~13.3，P=0.001）与≥3级白细胞和（或）血小板减少的发生显著相关。与未发生≥3级白细胞和（或）血小板减少相比，发生≥3级白细胞和（或）血小板减少且停药>2周与较低的完全细胞遗传学反应率（OR=0.4，95%CI 0.3~0.6，P<0.001）显著相关；发生≥3级白细胞和（或）血小板减少，无论停药是否>2周，均与较低的主要分子学反应率（OR=0.3，95%CI 0.2~0.5，P<0.001；OR=0.7，95%CI 0.5~1.0，P=0.036）和MR4.5率（OR=0.2，95%CI 0.1~0.5，P=0.002；OR=0.7，95%CI 0.4~1.1，P=0.110）相关，但不影响疾病进展和生存。 结论： 严重的白细胞和（或）血小板减少是TKI治疗中常见的不良反应，女性、诊断时WBC ≥100×109/L和CP-Sokal高危、原始细胞增多型AP是严重的白细胞和（或）血小板减少发生的高危人群。发生严重的白细胞和（或）血小板减少降低了TKI治疗中的细胞遗传学和分子学反应率。.
Keywords: Hematologic toxicity; Leukemia, myeloid, chronic, BCR-ABL (+); Tyrosine kinase inhibitors.