慢性髓性白血病患者服用酪氨酸激酶抑制剂期间发生的严重血液学不良反应及其对治疗反应的影响

OBJECTIVE: 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 ≥100×10(9)/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. CONCLUSION: Severe leukopenia and/or thrombocytopenia were common adverse events during TKI therapy. Female patients, WBC ≥100×10(9)/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.