二代酪氨酸激酶抑制剂一线治疗慢性髓性白血病慢性期患者发生严重血细胞减少的相关因素及其对治疗反应和结局的影响

OBJECTIVE: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia（CP-CML）receiving initial second-generation tyrosine kinase inhibitors（2G-TKI）. METHODS: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. RESULTS: Data from 267 patients who received initial 2G-TKI, including nilotinib（n＝239, 89.5％）and dasatinib（n＝28, 10.5％）, were interrogated. The median age was 36（range, 18–73）years, and 156（58.4％）patients were male. At a median treatment period of 1.0（0.1–3.0）month, 43（16.1％）patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0（0.1–24.6）month. Male（OR＝2.9, 95％CI 1.2-6.8; P＝0.018）, age of ≥36 years（OR＝3.2, 95％ CI 1.4–7.2, P＝0.005）, a spleen below a costal margin of ≥7 cm（OR＝2.8, 95％ CI 1.2–6.6, P＝0.020）, and a hemoglobin（HGB）level of <100 g/L（OR＝2.9, 95％ CI 1.3–6.8, P＝0.012）at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups（P < 0.001）. Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response（CCyR, HR＝0.5, 95％ CI 0.3–0.7, P<0.001）and major molecular response（MMR, HR＝0.4, 95％ CI 0.3–0.8, P＝0.004）and was not significantly associated with failure, progression, and survival. CONCLUSION: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.