Chronic myeloid leukemia (CML) is treated with tyrosine kinase inhibitors (TKI) that target the pathological BCR-ABL1 fusion oncogene. The objective of this statistical meta-analysis was to assess the prevalence of other hematological adverse events (AEs) that occur during or after predominantly first-line treatment with TKIs. Data from seventy peer-reviewed, published studies were included in the analysis. Hematological AEs were assessed as a function of TKI drug type (dasatinib, imatinib, bosutinib, nilotinib) and CML phase (chronic, accelerated, blast). AE prevalence aggregated across all severities and phases was significantly different between each TKI (p< 0.05) for anemia—dasatinib (54.5%), bosutinib (44.0%), imatinib (32.8%), nilotinib (11.2%); neutropenia—dasatinib (51.2%), imatinib (29.8%), bosutinib (14.1%), nilotinib (14.1%); thrombocytopenia—dasatinib (62.2%), imatinib (30.4%), bosutinib (35.3%), nilotinib (22.3%). AE prevalence aggregated across all severities and TKIs was significantly (p< 0.05) different between CML phases for anemia—chronic (28.4%), accelerated (66.9%), blast (55.8%); neutropenia—chronic (26.7%), accelerated (63.8%), blast (36.4%); thrombocytopenia—chronic (33.3%), accelerated (65.6%), blast (37.9%). An odds ratio (OR) with 95% confidence interval was used to compare hematological AE prevalence of each TKI compared to the most common first-line TKI therapy, imatinib. For anemia, dasatinib OR = 1.65, [1.51, 1.83]; bosutinib OR = 1.34, [1.16, 1.54]; nilotinib OR = 0.34, [0.30, 0.39]. For neutropenia, dasatinib OR = 1.72, [1.53, 1.92]; bosutinib OR = 0.47, [0.38, 0.58]; nilotinib OR = 0.47, [0.42, 0.54]. For thrombocytopenia, dasatinib OR = 2.04, [1.82, 2.30]; bosutinib OR = 1.16, [0.97, 1.39]; nilotinib OR = 0.73, [0.65, 0.82]. Nilotinib had the greatest fraction of severe (grade 3/4) hematological AEs (30%). In conclusion, the overall prevalence of hematological AEs by TKI type was: dasatinib > bosutinib > imatinib > nilotinib. Study limitations include inability to normalize for dosage and treatment duration.
慢性粒细胞白血病（CML）的治疗主要采用靶向病理BCR-ABL1融合癌基因的酪氨酸激酶抑制剂（TKI）。本统计荟萃分析旨在评估以一线TKI治疗为主期间或之后发生的其他血液学不良事件（AEs）的患病率。分析纳入了七十项经同行评审的已发表研究数据。血液学AEs的评估依据TKI药物类型（达沙替尼、伊马替尼、博舒替尼、尼洛替尼）和CML分期（慢性期、加速期、急变期）进行。汇总所有严重程度和分期的AE患病率显示，不同TKI药物在各类血液学AE中存在显著差异（p<0.05）：贫血——达沙替尼（54.5%）、博舒替尼（44.0%）、伊马替尼（32.8%）、尼洛替尼（11.2%）；中性粒细胞减少——达沙替尼（51.2%）、伊马替尼（29.8%）、博舒替尼（14.1%）、尼洛替尼（14.1%）；血小板减少——达沙替尼（62.2%）、伊马替尼（30.4%）、博舒替尼（35.3%）、尼洛替尼（22.3%）。汇总所有严重程度和TKI类型的AE患病率显示，不同CML分期在各类血液学AE中存在显著差异（p<0.05）：贫血——慢性期（28.4%）、加速期（66.9%）、急变期（55.8%）；中性粒细胞减少——慢性期（26.7%）、加速期（63.8%）、急变期（36.4%）；血小板减少——慢性期（33.3%）、加速期（65.6%）、急变期（37.9%）。采用比值比（OR）及95%置信区间比较各TKI与最常用一线治疗药物伊马替尼的血液学AE患病率：贫血方面，达沙替尼OR=1.65[1.51,1.83]；博舒替尼OR=1.34[1.16,1.54]；尼洛替尼OR=0.34[0.30,0.39]。中性粒细胞减少方面，达沙替尼OR=1.72[1.53,1.92]；博舒替尼OR=0.47[0.38,0.58]；尼洛替尼OR=0.47[0.42,0.54]。血小板减少方面，达沙替尼OR=2.04[1.82,2.30]；博舒替尼OR=1.16[0.97,1.39]；尼洛替尼OR=0.73[0.65,0.82]。尼洛替尼的严重（3/4级）血液学AEs比例最高（30%）。综上所述，按TKI类型划分的血液学AEs总体患病率为：达沙替尼 > 博舒替尼 > 伊马替尼 > 尼洛替尼。研究局限性包括未能对药物剂量和治疗持续时间进行标准化调整。
肿瘤(癌症)患者之家