DataSheet_1_Impact of BCR-ABL1 Transcript Type on Outcome in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors: A Pairwise and Bayesian Network Meta-Analysis.docx

PurposeTo evaluate the impact of BCR-ABL1 transcript type on outcome in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs).MethodsPubMed, Embase and Cochrane library were systematically searched for relevant studies. Outcomes assessed were: major molecular response (MMR) at 6, 12, 18 and 60 months, deep molecular response (DMR) at 6, 12, 18 and 60 months, event-free survival (EFS), progression-free survival (PFS), overall survival (OS) and treatment-free remission (TFR). Odds ratios (ORs) and hazard ratios (HRs) were estimated and pooled using a random effect model.ResultsA total of 16 retrospective cohort studies involving 5,411 patients were included in this study. Compared with e13a2 transcripts, there was a statistically significant advantage for patients with e14a2 (alone or with co-expressed e13a2) in terms of MMR and DMR at 6, 12 and 18 months. This benefit was sustained up to 5 years for patients with e14a2 transcripts (OR 1.60, 1.23-2.07 and 2.21, 1.71-2.87, respectively), but not for patients with both transcripts. The expression of e14a2 also improved EFS (HR 0.71, 0.53-0.94) and OS (HR 0.76, 0.57-1.00) throughout treatment period. Importantly, having e14a2 transcripts were associated with a higher rate of TFR (OR 2.94, 1.70-5.08) in CML patients attempting TKI discontinuation. Bayesian network meta-analysis showed that e14a2 had the highest probability to be the most favorable transcript type for all outcomes, followed by both and e13a2.ConclusionsThe expression of e14a2 had a positive impact on MMR, DMR, EFS, OS and TFR. We suggest that in the future, the e14a2 transcript can be added to the list of prognostic factors to guide clinical decisions in treating CML.Systematic Review Registration[https://www.crd.york.ac.uk/PROSPERO/#myprospero], identifier PROSPERO (CRD42021288440).

目的：本研究的目的是评估BCR-ABL1转录型对接受酪氨酸激酶抑制剂（TKIs）治疗的慢性髓系白血病（CML）患者预后的影响。方法：对PubMed、Embase和Cochrane图书馆进行了系统检索，以获取相关研究。评估的结局包括：6、12、18和60个月时的主要分子反应（MMR）、深度分子反应（DMR）、无事件生存（EFS）、无进展生存（PFS）、总生存（OS）和无治疗缓解（TFR）。通过随机效应模型估计并汇总了优势比（ORs）和风险比（HRs）。结果：共纳入16项回顾性队列研究，涉及5,411名患者。与e13a2转录型相比，e14a2转录型（单独或与共表达的e13a2）的患者在6、12和18个月时的MMR和DMR方面具有统计学上的显著优势。这种益处对于e14a2转录型的患者可以持续至5年（OR 1.60，1.23-2.07和2.21，1.71-2.87，分别），但对于同时具有两种转录型的患者则无此优势。e14a2的表达在整个治疗期间也改善了EFS（HR 0.71，0.53-0.94）和OS（HR 0.76，0.57-1.00）。重要的是，具有e14a2转录型的患者在尝试TKI停药的患者中与更高的TFR率相关（OR 2.94，1.70-5.08）。贝叶斯网络meta分析显示，e14a2具有最高概率成为所有结局中最有利的转录型，其次是同时存在e13a2和e14a2。结论：e14a2的表达对MMR、DMR、EFS、OS和TFR有积极影响。我们建议，在未来，e14a2转录型可以加入预测因素列表，以指导CML的临床治疗决策。系统评价注册：[https://www.crd.york.ac.uk/PROSPERO/#myprospero]，标识符PROSPERO（CRD42021288440）。