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骨髓纤维化中的干扰素治疗:系统评价和荟萃分析。

Interferon Therapy in Myelofibrosis: Systematic Review and Meta-analysis.

机构信息

Department of Internal Medicine, Section of Hematology, Yale School of Medicine, New Haven, CT.

Division of Hematology and Oncology, University of Alabama School of Medicine, Birmingham, AL.

出版信息

Clin Lymphoma Myeloma Leuk. 2020 Oct;20(10):e712-e723. doi: 10.1016/j.clml.2020.05.018. Epub 2020 May 28.

Abstract

BACKGROUND

Myelofibrosis (MF) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by progressive bone marrow failure, increased risk of progression to acute myeloid leukemia, and constitutional symptoms. For over 3 decades, various formulations of interferon (IFN) have been used for the treatment of MF, with variable results, and the role of IFN in the treatment of MF is evolving.

PATIENTS AND METHODS

For this systematic review and meta-analysis, Medline and Embase via Ovid, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science were searched from inception through March 2019 for studies of pegylated IFN (peg-IFN) and non-peg-IFN in MF patients. The primary outcome of overall response rate was defined as a composite of complete response, partial response, complete hematologic response, and partial hematologic response. Random-effects models were used to pool overall response rate, and metaregression analyses were performed to compare peg-IFN and non--peg-IFN formulations.

RESULTS

Among the 10 studies with 141 MF patients included, the overall response rate was 49.9% (95% confidence interval [CI], 30.4-69.3), and there was no statistically significant difference (P = .99) between peg-IFN (50.0%; 95% CI, 26.2-73.9; I = 76.9%) and non-peg-IFN (49.6%; 95% CI, 20.5-79.0; I = 56.7%). Treatment discontinuation resulting from adverse events was common with non-peg-IFN at 35.8% (95% CI, 3.5-68.1) per year, and less in the one study on peg-IFN (0.5% per year).

CONCLUSION

IFN can lead to hematologic improvements in a subset of MF patients, but study quality is limited and heterogenous. Biomarkers predicting response to IFN and formulations with improved tolerability are needed.

摘要

背景

骨髓纤维化(MF)是一种费城染色体阴性骨髓增殖性肿瘤,其特征为进行性骨髓衰竭、向急性髓系白血病进展的风险增加以及全身症状。30 多年来,各种干扰素(IFN)制剂已被用于 MF 的治疗,但疗效各异,IFN 在 MF 治疗中的作用也在不断发展。

患者和方法

本系统评价和荟萃分析检索了 Medline 和 Embase 通过 Ovid、Scopus、Cochrane 中央对照试验注册中心(CENTRAL)和 Web of Science,从开始至 2019 年 3 月,检索关于聚乙二醇干扰素(peg-IFN)和非 peg-IFN 在 MF 患者中的研究。总体反应率的主要结局定义为完全缓解、部分缓解、完全血液学缓解和部分血液学缓解的综合。采用随机效应模型汇总总体反应率,并进行荟萃回归分析比较 peg-IFN 和非 peg-IFN 制剂。

结果

纳入的 10 项研究共 141 例 MF 患者,总体反应率为 49.9%(95%置信区间[CI],30.4-69.3),peg-IFN(50.0%;95%CI,26.2-73.9;I²=76.9%)和非 peg-IFN(49.6%;95%CI,20.5-79.0;I²=56.7%)之间无统计学差异(P=0.99)。非 peg-IFN 治疗相关不良事件导致停药的发生率较高,每年为 35.8%(95%CI,3.5-68.1),而 peg-IFN 治疗相关不良事件导致停药的发生率每年为 0.5%。

结论

IFN 可使一部分 MF 患者的血液学得到改善,但研究质量有限且存在异质性。需要预测 IFN 反应的生物标志物和具有更好耐受性的制剂。

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