Hematology Service, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
Centre Léon Bérard, Université Claude Bernard Lyon 1, Lyon, France.
PLoS One. 2022 Jun 9;17(6):e0257673. doi: 10.1371/journal.pone.0257673. eCollection 2022.
Currently, there are no approved options to prevent or treat chemotherapy-induced thrombocytopenia (CIT). We performed a systematic literature review and meta-analysis on use of thrombopoietic agents for CIT.
We searched Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PubMed, EMBASE, ClinicalTrials.gov, and health technology assessments from January 1995 to March 2021 for studies evaluating thrombopoietic agents for CIT, including recombinant human thrombopoietin (rhTPO), megakaryocyte growth and development factor (MGDF), romiplostim, and eltrombopag. Random effects meta-analyses were conducted for efficacy and safety endpoints.
We screened 1503 titles/abstracts, assessed 138 articles, and abstracted data from 39 publications (14 recombinant human thrombopoietin, 7 megakaryocyte growth and development factor, 9 romiplostim, 8 eltrombopag, and 1 romiplostim/eltrombopag). Random effects meta-analyses of data from multiple studies comparing thrombopoietic agents versus control (comparator, placebo, or no treatment) showed that thrombopoietic agents did not significantly improve chemotherapy dose delays and/or reductions (21.1% vs 40.4%, P = 0.364), grade 3/4 thrombocytopenia (39.3% vs 34.8%; P = 0.789), platelet transfusions (16.7% vs 31.7%, P = 0.111), grade ≥ 2 bleeding (6.7% vs 16.5%; P = 0.250), or thrombosis (7.6% vs 12.5%; P = 0.131). However, among individual studies comparing thrombopoietic agents with placebo or no treatment, thrombopoietic agents positively improved outcomes in some studies, including significantly increasing mean peak platelet counts (186 x 109/L with rhTPO vs 122 x 109/L with no treatment; P < 0.05) in one study and significantly increasing platelet count at nadir (56 x 109/L with rhTPO vs 28 x 109/L with not treatment; P < 0.05) in another study. Safety findings included thrombosis (n = 23 studies) and bleeding (n = 11), with no evidence of increased thrombosis risk with thrombopoietic agents.
Our analyses generate the hypothesis that thrombopoietic agents may benefit patients with CIT. Further studies with well-characterized bleeding and platelet thresholds are warranted to explore the possible benefits of thrombopoietic agents for CIT.
目前，尚无预防或治疗化疗引起的血小板减少症（CIT）的获批方案。我们对用于 CIT 的促血小板生成药物进行了系统的文献回顾和荟萃分析。
我们检索了 Cochrane 对照试验中心注册库、Cochrane 系统评价数据库、PubMed、EMBASE、ClinicalTrials.gov 和健康技术评估数据库，检索时间为 1995 年 1 月至 2021 年 3 月，评估了用于 CIT 的促血小板生成药物的研究，包括重组人血小板生成素（rhTPO）、巨核细胞生长和发育因子（MGDF）、罗米司亭、艾曲波帕。对疗效和安全性终点进行了随机效应荟萃分析。
我们筛选了 1503 篇标题/摘要，评估了 138 篇文章，并从 39 篇出版物中提取数据（14 篇 rhTPO、7 篇 MGDF、9 篇罗米司亭、8 篇艾曲波帕和 1 篇罗米司亭/艾曲波帕）。与对照组（安慰剂或无治疗）相比，比较促血小板生成药物的多项研究的随机效应荟萃分析显示，促血小板生成药物并未显著改善化疗剂量延迟和/或减少（21.1% vs 40.4%，P = 0.364）、3/4 级血小板减少症（39.3% vs 34.8%；P = 0.789）、血小板输注（16.7% vs 31.7%，P = 0.111）、≥2 级出血（6.7% vs 16.5%；P = 0.250）或血栓形成（7.6% vs 12.5%；P = 0.131）。然而，在比较促血小板生成药物与安慰剂或无治疗的个别研究中，促血小板生成药物在一些研究中改善了结局，包括一项研究中显著增加了平均血小板峰值计数（rhTPO 组为 186×10^9/L，无治疗组为 122×10^9/L；P < 0.05），另一项研究中显著增加了血小板计数最低点（rhTPO 组为 56×10^9/L，无治疗组为 28×10^9/L；P < 0.05）。安全性发现包括血栓形成（n = 23 项研究）和出血（n = 11 项研究），未发现促血小板生成药物增加血栓形成风险的证据。
我们的分析提出了这样一种假设，即促血小板生成药物可能对 CIT 患者有益。需要进一步的研究，对出血和血小板阈值进行良好的特征描述，以探索促血小板生成药物对 CIT 的可能益处。
