Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY.
Department of Internal Medicine, Section of Hematology, Yale School of Medicine, New Haven, CT.
Haematologica. 2020 Jan;105(1):102-111. doi: 10.3324/haematol.2019.219345. Epub 2019 Apr 19.
Immunosuppressive therapy (IST) is one therapy option for treatment of patients with lower-risk myelodysplastic syndromes (MDS). However, the use of several different immunosuppressive regimens, the lack of high-quality studies, and the absence of validated predictive biomarkers pose important challenges. We conducted a systematic review and meta-analysis according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and searched MEDLINE PubMed, Ovid EMBASE, COCHRANE registry of clinical trials (CENTRAL), and the Web of Science without language restriction from inception through September 2018, as well as relevant conference proceedings and abstracts, for prospective cohort studies or clinical trials investigating IST in MDS. Fixed and Random-effects models were used to pool response rates. We identified nine prospective cohort studies and 13 clinical trials with a total of 570 patients. Overall response rate was 42.5% [95% confidence interval (CI): 36.1-49.2%] including a complete remission rate of 12.5% (95%CI: 9.3-16.6%) and red blood cell transfusion independence rate of 33.4% (95% CI: 25.1-42.9%). The most commonly used forms of IST were anti-thymocyte globulin alone or in combination with cyclosporin A with a trend towards higher response rates with combination therapy. Progression rate to acute myeloid leukemia was 8.6% per patient year (95%CI: 3.3-13.9%). Overall survival and adverse events were only inconsistently reported. We were unable to validate any biomarkers predictive of a therapeutic response to IST. IST for treatment of lower-risk MDS patients can be successful to alleviate transfusion burden and associated sequelae.
免疫抑制治疗(IST)是治疗低危骨髓增生异常综合征(MDS)患者的一种治疗选择。然而,由于使用了几种不同的免疫抑制方案、缺乏高质量的研究以及缺乏经过验证的预测生物标志物,这带来了重要的挑战。我们根据观察性研究的荟萃分析(MOOSE)指南进行了系统评价和荟萃分析,并在无语言限制的情况下从成立到 2018 年 9 月在 MEDLINE PubMed、Ovid EMBASE、COCHRANE 临床试验注册中心(CENTRAL)和 Web of Science 进行了检索,还检索了相关的会议记录和摘要,以寻找前瞻性队列研究或临床试验,调查 MDS 中的 IST。我们使用固定效应模型和随机效应模型来汇总反应率。我们确定了 9 项前瞻性队列研究和 13 项临床试验,共 570 名患者。总反应率为 42.5%[95%置信区间(CI):36.1-49.2%],包括完全缓解率 12.5%(95%CI:9.3-16.6%)和红细胞输血独立性率 33.4%(95%CI:25.1-42.9%)。最常用的 IST 形式是单独使用抗胸腺细胞球蛋白或与环孢素 A 联合使用,联合治疗的反应率呈上升趋势。向急性髓细胞白血病进展的患者年发生率为 8.6%(95%CI:3.3-13.9%)。总体生存和不良事件仅报告不一致。我们无法验证任何预测 IST 治疗反应的生物标志物。IST 治疗低危 MDS 患者可以成功缓解输血负担和相关并发症。