Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
PLoS One. 2021 Mar 30;16(3):e0249087. doi: 10.1371/journal.pone.0249087. eCollection 2021.
To compare the effectiveness and safety of intensive antileukemic therapy to less-intensive therapy in older adults with acute myeloid leukemia (AML) and intermediate or adverse cytogenetics, we searched the literature in Medline, Embase, and CENTRAL to identify relevant studies through July 2020. We reported the pooled hazard ratios (HRs), risk ratios (RRs), mean difference (MD) and their 95% confidence intervals (CIs) using random-effects meta-analyses and the certainty of evidence using the GRADE approach. Two randomized trials enrolling 529 patients and 23 observational studies enrolling 7296 patients proved eligible. The most common intensive interventions included cytarabine-based intensive chemotherapy, combination of cytarabine and anthracycline, or daunorubicin/idarubicin, and cytarabine plus idarubicin. The most common less-intensive therapies included low-dose cytarabine alone, or combined with clofarabine, azacitidine, and hypomethylating agent-based chemotherapy. Low certainty evidence suggests that patients who receive intensive versus less-intensive therapy may experience longer survival (HR 0.87; 95% CI, 0.76-0.99), a higher probability of receiving allogeneic hematopoietic stem cell transplantation (RR 6.14; 95% CI, 4.03-9.35), fewer episodes of pneumonia (RR, 0.25; 95% CI, 0.06-0.98), but a greater number of severe, treatment-emergent adverse events (RR, 1.34; 95% CI, 1.03-1.75), and a longer duration of intensive care unit hospitalization (MD, 6.84 days longer; 95% CI, 3.44 days longer to 10.24 days longer, very low certainty evidence). Low certainty evidence due to confounding in observational studies suggest superior overall survival without substantial treatment-emergent adverse effect of intensive antileukemic therapy over less-intensive therapy in older adults with AML who are candidates for intensive antileukemic therapy.
为了比较强化抗白血病治疗与非强化治疗在伴有中间或不良细胞遗传学特征的老年急性髓系白血病（AML）患者中的疗效和安全性，我们在 Medline、Embase 和 CENTRAL 中检索文献，以确定截至 2020 年 7 月的相关研究。我们使用随机效应荟萃分析报告了合并的风险比（HR）、风险比（RR）、均数差（MD）及其 95%置信区间（CI），并使用 GRADE 方法评估证据质量。两项纳入 529 例患者的随机试验和 23 项纳入 7296 例患者的观察性研究符合纳入标准。最常见的强化干预措施包括基于阿糖胞苷的强化化疗、阿糖胞苷与蒽环类药物的联合治疗或柔红霉素/伊达比星，以及阿糖胞苷联合伊达比星。最常见的非强化治疗包括单独使用低剂量阿糖胞苷或联合克拉屈滨、阿扎胞苷和低甲基化药物化疗。低质量证据表明，与非强化治疗相比，接受强化治疗的患者可能具有更长的生存时间（HR 0.87；95%CI，0.76-0.99）、更高的接受异基因造血干细胞移植的可能性（RR 6.14；95%CI，4.03-9.35）、更少的肺炎发作（RR，0.25；95%CI，0.06-0.98），但更严重、治疗引起的不良事件的数量更多（RR，1.34；95%CI，1.03-1.75），且重症监护病房住院时间更长（MD，6.84 天；95%CI，3.44 天至 10.24 天，极低质量证据）。由于观察性研究中的混杂因素，低质量证据表明，在适合强化抗白血病治疗的 AML 老年患者中，强化抗白血病治疗的总生存优于非强化治疗，且没有明显的治疗引起的不良作用。
