Mantha Simon, Goldman Debra A, Devlin Sean M, Lee Ju-Whei, Zannino Diana, Collins Marnie, Douer Dan, Iland Harry J, Litzow Mark R, Stein Eytan M, Appelbaum Frederick R, Larson Richard A, Stone Richard, Powell Bayard L, Geyer Susan, Laumann Kristina, Rowe Jacob M, Erba Harry, Coutre Steven, Othus Megan, Park Jae H, Wiernik Peter H, Tallman Martin S
Department of Medicine, Hematology Service, and.
Department of Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
Blood. 2017 Mar 30;129(13):1763-1767. doi: 10.1182/blood-2016-10-747170. Epub 2017 Jan 12.
Acute promyelocytic leukemia (APL) is commonly complicated by a complex coagulopathy. Uncertainty remains as to which markers of bleeding risk are independent predictors. Drawing from 5 large clinical trials that included all- retinoic acid (ATRA) as part of induction, we assessed known determinants of bleeding at baseline and evaluated them as potential predictors of hemorrhagic death (HD) in the first 30 days of treatment. The studies included were ALLG APML3 (single arm of ATRA + idarubicin ± prednisone), ALLG APML4 (single arm of ATRA + idarubicin + arsenic trioxide + prednisone), CALGB C9710 (single arm of ATRA + cytarabine + daunorubicin), Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E2491 (intergroup I0129, consisting of daunorubicin + cytarabine vs ATRA), and SWOG S0521 (single-arm induction of ATRA + cytarabine + daunorubicin). A total of 1009 patients were included in the original trials, of which 995 had sufficient data to be included in our multivariate analysis. In this final cohort, there were 37 HD cases during the first 30 days following induction, for an estimated cumulative incidence of 3.7% (95% confidence interval [CI], 2.6% to 5.0%). Using multivariate Cox proportional hazards regression, the hazard ratio of HD in the first 30 days was 2.17 (95% CI, 0.84-5.62) for an ECOG performance status of 3-4 vs 0-2 and 5.20 (95% CI, 2.70-10.02) for a white blood cell count of ≥20 000/μL vs <20 000/μL. In this large cohort of APL patients, high white blood cell count emerged as an independent predictor of early HD.
急性早幼粒细胞白血病（APL）通常并发复杂的凝血病。关于哪些出血风险标志物是独立预测因素仍存在不确定性。我们从5项将全反式维甲酸（ATRA）作为诱导治疗一部分的大型临床试验中提取数据，评估了基线时已知的出血决定因素，并将其作为治疗前30天内出血性死亡（HD）的潜在预测因素进行评估。纳入的研究包括ALLG APML3（ATRA + 伊达比星 ± 泼尼松单臂试验）、ALLG APML4（ATRA + 伊达比星 + 三氧化二砷 + 泼尼松单臂试验）、CALGB C9710（ATRA + 阿糖胞苷 + 柔红霉素单臂试验）、东部肿瘤协作组 - 美国放射学会影像网络（ECOG - ACRIN）E2491（I0129组间试验，由柔红霉素 + 阿糖胞苷与ATRA对比）以及SWOG S0521（ATRA + 阿糖胞苷 + 柔红霉素单臂诱导试验）。原始试验共纳入1009例患者，其中995例有足够数据纳入我们的多变量分析。在这个最终队列中，诱导后前30天内有37例HD病例，估计累积发病率为3.7%（95%置信区间[CI]，2.6%至5.0%）。使用多变量Cox比例风险回归分析，ECOG体能状态为3 - 4级与0 - 2级相比，治疗前30天内HD的风险比为2.17（95%CI，0.84 - 5.62）；白细胞计数≥20 000/μL与<20 000/μL相比，HD的风险比为5.20（95%CI，2.70 - 10.02）。在这个大型APL患者队列中，高白细胞计数成为早期HD的独立预测因素。
