Determinants of fatal bleeding during induction therapy for acute promyelocytic leukemia in the ATRA era.

Publication Type:

Journal Article

Source:

Blood (2017)

Abstract:

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 five large clinical trials that included 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), 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% CI=2.6-5.0%). Using multivariate Cox proportional hazards regression, the hazard ratio (HR) of hemorrhagic death in the first 30 days was 2.17 (95% CI=0.84-5.62) for an ECOG performance status (PS) of 3-4 vs 0-2 and 5.20 (95% CI=2.70-10.02) for a white blood cell count of ≥20000/mcL vs <20000/mcL. In this large cohort of APL patients, high WBC emerged as an independent predictor of early hemorrhagic death.