Predictors of Thrombohemorrhagic Early Death in Children and Adolescents with t(15;17)-Positive Acute Promyelocytic Leukemia Treated with ATRA and Chemotherapy

Clinical trials on childhood acute promyelocytic leukemia (APL) report early death (ED) rates of 3-8%, but predictors of thrombohemorrhagic (TH)-ED are not well understood. In a retrospective study, we aimed to determine the incidence and predictors of TH-ED in childhood APL. Data were analyzed from children and adolescents with t(15;17)-positive APL (n = 683) who started treatment with all-trans retinoic acid (ATRA) and chemotherapy in different international studies. Demographic data; initial white blood cell (WBC), peripheral blood (PB) blast, and platelet counts; hemoglobin value; coagulation parameters; morphologic variant (M3 or M3v); and induction details were analyzed. Early death was defined as death occurring within 30 days of presentation. The incidence of ED was 4.7% (32 of 683 patients). Predictors of TH-ED were identified by univariable and multivariable Cox proportional hazard regression analyses (n = 25). In univariable analysis, high WBC ($>$10 x 10(9)/L) (P $<$ 0.001) and high PB blast ($>$30 x 10(9)/L) (P $<$ 0.001), M3v (P $<$ 0.01), and black ethnicity (P $<$ 0.001) were independent predictors of TH-ED. In multivariable analysis, high WBC count (P $<$ 0.01) and obesity (i.e., body mass index $>$/=95th percentile for age) (P = 0.03) were predictors of TH-ED. Initial high WBC counts and obesity are likely predictors of TH-ED in childhood APL. The efficacy of novel drugs for APL-associated coagulopathy or of frontline arsenic trioxide and ATRA combination regimens in reducing ED rates in childhood APL remains to be established.

Annals of Hematology