Predictors of thrombohemorrhagic early death in children and adolescents with t(15;17)-positive acute promyelocytic leukemia treated with ATRA and chemotherapy

Oussama Abla, Raul C. Ribeiro, Anna Maria Testi, Pau Montesinos, Ursula Creutzig, Lillian Sung, Giancarlo Di Giuseppe, Derek Stephens, James H. Feusner, Bayard L. Powell, Henrik Hasle, Gertjan J.L. Kaspers, Luciano Dalla-Pozza, Alvaro Lassaletta, Martin S. Tallman, Franco Locatelli, Dirk Reinhardt, Francesco Lo-Coco, Johann Hitzler, Miguel A. Sanz

Research output: Contribution to journalArticlepeer-review

Abstract

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 × 109/L) (P < 0.001) and high PB blast (>30 × 109/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.

Original languageEnglish
Pages (from-to)1449-1456
Number of pages8
JournalAnnals of Hematology
Volume96
Issue number9
DOIs
Publication statusPublished - Sep 1 2017

Keywords

  • APL
  • Children
  • Early death
  • Predictors

ASJC Scopus subject areas

  • Hematology

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