PMID- 28597167 OWN - NLM STAT- MEDLINE DCOM- 20170817 LR - 20220318 IS - 1432-0584 (Electronic) IS - 0939-5555 (Linking) VI - 96 IP - 9 DP - 2017 Sep TI - Predictors of thrombohemorrhagic early death in children and adolescents with t(15;17)-positive acute promyelocytic leukemia treated with ATRA and chemotherapy. PG - 1449-1456 LID - 10.1007/s00277-017-3042-6 [doi] AB - 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. FAU - Abla, Oussama AU - Abla O AUID- ORCID: 0000-0001-7446-6274 AD - Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada. oussama.abla@sickkids.ca. FAU - Ribeiro, Raul C AU - Ribeiro RC AD - Division of Leukemia/Lymphoma, Department of Oncology, St. Jude Children's Research Hospital, Memphis, USA. FAU - Testi, Anna Maria AU - Testi AM AD - Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy. FAU - Montesinos, Pau AU - Montesinos P AD - Department of Hematology, Hospital Universitari i Politecnic La Fe, Valencia, and Centro de Investigacion Biomedica en Red de Cancer, Instituto Carlos III, Madrid, Spain. FAU - Creutzig, Ursula AU - Creutzig U AD - Department of Paediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany. FAU - Sung, Lillian AU - Sung L AD - Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada. FAU - Di Giuseppe, Giancarlo AU - Di Giuseppe G AD - Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada. FAU - Stephens, Derek AU - Stephens D AD - Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada. FAU - Feusner, James H AU - Feusner JH AD - Division of Hematology/Oncology, Children's Hospital and Research Center Oakland, Oakland, USA. FAU - Powell, Bayard L AU - Powell BL AD - Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, USA. FAU - Hasle, Henrik AU - Hasle H AD - Department of Paediatrics, Aarhus University Hospital, Aarhus, Denmark. FAU - Kaspers, Gertjan J L AU - Kaspers GJL AD - Department of Pediatric Oncology/Hematology, University Medical Center, Amsterdam, Netherlands. FAU - Dalla-Pozza, Luciano AU - Dalla-Pozza L AD - Department of Oncology, The Children's Hospital at Westmead, Westmead, Australia. FAU - Lassaletta, Alvaro AU - Lassaletta A AD - Pediatric Hematology-Oncology Department, Instituto Carlos III, Madrid, Spain. FAU - Tallman, Martin S AU - Tallman MS AD - Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, USA. FAU - Locatelli, Franco AU - Locatelli F AD - Department of Pediatric Hematology-Oncology, IRCCS Ospedale Bambino Gesu, Rome, Italy. AD - University of Pavia, Pavia, Italy. FAU - Reinhardt, Dirk AU - Reinhardt D AD - Department of Haematology-Oncology, University of Essen, Duisburg, Germany. FAU - Lo-Coco, Francesco AU - Lo-Coco F AD - Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy. FAU - Hitzler, Johann AU - Hitzler J AD - Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada. FAU - Sanz, Miguel A AU - Sanz MA AD - Department of Hematology, Hospital Universitari i Politecnic La Fe, Department of Medicine, University of Valencia, Valencia, Spain. AD - Centro de Investigacion Biomedica en Red de Cancer, Instituto Carlos III, Madrid, Spain. LA - eng PT - Clinical Trial PT - Journal Article PT - Multicenter Study DEP - 20170608 PL - Germany TA - Ann Hematol JT - Annals of hematology JID - 9107334 RN - 5688UTC01R (Tretinoin) SB - IM MH - Adolescent MH - Adult MH - Child MH - Child, Preschool MH - Chromosomes, Human, Pair 15/*genetics MH - Chromosomes, Human, Pair 17/*genetics MH - *Disseminated Intravascular Coagulation/blood/chemically induced/genetics/mortality MH - Female MH - Humans MH - Infant MH - Infant, Newborn MH - Leukemia, Promyelocytic, Acute/blood/drug therapy/genetics/mortality MH - Leukocyte Count MH - Male MH - Obesity/blood/drug therapy/genetics/mortality MH - Risk Factors MH - *Translocation, Genetic MH - *Tretinoin/administration & dosage/adverse effects OTO - NOTNLM OT - APL OT - Children OT - Early death OT - Predictors EDAT- 2017/06/10 06:00 MHDA- 2017/08/18 06:00 CRDT- 2017/06/10 06:00 PHST- 2017/01/27 00:00 [received] PHST- 2017/05/30 00:00 [accepted] PHST- 2017/06/10 06:00 [pubmed] PHST- 2017/08/18 06:00 [medline] PHST- 2017/06/10 06:00 [entrez] AID - 10.1007/s00277-017-3042-6 [pii] AID - 10.1007/s00277-017-3042-6 [doi] PST - ppublish SO - Ann Hematol. 2017 Sep;96(9):1449-1456. doi: 10.1007/s00277-017-3042-6. Epub 2017 Jun 8.