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Risk Markers for Significant Bleeding and Thrombosis in Pediatric Acute Promyelocytic Leukemia; Report From the Children’s Oncology Group Study AAML0631

Rajpurkar, Madhvi, MD*; Alonzo, Todd A., PhD; Wang, Yi-Cheng, MS; Gerbing, Robert B., MA; Gamis, Alan S., MD, MPH§; Feusner, James H., MD; Gregory, John, MD; Kutny, Matthew A., MD#

Journal of Pediatric Hematology/Oncology: January 2019 - Volume 41 - Issue 1 - p 51–55
doi: 10.1097/MPH.0000000000001280
Original Articles

Acute promyelocytic leukemia (APL) is characterized by a heightened risk of coagulopathy with significant morbidity and mortality. Here we report our evaluation of presenting white blood cell (WBC) and the International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) scoring system as markers for early death and nonlethal coagulopathy in pediatric APL. We evaluated 79 pediatric patients treated on a Children’s Oncology Group phase III clinical trial. There were 4 early deaths and 13 nonlethal, clinically significant (grade III to IV) coagulopathy events during induction. Elevated presenting WBC was significantly associated with early death but not with both lethal and nonlethal coagulopathy events. An ISTH DIC score of ≥5 (the original ISTH criteria for overt DIC) was not associated with either early deaths or coagulopathy events. An ISTH DIC score threshold of 6, however, was significantly associated with early death (12% score ≥6 vs. 0% score <6) and with both lethal and nonlethal coagulopathy events (35% score ≥6 vs. 11% score <6). In pediatric APL patients, the presenting WBC is a marker for risk of early death. Although the ISTH score using a cutoff of ≥6 showed improved correlation with adverse coagulation events during induction, the sensitivity was only 70.6% (95% confidence interval, 44.0%-89.7%) and the specificity was 64.5% (95% confidence interval, 51.3%-76.3%). Thus, there is a strong need to identify other biomarkers that can predict APL-associated coagulopathy.

*Carman and Ann Adams Department of Pediatrics, Children’s Hospital of Michigan, Wayne State University, Detroit, MI

Keck School of Medicine, University of Southern California, Los Angeles

Children’s Oncology Group, Monrovia

Department of Hematology/Oncology, Children’s Hospital and Research Center Oakland, Oakland, CA

§Division of Hematology/Oncology, Children’s Mercy Hospital and Clinics, Kansas City, MO

Atlantic Health System, Goryeb Children’s Hospital, Morristown, NJ

#Department of Pediatrics Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL

Supported by NIH grants to the Children’s Oncology Group including U10-CA98543 (Chair’s Grant), U10-CA98413 (Statistics and Data Center Grant), U10CA180886 (NCTN Operations Center Grant), and U10CA180899 (NCTN Statistics and Data Center). Generous funding was also provided by The St Baldrick’s foundation to support the AAML0631 trial and by The Andrew McDonough B+ Foundation for statistical support.

The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

The authors declare no conflict of interest.

Reprints: Matthew A. Kutny, MD, 1600 7th Avenue S, 512 Lowder, Birmingham, AL 35216 (e-mail: mkutny@peds.uab.edu).

Received May 4, 2018

Accepted July 7, 2018

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.