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Outcome of Pediatric Acute Myeloid Leukemia Patients Receiving Intensive Care in the United States

Maude, Shannon L. MD, PhD1,2; Fitzgerald, Julie C. MD, PhD3,4; Fisher, Brian T. DO, MSCE2,4,5,6; Li, Yimei PhD1,4; Huang, Yuan-Shung MS6; Torp, Kari BA1; Seif, Alix E. MD, MPH1,2; Kavcic, Marko MD1; Walker, Dana M. MD, MSCE7; Leckerman, Kateri H. MS5; Kilbaugh, Todd J. MD2,3,4; Rheingold, Susan R. MD1,2; Sung, Lillian MD, PhD8; Zaoutis, Theoklis E. MD, MS2,4,5,6,9; Berg, Robert A. MD, FCCM2,3; Nadkarni, Vinay M. MD, MS, FCCM2,3; Thomas, Neal J. MD, MS, FCCM10; Aplenc, Richard MD, PhD1,2,4,6,9

Pediatric Critical Care Medicine: February 2014 - Volume 15 - Issue 2 - p 112–120
doi: 10.1097/PCC.0000000000000042
Feature Articles

Objective: Children with acute myeloid leukemia are at risk for sepsis and organ failure. Outcomes associated with intensive care support have not been studied in a large pediatric acute myeloid leukemia population. Our objective was to determine hospital mortality of pediatric acute myeloid leukemia patients requiring intensive care.

Design: Retrospective cohort study of children hospitalized between 1999 and 2010. Use of intensive care was defined by utilization of specific procedures and resources. The primary endpoint was hospital mortality.

Setting: Forty-three children’s hospitals contributing data to the Pediatric Health Information System database.

Patients: Patients who are newly diagnosed with acute myeloid leukemia and who are 28 days through 18 years old (n = 1,673) hospitalized any time from initial diagnosis through 9 months following diagnosis or until stem cell transplant. A reference cohort of all nononcology pediatric admissions using the same intensive care resources in the same time period (n = 242,192 admissions) was also studied.

Interventions: None.

Measurements and Main Results: One-third of pediatric patients with acute myeloid leukemia (553 of 1,673) required intensive care during a hospitalization within 9 months of diagnosis. Among intensive care admissions, mortality was higher in the acute myeloid leukemia cohort compared with the nononcology cohort (18.6% vs 6.5%; odds ratio, 3.23; 95% CI, 2.64–3.94). However, when sepsis was present, mortality was not significantly different between cohorts (21.9% vs 19.5%; odds ratio, 1.17; 95% CI, 0.89–1.53). Mortality was consistently higher for each type of organ failure in the acute myeloid leukemia cohort versus the nononcology cohort; however, mortality did not exceed 40% unless there were four or more organ failures in the admission. Mortality for admissions requiring intensive care decreased over time for both cohorts (23.7% in 1999–2003 vs 16.4% in 2004–2010 in the acute myeloid leukemia cohort, p = 0.0367; and 7.5% in 1999–2003 vs 6.5% in 2004–2010 in the nononcology cohort, p < 0.0001).

Conclusions: Pediatric patients with acute myeloid leukemia frequently required intensive care resources, with mortality rates substantially lower than previously reported. Mortality also decreased over the time studied. Pediatric acute myeloid leukemia patients with sepsis who required intensive care had a mortality comparable to children without oncologic diagnoses; however, overall mortality and mortality for each category of organ failure studied was higher for the acute myeloid leukemia cohort compared with the nononcology cohort.

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1Division of Oncology, The Children’s Hospital of Philadelphia, Philadelphia, PA.

2Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

3Department of Anesthesia and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA.

4Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

5Division of Infectious Diseases, The Children’s Hospital of Philadelphia, Philadelphia, PA.

6Center for Pediatric Clinical Effectiveness, The Children’s Hospital of Philadelphia, Philadelphia, PA.

7Bristol-Myers Squibb, Hopewell, NJ.

8Division of Haematology/Oncology and Program in Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada.

9Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

10Division of Pediatric Critical Care Medicine, Department of Pediatrics and Public Health Sciences, Penn State Hershey Milton S. Hershey Medical Center, Hershey, PA.

Drs. Maude and Fitzgerald contributed equally as first authors.

This work was performed at The Children’s Hospital of Philadelphia.

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Dr. Maude is supported by the Abramson Cancer Center’s Paul Calabresi Career Development Award K12 CA076931 from the National Institutes of Health and the When Everyone Survives Foundation. Dr. Fisher is currently receiving a grant from Pfizer. Dr. Seif received an Alex’s Lemonade Stand/Center for Childhood Cancer Research Seed Grant for this study. She is currently receiving grants from the Canuso Foundation, the American Society of Blood & Marrow Transplantation, and the American Cancer Society. Dr. Kavcic receives research funding from the Slovenian Ministry of Education, Science, Culture and Sport (grant J3-4220). Dr. Zaoutis is a consultant for Merck, Pfizer, Astellas, Hemocue, and Cubist and is currently receiving a grant from Merck. Dr. Nadkarni is currently receiving grant support from Laerdal. Dr. Thomas is on the Scientific Advisory Board for Discovery Laboratories. Dr. Aplenc received grant R01 CA165277 from National Institutes of Health for this study.

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©2014The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies