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Author Notes:

Lane H Miller, MD MSc, Cancer and Blood Disorders Center, Children’s Minnesota, 2530 Chicago Avenue South, CSC175, Minneapolis, MN 55404, Phone: 404-556-6586, Fax: 612-813-6325.lane.miller@childrensmn.org.

Study concept: LM, FK, SC, WW, AM. Data collection: LM. Data analysis and creation of tables/figures: LM, KA, MK, SC, WW. Initial draft of manuscript: LM. Critical revision and approval of final version: all authors.

The authors acknowledge the support of the Emory University School of Medicine and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta. We would also like to recognize the 105 children with de novo acute myeloid leukemia who contributed invaluable information to this study and whose experiences have provided vital insights into the care for future children.

The authors declare no conflicts of interest.



  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Hematology
  • Pediatrics
  • adverse
  • AML
  • fluid
  • induction
  • infection
  • respiratory

Impact of fluid overload and infection on respiratory adverse event development during induction therapy for childhood acute myeloid leukemia


Journal Title:



Volume 66, Number 12


, Pages e27975-e27975

Type of Work:

Article | Post-print: After Peer Review


Background: Treatment-related morbidity and mortality occur frequently in childhood acute myeloid leukemia (AML) induction. Yet the contributions of respiratory adverse events (AEs) within this population are poorly understood. Furthermore, the roles of fluid overload (FO) and infection in AML pulmonary complications have been inadequately examined. Objectives: To describe the incidence, categories, and grades of respiratory AEs and to assess the associations of FO and infection on respiratory AE development in childhood AML induction. Methods: We retrospectively examined the induction courses of a cohort of de novo pediatric AML patients for any NCI CTCAE grade 2 to 5 respiratory AE, FO, and systemic/pulmonary infection occurrence. Demographic, disease, and treatment-related data were abstracted. Descriptive, univariate, survival, and multivariable analyses were conducted. Results: Among 105 eligible subjects from 2009 to 2016, 49.5% (n = 52) experienced 63 discrete respiratory AEs. FO occurred in 28.6% of subjects (n = 30), with half occurring within 24 hours of hospitalization. Positive FO status < 10 days (aHR 5.5, 95% CI 2.3-12.8), ≥ 10 days (aHR 13, 95% CI 4.1-41.8), and positive infection status ≥ 10 days into treatment (aHR 14.9, 5.4-41.6) were each independently associated with AE development. Conclusions: We describe a higher incidence of respiratory AEs during childhood AML induction than previously illustrated. FO occurs frequently and early in this course. Late infections and FO at any time frame were strongly associated with AE development. Interventions focused on the prevention and management of FO and infectious respiratory complications could be instrumental in reducing preventable treatment-related morbidity and mortality.

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