A retrospective study showed a high incidence of respiratory adverse events in pediatric patients with acute myeloid leukemia (AML) receiving induction chemotherapy. The findings from this study were published in Pediatric Blood & Cancer.

Although supportive care measures such as hospitalization during periods of neutropenia, the use of broad spectrum antibiotics and antifungals in select patients with fever, and limitations on corticosteroid use have improved outcomes for children and adolescents with AML, estimated mortality rates in this population of patients who are treated with induction chemotherapy range from 4% to 11%. Nevertheless, the contribution of respiratory adverse events to the morbidity and mortality of these patients has not been well characterized.

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The aim of this study was 2-fold: to characterize respiratory adverse events, specifically grade 2 to grade 5 hypoxia, pulmonary edema, pleural effusion, dyspnea, apnea, acute respiratory distress syndrome (ARDS), pulmonary hemorrhage, and bronchospasm/laryngospasm, occurring in children and adolescents with AML during induction therapy and to evaluate whether associations exist between fluid overload, as well as systemic and pulmonary infections, and the development of respiratory adverse events in this population of patients. 

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This study included 105 children and adolescents with newly diagnosed de novo AML treated with conventional induction chemotherapy at Children’s Healthcare of Atlanta between March 2009 and December 2016. In this patient cohort, the median age at diagnosis was 7 years, and race/ethnicity was classified as white/non-Hispanic and black/non-Hispanic in approximately 52% and 35% of patients, respectively.

A key finding from this study was the occurrence of 63 respiratory adverse events in 49.5% (n=52) of patients, with more than 90% of these events classified as severe; these included grade 3 to 5 hypoxia in 24.8% of patients.

In contrast, the rate of grade 3/5 hypoxia reported in an analysis of results of 2 clinical trials involving a similar patient population was 6%. “A discordance likely related to under recognition of respiratory adverse events in prior multi-institutional cohort analyses,” the researchers commented.

Notably, although fluid overload was found to occur in 28.6% (n=30) of patients, half of these events occurred within 24 hours of hospitalization, often prior to initiation of chemotherapy; whereas the other half occurred 10 or more days after treatment initiation. On multivariate analysis adjusted for age, race/ethnicity, platelet count, and infection, fluid overload was associated with increased risk of a respiratory adverse event both before day 10 (hazard ratio [HR], 5.5; 95% CI, 2.3-12.8) and from day 10 and beyond (HR, 13.0; 95% CI, 4.1-41.8).

“Fluid overload is an iatrogenic and modifiable risk factor, yet the construct of fluid overload is not included in the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) versions 4.0 and 5.0” the researchers pointed out.

In addition, respiratory infections occurred in 39% (n=41) of patients; a positive infection status at 10 or more days following treatment initiation was also independently associated with the development of respiratory adverse events (HR, 14.9; 95% CI, 5.4-41.6).

Five patients (4.8%) died during induction chemotherapy. The deaths were attributed to ARDS in 2 patients and hypoxia not otherwise specified in 1 patient (with each of those 3 patients experiencing invasive fungal infection), as well as apnea secondary to left frontal intraparenchymal hemorrhage in 1 patient, and uncal herniation in a patient with coagulopathy.

Limitations of this study included challenges associated with retrospective assessment of fluid overload and the omission of incidences of fever of unknown origin as well as nonpulmonary infections.

Nevertheless, the study authors concluded that these “data support a need for the prospective management of fluid overload and systemic or pulmonary infection as risk factors for respiratory adverse event development during the initial pediatric AML course. Cooperative and institutional protocols should consider providing explicit fluid management guidelines directed to recognition of fluid overload, maintenance of net-neutral fluid balance, and standardization of grading and reporting of fluid overload status.”

The study authors suggest scheduled incentive spirometry, positive expiratory pressure, and early frequent ambulation for all children and adolescents with AML.


Miller LH, Keller F, Mertens A, et al. Impact of fluid overload and infection on respiratory adverse event development during induction therapy for childhood acute myeloid leukemia [published online September 10, 2019]. Pediatr Blood Cancer. doi: 10.1002/pbc.27975

This article originally appeared on Oncology Nurse Advisor