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

Abstract

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.

Fluid overload is associated with increased 90-day mortality in AML patients undergoing induction chemotherapy

“…In (12)(13)(14). As mentioned above, the FO definition in this study (solely based on weight gain) and its screening timepoint (limited to day 7 of induction chemotherapy) as well as the assumption that AML patients suffer from weight loss during the screening episode (due to active cancer disease, chemotherapy-induced nausea and vomiting, etc.)…”

“…Traditionally, AML patients receive crystalloid fluids to prevent TLS. However, Miller et al have illustrated that a significant proportion of pediatric patients received hyperhydration although they were not at high risk for developing TLS ( 13 ). It is important to note that conservative fluid balance strategies have been successfully applied in critically ill patients, including sepsis patients, stem cell transplant recipients, and trauma patients.…”

“…In this single-center study, we retrospectively included all patients aged ≥18 with AML (excluding acute promyelocytic leukemia) who underwent intensive induction chemotherapy between 2014 and 2019. There is no standard definition for FO in hematological patients (12)(13)(14). Since AML patients suffer from body weight loss especially during initial diagnosis leading to possible underestimation FO incidence, we chose a comparably low cutoff at 5%.…”

“…Miller et al focused on pediatric AML patients; FO occurred in 30 (28.6%) of 105 pediatric AML patients during induction chemotherapy. FO was more likely in patients aged ≥ 10 years and also in patients with infection, hyperleukocytosis, and low hemoglobin levels at diagnosis ( 13 ). Potentially modifiable risk factors such as the volume of crystalloid fluids applied during induction were not analyzed.…”