Incidence and Predictors of Respiratory Adverse Events during Induction Therapy in Children with Acute Myeloid Leukemia Open Access

Abstract

Background: Survival in childhood acute myeloid leukemia (AML) has plateaued at 60-70%, with induction death occurring in 4-11% of patients. While pulmonary complications are known to contribute to pediatric AML induction morbidity and mortality, our understanding of the incidence, categories, and risk factors for respiratory adverse events (AEs) is incomplete. Objectives: To estimate the incidence of respiratory AEs occurring during induction therapy for pediatric AML, categorize and grade these AEs, and identify risk factors for AE development. Methods: Using manual chart abstraction, we retrospectively followed a cohort of de novo pediatric AML patients (age ≤ 21) from initial presentation through day 42 of induction chemotherapy. Outcomes included any NCI CTCAE grade 2-5 respiratory AE or death from another cause. Demographic, disease, and treatment-related data were abstracted. Descriptive statistics, survival analysis, bivariate analysis, and multivariable analysis were performed (SAS v9.4, Cary, NC). Results: Among 113 eligible subjects, 53.1% (n = 60) experienced 74 grade 2-5 respiratory AEs. Mechanical ventilation was required in 23% of all respiratory AEs (n = 17). Peaks in incidence occurred between days 0-7 and days 14-21. Induction death occurred in 4.4% (n = 5). Fluid overload at any time (aOR 47.6 [95% CI: 5.7-395.1]) and older age at diagnosis (aOR 1.12 [95% CI: 1.01-1.24]) were estimated to be associated with AE occurrence. Positive fluid overload status (aHR 5.63 [95% CI: 3.42-9.29]), positive infection status (aHR 2.29 [95% CI: 1.30-4.02]), elevated initial WBC (aHR 1.003 [95% CI: 1.000-1.005]), and male gender (aHR 1.59 [95% CI: 1.05-2.38]) were estimated to be associated with increased hazard for AE development. Conclusion: We describe a higher incidence of respiratory AEs during childhood AML induction than previously described. Fluid overload at any time and older age at diagnosis are associated with AE development. Positive fluid overload status, positive infection status, elevated initial WBC, and male gender were associated with increased hazard for AE development. Interventions focused on fluid overload and infection prevention and management should be further addressed in this population to reduce early respiratory complications and prevent potential morbidity and mortality.

Table of Contents

Table of Contents

A.    INTRODUCTION.…………………………………………………………………..1

B.    BACKGROUND…………………………………………………………………….3

C.   METHODS…………………………………………………………………………10

D.   RESULTS…………………………………………………………………………..17

E.    DISCUSSION/CONCLUSIONS………………………………………………….23

F.    REFERENCES…………………………………………………………………….32

G.   TABLES/FIGURES………………………………………………………………..37

List of Tables and Figures

 

Table 1            NCI CTCAE category and grade for respiratory AEs…………………….38

Table 2            Bivariate analysis of respiratory AE vs no respiratory AE groups………40

Table 3            Bivariate analysis of early versus late respiratory AEs…………………..41

Table 4            Multivariable logistic regression analysis (respiratory AE vs no respiratory AE)……………………………………………………………………………..42

Table 5            Multivariable survival analysis with Cox PH model for recurrent events                               (respiratory AE vs no respiratory AE)………………………………………43

Figure 1           CONSORT diagram demonstrating subject eligibility……………………..37

Figure 2           Time-to-event distribution from initial presentation………………………..39

Figure 3           Survival analysis: time to fluid overload state……………………………...44

Figure 4           Total days in fluid overload state……………………………………………45

Figure 5           Infection subtypes…………………………………………………………….46

Figure 6           Survival analysis: time to infection state……………………………………47

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Oncology
Keyword	pediatric acute myeloid leukemia respiratory adverse events
Committee Chair / Thesis Advisor	Woods, William, Emory University
Committee Members	Klein, Mitchel, Emory University Collins, Jeffrey, Emory University

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