Prevalence and Trajectory of Symptoms in Pediatric Leukemia and Lymphoma Patients
Authors: Dobrozsi Sarah K. , Zhang Liyun , Hoffmann Raymond G , Panepinto Julie A. 
Published: October 2019

Abstract
Introduction: Children treated for leukemia and lymphoma receive multi-agent chemotherapy and experience toxicities related to their disease and treatment. Commonly described symptoms in cross-sectional studies of symptom prevalence during treatment are nutrition concerns, nausea/vomiting (n/v), pain, fatigue, and emotional distress. The evolution of these symptoms over the course of treatment and the relationship between symptoms and intensity of therapy remain unknown. We hypothesize that symptom prevalence will change over time (nutrition concerns will decrease, n/v will decrease, pain will increase, fatigue will increase, and emotional distress will increase) and patients who receive more intense treatments will experience more symptoms.
Methods: As part of a prospective study investigating the burden of cancer treatment, a retrospective chart review of 44 children treated for leukemia or lymphoma at a single institution was performed. Clinician documentation of nutrition concerns, n/v, pain, fatigue and emotional distress was abstracted from all outpatient clinic visits over the first six months of cancer treatment. Each symptom was recorded as present or absent in the documentation at each clinic visit. The Intensity of Treatment Rating Scale was used to determine intensity of treatment. Data were analyzed using a logistic generalized linear mixed model to model the trajectory of each symptom over time, and consider the covariates of diagnosis and intensity of treatment.
Results: The median age of the sample population is 9.2 years, 59% are male. Fifty percent of patients were treated for ALL, 14% for AML, and the remainder for lymphoma. Treatment regimens were classified as moderately intensive (43.2%), very intensive (38.6%), and most intensive (18.2%). Eighty percent of patients reported concerns regarding nutrition at some point during the first six months of therapy, 86% reported n/v, 86% reported pain, 71% reported fatigue, and 30% reported emotional distress. Nutrition concerns were reported at 23% of all clinic visits, n/v at 14%, pain at 20%, fatigue at 3.9%, and emotional distress at 1.3%.
Univariate analyses reveals that children with leukemia have a higher prevalence of nutrition concerns than children with lymphoma (p=0.0229). When adjusted for time from diagnosis, the prevalence of nutrition concerns decreases with time in lymphoma patients (p=0.0334) where they remain constant in leukemia patients (p=0.0449). When adjusted for intensity of treatment, the prevalence of nutrition concerns decreases over time, with the low intensity therapy group decreasing to zero (p=0.0004). Leukemia patients have a lower prevalence of n/v than lymphoma patients (p=0.0366). Neither time nor intensity of treatment has an effect on prevalence. Prevalence of pain decreases slightly over time but does not reach statistical significance for leukemia or lymphoma patients (p=0.0554). Pain decreases over time for patients who receive less intensive therapy compared to patients who receive high intensity therapy over time (p=0.0375). Fatigue and emotional distress were not modeled due to low prevalence.
Conclusion: Children with newly diagnosed leukemia/lymphoma experience symptoms over the first six months of therapy that change over time. Nutrition concerns are more prevalent in children with leukemia and remain constant throughout the first six months of treatment. Patients with either leukemia or lymphoma who receive low intensity therapy have the least difficulty with nutrition. Pain also improves over time for patients who receive less intensive therapy, but remains constant for those with more intense therapy. The low to zero prevalence of fatigue and emotional distress symptoms likely reflect unrecognized symptoms by the clinician.
Improved detection and understanding of symptom trajectory during active treatment can both guide appropriate use of supportive care resources and allow for improved anticipatory guidance for families. As part of an ongoing prospective trial, we plan to correlate the findings described here with data on patient function using patient-reported outcome measures, to improve understanding of the burden of cancer therapy and direct supportive care to minimize symptoms during treatment.

Disclosures
No relevant conflicts of interest to declare.