Abstract
As survival of acute lymphoblastic leukemia (ALL) exceeds 90%, limiting therapy-related toxicity has become a key challenge. Cardio-metabolic dysfunction is a challenge during and after childhood ALL therapy. In a single center study, we measured triglycerides (TG), total cholesterol (TC), high (HDL) and low density lipoproteins (LDL) levels at diagnosis and assessed the association with BMI, early therapy response, on-therapy hyperlipidemia and the toxicities; thromboembolism, osteonecrosis and pancreatitis. We included 127 children (1.0–17.9 years) all treated according to the NOPHO ALL2008 protocol. Dyslipidemia was identified at ALL-diagnosis in 99% of the patients, dominated by reduced HDL levels (98%) and mild hypertriglyceridemia (61%). Hypertriglyceridemia was not associated with body mass index (P = 0.71). Five percent of patients had mild hypercholesterolemia, 14% had mild hypocholesterolemia, 13% had decreased and 1% elevated LDL-levels. Increased TG and TC levels at ALL-diagnosis were not associated with any on-therapy lipid levels. Lipid levels and BMI were not associated to MRD after induction therapy; However, BMI and hypercholesterolemia were associated with worse risk group stratification (P<0.045 for all). The cumulative incidence of thromboembolism was increased both for patients with hypo- (20.0%) and hypercholesterolemia (16.7%) compared to patients with normal TC levels (2.2%) at diagnosis (P = 0.0074). In conclusion, dyslipidemic changes were present prior to ALL-therapy in children with ALL but did not seem to affect dysmetabolic traits during therapy and were not predictive of on-therapy toxicities apart from an association between dyscholesterolemia at time of ALL-diagnosis and risk of thromboembolism. However, the latter should be interpreted with caution due to low number in the groups.
Highlights
Intensification of therapy has yielded survival rates above 90 percent in children with acute lymphoblastic leukemia (ALL)[1]
Patients were stratified into high risk (HR) or non-HR treatment groups at time of diagnosis based on white blood cell count (WBC) and immunophenotype
Following induction and consolidation patients were subsequently stratified into three risk groups; standard risk (SR), intermediate risk (IR), and HR based on cytogenetics as well as treatment response measured through levels of minimal residual disease (MRD)
Summary
Intensification of therapy has yielded survival rates above 90 percent in children with acute lymphoblastic leukemia (ALL)[1]. This intensification has led to severe therapy-. The funders provided support in the form of salaries for authors [PRM, BOW, SSM]. The Steno Diabetes Center Copenhagen provided support in the form of a salary for AV. AstraZeneca provided support for the study in the form of a salary for AV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section
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