Dyslipidemia at diagnosis of childhood acute lymphoblastic leukemia

PLoS One. 2020 Apr 6;15(4):e0231209. doi: 10.1371/journal.pone.0231209. eCollection 2020.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Asparaginase / metabolism
  • Body Mass Index
  • Child
  • Child, Preschool
  • Dyslipidemias / complications*
  • Dyslipidemias / epidemiology
  • Female
  • Humans
  • Hypercholesterolemia / complications
  • Hypercholesterolemia / epidemiology
  • Hypertriglyceridemia / complications
  • Hypertriglyceridemia / epidemiology
  • Infant
  • Male
  • Osteonecrosis / complications
  • Pancreatitis / complications
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / epidemiology
  • Retrospective Studies
  • Risk
  • Steroids / metabolism
  • Thromboembolism / complications
  • Treatment Outcome

Substances

  • Steroids
  • Asparaginase

Grants and funding

This study was supported by the Danish Childhood Cancer Foundation, The Danish diabetes Academy supported by the Novo Nordisk Fonden, University of Copenhagen, Dagmar Marshalls Foundation, Axel Muusfelts Foundation and Danish Cancer Research Foundation. 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.