Metabolic syndrome as a late effect of childhood hematopoietic stem cell transplantation – A thorough statistical evaluation of putative risk factors

Tina Gerbek*, Birthe Lykke Thomsen, Ena Muhic, Terkel Christiansen, Kaspar Sørensen, Marianne Ifversen, Klaus Kofoed, Klaus Müller

*Corresponding author for this work

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Abstract

Background: Metabolic syndrome (MetS) is frequent among survivors of childhood hematopoietic stem-cell transplantation (HSCT), but assessment of risk factors is challenged by survivor and participation bias in long-term follow-up studies. Methods: A cohort of 395 pediatric patients transplanted between 1980 and 2018 was investigated. MetS was assessed at follow-up between December 2018 and March 2020. Two composite outcomes ((a) combining MetS and death, (b) combining MetS, death, and nonparticipation) were considered to address the risk of selection bias. Results: Among 234 survivors invited to the follow-up, 96 individuals (median age 27 years) participated. MetS prevalence was 30% among participants. The only significant HSCT risk factor was a variable combining HSCT indication and conditioning with total-body irradiation (TBI) (p =.0011). Compared to acute leukemias (AL) treated with high-grade TBI (8–12 Gy), a lower MetS prevalence was seen for nonmalignant diseases treated with no/low-grade TBI (0–4.5 Gy) (OR = 0.04, 95% confidence interval (CI): 0.00–0.23). Analyses of the composite outcomes indicated overestimation of the effect of high-grade TBI due to selection bias. Scrutiny showed strong residual confounding between HSCT indication and high-grade TBI within AL-patients. The HSCT effect on MetS reflected HSCT effects on high-density-lipoprotein (HDL) and triglycerides. Compared to AL treated with high-grade TBI, nonmalignant diagnoses treated with no/low-grade TBI had higher HDL (+40%, 95% CI: +21% to +62%) and lower triglyceride (−59%, 95% CI: −71% to −42%). Conclusion: The TBI effect on MetS may be overestimated in follow-up studies due to selection bias and confounding. The TBI effect was confined to the potentially modifiable MetS criteria HDL and triglyceride.

Original languageEnglish
Article numbere14530
JournalPediatric Transplantation
Volume27
Issue number4
Number of pages14
ISSN1397-3142
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.

Keywords

  • childhood hematopoietic stem cell transplantation
  • late effects
  • metabolic syndrome

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