JMIR Publications

ABSTRACT

Background:

Survivors of hematopoietic stem cell transplantation (HSCT) in childhood face a high risk of metabolic and cardiovascular disease, as well as accelerated aging. The prevalences of these severe late effects vary widely, because previous estimates are based on small cohorts or mixed populations of patients transplanted for both malignant and non-malignant diseases, and their co-occurrence was not assessed. Therefore, the true burden of these complications in survivors treated for hematological malignancies remains unclear. Moreover, the role of potentially modifiable risk factors, such as health behaviors and inflammation, has not yet been determined.

Objective:

To determine the prevalence of and risk factors, including treatment-related factors, inflammation, and health behaviors, for metabolic syndrome (MetS), endothelial dysfunction (ED) and accelerated aging, in a large representative cohort of Dutch survivors of HSCT in childhood. Additionally, the study will examine the co-occurrence of these late effects.

Methods:

This cross-sectional cohort study will combine two cohorts of survivors of HSCT in childhood for a hematological malignancy. The first cohort consists of 102 survivors transplanted before 2002 from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER-2 cohort (cohort I). The second cohort, will include survivors transplanted between 2002-2021 (cohort II, aim n=120), who will visit the late effects outpatient (LATER) clinic of the Princess Máxima Center between 2024-2026. Key outcomes will be the prevalence of MetS (three or more out of five clinical criteria), accelerated aging (three out of five biological and clinical criteria), and ED assessed by peripheral artery tonometry (EndoPAT), and their co-occurrence. A broad range of potential (modifiable) risk factors will be investigated, including treatment-related factors, transplant complications, such as graft-versus-host disease (GvHD), and health behaviors, including physical activity, dietary intake and status assessed with nutritional biomarkers, substance use, sun exposure and relaxation.

Results:

This study will provide insight into the prevalence of and potentially modifiable risk factors, including those that have not been previously examined, for MetS, ED, and accelerated aging in survivors of HSCT for a hematological malignancy in childhood.

Conclusions:

The findings will inform surveillance guidelines and support the development of health behavioral and anti-inflammatory interventions to mitigate the risk of these severe late effects. Clinical Trial: Registered at toetsingonline.nl, NL83998.041.23