Prevalence of and Risk Factors for Metabolic Syndrome, Vascular Damage, and Accelerated Aging (MetVasA) After Pediatric Hematopoietic Stem Cell Transplantation for Hematological Malignancy: Protocol for a Cross-Sectional Cohort Study

BACKGROUND: Survivors of hematopoietic stem cell transplantation (HSCT) in childhood face a high risk of metabolic and cardiovascular disease as well as accelerated aging. Estimates of the prevalence of these severe late effects have varied widely because they have been based on small cohorts or mixed populations of patients that received transplantations for both malignant and nonmalignant diseases, and the co-occurrence of these late effects was not assessed. Therefore, the true burden of these complications in survivors of hematological malignancies remains unclear. Moreover, the role of potentially modifiable risk factors such as health behaviors and inflammation has not yet been determined. OBJECTIVE: This study aims to determine the prevalence of metabolic syndrome (MetS), endothelial dysfunction (ED), and accelerated aging and their risk factors, including treatment-related factors, inflammation, and health behaviors, 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 2 cohorts of survivors of HSCT in childhood for a hematological malignancy. The first cohort (cohort 1; n=102) consists of survivors who received transplantations before 2002 and were participants of the Dutch Childhood Cancer Survivor Study LATER 2 cohort, a nationwide cohort study focusing on late effects among long-term childhood cancer survivors. The second cohort will include survivors who received transplantations between 2002 and 2021 (cohort 2; projected n=120) and visited the late effects (LATER) outpatient clinic of the Princess Máxima Center between 2024 and 2026. Key outcomes will be the prevalence of MetS (≥3 of 5 clinical criteria), accelerated aging (3 of 5 biological and clinical criteria), and ED (assessed by endothelial peripheral arterial tonometry) and their co-occurrence. A broad range of potential and modifiable risk factors will be investigated, including treatment-related factors; transplant complications (eg, graft-versus-host disease); and health behaviors, including physical activity, dietary intake and status assessed with nutritional biomarkers, substance use, sun exposure, and relaxation. RESULTS: Patient recruitment started in January 2024 and is estimated to last until June 2026. As of September 2025, a total of 77 participants have been included in the study. CONCLUSIONS: This study will provide insight into the prevalence of MetS, ED, and accelerated aging, as well as potentially modifiable risk factors, including those that have not been previously examined, among survivors of HSCT for hematological malignancies in childhood. 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. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/77429.