[K08] Muscle health and impaired glucose tolerance in adolescent and young adult hematopoietic cell transplantation survivors
Ente: National Cancer Institute
Scadenza: 2030-07-31
Importo max: 280.931 EUR
Paese: US
Descrizione
PROJECT SUMMARY
Adolescents and young adults (AYAs, 15–39 years old) with cancer undergoing allogeneic hematopoietic cell
transplantation (HCT) are a growing population who have experienced inferior improvements in outcomes
compared to younger non-AYAs. AYAs undergoing HCT are at high risk of developing treatment-related
complications, attributed to the delivery of intensive treatments for biologically aggressive cancers in this age
group. Studies conducted in mostly non-AYAs have shown that nearly 60% of patients develop impaired glucose
tolerance (IGT), a precursor to diabetes, by just 100 days post-HCT. This underscores the need for early
detection and treatment of IGT after HCT. Skeletal muscle is a key endocrine organ involved in >80% of the
body’s insulin-stimulated glucose utilization. HCT-related risk factors such as total body irradiation, corticosteroid
exposure, graft-versus-host disease, and associated inflammation may contribute to acute declines in skeletal
muscle in the months after HCT. Impairments in skeletal muscle strength, mass, and performance are associated
with IGT risk in the general population, in whom skeletal muscle is the first endocrine organ to contribute to
insulin resistance. AYAs are at particular risk of developing skeletal muscle impairment due to cancer treatment
and HCT delivered during periods of physiologic vulnerability (i.e., during key periods of growth and
development). However, there is limited information on how HCT-related exposures impact skeletal muscle
health among AYAs in the early (<1y) post-HCT period, and how these changes contribute to the pathogenesis
of IGT. Our central hypothesis is that among AYAs with cancer, HCT and related factors negatively alter skeletal
muscle health, resulting in increased risk of IGT. To test this hypothesis, we will assess for IGT in a group of AYA
HCT survivors over time. IGT will be defined using the 2-hour oral glucose tolerance test, which is a preferred
screening test for IGT as it reflects the relationship between glucose and insulin. Using a longitudinal study
design with study assessment time points of pre-HCT and 6 months and 1 year post-HCT, we will delineate
changes in skeletal muscle strength, mass, and performance (Aim 1.1), identify blood biomarkers correlating
with changes in skeletal muscle health post-HCT (Aim 1.2), and determine the association between individual
domains of skeletal muscle health and IGT (Aim 2). The proposed research will define the trajectory of skeletal
muscle health, and its association with IGT risk, in AYA HCT survivors. This would serve as the foundation for an
R01-funded study to develop tailored approaches to mitigate skeletal muscle impairments and IGT among HCT
survivors.
Istituzione: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
PI: RUSHA BHANDARI
Progetto: 1K08CA304491-01A1
Settori: National Cancer Institute
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