Adult survivors of acute leukemia in childhood have a higher than expected frequency of obesity early mortality from cardiovascular disease, and an increased risk for the metabolic syndrome (MS), and this may be more common in individuals who received hematopoietic cell transplant (HCT) as part of their therapy. The major objective of this research is to evaluate the relationship between HCT specific treatment exposures and the development of insulin resistance and the MS in adolescent and young adult survivors after HCT for treatment of hematologic malignancies in childhood, and this application is the result of the successful progression of Dr. Baker's recent K23 award, funded to study late effects in survivors after HCT.
The specific aims of this proposal are: 1) to measure insulin resistance (IR, euglycemic insulin clamp) serum insulin, glucose, and lipids;to obtain blood pressure, and anthropometric measurements;and DEXA scans in 190 survivors of HCT and 190 controls;2) evaluate the association of specific HCT treatments exposures with the development of the MS;3) to measure cytokines, CRP and adipokines;4) to measure early signs of impaired endothelial function and sub-clinical cardiovascular disease;and 5) to obtain measures of dietary intake and physical activity in HCT survivors and controls. These data will address the hypotheses that a) HCT survivors will be more IR, and that IR will increase independent of age with longer follow-up after HCT, b) specific HCT treatment exposures will be associated with growth hormone deficiency and higher degrees of IR, c) allogeneic HCT will be associated with higher levels of inflammatory mediators associated with IR, d) vascular measurements of sub-clinical cardiovascular changes will be higher in survivors with MS and will be associated with total body irradiation exposure (TBI), e) HCT survivors will be less physically active and this will be correlated with exposure to TBI and with having had graft vs. host disease. This research offers a significant and exciting opportunity to explore a potentially modifiable late effect of childhood cancer treatment, the MS and the associated heightened risk for premature cardiovascular disease and type 2 diabetes. Since HCT is a widely applied therapeutic modality for leukemia as well as many other malignant and non-malignant diseases in children and adults with thousands of individuals worldwide every year becoming survivors, it is an increasingly important group to study.
|Ketterl, Tyler G; Chow, Eric J; Leisenring, Wendy M et al. (2018) Adipokines, Inflammation, and Adiposity in Hematopoietic Cell Transplantation Survivors. Biol Blood Marrow Transplant 24:622-626|
|Slater, Megan E; Steinberger, Julia; Ross, Julie A et al. (2015) Physical Activity, Fitness, and Cardiometabolic Risk Factors in Adult Survivors of Childhood Cancer with a History of Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 21:1278-83|
|Petryk, Anna; Polgreen, Lynda E; Barnum, Jessie L et al. (2015) Bone mineral density in children with fanconi anemia after hematopoietic cell transplantation. Biol Blood Marrow Transplant 21:894-9|
|Petryk, A; Polgreen, L E; Zhang, L et al. (2014) Bone mineral deficits in recipients of hematopoietic cell transplantation: the impact of young age at transplant. Bone Marrow Transplant 49:258-63|
|Baker, K S; Chow, E; Steinberger, J (2012) Metabolic syndrome and cardiovascular risk in survivors after hematopoietic cell transplantation. Bone Marrow Transplant 47:619-25|
|Parsons, Susan K; Phipps, Sean; Sung, Lillian et al. (2012) NCI, NHLBI/PBMTC First International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: health-related quality of life, functional, and neurocognitive outcomes. Biol Blood Marrow Transplant 18:162-71|
|Bunin, Nancy; Small, Trudy; Szabolcs, Paul et al. (2012) NCI, NHLBI/PBMTC first international conference on late effects after pediatric hematopoietic cell transplantation: persistent immune deficiency in pediatric transplant survivors. Biol Blood Marrow Transplant 18:6-15|
|Pulsipher, Michael A; Skinner, Roderick; McDonald, George B et al. (2012) National Cancer Institute, National Heart, Lung and Blood Institute/Pediatric Blood and Marrow Transplantation Consortium First International Consensus Conference on late effects after pediatric hematopoietic cell transplantation: the need for pediatric-s Biol Blood Marrow Transplant 18:334-47|
|Nieder, Michael L; McDonald, George B; Kida, Aiko et al. (2011) National Cancer Institute-National Heart, Lung and Blood Institute/pediatric Blood and Marrow Transplant Consortium First International Consensus Conference on late effects after pediatric hematopoietic cell transplantation: long-term organ damage and dys Biol Blood Marrow Transplant 17:1573-84|
|Dvorak, Christopher C; Gracia, Clarisa R; Sanders, Jean E et al. (2011) NCI, NHLBI/PBMTC first international conference on late effects after pediatric hematopoietic cell transplantation: endocrine challenges-thyroid dysfunction, growth impairment, bone health, & reproductive risks. Biol Blood Marrow Transplant 17:1725-38|
Showing the most recent 10 out of 11 publications