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National Institutes of Health: National Cancer Institute: Division of Cancer Control and Population Sciences
Grant Details

Grant Number: 5R01CA112530-05 Interpret this number
Primary Investigator: Baker, Kevin
Organization: Fred Hutchinson Cancer Research Center
Project Title: Metabolic Syndrome Following Transplant for Leukemia
Fiscal Year: 2010
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Abstract

DESCRIPTION (provided by applicant): 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.

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Publications

Physical Activity, Fitness, and Cardiometabolic Risk Factors in Adult Survivors of Childhood Cancer with a History of Hematopoietic Cell Transplantation.
Authors: Slater M.E. , Steinberger J. , Ross J.A. , Kelly A.S. , Chow E.J. , Koves I.H. , Hoffmeister P. , Sinaiko A.R. , Petryk A. , Moran A. , et al. .
Source: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2015 Jul; 21(7), p. 1278-83.
EPub date: 2015-04-10.
PMID: 25865649
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Bone mineral density in children with fanconi anemia after hematopoietic cell transplantation.
Authors: Petryk A. , Polgreen L.E. , Barnum J.L. , Zhang L. , Hodges J.S. , Baker K.S. , Wagner J.E. , Steinberger J. , MacMillan M.L. .
Source: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2015 May; 21(5), p. 894-9.
EPub date: 2015-01-13.
PMID: 25591848
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Bone mineral deficits in recipients of hematopoietic cell transplantation: the impact of young age at transplant.
Authors: Petryk A. , Polgreen L.E. , Zhang L. , Hodges J.S. , Dengel D.R. , Hoffmeister P.A. , Steinberger J. , Baker K.S. .
Source: Bone marrow transplantation, 2014 Feb; 49(2), p. 258-63.
EPub date: 2013-10-14.
PMID: 24121211
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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-specific long-term follow-up guidelines.
Authors: Pulsipher M.A. , Skinner R. , McDonald G.B. , Hingorani S. , Armenian S.H. , Cooke K.R. , Gracia C. , Petryk A. , Bhatia S. , Bunin N. , et al. .
Source: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2012 Mar; 18(3), p. 334-47.
EPub date: 2012-01-14.
PMID: 22248713
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NCI, NHLBI/PBMTC First International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: health-related quality of life, functional, and neurocognitive outcomes.
Authors: Parsons S.K. , Phipps S. , Sung L. , Baker K.S. , Pulsipher M.A. , Ness K.K. .
Source: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2012 Feb; 18(2), p. 162-71.
EPub date: 2011-12-10.
PMID: 22155139
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NCI, NHLBI/PBMTC first international conference on late effects after pediatric hematopoietic cell transplantation: persistent immune deficiency in pediatric transplant survivors.
Authors: Bunin N. , Small T. , Szabolcs P. , Baker K.S. , Pulsipher M.A. , Torgerson T. .
Source: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2012 Jan; 18(1), p. 6-15.
EPub date: 2011-11-17.
PMID: 22100979
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NCI, NHLBI/PBMTC first international conference on late effects after pediatric hematopoietic cell transplantation: endocrine challenges-thyroid dysfunction, growth impairment, bone health, & reproductive risks.
Authors: Dvorak C.C. , Gracia C.R. , Sanders J.E. , Cheng E.Y. , Baker K.S. , Pulsipher M.A. , Petryk A. .
Source: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2011 Dec; 17(12), p. 1725-38.
EPub date: 2011-10-17.
PMID: 22005649
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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 dysfunction.
Authors: Nieder M.L. , McDonald G.B. , Kida A. , Hingorani S. , Armenian S.H. , Cooke K.R. , Pulsipher M.A. , Baker K.S. .
Source: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2011 Nov; 17(11), p. 1573-84.
EPub date: 2011-10-01.
PMID: 21963877
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Long-term consequences of hematopoietic stem cell transplantation: current state of the science.
Authors: Baker K.S. , Armenian S. , Bhatia S. .
Source: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2010 Jan; 16(1 Suppl), p. S90-6.
EPub date: 2009-09-24.
PMID: 19782145
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