Abstract/Details

Pharmacogenetic and Pharmacogenomic Studies in Pediatric Leukemia


2011 2011

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Abstract (summary)

Although current chemotherapy protocols have substantially improved the survival of children with acute leukemia, not all children are cured and many suffer treatment related toxicities. We have sought to improve the outcome of children with leukemia through pharmacogenomic and pharmacoepidemiology studies that are aimed at better defining patient populations at risk for adverse outcome and improving the utilization of supportive care resources. Specifically, we have demonstrated that group sequential methods (GSM) can be used to conserve valuable biosamples in pharmacogenomic studies in the case of a null result. We have also used the Children's Oncology Group (COG) clinical trials as a platform to demonstrate that CYP3A genotypes do not modify relapse risk but may modify the risk of vincristine associated neurological toxicities. Finally, we have merged data from COG with the Pediatric Health Information Systems (PHIS) administrative data set for patients enrolled on a Phase III trial of treatment for de novo acute myeloid leukemia. This merged data may be used not only for analysis of resource utilization, but may also be useful for monitoring Phase III clinical trials prospectively for treatment related toxicities. Ongoing studies are examining the concordance between toxicities reported in COG and PHIS data, the establishment of a chart-review based “gold standard” for determination of the sensitivity, specificity, positive predictive value, and negative predictive value of toxicities defined by COG and PHIS data, and the analysis of resource utilization for patient enrolled on COG AML studies.

Indexing (details)


Subject
Epidemiology
Classification
0766: Epidemiology
Identifier / keyword
Health and environmental sciences; Chemotherapy; Pediatric leukemia; Pharmacogenetics
Title
Pharmacogenetic and Pharmacogenomic Studies in Pediatric Leukemia
Author
Aplenc, Richard
Number of pages
22
Publication year
2011
Degree date
2011
School code
0175
Source
DAI-B 72/09, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781124726045
Advisor
Rebbeck, Timothy
University/institution
University of Pennsylvania
University location
United States -- Pennsylvania
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3462212
ProQuest document ID
878140118
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/878140118
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