|Grant Number:||5R01CA133881-03 Interpret this number|
|Primary Investigator:||Aplenc, Richard|
|Organization:||Children'S Hosp Of Philadelphia|
|Project Title:||Genetic Predictors of Aml Treatment Response|
DESCRIPTION (provided by applicant): Although acute myeloid leukemia (AML) causes substantial treatment burden in both children and adults, AML treatment response remains incompletely understood. This application proposes a genome-wide association study (GWAS) of pediatric AML treatment response. Two hypotheses underlie this application. First, somatic genetic variation will modify AML relapse and treatment related infection risk. Second, clinical trial simulations (CTS) may define how genetic variation data may be used to modify AML treatment. These hypotheses will be tested in three specific aims. Aim 1 will use the Illumina Human 610 HH Bead Chip to perform a GWAS with 840 patients to identify genotypes associated with AML relapse and infectious complication risk. Aim 2 will use the Illumina Infinium" Chip to validate 4% of SNPs found in Aim 1 in 1,160 Caucasian patients and 750 non-Caucasian patients. Aim 3 will use CTS to test the clinical applicability of infection susceptibility genotypes discovered and validated in the first two aims. This application has significance both as the first GWAS in AML and as a novel step towards translating genetic variability data into the clinical care of patients. Furthermore, since pediatric and adult AML share common molecular pathologies and treatment strategies, this research may inform the care of both adult and pediatric AML patients. PUBLIC HEALTH RELEVANCE: Acute myeloid leukemia (AML) causes a substantial disease and treatment burden in both children and adults. This application will provide data on the role of somatic genetic variability in AML treatment response and will use clinical trial simulations to model the application of genotype data to clinical patient care. Thus, this application may not only inform the care of adult and pediatric AML patients, but may also provide important insights into the translation of genotype data into patient care.
Antifungal prophylaxis associated with decreased induction mortality rates and resources utilized in children with new-onset acute myeloid leukemia.
Authors: Fisher BT, Kavcic M, Li Y, Seif AE, Bagatell R, Huang YS, Zaoutis T, Torp K, Leckerman KH, Aplenc R
Source: Clin Infect Dis, 2014 Feb;58(4), p. 502-8.
EPub date: 2013 Nov 23.
Patient and hospital factors associated with induction mortality in acute lymphoblastic leukemia.
Authors: Seif AE, Fisher BT, Li Y, Torp K, Rheam DP, Huang YS, Harris T, Shah A, Hall M, Fieldston ES, Kavcic M, Vujkovic M, Bailey LC, Kersun LS, Reilly AF, Rheingold SR, Walker DM, Aplenc R
Source: Pediatr Blood Cancer, 2013 Nov 19;null, p. null.
EPub date: 2013 Nov 19.
Zoonotic infections in pediatric patients with acute leukemia.
Authors: Lothstein K, Fisher B, Li Y, Seif A, Harris T, Torp K, Kavcic M, Huang YS, Rheingold SR, Aplenc R
Source: Pediatr Blood Cancer, 2013 Dec;60(12), p. E160-2.
EPub date: 2013 Aug 19.
Induction mortality, ATRA administration, and resource utilization in a nationally representative cohort of children with acute promyelocytic leukemia in the United States from 1999 to 2009.
Authors: Fisher BT, Singh S, Huang YS, Li Y, Gregory J, Walker D, Seif AE, Kavcic M, Aplenc R
Source: Pediatr Blood Cancer, 2014 Jan;61(1), p. 68-73.
EPub date: 2013 Jul 18.