Single Nucleotide Polymorphisms and Relapse Risk in Standard Risk ALL
- Determine the role of single nucleotide polymorphisms (SNPs) in determining response to
therapy in pediatric patients with acute lymphoblastic leukemia.
- Compare the association between SNPs and treatment outcome and toxicity in patients
enrolled on protocol CCG-1891 vs protocol CCG-1952.
- Determine the role of SNPs in drug metabolizing enzymes and the development of
veno-occlusive disease in patients enrolled on CCG-1952.
- Evaluate interactions between genotypes and other risk factors for treatment response
in these patients.
- Determine predictive models utilizing genetic information and clinical data to predict
treatment response and toxicity in these patients.
OUTLINE: Tumor tissue samples undergo genotype assessment on the Pyrosequencing platform.
Contingency tables and X^2 test performs a univariate analysis of the risk of relapse and
genotype, and multivariable analyses using logistic regression. Cox proportional hazards
evaluate the risk of relapse given genotype and other confounders. Genotype patterning,
classification and regression trees, and multifactor dimensionality reduction evaluates for
patterns of single nucleotide polymorphisms associated with toxicity and relapse risk.
PROJECTED ACCRUAL: A total of 800 patients (200 with relapsed disease and 600 without
relapsed disease) will be accrued for this study.
Role of single nucleotide polymorphisms (SNPs) in determining response to therapy
Richard Aplenc, MD, MSCE
Children's Hospital of Philadelphia
United States: Federal Government