Using Pharmacogenomics Testing to Optimize Care in Children with Acute Hematologic Malignancies

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.5062-5062
• Main Author: Kissoon, Trisha
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-129511

Background Inter-patient variation in the pharmacokinetics of drugs can result in unpredictable variability in occurrence of adverse events and toxicity as well as variation in therapeutic efficacy. Although a multitude of factors contribute to this observed variation, inherited variation in genes involved in drug metabolism and transport has been shown to play a significant role. Genetic polymorphisms can influence the gene expression and/or activity, thereby impacting drug pharmacokinetics and causing inter-individual variation in drug levels which can alter risk of toxicity or therapeutic efficacy. The goal of this study is to identify pharmacogenomic biomarkers predicting drug response and toxicity in children receiving chemotherapy for acute hematologic malignancies. Identification of such biomarkers will establish relevant biomarkers for allowing for personalizing therapy to achieve maximum benefit and minimal side effects in future studies. Study Design and Methods: Study Population Male and female participants are included with no restrictions based on racial and/or ethnic origin. All patients aged 26 years of younger who have received at least one year of treatment for acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) and have experienced organ toxicity CTCAE v5.0 Grade 3 or higher at the University of Florida are offered participation. Subjects meeting eligibility criteria are excluded if they cannot provide a blood specimen. Study Design This pilot study proposes to identify and characterize pharmacogenomic variations that lead to different systemic toxicity profiles in pediatric patients receiving commonly used chemotherapy agents for ALL and AML. Agents of interest include drugs used during induction chemotherapy cycles which include Vincristine, Methotrexate, Cytarabine, Daunorubicin, Prednisone, Dexamethasone, 6-thioguanine, Cyclophosphamide, 6-mercaptopurine, and Etoposide. A single-nucleotide polymorphism (SNP) panel to evaluate SNPs in pharmacokinetic pathway genes of the selected drugs has been created. Genotyping is performed using Taqman genotyping assays and the Quant studio real time PCR system. We are investigating genes involved in the pharmacokinetics of the selected chemotherapy agents such as ABCB1, GSTM1, GSTT1, BCL2, MCL1, BCL2L11, MTHFR, SLC29A1, FMO3, DYNC2H1, TPMT, NUDT15, GSTP1, SOD2, and TP53. Toxicities that are correlated to SNP genotypes include the following: renal injury defined as creatinine clearan