The Promise of Pharmacogenomics in Reducing Toxicity During Acute Lymphoblastic Leukemia Maintenance Treatment
نویسندگان
چکیده
Pediatric acute lymphoblastic leukemia (ALL) affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2-3years. While the primary drugs used in the maintenance phase, 6-mercaptopurine (6-MP) and methotrexate (MTX), are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity. For both drugs, pharmacogenomic factors have been identified that could explain a large amount of the variance in toxicity between patients, and may serve as effective predictors of toxicity during the maintenance phase of ALL treatment. 6-MP toxicity is associated with polymorphisms in the genes encoding thiopurine methyltransferase (TPMT), nudix hydrolase 15 (NUDT15), and potentially inosine triphosphatase (ITPA), which vary between ethnic groups. Moreover, MTX toxicity is associated with polymorphisms in genes encoding solute carrier organic anion transporter family member 1B1 (SLCO1B1) and dihydrofolate reductase (DHFR). Additional polymorphisms potentially associated with toxicities for MTX have also been identified, including those in the genes encoding solute carrier family 19 member 1 (SLC19A1) and thymidylate synthetase (TYMS), but their contributions have not yet been well quantified. It is clear that pharmacogenomics should be incorporated as a dosage-calibrating tool in pediatric ALL treatment in order to predict and minimize the occurrence of serious toxicities for these patients.
منابع مشابه
T Regulatory Cells Frequency During Maintenance Phase Chemotherapy for Pediatric Acute Lymphoblastic Leukemia
Background: Drugs used in cancer treatment specifically kill T regulatory cells. Objective: To determine different phenotypes of T regulatory cells during the maintenance phase chemotherapy for pediatric acute lymphoblastic leukemia (ALL). Materials: We evaluated the percentages of regulatory T cells by flow cytometry. Soluble CTLA-4 (sCTLA-4) ...
متن کاملEvaluation of neuropathy during intensive vincristine chemotherapy for non-Hodgkin\'s lymphoma and Acute Lymphoblastic Leukemia
Back ground: Vincristine (VCR), is a chemotherapy drug, useful in the treatment of leukemia, lymphoma and solid tumor and it is a potent neurotoxin and sensory neuropathy drug which a common behavioral toxicity of this drug. Neuropathy is common squeal of intensive chemotherapy protocols that contain vincristine and corticosteroids. Materials and Methods: This study was a retrospective and ...
متن کاملOverview the Causes of Early Deaths and Advance Supportive Care in Children with Acute Lymphoblastic Leukemia: A Systematic Review
Introduction: The objective of this study is to determine the major causes of early death in acute lymphoblastic leukemia (ALL). Methods: The following databases including PubMed, EMBASE, Science Direct and Google Scholar were searched for following terms: “acute lymphoblastic leukemia”, “early mortality”, “early death “ and “death in induction phase “. Inclusion criteria were all studies abo...
متن کاملMetronomic Effect as A New Hypothesis in Maintenance Therapy of Acute Lymphoblastic Leukemia
متن کامل
Medium and High-Dose Methotrexate-Induced Toxicity in Children with Acute Lymphoblastic Leukemia
Background: Methotrexate has an important role in treatment of acute leukemia. We measured methotrexate level in CSF and blood of children with acute lymphoblastic leukemia to determine complications and outcomes. Materials and Methods: One hundred and twenty patients (73 male, 47 female), with mean age at diagnosis of 6.1 years (11mo_15years) entered the study. Patients were divided into two...
متن کامل