Pharmacogenetic Predictors of Treatment-Related Toxicity Among Children With Acute Lymphoblastic Leukemia

Rochelle R. Maxwell, Peter Cole

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

Purpose of Review: The aim of this review is to summarize the most recent and most robust pharmacogenetic predictors of treatment-related toxicity (TRT) in childhood acute lymphoblastic leukemia (ALL). Recent Findings: Multiple studies have examined the toxicities of the primary chemotherapeutic agents used to treat childhood ALL in relation to host genetic factors. However, few results have been replicated independently, largely due to cohort differences in ancestry, chemotherapy treatment protocols, and definitions of toxicities. To date, there is only one widely accepted clinical guideline for dose modification based on gene status: thiopurine dosing based on TPMT genotype. Based on recent data, it is likely that this guideline will be modified to incorporate other gene variants, such as NUDT15. Summary: We highlight genetic variants that have been consistently associated with TRT across treatment groups, as well as those that best illustrate the underlying pathophysiology of TRT. In the coming decade, we expect that survivorship care will routinely specify screening recommendations based on genetics. Furthermore, clinical trials testing protective interventions may modify inclusion criteria based on genetically determined risk of specific TRTs.

Original languageEnglish (US)
Pages (from-to)176-186
Number of pages11
JournalCurrent Hematologic Malignancy Reports
Volume12
Issue number3
DOIs
StatePublished - Jun 1 2017

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Pharmacogenetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Guidelines
Therapeutics
Clinical Protocols
Genes
Genotype
Clinical Trials
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Keywords

  • Acute lymphoblastic leukemia
  • Chemotherapy toxicity
  • Genetic polymorphisms
  • Pediatric cancer
  • Pharmacogenetics

Cite this

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abstract = "Purpose of Review: The aim of this review is to summarize the most recent and most robust pharmacogenetic predictors of treatment-related toxicity (TRT) in childhood acute lymphoblastic leukemia (ALL). Recent Findings: Multiple studies have examined the toxicities of the primary chemotherapeutic agents used to treat childhood ALL in relation to host genetic factors. However, few results have been replicated independently, largely due to cohort differences in ancestry, chemotherapy treatment protocols, and definitions of toxicities. To date, there is only one widely accepted clinical guideline for dose modification based on gene status: thiopurine dosing based on TPMT genotype. Based on recent data, it is likely that this guideline will be modified to incorporate other gene variants, such as NUDT15. Summary: We highlight genetic variants that have been consistently associated with TRT across treatment groups, as well as those that best illustrate the underlying pathophysiology of TRT. In the coming decade, we expect that survivorship care will routinely specify screening recommendations based on genetics. Furthermore, clinical trials testing protective interventions may modify inclusion criteria based on genetically determined risk of specific TRTs.",
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Pharmacogenetic Predictors of Treatment-Related Toxicity Among Children With Acute Lymphoblastic Leukemia. / Maxwell, Rochelle R.; Cole, Peter.

In: Current Hematologic Malignancy Reports, Vol. 12, No. 3, 01.06.2017, p. 176-186.

Research output: Contribution to journalReview article

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N2 - Purpose of Review: The aim of this review is to summarize the most recent and most robust pharmacogenetic predictors of treatment-related toxicity (TRT) in childhood acute lymphoblastic leukemia (ALL). Recent Findings: Multiple studies have examined the toxicities of the primary chemotherapeutic agents used to treat childhood ALL in relation to host genetic factors. However, few results have been replicated independently, largely due to cohort differences in ancestry, chemotherapy treatment protocols, and definitions of toxicities. To date, there is only one widely accepted clinical guideline for dose modification based on gene status: thiopurine dosing based on TPMT genotype. Based on recent data, it is likely that this guideline will be modified to incorporate other gene variants, such as NUDT15. Summary: We highlight genetic variants that have been consistently associated with TRT across treatment groups, as well as those that best illustrate the underlying pathophysiology of TRT. In the coming decade, we expect that survivorship care will routinely specify screening recommendations based on genetics. Furthermore, clinical trials testing protective interventions may modify inclusion criteria based on genetically determined risk of specific TRTs.

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