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



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. 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.
The Children's Hospital at Montefiore, 3415 Bainbridge Avenue, Bronx, NY, 10467, USA.
Rochelle R
RR
Maxwell
The Children's Hospital at Montefiore, 3415 Bainbridge Avenue, Bronx, NY, 10467, USA. peter.cole@einstein.yu.edu.|Albert Einstein College of Medicine, 1225 Morris Park Avenue, Van Etten Building, Room VE 6A03, Bronx, NY, 10461, USA. peter.cole@einstein.yu.edu.
Peter D
PD
Cole
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000209:etiology; D006801:Humans; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D011379:Prognosis; D016896:Treatment Outcome
D000970:Antineoplastic Agents
Acute lymphoblastic leukemia; Chemotherapy toxicity; Genetic polymorphisms; Pediatric cancer; Pharmacogenetics