Novel risk factors for glucarpidase use in pediatric acute lymphoblastic leukemia: Hispanic ethnicity, age, and the ABCC4 gene.
Pediatr Blood Cancer
; 68(8): e29036, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-33788417
ABSTRACT
BACKGROUND:
Carboxypeptidase G2 (CPDG2 ; glucarpidase) is a rescue drug for patients at risk for kidney injury from high-dose methotrexate (MTX). As there are no strategies for predicting patients who will require CDPG2 , we evaluated the role of demographic, clinical, and genetic factors for CPDG2 use. PROCEDURE Cases who received CPDG2 and controls who did not were identified by chart review of acute lymphoblastic leukemia (ALL) patients who received MTX doses between 1000 and 5000 mg/m2 between 2010 and 2017. We used multivariable Bayesian logistic regression to evaluate the association of CPDG2 use with demographic and clinical variables and, on a subset of patients, with genetic ancestry and 49 single nucleotide variants previously associated with MTX toxicity.RESULTS:
We identified 423 patients who received 1592 doses of MTX. Of the 18 patients who received CPDG2 , 17 (94%) were Hispanic. No patients who received 1000 or 2000 mg/m2 of MTX received CPDG2 . Hispanic ethnicity (odds ratio 4.68; 95% compatibility interval 1.63-15.06) and older age (1.87 [1.17-3.17]) were associated with receiving CPDG2 . Of the 177 patients in the genomic cohort, 11 received CPDG2 . Each additional G allele of rs7317112 in ABCC4 increased the odds of requiring CPDG2 (3.10 [1.12-6.75]). Six other loci (NTRK1/rs10908521, TSG1/rs9345389, STT3B/rs1353327, SCLO1B1/rs4149056, GATA3/rs3824662, ARID5B/rs10821936) demonstrated probabilities of association between 88% and 97%.CONCLUSION:
We demonstrated that demographic characteristics, including Hispanic ethnicity and age, are associated with CPDG2 use. Additionally, we provide evidence that inherited genetic variation is associated with risk of requiring CPDG2 . If validated in independent populations, this information could be leveraged to develop targeted toxicity prevention strategies for children with ALL.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Gama-Glutamil Hidrolase
/
Proteínas Associadas à Resistência a Múltiplos Medicamentos
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
Tipo de estudo:
Etiology_studies
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Prognostic_studies
/
Risk_factors_studies
Aspecto:
Determinantes_sociais_saude
Limite:
Child
/
Humans
Idioma:
En
Revista:
Pediatr Blood Cancer
Ano de publicação:
2021
Tipo de documento:
Article