Response to glucocorticoids and toxicity in childhood acute lymphoblastic leukemia: role of polymorphisms of genes involved in glucocorticoid response.

Full Abstract

BACKGROUND: Glucocorticoids (GCs) play a fundamental role in the treatment of pediatric acute lymphoblastic leukemia (ALL), but therapy with these agents often results in a number of severe side effects. The aim of our study was to evaluate the association between polymorphisms of genes encoding for proteins involved in the pharmacokinetics/pharmacodynamics of these drugs and the occurrence of side effects, in particular infections, in a small population of ALL children. PROCEDURE: Common polymorphisms of NR3C1, ABCB1, glutathione-S-transferase (GST)-M1, GST-P1, GST-T1, and IL-10 genes were analyzed in 36 pediatric patients with ALL, treated according to the AIEOP-BMF ALL 2000 study protocol. Toxicities occurring during the induction and reinduction periods were assessed and their association with genotypes was evaluated. RESULTS: In univariate analysis, the risk of severe infections was increased in subjects with the GST-M1 null genotype, while patients with the GST-M1 normal genotype had significantly more moderate degree infections. The results were confirmed by multivariate analysis. Selection from the reference models of independent variables based on Akaike Information Criteria (AIC) scores maintained the GST-M1 genotype variable in the model to predict severe infections, and the ABCB1 C3435T and GST-M1 genotype variables in the model for moderate infections. CONCLUSIONS: GST-M1 genotype may influence the severity of infections in ALL children during GC administration.

Author information

Author/s: Marino, Sara (S); Verzegnassi, Federico (F); Tamaro, Paolo (P); Stocco, Gabriele (G); Bartoli, Fiora (F); Decorti, Giuliana (G); Rabusin, Marco (M);

Affiliation: I.R.C.C.S Burlo Garofolo, UO Pediatric Hemato-Oncology, Trieste, Italy.

Journal and publication information

Publication Type: Journal Article; Randomized Controlled Trial

Journal: Pediatric blood & cancer (Pediatr Blood Cancer), published in United States. (Language: eng)

Reference: 2009-Dec; vol 53 (issue 6) : pp 984-91

Dates: Created 2009/09/16; Completed 2009/10/13;

PMID: 19621425, status: MEDLINE (last retrieval date: 10/13/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adolescent
Child
Child, Preschool
Dexamethasone - administration & dosage
Female
Glucocorticoids - administration & dosage; toxicity
Glutathione Transferase - genetics
Humans

Associated Chemicals: Glucocorticoids (0) ; Dexamethasone (50-02-2) ; Prednisone (53-03-2) ; Methotrexate (59-05-2) ; Glutathione Transferase (EC 2.5.1.18) ; glutathione S-transferase M1 (EC 2.5.1.18)

These are the highest related articles currently in the database: