Pharmacogenomics and variations in the risk of toxicity during the consolidation/maintenance phases of the treatment of pediatric B-cell leukemia patients from an admixed population in the Brazilian Amazon. (November 2018)

• Record Type: Journal Article
• Authors: de Carvalho, Darlen Cardoso; Wanderley, Alayde Vieira; dos Santos, André Mauricio Ribeiro; Fernandes, Marianne Rodrigues; Cohen Lima de Castro, Amanda de Nazaré; Leitão, Luciana Pereira Colares; de Carvalho, João Augusto Nunes; de Souza, Tatiane Piedade; Khayat, André Salim; dos Santos, Sidney Emanuel Batista; de Assumpção, Paulo Pimentel; dos Santos, Ney Pereira Carneiro
• Is Part Of: Leukemia research. Volume 74(2018)
• Page Start: 10
• Page End: 13
• Publication Date: 2018-11
• Subjects: Pharmacogenetics -- Pediatrics -- ALL -- SLCO1B1 -- ABCC3; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2018.09.003
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: During the consolidation phase, 45.5% of the patients presented at least one episode of toxicity. During the maintenance phase, 19.8% of the patients suffered some type of toxicity. The rs2306283 ( SLCO1B1 ) mutant allele increased the risk of neurotoxicity. The AA genotype of the rs9895420 polymorphism ( ABCC3 ) has a protective effect on gastric toxicity. Abstract: The treatment of Acute Lymphoblastic Leukemia (ALL) in children has a high clinical success rate, although toxicological complications are frequent, and often result in the interruption of the treatment. Various studies have shown that toxicities resulting from the treatment are influenced by pharmacogenetic variants. Most of this research has focused on relatively homogeneous populations, and the influence of these variants in highly admixed populations, such as that of Brazil, is still poorly understood. The present study investigated the association between pharmacogenetic variants and severe toxicities in pediatric B-cell ALL patients from an admixed population of the Brazilian Amazon. The rs2306283 (of SLCO1B1) mutant allele increased the risk of neurotoxicity threefold, and the homozygous mutant rs9895420 (of ABCC3 ) genotype was associated with a fivefold increase in protection against severe gastrointestinal toxicity. This indicates that the rs2306283 and rs9895420 polymorphisms may be relevant to the prediction of severe toxicity in pediatric ALL patients.