Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina. Issue 5 (May 2015)

• Record Type: Journal Article
• Authors: Aráoz, Hilda Verónica; D'Aloi, Karina; Foncuberta, María Eugenia; Sanchez La Rosa, Christian Germán; Alonso, Cristina Noemí; Chertkoff, Lilien; Felice, Marisa
• Is Part Of: Leukemia & lymphoma. Volume 56:Issue 5(2015:May)
• Page Start: 1370
• Page End: 1378
• Publication Date: 2015-05
• Subjects: Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2014.951844
• Languages: English
• ISSNs: 1042-8194

Abstract

<abstract> <title>Abstract</title> <p>The aim of this study was to evaluate the influence of the most common genetic variants in methylenetetrahydrofolate reductase (<italic>MTHFR</italic>), thiopurine methyltransferase (<italic>TPMT</italic>) and glutathione-S-transferases (<italic>GSTs)</italic> on the outcome of acute lymphoblastic leukemia (ALL) treatment in Argentinean children. Two hundred and eighty-six patients with ALL treated with two Berlin–Frankfurt–Münster (BFM)-based protocols were analyzed. Ten genetic variants were studied. Toxicity was evaluated during the consolidation phase. Children who received 2 g/m²/day of methotrexate and carried at least one 677T allele in <italic>MTHFR</italic> showed an increased risk of developing severe leukopenia (<italic>p</italic> = 0.004) and neutropenia (<italic>p</italic> = 0.003). Intermediate-risk (IR) patients with a heterozygous <italic>TPMT</italic> genotype had a higher probability of event-free survival than those with a wild-type genotype. Genotyping of <italic>MTHFR</italic> polymorphisms might be useful to optimize consolidation therapy, reducing the associated severe hematologic toxicity. Further studies are necessary to establish the usefulness of <italic>MTHFR</italic> and <italic>TPMT</italic> variants as additional markers to predict outcome in the IR group.</p> </abstract>