TPMT polymorphisms and minimal residual disease after 6-mercaptopurine post-remission consolidation therapy of childhood acute lymphoblastic leukaemia.

Autor: Dreisig K; Pediatric Oncology research laboratory, The University Hospital Rigshospitalet, Copenhagen, Denmark., Brünner ED; Pediatric Oncology research laboratory, The University Hospital Rigshospitalet, Copenhagen, Denmark., Marquart HV; The Tissue Typing Laboratory, Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Helt LR; Pediatric Oncology research laboratory, The University Hospital Rigshospitalet, Copenhagen, Denmark., Nersting J; Pediatric Oncology research laboratory, The University Hospital Rigshospitalet, Copenhagen, Denmark., Frandsen TL; Department of Pediatrics and adolescent medicine, The University Hospital Rigshospitalet, Copenhagen, Denmark., Jonsson OG; Department of Pediatrics, University of Iceland, Reykjavík, Iceland., Taskinen M; Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Children and Adolescents, Helsinki University Hospital, Helsinki, Finland., Vaitkeviciene G; Children's Hospital, Vilnius University Hospital Santaros Klinikos and Vilnius University, Vilnius, Lithuania., Lund B; Department of Pediatrics, St. Olavs Hospital, Trondheim; Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway., Abrahamsson J; Department of Pediatrics, Institution for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Lepik K; Tallinn Children's Hospital, Tallinn, Estonia., Schmiegelow K; Pediatric Oncology research laboratory, The University Hospital Rigshospitalet, Copenhagen, Denmark.; Department of Pediatrics and adolescent medicine, The University Hospital Rigshospitalet, Copenhagen, Denmark.; Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Pediatric hematology and oncology [Pediatr Hematol Oncol] 2021 Apr; Vol. 38 (3), pp. 227-238. Date of Electronic Publication: 2020 Nov 18.
DOI: 10.1080/08880018.2020.1842570
Abstrakt: Bone marrow minimal residual disease (MRD) is the strongest predictor of relapse in children with acute lymphoblastic leukemia (ALL). 6-mercaptopurine (6MP) in ALL therapy has wide inter-individual variation in disposition and is strongly influenced by polymorphisms in the thiopurine methyltransferase ( TPMT ) gene. In 952 patients treated according to the NOPHO ALL2008 protocol, we explored the association between thiopurine disposition, TPMT genotypes and MRD levels after consolidation therapy with 6MP, high-dose methotrexate (HD-MTX), asparaginase, and vincristine. The levels of the cytotoxic DNA-incorporated thioguanine were significantly higher on day 70-79 in G460A/A719G TPMT heterozygous ( TPMT HZ ) compared to TPMT wild type ( TPMT WT ) patients (mean: 230.7 vs. 149.7 fmol/µg DNA, p = 0.002). In contrast, TPMT genotype did not associate with the end of consolidation MRD levels irrespective of randomization of the patients to fixed dose (25 mg/m 2 /day) or 6MP escalation (up to 50 or 75 mg/m 2 /day) during consolidation therapy.
Databáze: MEDLINE
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