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

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  1. Gene dose effects of GSTM1, GSTT1 and GSTP1 polymorphisms on outcome in childhood acute lymphoblastic leukemia

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  2. Plasma cytokine profiles at diagnosis in pediatric patients with non-hodgkin lymphoma

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  3. Duration of adrenal insufficiency during treatment for childhood acute lymphoblastic leukemia

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  4. Acute respiratory failure in 3 children with juvenile myelomonocytic leukemia

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  1. Increments in DNA-thioguanine level during thiopurine enhanced maintenance therapy of acute lymphoblastic leukemia

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  2. Selection criteria for assembling a pediatric cancer predisposition syndrome gene panel

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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 (TPMTHZ) compared to TPMT wild type (TPMTWT) 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/m2/day) or 6MP escalation (up to 50 or 75 mg/m2/day) during consolidation therapy.

Original languageEnglish
JournalPediatric Hematology and Oncology
Volume38
Issue number3
Pages (from-to)227-238
Number of pages12
ISSN0888-0018
DOIs
Publication statusPublished - Apr 2021

    Research areas

  • Childhood acute lymphoblastic leukemia, 6-mercaptopurine, minimal residual disease, thiopurine methyltransferase

ID: 61695705