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Methotrexate consolidation treatment according to pharmacogenetics of MTHFR ameliorates event-free survival in childhood acute lymphoblastic leukaemia

The Pharmacogenomics Journal volume 12, pages 379–385 (2012)Cite this article

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Abstract

Recent advances in treatment for childhood acute lymphoblastic leukaemia (ALL) have significantly increased outcome. High-dose methotrexate (MTX) is the most commonly used regimen during the consolidation period, but the optimal dose remains to be defined. We investigated the usefulness of the MTHFR genotype to increase the MTX dosage in the consolidation phase in 141 childhood ALL patients enrolled in the ALL/SHOP-2005 protocol. We also investigated the pharmacogenetic role of polymorphisms in genes involved in MTX metabolism on therapy-related toxicity and survival. Patients with a favourable MTHFR genotype (normal enzymatic activity) treated with MTX doses of 5 g m−2 had a significantly lower risk of suffering an event than patients with an unfavourable MTHFR genotype (reduced enzymatic activity) that were treated with the classical MTX dose of 3 g m−2 (P=0.012). Our results indicate that analysis of the MTHFR genotype is a useful tool to optimise MTX therapy in childhood patients with ALL.

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Acknowledgements

We are indebted to the members of the Spanish Society of Paediatric Haematology and Oncology who participated in the ALL/SHOP-2005 protocol. We thank Carolyn Newey for English language editing.

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Authors and Affiliations

  1. Department of Genetics, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    J Salazar, E del Río & M Baiget

  2. Centre for Biomedical Network Research on Rare Diseases, U705, (CIBERER), Barcelona, Spain,

    J Salazar, E del Río & M Baiget

  3. Department of Haematology, Hospital Althaia, Manresa, Spain

    A Altés

  4. Department of Paediatric Haematology, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain

    J Estella & S Rives

  5. Department of Paediatric Oncology, Hospital General Universitario de Alicante, Alicante, Spain

    M Tasso

  6. Department of Paediatric Oncology, Hospital de Cruces, Bizkaia, Spain

    A Navajas

  7. Department of Paediatric Oncology, Hospital Virgen del Camino, Pamplona, Spain

    J Molina

  8. Department of Paediatric Haematology and Oncology, Hospital Universitario Madrid Montepríncipe, Madrid, Spain

    M Villa

  9. Department of Paediatric Haematology and Oncology, Hospital Universitario Doce de Octubre Madrid, Madrid, Spain

    J L Vivanco

  10. Department of Paediatric Haematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    M Torrent & I Badell

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  1. J Salazar
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  2. A Altés
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  12. M Baiget
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  13. I Badell
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Correspondence to I Badell.

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Salazar, J., Altés, A., del Río, E. et al. Methotrexate consolidation treatment according to pharmacogenetics of MTHFR ameliorates event-free survival in childhood acute lymphoblastic leukaemia. Pharmacogenomics J 12, 379–385 (2012). https://doi.org/10.1038/tpj.2011.25

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