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Therapy

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts and treatment outcome in children with B-progenitor-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study

Leukemia volume 19, pages 533–536 (2005)Cite this article

Abstract

We reported that children with B-progenitor-cell acute lymphoblastic leukemia (BpALL) treated in the early 1980s whose lymphoblasts accumulated high levels of methotrexate (MTX) and of methotrexate polyglutamates (MTXPGs) in vitro had an improved 5-year event-free survival (EFS) (65% (standard error (s.e.) 12%) vs 22% (s.e. 9%)). We repeated this study in children with BpALL treated in the early 1990s. The major change in treatment was the addition of 12 24-h infusions of 1 g/M2 MTX with leucovorin rescue (IDMTX). In 87 children treated on Pediatric Oncology Group (POG) study 9005 and POG 9006, the 5-year EFS for those whose lymphoblasts accumulated high levels of MTX and MTXPGs (79.2%, s.e. 8.3%) was not significantly different from that of patients with lesser accumulation of MTX and MTXPGs (77.7%, s.e. 5.4%). These findings support the notion that higher dose MTX therapy has contributed to increased cure, particularly for patients whose lymphoblasts accumulate the drug less well.

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Acknowledgements

This research was supported in part by the following grants from the National Cancer Institute: CA-33587, CA-25408, CA-32053, CA-03161, CA-29139, CA-53490, CA-33625, CA-29691, CA-28841, CA-31566, CA-52317 and CA-15989. In addition, it was supported by grants from the National Cancer Institute of Canada, the Cancer Research Society and the McGill University – Montreal Children's Hospital Research Institute, and assisted by the Penny Cole Fund, the Fast Foundation, the InterService Clubs Council Telethon of Stars, the Lamplighters Children's Cancer-Leukemia Association, the Children's Cancer Fund, the Debbie Saunders Fund, the friends of Ande, the Midwest Athletes against Childhood Cancer (MACC Fund), the American Lebanese Syrian Associated Charities (ALSAC) and the American Cancer Society.

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Authors and Affiliations

  1. The Penny Cole Hematology Research Laboratory, McGill University – Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada

    V M Whitehead, M J Vuchich & C Payment

  2. Department of Pediatrics, McGill University, Montreal, PQ, Canada

    V M Whitehead & P A Koch

  3. Department of Statistics, College of Medicine, The Children's Oncology Group Research Data Center, University of Florida, Gainesville, FL, USA

    J J Shuster

  4. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    D H Mahoney Jr

  5. Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA

    S J Lauer

  6. Department of Pediatrics, Section of Medical Genetics, Children's Mercy Hospital, Kansas City, MO, USA

    L D Cooley

  7. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    A T Look

  8. Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA

    D J Pullen

  9. Department of Pediatrics, Midwest Children's Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA

    B Camitta

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  1. V M Whitehead
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  2. J J Shuster
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  7. P A Koch
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  9. A T Look
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  11. B Camitta
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Correspondence to V M Whitehead.

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Whitehead, V., Shuster, J., Vuchich, M. et al. Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts and treatment outcome in children with B-progenitor-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study. Leukemia 19, 533–536 (2005). https://doi.org/10.1038/sj.leu.2403703

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