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Post-Transplant Events

Folic acid supplementation during methotrexate immunosuppression is not associated with early toxicity, risk of acute graft-versus-host disease or relapse following hematopoietic transplantation

Bone Marrow Transplantation volume 37, pages 687–692 (2006)Cite this article

Abstract

Methotrexate (MTX) is used as an immunosuppressive agent for acute graft-versus-host disease (GVHD) prophylaxis following hematopoietic cell transplantation (HCT). Concerns that folate intake may impair MTX effectiveness or selectively rescue leukemic cells have led to variations in clinical practice regarding supplemental folic acid during MTX administration. A retrospective, observational study was undertaken to determine the association between folic acid intake (days 0–18 post transplant) and MTX toxicity and efficacy following HCT. The study population consisted of 311 adult patients who received a myeloablative HCT for chronic myelogenous leukemia, all four scheduled doses of MTX, and did not require leucovorin rescue. Multiple linear regression models were used to assess the relationships between folic acid intake (days 0–18 post-HCT) and oral mucositis index (OMI) scores, time to engraftment and risk of detectable acute GVHD. No statistically significant differences in mean OMI scores, time to engraftment, risk of acute GVHD, days to acute GVHD, risk of relapse or survival were observed when comparing patients taking, on average, <400 (14%), 400 (58%) or >400 μg (28%) folic acid per day. Our results suggest that concurrent folic acid supplementation does not change MTX effectiveness or toxicity in this patient population.

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Acknowledgements

This project would not have been possible without the support of colleagues from the Fred Hutchinson Cancer Research Center, Seattle, WA, USA including clinical data support from Gary Schoch, and clinical nutrition data from the Seattle Cancer Care Alliance Clinical Nutrition Staff. And, we are extremely grateful to the patients who consented to participate in this, and other, research studies. Research Program Project Grant (P01) funding was provided by the National Heart, Lung and Blood Institute (HL36444) and the National Cancer Institute (CA18029) and a Cancer Center Support Grant (P30) from the National Cancer Institute (CA15704). Support for KR was provided by National Cancer Institute training grant R25 CA94880.

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Authors and Affiliations

  1. Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    K Robien, J D Potter & C M Ulrich

  2. Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA

    K Robien

  3. University of Minnesota Cancer Center, Minneapolis, MN, USA

    K Robien

  4. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    M M Schubert, P Martin & R Storb

  5. Department of Public Health Sciences, University of Alberta, Edmonton, AB, Canada

    Y Yasui

  6. Department of Epidemiology, University of Washington, Seattle, WA, USA

    J D Potter & C M Ulrich

Authors
  1. K Robien
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  2. M M Schubert
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  3. Y Yasui
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  4. P Martin
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  5. R Storb
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  6. J D Potter
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  7. C M Ulrich
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Corresponding author

Correspondence to K Robien.

Additional information

Presented as an oral and poster presentation at the 13th International Symposium on the Chemistry and Biology of Pteridines and Folates, Egmond aan Zee, the Netherlands, 2005.

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Robien, K., Schubert, M., Yasui, Y. et al. Folic acid supplementation during methotrexate immunosuppression is not associated with early toxicity, risk of acute graft-versus-host disease or relapse following hematopoietic transplantation. Bone Marrow Transplant 37, 687–692 (2006). https://doi.org/10.1038/sj.bmt.1705303

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