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Fludarabine metabolite level on day zero does not affect outcomes of hematopoietic cell transplantation in patients with normal renal function

Bone Marrow Transplantation volume 49, pages 589–591 (2014)Cite this article

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Fludarabine, an immunosuppressive and cytotoxic purine analog, is a common constituent of conditioning for hematopoietic cell transplantation (HCT). Fludarabine (F-ara-AMP) is a prodrug that is dephosphorylated in plasma to 9-beta-D-arabinosyl-2-fluoroadenine (F-ara-A). On entry into a cell, F-ara-A is phosphorylated to F-ara-ATP, which interferes with DNA replication, transcription and translation, and induces apoptosis.1, 2

Owing to variable renal clearance,3 F-ara-A levels on day 0 (immediately before graft infusion) may be variable. The clinical relevance of the F-ara-A persisting in plasma on day 0 is unknown. High day 0 levels may negatively impact the hematopoietic stem cells or lymphocytes infused with the graft, which could increase the likelihood of infections or relapse (by abrogating a graft-vs-leukemia reaction) or decrease the likelihood of GVHD. In addition, a high day 0 level may be a surrogate for a high area under the time–concentration curve (AUC), which could be associated with decreased likelihood of relapse or increased likelihood of death due to organ toxicity. The goal of this study was to assess the relationship between day 0 F-ara-A levels and clinical outcomes.

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Acknowledgements

We would like to thank the patients for participating in research that could not benefit them but only future patients. This study could not have happened without the dedication of Mamta Kantharia, Ramya Krishnan, Glennis Doiron, as well as the staff of the Alberta Blood and Marrow Transplant Program, including data managers (including Diana Quinlan and Maggie Young), inpatient and outpatient nurses (led by Lorraine Harrison, Joanne Leavitt and Naree Ager), and physicians, including Drs Douglas A. Stewart, Nancy Zacarias, Nizar Bahlis, Michelle Geddes, Mona Shafey, Loree Larratt, Minakshi Taparia and Robert Turner. This work was in part funded by Alberta Heritage Foundation for Medical Research, Canada Research Chair Program, Alberta Innovates-Health Solutions and Alberta Cancer Foundation.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Calgary & Alberta Health Services, Calgary, Alberta, Canada

    C D Griffiths, E S M Ng, S B Kangarloo, T S Williamson, M A Chaudhry, R Booker, P Duggan, P Yue, L Savoie, C Brown, N Cox-Kennett, J A Russell, A Daly & J Storek

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  1. C D Griffiths
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  2. E S M Ng
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  3. S B Kangarloo
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  4. T S Williamson
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  7. P Duggan
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  8. P Yue
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  13. A Daly
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  14. J Storek
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Correspondence to C D Griffiths.

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Griffiths, C., Ng, E., Kangarloo, S. et al. Fludarabine metabolite level on day zero does not affect outcomes of hematopoietic cell transplantation in patients with normal renal function. Bone Marrow Transplant 49, 589–591 (2014). https://doi.org/10.1038/bmt.2013.234

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