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Oral fludarabine is an effective and convenient alternative to intravenous fludarabine in fludarabine melphalan based reduced intensity conditioning regimens

Bone Marrow Transplantation volume 55, pages 1638–1641 (2020)Cite this article

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The use of reduced intensity conditioning (RIC) in allogeneic hematopoietic stem cell transplantation (allo-HCT) has increased in the past decade, expanding access to allo-HCT for older patients or those with co-morbidities or poor performance status. RIC minimises early toxicity and permits sustained engraftment with graft versus malignancy effect [1]. Fludarabine phosphate (Flu) is a purine analogue, commonly used in combination with melphalan (FluMel) or busulfan (FluBu), in RIC regimens internationally [1].

In 1999, a pharmacokinetic study of an oral formulation (10 mg immediate-release tablet) of Flu in patients with “low-grade” non-Hodgkin’s lymphoma and B-cell chronic lymphocytic leukaemia (CLL) [2], analyzed plasma concentrations of the main metabolite of Flu, 2-fluoro-arabinofuranosyl-adenine (2F-ara-A). Oral administration resulted in a dose dependent increase in Cmax and AUC (0–24 h) of 2F-ara-A, and achieved an AUC(0–24 h) similar to intravenous (IV) administration, although at a lower Cmax. Bioavailability was ~55%, with low intraindividual variation. Following this, a prospective, multicentre, open-label phase II clinical trial of 78 previously treated CLL patients [3] was conducted, replacing 20–30 mg/m2/d of IV Flu with oral Flu 40 mg/m2/d for 5 days. This study demonstrated that oral Flu had clinical efficacy and a safety profile similar to the IV formulation.

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References

  1. Barrett A, Savani B. Stem cell transplantation with reduced-intensity conditioning regimens: a review of ten years experience with new transplant concepts and new therapeutic agents. Leukemia. 2006;20:1661.

    Article  CAS  Google Scholar 

  2. Foran JM, Oscier D, Orchard J, Johnson SA, Tighe M, Cullen MH, et al. Pharmacokinetic study of single doses of oral fludarabine phosphate in patients with “low-grade” non-Hodgkin’s lymphoma and B-cell chronic lymphocytic leukemia. J Clin Oncol. 1999;17:1574.

    Article  CAS  Google Scholar 

  3. Boogaerts M, Van Hoof A, Catovsky D, Kovacs M, Montillo M, Zinzani P, et al. Activity of oral fludarabine phosphate in previously treated chronic lymphocytic leukemia. J Clin Oncol. 2001;19:4252–8.

    Article  CAS  Google Scholar 

  4. Ruutu T, Volin L, Parkkali T, Juvonen E, Elonen E. Cyclosporine, methotrexate, and methylprednisolone compared with cyclosporine and methotrexate for the prevention of graft-versus-host disease in bone marrow transplantation from HLA-identical sibling donor: a prospective randomized study. Blood. 2000;96:2391–8.

    Article  CAS  Google Scholar 

  5. Przepiorka D, Weisdorf D, Martin P, Klingemann H, Beatty P, Hows J, et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transpl. 1995;15:825–8.

    CAS  Google Scholar 

  6. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man: a long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17.

    Article  CAS  Google Scholar 

  7. Oran B, Giralt S, Saliba R, Hosing C, Popat U, Khouri I, et al. Allogeneic hematopoietic stem cell transplantation for the treatment of high-risk acute myelogenous leukemia and myelodysplastic syndrome using reduced-intensity conditioning with fludarabine and melphalan. Biol Blood Marrow Transpl. 2007;13:454–62.

    Article  CAS  Google Scholar 

  8. Bryant A, Nivison-Smith I, Pillai E, Kennedy G, Kalff A, Ritchie D, et al. Fludarabine Melphalan reduced-intensity conditioning allotransplanation provides similar disease control in lymphoid and myeloid malignancies: analysis of 344 patients. Bone Marrow Transpl. 2014;49:17.

    Article  CAS  Google Scholar 

  9. Kröger N, Solano C, Wolschke C, Bandini G, Patriarca F, Pini M, et al. Antilymphocyte globulin for prevention of chronic graft-versus-host disease. New Engl J Med. 2016;374:43–53.

    Article  Google Scholar 

  10. von dem Borne PA, Starrenburg CW, Barge RM, Marijt EW, Falkenburg JH, Willemze R. Comparable engraftment and chimerism kinetics using oral and intravenous fludarabine as part of a reduced intensity conditioning regimen. Bone Marrow Transpl. 2008;42:137–8.

    Article  Google Scholar 

  11. Velazquez-Sanchez-de-Cima S, Zamora-Ortiz G, Hernandez-Reyes J, Rosales-Duron AD, Gonzalez-Ramirez MP, Martagon-Herrera NA, et al. Oral versus intravenous fludarabine as part of a reduced-intensity conditioning for allogeneic stem cell transplantation. Acta Haematol. 2014;132:125–8.

    Article  CAS  Google Scholar 

  12. Delgado J, Marco A, Moreno E, Pinana J, Valcarcel D, Martino R, et al. Reduced-intensity conditioning allogeneic hematopoietic cell transplantation using oral fludarabine as part of the conditioning regimen. Cytotherapy. 2009;11:356–61.

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank our clinical colleagues in the haematology department and the blood and marrow transplantation team at Royal North Shore Hospital for their contribution to patient care.

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Authors and Affiliations

  1. Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, Sydney, NSW, Australia

    Y. Lwin, J. Lindsay, C. Reid, K. Wong, I. Kerridge, C. Arthur, K. Fay, W. Stevenson & M. Greenwood

  2. Northern Clinical School, University of Sydney, Sydney, NSW, Australia

    I. Kerridge, W. Stevenson & M. Greenwood

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  1. Y. Lwin
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Correspondence to Y. Lwin.

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Lwin, Y., Lindsay, J., Reid, C. et al. Oral fludarabine is an effective and convenient alternative to intravenous fludarabine in fludarabine melphalan based reduced intensity conditioning regimens. Bone Marrow Transplant 55, 1638–1641 (2020). https://doi.org/10.1038/s41409-019-0713-z

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