Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Deferasirox increases BU blood concentrations

Bone Marrow Transplantation volume 47, pages 315–316 (2012)Cite this article

BU is commonly used in combination with fludarabine or CY for conditioning before hematopoietic SCT due to a favorable toxicity profile.1, 2 However, as the pharmacokinetics (PK) of BU can be unpredictable there is inter-patient variability in the systemic concentrations of the drug after weight-based dosing. Supra-therapeutic levels may increase the risk of non-relapse mortality,3 whereas sub-therapeutic levels may lead to disease relapse.4 Therapeutic drug monitoring has been attempted to tailor the dose for each patient and achieve a target area under the curve (AUC).5 For this reason, blood sampling strategies have been adopted to determine the BU dose required to achieve a desired target AUC.6 Although the exact mechanism of BU metabolism is unknown, it is believed that the drug undergoes glucuronidation and subsequent metabolism through the liver.7 Therefore, there is potential for drug–drug interactions that may increase or decrease the clearance of BU. Newer drugs are now being introduced into the SCT arena, but their effect on BU metabolism remains unknown. We describe a case that demonstrates the significant effect of deferasirox on BU blood concentrations.

A 59-year-old female with a 4-year history of transfusion-dependent hypoplastic MDS resistant to treatment with immunosuppression was referred for allo-SCT from a matched related donor after progression to refractory anemia with excess of blasts 2 (RAEB-2). At 2 weeks before a myeloablative transplant conditioned with the FluBu regimen, she was electively admitted to receive a BU test dose at 0.8 mg/kg administered intravenously. The target AUC for the pre-transplant test dose is 1200 μM min. This patient was given 48 mg of BU after which eight blood samples were drawn to determine her BU AUC. Blood samples were processed and shipped to the Seattle BU PK Laboratory for analysis. Her AUC was reported as 1868 μM min with a BU clearance rate of 1.74 mL/min/kg. On the basis of these results, a 124-mg dose would be given for each daily dose for the conditioning regimen. Her AUC was noted to be higher than expected, especially given the absence of any liver dysfunction or known drug interactions extrapolated from patient history that would increase the levels. The patient was re-admitted after 1 month to start her preparative regimen. There were no documented changes in her home medications based on a discussion with the patient and her family. PK studies were again conducted for the first of four doses of BU for the conditioning regimen. The target AUC for each dose of the conditioning regimen is 4800 μM min. Her AUC was reported as 4692 μM min with a clearance rate of 2.76 mL/min/kg, both of which correlated with normal and expected values for the patient. On the basis of these results, the dose for SCT would be 215 mg, twice the dose that was determined pre-transplant.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Chunduri S, Dobogai LC, Peace D, Saunthararajah Y, Quigley J, Chen YH et al. Fludarabine/i.v. BU conditioning regimen: myeloablative, reduced intensity or both? Bone Marrow Transplant 2008; 41: 935–940.

    Article  CAS  PubMed  Google Scholar 

  2. Andersson BS, de Lima M, Thall PF, Wang X, Couriel D, Korbling M et al. Once daily i.v. busulfan and fludarabine (i.v. Bu-Flu) compares favorably with i.v. busulfan and cyclophosphamide (i.v. BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant 2008; 14: 672–684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Geddes M, Kangarloo SB, Naveed F, Quinlan D, Chaudhry MA, Stewart D et al. High busulfan exposure is associated with worse outcomes in a daily i.v. busulfan and fludarabine allogeneic transplant regimen. Biol Blood Marrow Transplant 2008; 14: 220–228.

    Article  CAS  PubMed  Google Scholar 

  4. Slattery JT, Clift RA, Buckner CD, Radich J, Storer B, Bensinger WI et al. Marrow transplantation for chronic myeloid leukemia: the influence of plasma busulfan levels on the outcome of transplantation. Blood 1997; 89: 3055–3060.

    CAS  Google Scholar 

  5. Andersson BS, Thall PF, Madden T, Couriel D, Wang X, Tran HT et al. Busulfan systemic exposure relative to regimen-related toxicity and acute graft-versus-host disease: defining a therapeutic window for i.v. BuCy2 in chronic myelogenous leukemia. Biol Blood Marrow Transplant 2002; 8: 477–485.

    Article  CAS  PubMed  Google Scholar 

  6. Beri R, Chunduri S, Sweiss K, Peace DJ, Mactal-Haaf C, Dobogai LC et al. Reliability of a pretransplant i.v. BU test dose performed 2 weeks before myeloablative FluBu conditioning regimen. Bone Marrow Transplant 2010; 45: 249–253.

    Article  CAS  PubMed  Google Scholar 

  7. McCune JS, Gibbs JP, Slattery JT . Plasma concentration monitoring of busulfan: does it improve clinical outcome? Clin Pharmacokinet 2000; 39: 155–165.

    Article  CAS  PubMed  Google Scholar 

  8. Yang LP, Keam SJ, Keating GM . Deferasirox: a review of its use in the management of transfusional chronic iron overload. Drugs 2007; 67: 2211–2230.

    Article  CAS  PubMed  Google Scholar 

  9. Stumpf JL . Deferasirox. Am J Health Syst Pharm 2007; 64: 606–616.

    Article  CAS  PubMed  Google Scholar 

  10. Majhail NS, Lazarus HM, Burns LJ . Iron overload in hematopoietic cell transplantation. Bone Marrow Transplant 2008; 41: 997–1003.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Hematology/Oncology, Chicago, IL, USA

    K Sweiss, P Patel & D Rondelli

  2. Cancer Center, University of Illinois at Chicago, Chicago, IL, USA

    D Rondelli

Authors
  1. K Sweiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Rondelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D Rondelli.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sweiss, K., Patel, P. & Rondelli, D. Deferasirox increases BU blood concentrations. Bone Marrow Transplant 47, 315–316 (2012). https://doi.org/10.1038/bmt.2011.75

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2011.75

This article is cited by

Search

Advanced search

Quick links