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Conditioning Regimens

Pharmacokinetic targeting of i.v. BU with fludarabine as conditioning before hematopoietic cell transplant: the effect of first-dose area under the concentration time curve on transplant-related outcomes

Bone Marrow Transplantation volume 46, pages 1418–1425 (2011)Cite this article

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Abstract

We used pharmacokinetic (PK) targeting of BU in 145 consecutive patients treated with fludarabine and i.v. BU. BU was given once daily at 130 mg/m2 per day on days 1 and 2; doses for days 3 and 4 were adjusted in 92 patients (63%) to an average daily area under the concentration-time curve (AUC) of 5300 μM/min. In the remaining 53 patients, the first-dose AUC was within the target range and no dosing adjustments were required. First-dose AUC, maximum concentration and clearance were not correlated with age, race, ethnicity, performance status, or hematopoietic cell transplant comorbidity index. Women had higher clearance than men (median 2.9 vs 2.5 mL/min/kg; P=0.001). BU toxicities were not associated with first-dose AUC or any other PK parameter measured. First-dose BU AUC was not associated with non-relapse mortality (NRM) or survival, but higher AUC was predictive of relapse. We did not find an increased risk of toxicity or NRM in patients with high first-dose AUC presumably because of the dose adjustment. We conclude that PK targeting of BU as described here provides a simple, safe and effective method of delivering high BU doses before transplantation in a wide variety of patients.

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Author notes

  1. J Perkins and T Field: These authors contributed equally to this work.

Authors and Affiliations

  1. Blood and Marrow Transplant Program, H. Lee Moffitt Cancer Center, Tampa, FL, USA

    J Perkins, T Field, M A Kharfan-Dabaja, E Ayala, L Perez, H Fernandez & C Anasetti

  2. Biostatistics Core, H. Lee Moffitt Cancer Center, Tampa, FL, USA

    J Kim

  3. Department of Pharmacy, H. Lee Moffitt Cancer Center, Tampa, FL, USA

    K Fancher & C Tate

  4. Clinical Toxicology Laboratory, University of Pennsylvania Medical Center, Philadelphia, PA, USA

    L M Shaw, M C Milone, J A Gardiner & S Miller

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Correspondence to J Perkins.

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Competing interests

Janelle Perkins, Teresa Field and Claudio Anasetti received research support from PDL Biopharma for this project.

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Supplementary Information accompanies the paper on Bone Marrow Transplantation website

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Perkins, J., Field, T., Kim, J. et al. Pharmacokinetic targeting of i.v. BU with fludarabine as conditioning before hematopoietic cell transplant: the effect of first-dose area under the concentration time curve on transplant-related outcomes. Bone Marrow Transplant 46, 1418–1425 (2011). https://doi.org/10.1038/bmt.2010.315

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