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Conditioning Regimens

Targeted i.v. BU and fludarabine (t-i.v. BU/Flu) provides effective control of AML in adults with reduced toxicity

Bone Marrow Transplantation volume 46, pages 641–649 (2011)Cite this article

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Abstract

Myeloablative doses of BU and fludarabine followed by allogeneic hematopoietic cell transplantation offer effective therapy for AML. We anticipated that pharmacokinetic targeting of i.v. BU to 5300 μ/L min/day × 4 (targeted i.v. BU and fludarabine (t-i.v. BU/Flu)) would limit nonrelapse mortality (NRM) in adults up to 70 years of age. We assessed the safety and efficacy of t-i.v. BU/Flu in a series of 100 adults (median age 48, range 22–69 years) with AML in the first CR (CR1) with high risk of treatment failure (n=49), second CR (CR2, n=25), relapsed disease (REL, n=9), primary induction failure (PIF, n=16) and untreated (n=1). NRM was 3% at 100 days and 15% at 1 year. The cumulative incidence of relapse was 30.6% for CR1, 41.7% for CR2, 55.6% for REL and 58.6% for PIF. OS for primary AML in CR1 was 66% (95% confidence interval (CI): 46–80%) at 1 year, and 62% (95% CI: 42–77%) at 2 years. On multivariable modeling, remission status, moderate/severe chronic GVHD and day-90 BM chimerism ⩾90% predicted improved OS. Importantly, there was no effect of age. t-i.v. BU/Flu provides effective disease control with encouraging NRM in patients up to age of 70 years.

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Authors and Affiliations

  1. Department of Blood and Marrow Transplantation, University of South Florida, Tampa, FL, USA

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

  2. Department of Oncological Sciences, University of South Florida, Tampa, FL, USA

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

  3. Department of Biostatistics, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA

    J Kim

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C Anasetti and J Perkins have received research support from PDL Biopharma for conducting research on targeted BU conditioning. The remaining authors declare no conflict of interest.

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Pidala, J., Kim, J., Anasetti, C. et al. Targeted i.v. BU and fludarabine (t-i.v. BU/Flu) provides effective control of AML in adults with reduced toxicity. Bone Marrow Transplant 46, 641–649 (2011). https://doi.org/10.1038/bmt.2010.190

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