1. Safety and Efficacy of Targeted-Dose Busulfan and Bortezomib as a Conditioning Regimen for Patients with Relapsed Multiple Myeloma Undergoing a Second Autologous Blood Progenitor Cell Transplantation 
César O. Freytes, Juan J. Toro, Rosa F. Yeh, Edward A. Stadtmauer, Voravit Ratanatharathorn, Görgün Akpek, Entezam Sahovic, Guido J. Tricot, Paul J. Shaughnessy, Darrell J. White, Tulio E. Rodriguez, Scott R. Solomon, Louie H. Yu, Cathy Zhao, Shiva Patil, Elizabeth Armstrong, Angela Smith, Agnes Elekes, Kazunobu Kato, Donna E. Reece 
Biology of Blood and Marrow Transplantation 
Volume 20, Issue 12, Pages (December 2014)
DOI: /j.bbmt
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2. Figure 1
Preconditioning test pharmacokinetics (PK) (first PK) and conditioning regimen. A test dose, .8 mg/kg, of i.v. busulfan (Bu) based on actual body weight (BW) or adjusted ideal BW was administered over 2 hours between days −12 and −9. Plasma samples were used to calculate Bu concentrations at the laboratory of Seattle Cancer Care Alliance. Bu exposure was measured as area under the curve (AUC) using WinNonlin software and the individualized daily dose for the conditioning regimen was calculated as: (test PK dose/test PK AUC) × target daily AUC, to achieve 20,000 μM × minute as a total AUC, including the AUC exposure from the test PK. The individualized dose of i.v. Bu was administered over 3 hours once daily from day −5 through day −2. The second PK (confirmatory PK) was performed on day −5. Only when confirmatory PK analysis indicated that Bu exposure would be outside the target range were doses on days −3 and −2 adjusted. Bortezomib (1.3 mg/m2 once daily) was administered as a 3 to 5-second bolus i.v. injection on day −1.
Biology of Blood and Marrow Transplantation  , DOI: ( /j.bbmt )
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3. Figure 2
Pharmacokinetics (PK) sampling times for preconditioning test PK (first PK) and confirmatory PK (second PK). For test PK, 6 serial blood samples were drawn at the end of infusion (EOI) after a 2-hour infusion of i.v. Bu, EOI + 15 minutes, EOI + 30 minutes, and 4, 5, and 6 hours after the start of the infusion of intravenous (i.v.) Bu. For the confirmatory PK, plasma samples were collected at the EOI after a 3-hour infusion of i.v. Bu, EOI + 15 minutes, EOI + 30 minutes, 4.5, 6, and 8 hours after start of the infusion of i.v. Bu.
Biology of Blood and Marrow Transplantation  , DOI: ( /j.bbmt )
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4. Figure 3
(A) Preconditioning test pharmacokinetics (PK) results. After a test i.v. Bu dose of .8 mg/kg, 40% of patients had an area under the curve (AUC) outside of the expected range: n = 11 (<1000 μM × minute) or n = 1 (>1500 μM × minute). (B) Total estimated AUC from preconditioning test PK and 4-day conditioning. Histograms indicate total Bu AUC exposure from a test dose (.8 mg/kg) and from 4-day administration during the conditioning regimen using individualized doses of i.v. Bu. The total estimated AUC exposure over 5 days fell within the target range (AUC, 20,000 μM × minute ± 20%).
Biology of Blood and Marrow Transplantation  , DOI: ( /j.bbmt )
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