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Pretransplant Absolute Lymphocyte Counts Impact the Pharmacokinetics of Alemtuzumab.

Authors
  • Marsh, Rebecca A1
  • Fukuda, Tsuyoshi2
  • Emoto, Chie2
  • Neumeier, Lisa3
  • Khandelwal, Pooja3
  • Chandra, Sharat3
  • Teusink-Cross, Ashley3
  • Vinks, Alexander A2
  • Mehta, Parinda A3
  • 1 Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio. Electronic address: [email protected]
  • 2 Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio; Division of Pharmacology, Cincinnati Children's Hospital, Cincinnati, Ohio.
  • 3 Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio.
Type
Published Article
Journal
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
Publication Date
Apr 01, 2017
Volume
23
Issue
4
Pages
635–641
Identifiers
DOI: 10.1016/j.bbmt.2017.01.071
PMID: 28089878
Source
Medline
Keywords
License
Unknown

Abstract

Alemtuzumab is frequently used as part of reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic cell transplantation (HCT) in pediatric patients with nonmalignant diseases. We previously suggested an optimal day 0 targeted range of alemtuzumab, but there are no pediatric data regarding the pharmacokinetics (PK) of subcutaneous alemtuzumab to guide precision dosing trials. The goal of this study was to prospectively characterize alemtuzumab PK and to explore absolute lymphocyte count (ALC) as a predictor of interindividual variability. We prospectively enrolled 23 patients who received an alemtuzumab, fludarabine, and melphalan RIC regimen. Seventeen patients completed study and received 1 mg/kg alemtuzumab divided over 5 days subcutaneously, starting on day -14. The median age was 7 years (range, .5 to 18). Blood sampling for PK measurements and descriptive PK analyses were performed. The median maximum alemtuzumab concentration was 2.39 µg/mL (interquartile range, 1.98 to 2.92). The median terminal half-life was 5.2 days (interquartile range, 2.7 to 7.8). The median concentration at day 0 was 1.27 µg/mL (interquartile range, .35 to 1.51). Importantly, day 0 alemtuzumab levels and area under the curve negatively correlated with predose ALC and ALC area-time, respectively. In conclusion, we reported the PK of subcutaneous alemtuzumab given to pediatric allogeneic HCT patients and observed that almost all patients have persistence of lytic levels of alemtuzumab beyond day 0, at levels in excess of that needed to reduce the risk of acute graft-versus-host disease. Additionally, levels correlate with pretransplant ALC. These results will allow the development of population PK models for precision dosing trials.

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