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Biology of Blood and Marrow Transplantation
Article . 2017 . Peer-reviewed
License: CC BY NC ND
Data sources: Crossref
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Biology of Blood and Marrow Transplantation
Article
License: CC BY NC ND
Data sources: UnpayWall
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Pretransplant Absolute Lymphocyte Counts Impact the Pharmacokinetics of Alemtuzumab

Authors: Rebecca A, Marsh; Tsuyoshi, Fukuda; Chie, Emoto; Lisa, Neumeier; Pooja, Khandelwal; Sharat, Chandra; Ashley, Teusink-Cross; +2 Authors

Pretransplant Absolute Lymphocyte Counts Impact the Pharmacokinetics of Alemtuzumab

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.

Keywords

Transplantation Conditioning, Adolescent, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease, Infant, Antineoplastic Agents, Immunological, Child, Preschool, Humans, Lymphocyte Count, Prospective Studies, Child, Alemtuzumab, Melphalan, Vidarabine, Half-Life

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
26
Top 10%
Top 10%
Top 10%
hybrid