Alemtuzumab clearance, lymphocyte count, and T‐cell chimerism after hematopoietic stem cell transplant in sickle cell disease

Study Objective Alemtuzumab is a monoclonal antibody that targets the cell surface antigen CD52 on lymphocytes. Although it is used for the treatment of hematologic malignancies, such as chronic lymphocytic leukemia, and incorporated into many hematopoietic stem cell transplant (HSCT) conditioning r...

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Bibliographic Details
Published in:Pharmacotherapy 2022-01, Vol.42 (1), p.14-22
Main Authors: Furstenau, Dana, Peer, Cody J., Hughes, Thomas E., Uchida, Naoya, Tisdale, John, Hall, Oliver Morgan, Figg, William D., Hsieh, Matthew
Format: Article
Language:English
Subjects:
Adult
alemtuzumab
Alemtuzumab - pharmacokinetics
Anemia, Sickle Cell - metabolism
Anemia, Sickle Cell - therapy
CD14 antigen
CD3 antigen
Cell number
Cell surface
Chimerism
Chronic lymphocytic leukemia
Cyclophosphamide
Drug Elimination Routes
Graft rejection
Grafts
hematopoietic stem cell transplant
Hematopoietic Stem Cell Transplantation
Hematopoietic stem cells
Humans
Lymphatic leukemia
Lymphocyte Count
Lymphocytes
Monoclonal antibodies
Patients
Pharmacodynamics
Pharmacokinetics
Radiation
Sickle cell disease
Stem cell transplantation
T-Lymphocytes
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Summary:Study Objective Alemtuzumab is a monoclonal antibody that targets the cell surface antigen CD52 on lymphocytes. Although it is used for the treatment of hematologic malignancies, such as chronic lymphocytic leukemia, and incorporated into many hematopoietic stem cell transplant (HSCT) conditioning regimens, few studies have evaluated the pharmacology of alemtuzumab in adult patients with sickle cell disease (SCD). We therefore examined the pharmacokinetics (PK) and pharmacodynamics (PD) of alemtuzumab in adults with SCD who received a matched related donor HSCT to determine if the clearance of alemtuzumab affects transplant outcomes. Design PK and PD analysis of patient data from a single‐center clinical trial. Setting Clinical research center. Patients Twenty‐two adult patients with SCD who received one of two nonmyeloablative allogeneic HSCT regimens: alemtuzumab and total body irradiation (Alem‐TBI) or pentostatin, cyclophosphamide, alemtuzumab, and total body irradiation (Pento‐Cy‐Alem‐TBI). Measurements and Main Results Alemtuzumab serum concentrations, absolute lymphocyte counts, T‐cell (CD3), and myeloid (CD14/15) chimerism were collected at distinct time points and analyzed. A semi‐mechanistic PK population model was built to understand inter‐individual differences in pharmacology. Alemtuzumab was detectable up to 28 days post‐HSCT. The mean alemtuzumab level 7 days after transplant for patients on Alem‐TBI was 818 ng/ml, significantly lower than the mean level of 1502 ng/ml for patients on Pento‐Cy‐Alem‐TBI (p 
ISSN:0277-0008
1875-9114
DOI:10.1002/phar.2641