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Kinetics of CLL cells in tissues and blood during therapy with the BTK inhibitor ibrutinib.
- Source :
-
Blood [Blood] 2014 Jun 26; Vol. 123 (26), pp. 4132-5. Date of Electronic Publication: 2014 May 14. - Publication Year :
- 2014
-
Abstract
- The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has excellent clinical activity in patients with chronic lymphocytic leukemia (CLL). Characteristically, ibrutinib causes CLL cell redistribution from tissue sites into the peripheral blood during the initial weeks of therapy. To better characterize the dynamics of this redistribution phenomenon, we correlated serial lymphocyte counts with volumetric changes in lymph node and spleen sizes during ibrutinib therapy. Kinetic parameters were estimated by applying a mathematical model to the data. We found that during ibrutinib therapy, 1.7% ± 1.1% of blood CLL cells and 2.7% ± 0.99% of tissue CLL cells die per day. The fraction of the tissue CLL cells that was redistributed into the blood during therapy was estimated to be 23.3% ± 17% of the total tissue disease burden. These data indicate that the reduction of tissue disease burden by ibrutinib is due more to CLL cell death and less to egress from nodal compartments.<br /> (© 2014 by The American Society of Hematology.)
- Subjects :
- Adenine analogs & derivatives
Agammaglobulinaemia Tyrosine Kinase
Aged
Aged, 80 and over
Female
Humans
Male
Middle Aged
Neoplastic Cells, Circulating metabolism
Neoplastic Cells, Circulating pathology
Piperidines
Leukemia, Lymphocytic, Chronic, B-Cell blood
Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
Leukemia, Lymphocytic, Chronic, B-Cell enzymology
Leukemia, Lymphocytic, Chronic, B-Cell pathology
Models, Biological
Protein Kinase Inhibitors administration & dosage
Protein-Tyrosine Kinases antagonists & inhibitors
Pyrazoles administration & dosage
Pyrimidines administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 123
- Issue :
- 26
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 24829205
- Full Text :
- https://doi.org/10.1182/blood-2014-02-554220