Treatment of chronic lymphocytic leukemia requires targeting of the protective lymph node environment with novel therapeutic approaches

2012 ◽  
Vol 53 (4) ◽  
pp. 537-549 ◽  
Author(s):  
Rachel E. Hayden ◽  
Guy Pratt ◽  
Claudia Roberts ◽  
Mark T. Drayson ◽  
Chris M. Bunce
Blood ◽  
1972 ◽  
Vol 40 (3) ◽  
pp. 303-310 ◽  
Author(s):  
Seth Pincus ◽  
Celso Bianco ◽  
Victor Nussenzweig

Abstract In the present study we present evidence that the proportion of complement-receptor lymphocytes (CRL) is greatly increased in the circulation in most cases of chronic lymphocytic leukemia (CLL). Lymphocytes (> 99% pure, 70% recovery) were obtained from the peripheral blood of normal individuals by separation of the mononuclear cells from the leukocyte-enriched plasma by differential flotation in Hypaque-Ficoll and incubation of the mononuclear cells with iron-containing particles followed by removal of the phagocytes with a magnet. Complement - receptor lymphocytes were detected by incubating lymphocytes with sheep erythrocytes coated with antibody and mouse complement (EAC) and counting the EAC—CRL rosettes under the microscope. 7.1 ± 3.8% of normal peripheral blood lymphocytes, 31.0 ± 6.9% of lymph node, and 59.6 ± 13.2% of tonsil lymphocytes bind EAC. The binding was C3-dependent since it could be inhibited specifically by papain fragments of rabbit antibodies to mouse C3. Among lymphocytes from the peripheral blood of patients with CLL, 50.7 ± 25.0% bear the complement receptor. These results suggest that CLL preferentially affects B cells.


Blood ◽  
2019 ◽  
Vol 133 (12) ◽  
pp. 1298-1307 ◽  
Author(s):  
Deborah M. Stephens ◽  
John C. Byrd

Abstract Chronic lymphocytic leukemia (CLL) therapy has changed dramatically with the introduction of several targeted therapeutics. Ibrutinib was the first approved for use in 2014 and now is used for initial and salvage therapy of CLL patients. With its widespread use in clinical practice, ibrutinib’s common and uncommon adverse events reported less frequently in earlier clinical trials have been experienced more frequently in real-world practice. In particular, atrial fibrillation, bleeding, infections, and arthralgias have been reported. The management of ibrutinib’s adverse events often cannot be generalized but must be individualized to the patient and their long-term risk of additional complications. When ibrutinib was initially developed, there were limited therapeutic alternatives for CLL, which often resulted in treating through the adverse events. At the present time, there are several effective alternative agents available, so transition to an alternative CLL directed therapy may be considered. Given the continued expansion of ibrutinib across many therapeutic areas, investigation of the pathogenesis of adverse events with this agent and also clinical trials examining therapeutic approaches for complications arising during therapy are needed. Herein, we provide strategies we use in real-world CLL clinical practice to address common adverse events associated with ibrutinib.


2012 ◽  
Vol 20 (4) ◽  
pp. 1360-1364 ◽  
Author(s):  
Jeffrey M. Farma ◽  
Jonathan S. Zager ◽  
Victor Barnica-elvir ◽  
Christopher A. Puleo ◽  
Suroosh S. Marzban ◽  
...  

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