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About the Authors:
Jiahui Yang
Affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Sivasubramanian Baskar
Affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Ka Yin Kwong
Affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Michael G. Kennedy
Affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Adrian Wiestner
Affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Christoph Rader
* E-mail: [email protected]
Affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Introduction
Chronic lymphocytic leukemia (CLL) is characterized by the presence of a monoclonal B-cell population with a count of >5,000 cells/µL in the peripheral blood [1], [2]. In the United States of America, CLL is the most common leukemia with roughly 15,000 new cases and 5,000 deaths per year. Whereas approximately half of CLL patients have an indolent clinical course that does not require treatment for many years, a more aggressive clinical course that necessitates treatment within a few years is diagnosed for the other half. These differences in clinical course correlate with molecular markers, including the mutational status of the surface immunoglobulins and the expression of intracellular tyrosine kinase ZAP-70. Despite a typically lower expression of CD20 compared to normal B cells, the combination of fludarabine and cyclophosphamide (FC) with the chimeric mouse/human anti-CD20 IgG1 monoclonal antibody (mAb) rituximab (FCR) [3] has become standard first-line treatment that was approved by the Food and Drug Administration (FDA) in 2010. In addition, alemtuzumab, a humanized anti-CD52 IgG1 mAb, was FDA-approved in 2001 as single agent for CLL therapy. Alemtuzumab is frequently used for second-line treatment, but is ineffective in CLL patients with bulky lymphadenopathy. In 2009, fully human IgG1 mAb ofatumumab, which binds to a CD20 epitope different from rituximab, was FDA-approved for treating CLL patients refractory to fludarabine and alemtuzumab.
With...