Chronic lymphocytic leukemia is a malignancy of mature B cells characterized by progressive lymphocytosis, lymphadenopathy, splenomegaly, and cytopenias. The progressive accumulation of leukemic B cells is a consequence of defective apoptosis and survival signals derived from the microenvironment. Progressive disease results in dysregulation of the cellular and humoral components of the effector immune system, with a resultant increase in the incidence of infectious complications, which constitutes the leading cause of morbidity and mortality in this disease. Significant therapeutic advances have been realized in recent years, especially with the development of well-tolerated targeted antibodies and kinase inhibitors. Although not curative, these therapies have resulted in significant improvements in patient outcomes with substantial increases in progression-free and overall survival intervals. Multiple novel agents are also in development with the potential to alter the treatment paradigms for this disease and ultimately to effect a cure.
DEFINITION AND EPIDEMIOLOGY
Chronic lymphocytic leukemia (CLL) is one of the most common leukemias in the Western Hemisphere. CLL is a malignant lymphoid neoplasm that is characterized by the accumulation of a population of small mature B cells. The diagnosis of CLL requires the presence of at least 5000 circulating B cells/μL, with clonality demonstrated by flow cytometry according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria.1 Over the last two centuries, significant strides have been made in the understanding of the disease pathophysiology, clinical features, and complications arising from CLL. CLL was initially described by Virchow in the 1840s concerning patients with lymph node enlargement and leukocytosis. Subsequent studies revealed the involvement of the spleen and marrow and led to the introduction of the term lymphosarcoma. Ensuing natural history studies established the malignant and clonal nature of the disease and categorized patients based on clinical presentation. Surveillance, Epidemiology, and End Results (SEER) program data from 2013 estimated the prevalence of CLL in the United States at 126,553 patients, of whom 72,569 were males. The American Cancer Society estimated 15,720 new cases of CLL in 2014, with a median age of diagnosis of 72 years. This cancer is more common in men,2 uncommon in patients younger than the age of 40 years, and extremely rare in children. The risk also increases progressively with age3 and decreases with increasing parity in women.4 It is also relatively uncommon in Asians,5 even in Asian immigrants to the Western Hemisphere,6 suggesting a possibility of a genetic predisposition. In the last few years, there has been tremendous growth in the understanding of the disease biology, which has resulted in the development of numerous new therapeutic options with resultant transformation in the management of this illness. Despite the significant improvement in the prognosis of this disease, cure currently remains elusive.
Acronyms and Abbreviations:
ABC, activated B cell; ABVD, Adriamycin, bleomycin, vinblastine, and dacarbazine; ADCC, antibody-dependent cell-mediated cytotoxicity; ADP, adenosine diphosphate; AIHA, autoimmune hemolytic anemia; ALL, ...