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Chronic lymphocytic leukemia (CLL) is a neoplastic disease characterized by the accumulation of a monoclonal population of small, mature-appearing CD5+ B lymphocytes in the blood, marrow, and lymphoid tissues. The causes of this disease are unknown, although genetic factors have been found to play a role. The median age of onset is approximately 67 years and men are affected twice as often as women. Lymphadenopathy occurs in approximately 80 percent and splenomegaly in approximately 50 percent of patients at the time of diagnosis. The leukemic cells from most CLL patients have clonal chromosomal abnormalities, of which del 13q14-23.1 is the most common, followed in frequency by trisomy 12, del 11q22.3-q23.1, del 6q21-q23, del 17p13.1, and 14q abnormalities. There is a wide variation in the rate of clinical progression. Many patients are asymptomatic at the time of diagnosis and are observed without treatment until they develop symptoms or evidence of disease progression. Chlorambucil and prednisone had been the mainstay of treatment for approximately 45 years. Deoxyadenosine analogues, such as fludarabine; newer alkylating agents, such as bendamustine; and monoclonal antibodies, notably alemtuzumab and rituximab, alone or in combination with purine analogues, alkylating agents, or glucocorticoids, have improved treatment response rates. Nonmyeloablative hematopoietic stem cell transplantation can be used selectively for some patients and experimental immune-gene therapy may be available in the future. The advanced age of most patients and associated comorbidities requires careful analysis to ensure that therapy will likely provide a net benefit to the patient. Prolymphocytic leukemia is the involvement of blood and marrow with a less-mature-appearing clonal population of lymphocytes, most of which have a lymphoblast appearance. The immune phenotype may be that of a B cell or, less frequently, a T cell. The disease is more aggressive than CLL. Rearrangements and mutations in the ataxia-telangiectasia mutated gene and in T-cell leukemia-1 and related genes apparently contribute to the pathogenesis of T-cell prolymphocytic leukemia. Approximately one-third of patients have erythroderma. Treatment with deoxyadenosine analogues can be effective in a subset of patients with this disease. Investigation into the use of new agents, stem cell transplantation, and/or monoclonal antibodies, such as alemtuzumab, is ongoing, as there are no established cures for T-cell prolymphocytic leukemia.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: ATM gene, ataxia-telangiectasia mutated gene; BCL-1, B-cell leukemia 1; β2M, β2-microglobulin; CAP, cyclophosphamide, doxorubicin, and prednisone without vincristine; CCP, cladribine in combination with cyclophosphamide and prednisone; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; CLL, chronic lymphocytic leukemia; CR, complete remission; CRi, complete remission with incomplete resolution of cytopenias; CVP, cyclophosphamide, vincristine, and prednisone; DiSC, differential staining cytotoxicity; FC, fludarabine, cyclophosphamide; FCR, fludarabine, cyclophosphamide, and rituximab; FDA, U.S. Food and Drug Administration; FISH, fluorescence in situ hybridization; GFR, glomerular filtration rate; GM-CSF, granulocyte-macrophage colony-stimulating factor; HCV, type C hepatitis virus; HTLV-I, human T-cell lymphotropic virus type I; Ig, immunoglobulin; IgHV, immunoglobulin heavy chain variable region; IV, intravenous; LDT, lymphocyte doubling time; ...

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