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Chronic Lymphocytic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - General Information About Chronic Lymphocytic Leukemia

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Confusion with other diseases may be avoided by determination of cell surface markers. CLL lymphocytes coexpress the B-cell antigens CD19 and CD20 along with the T-cell antigen CD5.[32] This coexpression only occurs in one other disease entity, mantle cell lymphoma. CLL B cells express relatively low levels of surface-membrane immunoglobulin (compared with normal peripheral blood B cells) and a single light chain (kappa or lambda).[15] CLL is diagnosed by an absolute increase in lymphocytosis and/or bone marrow infiltration coupled with the characteristic features of morphology and immunophenotype, which confirm the characteristic clonal population.

The differential diagnosis must exclude hairy cell leukemia and Waldenström macroglobulinemia. (Refer to the PDQ summaries on Hairy Cell Leukemia and Adult Non-Hodgkin Lymphoma Treatment for more information.) Waldenström macroglobulinemia has a natural history and therapeutic options similar to CLL, with the exception of hyperviscosity syndrome associated with macroglobulinemia as a result of elevated immunoglobulin M. Prolymphocytic leukemia (PLL) is a rare entity characterized by excessive prolymphocytes in the blood with a typical phenotype that is positive for CD19, CD20, and surface-membrane immunoglobulin and negative for CD5. These patients demonstrate splenomegaly and poor response to low-dose or high-dose chemotherapy.[15,33]

Cladribine (2-chlorodeoxyadenosine) appears to be an active agent (60% complete remission rate) for patients with de novo B-cell prolymphocytic leukemia.[34][Level of evidence: 3iiiDiv] Alemtuzumab (campath-1H), an anti-CD52 humanized monoclonal antibody, has been used for 76 patients with T-cell prolymphocytic leukemia after failure of prior chemotherapy (usually pentostatin or cladribine) with a 51% response rate (95% confidence interval, 40%–63%) and median time to progression of 4.5 months (range, 0.1–45.4 months).[35][Level of evidence: 3iiiDiv] These response rates have been confirmed by other investigators.[36] Patients with CLL who show prolymphocytoid transformation maintain the classic CLL phenotype and have a worse prognosis than PLL patients.

Large granular lymphocytic leukemia is characterized by lymphocytosis with a natural killer cell immunophenotype (CD2, CD16, and CD56) or a T-cell immunophenotype (CD2, CD3, and CD8).[37,38,39] These patients often have neutropenia and a history of rheumatoid arthritis. The natural history is indolent, often marked by anemia and splenomegaly. This condition appears to fit into the clinical spectrum of Felty syndrome.[40] Therapy includes low doses of oral cyclophosphamide or methotrexate, cyclosporine, and treatment of the bacterial infections acquired during severe neutropenia.[37,39,41,42]

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