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    Treatment must be individualized based on the clinical behavior of the disease.[17] As found in one report, CLL occurs primarily in middle-aged and elderly adults, with increasing frequency in successive decades of life.[18] The clinical course of this disease progresses from an indolent lymphocytosis without other evident disease to one of generalized lymphatic enlargement with concomitant pancytopenia.Complications of pancytopenia, including hemorrhage and infection, represent a major cause of death in these patients.[19] Immunological aberrations, including Coombs-positive hemolytic anemia, immune thrombocytopenia, and depressed immunoglobulin levels may all complicate the management of CLL.[20] Prognostic factors that may help predict clinical outcome include cytogenetic subgroup, immunoglobulin mutational status, ZAP-70, and CD38.[2,21-29] (Refer to the Prognostic Factors section in the Stage Information for Chronic Lymphocytic Leukemia section of this summary for more information.) Patients who develop an aggressive high-grade non-Hodgkin lymphoma, usually diffuse large B-cell lymphoma and termed a Richter transformation, have a poor prognosis.[30] Patients with CLL are also at increased risk for other malignancies, even before therapy.[31] A population-based analysis of almost 2 million cancer patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database suggests that cancer-specific survival for patients with pre-existing CLL who subsequently develop colorectal and breast cancer is significantly lower (hazard ratio [HR], 1.46; = .005 for breast cancer) than cancer-specific survival for patients with colorectal and breast cancer who do not have antecedent CLL, after adjusting for age, sex, race, and disease stage, and excluding CLL-related deaths.[32] Confusion with other diseases may be avoided by determination of cell surface markers.Large granular lymphocyte (LGL) leukemia is characterized by lymphocytosis with a natural killer cell immunophenotype (CD2, CD16, and CD56) or a T-cell immunophenotype (CD2, CD3, and CD8).[38-40] These patients often have neutropenia and a history of rheumatoid arthritis.The natural history is indolent, often marked by anemia and splenomegaly.

    The early recognition of infections and the institution of appropriate therapy are critical to the long-term survival of these patients.

    It is frequently advisable to control the autoimmune destruction with corticosteroids, if possible, before administering marrow-suppressive chemotherapy because the patients may be difficult to transfuse successfully with either red blood cells or platelets.

    Alternate therapies include high-dose immune globulin, rituximab, cyclosporine, azathioprine, splenectomy, and low-dose radiation therapy to the spleen.[10,11] Tumor lysis syndrome is an uncommon complication (presenting in 1 out of 300 patients) of chemotherapy for patients with bulky disease.[12] About 1% of morphologic CLL cases express T-cell markers (CD4 and CD7) and have clonal rearrangements of their T-cell receptor genes.

    These patients have a higher frequency of skin lesions, more variable lymphocyte shape, and shorter median survival (13 months) with minimal responses to chemotherapy.[13] Computed tomographic (CT) scans have a very limited role in following patients after completion of treatment; the decision to treat for relapse was determined by CT scan or ultrasound in only 2 of 176 patients in three prospective trials for the German CLL Study Group.[14] Because of the indolent nature of stage 0 chronic lymphocytic leukemia (CLL), treatment is not indicated.[1] The French Cooperative Group on CLL randomly assigned 1,535 patients with previously untreated stage A disease to receive either chlorambucil or no immediate treatment and found no survival advantage for immediate treatment with chlorambucil.[2][Level of evidence: 1ii A] A meta-analysis of six trials of immediate versus deferred therapy with chlorambucil (including the aforementioned trial by the French Cooperative Group) showed no difference in overall survival at 10 years.[3][Level of evidence: 1ii A] Whether immediate therapy with the nucleoside analogs or other newer strategies will be superior to a watchful waiting approach is uncertain.

    Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients.

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