Treatment of chronic lymphocytic leukemia (CLL) ranges from periodic observation with treatment of infectious, hemorrhagic, or immunologic complications to a variety of therapeutic options, including steroids, alkylating agents, purine analogs, combination chemotherapy, monoclonal antibodies, and transplant options. Because this disease is generally not curable, occurs in an elderly population, and often progresses slowly, it is most often treated in a conservative fashion. In asymptomatic patients, treatment may be deferred until the patient becomes symptomatic as the disease progresses. Since the rate of progression may vary from patient to patient, with long periods of stability and sometimes spontaneous regressions, frequent and careful observation is required to monitor the clinical course.
A meta-analysis of randomized trials showed no survival benefit for immediate versus delayed therapy for patients with early stage disease, nor for the use of combination regimens incorporating an anthracycline compared with a single-agent alkylator for advanced stage disease.[Level of evidence: 1iiA] A variety of clinical factors, including IgVH mutation, chromosomal abnormalities by fluorescent in situ hybridization analysis or cytogenetics, beta-2-microglobulin, and lymphocyte doubling time may be helpful in predicting progression of disease.
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Infectious complications in advanced disease are in part a consequence of the hypogammaglobulinemia and the inability to mount a humoral defense against bacterial or viral agents. Herpes zoster represents a frequent viral infection in these patients, but infections with Pneumocystis carinii and Candida albicans may also occur. The early recognition of infections and the institution of appropriate therapy are critical to the long-term survival of these patients. A randomized study of intravenous immunoglobulin (400 mg/kg every 3 weeks for 1 year) in patients with CLL and hypogammaglobulinemia produced significantly fewer bacterial infections and a significant delay in onset of first infection during the study period. There was, however, no effect on survival. Routine chronic administration of intravenous immunoglobulin is expensive, and the long-term benefit (>1 year) is unproven.[5,6]
Second malignancies and treatment-induced acute leukemias may also occur in a small percentage of patients. Transformation of CLL to diffuse large cell lymphoma (Richter syndrome) carries a poor prognosis with a median survival of less than 1 year, though 20% of the patients may live more than 5 years after aggressive combination chemotherapy. (Refer to the PDQ summary on Adult Non-Hodgkin Lymphoma Treatment for more information.)