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Disease-specific complications of chronic lymphocytic leukemia.

The majority of disease-specific complications in chronic lymphocytic leukemia (CLL), notably infection and autoimmunity, relate to the underlying alterations in immune function. Both cellular and humoral immunity are impaired with qualitative and quantitative defects in B cells, T cells, NK cells, neutrophils and the monocyte/macrophage lineage. Virtually all patients have reduced immunoglobulin levels, even in early stages, and this is associated with an increased frequency and severity of infection. Although prophylactic intravenous immunoglobulin may be of clinical benefit in selected patients, it does not reduce mortality and is certainly not cost-effective. Autoimmune complications occur in up to a quarter of CLL patients and predominantly target blood cells. Autoimmune hemolytic anemia (AHA) is the most common manifestation; immune thrombocytopenia, pure red cell aplasia and autoimmune neutropenia are less common, while non-hematological autoimmunity is rare. The UK CLL4 trial is the largest prospective trial in CLL to examine the significance of both a positive direct antiglobulin test (DAT) and AHA. The study confirmed the usefulness of the DAT in predicting the development of AHA or not, demonstrated that AHA occurred more frequently in patients receiving treatment with chlorambucil or fludarabine alone compared with the combination of fludarabine and cyclophosphamide, and showed that a positive DAT and the development of AHA were poor prognostic markers. Management of CLL-associated autoimmunity rests on good supportive care and the use of immunosuppressive therapies such as steroids and cyclosporine. Splenectomy remains useful, and monoclonal antibodies (rituximab and alemtuzumab) have given promising results.

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