Disease-Specific Complications of Chronic Lymphocytic Leukemia

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Hematology 2008

Disease-Specific Complications of Chronic Lymphocytic Leukemia

Dearden1

Correspondence: Dr Dearden BSc MD FRCP FRCPath, Department of

Haemato-Oncology, The Royal Marsden NHS Foundation Trust and Institute of Cancer

Research, Downs Road, Sutton, Surrey, SM2 5PT, UK; Phone: +44 208 661 3655; Fax:

+44 208 642 9634.

Abstract

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.