Elsevier

Seminars in Oncology

Volume 33, Issue 2, April 2006, Pages 230-239
Seminars in Oncology

Autoimmune Complications of Chronic Lymphocytic Leukemia

https://doi.org/10.1053/j.seminoncol.2006.01.011Get rights and content

Autoimmune complications are common in chronic lymphocytic leukemia (CLL), occurring in up to a quarter of all patients during the course of the illness. By far the most common manifestation is autoimmune hemolytic anemia (AIHA), followed by immune thrombocytopenia (ITP). It is not true to say that autoimmunity is confined to the formed elements of the blood since conditions such as paraneoplastic pemphigus and acquired angioedema do occur in CLL, but nonhematologic autoimmunity is very rare indeed. The pathogenesis of autoimmunity in CLL is unknown. It may be related to the ability of the CLL cells to act as antigen-presenting cells (APCs), and to process antigen (particularly the Rh protein) so as to reveal cryptic peptides that are seen as foreign by helper T cells. It is likely that a failure of regulatory T-cell function is also involved. Autoimmune episodes may be triggered by treatment, particularly with purine analogues. Such episodes are often severe and may be fatal. Treatment of CLL-associated autoimmunity follows conventional protocols, but non-response to primary treatments is not uncommon. Promising results have been obtained with cyclosporine and rituximab.

Section snippets

Clinical Features

Autoimmunity in CLL is overwhelmingly AIHA. This section is not a comprehensive description of this condition, which can be found in standard text books, but a reminder of clinical features that are all too often forgotten. Even though AIHA is so common in CLL the diagnosis is frequently missed. A direct antiglobulin test (DAT) should be part of the standard work-up of all patients with CLL, and it should be repeated whenever the patient becomes anemic and before each round of treatment.

The

Autoantibodies Produced by Tumor Cells

The simplest explanation for autoimmunity in CLL is that the tumor cells are manufacturing the autoantibody. The CLL cell does secrete immunoglobulin. Using a sensitive radioassay, Stevenson et al30 demonstrated secretion of small amounts of idiotypic IgM by CLL cells. The immunoglobulin secreted by CLL cells is often autoreactive. Stimulation by phorbol ester induced the CLL cells from 12 of 14 patients to secrete IgM that reacted with a variety of autoantigens, including the Fc portion of

Treatment

There are very few data addressing the problem of how to treat the autoimmune complications of CLL. In general, treatment has been the same as when the disease occurs spontaneously. However, some treatments are less appropriate and there is also the question of whether and how to treat the CLL itself. The possibility that the immunosuppression caused by the disease or its treatment has triggered the autoimmunity has to be weighed against the prospect that treating the disease will eliminate the

Conclusion

The autoimmune complications of CLL appear to be a feature of the failing immune system, and may well be chiefly attributed to the loss of regulatory T cells, which is made worse by most forms of treatment, especially when it involves the use of purine analogues. The particular pattern of autoimmunity, mainly involving the destruction of the formed elements of the blood, may be related to the ability of the CLL cell to act as an APC. Autoimmune complications are frequently severe and may be

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