The immunodeficiency of chronic lymphocytic leukaemia

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British Medical Bulletin Advance Access published online on August 27, 2008

British Medical Bulletin, doi:10.1093/bmb/ldn034

The immunodeficiency of chronic lymphocytic leukaemia

A. D. Hamblin and T. J. Hamblin*

Cancer Sciences Division, University of Southampton, Southampton, UK

* Correspondence to: Professor T. J. Hamblin, 15 Queens Park South Drive,

Bournemouth BH8 9BQ, UK. E-mail: terjoha@...

Introduction: Patients with chronic lymphocytic leukaemia (CLL) have progressive

immunodeficiency and infection is the commonest cause of death. This review

seeks to identify the extent of the abnormality, its cause, clinical

significance and any possible remedy.

Sources of data: TJH has studied CLL for the past 40 years and has scanned or

read every paper he could find published on the topic since 1970 and most of

those of historical importance published before that date. He has read around

the subject, covering relevant articles on immunology, cell biology, oncology

and genetics. Furthermore, he has attended most major meetings dealing with CLL

in this time and has written many reviews to update the state of knowledge about

the topic. He receives weekly updates of papers published on CLL from PubMed and

Science Direct with the keywords 'chronic lymphocytic leukaemia'.

Areas of agreement: The immunodeficiency chiefly manifests as

hypogammaglobulinaemia but involves all elements of the immune system. It is

caused by the interpolation of tumour cells among immunological cells and

mediated by bi-directional cell contact and secretion of cytokines, which both

sustain and invigorate the tumour and suppress immunity. CLL treatment generally

makes the immunodeficiency worse. Intravenous immunoglobulin is clinically

effective but not cost-effective, while prophylactic antibiotics are useful in

appropriate circumstances. Vaccination against infectious disease is usually

ineffective.

Areas of controversy: Exactly how the presence of tumour cells in the immune

organs renders the patient immunodeficient is controversial as is the clinical

significance of minor degrees of immunodeficiency in early or indolent cases.

The immunosuppressive effect of most forms of treatment is agreed, but how much

this should figure in the choice of treatment is a matter of dispute.

Growing points: The study of tumour-stromal interactions is an area of intense

research.

Areas timely for developing research: There has been little done to develop

better vaccination strategies in patients with CLL, and although effective

antimicrobials have been developed to protect against opportunistic infections,

many are both expensive and inconvenient. More work is necessary to define

precisely which patients should be offered them and when.