Immunideficiency 5

Potential remedies for the immunodeficiency

As has already been seen just treating the CLL does not restore immunity and guidelines do not recommend immunodeficiency as a reason for beginning treatment [27].

Intravenous immunoglobulin

The chief means of improving the immune defect has been the use of intravenous immunoglobulin (ivIg) infusions. It should be remembered that immunoglobulin infusions only contain significant amounts of IgG and will not restore deficiencies of other immunoglobulin classes. The use of ivIg in CLL is controversial [27, 28]. Several clinical trials have demonstrated that it reduces the incidence of mild and moderate bacterial infections but none have shown a decrease in mortality. When the need to regularly attend hospital is taken into consideration, there may be no improvement in quality of life. One study estimated that the cost of one quality adjusted life year was $6 million [29]. IvIg only becomes cost effective if it is better targeted [3]. Our own practice is to confine treatment to patients whose serum IgG is less than 300mg/dL who have had at least two bacterial infections in a 12 month period. We recommend a dose of 250 mg/kg given every four weeks. Arrangements are available for patients to self-administer the immunoglobulin infusions at home.

Prophylactic antimicrobial agents

There are no clinical trials of prophylactic antimicrobial agents in CLL [27]. Although the use of cycling antibiotics to prevent infections is very common in patients with recurrent chest infections due to bronchiectasis, or recurrent urinary tract infections, there are no studies of the efficacy or cost effectiveness of this approach in CLL. Nevertheless, some patients with recurrent sinusitis clearly benefit from this sort of approach.

There are similarly no trials or prophylactic antimicrobials in patients with low CD4+ T cells levels following treatment with purine analogues or alemtuzumab [27, 28]. Current practice derives from what has been used in patients with AIDS. Prophylaxis against Pneumocystis jirovecii is normally with cotrimoxazole 960 mg on alternate days continued for a minimum of six months after stopping therapy. Some authorities recommend monitoring the count of CD4+ T cells and continuing the cotrimoxazole until the count is greater than 0.2 x 109/L. For patients who cannot tolerate cotrimoxazole, penatmidine 300mg by inhalation every four weeks is available. Alternatives are dapsone 100 mg daily or Atovaquone 750 mg twice daily, though this is an unlicensed indication in the UK.

In patients with a history of herpes simplex or herpes zoster prophylaxis with aciclovir should certainly be given following treatment with either fludarabine or alemtuzumab [27, 28]. The dose that should be used has not been established; between 400 mg and 1600 mg per day have been variously recommended on the basis of experience with AIDS patients or those undergoing stem cell transplantation. Again treatment usually continues for six months after treatment stops,though some would advocate monitoring the count of CD4+ T cells. In patients who receive treatment with alemtuzumab, though not in those receiving purine analogues, monitoring for CMV reactivation should be undertaken weekly. Evidence of reactivation should be treated with either ganciclovir 5 mg/kg iv twice daily or oral valganciclovir 900mg twice daily.

Antifungal prophylaxis is also indicated in patients receiving either purine analogue or alemtuzumab treatment. The choice of agent should be between itraconazole, voriconazole, posaconazole and caspofungin.

References

27. Oscier D, Fegan C, Hillmen P et al. Guidelines on the diagnosis and management of chronic lymphocytic leukemia. Br J Haematol 2004; 125:294-317
28. Morrison VA. Management of infectious complications in patients with chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2007; 2007:332-8.
29. Weeks JC, Tierney MR, Weinstein MC. Cost effectiveness of prophylactic intravenous immune globulin in chronic lymphocytic leukemia. New Engl J Med 1991; 325:81-6.