Infections by Professor T Hamblin

INFECTIONS

By Dr T.Hamblin

Infections are common in CLL. The main cause is falling immunoglobulin levels. There is clear evidence that patients with serum IgG levels less than 400 mg/L and more than 2 bacterial infections a year get benefit from regular IV Ig infusions every 3 weeks. That is about all that is proven.

All patients with CLL have a diminished immune response which means that they have difficulty making antibodies to bacteria, even after vaccination. This is particularly so against bacteria with polysaccharide cell walls where the re- sponse is "T-independent". Examples of such bacteria are Pnemococcus and Haemophilus, so vaccines such as pneumovax don't work.

Vaccines that contain protein are a bit better with an average response rate of about 40%. There are so-called "conjugated vaccines" where protein is conjugated to the polysaccharide, and response to these is better.

There is a further trick to help the immune response, which involves raising the level of blood histamine, which in turn enhances the response to IL-2, one of the "cytokines" that stimulates T cells in the immune response. This is done by blocking the H2 receptors for histamine so there is a compensatory increased secretion of hista- mine. The way this is done is to take ranitidine 300 mg twice daily with the first vaccination, to have a boost of vaccine at 45 days and to continue the ranitidine for 90 days. This increases the response rate to 90%.

Patients who have fludarabine or Campath treatment have low CD4+ T cells, sometimes as low as is found in AIDS patients, and especially after fludarabine they are likely to remain this low for 2 years. This leaves patients susceptible to the same infections as AIDS patients – pneumocystis carinii, herpes zoster, herpes simplex, CMV, and funguses. That's why it is recommended that patients take prophylactic Bactrim, acyclovir and possible fluconazole.

Patients who need prophylaxis are best advised to keep ringing the changes on their antibiotics. There are several that fit the bill.

Added to the problem of infection is the related problem of autoimmunity. Nobody clearly understands why CLL patients are so prone to autoimmune disease. I think it is because the same T cells that control the production of antibody are responsible for suppressing the production of anti-self antibodies. But treatment of autoimmunity, makes immunodeficiency worse.

Unfortunately, patients may be unwell with CLL, with fevers and fatigue, when no infection can be detected. This may be due to the disease or the body's attempt to fight it. It is often mediated through cytokines such as TNF and IL-1 or IL-6. Symptoms may be relieved by corticosteroids like prednisolone, but these have side effects with prolonged use.

Sometimes symptoms can be controlled with Tylenol or Ibuprofen like drugs. Others swear by the unconventional green tea. If the symptoms are bad enough the CLL has to be treated. Unfortunately some patients continue with the symptoms even after treatment.

(From ‘ACOR’ Professor’s posts)