Treating high white cell counts.

A lot of people have asked about whether treatment should be started because the white count has reached such and such a level.

The answer is we don't treat white counts we treat patients.

To some extent the white count reflects the amount of CLL the patient has, but this is not a straightforward relationship. What is harmful about CLL is its effect on the rest of the body. The most common complication that is an indication for treatment is suppression of the normal bone marrow - anemia, thrombocytopenia and less commonly, neutropenia. This would make the dice Rai stage III of IV or Binet stage C. Everybody agrees that this is an indication for treatment. Mere enlargement of lymph nodes or spleen (Rai stage I or II, Binet stage A or B) is not necessarily an indication to treat, but it may be. If the enlarged spleen is causing anemia or thrombocytopenia then it may be indicated to try and shrink it, if the lymph nodes are bulky and causing discomfort then shrinking them is indicated. Some people want lymph nodes treated because they are unsightly.

If autoimmune complications occur, sometimes it is necessary to treat the CLL in order to control the hemolytic anemia or the ITP (or very rarely the pemphigus which is the other autoimmune complication sometimes seen in CLL). But this is not always the case. Some patients present with auto immune hemolytic anemia and are incidentally found to have CLL. Once the anemia is controlled the CLL may never need treatment.

If systemic symptoms occur - weight loss, fever, night sweats - this is an indication for treatment. Such symptoms often occur when there are enlarged nodes in the abdomen - these are called retroperitoneal nodes, they lie just in front of the spine and are too deep to be felt with the hand. They can be picked up by ultrasound, or by CATscan and are the reason that some doctors like to use a CATscan in examining patients (but if you are worried about radiation, ultrasound is quite safe)

Retroperitoneal glands are pretty unusual in CLL, but there are 3 things to know about them. 1 they are common in patients with del 11q by FISH 2 the may compress the ureters - the tubes draining the kidneys - and cause an obstruction. 3 they may be a sign of Richter's syndrome - the development of a high grade lymphoma on top of the CLL.

So, a very high white count makes a doctor worry that all these things might be going on.

There is another complication of very high white counts. The blood becomes very viscous and flows slowly. When this happens, small arteries become blocked and there is a risk of a stroke. How high is dangerous. For CLL no one really knows. It is not the same for all types of white cells. With acute myeloid leukemia it is dangerous at a lower level.

The highest white count I have seen was 735,000. This was a woman who was admitted to hospital with a fatal stroke. But she had both CLL and acute myeloid leukemia (the combination is very rare, I have seen it 4 times in 30 years). I have had two other patients with white counts over 400,000. Both of these had herpes infections, one simplex and one zoster, before the era of acyclovir. In both cases treatment with chemotherapy made the herpes worse, so I treated them with leucapheresis.

These cases illustrate the fact that very high white counts rarely come alone. Both these patients had major immunodeficiencies.

The next question is why we should watch and wait while the white count is rising. The answer is that clinical trials have shown that treating before symp toms arise does not improve survival. But those trials involved treatment with chlorambucil and were conducted before we had the information from VH genes, ZAP-70, and FISH that give us a better appreciation of who will progress and who will not. So it is probably time to consider new clinical trials on whether better treatment given early to patients with bad prognostic factors produces a better outcome than the same treatment given when the patients develops symptoms.

This will still leave a decision to make about the patient whose CLL is probably not going to kill him, but is faced with a rising white count.

Oh, a final thought about staging. Both the Rai and Binet staging was done by physical examination and the predictions made by them refer to clinical staging , not radiological staging. Using a CAT scan invalidates the staging. This is especially important for spleen size. Almost everybody with CLL has a spleen 1 or 2 cm larger than normal on CAT scan. this is of absolutely no significance. Onlt spleen that can be felt with the hand are significant. Only is a patient is rather overweight and teh spleen cannot easily be felt is an ultra sound or CT scan warranted, and then it is only significant of the spleen protrudes below the ribs.