When to Treat?
Professor Terry Hamblin
A doubling time of 6 months is one of the NCI indications for treatment. What you have to be certain of is that it is a sustained doubling time. Sometimes there are temporary blips in the lymphocyte count. Therefore, you need to have several measurements on the graph.
FCR is the treatment that produces the highest response rate and the longest remissions in Phase 2 trials. So far there is no head to head comparison with either FR or FC - these are going on at the moment. There is also no evidence that any treatment gives a longer overall survival than chlorambucil. Because FCR causes profound immunodeficiency for a long time and because there is a worry that it might increase the risk of secondary cancers including myelodysplastic syndrome and Richter's syndrome, some are reluctant to use it as first line treatment.
The present state of CLL research does not allow us to put any figures on the risks involved, nor to judge the possible benefits. There are several new agents in the pipeline that may be less damaging, but again it is early days as yet.
In recent studies (like the recently reported German trial and the British CLL4 trial which will be presented at ASH) the factor that most determines long survival is not what treatment was given, but whether the patient's CLL had mutated or unmutated VH genes, and whether the FISH showed
del 17p or del 11q.
Current studies are adding mitoxantrone to FCR and still others top up the mixture with Campath to mop up minimal residual disease. It is not yet known whether either of these manoeuvres will add anything beneficial, though they will certainly add toxicity.
Outside of a trial I try to tailor treatment to patient so I like to know as much about a patient as I can find out - including what the prognostic factors are.
Terry Hamblin (reply to a post from a CLL patient member on the ACOR list)
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What are the indications for treatment? The National Cancer Institute has issued guidelines on this.
One of the items on the following list must be present:
- Weight loss of more than 10% of body weight in the previous 6 months;
- Extreme fatigue so that the patient cannot work of perform usual activities;
- Fevers of greater than 100.5=B0F for at least 2 weeks without evidence of infection;
- Night sweats without evidence of infection. They have to be severe.
- Evidence of bone marrow failure shown by the development of, or worsening of, anemia or thrombocytopenia
- Autoimmune hemolytic anemia and/or thrombocytopenia poorly responsive to corticosteroids.
- Massive splenomegaly (>6cm below the costal margin).
- Massive lymph nodes or clusters of nodes (>10cm in longest diameter).
- Increase in lymphocyte count by >50% over two months or anticipated doubling time of <6 months.
- A high lymphocyte count is not in itself an indication for treatment.