Is CLL curable?

11 April 2005

Let's start by saying that CLL is best regarded as 2 diseases. We will call them U-CLL and M-CLL (for unmutated and mutated, though these categories have fuzzy edges and may nor be precisely defined by mutations in the VH genes)

The majority of patients with M-CLL will live for a very long time and quite a large percentage will never need any treatment. Those that do need treatment will have a very high response rate and will get very long remissions. Some of these patients will appear to be cured, though this may just mean that their remissions will last longer than they do. We did a stem cell autograft on one such patient in 1987 who survived for 13 years before dying of lung cancer. He had no detectable CLL at post mortem, though this was before the time of PCR.

The question with M-CLL is whether it is right to make strenuous efforts to eliminate evry CLL cell when they might survive for 30 years plus without the sort of treatment that might have severe side effects.

U-CLL is different. Almost every patient will eventually need treatment, though we have one patient who survived 20 years without before dying of something else and others who have gone more than 5 years w&w before needing treatment. It is this group that doctors are concentrating on treatment. FCR or FCM (M stands for mitoxantrone) produce high remission rates and fairly long ( perhaps 5 years) progression free survivals. Some people want to try FCMR. We can't prove that everyone will relapse, but certainly relapse are beginning to happen, first molecular relapses and later clinical relapses. My suspicion is that they will all relapse, but there may be some lucky ones. There are several suggestions on where we should go from here. There is the allograft option, though even the reduced intensity conditioning version of this is hazardous and may involve chronic graft versus host disease, which is no picnic. Others have suggested earlier treatment - when the poor prognostic markers are found, rather than waiting until the disease progresses. No-one knows whether this would be better but some want to try. Another option is consolidation with Campath, trying to eliminate any residual disease. another option is maintenance Rituximab. There may be other options in the pipeline.

So it's not hopeless.

12 April 2005

I deliberately hedged on this question "We will call them U-CLL and M-CLL
(for unmutated and mutated, though these categories have fuzzy edges and may nor
 be precisely defined by mutations in the VH genes)" was what I said. A few
patients with mutated VH genes do have progressive disease. Patients whose
mutated VH gene is VH3-21 have a poor prognosis. There are a few patients with
mutated VH genes who are ZAP-70 positive or CD38 positive and some of these
have  a poor prognosis. We occasionally see patients with del 17p among the
mutated  subset and we are not sure what this means. There are some patients with
between  2-3% mutations who behave as if they were unmutated. Although the
mutational  status of the VH gene is very definitely my baby, I am not going to
be  absolutist about it. Remember that our motto is treat the patient, not the
numbers. This applies equally to the VH mutations as it does to the white
count.