Your first reaction to having CLL

What do you do first when confronted with a diagnosis of CLL?

The first thing is don't panic. Three quarters of cases are diagnosed because you had a blood test for something else. When it is first diagnosed you have probably had it for years, so the day of diagnosis is not a special day in the history of your disease. It may be a special day in your life, but your disease isn't interested in that. It is plodding its weary way along a long path and it just so happens that it has been noticed for the first time.

You sometimes hear people say, "I was lucky; the doctors caught it in time." For CLL, there is absolutely no evidence that catching it early makes any difference to the outcome. Almost certainly the first type of management you will be offered is watch and wait and about a quarter of patients will never need treatment.

In the old days doctors never used to tell a patient that they had CLL so as not to frighten them and there was some merit in this. We now call many cases of what was then known as CLL by a different name. They are now called monoclonal B cell lymphocytosis (MBL) which is believed to turn into CLL at the rate of 1% a year. Since the average age of diagnosis is 70, in most patients this is never going to happen. There are still patients walking around with the diagnosis of 'leukemia' attached to them worrying about their future when they shouldn't be.

As an aside I should say that the same is probably true for certain types of cancer as well. Prostate cancer and breast cancer are examples of this - especially when the diagnosis has been made by a screening test.

We need to explore the reasoning behind watch and wait. Some twenty years ago there were a lot of trials involving more than 2000 people who were randomized to treatment at the time of diagnosis or treatment when the disease progressed. There was absolutely no difference in survival. Indeed there was a suggestion at 6 years follow up that those who had treatment did slightly worse.

I need to qualify this reasoning. At the time of the trials, treatment was not very good - nobody got cured however early they were treated. Also at that time we had no way of picking which patients would progress and which would not. So some patients who would never need treatment were treated unnecessarily.

Because of this some people think it is necessary to repeat these trials, only this time confining treatment to those who are just about guaranteed to need treatment eventually and using agents that are much more effective than they were 20 years ago. These trials are taking place in Germany, the USA and the UK, but because the outcome measure is overall survival we will not be getting an answer anytime soon.

So how does a doctor work out who needs treatment? Some patients clearly need treatment pretty soon. These are picked out by either symptoms or clinical stage. Some patients are definitely ill when they are first seen. Those with fever that isn't caused by an infection, or severe fatigue that really stops them doing anything, or weight loss - more than 10% over the past 6 months (that wasn't being aimed at by a diet and exercise program) or such severe sweats at night that they have to change nightclothes or even bedclothes. Such symptoms are usually the result of a large volume of disease - which may not be apparent on clinical examination, because it is located at the back of the tummy behind all the normal tummy organs (so called retroperitoneal disease).

It is also generally agreed that patients with Rai stage 3 or 4 or those with Binet stage C disease need treatment. Kanti Rai from Long Island and Jacque-Louis Binet from Paris are very senior CLL specialists who gave their names to staging systems that are used in America and Europe respectively. Rai stage 3 or 4 and Binet stage C are signs that the bone marrow has started to fail. Rai stage 3 means the hemoglobin (Hb) is less than 11 g/dL and Binet stage C means that the Hb is less than 10 g/dL. I have no idea why the two experts chose different levels as a trigger nor why it is the same for men and women. An Hb of 10 for a man means that he has lost 3.5 g while an Hb of 11 for a woman means she has lost only 0.5 g. Crazy isn’t it?

In my own practice I tend to take an Hb of 10 as a trigger for treatment, though I am quite willing to start if I see a consistent downward trend. Incidentally you will see that I am using Hb as an abbreviation for hemoglobin rather than Hg which many patients tend to use. The reason for this is that Hg has already been taken; it is the chemical symbol for mercury, which we use in medicine when measuring blood pressure. Aim for 120/80 mm of Hg. It is also important to be sure that the low Hb is caused by marrow failure. It would be silly and fruitless to use chemotherapy to treat simple iron deficiency. This is especially important when the anemia is cause by autoimmune hemolysis (which occurs in 15% of patients with CLL). The treatment for autoimmunity in CLL is usually steroids, and only if it can’t be controlled by steroids is it right to treat the CLL.

The trigger level for a low platelet count to start treatment is 100,000 per cu mm for both European and American staging systems. Again, this is a bit arbitrary. Sometimes, the platelet count will hover around 100,000 for months. It doesn’t necessarily mean that treatment starts when it touches 99,000 for a few hours. We are more concerned by the rate of fall. We might start treatment at 120,000 if the fall is very rapid. We have to worry about autoimmunity with platelets also and about a condition called hypersplenism where a large spleen acts as a reservoir for platelets so that they are rather low in the blood. Neither is an indication for treatment, but there is no easy test for either of them. Most times the doctor has to make a judgment call.

Other reasons for beginning treatment relate to the size of the spleen or enlarged lymph nodes. Here again we run into a problem because the staging systems were designed to be operated without using CT scans. You are Rai stage 2 because your spleen can be felt, not because a CT image says it is enlarged. The spleen is an organ whose job it is to get rid of dead and dying blood cells, but it also has important jobs to do in the immune system. It lives under the ribs on the left and as it enlarges it migrates towards your belly button. When you take a big breath you can feel it emerge from beneath the ribs. The pundits have decreed that treatment should begin when the spleen is enlarged 6 cm below the edge of the ribs (that’s 2 and a half inches for those not used to metric measurements). In real life that means that the spleen is about three times its normal size.

The same problem involves lymph nodes. The staging systems are about what you can feel, not what you can see on a CT scan. Doctors are expected to look in the neck, under the armpits and in the groin. Any node or group of nodes that is 10 cm (4 inches) in diameter is an indication for treatment.

What is not an indication for treatment is the height of the white count. For other types of leukemia high white counts are a worry because they can cause sludging in small blood vessels and lead to a stroke or blindness. This does not happen in CLL. Even if your white count is a million, it is not dangerous. However, rapid rises in white count may be an indication of rapid progression of your disease and rapidly progressive disease needs treating. If your white count doubles in six months then treat. If it increases by 50% in two months, then treat. There is a proviso here. It is not the rate of increase that matters but what it represents. It represents rapidly progressing disease. But if the white count goes up because of an infection or a vaccination or because you have had some steroids it doesn’t represent rapidly progressive disease and it isn’t an indication for treatment. Also, if it starts from a low base – less than 30,000 – then there is no correlation with disease progression and it should be ignored. Rapidly progressive disease can also be recognized if the spleen or lymph nodes enlarge over a short period of time, no matter what is happening to the white count.

So to summarize: 1] There is no point in treating CLL just because you have it. In most cases you can’t cure it.
2] If it is causing symptoms it ought to be treated for symptom relief.
3] If it is causing organ failure (usually the bone marrow)it ought to be treated to spare the failing organ.
4] If it is progressing rapidly it ought to be treated because it will kill you if it isn’t.

I will write again on this topic later.