If the aims of treatment are to live as long as possible and as well as possible, it may be that these aims are not compatible. We can make you live longer but you won’t be as well or we can keep you well but you won’t live quite so long. What I mean is you may have to compromise.
There’s a quote from Edmund Burke, “All government, indeed every human benefit and enjoyment, every virtue, and every prudent act, is founded on compromise and barter.”
The compromise is this. Left alone CLL will probably kill you. Even in the most benign cases the ability to respond to infection seeps slowly away. On the other hand the treatment is harmful too; the harm it does also damages the immune system.
Let us examine these questions. Unless the Lord returns first we are all going to die. Someone once said, “Life is a sexually transmitted condition that is universally fatal.”
Death is caused by violence or disease. Assuming we are not murdered, hit by a bus or some other traumatic intervention our body will get a disease and no longer be able to sustain itself. Infection, cancer, heart disease, brain failure; we used to call it old age. We can dissect out the cause of old age, but we can’t do much about it. It’s like running an old car; replace the brakes and the muffler blows, the gaskets leak, the tyres are threadbare, the pistons rattle, bodywork rusts. These bodies wear out. With CLL they wear out quicker. My oldest survivor was 106. Without CLL she might have lived to 107.
CLL can kill in fairly obvious ways. Marrow failure opens the way to infection, bleeding and, without transfusion, heart failure from anemia. Infection is probably the single commonest cause of death. Another cancer, whether a melanoma, squamous cell cancer of the skin, lymphoma or lung cancer may seem just another bit of bad luck, but though it’s hard to prove, it probably wouldn’t have happened without the CLL. But no-one can put their hand on their heart and say that the treatment of the CLL didn’t make these outcomes more likely.
Sometimes the CLL gallops. It becomes inevitable that you have to put a halter on it to slow it down. But more often it canters, trots or walks. Sometimes it seems to stand still like a dressage pony making grandmother’s footsteps, now forward, now back. Then you have to decide how much treatment and when.
Except in the most virulent cases I prefer to take the long view. I’m not much interested in treating a blood count. Treating a blood count is like polishing the bodywork while the engine is disintegrating. I have two concerns. I want the bone marrow to go on making blood cells, and I want to stop the immune system falling apart. So unless the bone marrow is threatened I prefer to avoid treatment. The CLL will eat away at the immune system, but it will do it slowly. Every treatment that I know will make the immune system worse. There is no way of treating the CLL that will restore the damaged immune system.
So, supportive care is the first thing. Blood transfusion or erythropoietin to keep the haemoglobin high. Surgery for an uncomfortable spleen or one that is consuming red cells or platelets. Irradiation of large or uncomfortable peripheral lymph nodes. Antibiotics for infections. And when infections are caused by low serum immunoglobulins then intravenous immunoglobulin infusions on a regular basis. Do what you can to avoid having to have treatment.
If treatment is inevitable, my choice would be the treatment that is least harmful. At the moment this is rituximab. It only works in about half the patients, and it does lower the levels of normal B cells, but this is transient and they quickly return. Rituximab plus a growth factor like G-CSF or GM-CSF may well be more effective. So if it works for you and gives you a year off treatment then go for it, and don’t be afraid to repeat it. True rituximab resistance is very rare. In some patients increasing the dose will turn a non-responder into a responder.
It’s after that that you have to think about chemotherapy, and that is the subject of another article.