December 14th 2005
Three-quarters of all cases of CLL are discovered by accident. The patient has a blood test for some other reason or, these days, for no very good reason at all.
Everybody thinks that CLL is getting commoner and they blame the increased use of pesticides in farming, or the nuclear testing in the sixties or diesel fumes or global warming or mobile phone masts or sunspot activity or Chernobyl or whatever is the current scare story in the newspapers. I suspect that it is not getting commoner at all - it is simply that we are recognising cases that we never used to find.
When I was young, everyday I looked at all the blood tests performed on everyone from a population of half a million. On a good day there were 300 blood counts. Thirty years later my responsibilities had diminished; I only looked at the blood counts from a quarter of a million. But most days there were over 700 tests. Thirty years ago you needed to have a lymphocyte count in the blood of 15,000 befor you could diagnose CLL. Today it is only 5000. Thirty years ago we had just discovered that CLL was a B cell neoplasm. Today we can distinguish several types of B cell neoplasm in the blood. We now know that 3.5% of people over 40 have a population of monoclonal B cells indistinguishable from CLL cells in their blood. The harder you look; the more you find.
The 25% in whom the CLL is not found by chance have a variety of symptoms and signs. (A symptom is something the patient feels; a sign is a physical abnormality the doctor finds.) The commonest finding is an enlarged lymph node.
Lymphocytes circulate through the body like other blood cells. For many their journey is just like other blood cells: out in the arteries, home in the veins. They have another circulation, though. The little thin-walled blood vessels that join the arteries to the veins are called capillaries. Lymphocytes can squeeze out through the walls of the capillaries and enter the tissues. From here they make their way home via the lymphatics, which are like veins for white blood cells. Lymph nodes are like stations on the lymphatic railway. They are normally small - about the size of a split pea - and organised. The job of lymphocytes is to fight against foreign invaders, and the lymph node is where they get their training and their orders before going into battle.
Lymph nodes enlarge during an immune response - you often feel 'glands' in your neck when you have a sore throat. In CLL they enlarge because the cells that are growing in an uncontrolled way normally live in the lymph nodes. In CLL we look for lymph nodes in particular places: the neck - we call these cervical nodes; the armpit - axillary nodes; and the groin - inguinal nodes. But there are lymph nodes all over the body and in CLL any lymph node can enlarge. Mostly they can't be felt, but there are some characteristic lymph nodes that are sometimes felt: submental nodes are under the point of the chin and epitrochlear nodes by the elbow. Lymph nodes at the back of the tummy - retroperitoneal nodes - cannot be felt with the hand but may be shown up by CT scan or ultrasound. Nodes in the chest also have to be visualized by some sort of imaging technique.
The spleen is about the size of a fist and is found deep under the ribs on the left of the tummy. It enlarges in CLL, but it has to get to three times its normal size before it can be felt. As it gets bigger it grows across the tummy towards the right groin. It seldom gets as big as this in CLL but it can grow this large in some kinds of hematological cancers. When it is examined by CT scan in CLL it is almost always found to be enlarged and patients think that they must therefore have advanced stage disease. This is misleading. As far as CLL is concerned a spleen is only considered to be enlarged if the doctor can feel it with his/her hand.
The spleen can be though of as a large lymph node attached to the blood circulation. But it also has other roles. It is the last resting place for dying red cells and platelets. When it enlarges it is apt to take out red cells and platelets before they are ready to go. This is known as hypersplenism and it results in anemia and thrombocytopenia.
Anemia means a reduction of the amount of hemoglobin in the blood (the abreviation in Hb not Hg; Hg is the abreviation for Mercury). Men and women have different normal ranges for Hb. For men it is 13.5 - 17 g/dL, for women 11.5 - 15 g/dL. Anemia cause tiredness, breathlessness, weakness, pale skin and mucous membranes and, in severe cases, the features of heart failure; but in many cases mild anemia has no signs or symptoms. Anemia in CLL is caused by suppression of the bone marrow by the infiltrating lymphocytes, or by hemolysis - the distruction of red cells by an antibody, or by hypersplenism. Of course CLL patients can become anemic for reasons unrelated to CLL, such as iron deficiency or pernicious anemia.
Thrombocytopenia means a reduction of the platelets in the blood. The normal range for platelets is 150,000 to 400,000 per cubic millimeter. The features of thrombocytopenia are bleeding and bruising. Platelets are there to plug holes in broken blood vessels and to help the blood to clot. Bleeding into the skin is called purpura and there are two types: petechiae are tiny pinhead sized blood spots; echymoses are anything larger. Thrombocytopenia can have the same causes as anemia: marrow infiltration, immune destruction and hypersplenism.
Patients may also suffer from so-called B symptoms. B symptoms come from Hodgkin's disease doctors who used them to decide whether to treat with chemotherapy or radiotherapy and they have been imported into CLL theology where they don't necessarily fit precisely. There are three types of B symptom: fever, weight loss and night sweats. Some doctors and most patients think that fatigue ahould also be a B symptom in CLL. I shall write about fatigue on another occasion.
Patients with CLL are more susceptible to infections that normal - they have an immunodeficiency. I will write about this in detail later.
To summarize: Most patients with CLL are discovered because they have a blood test for some other reason. If patients have signs or symptoms, the commonest is enlarged lymph nodes, but the spleen (or more rarely the liver) may also be enlarged. In the most severe cases there may be anemia or thrombocytopenia. Some patients have B symptoms and all have a degree of immunodeficiency.