Monday, December 19, 2005

Natural history of CLL

Natural history is a bit of medical jargon. It means what happens if the disease is left to itself without treatment. For CLL this is very variable.

Some people who are diagnosed with CLL continue to have a raised white cell count, but never develop enlarged lymph nodes or spleen; never develop anemia, neutropenia or thrombocytopenia; never get ill. They die at 105 of something else.

Some people already have large lymph nodes that get bigger, a large spleen that becomes enormous; are anemic making them short of breath, neutropenic so that they catch pneumonia and are thrombocytopenic and bruising easily or bleeding uncontrollably.

And in between almost every variation occurs.

Lymph node enlargement is mainly very superficial. In the neck, groin and armpits the nodes are easlily felt. They tend to be multiple, not painful or tender, quite soft and rubbery and of sizes varying from a small pea to a quail's egg. (How many have seen a quail's egg? If you saw the TV production of Brideshead Revisited you will remember that Sebastian served a huge plate of quail's eggs in his rooms at Oxford.

The spleen enlarges from under the left ribcage. I have only once seen it go past the umbillicus.

The anemia is normochromic, normocytic. That means the red cells are of a normal color and normal size. Severe anemia is unusual and makes one think of autoimmunity.

Autoimmune hemolytic anemia (AIHA) occurs in between 10 and 20% of cases (depending on which paper you read). CLL is actually the commonest known cause of AIHA, acounting for about 25% of cases. An antibody is produced directed against the patient's own red blood cells. It is not made by the CLL cells themselves but by the residual normal B cells. The antibody latches on to the red cells and fixes complement. Complement is a cascade of blood proteins that react one with another from C1 to C9. C9 provides the killer blow and punches a hole in the red cell. However, in AIHA realted to CLL the activation of complement seldom goes beyond C3. C3 makes red cells more attractive to macrophages and as the blood circulates through the spleen the red cells get snaffled by the macrophages there.

Immune thrombocytopenic purpura (ITP) occurs in between 1 and 2% of cases. Again it is cause by an autoantibody. Platelets coated by antibody also get snaffled by the spleen.

Pure red cell aplasia may be an autoimmune disease directed against the red cell precursors so that no red cells are made by the bone marrow. However, it may be that the mere presence of large numbers of CLL cells in the bone marrow is enough to inhibit red cells from growing there.

Most patients with CLL get immunodeficient. The most obvious manifestation of this is the fall in the serum imunoglobulins. The fall is greatest in those who have had it the longest and in the greatest bulk. Patients suffer from sinus infections and pneumonia. Between a quarter and a third get shingles.

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