PLL

There has been a bit of discussion about transformation of CLL to PLL. I have been saying that it doesn't happen. This has caused some confusion, so let's see if I can straighten things out.

Prolymphocytic leukemia is quite a different disease from CLL. It has bright surface Ig, it is CD5 negative, CD23 negative, FMC7 positive, CD22 positive and it has more than 55% prolymphocytes on the blood film. Often there is a paraprotein and while the spleen is enlarged, the lymph nodes are not. It is also very rare. I have 7 cases on my books, compared to over 800 CLLs.

Most of the confusion arised from a condition known as CLL/PLL. This condition has between 15% and 55% prolymphocytes in the blood but the cell markers are those of CLL, not PLL. In the 1980s the FAB group (nothing to do with the fab four, it stands for French-American-British) having divided up the acute leukemias and MDS, decided to have a go at the chronic lymphoproliferative disorders. They divided up CLL into typical and two types of atypical CLL. One sort of atypical CLL was CLL/PLL. In a big series of patients, my group and Danny Catovsky's group demonstrated that there was a close correlation between atypical CLL and trisomy 12.

Although people talk about prolymphocytoid transformation of CLL, which seems to imply increasing numbers of prolymphocytes over time, this does not really happen with trisomy 12. There are variable numbers of increased prolymphocytes, but this is a pretty permanent state. I followed one such woman for 20 years with no change in the percentage of prolymphocytes. She had a big spleen, a high white count, a paraprotein, but CLL type cell markers and mutated VH genes. She was non-progressive. If we go back to the papers in Brit J Haem by Junia Melo and David Galton that described CLL/PLL we find that this is just what they descibed.

Here is a section of a paper that I wrote which reviewed the Melo papers:

"Contrary to the common perception, in a study of 55 cases of CLL/PLL half showed a stable picture without a progressive increase in prolymphocytes. The prognosis of this group was similar to that of stable CLL without prolymphocytes. In one third of cases the increase in prolymphocytes was unsustained and in only 18% was there a definite progression towards a more malignant phase of the disease."

In other words a third of patients had a transient increase in prolymphocytes - perhaps triggered by infection or vaccination, and only 18% had a real prolymphocytoid transformation to a more malignant phase. 18% of 55 is 10 cases.

So what was going on with these 10? Trisomy 12 is not the only chromosomal abnormality found in atypical CLL. The very rare t(14;19) translocation involving bcl3 has an excess of prolymphocytes anda poor prognosis. But 80% of patients with p53 mutations or deletions also have atypical morphology. P53 aberrations are likely to occur as a form of chromosomal evolution, and are associated with an increased aggressiveness. I have certainly seen this effect. But note this is not prolymphocytic, but prolymphocytoid transfomation. The cell markers remain typical of CLL.

Part of the confusion lies in the rather atypical immunophenotype of trisomy 12 cells. The surface Ig is rather stronger than normal in CLL and CD20 is also stronger. FMC7 is also moderately positive. These markers have a superficial resemblance to those of PLL but they are quite distinct.

Just to confuse matters more, a minority of PLLs are CD5 positive. We published a paper from my group and the French group from Nantes which exposed these as a variant form of mantle cell lymphoma. They are not the blastic form of MCL that has been described previously, but what appears to be PLL with mantle cell markers including the cyclin D1 and the t(11;14) translocation. They have a dreadful prognosis on the whole.

Is everybody thoroughly confused? Well that's better than being so sure of yourself that you treat zebras like white horses that have caught the sun behind prison bars.