For the past 30 years CLL has been staged by one of two systems devised by two of the great researchers in CLL. Kanti Rai operating in Long Island and Jacques-Louis Binet practising in Paris have been guiding lights for generations of hematologists.
Both staging systems give an estimate of how advanced the disease is based on simple measurements available to everybody.
The Rai system has 5 groups:
Stage 0: Lymphocytosis only.
Stage I: Lymphocytosis plus enlarged lymph nodes
Stage II: Lymphocytosis plus enlarged spleen or liver.
Stage III: Lymphocytosis plus anemia
Stage IV: Lymphocytosis plus thrombocytopenia.
Anemia is defined as an Hb less than 11 g/dL and thrombocytopenia as a platelet count less than 100,000 /cu mm.
Later, stages I and II were combined to be called intermediate-risk and III and IV combined to be called high-risk.
The Binet system has only 3 groups:
Stage A: Lymphocytosis and fewer than 3 lymph node areas involved
Stage B: Lymphocytosis and 3 or more lymph node areas involved
Stage C: Lymphocytosis and anemia or thrombocytopenia or both.
"Lymph node areas" refer to enlargement of lymph nodes in cervical (neck), axillary (armpit) or inguinal (groin) areas or enlargement of spleen or liver.
Anemia for Binet has to be more severe than Rai: Hb less than 10 g/dL, but thrombocytopenia is the same, platelet count less than 100,000 per cu mm.
These staging systems have served us very well, though they have some drawbacks. It has to be emphasized that anemia or thrombocytopenia must be caused by bone marrow infiltration to move a patient into advanced stage disease. Hemolytic anemia or simple iron deficiency don't count and nor does ITP (I'll explain later).
It is important to note that the stage is just a snapshot for how things are now. If a patient is stage C or III or IV the disease is advanced and the prognosis is likely to be poor, but stage A or 0 or I or II disease may be advanced stage in 6 months or 5 years or never. Since the vast majority of patients have early stage disease when diagnosed the future cannot be predicted by staging. It is also important to recognise that a low stage after treatment does not carry the same implications as a low stage before treatment. Stage 0 disease has an average survival of 10 years or more. If you were stage III and become stage 0 after treatment with FCR it doesn't mean that you now have an average survival of more than 10 years. This is especially the case when you are moved out of stage III by treatment with erythropoietin, which raises the Hb without doing anything to the disease. It just makes the bone marrow try harder. You still have the same prognosis as everybody else with stage III.
Another problem is that the normal Hb is higher for men than women - it doesn't have so far to fall before a woman enters stage III or C. This may account for why men do worse than women with this disease. Advanced stage men are already worse off than advanced stage women.
Cropping up a lot this year has been staging by CT scan. All the prognostic information associated with Rai and Binet staging is dependent on clinical staging. To call a patients stage II because a spleen is a bit enlarged on CT scan plays the patient false. A few retroperitoneal lymph nodes do not make a patient stage I. It is only what can be felt with the hand or seen on a blood count that matters. Kanti Rai himself this year said that if CT scans were to be taken into account then all the data on the natural history of CLL accumulated over the past 30 years will have to be jettisoned.
The French group later defined a type of smoldering CLL: Lymphocytosis only with a lymphocyte count no higher than 30,000 per cu mm and an Hb greater or equal to 12 g/dL. They called this group stage A' and other stage A patients stage A''.
The Spanish group also had a version of smoldering leukemia that was a bit more stringent. They required a lymphocyte count no greater than 30,000 per cu mm, and Hb greater or equal to 13 g/dL, non-diffuse bone marrow histology and a lymphocyte doubling time greater than 12 months.
The last thing I want to say about staging is to beware of the Ann Arbor staging method. This is for lymphomas not CLL. Anybody who has bone marrow involvement is stage IV by Ann Arbor. Everybody with CLL has bone marrow involvement, even those with Rai stage 0. Since stage IV is regarded as an indication for treatment, many people have been treated inappropriately.