Unlike the three other types of leukemia, the cell of origin in CLL is not the bone marrow stem cell but rather a mature lymphocyte (lymph cell).
This cell does not have the innate explosive growth capacity of a stem cell or the ability to form any cell other than another lymphocyte.
These differences account, in part, for the less aggressive course of CLL in comparison to the other leukemias. CLL is often diagnosed when routine blood testing reveals an elevated white blood cell count and all other laboratory tests are normal. The abnormal lymphocytes of CLL may reach very high levels in the bloodstream without causing ill effects.
CLL is the most common form of inherited leukemia, although the vast majority of cases do not run in families. Patients with a family history of CLL may wish to help researchers discover the genes responsible for this inheritance pattern by donating a sample of blood. They can ask their oncologist or a genetics counselor for the name of a center that is researching familial CLL.
Like other leukemias, CLL cells are found in the circulation and bone marrow. Unlike the others, however, CLL is also typically found in the spleen and lymph nodes. CLL is staged in the
Low-risk CLL includes stage 0 (lymphocytosis only); intermediate-risk disease includes stage I (enlarged lymph nodes) and stage II (enlarged liver or spleen); high-risk CLL includes stage III (anemia) and stage IV (low platelet count). The higher the risk category, the greater the need for treatment.
The growth of CLL in lymph nodes is very similar to the pattern of growth of lymphomas. Indeed, oncologists think of CLL more as a lymphoma than a leukemia, and it is treated most successfully with the same chemotherapy drugs and antibody treatments used to treat lymphoma.
Although the treatment of CLL improves every year, the only known way to cure CLL is with a stem cell transplant from another individual. However, because CLL mainly affects older individuals and this procedure is risky, only a small percentage of CLL patients are suitable candidates for it. For any patient, treatment recommendations are based on the stage of the disease, the patient’s health, and estimates of the aggressiveness of the CLL, which varies from patient to patient.
I recently met a seventy-four-year-old man in excellent health who was referred to me after he was incidentally noted to have an elevation of the lymphocyte count on routine blood testing by his primary care physician. D. was a retired businessman who played tennis six days a week and worked around the house on the seventh day. He had never felt physically better in his life.
I could tell from looking at a slide of his blood under the microscope that the leukemia cells in his circulation were characteristic of CLL. Specialized testing of the blood with flow cytometry would later confirm the diagnosis (a bone marrow biopsy is not essential to make the diagnosis of CLL).
Because he felt so well, D. was understandably dumbfounded when I told him he had leukemia. As is often the case in CLL, however, certain features of his disease indicated that he would not likely need any treatment for many years. Instead, he would see me four times a year to monitor the disease, a policy called observation or “watch and wait” (also called “watch and worry” by some patients).
In contrast, I also care for S., a forty-five-year-old woman who required treatment with two chemotherapy drugs (Fludara and Cytoxan) plus an immune therapy (Rituxan) for CLL that had grown to the point that the lymph nodes in her neck were bulging visibly and her energy was declining.
After one course of treatment, her lymph nodes could no longer be felt. She continued to work throughout her six courses of treatment and is now back to having the CLL merely observed. S. will ultimately require additional treatments when the disease returns, but it cannot be predicted when this will occur.
These two cases illustrate the range of behaviors of CLL. To some, CLL is a problem only in name; it will not shorten their life span. To others, it is a life-threatening cancer.
To help predict the future behavior of each newly diagnosed case, oncologists often test the CLL cells (which can be obtained from the blood or bone marrow) in several ways.
These include:
1. Analysis of the chromosomes of the CLL cells; some abnormalities portend an indolent or slow course, whereas others predict a more aggressive course.
2. Assessment (by flow cytometry) of whether the cells possess two markers, ZAP-70 and CD-38. CLL that contains both markers tends to be more aggressive, whereas CLL that contains neither marker tends to be the least aggressive; the presence of one marker predicts an intermediate aggressiveness.
3. Determination of the status of a segment of CLL DNA called IgVH (pronounced I, G, V, H). IgVH status is either “mutated” or “nonmutated”; the mutated group carries the more favorable prognosis.
