PRESIDENT'S CORNER: Opinions & Reports from Dr. Michael Keating
Understanding CLL & SLL
Both leukemia and lymphoma are diseases of B-lymphocytes, which are a type of white blood cell involved in the immune system. The term leukemia was coined by Dr. Rudolph Virchow, a renowned German pathologist, in 1856. While performing autopsies, Dr. Virchow observed that patients who had enlargement of lymph glands, spleen and liver, and abnormal appearing bone marrow, also had white streaks in their blood. Accordingly, leukemia translates to mean “white blood”.
The term lymphoma can be broken down into two parts. The suffix –“oma” describes swelling or presence of a tumor. This suffix is used often in medical terminology. “Lymph-” describes the location of the tumor which is the lymphatic system. The lymphatic system is where white blood cells reside when they are not circulating in the body fighting illness and disease.
Chronic lymphocytic leukemia (CLL) is classified as a leukemia because it primarily affects the blood and is characterized by an elevated white blood cell count. Its lymphoma counterpart, small lymphocytic lymphoma (SLL), infiltrates the lymphatic system, but does not affect the white blood cell count because only a small number of these cells circulate in the blood. Although CLL and SLL do vary slightly, a number of studies have now been conducted which confirm that the cell of origin in CLL and SLL is identical. Both CLL and SLL start in the bone marrow and are sent through the blood stream to various sites in the body including the lymph glands and the spleen. B-lymphocytes, including SLL cells, normally attach to receptor molecules in the lymph glands and the spleen and take up residence in those sites so that they can mature further and conduct their functions as immune cells. A number of CLL cells do not have these attachment molecules and therefore continue to circulate so that the white cell count gradually increases in the blood stream. Apart from the attachment molecules, CLL and SLL have the same genetic pattern and the same prognostic markers. Survival and response to treatment tend to be very similar.
Patients are often confused when they are initially diagnosed with CLL, yet a subsequent lymph gland biopsy describes the diagnosis as SLL or SLL/CLL. This does not mean that a patient has lymphoma in addition to CLL. Rather, the pathologist (the scientist who examines biopsies and determines diagnosis) has identified cells present in a particular pattern in the lymph gland, which is indicative of SLL, but may not be aware that the white blood cell count is increased. Patients sometimes think that if a lymphoma is reported by the pathologist that this may be a sign of a transformation (Richter’s transformation) which has a high risk prognosis. This is not so, and it is important that these issues be addressed with a hematologist to discuss the pathologic diagnosis.
A difficult feature for CLL/SLL patients to understand is that lymphomas have a different staging system than CLL. The lymphoma staging system, known as the Ann Arbor classification, determines the disease stage based on the location of the disease and whether there is bone marrow involvement. In patients with CLL the bone marrow is always involved. The same is true for almost all SLL patients. Consequently, SLL patients who have involvement of the bone marrow will be classified as having stage IV disease under the Ann Arbor classification. This suggests, sometimes incorrectly, a more progressive/advanced disease in these patients. However the Rai and Binet classifications used in CLL focus more on whether the lymph glands and spleen can be examined by feel and whether the production of normal red cells and platelets will be normal. Thus, the staging classifications are quite different. The Ann Arbor staging system is not helpful in separating patients according to a particular prognosis, whereas, the Rai and Binet staging systems are very good at identifying prognosis in both SLL and CLL.
Hopefully this description will help patients identify that CLL and SLL are the same disease with similar indications for treatment. A diagnosis of both CLL and SLL does not indicate advanced disease; it simply means their malignant cells are diverse. Rest assured all of the progress which is being made in CLL is equally applicable to patients with SLL.