IMMUNE DISORDERS IN CLL
The etiology of CLL is unknown. Despite occasional familial clusterings of CLL, no firm genetic basis for the disease has been found, nor does exposure to radiation or other potentially mutagenic agents such as alkylating agents appear to predispose. Consistent chromosomal abnormalities have not been found and, to date, no convincing data support a viral etiology.
A major contribution to understanding the natural history of CLL is the clinical staging system devised by Rai et al., which identifies prognosis according to the state of illness at the time of first diagnosis (Table 54-7). The stages of the disease reflect the concept of the “accumulative” nature of CLL. Stage 0 is lymphocytosis alone. Stages I and II reflect the development of increasing tumor mass (nodes, liver, or spleen), while the anemia and thrombocytopenia of stages III and IV indicate bone marrow replacement interfering with normal hematopoiesis, and splenomegaly causing decreased red blood cell and platelet survival. Most patients are in stage 0, I? or II at the time of diagnosis.
Figure 54-6 plots the median duration of survival from the time of diagnosis of 125 patients studied by Rai et al. As can be seen, although the median survival was 71 months, the duration depended considerably on the clinical stage. Although palliative treatment exists, there is no cure for CLL.
Treatment is generally withheld in the asymptomatic stage. When symptoms such as enlarging lymph nodes, splenomegaly, progressive anemia, and/or thrombocytopenia occur, alkylating agents (e.g., chlorambucil) and prednisone prove beneficial. Radiotherapy to the spleen or to areas of bulky adenopathy may be useful.
Hairy cell leukemia (HCL) (also called leukemic reticuloendotheliosis) is a neoplastic disorder characterized by “hairy cells” in the peripheral smear and bone marrow. Hairy cells look like lymphocytes with fine cytoplasmic projections. Unlike B cells, they are capable of phagocytosis. The cells stain positive for tartrate-re-sistant acid phosphatase (TRAP).
HCL is more common in men than women and usually presents as a slowly developing pancytopenia with splenomegaly. Splenectomy may be useful if the spleen enlarges painfully or severe cytopenia develops. Chemotherapy has not helped most patients with hairy cell leukemia. The median survival for patients with hairy cell leukemia is three to five years; some patients live many years after diagnosis with little treatment.