Studies in chronic lymphocytic leukemia: further studies of the proliferative abnormality of the blood lymphocyte.

A NUMBER OF STUDIES have demonstrated that peripheral lymphocytes from patients with advanced chronic lymphocytic leukemia ( CLL) show a greatly reduced transformation to blast cells ( “immunoblasts”) in response to phytohemagglutinin (PHA) in vitro?5 The metabolic events involved in lymphocyte transformation were investigated by an analysis of the kinetics of RNA and DNA synthesis employing this method.6’7 Rubin et al. demonstrated that about 26 per cent of CLL lymphocytes become transformed only after 5-7 days rather than in 2-3 days, at which time 60-80 per cent of normal lymphocytes respond. In the present study, the late-responding lymphocytes of CLL were identified as abnormal cells distinct from any population thus far detected in normal individuals. CLL is a disease of many variations. Many cases are apparently “benign” and asymptomatic.8 Such cases may go along for many years without symptoms and with no or slight enlargement of lymph nodes or spleen. These cases may exhibit a slight to moderate leukocytosis of 15,000 to 50,000 per cu.mm., a marked lymphocytosis of 60-90 per cent, and a marrow containing a considerable proportion (50-90 per cent) of small lymphocytes. As these cases are observed over a 10 to 25 year period, there is almost invariably a gradual increase in leukocytes of the lymphocytic variety to levels of 100,000 per cu.mm. or greater, with a simultaneous marked increase in lymph node enlargement and splenomegaly. Symptoms such as fatigue and night sweats are usually present at this stage. Some cases, apparently more “aggressive” from the beginning, show marked lymphadenopathy and systemic symptoms as first manifestations. The cases of CLL which served as the basis for this report could be divided into those with relatively low lymphocyte counts (“low count cases”) and those