In Waldenstrom's macroglobulinemia the quantity of detectable circulating monoclonal B lymphocytes correlates with clinical course.

Using a sensitive flow-cytometer-based method of detecting small numbers of morphologically normal monoclonal B lymphocytes, we have investigated the presence and quantity of these cells in the blood of 12 patients with Waldenstrom's macroglobulinemia. All 12 patients, including 6 at the time of asymptomatic presentation, had such circulating monoclonal cells. By comparison, 2 of 7 patients with multiple myeloma had such cells, and prior studies have shown that 80% of patients with non-Hodgkin's lymphoma exhibit blood involvement by these criteria. Enzymatic removal of surface immunoglobulin (lg) with subsequent regeneration by the cells after overnight culture established that the monoclonal surface lg being studied was of intrinsic cell membrane origin and not passively adsorbed serum lg. Serial studies were performed in 7 patients. In the 4 cases where a clinical response to therapy and a decrease in serum IgM level was seen, there was a corresponding decrease in the estimated number of abnormal cells. In the 3 cases where there was neither clinical nor serum M-component evidence of response, the estimated percent abnormal cells likewise increased or remained constant. We conclude that patients with Waldenstrom's macroglobulinemia have a significant number of peripheral blood monoclonal B lymphocytes, even early in their disease, and that for a given patient, serial determinations of the number of these cells as estimated by flow cytometry reflects the clinical activity of the disease.