Detection of tumor cells in the peripheral blood of nonleukemic patients with B-cell lymphoma: Analysis of 'clonal excess'

Patients with malignant lymphocytic lymphoma often respond to therapy with the disappearance of mass disease and achievement of complete clinical remission. Since the disease usually reappears and eventually causes death, it appears that disseminated disease continues to exist undetected by current methods of clinical analysis. Samples of peripheral blood from nonleukemic patients with malignant lymphocytic lymphoma were examined for an excess of cells bearing the same immunoglobulin light-chain type as tumor cells from tissues involved with the lymphoma. Cells from tumor-bearing tissue and from peripheral blood (which appeared normal by the usual laboratory criteria) were stained with the anti-light-chain reagents, and the fluorescence intensity of individual cells was quantified using the fluorescence-activated cell sorter. Comparison of the number of κ⁺ and λ⁺ cells at each level of fluorescence intensity detected monoclonal populations representing as little as 0.1% of the lymphocytes. Though increases in the proportion of monocytes or null cells to lymphocytes prevented complete analysis of B-cell staining in some cases, all peripheral blood samples from patients with lymphoma that could be analyzed (11/20) exhibited evidence of 'clonal excess'. Thus, the recognition of an excess of cells bearing the same light-chain type in both blood and tumor tissue provides strong evidence that the circulating monoclonal lymphocytes were tumor cells.