Heterogeneity among the non-Hodgkin's lymphomas. Implications for autologous bone marrow transplantation with in vitro purging using monoclonal antibodies.

Abstract

To investigate the possible implications of heterogeneity among the non-Hodgkin's lymphomas for bone marrow purging using complement-fixing monoclonal antibodies to lymphoma-associated antigens, a panel of large cell lymphoma cell lines of diverse phenotypes was treated with monoclonal antibodies DLC-48 and LN-1. An association was demonstrated between the percentage of suppression of colony formation by the cell line and both the percentage of cells staining with the antibody and the intensity of its binding. Flow cytometric analysis of cells surviving treatment with antibody and complement demonstrated that the population that escaped lysis showed weak immunofluorescent staining. Similarly, 40% of the clones derived from cells surviving treatment with antibody and complement stained weakly compared with the parent cell line. For a given fluorescence intensity, cells differed in their susceptibility to treatment. Some cells with moderate to strong staining survived incubation with antibody and complement. In five cases, treatment of bone marrow contaminated with malignant lymphoma cells resulted in complete eradication of even cells with weak staining. In two cases, a population of cells that stained dimly survived treatment with either antibody. DNA-content analysis showed that the cell cycle distribution of cells surviving treatment with DLC-48 or LN-1 and complement was similar to that of cells treated with control antibody 46-1G7 and complement. Phenotypic heterogeneity may hinder efforts to purge malignant lymphoma cells from human bone marrow with complement-fixing monoclonal antibody reagents. Relative resistance to complement-mediated lysis may underlie differences in the susceptibility of cells to treatment and also limit the effectiveness of this technique.