Pure red cell aplasia and hypogammaglobulinemia associated with Tr-cell chronic lymphocytic leukemia

Abstract

A 72-yr-old male with Tr-cell chronic lymphocytic leukemia (Tr-CLL) exhibited pure red cell aplasia (PRCA) and hypogammaglobulinemia. During a remission of Tr-CLL, and while receiving cyclophosphamide therapy, he recovered from PRCA and hypogammaglobulinemia. To investigate the pathogenesis of PRCA and hypogammaglobulinemia, we used coculture techniques to study the effect of the malignant Tr cells on erythroid colony formation and B-cell differentiation to immunoglobulin- producing cells. Varying numbers of malignant Tr cells (2 X 10 to 2 X 10(5) cells) were cocultured with 2 X 10(5) normal bone marrow cells. The malignant Tr cells caused a marked reduction of erythroid colony formation in the plasma clot system. This suppression of erythroid colony formation was reversed when the malignant Tr cells were pretreated with antilymphocyte serum and complement. There was no evidence of inhibitory effects in the serum or the supernatant media of the malignant Tr cells stimulated with phytohemagglutinin (PHA). The malignant Tr cells, stored at --80 degrees C before transfusion, were also capable of suppressing autologous erythroid colony formation after recovery from PRCA. In addition, malignant Tr cells were found to have strong suppressor activity against the immunoglobulin biosynthesis by allogeneic B cells. The in vitro suppressions of both erythroid colony formation and B-cell differentiation provide an explanation for the association of PRCA and hypogammaglobulinemia with Tr-CLL.