Myeloproliferation in long‐term plasmacytoma‐regressor mice

MOPC‐315 plasmacytoma‐bearing BALB/c mice were treated with high doses of melphalan, causing a permanent and complete regression of the tumor. In the present study we analyzed plasmacytoma‐regressor mice (PRM) 3–6 months after plasma‐cytoma regression. A second group of otherwise untreated normal mice was treated with melphalan (M—control group). A third group of mice remained untreated and served as an age‐and sex‐matched control group. PRM were cachectic and had an increased mortality rate compared to the M and the C control groups. Histopathological examination indicated that the spleen of PRM showed pronounced abnormalities, primarily in the red pulp. These abnormalities consisted of extramedullary hematopoiesis and myeloid‐granulocytic hyperplasia. Spleens of M mice showed similar abnormalities but to a much lesser extent. Flow cytometric analysis of cellular surface markers of PRM splenocytes indicated a high number of large MAC‐1‐and GR‐1‐positive cells compared to splenocytes of M or C controls. These large cells also expressed For receptors (FcτRII), stained positively with non‐specific esterase and adhered to plastic dishes; a certain percentage expressed MAC‐2 and MAC‐3 antigens. A quantitative suppression of CD4+ T cells and of B cells was also shown. Circulating levels of TNF were higher in PRM than in M or C mice. The capacity of splenocytes from PRM to secrete factors that stimulated CFU‐GM colony formation in soft agar by bone‐marrow cells from normal mice was significantly up‐regulated compared to that of splenocytes from M or C mice. PRM‐derived splenocytes also reacted significantly better to rIL‐3 and rGM‐CSF than splenocytes from M or C controls. We conclude that the splenic myeloproliferation in PRM was not caused by melphalan chemotherapy alone and is an abnormality related to the primary tumor, possibly in conjunction with chemotherapy. No evidence of a secondary overt malignancy was obtained.