Effects on bone marrow cells of oral treatment with podophyllotoxin derivatives in rheumatoid arthritis

SPG 827, a mixture of podophyllotoxin derivatives, has been thought to alleviate the symptoms of rheumatoid arthritis (RA) by arresting cell division in metaphase (i.e. resulting in an increase of the mitotic index) of rapidly proliferating cells of the immune apparatus. In contrast, the present study produced evidence that peroral SPG treatment of RA patients reduced the mitotic index of bone marrow cells, mainly in erythropoiesis. At the same time, slight megaloblastic changes appeared in the erythroblasts. These observations suggest that SPG treatment induced an interphase block in the G2 phase of the cell cycle, analogous to the cell action of the newer podophyllotoxin derivatives teniposide and etoposide. It may be that part of the clinical effect of SPG in rheumatoid arthritis is due to the described interphase-blocking activity.