CHROMOSOMAL CHANGES IN RHEUMATOID-ARTHRITIS PATIENTS TREATED WITH CPH82

Chromosomal changes were assessed in 19 patients with rheumatoid arthr itis (RA) treated with CPH82, a benzylidated podophyllotoxin glycoside , for up to one ve:lr. The frequency of chromosomal aberrations (CA) a nd sister chromatid exchanges (SCE) in peripheral lymphocytes increase d significantly after 12 weeks of treatment and remained elevated afte r 48 weeks treatment in peripheral lymphocytes. The number of CA and S CE were significantly increased in CPH82 treated patients compared wit h the RA patients treated with other disease modifying anti-rheumatic drugs (sulphasalazine, gold, D-penicillamine, azathioprine, methotrexa te, cyclophosphamide). Only two patients treated with cyclophosphamide and azathioprine had changes of comparable levels, The results of thi s study suggest a mutagenic potential of CPH82 similar to that describ ed for other immunosuppressive drugs and the newer podophyllotoxin der ivatives, etoposide and teniposide.