Late immune and haemopoietic functions in plasmacytoma-bearing mice cured by melphalan.
Alkylating agents can cause latent and permanent damage to the bone marrow. We compared the long term effects of melphalan on a number of immune and haemopoietic functions of plasmacytoma bearing BALB/c mice with that of normal mice treated with a similar dose of melphalan. The drug administered orally at a dose of 250 micrograms and 400 micrograms on day 14 and 24 following i.m. inoculation of MOPC-315 plasmacytoma cells resulted in cure of the mice. Their spleen cells showed a permanent impairment of MLR activity, T-cell number and IL-2 production as well as a mild suppression of NK activity for one year after cessation of melphalan therapy. The number of B cells was elevated. In contrast, plasmacytoma-free mice treated with melphalan retained long term normal immune functions, although shortly after melphalan therapy a temporary suppression was noted. On the other hand, melphalan was responsible for bone marrow myeloid stem cell damage since the number of myeloid progenitor cell (CFU-GM) colonies was reduced in both melphalan-treated groups compared to untreated normal controls. Plasmacytoma bearing mice had a shorter survival. These results demonstrate that some late sequelae of alkylating agents are not due to the drug alone; shorter survival and T-cell deficiency are related to the previous presence of the tumour.
Sagi
O
O
Department of Microbiology, Sheba Medical Center, Sackler Faculty of Medicine, Israel.
Witz
I P
IP
Ramot
B
B
Sahar
E
E
Douer
D
D
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects; D007958:Leukocyte Count; D008214:Lymphocytes / Q000187:drug effects*; D008558:Melphalan / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D010954:Plasmacytoma / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects
D008558:Melphalan