J. Radl et al., TENFOLD INCREASED INCIDENCE OF SPONTANEOUS MULTIPLE-MYELOMA IN LONG-TERM IMMUNOSUPPRESSED AGING C57BL KALWRIJ MICE/, Clinical immunology and immunopathology, 79(2), 1996, pp. 155-162
Persons undergoing maintenance immunosuppressive treatment (MIST) were
shown to be at increased risk for the development of early malignanci
es, often of cells of the immune system. Very little is known about th
e late effects of MIST. Some clinical studies indicated an age-related
increase in the incidence of plasma-cell disorders, in particular in
that of multiple myeloma (MM). In the present study the influence of M
IST on the development of monoclonal B-cell proliferative disorders, m
onoclonal gammopathies (MG), was studied in an animal model, the C57BL
/KaLwRij mouse. This strain is known for its susceptibility to develop
with aging MG similar to those in humans. Two widely used treatment p
rotocols (azathioprine/prednisolone and Cyclosporin A/prednisolone) we
re tested in young and adult mice. Both regiments were shown to increa
se 10-fold the incidence of spontaneous multiple myeloma. Unexpectedly
, the same high incidence of MM and in addition the development of a l
ife-shortening lymphoblastic lymphoma were found in a high frequency i
n the control group that received Cremophor EL only, i.e., the solvent
of Cyclosporin A. Repeated experiments with another lot of Cremophor
showed a 6-fold increased frequency of MM but no lymphoblastic lymphom
a. With respect to the life-span and the incidence of hemopoietic neop
lasms the least harmful drugs for MIST appeared to be azathioprine/pre
dnisolone. The results of the experiments in this C57BL/KaLwRij mouse
model ave a warning for increased incidence of MM in susceptible aging
individuals and address a question whether Cremophor EL is a safe sol
vent for Cyclosporin A. (C) 1996 Academic Press, Inc.