BCG treatment of residual disease in acute leukemia: studies in a rat model for human acute myelocytic leukemia (BNML).

The effect of a single injection of Pasteur BCG on the growth of a myelocytic leukemia transplantable in the Brown Norway rat (BNML) was studied. BCG (3.0 mg i.v.) caused a 6-fold increase in spleen weight with marked granuloma formation. After aspecific immunostimulation the TD50 for leukemic cells increased from 38.8 to 302.2 cells. Cyclophosphamide (100 mg/kg) given 48 h prior to BCG did not influence the anti-tumor immune response. However, cyclophosphamide injected after BCG partly abolished its activity. After high-dose chemo-radiotherapy of leukemic rats BCG significantly hampered the outgrowth of residual leukemic cells. Relapse from leukemia could even be avoided completely when BCG was injected after cyclophosphamide (100 mg/kg) and total body irradiation (7.0 Gy) followed by isologous bone marrow transplantation. These results are discussed in relation with the tumor load at the time of maximal immunostimulation. Finally, the data are extrapolated to those of the many controversial clinical studies.