Adjuvant Immunotherapy with BCG for Malignant Brain Tumors

Abstract

Old reported in 1961 that BCG inoculations apparently prevented the establishment of tumor by chemical agent in animals, and Mathe and Morton reported good results using BCG for leukaemia and melanoma patients.
The PPD reaction and the number of peripheral lymphocytes of patients with neurosurgical diseases were studied. BCG (0.1-8 mg) was inoculated, from once to several times, intradermally to 68 patients with malignant brain tumors whose PPD reactions were negative.
The results were as follows: 1. Most patients with malignant brain tumors showed negative PPD reactions and lymphocytopenia. On the other hand, PPD reactions on patients with benign tumors or without tumor were mostly positive, and lymphocytopenia was rarely noted; 2. In 69.2% of cases, PPD reaction turned to positive after BCG inoculation; 3. The prognosis was compared between the glioma patients with or without BCG inoculation. The 2-year and 3-year survival rates of the former group were 68.40% and 37.5% respectively, which were significantly higher than those of the latter group (2-year survival: 25.0%, 3-year: 12.5%). The average survival time of the former was about 24 months which was about 7 months longer than that of the latter. As for the patients with metastatic brain tumors, the prognosis of the BCG combined group was best, among the 5 groups treated with various combination of therapies; 4. When prognosis were compared between patients whose PPD reaction turned to positive and whose PPD reaction remained negative after the repetitive inoculation of BCG, it revealed that the survival rate was significantly higher in the former.
Two cases, one with glioblastoma multiforme and the other with metastatic brain tumor from the uterus, who showed good clinical courses by BCG therapy are also presented.
Among the side effects of BCG, fever, local pain and ulceration, and appetite loss were common, but they were transient and easily controlled. No cases of anaphylaxis, or dysfunction of liver and/or kidney were recognized.
Though the mechanism of BCG effects to malignant tumors has not yet been well elucidated, following mechanisms are suggestive: 1. It stimulates the reticuloendothelial system to increase the number of macrophages; 2. Its adjuvant action increases the antigenicity of the tumor, and makes the host easier to recognize the tumor specific antigen; 3. It involves non-specifically the tumor cells in the specific inflammatory reaction when introduced into the tumor.
It is concluded that the immunosurveillance systems in patients with malignant brain tumors have deteriorated, and the use of BCG as an adjuvant immunotherapy for such cases is recommended.