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Inhibition of the Primary Immune Response in Man by Anti-Metabolites

( Medicine Branch, National Cancer Institute, and Ophthalmology Branch, National Institute of Neurologic Diseases and Blindness, Bethesda, Maryland)

The effect of anti-tumor agent therapy on the primary immune response was studied in 45 patients with malignant and inflammatory diseases. The % complete inhibition of the primary response to tularemia and to Vi and pneumococcal polysaccharide antigens by 6 therapeutic programs were: intermittent i.v. methotrexate, 50%; intensive 5-day methotrexate, 71%; daily i.v. methyl-GAG,¹ 46%; intensive 5-day 6-mercaptopurine, 75%; 6-mercaptopurine, methotrexate, vincristine, and prednisone in combination, 60%; vincristine and prednisone in combination, 60%.

At least 25% of antigenic stimulations in each treatment program resulted in low but significant antibody titers in spite of chemotherapy.

There was an inverse relationship between antigenic strength and the degree of suppression of the immune response to the given antigen.

The degree of immunosuppression did not correlate with the toxicity of the treatment programs.

Chemotherapy did not affect isoantibody titers or established delayed hypersensitivity.

¹ The following abbreviations are used: methyl-GAG, methylglyoxal bis-guanylhydrazone; MTX, methotrexate; 6-MP, 6-mercaptopurine; Pred, prednisone; VCR, vincristine; Vi, Vi antigen; Tu, tularemia vaccine; Pn, pneumococcus Type III polysaccharide.

Received 2/19/65.