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Inhibition of in Vitro Lymphocyte Transformation during Chemotherapy in Man¹

Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland

The in vitro transformation responses of lymphocytes to stimulation with phytohemagglutinin (PHA) and smallpox vaccine (vaccinia) were studied in cells from 20 patients with ocular and malignant diseases receiving chemotherapy. The transformation of lymphocytes to lymphoblast-like cells was reduced from 71% in the pretreatment PHA-stimulated cultures to 1.5% during therapy. The response to vaccinia was reduced from 12% before therapy to 0% during therapy. The mitotic indices fell from 1.5% (PHA) and 1.2% (vaccinia) to 0% for each during therapy.

Intensive combination therapy with parenteral 6-mercaptopurine and methotrexate, with or without prednisolone completely abolished transformation after 3 days of treatment. Substantial recovery occurred within 3 days after the end of therapy. Nontoxic therapy with methotrexate or 6-mercaptopurine which did not induce leukopenia took 2–5 weeks to cause maximum suppression.

The abnormality seemed due to intrinsic damage to the lymphocytes and not to persistent antimetabolite in the plasma.

In vitro lymphocyte transformation is an easy and reproducible way of evaluating the immune competence of an individual's circulating lymphocytes.

¹ Presented in part at the Annual Meeting of the American Association for Cancer Research, held at Philadelphia, Pa., April 9, 1965.

² Present address: M. D. Anderson Hospital and Tumor Institute, The University of Texas, Houston, Texas.

Received 7/ 2/65. Accepted 8/18/66.