Effect of adriamycin and high-dose methotrexate chemotherapy onin vivo andin vitro cell-mediated immunity in cancer patients

Adjuvant chemotherapy with adriamycin (ADR) and high-dose methotrexate (HDM) with citrovorum rescue appears to hold promise for preventing recurrence of sarcomas following surgery. However, the effect of prolonged treatment with these agents on both in vivo and in vitro cell-mediated immunity (CMI) is unknown. To assess in vitro CMI, cryopreserved lymphocytes from 18 patients, collected before and at monthly intervals following initiation of biweekly ADR and HDM therapy, were tested simultaneously for stimulation to phytohemagglutinin, poke-weed mitogen, Concanavalin A, and pooled allogeneic lymphocytes by a micro-test technique. In vivo CMI was determined by serial skin-testing with 2,4,-dinitrochlorobenzene (DNCB). No significant overall change was noted for any of the in vitro lymphocyte function tests. DNCB skin test ratings, peripheral leukocyte counts and absolute lymphocyte counts did not change significantly during the study. Lymphocytes from a second group of patients were tested before, at 24 and 48 hours after HDM therapy. In vitro lymphocyte function tests were significantly depressed 24 hours following treatment, but returned to pretreatment levels at 48 hours. Long-term adjuvant ADR and HDM therapy does not appear to alter in vivo and in vitro CMI, although transient depressions were noted. The preservation of intact CMI may account in part, for the effectiveness of these agents as surgical adjuvants.