Impairment of concanavalin A-inducible suppressor activity following administration of cyclophosphamide to patients with advanced cancer

Abstract

We have shown that cyclophosphamide (CY) can augment the development of delayed-type hypersensitivity to a primary antigen in patients with advanced cancer. In the present study, we administered CY (1000 mg/sq m) to 19 patients with advanced, metastatic cancer and monitored the compositional and functional changes in their peripheral blood mononuclear cells. Within 2 days of administration of CY, the lymphocyte count fell significantly (mean decrease = 26.0%) and remained significantly depressed through Day 14 with recovery beginning by Day 21. T- and B-lymphocytes were depleted to about the same degree at each time point. Moreover, there was no selective depletion of the Leu 2(+) (suppressor-cytotoxic) or Leu 3(+) (helper-inducer) subsets of T-lymphocytes. Proliferative responses to mitogens (phytohemagglutinin, concanavalin A, pokeweed mitogen) and to allogeneic cells fell significantly within 1 day of administration of CY and continued to be diminished on Day 2. However, these responses recovered to pretreatment levels by Day 3, and, in some cases, exceeded pretreatment levels on Day 7. Concanavalin A-inducible suppressor activity was also diminished on Day 1 (mean decrease, 23.4%) and Day 2 (mean decrease, 39.2%). However, in contrast to the proliferative responses, suppressor activity continued to be significantly impaired on Day 3 (mean decrease, 31.6%) and only partially recovered by Day 7 (mean decrease, 22.1%). Both concanavalin A-inducible suppression and proliferative responses declined again on Days 14 and 21. Thus, between 3 and 7 days after administration of CY, there appeared to be impairment of nonspecific T-cell-mediated suppressor activity of peripheral blood lymphocytes that was not merely a reflection of impaired lymphocyte function in general. This could account for the augmented delayed-type hypersensitivity responses of CY-treated patients.