In vivo amifostine (WR-2721) prevents chemotherapy-induced apoptosis of peripheral blood lymphocytes from cancer patients.

Aim of this work was to evaluate whether in vivo amifostine (WR-2721, ethanethiol, 2-[(3-aminopropyl)amino]-,dihydrogen phosphate (ester), Ethyol) pretreatment was able to prevent the apoptosis of peripheral blood lymphocytes (PBLs) induced by cytotoxic drugs. The study included 19 patients with advanced gynaecological cancers who received neoadjuvant polychemotherapy consisting of three cycles of cysplatin, adriamycin, and cyclophosphamide. Five patients received randomly amifostine pretreatment (910 mg/m2). PBLs apoptosis was measured through flow-cytometry using two different methods: a) DNA fragmentation of PBLs cultured in vitro for one hour; b) measurement of early apoptotic cells through Apostain uptake by fresh PBLs. The percentage of apoptotic PBLs was increased in all patients 24 hr after the first chemotherapy cycle (27.1 +/- 15.6 vs 6.3 +/- 6.2, p<.0001). A similar increase was observed in the following chemotherapy cycle. Amifostine pretreatment prevented the apoptosis of PBLs induced by chemotherapeutic drugs. Amifostine also prevented the reduction of lymphocyte number determined by chemotherapy. The results demonstrate that amifostine protects peripheral lymphocytes from the apoptotic damage induced by chemotherapy. This effect may explain the mechanism by which amifostine prevents the chemotherapy-associated reduction of leukocyte number.