The potential role of amifostine (Ethyol) in haematological malignancies

Autologous bone marrow transplantation (ABMT) has considerably developed in the past 20 years. In AML, the beneficial role of purging the graft with cyclophosphamide derivatives (4-HC or mafosfamide) has been strongly suggested by retrospective studies from the European Cooperative Group for Blood and Marrow Transplantation and by single institution studies. Also, gene marking experiments have clearly shown that tumour cells infused with unpurged marrow indeed recirculate and in some instances, induce or contribute to tumour recurrence. Amifostine protects normal progenitor cells without concomitantly protecting colony forming unit leukaemic progenitors (CFUL). In comparative in vitro studies, we have shown that pre-incubation of normal marrow contaminated by leukaemic progenitors with amifostine followed by mafosfamide, results not only in a protection of the more mature progenitors (CFUGM, BFUE), but also sensitises leukaemic progenitors, so that in the end, the therapeutic index of mafosfamide is increasing by 6 logarithms. In the clinical field, it has been shown in patients with breast cancer autografted with protection by amifostine results in a shortening of the duration of aplasia of about 10 days. A European randomised study evaluating amifostine in the context of autografting for acute leukaemia has just started.