300 q 2000 Blackwell Science Ltd Amifostine can reduce mucosal damage after high-dose melphalan conditioning for peripheral blood progenitor cell autotransplant: a retrospective study D. Capelli, 1 G. Santini, 2 C. De Souza, 2 A. Poloni, 1 G. Marino, 2 M. Montanari, 1 M. Lucesole, 1 M. Brunori, 1 D. Massidda, 1 M. Offidani, 1 P. Leoni 1 and A. Olivieri 1 1 Department of Haematology, University of Ancona, Torrette Hospital, Ancona, and 2 Department of Haematology, San Martino Hospital, Genova, Italy Received 2 October 1999; accepted for publication 21 February 2000 Summary. Amifostine (WR-2721; Ethyol) is a well-known cytoprotector, but a possible role in preventing extra- haematological toxicity after high-dose therapy (HDT) has never been investigated. We compared two historical groups of patients who either received (group A, n  35) or did not receive (group B, n  33) amifostine (740 mg/m 2 ) before high-dose (HD) melphalan, followed by autologous infusion of peripheral blood progenitor cells (PBPCs). Amifostine was well tolerated at this dose level. Emesis grade 1±2 was the most important side-effect, but the interruption of infusion was never required. The incidence and median duration of severe mucositis (grade 3±4) was 21% and 0 d (range 0±11 d) in group A and 53% and 7 d (range 0±11 d) in group B. The duration of analgesic therapy was also significantly lower in group A (0 d; range 0±12) than in group B (6 d, range 0±20) (P  0´0001). Severe diarrhoea (3% vs. 25%; P  0´01) and emesis (9% vs. 34%; P  0´01) were also reduced in group A in comparison with group B. No differences were observed between the two groups for haematological recovery. This retrospective study strongly suggests that amifostine can reduce severe mucositis and the use of analgesic drugs in this setting. A randomized study is warranted to confirm these preliminary results. Keywords: amifostine, mucositis, analgesic opioid therapy, PBPC autotransplant, cytoprotection. The low selectivity of chemotherapeutic agents in killing tumour cells instead of normal tissue still remains an unsolved problem that often limits the dose intensity administration and causes chemotherapy-related side- effects, sometimes life-threatening, affecting the quality of life of patients and increasing supportive care costs. Some preliminary data have suggested the efficacy of amifostine in reducing the toxicity of chemotherapy on normal cells without loss of anti-tumour effect. Amifostine (WR-2721, Ethyol) is a phosphorylated aminothiol that is rapidly cleared from the plasma (Grdina & Sigdestad, 1989; Capizzi, 1996) and is metabolized afterwards into an active free thiol metabolite (WR-1065) that is rapidly taken up into cells (Davidson et al, 1980; Shaw et al, 1988). The role of amifostine in protecting normal tissues from radiotherapy and alkylating and platinum agent toxicity has been shown to be due to both a modification of the DNA target of the chemotherapeutic agents and to its well-known oxygen free radical scavenger activity (Myers et al, 1977; De Neve et al, 1988; Treskes et al, 1992; List et al, 1996). In vitro studies showed that preincubation with amifostine or WR-1065 enhanced the colony-forming ability of the bone marrow progenitors and protected these progenitors from the cytotoxic action of several drugs (Wasserman et al, 1981; ; Doz et al, 1991; Douay et al, 1995a; List et al, 1996, 1998). Moreover, ex vivo pretreatment with amifostine protects haemopoietic progenitors against alkylating agents in purging models using both bone marrow (Douay et al, 1995b) and peripheral blood (Poloni et al, 1999) progenitor cells. Preclinical animal studies indicated that amifostine could increase the radiochemoprotection of normal tissues and this effect tended to be greater in the normal than in the malignant tissues (Calabro-Jones et al, 1985; Schuchter & Glick, 1993; Capizzi, 1996). Phase II and III clinical trials in patients who received British Journal of Haematology , 2000, 110, 300±307 Correspondence: Debora Capelli, Department of Haematology, University of Ancona, Ospedale Regionale Torrette, Via Conca, 60020 Ancona, Italy. E-mail: clinemat@popcsi.unian.it