Amifostine can reduce mucosal damage after high‐dose melphalan conditioning for peripheral blood progenitor cellautotransplant: a retrospective study

Abstract

Summary. Amifostine (WR-2721; Ethyol) is a well-known cytoprotector, but a possible role in preventing extrahaematological 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.

A prospective, randomized trial for the prevention of mucositis in patients undergoing hematopoietic stem cell transplantation

“…With regard to the cytoprotective activity of amifostine, it has been shown to reduce mucositis and complications associated with high-dose chemotherapy in some studies. [25][26][27] However, unlike amifostine, which is systemically administered, the agents used in this trial were all topical and therefore not associated with systemic side effects.…”

“…Mixed results List (+) 25 Capelli et al (+) 26 Chauncey et al 27 (negative for mucositis) Lactobacillus counts (Caphosol s ) (259023571794144 vs fluoride 209742797848, P ¼ 0.7589) were not significantly different for the two groups. Additionally, all patients had dental prophylaxis advice at the screening visit and those who had high counts were treated with chlorhexidine prior to hospitalization.…”

“…A number of studies have attempted to evaluate different agents or strategies to prevent or treat mucositis associated with high-dose chemotherapy, with conflicting results (Table 1). [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] Prior studies on oral health-care management in oncology patients undergoing head and neck radiation, with or without chemotherapy, have suggested that a preventive regimen designed to address the reduced salivary flow and/or xerostomia was effective in reducing and controlling both the incidence and severity of mucositis. 9,28 The system used in these prior studies consisted of a high fluoride gel administered together with a neutral supersaturated Ca 2+ /PO 4 3À mouth rinse (Caphosol s ).…”

Activity of single-agent melphalan 220–300 mg/m2 with amifostine cytoprotection and autologous hematopoietic stem cell support in non-Hodgkin and Hodgkin lymphoma

“…17 MEL has pharmacokinetic features 12 that match well with those of AF 18 and the presumed requirement for the active intracellular moiety, WR-1065. 19 In addition, MEL has a wide spectrum of antitumor activity against a variety of hematologic and nonhematologic neoplasms.…”

“…[40][41][42][43][44][45][46] These reports have been heterogeneous in design as well as patient-, disease-and treatment-related factors, and have, not surprisingly, had variable outcomes. That said, they are consistent with the hypothesis that AF provides useful cytoprotection in some circumstances.…”