A NEW IN-VITRO ASSAY FOR QUANTITATION OF CHEMOTHERAPY-INDUCED MUCOSITIS

Patients receiving high-dose chemotherapy (HD-CT) are at risk of sever e mucositis. Most prevention studies evaluate the degree of mucositis on clinical, and therefore subjective, measurements. The aim of this s tudy was to develop an objective in vitro assay of chemotherapy-induce d mucositis. Twelve patients with locally advanced breast carcinoma re ceived HD-CT followed by peripheral stem cell reinfusion. Before and t wice weekly after HD-CT, the mucosa was evaluated by an oral washing, a buccal smear and the World Health Organization (WHO) toxicity gradin g; furthermore, blood leucocyte levels were determined. For the oral w ashings, the percentage of viable epithelial cells was determined by t rypan blue dye exclusion and leucocytes were counted by fluorescence m icroscopy after incubation with acridine orange. Maturity of buccal ce lls was assessed by staining buccal smears for morphology according to Papanicolaou (Whitacker D and Williams V, 1994). Eight healthy volunt eers served as controls. The mean percentage (+/- s.e.m.) of viable or al epithelial cells was stable in controls (44 +/- 2%). In patients, t hey increased after HD-CT, which was significant after day 7 compared with pretreatment (P less than or equal to 0.05). In addition, a shift from mature to immature epithelial cells in buccal smears was observe d. Oral leucocyte levels were closely correlated with the blood leucoc yte counts. The WHO score followed the results of these other evaluati ons with some delay. The viability of buccal cells obtained by oral wa shings increases after HD-CT. This is possibly because of desquamation of the upper oral mucosa layer, with a shift from mature to more imma ture cells. These data can be quantitated, and this assay may therefor e be useful in studies aimed at prevention of mucositis.