BACKGROUND: Oral mucositis is a complication of intensive chemotherapy and radiotherapy with no effective treatment. We tested the ability of palifermin (recombinant human keratinocyte growth factor) to decrease oral mucosal injury induced by cytotoxic therapy. METHODS: This double-blind study compared the effect of palifermin with that of a placebo on the development of oral mucositis in 212 patients with hematologic cancers; 106 patients received palifermin (60 μg per kilogram of body weight per day) and 106 received a placebo intravenously for three consecutive days immediately before the initiation of conditioning therapy (fractionated total-body irradiation plus high-dose chemotherapy) and after autologous hematopoietic stem-cell transplantation. Oral mucositis was evaluated daily for 28 days after transplantation. RESULTS: The incidence of oral mucositis ofWorld Health Organization (WHO) grade 3 or 4 was 63 percent in the palifermin group and 98 percent in the placebo group (P<0.001). Among patients with this degree of mucositis, the median duration of mucositis was 6 days (range, 1 to 22) in the palifermin group and 9 days (range, 1 to 27) in the placebo group. Among all patients, regardless of the occurrence of mucositis, the median duration of oral mucositis of WHO grade 3 or 4 was 3 days (range, 0 to 22) in the palifermin group and 9 days (range, 0 to 27) in the placebo group (P<0.001). As compared with placebo, palifermin was associated with significant reductions in the incidence of grade 4 oral mucositis (20 percent vs. 62 percent, P<0.001), patient-reported soreness of the mouth and throat (area-under-the-curve score, 29.0 [range, 0 to 98] vs. 46.8 [range, 0 to 110]; P<0.001), the use of opioid analgesics (median, 212 mg of morphine equivalents [range, 0 to 9418] vs. 535 mg of morphine equivalents [range, 0 to 9418], P<0.001), and the incidence of use of total parenteral nutrition (31 percent vs. 55 percent, P<0.001). Adverse events, mainly rash, pruritus, erythema, mouth and tongue disorders, and taste alteration, were mild to moderate in severity and were transient. CONCLUSIONS: Palifermin reduced the duration and severity of oral mucositis after intensive chemotherapy and radiotherapy for hematologic cancers.