Severity, Frequency, and Risk Factors for Oral Mucositis after BEAM High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation and Preliminary Results with Palifermin Versus Best Supportive Care.

Mucositis being an adverse effect of high-dose chemotherapy (hd CTx) may compromise results of peripheral blood stem cell transplantation (PBSCT). Keratinocyte growth factor can effectively decrease its severity and frequency. Here, the mucositis rate after BEAM hd CTx followed by auto-PBSCT was analyzed. A total of 50 patients (median age: 55 years, range; 19–70) with high-risk, refractory or relapsed lymphoma were included in a prospective analysis at our center, and mucositis was graded according to WHO. After BEAM-hd CTx, WHO grade 2 mucositis developed in 30%, grade 3 in 10% and grade 4 in 4%. Odds ratios (OR) for mucositis grade 2 or higher were increased to 2.1 (95% CI 0.6–6.7) for female sex, to 1.9 (CI 0.5–6.7) for higher pretreatment (>8 CTx-cycles), and 3.1 (CI 0.9–10.5) with previous mucositis. We found no association for older age, lymphoma type (indolent vs. high-grade NHL/Hodgkin’s disease), previous radiotherapy, Karnofsky index, oral hygiene or leukopenia prior to auto-PBSCT. The OR for mucositis with parental nutrition was estimated with 2.2 (CI 0.6–7.7) and for opioid use with 8.7 (CI 2.2–33.7) (p=0.0025), both being directly influenced by the extend and severity of oral mucositis. As expected, myelosuppression was the main toxicity of hd-BEAM: WBC >1.000/ml were reached after a median of 10 days (range 7–15), platelets >20.000/ml after 11 days (range 7–45). The median numbers of red blood cell and platelet units transfused were 5 (range 1–21) and 4 (range 1–35), respectively. The event free survival at 6, 12 and 24 months was 81.9% (CI 71.2–92.6%), 70.5% (CI 57.3–83.6%), and 66% (CI 51.2–80.9%), and the overall survival 83.9% (CI 73.7–94.1%), 79.2% (CI 67.7–90.8%) and 79.2% (CI 67.7–90.8%), respectively. Subsequently, 10 lymphoma patients have been accrued in the follow-up study comparing palifermin to best supportive care (BSC) after hd-BEAM conditioning. All 5 patients receiving palifermin showed only WHO grad 1 mucositis, whereas in the control group one patient each had grade 1, 2 and 3 mucositis and 2 patients are still being treated. In conclusion, we found females, extensive pretreatment and previous mucositis as potential risk factors for the development of mucositis, the latter greatly influencing parental nutrition and opioid use. Although the incidence of grade 2–4 mucositis varies with different CTx-schedules and -intensity, it severely affects supportive measures. Decrease in its severity and duration will substantially reduce side-effects of PBSCT further.