Evaluation of Mucositis in Pediatric Hematopoietic Cell Transplant Patients Receiving Palifermin

Abstract

Background Oral mucositis (OM) occurs in up to 70-80% of children undergoing myeloablative conditioning during hematopoietic cell transplant (HCT). OM has various negative clinical sequelae; therefore, efforts to prevent this common transplant complication have important potential clinical benefits. The keratinocyte growth factor, palifermin, stimulates the proliferation of mucosal cells and may be protective against the development of OM when administered to patients receiving regimens containing total body irradiation (TBI) or alkylating agents. Methods We performed a retrospective review of children (up to age 21 years) undergoing autologous or allogeneic HCT who received palifermin in the peri-transplant period over a 5-year period (2014-2018) at our institution. Subjects were included if they received TBI (≥12 Gy) or multiple alkylating agents (including melphalan) as part of their conditioning regimen. The recommended dosing is 60 mcg/kg/day intravenously 3 days before conditioning and 3 doses post-HCT on days 0, +1, +2. We excluded children who completed the pre-transplant palifermin doses greater than 48 hours prior to initiation of the conditioning regimen and those who did not receive all 6 planned doses. The primary outcome was the incidence, severity, and duration of mucositis. Secondary outcomes included the need for supportive care measures such as parenteral nutrition (PN) and patient controlled analgesia (PCA) use. We also examined the cost associated with palifermin use. Results A total of 44 children were evaluated. Ten children were excluded due to inappropriate palifermin dosing, two were excluded for infectious complications that resulted in aborting the preparative regimen, and two had incomplete data during chart review. Thirty remaining evaluable subjects were included in the full analysis. The most common chemotherapy-only conditioning regimens were carboplatin/etoposide/melphalan (n=8) and fludarabine/melphalan/thiotepa (n=7); 12 patients received TBI. Twenty-two patients (73.3%) developed Grade 3 or 4 mucositis (Grade 3, n=17; Grade 4, n=5). The median duration of mucositis, PN use, and PCA were 15 days (IQR 10-20), 18 days (IQR 13-25), and 10.5 days (IQR 7-16), respectively. The median hospital length of stay was 33 days (IQR 27-45). When subjects who were excluded due to inappropriate dosing were included in the analysis, there were no significant changes in the primary and secondary outcome measures. The average cost of palifermin per patient is approximately $15,350, translating to $135,080 of additional overall charges annually. Conclusion Despite the use of palifermin, the incidence of severe OM was high in our pediatric population. Given concerns regarding cost and questionable efficacy, the role of palifermin in HCT supportive care remains uncertain.