Reliability and efficacy of palifermin in prevention and managmenent of oral mucositis in paediatric patients with acute lymphoblastic leukemia: a randomized, double-blind controlled clinical trial

Aim. Oral mucositis (OM) is a frequent complication of myeloablative and Hematopoietic Stem Cells Transplantation therapy (HSCT) with no effective treatment. Palifermin, a recombinant human keratinocyte growth factor, specifically stimulates the growth and anti-apoptotic potential of epithelial cells expressing the KGF receptor without directly affecting non-epithelial cells lacking this receptor and was demonstrated as useful in preserving the integrity of the epithelial lining in animals undergoing chemoradiotherapy followed by hematopoietic stem cell transplantation. This randomized-controlled trial studied the efficacy of Palifermin, administered as a dose during HSCT therapy, as primary prophylaxis on paediatric patients with Acute Lymphoblastic Leukemia (ALL). Methods. Fifty-six patients (aged 7-16 years old) with B-cell acute lymphoblastic leukemia (B-ALL) classified according to the WHO classification. The patients underwent allogenic HSCT conditioned by myeloablative regimen. Patients in the Palifermin group were randomly assigned in a 1:1 ratio to receive Palifermin, 60 μg/kg, intravenously as a single dose 3 days before and after transplant conditioning regimen cycle. The patients in the Control group received only a placebo treatment that consisted in a mouthwash containing 2% mepivacaine and dexamethasone and 0.05% chlorexidine for three times/ day 3 days before and after transplant conditioning regimen cycle. OM-related assessments were the WHO oraltoxicity scale and the patient-reported outcomes (PRO). Maximum severity of OM (WHO grades 0/1, 2, 3 or 4) was the primary efficacy end point. Secondary efficacy end points included incidence and duration of ulcerative OM (WHO grades 2, 3 and 4), incidence and duration of severe OM (WHO grades 3 and 4) limitations. Results. The administration of Palifermin was generally safe and without considerable complications. The only adverse reactions were rashes, erythema, and altered taste. There was a statistically significant reduction in the incidence of OM ≥ grade 1, 2 and 3 in the Palifermin group compared to the Control group. There was also a reduction in the degree of severity of mucositis in the Palifermin group, with an average of 1.65 grade in the Palifermin group, and of 2.33 in the Control group and the reduction of the use of opioid analgesics. The results were confirmed at 60 days after the last transplant conditioning regimen cycle during the routine check up sessions. Conclusion. This study indicates that a single dose of Palifermin used as primary prophylaxis during HSTC therapy can prevent severe OM in paediatric patients with ALL. The findings of the study also suggest that Palifermin used as secondary prophylaxis can prevent the recurrence of severe OM in high-risk patients with previous mucosal injury. The reduction in OM had several clinical benefits, including the relief of mucosal pain; decreased use of narcotics; and improvements in the ability to drink, eat, and, in general, the quality of life in paediatric patients with ALL.