Adding Palifermin in Allogeneic and Autologous Stem Cell Transplantation Resulted in Reduced Oral Mucositis and Enhanced Intestinal Mucosal Recovery Measured by Citrulline Serum Levels.

Background: In this ongoing prospective open label study we evaluate the effect of Palifermin on the development of oral and intestinal mucositis in 25 patients undergoing allogeneic or autologous hematopoietic stem cell transplantation (allo/auto-HSCT).

Methods: Twenty-five patients, transplanted for acute or chronic leukemia (n=20) and non-Hodgkin’s lymphoma (NHL, n=5) received 60 μg Palifermin per kilogram of body weight per day for three consecutive days before the initiation of conditioning therapy and immediately after HSCT. The control group comprised 9 patients diagnosed with acute leukaemia (n=6) and NHL (n=3). In the Palifermin group the distribution between allo- and auto-HSCT was 16 and 9 compared to 5 and 4 in the control group. Conditioning therapy consisted of fractionated total-body irradiation/Cyclophosphamide in case of leukemia and chemotherapy only based regimens in NHL patients. Oral mucositis was graded daily according to World Health Organisation (WHO) criteria. The intestinal mucosal barrier damage was assessed by analyzing Citrulline serum levels on HSCT days -12, -6, 0, +7, +14 and +21.

Results: No severe side effects were observed in our patient cohort. Our preliminary analysis demonstrates a significant decrease in the incidence of oral mucositis WHO grade 3 or 4 with 24 percent in the Palifermin group as opposed to 78 percent in the control group (p=0,013). The median duration of mucositis was 4,7 days (range 0–19) in the Palifermin group compared to 9,3 days (range 0–19) in controls (p=0,037). Whereas 17 evaluable patients in both groups showed a similar decline in Citrulline serum concentrations until day +7 - reflecting a maximal intestinal mucosal barrier injury at this timepoint - a significantly faster recovery of Citrulline levels (18,5 vs 13,8 μM, p=0,04) in Palifermin recipients at day +21 could be found. The use of opioid analgesics as determined by morphine equivalents (median 105mg vs 112mg) was almost equal. However, there was a trend in the duration of total parenteral nutrition (14 vs 18 days, p=ns) in favor of the Palifermin group. Acute graft versus host disease grade I-IV was observed in 29%, grade III-IV in 21% of Palifermin treated patients after an allo-HSCT.

Conclusions: Palifermin was generally well tolerated and reduces the incidence and duration of WHO grade 3 and 4 oral mucositis. Further, it promotes a faster recovery of intestinal mucosal damage in allogeneic and autologous HSCT recipients.