The Significance of Palifermin (Kepivance) in Reduction of Oral Mucositis (OM) Incidence and Acute Graft Versus Host Disease (aGvHD) in Patients with Hematological Diseases Undergoing HSCT.

AIMS:

OM is a frequent complication of the myeloablative therapy and HSCT.

In this Polish multi-center study we assessed the ability of palifermin (rHu-KGF1) to reduce the incidence, duration and severity of OM induced by high-dose chemotherapy followed by HSCT in patients with hematological diseases. We also evaluated the requirement for analgesics and total parenteral nutrition (TPN) caused by OM, incidence of febrile neutropenia and severe infections, the influence of palifermin on the engraftment, aGvHD and hospitalization.

METHODS AND RESULTS:

106 patients with hematological diseases were enrolled to the study.

53 of them (50%) received palifermin (60 μg/kg/day) for 3 consecutive days before and after conditioning therapy and they were transplanted between June 2005 and March 2006. Each reporting center submitted equal number of patients to palifermin and control group. Both groups were similar in terms of sex, age, diagnosis, type of transplant and conditioning regimens. The patients in control group were transplanted between December 2000 and 2005.

The median age of palifermin and control group was 37,0 years (range, 19 to 58) and 36,1 years (range, 18 to 64), respectively. 29 (54,7 %) autologous and 24 (45,3 %) allogeneic HSCT were performed in both groups. OM was assessed daily after HSCT according to the WHO scale.

The incidence of OM of grade 1–4 was 58 % vs 94 % and grade 3–4, 13 % vs 43 % in palifermin group vs. control group, respectively (p<0,001). The median duration of OM grade 1–4 was 4,0 days (range, 0 to 16) in palifermin group and 9,0 days (range, 0 to 28) in control group (p<0,001). As compared with control, palifermin group was also associated with significant reductions in the use of analgesics (32 vs. 75,5 %; p<0,001), opioid analgesics (24 vs. 64 %; p<0,001) and TPN (11 vs. 45 %; p<0,001). Moreover, we observed reduction of the incidence of aGvHD in palifermin group (25 vs.50 %; p=0,03), especially gastrointestinal form (8,3 vs. 29,2 %; p=0,03).

No statistically significant differences in the incidence of febrile neutropenia, severe infections and the median duration of hospitalization were observed between groups. Also palifermin did not appear to impair engraftment.

The drug was generally well tolerated. Adverse events, mainly rash, pruritus, erythema, generalized edema, mouth/tongue thickness and discoloration and taste alteration were mild to moderate in severity and were transient.

CONCLUSIONS: Administration of palifermin significantly reduced the incidence, severity and duration of OM and did not have negative effect on engraftment in the patients with hematological diseases after HSCT. It seems that it could also reduce the incidence of aGvHD, especially gastrointestinal form. It was generally well tolerated and safe.