Prevention of Oral Mucositis with Palifermin in Patients Treated with High-Dose Chemotherapy and Autologous Stem Cell Transplantation. A Single Center Experience.

It was demonstrated in a placebo controlled randomized study that Palifemin decrease the severity of oral mucositis in patients (pts) treated with total body irradiation (TBI), high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). The benefit of this treatment in pts who are not receiving TBI-containing conditioning regimen is still unclear. We evaluated prospectively the effect of Palifermin on mucositis prevention in 34 consecutive pts treated with HDCT and ASCT compared to an historical group of pts who did not receive Palifermin.

Between 03/2005 and 05/2006, 34 pts (Group A) treated with Melphalan 200 (n=15) or BEAM (n=19) gave informed consent and received 6 injections of 0.06 mg/kg of Palifermin (3 days (d.) before HDCT and 3 d. following ASCT). Four were excluded from efficacy analysis, 2 of them due to Melphalan dose reduction and 2 due to early discontinuation of Palifermin. They were compared to 77 pts (Group B) treated with Melphalan 200 (n=43) or BEAM (n=34) from 2003 to 2005. WHO grading was used for toxicity assessment.

The median age was 55 years in group A (Range 28–67) and 54 years in group B (Range 19–66). The median count of CD34 cells/kg infused was 4.2 millions (Range 1.96–23.9) in group A and 3.85 millions (Range 1.8–16.2) in group B. The median time for engraftment was the same in both groups and was respectively 11 d. for neutrophils (Range 8–12) and 11 d. for platelets (Range 8–13) in group A, 11 d. for neutrophils (Range 8–13) and 11 d. for platelets (Range 8–18) in group B. Severe oral mucositis (Grade 3 and 4) was lower in group A (17%) than in group B (44%). The incidence of grade 2 or more digestive mucositis was similar in the 2 groups (66% vs.60%) as well as the total opioid use (43% vs 57%). All patients but one in the group B developed fever. Fever of unknown origin were more frequent in group A due to less fever attributed to grade 3 or 4 mucositis.In group A, all but 3 pts developed toxicities. Grade 3 or 4 toxicities consisted in erythematous rash in 15 pts (44%), generalized oedema in 2 and odynophagia in 1. Grade 1 or 2 toxicities were pruritis (24%), rash (32%), localized oedema (26%) and buccal discomfort (41%). 1 pt died at d.12 from an hemophagocytic syndroma and onother at d.90 from a rapidly progressive colorectal cancer.

We conclude that the use of Palifermin reduced the incidence of grade 3 or 4 mucositis in our group of pts treated without TBI, but did not decrease either digestive mucositis or the use of morphinic. The benefit of Palifermin on mucositis prevention has still to be balanced again the risk of discomfort and toxicities of this drug. Large randomized studies are still needed before recommending the systematic administration of Palifermin to pts receiving Melphalan 200 or BEAM as conditioning regimen before ASCT.