Use of a Super-Saturated Calcium Phosphate Mouth Rinse for Prevention and Treatment of Oral Mucositis Results In Faster Engraftment and Hospital Discharge Than Using a Sodium Bicarbonate Rinse Alone After Autologous Transplantation

Oral mucositis is a common toxicity associated with cancer therapies and increases risk for infection, mortality, and extended hospital stay. Prophylactic use of a supersaturated calcium phosphate mouth rinse (SSCPR, Caphosol®) was found in a phase III study to reduce the frequency, intensity, and duration of oral mucositis in patients (pts) undergoing allogeneic or autologous hematopoietic stem cell transplantation (Papas, et al. Bone Marrow Transpl 2003;31:705). That study also found a faster time to recovery of an absolute neutrophil count (ANC) ≥0.2×10⁹/l, but not for other engraftment endpoints, likely a result of the mixed pt population studied.

A single-center retrospective review of two uniform populations undergoing autologous peripheral blood stem cell transplantation (PBSCT) to determine if an effective regimen of mucositis prophylaxis results in faster engraftment and shorter hospital stays.

Two different uniform population of pts ≤70 years of age with Hodgkin or non-Hodgkin lymphoma (HL/NHL) and multiple myeloma (MM) undergoing PBSCT between 1/1/07 and 12/31/09 (Table 1). MM pts were conditioned with single dose melphalan (N= 16 with 140 mg/m²; N= 203 with 200 mg/m²). HL/NHL pts were conditioned with BEAM. Oral ice chips were given during the melphalan infusion for all pts. Filgrastim, 5 ug/kg, was given on days +3, +5, +7, +9 and then daily until granulocyte engraftment. A regimen of oral hygiene using sodium bicarbonate (NaHCO₃) tooth cleaning after each meal with as needed rinsing was encouraged. SSCPR was added to this regimen in May 2008 with pts instructed to rinse 4-times daily after teeth cleaning and as needed. Granulocyte engraftment was defined as the first day with a rising ANC ≥0.5×10⁹/l, and platelet engraftment was defined as the first day of a rising platelet count ≥20×10⁹/l. Prospective scoring of mucositis was not performed and the use of intravenous fluconazole, ciprofloxacin, and/or acyclovir prophylaxis was recorded as a surrogate indicator of severe mucositis. Engraftment times and time to hospital discharge were estimated using the method of Kaplan and Meier, and the groups were compared using the log-rank test. The Mann-Whitney U test was used to assess differences in median values of age and CD34 cells infused, and Fisher's Exact test was used to assess the significance of differences categorical parameters.

Results: No differences were found between the control and study populations for age, gender, diagnosis, or CD34+ cell content of the graft (Table 1). For the HL/NHL control group one pt failed to engraft and was censored at the time of infusion of backup PBSC. In the MM groups no pts failed to engraft. No pts for either diagnosis were censored for death or relapse before hospital discharge. For both populations, pts using SSCPR achieved the primary endpoints of engraftment and were discharged home a median of 1 day faster than the respective control group pts (Table 2). 18 pts in the HL/NHL control group and 20 pts in the SSCPR group experienced febrile neutropenia (p=1.0) and 4 pts in each group were given intravenous medications (p=1.0). 73 pts in the MM control group and 53 pts in the SSCPR group experienced febrile neutropenia (p=0.22). 11 pts in the control group and 10 pts in the SSCPR group were given intravenous medications (p=1.0). These retrospective data of sequentially treated cohorts suggest that an effective regimen of mucositis prophylaxis may result in faster engraftment and shorter hospital stays with fewer days of antibiotics and cytokines. This retrospective study lacks detail regarding the incidence of mild/moderate mucositis and a mechanism of this action cannot be discerned from these data.

Rowley:EUSA Pharmaceautical: Speakers Bureau.