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

Abstract 4517

Oral mucositis is a common toxicity associated with many cancer therapies and has been correlated with 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, possibly a result of the mixed pt population studied. We performed a single-center retrospective review of a uniform population of pts <70 years of age with Hodgkin or non-Hodgkin lymphoma undergoing autologous peripheral blood stem cell transplantation between January 1,2007 and December 31, 2009 (Table 1). All pts were conditioned with the BEAM (carmustine, etoposide, cytarabine, melphalan) regimen with oral ice chips given during the melphalan infusion. Filgrastim, 5 ug/kg, was given on days +3, +5, +7, +9 and then daily until granulocyte engraftment. A routine 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 April 2008 with pts instructed to rinse 4-times daily after teeth cleaning and as needed for comfort. 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 two groups were compared using the log-rank test. The Mann-Whitney U test was used to assess the differences in median values of age and CD34 cells infused, and Fisher's Exact test was used to assess the significance of differences in other clinical parameters. No significant differences were found between the control and study populations for age, gender, diagnosis, or CD34+ cell content of the graft. One control group pt failed to engraft and was censored at the time of infusion of backup PBSC. The primary endpoint of an ANC ≥0.5×10⁹/l was achieved for all other pts (Table 2) and no pts were censored for death or relapse before hospital discharge. Pts using SSCPR achieved the primary endpoint of engraftment and were discharged home a median of 1 day faster than the control group pts. 18 pts in the 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). These retrospective data of sequentially treated cohorts suggest that an effective regimen of mucositis prophylaxis may result in faster engraftment and shorter hospital stays. Potential cost savings include 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. A preliminary analysis of pts being treated for myeloma shows a similar improvement in engraftment kinetics, indicating this effect is not limited to the BEAM regimen.