Markiewicz, M., Dzierzak-Mietla, M., Frankiewicz, A., Zielinska, P., Koclega, A., Kruszelnicka, M., & Kyrcz-Krzemien, S. (2012). Treating oral mucositis with a supersaturated calcium phosphate rinse: comparison with control in patients undergoing allogeneic hematopoietic stem cell transplantation. Supportive Care in Cancer, 20, 2223–2229.

To evaluate the efficacy of supersaturated calcium phosphate rinse (SCPR) with customary care (topical mouth solutions) on measures of severity and consequent interventions and complications  

In the treatment group, patients rinsed their mouths four times daily with the SCPR. In the control group, patients received customary topical mouth care with the extract of salvia leaves (twice daily), providone-iodine mouth solution (1% water solution of iodide with polyvinylpyrrolidone) once daily, and fluconazole mouth solution (50 mg fluconazole, 50 mg glycerine, 10 g vitamin A, and 10 g vitamin E with or without 2.5 g benzociaine) twice daily.

The SCPR treatment was administered from the first day of conditioning until patients reached the absolute neutrophil count of greater or equal to 0.2 g/l (a value that was considered an indication of the beginning of neutrophil recovery). Patients self-assessed the level of pain in the mouth and pharynx using a 0–10 visual analog scale (VAS) and measured swallowing problems using a 0–5 VAS.

The same experienced hematologist performed a physical examination of the oral cavity each day throughout the study, ranking cases according to the World Health Organization (WHO) scale for grading oral toxic effects of cancer treatment.

• The study reported on a sample of 40 patients. The SCPR group mean age was 38, with a range of 19–57 years. The control group mean age was 26, with a range of 20–57 years.
• The SCPR group had 13 males and 7 females, and the control group had 11 males and 9 females.
• The SCPR group had 8 patients with acute myelogenous leukemia (AML), 5 with acute lymphocytic leukemia (ALL), 2 with chronic myelogenous leukemia (CML), 3 with paroxysmal nocturnal hemoglobinuria (PNH), and 2 with other cancers (osteomyelfibrosis, myelodysplastic syndrome, severe aplastic anemia).
• The control group consisted of 12 patients with AML, 5 patients with ALL, 1 patient with PNH, and 2 patients with other (see above).
• In the SCPR group, 9 patients were receiving busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg), 5 patients were receiving total body irradiation (TBI) of 12 Gy and 120 mg/kg cyclophosphamide, and 6 were receiving treosulfan (42 g/m²) and fludarabine (150 mg/m²).
• In the control group, 9 patients were receiving busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg), 5 were receiving TBI (12 Gy) and 120 mg/kg cyclophosphamide, 4 were receiving treosulfan (42 g/m²) and fludarabine (150 mg/m²), 1 was receiving treosulfan (20 g/m²) and cyclophosphamide (160 mg/kg) and 1 was receiving cyclophosphamide (200 mg/kg). 
• In the SCPR group, 5 patients were receiving transplants from sibling donors and 15 from unrelated donors. In the control group, 4 were receiving transplants from sibling donors and 16 from unrelated donors.

This was a single-site study conducted in an inpatient setting. The study was conducted at the Department of Hematology and Bone Marrow Transplantation at the Medical University of Silesia in Katowice, Poland, in 2009.

• Patients were undergoing the active treatment phase of care.
• This study has clinical applicability for end of life and palliative care.

This was a prospective randomized, non-blinded, controlled trial with 40 consecutive patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Half of the patients received treatment with the supersaturated rinse, and the remaining half received customary care with topical mouth solutions. Patients enrolled in this study underwent transplantation in the Medical University of Silesia in Katowice, Poland, in 2009.

The World Health Organization scale (WHO) was used to measure severity of mucositis. Duration was recorded in days. Peak mean pain in mouth was recorded using a 0–10 visual analog scale (VAS). Peak mean swallowing problems were recorded using a 0–5 VAS. Days to absolute neutrophil count of more than 0.5 g/L and days to platelets of more than 20 g/L were recorded.  

Interventions and complications were measured in terms of duration of analgesics used (days), duration of total parenteral nutrition (TPN) (days), use of granulocyte colony-stimulating factor (G-CSF), incidence of acute graft-versus-host disease (aGVHD), degree of aGVHD, and incidence of infectious complications.

• Compared with the control group, the SCPR mouth rinse group demonstrated significantly lower means measures of oral toxicity, peak mouth pain, and disease course duration.
• WHO oral toxicity scores were statistically lower in the SCPR group (p = 0.02) compared to the control group.
• Disease course for the SCPR group was statistically shorter (p = 0.02) and peak mouth pain was statistically lower in the SCPR group (p = 0.005).
• Days of analgesic needs were shorter for the SCPR group (p = 0.047).
• The need for patients needing TPN in the SCPR group was lower (p = 0.02), and the mean days of TPN was lower in the SCPR group (p = 0.009).

The findings in this prospective randomized, controlled study confirm findings in a 1992 report of a double-blind, prospective, randomized, controlled trial of 95 patients undergoing HSCT. In that trial, SCPR produced statistically significantly lower measures of pain duration, disease course duration, use of analgesics (morphine), and duration of time to absolute neutrophil recovery than did a fluoride rinse, demonstrating the SCPR regimen has a significant positive effect on oral mucositis associated with chemotherapy and radiotherapy.

• The sample size was small with fewer than 100 patients.
• The iodine solution (red) contrasted dramatically in color with the SCPR solution (colorless), thus making it difficult to disguise the difference and, therefore, making the study unblinded.
• The red color of the iodine solution may have obscured assessment of the oral cavity.
• It may be able to generalize these results to other settings because the control group treatment is not necessarily widely accepted as the standard of care for the prevention and treatment of mucositis. 

These results warrant confirmation in controlled, multicenter, randomized trials. The use of a supersaturated calcium phosphate rinse holds promise for the prevention and early resolution of oral mucositis and appears to have no significant side effects when used four times daily in patients receiving stem cell transplant.