Lilleby, K., Garcia, P., Gooley, T., McDonnnell, P., Taber, R., Holmberg, L., … Bensinger, W. (2006). A prospective, randomized study of cryotherapy during administration of high-dose melphalan to decrease the severity and duration of oral mucositis in patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation. Bone Marrow Transplantation, 37, 1031–1035.

• Patients were randomly assigned to use either ice chips or room-temperature normal saline (NS) rinses before, during, and after melphalan infusion, two days before peripheral blood stem cell transplantation (PBSCT).
• Patients in the ice chips group were instructed to place approximately 1 oz of crushed ice in the mouth. Ice was allowed to melt and was replenished as soon as it was completely melted. Patients were instructed to start 30 minutes before and continue for 6 hours after the end of the 30-minute melphalan infusion.
• Patients in the saline rinse group were instructed to swish 1 oz of room-temperature normal saline in the mouth and spit it out every 30 minutes.   
• Patients were instructed not to eat or drink anything extremely hot or cold during this period.
• The sample size was set at 40 to provide 91% power at a 0.05 significance level.

• The study reported on 41 randomized patients with 21 assigned to receive ice chips and 20 assigned to receive NS. One patient in the NS group withdrew because the patient wanted ice chips. Therefore, data was collected for 21 patients in the ice chips group and 19 in the NS group.
• Patients had to be 18 years or older with multiple myeloma scheduled to receive single-agent melphalan at 200 mg/m² followed by autologous PBSCT.
• Patients were stratified by age less than or greater than 60 years.

This was a randomized trial.

• Patients completed questionnaires that addressed overall health as well as mouth and throat soreness.
• Patients rated difficulties swallowing, drinking, eating, talking, sleeping, and tasting on a 0–4 scale with 0 = no difficulty and 4 = unable to perform.
• Patients rated mouth and throat soreness on a 0–10 scale.  
• Clinical providers and nurses conducted oral assessments as part of routine care using National Cancer Institute (NCI) common toxicity criteria.

• Fewer patients in the ice chips group (14%) experienced grade 3–4 mucositis than in the NS group (75%) (p = 0.0005).
• Patients in the ice chips group required fewer days of total parenteral nutrition (TPN) than the NS group (2 versus 5.5; p = 0.04).
• Patients in the ice chips group also required fewer days of IV narcotics than the NS group (0 versus 5.5; p = 0.0003).
• No significant difference was found in days of hospitalization.
• Patients in the ice chips group experienced significantly less difficulty with activities of eating, talking, sleeping, and tasting.

• The sample size was small.  
• Some inconsistencies occurred with protocol compliance such as variations in the length of time that ice was used and lack of reporting how long ice was used. Some patients complained of coldness and stopped using the ice chips. Additionally, four patients did not fill out any pain reports or record other activities.

Cryotherapy was associated with improved outcomes. Research is needed to determine the required length of cryotherapy.