Mori, T., Yamazaki, R., Aisa, Y., Nakazato, T., Kudo, M., Yashima, T., … Okamoto, S. (2006). Brief oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients. Support Care Cancer,  4, 392–395.

To determine if shorter duration of cryotherapy would minimize side effects without affecting efficacy

Patients were instructed to use cryotherapy 15 minutes before, for 15 minutes during, and for an additional 30 minutes after receiving high-dose melphalan infusion (140 mg/m²). The cryotherapy consisted of continuously swirling ice chips in the mouth and gargling with and swallowing ice-cold water every 10-20 minutes throughout a total of 60 minutes. These patients were compared to 18 historical controls who used cryotherapy for 120 minutes. The 17 patients in the study received fludarabine 25 mg/m² daily for five days and melphalan 70 mg/m² per day over 15 minutes for two days, two days prior to hematopoietic stem cell transplantation (HSCT). Some patients received additional chemotherapy or radiation therapy.

The National Cancer Institute (NCI) common toxicity criteria (CTC) were used to evaluate stomatitis.

Two of the 17 patients in the study (11.1%) developed grades 2–3 oral mucositis, compared to two out of 18 historical controls (11%) who used cryotherapy for a longer time period. Although this is not a statistically significant difference, patients in the study group did report significantly lower incidence of unpleasant symptoms compared to those in the historical control group (p < 0.001).

This article provided an interesting discussion and rationale for adjusting the length of oral cryotherapy to relieve patient discomfort.

The sample size was small, and this was not a controlled study.