Aisa, Y., Mori, T., Kudo, M., Yashima, T., Kondo, S., Yokoyama, A., … Okamoto, S. (2005). Oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients. Supportive Care in Cancer, 13, 266–269.

Patients kept ice chips and ice-cold water in their mouths for 15 minutes before and during as well as for an additional 90 minutes after melphalan infusion. Patients were advised to continue swirling ice chips around in their mouths and to gargle and swallow ice-cold water every 10–20 minutes throughout oral cryotherapy. Patients were consecutively compared with a historical control group (no cryotherapy). Fludarabine was administered at 25 mg/m² daily for five days; melphalan was administered at 70 mg/m² daily for 15 minutes for two days.

The sample consisted of 18 patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) receiving fludarabine and high-dose melphalan (140 mg/m²).

Common toxicity criteria (CTC) grading of stomatitis (0–4) was done every day from the first day of HSCT to day 28. The maximum grade recorded for each participant was considered that patient's grade.

• The cryotherapy group reported less moderate to severe mucositis with 2 out of 18 patients (11.1%) in the cryotherapy experiencing moderate to severe mucositis (grade 2 or 3) and 6 out of 7 patients (85.7%) in the historical control group experiencing grade 2 or 3 mucositis (p = 0.001).
• No patients in the cryotherapy or control group developed grade 4 mucositis.
• Side effects included chills (n = 7; 39%) and nausea (n = 4; 22%), and one patient discontinued cryotherapy.

The sample size was small sample, and the control group was based on historical reports.