A Randomized Study to Compare the Effect of 2-Hour and 6-Hour Schedules of Cryotherapy On the Incidence of Severe Mucositis in High Dose Melphalan

Objectives:

The primary objective is to measure the maximum inpatient mucositis grade after 2- vs. 6-hours standardized cryotherapy regimens in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation(HSCT). Secondary objectives include: comparison of neutropenic fever and bacteremia incidence after 2- vs. 6-hour cryotherapy regimens, and comparison of patient-reported symptoms experienced with cryotherapy after 2- vs 6-hour cryotherapy regimens.

 Background:

High dose Melphalan, a chemotherapy known to cause mucositis in up to 40% of patients receiving it, is used as the preparative regimen for patients with multiple myeloma receiving autologous HSCT. The Oncology Nursing Society Putting Evidence into Practice resource categorizes use of cryotherapy for patients receiving bolus dose Melphalan as “likely to be effective” in reducing mucositis.  Evidence supporting this included a randomized clinical trial comparing no cryotherapy to 7 hours. Additional prospective convenience sample studies showed shorter durations to also be effective. 

 Methods:

A randomized clinical trial to compare the incidence and severity of mucositis between the standard practice of 6 hours of cryotherapy and 2 hours, based on previously cited evidence and the half-life of Melphalan was developed.  After enrollment, patients are computer randomized to treatment with either 2 or 6 hours of cryotherapy. Cryotherapy is standardized to the use of shaved ice, with 1 ounce placed in the mouth, allowed to melt and then replaced. Compliance is monitored by the nursing staff. The patient completes an evaluation of the cryotherapy experience, as well as the Patient-Reported Oral Mucositis Symptom Scale daily, noting subjective symptoms. Mucositis is graded daily by a nurse practitioner using the World Health Organization Oral Toxicity Scale. Pain medication and nausea/vomiting are obtained from the medical record. All measurements are completed until Day +21 or discharge. A Cochran-Mantel-Haenszel chi-square test will be used to compare the proportion of patients who develop severe mucositis (Grade 3-4) between the treatment arms.

 Results:

At the time of this submission, 37 patients have been treated on this study supported by a grant from The DAISY Foundation. Target enrollment is 142, with a full mid-point analysis planned. Current rate of enrollment is 2 subjects per week. The results of this study have implications to change practice with this regimen as well as other regimens that combine Melphalan with additional agents.