Discussion

1. A Randomized Study to Compare the Effect of Short and Long-term Schedules of Cryotherapy on the Incidence and Severity of Mucositis in High-Dose Melphalan in Autologous Bone Marrow Transplant Patients • Misty Lamprecht, MS, RN, CNS, AOCN; Karen Tackett, BSN, RN, OCN; Janine Overcash, PhD, GNP-BC; Craig Hofmeister, MD • The Ohio State University CCC – The James Design and Methods Statistical Analysis Discussion Objectives The preliminary statistical analyses were completed with data from the initial 60 patients enrolled on study. Primary Objective: To measure the maximum mucositis grade after 2- vs 6-hours cryotherapy in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation. Secondary Objectives: To compare the neutropenic fever and bacteremia incidence after 2- vs. 6-hours cryotherapy. To compare patient-reported mucositis-related symptoms after 2- vs. 6-hours cryotherapy utilizing the Patient-Reported Oral Mucositis Symptoms Scale (PROMS) This is a randomized, controlled, longitudinal study of multiple myeloma patients admitted for autologous stem cell transplant at a Midwestern comprehensive cancer center. Computerized randomization to 2- or 6-hours of cryotherapy is obtained prior to infusion of high-dose melphalan. Cryotherapy is standardized to 1 ounce of shaved ice (with or without flavoring) placed in the mouth, allowed to melt and then replaced. Compliance of cryotherapy is monitored by the patient’s nurse. At the end of cryotherapy, the patient completes a self-reported evaluation of their tolerance of cryotherapy. Daily, patients complete the Patient-Reported Oral Mucositis Symptoms Scale (PROMS), with notation of subjective symptoms. Mucositis is graded daily by the nurse practitioners with the WHO Oral Toxicity Scale. Use of pain medication and episodes of nausea/vomiting are recorded from the medical record. All measurements are completed until Day +21 or discharge. • This preliminary analysis compared the severity of mucositis between the 2- and 6-hour cryotherapy sessions. Length of hospital stay and peak grade of mucositis were analyzed using the Mann-Whitney tests of association. There was no statistical difference between the groups p<0.098 for length of stay and p<0.159 for peak mucositis severity. This preliminary analysis indicates the absence of statistically significant differences and thus far indicates that 2-hours of cryotherapy provides prevention of grade 3 or 4 mucositis in the same manner as 6-hours of cryotherapy. • Discomfort during cryotherapy was measured in both the 2- and 6- hour cryotherapy arms, specifically in regards to nausea/vomiting, headache, toothache, and chilling. Fisher’s exact tests were utilized for this comparison which revealed no statistically significant difference for each of these variables between groups. Of note, nausea/vomiting revealed a p<0.053 with greater incidence in the 6-hour cryotherapy group. • Limitations to this preliminary review of the data included the small sample size (n=60), although important trends were observed. The study will continue to accrue and attempt to answer these very important scientific questions. • 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 transplantation. Supportive Cancer Care, 13, 266-9. • Keefe DM, Schubert MM, Elting LS, Sonis ST, Epstein JB, Raber-Durlacher JE,…Peterson DE. (2007). Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer, 109(5), 820-831. • Kushner JA, Lawrence HP, Shoval I, Kiss TL, Devins GM, Lee L, Tenenbaum HC. (2008). Development and validation of a patient-reported oral mucositis symptom (PROMS) scale. Journal of the Canadian Dental Association, 74(1), 59-59j. • Lilleby K, Garcia P, Gooley T, McDonnell 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 transplantation. Bone Marrow Transplantation, 37, 1031-5. • 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 oral stomatitis in allogeneic hematopoietic stem cell transplant recipients. Supportive Cancer Care, 14, 392-395. • Tartarone A, Matera R, Romano G, Vigliotto ML, & DiRenzo N. (2005). Prevention of high-dose melphalan-induced mucositis by cryotherapy. Leukemia & Lymphoma, 46(4), 633-34. Mucositis Grading Background • High dose Melphalan, a chemotherapy drug known to cause mucositis, is used as a preparative regimen for multiple myeloma patients who receive stem cell transplants. • Cryotherapy can lessen the severity of mucositis as documented in the evidence: • Oncology Nursing Society’s ‘Putting Evidence into Practice’ categorizes cryotherapy as “likely to be effective” in reduction of mucositis with bolus dose melphalan. • A randomized clinical trial that compared saline rinses to 7 hours of cryotherapy supported a longer duration of cryotherapy to prevent or reduce mucositis. • Recent prospective studies have demonstrated shorter durations of cryotherapy (90-120 min.) to be effective in high-dose melphalan. • Theory of unpleasant symptoms • The theory of unpleasant symptoms was used as the conceptual framework for this study. Pain, changes in taste and difficulty with maintenance of oral intake are physiologic changes associated with mucositis. Nausea, headache, toothache and chilling are other symptoms associated with prolonged cryotherapy References Demographics Gender: Female n=25 41% Male n=35 57.4% Race: Caucasian n=53 86.9% African American n=6 9.8% Unknown n=1 1.6%