A Prospective, Randomized Clinical Trial of Cryotherapy Vs. Supersaturated Calcium Phosphate Rinses Vs. Saline Rinses for the Prevention of Oral Mucositis in Patients with Multiple Myeloma (MM) Receiving High-Dose Melphalan (HDM) and Autotransplantation

Background: Oral mucositis (OM) is a major complication of HDM. Previous studies analyzing the role of oral cryotherapy (CT) in the prevention of OM are small or include patients treated with multiple conditioning regimens.

Study Purpose: To compare the efficacy of CT plus saline solution (SS) mouth rinse vs. SS alone vs. supersaturated calcium phosphate rinses (Caphosol^®) to prevent HDM-induced OM in patients with MM undergoing autotransplantation

Methods: One hundred and seventeen MM patients, scheduled to receive HDM (140-200 mg/m2) followed by autotransplantation at the Audie L. Murphy Memorial Veterans Hospital in San Antonio, Texas, were randomized to the above mentioned groups (Table 1). Patients were assessed daily for OM until discharge or resolution of OM, using the World Health Organization (WHO) mucositis scale. Duration of OM, degree of oral pain and narcotic requirements were also evaluated.

Results: The study was stopped early due to the superiority of CT. Ninety percent of patients in the CT group did not experienced OM, compared to 36% and 34% in the Caphosol^ā and SS groups, respectively (P < 0.0001). None of the CT patients experienced grade 3-4 OM. There was a significant decrement in duration of OM in the CT group compared to the Caphosol^ā group (mean duration [MD] in days 0.8 vs. 4.77; p < 0.001) and the SS group (MD 5.55 days; p < 0.001). Duration of OM was shorter in the CT group compared to the SS group (MD .9 days vs. 3.38 days; p = 0.004) and the Caphosol^ā group (MD 2.97 days; p = 0.020). Patients in the CT group required less use of analgesics when compared with the SS group (p = 0.007).

Conclusion: CT significantly reduces OM incidence, severity and duration. . Patients who received CT had lower analgesic requirements than patients who received SS.

Table 1. Patient Characteristics
	Total	Caphosol®	Cryotherapy	Saline Solution	p-value
Patients, n	117	39	40	38
Age, median (range)	62 (39-75)	62 (45-68)	62 (39-75)	61.5 (43-70)	0.7696
Gender, n (%)           Male           Female	110 (94) 7  (6)	36 (92) 3 (8)	38 (95) 2 (5)	36 (95) 2 (5)	0.8962
Race/Ethnicity, n (%)           Caucasian           African Americans           Hispanic	56 (48) 40 (34) 21 (18)	23 (59) 11 (28) 5   (13)	16 (40) 15 (37) 9   (23)	17 (45) 14 (37) 7   (18)	0.5164
Karnofsky score, n (%)           70           80           90	1 (1)       16 (14)     100 (85)	0 (0)   6 (15) 33 (85)	1 (2.5)   6 (15)    33 (82.5)	0 (0)   4 (11)   7 (89)	0.8394
Serum Creatinine, mean (SD)	1.12 (0.67)	1.28 (0.93)	1.00 (0.29)	1.09 (0.63)	0.1715
Diabetes, n (%)           Yes           No	30 (26)   87 (74)	10 (26)   29 (74)	10 (25)   30 (75)	10 (26)   28 (74)	0.9912
Dentures, n (%)           Yes           No	32 (27)   85 (73)	9   (23)   30 (77)	13 (32)   27 (68)	10 (26)   28 (74)	0.6336
Smoking, n (%)           Yes or history           Never	89 (76)   28 (24)	30 (77)     9 (23)	30 (75)   10 (25)	29 (76)     9 (24)	0.9122

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