Cryoprevention for oral mucositis


Oral mucositis affects a majority (80%) of patients have high-dose chemotherapy and bone marrow transplantation.  Reviews have shown that cryoprevention using ice chips helps prevent oral mucositis in patients receiving chemotherapy (Dental Elf – 3rd Nov 2021). However, ice chips have been reported to cause tooth sensitivity, chills and nausea which could affect tolerability and adherence.

The aim of this trial was to compare conventional cryotherapy (ice chips, [IC]) with a novel intraoral cooling device (ICD).


This multi-centre randomised controlled trail (RCT) conducted in five Scandinavian centres was registered (NCT03203733) and has a published  protocol (Walladbegi et al -2018). Patients diagnosed with multiple myeloma or lymphoma, scheduled to receive conditioning with high-dose chemotherapy prior to autologous hematopoietic stem cell transplantation (ASCT) were randomised to either ice chips or novel intraoral cooling device (Cooral® Mouth device BrainCool AB, Lund, Sweden). Patients were randomised using permuted blocks stratified according to diagnosis. The primary outcome was the highest OM score during the study period, expressed as peak value on the Oral Mucositis Assessment Scale (OMAS-total). Dental staff assessing the clinical outcome were masked to the interventions. Tolerability and patient reported oral pain were secondary outcomes. Cooling sessions varied for myeloma and lymphoma patients. Ice chips were manufactured from tap water. The ICD is a closed-circuit system continuously circulating cold water.


  • 182 patients were randomised, 156 with multiple myeloma, 26 with lymphoma.
  • The primary outcome was analysed for 172 patients.
  • Oral mucositis of any grade was seen in 44.2% of patients.
  • Peak OMAS–total decreased with the coefficient (−0.297 units) more for ICD than for IC and increased with the coefficient (0.923 units) for lymphoma compared to multiple myeloma.
  • No statistically significant difference was found between IC and ICD in prevention of oral mucositis.
  • 5 % (4/80) of patients in the ICD group reported discomfort compared to 16.1% (14/87) in the IC group, odds ratio (OR) = 0.274 (95%CI; 0.086 to 0.873).
  • Clinical discomfort (NPRS ≥ 3) was reported by 23.2% (16/69) of patients in the ICD group and 36.8% (28/76) in the IC group OR = 0.518 (95%CI; 0.250 to 1.072).


The authors concluded: –

the present study emphasizes the importance of the strategy of cryoprevention to prevent OM. The conventional cooling method of IC was shown to be further improved using the ICD in prevention of OM for lymphoma patients. An estimated number needed to treat was calculated to 2.6, which means that this number of lymphoma patients had to be treated with IC to prevent one case of OM in comparison with ICD.


Oral mucositis (OM) is a very painful and unpleasant condition that also has significant economic considerations as OM associated hospitalisation costs for stem cell recipients are high as noted by this trial’s authors. Consequently, prevention of OM is an important aim. This well conducted multi-centre RCT compares cryotherapy using ice chips with a novel intraoral cooling device.

The findings suggest lower peak OMAS and less discomfort with the ICD compared with IC some of this may be due to the lower temperature of the ice ( -0.5°C) compared to the water temperature (8°C ±2 °C) used in the ICD. The cooling sessions were 1.5 hours long for the myeloma group and potentially up to 3.5 hours for the lymphoma group which some patients may find challenging with the ICD device in place. In addition, 20% of patients reported that the ICD was a poor fit and 30% reported rubbing discomfort both of which could potentially initiate oral mucosal ulceration.  In addition to the primary outcome of Peak OMAS a number of other outcomes were reported although the study was only powered to detect differences in Peak OMAS. So, while this trial demonstrates benefits from cryoprevention additional research needs to be conducted into the use of this novel ICD particularly as the use of ice chips is a simple and readily available method of delivering cryoprevention.

Note:- This new multi-centre trial was highlighted to the Dental Elf by @MDVicSel


Primary Paper

Walladbegi J, Henriksson R, Tavelin B, Svanberg A, Larfors G, Jädersten M, Schjesvold F, Mahdi A, Garming Legert K, Peterson DE, Jontell M. Efficacy of a novel device for cryoprevention of oral mucositis: a randomized, blinded, multicenter, parallel group, phase 3 trial. Bone Marrow Transplant. 2021 Nov 3. doi: 10.1038/s41409-021-01512-6. Epub ahead of print. PMID: 34728786.

Other references

Dental Elf – 3rd Nov 2021

Oral cryotherapy for preventing oral mucositis during chemotherapy


Walladbegi J, Svanberg A, Gellerstedt M. Protocol for a randomised controlled trial to study cryoprevention of chemotherapy-induced oral mucositis after autologous stem cell transplantation. BMJ Open. 2018 Oct 24;8(10):e021993. doi: 10.1136/bmjopen-2018-021993. Erratum in: BMJ Open. 2019 Jun 11;9(6):e021993corr1. PMID: 30361399; PMCID: PMC6224728.

Picture Credits

Photo by Scott Rodgerson on Unsplash


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