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Cryotherapy as prophylaxis against oral mucositis after high-dose melphalan and autologous stem cell transplantation for myeloma: a randomised, open-label, phase 3, non-inferiority trial

Bone Marrow Transplantation (2019) | Download Citation


The conditioning therapy used in connection with haematopoietic stem cell transplantation (HSCT) can induce painful oral mucositis, which has negative impacts on patient quality of life and survival, as well as on health-care costs. While cooling of the oral mucosa (cryotherapy) is regarded as standard prophylaxis against oral mucositis, the long duration of the treatment affects compliance owing to side effects. In this prospective, randomised trial, 94 patients (62 males/32 females; median age 59 years, range 34–69) with a diagnosis of myeloma who were undergoing autologous HSCT were randomised 1:1 to receive cryotherapy for 7 h (N = 46) or 2 h (N = 48). Oral mucositis was evaluated prospectively. No significant difference was observed with respect to the proportion of patients who showed grades 3 and 4 toxicity according to the WHO scale (2.1 and 4.3% for 2 and 7 h, respectively; 95% CI −0.09 to 0.049; p = 0.98) as between the groups. Two hours of cryotherapy was as effective as 7 h in terms of protecting against severe oral mucositis in connection with autologous HSCT for myeloma. This trial is registered with (NCT03704597).

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The trial was funded by the Healthcare Committee, Region Västra Götaland (Grant number VGFOUREG-64832). We thank all the patients for their participation in the trial.

Author contributions

J-EJ, who was the chief investigator, and BH, who was the principal investigator, developed the study design. All the authors participated in the planning and performance of the study and in the interpretation of the results. BH, JB, and LH performed the oral assessments. J-EJ identified eligible patients and drafted the manuscript, the final version of which was seen and approved by all contributors.

Author information


  1. Department of Haematology, Sahlgrenska University Hospital, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden

    • Jan-Erik Johansson
  2. Specialist clinic for Hospital Dentistry/Oral Medicine, Göteborg, Public Dental Service, Region Västra Götaland, Göteborg, Sweden

    • John Bratel
  3. Department of Haematology, Uddevalla Hospital, Uddevalla, Sweden

    • Mats Hardling
  4. Specialist Clinic for Hospital Dentistry, South Älvsborg Hospital, Borås, Sweden

    • Lena Heikki
  5. Department of Haematology, South Älvsborg Hospital, Borås, Sweden

    • Ulf-Henrik Mellqvist
  6. Department of Oral Medicine and Pathology, Institute of Odontology, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden

    • Bengt Hasséus


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Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Jan-Erik Johansson.

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