Study population

This study was part of the Ora-stem study, an international, prospective, longitudinal, multicentre study to investigate oral problems after conditioning therapy and ASCT [16]. In the present study (funded by Dutch Cancer Society, ACTA 2014-7468; trial register NTR5760), 51 MM patients treated with ASCT following HDM (200 mg/m²) were included in both Amsterdam University Medical Centre (location Academic Medical Centre (AMC)) or Radboud University Medical Centre (Radboudumc) Nijmegen between September 2015 and March 2017. According to a power analysis using a non-parametric longitudinal data analysis equation (difference in proportion 0.21, α of 0.05, 6 sample moments per patient, correlation between follow-up measurements 0.3 and 50% development of severe OM), 48 MM patients needed to be included to ensure a power of 0.80. Patients were excluded when they were not able to understand the provided information, a second SCT was planned in advance, the time before the ASCT was too short to consider study participation or when a transfer to another hospital was planned shortly after ASCT. Ethical approval was obtained (NL52117.018.15) and the study was conducted according to GCP guidelines and the World Medical Association Declaration of Helsinki. Before participating, all patients signed informed consent.

To prevent OM, most patients self-administered cryotherapy during the infusion of HDM. Cryotherapy was started 5–10 min before HDM infusion and was stopped directly after infusion (AMC) or 30 min after infusion (Radboudumc), according to local practice standards. Compliance with the cryotherapy protocol was monitored, but not enforced. Patients treated at the AMC received HDM infused over 2 days (30 min, 100 mg/m² each IV), while patients treated at the Radboudumc received one day infusion of HDM (1 h, 200 mg/m² IV). Safety controls and vital signs monitoring was standard practice including routine laboratory measurements (including blood counts and renal and liver chemistry).