Prevention of oral mucositis with cryotherapy in children undergoing hematopoietic stem cell transplantations-a feasibility study and randomized controlled trial

Tove Kamsvåg, Anncarin Svanberg, Karin Garming Legert, Johan Arvidson, Louise von Essen, Karin Mellgren, Jacek Toporski, Jacek Winiarski, Gustaf Ljungman, Tove Kamsvåg, Anncarin Svanberg, Karin Garming Legert, Johan Arvidson, Louise von Essen, Karin Mellgren, Jacek Toporski, Jacek Winiarski, Gustaf Ljungman

Abstract

Purpose: To evaluate the feasibility of oral cryotherapy (OC) in children and to investigate if OC reduces the incidence of severe oral mucositis (OM), oral pain, and opioid use in children undergoing hematopoietic stem cell transplantation (HSCT).

Methods: Fifty-three children, 4-17 years old, scheduled for HSCT in Sweden were included and randomized to OC or control using a computer-generated list. OC instructions were to cool the mouth with ice for as long as possible during chemotherapy infusions with an intended time of ≥ 30 min. Feasibility criteria in the OC group were as follows: (1) compliance ≥ 70%; (2) considerable discomfort during OC < 20%; (3) no serious adverse events; and (4) ice administered to all children. Grade of OM and oral pain was recorded daily using the WHO-Oral Toxicity Scale (WHO-OTS), Children's International Oral Mucositis Evaluation Scale, and Numerical Rating Scale. Use of opioids was collected from the medical records.

Results: Forty-nine children (mean age 10.5 years) were included in analysis (OC = 26, control = 23). The feasibility criteria were not met. Compliance was poor, especially for the younger children, and only 15 children (58%) used OC as instructed. Severe OM (WHO-OTS ≥ 3) was recorded in 26 children (OC = 15, control = 11). OC did not reduce the incidence of severe OM, oral pain, or opioid use.

Conclusion: The feasibility criteria were not met, and the RCT could not show that OC reduces the incidence of severe OM, oral pain, or opioid use in pediatric patients treated with a variety of conditioning regimens for HSCT.

Trial registration: ClinicalTrials.gov id: NCT01789658.

Keywords: Children; Feasibility; Hematopoietic stem cell transplantation; Oral cryotherapy; Oral mucositis.

Figures

Fig. 1
Fig. 1
Flowchart for enrollment, allocation, and analysis
Fig. 2
Fig. 2
Discomfort and degree of discomfort reported after oral cryotherapy. The same child could report more than one type of discomfort
Fig. 3
Fig. 3
Daily measurements for day 0–20 after HSCT for OC and control group respectively. a Grade of oral mucositis according to WHO-OTS in the OC group (n). b Grade of OM according to WHO-OTS in the control group. c Mean WHO-OTS score. d Children’s and parents’ proxy, mean ChIMES total score. e Children’s and parents’ proxy, mean NRS-score for oral pain. f CRP and s-albumin values. OC oral cryotherapy, WHO-OTS WHO Oral Toxicity Scale, ChIMES Children’s International Mucositis Evaluation Scale, NRS Numerical Rating Scale, CRP C-reactive protein

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