Vokurka, S., Bystricka, E., Scudlova, J., Mazur, E., Visokaiova, M., Vasilieva, E., …Streinerova, K. (2011). The risk factors for oral mucositis and the effect of cryotherapy in patients after the BEAM and HD-l-PAM 200 mg/m² autologous hematopoietic stem cell transplantation. European Journal of Oncology Nursing, 15, 508–512.

To evaluate the characteristics of oral mucositis in autologous hematopoietic stem cell transplantation (HSCT) after HD-L-PAM (high-dose [HD] methotrexate plus vincristine, HD-doxorubicin, cisplatin, and HD-melphalan) 200 mg/m² and BEAM (bis-chloroethylnitrosourea [BCNU], etoposide, cytarabine, melphalan) conditioning regimens and to analyze the impact of simple and basic clinical and laboratory factors on oral mucositis incidence

Patients who were admitted to a transplant hospital to receive BEAM or HD-L-PAM 200 mg/m² chemotherapy followed by autologous HSCT were recruited to the study. To be included, patients had to have healthy oral mucosa without symptoms of inflammation or local infection at baseline and signed informed consent. Patients were excluded from the study if they had a history of head or neck or total body radiotherapy, received keratinocyte growth factors or amifostine for oral mucositis prophylaxis, or participated in any other trial comparing any new drugs for oral mucositis prophylaxis or treatment. 

Oral cavity monitoring began on the first day of admission and continued throughout the inpatient stay. Beginning on the first day of chemotherapy administration, patients used mouthwash after main meals, before sleep, and as desired. Patients could use their mouthwash of choice, selecting from chlorhexidine, salvia officinalis, providone-iodine, normal saline, Listerine^®, benzydamine, or water. Patients were instructed to gargle for two minutes with the solution of choice. Patients were instructed to use soft toothbrushes. Cryotherapy with lollipops, ice-cold water, or crushed ice was added to the protocol in 2008.

Basic clinical and laboratory data representing individual variables, tested as oral mucositis risk factors, were recorded. Basic statistical univariate analyses were performed using statistical software with Mann-Whitney. The p values comparing the presence and absence of the characteristics and p values < 0.05 were considered indicative of statistically significant differences in relation to mucositis occurrence. 

• The study reported on 126 patients with a median age of 57 years and a range of 8–67 years.
• The sample was 57% male and 43% female.
• Patient diagnoses were chronic lymphocytic leukemia (2%), Hodgkin lymphoma (13%), non-Hodgkin lymphoma (31%), and multiple myeloma (54%).
• In all, 40% of patients were in complete remission and 60% were in partial remission.
• The median number of days since last chemotherapy administration was 72 with a range of 15–560.
• Additional patient data were as follows.
  • Diagnosed with diabetes mellitus, 7%
  • Wore removable dentures (prosthesis), 12%
  • Had a history of oral mucositis, 13%
  • Used cryotherapy of the oral cavity, 29%
• Laboratory values were as follows.
  • Absolute neutrophil count at baseline (x10 - 9/l = 2.3 [1.2–10.0])
  • Serum bilirubin level at baseline (umol/l = 11 [3–42])
  • Creatinine clearance at baseline (ml/min) = 102 (28-181)
  • Number of CD34+ cells in the graft (x10-6/kg) = 4.6 (1.4-17.9)

This was a multisite study conducted in the inpatient setting at the University Hospital in Pilsen, Czech Republic;  University Hospital in Olomouc, Czech Republic;  University Hospital in Kosice, Slovak Republic; Silesian Medical Academy in Katowice, Poland; and Pavlov Medical University in St. Petersburg, Russia.

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability to end-of-life and palliative care.

This was a multicenter, prospective, observational evaluation with oral cavity care.

• The World Health Organization (WHO) 0–4 mucositis grading scale was used.
• Oral cavity monitoring was stated on the first day of the conditioning and covered the whole inpatient stay.
• Oral mucositis was assessed daily by nurses who had attended a specific training course before data collection started. Interrater reliability testing was not performed. With 7% of patients, nurses assessing oral mucositis had not attended any specific oral mucositis training courses.
• Patients evaluated the tolerability of oral cryotherapy once daily using a 1–5 visual analog scale (VAS) with 1 = tolerable without any problems and 5 = intolerable.

• Overall, 62% of patients developed oral mucositis.
• Patients experienced the following grades of oral mucositis.
  • Grade 1: 31%
  • Grade II: 13.5%
  • Grade III: 16%
  • Grade IV: 1.5%
• Oral mucositis incidence was significantly lower in the cryotherapy group (22%) compared to the noncryotherapy group (78%).
• Univariate analysis of the noncryotherapy group (n = 90) found no significant differences between patients with respect to age, gender, performance status, body mass index (BMI), neutrophil count, bilirubin levels, creatinine clearance, number of CD34+ cells in the graft, number of days since the last chemotherapy, presence of removable dentures (prosthesis), or diabetes mellitus. 
• Oral mucositis occurred more often in patients receiving the BEAM conditioning regimen (86% versus 68%, p = 0.04) and in patients with a history of oral mucositis (100% versus 73%, p = 0.0182). 
• The fact that oral cryotherapy was not provided in some patients was the most significant and independent factor for oral mucositis development.

This observational study verified the potential efficacy and feasibility of oral cryotherapy in melphalan short-infusion administration with HD-L-PAM and multidrug BEAM conditioning regimens. Much larger and more homogenous cohorts of patients are needed for future research on the oral mucositis risk factors.

The study findings are limited because of the lack of random assignment, blinding, and an appropriate control group.

Based on the results of this observational trial, the nonprovision of oral cryotherapy is a risk for the development of oral mucositis in patients after autologous HSCT with BEAM or HD-L-PAM conditioning regimens. Maximum effort should be targeted toward the education of medical and nursing teams to implement cryotherapy as a standard prophylactic approach in melphalan regimens.