The Clinical Study Of Ozonated Water Mouthwash For Treatment Of Oral Mucositis In Patients With Hematological Malignancies

Background Chemotherapy is the major treatment in patients with hematologic malignancies. Research had shown that almost all patients receiving traditional high-dose chemotherapy and hemopoietic stem cell or bone marrow transplantation showed the miserable symptoms of mucositis, which also appeared about40%of patients receiving standard dose. The main symptoms of mucositis are pain, ulceration, nausea, vomiting and diarrhoea. For patients, the pain and ulceration associated with oral mucositis(OM) seriously compromises quality life in terms of the ability to eat, chew,and swallow. Serious consequences of OM include limited mouth open, impaired nutritional intake, increased risk of septicemia, even needed for breaks or completed cessation of cancer treatment. Despite a variety of agents have been tested for managment oral mucositis, it still remains as a signficant challenge for both patients and clinicians.Objective To evaluate the safety and efficacy of ozonated water (0.5mg/L)administered as topical mouthwash for treatment of chemotherapy-induced oral mucositis (OM).Patients and Methods Sixty-nine cases of hematological malignancies were randomly assigned to either the treatment group or the control group, who were consisted of thirty-four cases of Acute Myeloid Leukemia, seventeen cases of Acute Lymphoblastic Leukemia, thirteen cases of Non-Hodgkin’s Lymphoma, three cases of Multiple Myeloma, and two cases of Myelodysplastic Syndromes with OM. The treatment group received ozonated water0.5mg/L by mouthwash about five minutes each time and five times each day; The control group received compound lidocaine solution which were composed of normal saline (250mL), lidocaine hydrochloride injection (2%,5mL),vitamin B12(5mg) and gentamycin(80000U) with the same dose and times by mouthwash。The severity of OM was assessed by WHO grade scale daily. Self-reported quality of life (QOL) was assessed by patients every day. The clinical efficacy was evaluated in the fifth day of mouthwash. Adverse events related to the topical administration of ozonated water and compound lidocaine solution was graded based on the NCI CTCAE version4.0.Results1. The base characteristics:One case of IV degree of oral mucositis gave up cancer therapy due to economic reasons in the treatment group, a total of sixty-eight cases were analyzed finally. The base characteristics were similar (P>0.05) between two groups in terms of gender, age, types of diseases, the number of neutrophils before mouthwash, the times of previous chemotherapy, the times about previous occurrence of OM, the emergence time of OM, and the degrees of OM.2. The clinical efficacy:(1)The total effective rate of oral mucositis was higher for the treatment group than for control group(97.0%vs73.5%, P<0.05).(2)The duration of objective OM(WHO≥II degree),excluding patient’s self-decalaration (WHO=I degree), was significantly shorter in treatment group than in control group (4.30±2.37days vs8.15±3.07days, P<0.05).(3)The sore throat scores were significant differences between two groups(P<0.05); The sore throat scores were significant differences in five time points (P<0.05).There was a significant interaction between different time points and groups(P<0.05). The treatment group declined more evident than the control group in the sore throat scores. The least significant difference comparisons in difference time point showed that the sore throat scores were similar between the first day and the second day(P>0.05), and there were no significant differences on the other days(P<0.05).(4) Subgroup analysis:1)There were no significant differences between two groups in degrees of OM on the first, second, and third day(Pi>0.05;P2>0.05;P3>0.05). The differences of two groups were significant on the forth and fifth day(P4<0.05;P5<0.05).2)The duration of Ⅱ degree of oral mucositis was3.5(1-11)days in the treatment group and7.0(2-15)days in the control group, the differences were significant(P<0.05); The duration of III degree of oral mucositis of the treatment group and the control group were5.0(2～9)days and9.0(8～11)days, the differences of two groups were significant(P<0.05).3. The safety profile:None of patients reported adverse events associated with mouthwash.Conclusion The ozonated water (0.5mg/L) mouthwash formulation was safe and effective when used for the treatment of chemotherapy associated OM in patients with hematological malignancies.