Hematologic malignancies are the fifth most common type of cancer in the world. Patients with hematologic malignancies receive long-term and exhausting treatments such as chemotherapy, radiotherapy, hematopoietic stem cell transplantation and supportive therapies. Chemotherapy-induced nausea and vomiting has a significant impact on the daily lives of patients and causes physiological effects such as anorexia, malnutrition, weight loss, dehydration and electrolyte imbalance. It also has a negative impact on activities of daily living and psychological status, and may lead to poor adherence to chemotherapy regimens, refusal of chemotherapy or discontinuation of treatment. Oral mucosa is one of the areas most affected by the cytotoxic damage of chemotherapy. Disruption of the oral mucosa causes nausea, vomiting and feeding problems. Patients resort to non-drug approaches to manage these problems. It is important that these non-pharmacologic approaches are supported and controlled by reliable and evidence-based studies in order to prevent adverse effects on patient outcomes. In the literature, it has been determined that peppermint oil has antiemetic, antiseptic, anti-inflammatory, analgesic, antiseptic, antioxidant, antiviral, antifungal and spasmolytic effects, protects the integrity of the oral mucosa and has positive effects on nausea-vomiting and anorexia.

In this context, the aim of the study was to investigate the effect of a preventive oral care protocol with peppermint oil mouthwash on chemotherapy-induced nausea, vomiting and appetite in patients with hematologic malignancy.

Research Hypotheses H01: The protective oral care protocol applied with peppermint oil in patients with hematological malignancies has no effect on the development of chemotherapy-induced nausea and vomiting.

H02: The protective oral care protocol applied with peppermint oil in patients with hematological malignancies has no effect on the severity of chemotherapy-induced nausea and vomiting.

H03: The protective oral care protocol applied with peppermint oil in patients with hematological malignancies has no effect on the development of chemotherapy-induced anorexia.

H04: The protective oral care protocol applied with peppermint oil in patients with hematological malignancies has no effect on the severity of chemotherapy-induced anorexia.

Methods: The type of study is a single-blind randomized controlled experimental study. The research will be conducted between September 10, 2025, and April 10, 2026, with patients admitted to the hematology clinic of a university hospital for chemotherapy treatment. The study will be conducted with a total of 72 people who will be randomly assigned to the intervention (n=36) and control groups (n=36) by stratified and block randomization method. Patients who are 18 years of age or older, have hematologic malignancy, with a history of at least one chemotherapy cycle, and scheduled to receive chemotherapy with high or moderate emetogenic risk agents, do not have oral mucositis before chemotherapy, do not have metastasis, are literate and volunteer to participate in the study will be included in the study. Research data will be collected using the "Patient Introduction Form", "Rhodes Nausea-Vomiting and Retching Index", "Oral Assessment Guide", "Appetite Assessment Chart [(Visual Analog Scale (VAS)]", "Peppermint Oil Protective Oral Care Protocol", "Food Intake Record Form", "Allergic Reaction Monitoring Form" and "Patient Monitoring Form and Antiemetic Record Chart". In addition to the routine protective oral care (saline solution mouthwash and/or sodium bicarbonate mouthwash) in the clinic, "Peppermint Oil Protective Oral Care Protocol" will be applied to the intervention group for 6 days from the start of chemotherapy treatment. Patients will receive mouthwash prepared with 1 ml of peppermint oil and 50 ml of prepared drinking water 3 times a day. Patients in the intervention group will be monitored for 6 days by evaluating oral assessment, development of oral mucositis, appetite follow-up and compliance with mouthwash. The development of allergy due to the use of peppermint oil in each mouthwash application will be evaluated. The control group will not receive any oral care intervention by the researcher and will receive routine preventive oral care in the clinic. In the evaluation of the data, descriptive statistics, Chi-square / Fisher's Exact test will be used for the relationship between categorical variables, Mann Whitney U test, Wilcoxon test, Kruskal-Wallis H test will be used for the relationship between continuous variables in groups that do not show normal distribution; one-way analysis of variance / repeated measures analysis of variance, t test for dependent and independent groups will be used in groups with normal distribution. Correlation analysis and regression analysis will be used to examine the relationship between variables.

Background: Hematologic malignancies are a group of neoplasms caused by the uncontrolled proliferation of cells in lymphoid tissue or bone marrow. Hematologic malignancies are considered the fifth most common type of cancer worldwide. Hematologic malignancies are classified differently based on their pathophysiological characteristics, so the treatment method and protocol specific to the type of cancer also varies. Patients face long-term and exhausting treatments such as chemotherapy, radiotherapy, hematopoietic stem cell transplantation, and supportive therapies. Chemotherapy treatment in patients with hematological malignancies causes common symptoms such as pancytopenia, fatigue, oral mucositis, nausea/vomiting, and loss of appetite, depending on the characteristics of the drug. Chemotherapy (CT)-induced nausea and vomiting have a significant impact on patients' daily lives and cause physiological effects such as loss of appetite, malnutrition, weight loss, dehydration, and electrolyte imbalance and physiological effects such as decreased drug absorption or excretion by the kidneys. One of the areas most affected by the cytotoxic damage of chemotherapy is the oral mucosa. Damage to the oral mucosa, nutritional disorders, swallowing disorders, and the development of infections are among the many complications that negatively affect the patient's compliance with treatment. Damage to the oral mucosa associated with chemotherapy, as well as symptoms such as nausea, vomiting, and loss of appetite, can be prevented or reduced through effective nursing interventions and care. In addition to pharmacological methods, non-pharmacological methods are also used in many societies to control nausea, vomiting, and loss of appetite. Herbal products are the most commonly used complementary method by cancer patients to reduce chemotherapy-related side effects. Studies on the effect of herbal products in the management of nausea and vomiting can be found in the literature. A study evaluating the effect of peppermint oil on nausea, vomiting, and loss of appetite in cancer patients has been found. It is stated that medicinal peppermint essential oil may prevent nausea and vomiting due to its spasmolytic and antiseptic effects on the gastric tract and colon. In this context, it is anticipated that this research project, planned as an experimental study, will provide evidence for patient care by determining the effect of peppermint oil oral care on nausea, vomiting, and loss of appetite in patients diagnosed with hematological cancer. The research aims to determine whether a protective peppermint oil oral care protocol reduces the incidence/severity of nausea, vomiting, and loss of appetite in patients with hematological malignancies undergoing chemotherapy.

Methods: The type of study is a single-blind randomized controlled experimental study. The research will be conducted between September 10, 2025, and April 10, 2026, with patients admitted to the hematology clinic of a university hospital for chemotherapy treatment. The study will be conducted with a total of 72 people who will be randomly assigned to the intervention (n=36) and control groups (n=36) by stratified and block randomization method. Patients who are 18 years of age or older, have hematologic malignancy, with a history of at least one chemotherapy cycle, and scheduled to receive chemotherapy with high or moderate emetogenic risk agents, do not have oral mucositis before chemotherapy, do not have metastasis, are literate and volunteer to participate in the study will be included in the study. Individuals will be excluded from the study if they meet any of the following criteria: use of herbal remedies for nausea, vomiting, or anorexia; concurrent radiotherapy with chemotherapy; non-adherence to standard antiemetic therapy according to the chemotherapy preparation regimen and protocol; known allergy to peppermint oil; presence of psychiatric disorders; communication impairments (hearing or speech difficulties); altered level of consciousness; endotracheal intubation; requirement for oral care solutions differing from the clinic's routine procedures (other than saline or sodium bicarbonate); presence of chronic gastrointestinal diseases (including gastritis, gastric/peptic ulcer, ulcerative colitis, Crohn's disease, gastroesophageal reflux, irritable bowel syndrome, cirrhosis, or pancreatitis); migraine; brain metastases; hepatic or renal insufficiency; administration of low-emetogenic chemotherapy; or mucositis, as indicated by an Oral Assessment Guide score reflecting compromised oral health (15-24 points). Research data will be collected using the "Patient Introduction Form", "Rhodes Nausea-Vomiting and Retching Index", "Oral Evaluation Guide", "Appetite Monitoring Chart [(Visual Analog Scale (VAS)]", "Peppermint Oil Protective Oral Care Protocol", "Food Consumption Amount Chart", "Allergic Reaction Monitoring Form" and "Patient Monitoring Form and Antiemetic Record Chart". In addition to the routine preventive oral care (SF and/or sodium bicarbonate mouthwash) in the clinic, "Peppermint Oil Protective Oral Care Protocol" will be applied to the intervention group for 6 days from the start of chemotherapy treatment. Patients will receive mouthwash prepared with 1 ml of peppermint oil and 50 ml of prepared drinking water 3 times a day. Patients in the intervention group will be monitored for 6 days by evaluating oral assessment, development of oral mucositis, appetite follow-up and compliance with mouthwash. The development of allergy due to the use of peppermint oil in each mouthwash application will be evaluated. The control group will not receive any oral care intervention by the researcher and will receive routine preventive oral care in the clinic. In the evaluation of the data, descriptive statistics, Chi-square / Fisher's Exact test will be used for the relationship between categorical variables, Mann Whitney U test, Wilcoxon test, Kruskal-Wallis H test will be used for the relationship between continuous variables in groups that do not show normal distribution; one-way analysis of variance / repeated measures analysis of variance, t test for dependent and independent groups will be used in groups with normal distribution. Correlation analysis and regression analysis will be used to examine the relationship between variables.

The detailed description of the oral care protocol is presented below. Peppermint Oil Protective Oral Care Protocol

1. Materials

   • 1 ml peppermint oil
   • 1 disposable paper cup
   • 1 wooden stir stick
   • 50 ml bottled water or boiled and cooled tap water

2. Preparation of Peppermint Oil Mouthwash

   • Wash and dry hands thoroughly.
   • Pour 50 ml of bottled water or boiled and cooled tap water into the paper cup.
   • Add 1 ml of peppermint oil (kept at room temperature) into the cup.
   • Mix the water and peppermint oil using the wooden stir stick.

3. Application of Peppermint Oil Mouthwash

   • If lying in bed, sit upright before the procedure.
   • Take approximately 5 ml of the prepared solution into the mouth and gargle.
   • Gargle for about 30 seconds, then spit out the solution.
   • Do not swallow the solution.
   • If any discomfort occurs in the oral cavity, stop the procedure immediately and inform the researcher.
   • After completing the procedure, discard the used materials and wash your hands.

4. Recording of Mouthwash Application

   • Document the procedure in the Patient Monitoring Form.

5. Precautions

   • Perform peppermint oil mouthwash three times daily at the following times:

     • 07:00-08:00
     • 15:00-16:00
     • 22:00-23:00

   • Mouthwash use should begin concurrently with chemotherapy treatment.

   • Avoid drinking liquids or consuming food, and refrain from rinsing the mouth for at least 30 minutes after using the mouthwash.

   • Continue routine clinical oral care practices in addition to peppermint oil mouthwash.

   • Store peppermint oil at room temperature in a dark place away from direct light.

Inclusion Criteria:

• Age 18 years or older
• Clinical diagnosis of hematologic malignancy
• History of at least one chemotherapy cycle
• Scheduled to receive chemotherapy with high or moderate emetogenic risk agents
• No oral mucositis before chemotherapy
• No metastasis
• Literate (able to read and write)
• Volunteer to participate in the study

Exclusion Criteria:

• Use of herbal remedies for nausea, vomiting, or anorexia
• Concurrent radiotherapy with chemotherapy
• Non-adherence to standard antiemetic therapy according to the chemotherapy preparation regimen and protocol (e.g., use of antiemetics other than granisetron or metoclopramide)
• Known allergy to peppermint oil
• Psychiatric disorders
• Communication impairments (hearing or speech difficulties)
• Altered level of consciousness
• Endotracheal intubation
• Requirement for oral care solutions other than the clinic's routine procedures (saline or sodium bicarbonate)
• Chronic gastrointestinal diseases (gastritis, gastric/peptic ulcer, ulcerative colitis, Crohn's disease, gastroesophageal reflux, irritable bowel syndrome, cirrhosis, or pancreatitis)
• Migraine
• Brain metastases
• Hepatic or renal insufficiency
• Administration of low-emetogenic chemotherapy
• Mucositis (Oral Assessment Guide score: 15-24 points)