Ayşenur ÇETİN ÜÇERİZ RN, MSc^1*, Yasemin Özer Güçlüel, Rn, Msc, PhD²

¹Department of Nursing, Halic University, Faculty of Health Sciences, Istanbul, Turkey; Koc University Graduate School of Health Sciences, İstanbul, Turkey. ORCID: 0000-0002-6077-9760

²Department of Nursing, Halic University, Faculty of Health Sciences, Istanbul, Turkey. ORCID: 0000-0003-3325-8502

*Corresponding Author: Ayşenur ÇETİN ÜÇERİZ RN, MSc, Department of Nursing, Halic University, Faculty of Health Sciences, Istanbul, Turkey; Koc University Graduate School of Hea lth Sciences, İstanbul, Turkey. ORCID: 0000-0002-6077-9760

Abstract
Hematopoietic stem cell transplantation therapy is frequently used to treat aplastic anemia, a rare hematological disease. After hematopoietic stem cell transplantation, most patients may develop oral mucositis as a side effect of treatment. Oral mucositis is a severe condition characterized by erythema, edema, and ulcerations of the oral mucosa. It is stated that the severity of oral mucositis in hematopoietic stem cell transplantation patients directly affects the need for total parenteral nutrition, the incidence of infection, the increase in the use of narcotics, and the prolongation of hospital stay. This case report discussed the healing process of oral mucositis with the effect of treatment and nursing care in a patient who underwent hematopoietic stem cell transplantation. The patient was evaluated comprehensively since his hospitalization, the treatment and care process was managed by taking evidence-based interventions as a guide, and the patient's oral mucositis decreased from Grade III to Grade 0, and he was discharged on the 65th day after transplantation. In conclusion, in the hematopoietic stem cell transplantation process, it is recommended that nurses evaluate the patient with a holistic perspective, use evidence-based guidelines in their practices, record and report the results of the application, take an active role in the research, and increase the analyses.

Keywords: Hematopoietic stem cell transplantation, nursing care, oral mucositis

Oral mucositis (OM) is a severe condition characterized by erythema, edema, and ulcerations of the oral mucosa [23]. Head and neck radiation therapy is a complication of chemotherapy, chemoradiotherapy, and HSCT [13]. HSCT affects 75-100 % of patients, and these rates vary depending on stem cell transplantation preparation regimens. Oral intake may be impaired due to pain, leading to the need for parenteral nutrition in some cases [13]. Since oral lesions can weaken the mucosal barrier and cause local or systemic infection, they may cause prolonged hospital stays and interrupt existing treatment [13,18]. 

The goal of OM treatment is to prevent or reduce the severity of lesions, manage associated symptoms, and ensure continuity of cancer treatment [26]. Frequent evaluation of oral tissues before and during cancer treatment reduces the risk of infection and helps to determine the initial stages of oral mucositis [29]. In the treatment and care of oral mucositis, it is essential to adopt oral care protocols, follow up on oral and dental health, use various mouthwashes, and provide quality nursing care with frequent evaluation of patients [13,22]. This study examined the effect of treatment and nursing care on patients with oral mucositis who underwent HSCT.

Case Report
I was diagnosed with severe aplastic anemia and married 29, a 29-year-old female patient. With the patient's consent, allogeneic peripheral stem cell transplantation was performed on a 22-year-old male donor who is not a fully compatible relative of Human Leucocyte Antigen (HLA) on March 6, 2023. The preparation regimen was cyclophosphamide+fludarabine (RIC regimen). Graft Versus Host Disease (GVHD) prophylaxis, Antithymocyte Globulin (ATG) 20 mg/kg/day + Methotrexate (+1, +3, +6, +11) + Cyclosporine-a were preferred. Neutrophil engraftment occurred on day +29 (05.05.2023), but platelet engraftment did not happen when discharged on day +65.

The Oral Mucous Membrane Integrity Assessment and Monitoring Form and the World Health Organization Oral Toxicity Scale evaluated the patient's oral mucosa. Oral Mucositis Grade 0 was determined in the first evaluation. On the second day, the epigastric region was followed up with 500 mg sodium alginate, 213 mg sodium bicarbonate, and 325 mg calcium carbonate active suspension to the treatment plan due to complaints of pain and difficulty swallowing. Due to dryness in the lower lip, the patient was given D-alpha tocopheryl acetate (2*1) supplementation on the +7th day. When the patient's oral mucosa was evaluated on the +11th day, the treatment plan was updated with the significant increase in swallowing difficulty, and a swab sample was taken from the lesion in the mouth.

A swab from the oral lesion revealed positive HSV-1 DNA and negative HSV-2 DNA. In addition to swallowing difficulties and pain symptoms, the use of analgesics/narcotics was altered due to herpetic dermatitis on the lip on day 21 and was evaluated as OM Grade II (Table 1). CMV-DNA, HSV-DNA, and Candida were sent from the oral swab due to the presence of plaques on the patient's oral mucosa on the +26th day. Diffuse lesions in the mouth (punch hole) were seen on day +28 (Figure 1). Candida glabrata reproduction and Cytomegalovirus (CMV) were found negative in the swab sent from the mouth. Due to the increase in lesions in the mouth, the biopsy was performed on +35 days with suspicion of GVHD. OM Grade II was re-evaluated on +42 days with the regression of hemorrhagic lesions on the lip, white fungal plaque, and lip mucosa plaque.

The patient's mucositis showed significant regression on +51 day, and the biopsy result sent with suspicion of GVHD was negative. Although there were white plaques on the back of the tongue, mucositis regressed in other areas on day +58 (Figure 2), no pain symptoms were observed, and oral intake continued as fluid-soft. The nutrition team provided nutritional support, and psychosocial support was provided by the consultation-liaison psychiatry. Clinical nurses, Daily oral mucositis assessments were performed regularly. During the period when OM was at Grade II and Grade III level, information was given about the details that the patient should pay attention to in oral care (oral care 4 times a day with 8 hours intervals, mouthwashes to be used, etc.) and nutrition, and the patient was encouraged to perform self-care by cooperating with the patient. To ensure the control and follow-up of the malnutrition process, the patient's weight, waist circumference, and nutrition were also evaluated throughout the hospitalization, and follow-up was performed. Detailed information about the OM treatment process and nursing care is given in (Table 1). The patient was discharged with Grade 0 OM on the +65th day at the end of the whole treatment process and nursing care. 

Table 1. Findings on Oral Mucositis Process and Management

Figure 1. Intraoral pictures of the patient from different points after the development of oral mucositis due to chemotherapy

Figure 2. After the treatment, the patient's intraoral pictures from different points

According to various cancer and treatment methods, OM and other oral complications show different incidences. Their prevalence and severity vary depending on the type of transplantation and the preparation regimen and are seen as an essential complication [1,14]. 

Evidence-based therapies to ensure effective symptom management and improve quality of life in HSCT patients [11,12,30,37] and the implementation of nursing care is very important [2]. The literature recommends widespread use of oral care protocols to prevent OM since 2013 and collectively emphasizes oral care during treatment and regular evaluation of OM [7,19,35]. In the prevention and treatment of OM, oral care protocols, mouthwashes (normal saline, sodium bicarbonate, chlorhexidine gluconate), benzydamine, vitamin E, and glutamine use are included in the relevant literature [9,18,28,32]. In addition, it is reported in the research that mouthwashes such as normal saline and carbonated solutions that do not have medical content can be used 4-6 times/day in OM management. Chlorhexidine gluconate mouthwashes are an effective antiseptic, especially against gram-positive and gram-negative organisms, anaerobes, facultative anaerobes, and yeasts, and benzydamine hydrochloride is preferred as an analgesic in the prevention and treatment process of oral mucositis because it is a non-steroidal anti-inflammatory [9,18,28,32]. The effects of new methods and treatment modalities for the management of OM have become one of the areas where healthcare professionals are researching to establish evidence for the treatment of oral mucositis. For example, Silva et al. (2017) mentioned the use of dissolving pain lozenges for the local treatment of oral mucositis in their study, and in addition to cryotherapy, low-level laser therapy, herbal methods and nutritional supplements, apitherapy, essential oils and cognitive behavioral techniques are among these complementary therapies [11,32,34]. In light of all this information, considering the evidence-based care protocols in the OM process management of the case (Table 2), 0.9 % sodium chloride mouthwash, chlorhexidine gluconate, vitamin E, acyclovir use, 2 % morphine mouthwash, and super soft toothbrush were preferred in oral care 4-6 times/day.

During the treatment process in HSCT patients, it is essential not to consume foods that will damage the oral mucosa [11]. Especially in those with painful oral mucosa lesions, it is recommended to avoid acidic fruits, especially citrus fruits, acidic drinks, and spicy, salty, sharp, and rough surface foods [27]. In addition, studies have reported that products such as cold drinks, ice cream, and ice pieces held in the mouth will temporarily relieve pain [6,20,25]. In this case, the use of mucosa-irritating foods was prevented, oral care was done at least 4 times a day, nutrition education was given, and the patient was supported with cold application (ice pieces) and analgesics in severe pain.

Grade III OM is associated with mortality during periods of sepsis and immunosuppression. In the studies conducted on the subject, it has been stated that oral complications due to cancer treatment affect the quality of life and that there are delays in cancer treatment due to these problems affecting the compliance of patients with treatments [4,31,36]. In this case, the OM level progressed to Grade III, and the length of hospital stay was prolonged from +28 days to +65 days after HSCT, causing a delay in the treatment process.

Oncology nurses' use of competent, knowledgeable, evidence-based practices on oral care needs and assuming the role of caregiver, regular patient follow-up, active use of nurse-led patient education and follow-up systems, joint decision of physician and nurse on treatment and care, implementation of individual care plans on a patient basis, application of acute treatment when necessary according to the stage of mucositis contribute to OM management reported [3,5,8,18,21,24]. In this case, treatment and nursing care were applied in line with the literature and guidelines (Tables 1 and 2).

Table 2: Classification of recommendations according to level of evidence in the management of oral mucositis

* I: Meta-analyses of well-designed controlled trials, randomized trials (false-positive and false-negative error few), II: At least one well-designed experimental study, randomized studies (false-positive or false-negative error or both high), III: well-designed, semi-experimental studies, (non-randomized, single-group, pretest-posttest comparative, cohort, paired case-control studies), IV: Well-designed, non-experimental studies, (comparative,  correlational, descriptive studies and case analyses), V: Case report and clinical examples

**A: Type I evidence or Type II-III-IV evidence shows the same results, B: Type II-II or Type IV evidence shows the same results, C: Type II-II or Type IV evidence does not show continuity, D: There is little or no empirical evidence in this area [11,12,30,37].

Result
O.M., which is one of the common complications of the HSCT process and adversely affects the treatment process, was evaluated comprehensively since the patient's hospitalization, the treatment and care process was managed by taking evidence-based interventions as a guide, and the patient's O.M. decreased from Grade III to Grade 0 and was discharged on the 65th day after transplantation. In line with this result, it is recommended that nurses, who have a primary role in the HSCT process, evaluate the patient with a holistic perspective, use evidence-based guidelines as guidelines in their practices, record and report the results of their methods, take an active role in the researches and increase the analyses.

Informed Consent: Written and verbal consent was obtained from the individual E.K. who participated in the study. 

Conflict of Interest Statement: The authors have no conflict of interest to declare this was an unfunded study.

Author Contributions:
All authors contributed significantly to the concept and design of the article and its interpretation. All authors were involved in putting together materials, drafting, and critically reviewing for essential and relevant, applied intellectual content. All authors approved the final version, assumed responsibility for parts of the content, and agreed to be responsible, ensuring the accuracy and integrity of the work.

Financial Support: The authors have stated that they did not receive financial support for this study.

Acknowledgments: We would like to thank all health professionals in the Bone Marrow Transplantation Unit of Istanbul Faculty of Medicine for their support and contributions to the study and to our patient E.K., who wanted the disease process to be a hope for other hematopoietic stem cell transplantation patients.

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