AbstractThe number of allogeneic hematopoietic cell transplantation constantly increases. Therefore, there is an urgent need to carefully analyze the general and oral health state of people with acute myeloid leukemia who underwent this procedure. This study aimed to investigate the type and frequency of oral mucosal lesions in patients with acute myeloid leukemia after allogeneic hematopoietic cell transplantation, depending on the intensity of the conditioning regimen. Eighty patients diagnosed with acute myeloid leukemia were assigned to two groups based on the conditioning used before transplantation. The dental team investigated the oral mucosa in all patients thrice during the treatment. The most common oral pathological lesion in the study group was mucositis, which developed in a significantly higher percentage of patients who underwent myeloablation therapy compared to reduced intensity conditioning (p = 0.0335). Other frequently found eruptions included massive coating on the dorsal tongue surface, petechiae, and exfoliating cheilitis. The type of conditioning did not significantly influence their frequency. A significant increase in post-transplant lesions was observed on the lips, sublingual area, and floor of the mouth. There were no statistically significant differences in the site of lesions depending on the type of conditioning. Oral mucosal pathological changes in the study group were frequent. The type of conditioning influenced the frequency of mucositis but did not affect the frequency and the location of other types of oral mucosal lesions. Providing the patients qualified for chemotherapy with professional dental support is important.
IntroductionAcute myeloid leukemia (AML) is a proliferative disease of the hematopoietic system characterized by uncontrolled clonal proliferation of neoplastic hematopoietic precursors. A disturbed production of normal blood cells in the blood, bone marrow, and other tissues occurs. AML accounts for approximately 80% of all acute leukemias in adults. The disease risk increases with age. The average age of AML patients is 69 years1,2,3. The treatment options for AML depend on the patient’s age, general health, cytogenetic, and molecular risk. A therapeutic approach based on conventional chemotherapy caused total remission in 60–80% of adults under 60 years of age with AML de novo4,5. AML is the leading indication for allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Before this procedure, patients require high doses of antiproliferative and cytostatic drugs.
Although the intensive conditioning regimen (myeloablative conditioning, MAC) decreases the risk of relapse after transplantation, it is characterized by high toxicity6. Reduced-intensity conditioning (RIC), an alternative pre-transplant procedure, was designed to suppress the patient’s immune system enough to accept the donor stem cells while being less toxic than MAC. However, the risk of transplant rejection is higher for this type of treatment.During anticancer therapy, the regeneration of the damaged epithelial cells is disturbed. It may result from the direct action of cytostatics on the oral epithelium, from an impaired immune system function, and from decreased salivation. Oral erythema, erosions, and ulcers, which may become a portal of entry for several viral, fungal, and bacterial antigens appear frequently7,8,9. Infections are a common cause of morbidity and mortality in children and adults after hematopoietic cell transplantation (HCT).Due to antibiotic resistance, bacterial infections are associated with high mortality both after allo- and auto-HCTs. At the same time, invasive fungal disease remains a significant cause of morbidity and mortality, particularly after allo-HCT. A high risk of viral infection was mainly observed after allo-HCT, which could be attributed to the delayed immune reconstitution after transplantation10. Hematologic deficits, a common complication in AML subjects, also interfere with oral mucosa condition. Iron and vitamin B12 deficiencies may cause a reduction in the thickness of the oral epithelium, which makes it more vulnerable. In contrast, a decreased accessibility of transferrin-bound iron disrupts the lymphocytes and pro-inflammatory cytokine production11.Because the reduced intensity conditioning enables the treatment of older adults and patients with coexisting systemic diseases, the number of allo-HSCT procedures has been progressively increasing6. Therefore, there is a need for a thorough analysis of the health status of patients with AML after allo-HSCT, with particular attention to oral mucosal lesions.This study aimed to investigate the type and frequency of oral mucosal lesions in patients with acute myeloid leukemia after allogeneic hematopoietic cell transplantation, depending on the intensity of the conditioning regimen. The number of research in this field is minimal12,13,14. As those patients are at a high risk of developing several local complications of chemotherapy, a profound analysis of the oral cavity state is relevant to establish a uniform algorithm of dental care in this group.Materials and methodsThe study group consisted of 80 patients (42 women and 38 men), aged 19 to 69 years (mean 46.6 ± 13.6), diagnosed with AML, who underwent allogeneic hematopoietic cell transplantation in the Department of Hematology and Bone Marrow Transplantation of Poznan University of Medical Sciences (PUMS), Poland. Depending on the conditioning, the patients were assigned to one of two groups. The first group consisted of 54 patients (30 women and 24 men), with a mean age of 42.3 ± 11.9 years, who underwent myeloablation therapy (MAC). The other group consisted of 26 patients (12 women and 14 men) with a mean age of 55.5 ± 12.9 years, who were treated with reduced intensity therapy (RIC). The qualification of patients into MAC and RIC regimen was performed by a hematologist in the Department of Hematology and Bone Marrow Transplantation of PUMS based on the two major criteria: the age of the patient and the presence of concomitant diseases, as evaluated concerning the hematopoietic cell transplantation-specific comorbidity index (HCTCI) according to Charlson et al.15. Patients unable to give consent were not eligible for inclusion. Also, the patients who could not have oral examinations for any reason that impaired the examination, such as intubation or sedation, were excluded from the study.Cytostatics used in the MAC group included the following: fludarabine, busulfan, melphalan, and treosulfan, individually adjusted to each patient’s profile and applied in appropriate proportions as FluBu4 (34 patients), FluBu3 (12 patients), and MelFluTreo (8 patients). RIC therapy consisted of fudarabine, busulfan, cytarabine, and total body irradiation (TBI), used as FluBu2 (17 patients) or FluCyTBI (9 patients).The oral hygiene algorithm involved tooth brushing with a soft toothbrush four times a day and avoiding substances that cause local irritation (alcohol mouth rinses and acidic, salty, or dry foods). A supersaturated calcium phosphate electrolyte mouth rinse (Caphosol, Fomukal) was recommended for all patients and was used four times daily. A systemic antifungal drug (fluconazole) was included as a standard procedure in all patients. For the treatment of oral mucositis, patients were advised to use multipurpose mouthwashes and antifungals (benzocaine/natrium, boricum/glicerini, thymol/glycerini, and colistin/gentamycin/nystatin, amphotericin B)16,17. Morphine and tramadol were utilized in pain management (most common in mucositis-related pain, followed by pain in the musculoskeletal system).The examination of the oral cavity in each patient was performed three times according to the following scheme used in the Department of Hematology and Bone Marrow Transplantation of PUMS:
(A)
Preliminary examination - in the period preceding bone marrow transplantation, from day − 10 to day − 7.
(B)
First examination - after transplantation of hematopoietic cells from day + 3 to day + 7.
(C)
Second examination - after hematopoietic cell transplantation from day + 8 to day + 14.
The oral examination was performed on all patients by the dental team, comprised of two dentists experienced in oral pathology, using a standard dental diagnostic set and artificial light source. Pathological lesions on the oral mucosa were classified by type, location, and development time. All the lesions were photographed. Oral mucositis was evaluated according to a 5-point scale recommended by the World Health Organization (WHO)16,18. This paper presents the summarized rate of mucositis stages under “mucositis.”The study was approved by the Poznan University of Medical Sciences Ethics Committee (approval code: 783/16) and complied with the Declaration of Helsinki’s guidelines. All the patients were informed in detail about the nature of the study before consent was obtained for participation in this project.The results were statistically analyzed with Statistica.PL ver. 13.0 (StatSoft, Inc., 2014) for Windows with t-Student, Kruskal–Wallis, Mann–Whitney U test, and test of the difference between tests with p < 0.05 considered a significance level.ResultsWe have evaluated the frequency of oral mucosal lesions in patients with AML undergoing allo-HSCT depending on the conditioning type used. We have considered the lesions’ type, their location, and the moment of onset.The types and the frequency of pathological oral mucosal lesions in the study group are presented in Table 1.Table 1 The type and frequency of oral mucosal lesions in the study group.Full size tableMost observed oral mucosal lesions in patients undergoing bone marrow transplant included: mucositis, scalloped tongue, linea alba, morsicatio buccae, pigmented lesions, oedema, mucosal pallor, white patches, petechiae, depapilation of the tongue, exfoliative and angular cheilitis, bullae and vesicles.Considering the moment of onset, at least one pathological oral mucosal lesion was found in 67 (83%) patients in the preliminary examination, in 79 (98%) patients in the first-week examination, and in 69 (85%) patients in the second-week examination. The differences between the preliminary and first examinations and the first and second examinations were statistically significant (p = 0.0006, p = 0.0018). The most observed type of lesion after transplantation was mucositis, found in 53 (66%) patients during the first week and in 59 (74%) patients examined in the second week. In the preliminary evaluation, the type of lesions was detected in only 13 (16%) patients. The difference in lesion frequency between preliminary and post-transplant examinations was statistically significant (p < 0.0001).Another commonly observed lesion was the massive, removable coating on the dorsal tongue, found in 46 (57%), in 41 (51%), and in 33 (41%) patients, respectively, wherein the frequency of this finding decreased with each subsequent examination, with a statistically significant difference between the preliminary and second-week examination (p = 0.0417).Statistically significant increase in the frequency of petechiae was found after transplant- 21 (26%) and 17 (21%) patients compared to 5 patients (6%) before transplant (p = 0.0005, p = 0.0052), as in the case of exfoliative cheilitis, where the difference between preliminary and first examination was statistically significant (6 (7%) vs. 16 (20%); p = 0.0155).The types and the frequency of pathological oral mucosal lesions in the study group, depending on the conditioning type used, are presented in Table 2.Table 2 The type and frequency of oral mucosal lesions in the study group depending on the conditioning type used (MAC/RIC).Full size tableAmong the patients who underwent MAC conditioning, at least one oral mucosal lesion was found in 44 people (81%) upon the preliminary examination. In two consecutive post-transplant examinations it reached 54 (100%) and 45 (83%). The differences between the preliminary and first-week examinations (p = 0.0008) and the first-week and second-week examinations (p = 0.0015) were statistically significant.The most commonly observed oral lesion in the MAC group after the transplantation was mucositis, which was revealed in 40 (74%) patients during the first examination and 45 (83%) patients during the second. The frequency of those lesions increased significantly in the following post-transplant examinations compared to preliminary observation, where it was revealed in 9 subjects only (p < 0.0001, p < 0.0001). A massive coating on the dorsal tongue surface was found in 26 (48%), 27 (50%) and 20 (37%) patients, respectively. Less commonly observed lesions in the MAC group included linea alba and morsicatio buccae- 11 (20%), 9 (17%), and 8 (15%) patients, respectively. Exfoliative cheilitis was found in 5 (9%), 13 (24%), and 12 (22%) patients, respectively, and the difference between preliminary and first-week examination was statistically significant (p = 0.0357). In the following examinations, petechiae were observed in 3 (6%), 10 (19%), and 7 (13%) subjects, showing statistically significant differences between the preliminary and first-week examinations (p = 0.0411). Other lesions were found less frequently (from 0 to 11%). None of the patients from the MAC group revealed pigmented oral mucosa lesions.In the RIC group, at least one pathological mucosal lesion was detected in 23 (88%) patients before the transplantation and in 25 (96%) and 24 (92%) patients during the follow-up examinations. Comparing the frequency of oral mucosal lesions in the RIC group, the most observed finding in the subsequent examinations was a massive coating on the dorsal tongue surface and mucositis. In the following observations, the coated tongue was revealed in 20 (77%), 14 (54%), and 13 (50%) subjects, respectively. The difference between the preliminary and second examinations was statistically significant (p = 0.0432).In the RIC group, mucositis was found in 4 (15%) patients before the transplantation, half of the patients during the first-week evaluation, and 14 (54%) patients in the second week after transplantation. The differences between the preliminary, first, and second examinations were statistically significant (p = 0.0091, p = 0.0041). Petechiae were found in 2 (8%), 11 (42%), and 10 (38%) patients, respectively, showing statistically significant differences between the preliminary and following examinations (p = 0.0046, p = 0.0102). Linea alba and morsicatio buccae were observed in 2 (8%) patients in the preliminary examination and in 5 (19%) and 3 (12%) subjects in the subsequent examinations. Other lesions were found less often (from 0 to 12%). None of the patients from the RIC group suffered vesiculo-bullous lesions or atrophic tongue lesions (Table 2).A comparative analysis of the frequency of the oral mucosal lesions depending on the conditioning type used revealed statistically significant differences for mucositis, coating on the tongue, petechiae, and exfoliative cheilitis.In the first week after transplantation, mucositis was found in 40 (74%) patients in the MAC group and half of the RIC patients (50%). The difference was statistically significant (p = 0.0335). In the second post-transplant week, lesions of this type were observed in 45 (83%) MAC patients and 14 (54%) RIC patients. The difference was also statistically significant (p = 0.0059).In the preliminary examination, the massive, removable coating on the dorsal tongue was observed significantly more often in the RIC group- 20 patients (70%) compared to the MAC group- 26 patients (48%) (p = 0.0140). The coating was also more frequent during the following examinations in the RIC group. However, the differences were not statistically significant. In all the study periods, there was a higher frequency of petechiae found in the RIC group compared to the MAC, with statistically significant differences during the first- and second-week examinations. In the first examination, petechiae were found in 11 (42%) patients from the RIC group and 10 (19%) patients from the MAC (p = 0.0290); meanwhile, in the second examination, those lesions were found in 10 (38%), and 7 (13%) patients (p = 0.0103). Exfoliative cheilitis was observed most in the MAC group (9, 24 I, 22% in the following examinations), compared to the RIC group (4, 12, and 4%). However, the difference was statistically significant only for the second-week examinations (p = 0.0404).Figures 1, 2 and 3, and 4 illustrate the common oral mucosal findings in the study group.Fig. 1Petechiae on the buccal oral mucosa.Full size imageFig. 2Coating of the tongue.Full size imageFig. 3Erosions on the lower labial mucosa.Full size imageFig. 4Mucositis stage 2°on the ventral surface of the tongue.Full size imageThe analysis of the location of the oral mucosal lesions in patients with AML receiving allo-HSCT showed that at all stages of the study, pathological eruptions appeared mainly on the tongue– in 5 (64%) of patients in each group and on buccal mucosa- in 35, 44, and 48 subjects (44%, 55%, and 60%) (Table 3). A significant increase of the labial pathological lesions was revealed after the transplantation- 8 subjects (10%) vs. 19 (24%), and 20 (25%) (p = 0.0184, p = 0.0125), as in the sublingual area and the floor of the mouth − 7 subjects (9%) vs. 16 (20%), and 17 (21%) (p = 0.0482, p = 0.0335). No statistically significant differences in the location of the pathological lesions were revealed regarding the type of conditioning used. In the preliminary examination, lesions on the tongue were found in 31 (57%) patients from the MAC group and 20 (77%) from the RIC group. In both subsequent examinations, the frequency of the lingual lesions slightly increased in the MAC group- 61% (33 subjects), while it reduced in the RIC group (69%; 18 subjects). The number of patients with buccal lesions increased in both groups. In the MAC group, it reached 26 (48%), 29 (54%), and 33 (61%) patients in the subsequent examinations. In comparison, the frequency of buccal lesions in the RIC group was 36% in the preliminary and 58% in the post-transplant examinations. In both study groups, the other locations, like the sublingual area, the floor of the mouth, and the hard and soft palate, were involved less frequently. The percentage of patients with abnormal lesions in those regions was higher in the post-transplant examinations compared to the preliminary examination. However, the differences were not statistically significant. Before the transplantation, the labial lesions were observed in the MAC group in 6 (11%) subjects, while in both post-transplant examinations, it was found in 16 (30%) patients, showing a statistically significant difference (p = 0.0145). In the RIC group, during the following examination, the labial area was affected in 2 (8%), 3 (12%), and 4 (15%) patients. The lesions on the gingiva in the MAC group were revealed only in 3 (5.5%) subjects in the preliminary examination and 4 (7%) patients in both post-transplant examinations. In the RIC group, the lesions in this location were revealed in 2 (8%) patients before the transplantation and the first-week post-transplantation and 4 (15%) patients in the second-week examination (Table 3).Table 3 The location of the oral mucosal lesions in the Sudy group depending on the conditioning type used (MAC/RIC).Full size tableDiscussionDespite a rapid improvement in the treatment of AML with allo-HSCT, it has still been related to a risk of several complications. While the host is being prepared for a transplant procedure, high doses of cytostatic drugs are applied to achieve bone marrow suppression. That results in cytopenia, mainly granulocytopenia. The risk of viral, fungal, and bacterial infections rapidly grows, accompanied by gastrointestinal tract and mouth ulcers. Those complications develop due to a direct cytotoxic action of the drugs, a disruption of the immune system, and reduced saliva production. Oral mucosa lesions may cause severe discomfort and impair eating in patients receiving allo-HSCT. That often leads to malnutrition and dehydration. Recently, reduced-intensity conditioning (RIC) has become more popular. That allows the treatment of older people or patients with concomitant diseases. Reduced intensity of that treatment approach allows for a decrease in the risk of fatal complications induced by the therapy and lowers the risk of developing oral mucosal lesions. However, simultaneously, it creates a higher risk of disease recurrence. The attempts to establish conditioning protocols maintaining a high myeloablative potential with low toxicity are ongoing18,19. As the reduced intensity conditioning allows the treatment of geriatric patients and people with comorbidities, the number of allo-HSCTs constantly increases. Therefore, there is an urgent need to carefully analyze the general and oral health state of people with AML who underwent allo-HSCT.In our study, oral pathological lesions in patients with AML treated with allo-HSCT were observed frequently, wherein the highest rate of patients with those lesions was found in the first week post-transplantation. The frequency of those lesions decreased during the second week of the observation in both groups, remaining, however, on a high level. Following transplantation, mucositis was the most common symptom in the study group. Oral mucositis (OM) is a debilitating adverse effect of treatment during allogeneic hematopoietic stem cell transplantation (HSCT). Drug side effects lead to mucosal barrier injury, not only limited to the oral region but also the entire gastrointestinal mucosa17. According to literature reports, the frequency of this lesion is estimated to be between 70 and 100%12,18,20. In the Darczuk study, which evaluated the oral condition in patients treated with allo-HSCT for various systemic indications, mucositis was found in 83% of patients in the first week post-transplantation and 92% of patients in the second week post-transplantation13. In our study, the comparison of post-transplant mucositis frequency considering the type of conditioning used revealed a significantly higher rate of mucositis in patients undergoing myeloablative treatment.Similar results were presented by Murad et al. The frequency of mucositis was statistically significant in patients who received a myeloablative conditioning regimen (85% vs. 20%, p < 0.01) accompanied by prophylactic treatment. Their study enrolled patients who had undergone allogeneic stem cell transplantation. However, the common underlying diseases were beta-thalassemia major, acute lymphoblastic leukemia, aplastic anemia, and multiple myeloma. There was no patient with AML14.In their systematic review, Chaudhry et al. evaluated the frequency and intensity of mucositis concerning the conditioning approach in 640 patients who underwent allo-HSCT between 1990 and 201417. Frequency of 1–4° of mucositis reached 86.5% in the RIC group and 73.2% in the MAC group, while the most severe mucositis (2–4°) was found slightly more often in MAC compared to the RIC group- 79.7% vs. 71.5%. Although the MAC procedure is characterized by higher toxicity and could lead to a higher rate and more severe course of mucositis, those authors showed that the frequency and intensity of mucositis were comparable in both groups. According to the authors, that could result from the differences in the characteristics of the patients’ population, which were qualified for each group. People from the RIC group were older and suffered other systemic diseases. Another issue is that working definitions of conditioning regimens are based on doses that may not reflect variations in pharmacokinetic parameters17.A commonly observed lesion besides mucositis in all the examinations was a massive coating on the tongue. However, the frequency of this finding decreased over time. The formation of tongue coating is also a phenomenon observed in generally healthy individuals. It results from hyper-keratinization and elongation of the tongue papillae on the dorsal surface of the tongue and the presence of oral bacteria, exfoliated epithelium, or food residue among the papillae21. Therefore, any factors involved in the disability of keratinization and apoptosis of epithelial cells of the tongue and complex microbial colonization will profoundly affect the coating formation. According to van Tarnout et al., this lesion appears to be related to several factors, the level of oral hygiene being the strongest. Other factors like smoking, periodontal status, saliva characteristics, dietary habits, and the use of dentures were less obviously connected to tongue coating22. As stated in the Funahara report, an abnormal quantity and quality of tongue coating is related to dry mouth, depression of immunity, oral breathing, poor oral hygiene, smoking, old age, psychological stress, general disease, or medication side effects21. According to those authors, the increased amount of tongue coating after surgery was associated with increased bacterial count in the saliva. Therefore, tongue coating should be removed to minimize the risk of postoperative infectious complications in patients undergoing major oncologic or cardiac surgeries21. That refers also to our study population. The frequency of oral mucosa coating in the Busjan et al. study, which examined the oral health of patients with newly diagnosed acute leukemia, was estimated as 23%)23, which is much lower than in our observation, where the rate of this lesion in the preliminary examination reached 57%.Meanwhile, in none of the subjects in our study was a candidal infection revealed, which very often corresponds with the presence of a white-coated tongue. This observation can be explained by using antifungal therapy (fluconazole) in all patients qualified for the transplant procedure. Contrary to our observations, Ferrari Gomes et al. observed oral candidiasis in 7.6% of examined patients, with all diagnoses confirmed by culture24. Candidiasis was also found as a common infection in patients with leukemia or lymphoma treated with chemotherapy in the Ramírez-Amador study, with a prevalence of erythematous type. Following our observations, the authors emphasize that the rate of candidiasis in hospital-treated patients is usually effectively reduced by the preventive application of antifungals25.Petechiae and exfoliating cheilitis were also commonly observed, but their frequency increased significantly after transplantation compared to the initial examination. Petechiae, a manifestation of thrombocytopenia, were detected mainly in the sites exposed to irritation- on the buccal mucosa near the occlusion line and on the lips. In Ferrari Gomes et al. study, gingival bleeding and petechiae were observed in 15.2% of the hematology ward patients. The most common underlying disease in patients with these disorders was acute myeloid leukemia (41.7%). However, none of these patients were HSCT recipients24.Furthermore, it is essential to differentiate petechiae caused by trauma from those related to hematologic disorders or as a side effect of chemotherapy. As described in Nayak and Nayak study, oral petechiae or hemorrhagic bullae can be due to the thrombocytopenia secondary to myelophthisic involvement of the bone marrow by plasmacytosis, effects of the myeloma proteins on coagulation factors and platelet aggregation, and the effects of chemotherapy26. Adeyemo et al. also emphasize that spontaneous or induced prolonged and profuse mucosal bleeding, petechiae, ecchymosis, and hematoma are common secondary oral manifestations of leukemia27.Exfoliative cheilitis, defined as the non-specific chronic exfoliation of the superficial layers of epithelium at the vermilion border of the lips, was the oral condition most often observed in Ramírez-Amador study25.Contrary to the results of the other authors, which showed a high rate of oral HSV reactivation in seropositive patients (reported in 50 to 90% of cases) who underwent mainly myeloablative treatment, we did not reveal those types of lesions in any of the study participants24,28,29,30.Mucositis was found most frequently in the second week post-transplantation, while other oral pathological lesions were revealed most during the first week after transplantation. In Darczuk’s study, the highest number of pathological lesions in patients treated with allo-HSCT was observed in the second post-transplant week. Those included erosions, ulcers with edema, and exfoliative cheilitis (50%). Those findings appeared in over half of the examined subjects. During the first week of the observation, the author observed erythematous changes (75%), mucosal oedema (58%), and the overgrowth of filiform papillae (50%).Contrary to our observations, petechiae were found in none of the examined patients13. In the Grzegorczyk- Jaźwińska et al. study, the frequency of petechiae in the first weeks post-allo-HSCT was comparable to our results. In contrast, the frequency of exfoliative cheilitis and mucosal pallor was much higher (60% and 70%)31. Skallsjö et al. observed clinical oral mucosal findings in 67% of patients with AML after pre-HSCT chemotherapy. In this study, the most common patient-reported mucosal lesions other than mucositis were ulcerations (11%), bleeding from gingiva or oral mucosa (5%), and swollen gingiva (5%)32. Busjan et al. examined the oral health of patients with newly diagnosed acute leukemia. During the oral inspection, mucosal changes were found in 69.23% of the AML patients. Gingival hyperplasia was the most prevalent clinical finding (46%). Mucosal pallor (38%), petechia (23%), and coating of the mucosa (23%) were also observed. However, these patients were examined shortly after diagnosis, before the HSCT regimen23. Similar pathological lesions were described by many other authors24,25,28,33,34. None of the above analyses referred exclusively to patients with AML undergoing allogeneic HSCT. It seems that the type of conditioning does not influence the occurrence of oral pathological lesions other than mucositis during the first weeks after transplantation in patients with AML undergoing allo-HSCT. A detailed comparative analysis revealed only statistically significant differences regarding petechiae and exfoliative cheilitis. In both post-transplant examinations, a significantly higher rate of petechiae was found in the RIC group than in the MAC group.Meanwhile, exfoliative cheilitis was found more frequently in the MAC group (24% and 22% in the subsequent examinations) compared to RIC (12% and 4%), where the difference was significant only referred to the second-week examination. We did not find any literature reports on the frequency of oral pathological lesions depending on the conditioning type used in patients undergoing allo-HSCT in the early stage after the transplantation. Defining the oral cavity locations that are especially sensitive to the development of pathological lesions in patients with AML receiving allo-HSCT is a critical issue. It shows a necessity to maintain a special alert while examining those areas during routine dental follow-ups in those patients. In our study, the analysis of the lesions’ location in the early stage after the transplantation showed that those eruptions appeared mainly on the tongue (64% in both post-transplant examinations) and on the buccal mucosa (55% and 60%), which can be partially explained by an excessive exposition of those areas for the mechanical irritation. The frequency of labial lesions significantly increased in the post-transplant period. It also refers to the sublingual region and floor of the mouth. That could result from the exposition to dry, filtered air while staying in the hospital rooms, and the fact that sublingual mucosa is delicate and relatively thin makes it very sensitive. Similar results regarding the location of the oral pathological lesions were presented by Darczuk and Sook-Bin Woo13,35. In their studies, pathological eruptions appeared most on the buccal area, floor of the mouth, and lips. No statistically significant differences were revealed in the lesions’ location depending on the conditioning type regimen used.Limitations of the studyWe are aware of the limitations of this study, which included heterogeneity of the two study groups in terms of concomitant diseases and drug intake. Due to the rules of treatment qualification criteria, the MAC and RIC patients were not age-matched. RIC therapy is generally dedicated to older people with concomitant disorders other than AML compared to MAC. Further research on large samples is required to expand the knowledge on this topic.ConclusionThe results of our study indicate that pathological changes in the oral mucosa were frequent among the AML patients after allo-HSCT. The type of conditioning influenced the frequency of mucositis but did not affect the frequency and the location of other types of oral mucosal lesions.Pathological oral mucosal lesions may significantly interfere with the patient’s everyday functioning during the transplantation, so it is important to provide the patients qualified for MAC and RIC therapies with professional dental support.Considering the continuing growth in the number of transplantations performed on AML patients, further investigations of oral pathologies that accompany this disease and result from emerging treatment strategies are required.
Data availability
The data that support the findings of this study are available from the first author (Aleksandra Wysocka-Słowik) upon reasonable request.
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Download referencesFundingThe study was supported by the Poznań University of Medical Sciences grant No. 502-14-02209325-10853.Author informationAuthors and AffiliationsDepartment of Dental Surgery, Periodontology and Oral Mucosa Diseases, Poznań University of Medical Sciences, 70 Bukowska Street, Poznań, 60-812, PolandAleksandra Wysocka-Słowik, Zuzanna Ślebioda & Marzena Liliana WyganowskaDepartment of Prosthodontics and Gerostomatology, Poznań University of Medical Sciences, Poznań, PolandBarbara Dorocka-BobkowskaAuthorsAleksandra Wysocka-SłowikView author publicationsYou can also search for this author in
PubMed Google ScholarZuzanna ŚlebiodaView author publicationsYou can also search for this author in
PubMed Google ScholarBarbara Dorocka-BobkowskaView author publicationsYou can also search for this author in
PubMed Google ScholarMarzena Liliana WyganowskaView author publicationsYou can also search for this author in
PubMed Google ScholarContributionsA.W.-S. and Z.Ś. performed clinical examination and wrote the main manuscript text. A.W.-S., M.L.W. and B.D.B. provided funding. B.D.B amd M.L.W. edited and revised the manuscript. All authors reviewed and accepted the final version of the manuscript.Corresponding authorCorrespondence to
Zuzanna Ślebioda.Ethics declarations
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The authors declare no competing interests.
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Reprints and permissionsAbout this articleCite this articleWysocka-Słowik, A., Ślebioda, Z., Dorocka-Bobkowska, B. et al. Oral mucosal lesions in Polish patients with acute myeloid leukemia after allogeneic hematopoietic cell transplantation.
Sci Rep 15, 7862 (2025). https://doi.org/10.1038/s41598-025-92471-1Download citationReceived: 22 September 2024Accepted: 27 February 2025Published: 06 March 2025DOI: https://doi.org/10.1038/s41598-025-92471-1Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard
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KeywordsAcute myeloid leukemiaOral pathologyMucositisMAC conditioning regimenCancer chemotherapy protocols