Oral changes in patients undergoing hematopoietic stem cell transplantation and their risk factors: a cohort study

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Methods This longitudinal cohort study involved 30 patients receiving care at a bone marrow transplantation service in a Brazilian hospital. Data about oral physical examination, diagnosis of hematological disorder, transplant type, comorbidities, chemotherapy protocols, and oral risk factors were collected. Survival analysis was performed to estimate the onset time of oral alterations and investigate possible associations with risk factors. The significance level adopted was 5%. Results Most patients were male (57.7%), with a median age of 35 years, 93.3% developed oral alterations, and 53.3% presented local risk factors. Leukemias and multiple myeloma were the most common hematologic disorders (23.3%). FluBuMel was the most frequent conditioning protocol (46.7%). Buccal mucosa edema (83.3%) was the most common oral alteration, followed by oral mucositis (80%; grade 1: 54.2%). The mean follow-up time was 23 days, with the probability of the patient being free of oral alterations decreasing as time progressed. Mel200 protocol (HR 2.89; IC 0.04–1.02; p = 0.020), and autologous transplant (HR 3.41; CI 1.28–9.07; p = 0.004) were associated with an earlier occurrence of oral alterations, while allogenic related transplant was a protective factor (HR 0.48; CI 0.22–1.07; p = 0.040). Conclusion results indicate that the time of onset of oral alterations is affected by transplant type and conditioning protocol and suggest that the severity of the alterations is positively affected by the presence of dentists in the HSCT team. Hematologic neoplasms Hematopoietic stem cell transplantation Bone marrow Oral alterations Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Hematologic malignancies comprise a heterogeneous group of diseases originating from the malignant transformation of hematopoietic progenitor cells [ 1 ]. Therapeutic modalities for these malignancies are varied and include surgical resections, chemotherapy, radiotherapy, hematopoietic stem cell transplantation (HSCT), and, sometimes, a combination of multiple treatment regimens [ 2 , 3 ]. The treatment's choice will depend on genetic factors, molecular alterations, and clinical characteristics of the affected patients [ 2 , 4 ]. HSCT is an important and potentially curative treatment for some hematological disorders, consisting of the infusion of stem cells from the patient himself or a compatible donor [ 5 ]. It is considered a complex, long procedure, performed in stages, preceded by preconditioning with high doses of chemotherapy drugs [ 6 ], which may result in significant failures of the immune system of the patients. HSCT is indicated for various hematological disorders, whether malignant, such as leukemias, lymphomas, myelomas, and myelodysplastic syndrome, or non-malignant, such as aplastic anemia [ 2 , 5 , 6 ]. Chemotherapeutic preconditioning can lead to complications arising from the direct or indirect toxicities of the administered drugs [ 7 ]. Among the adverse effects that can occur in the oral environment, opportunistic infections, bleeding, disruptions in saliva production, gingival hyperplasia, and, primarily, oral mucositis are mentioned [ 7 , 8 ]. Therefore, the importance of understanding and accurate diagnosis reinforces the need for establishing oral care during HSCT to maintain the patient's oral health and prevent complications that could potentially interfere with the success of the treatment. In addition to the influence of the chemotherapeutic agents selected for the pre-transplantation conditioning protocol, oral factors linked to the patient, including saliva composition and quality, oral hygiene, microbial biofilm, and pre-existing conditions, are considered individual risks. These risks may contribute to the occurrence and/or aggravation of oral alterations associated with hematopoietic stem cell transplantation [ 3 , 9 ]. Given the above, this research aimed to identify the most prevalent oral alterations in patients with hematological disorders during hospitalization for hematopoietic stem cell transplantation. Additionally, we analyzed the time of development of these alterations during the hospitalization period, and we explored the factors inherent to the patient and the HSCT procedure that may contribute to the development of these oral alterations. Methods Study design and sample In this observational, longitudinal, prospective study, we evaluated the occurrence of oral alterations (time of onset, treatment, and follow-up) in patients with hematological disorders, admitted to the Bone Marrow Transplantation sector of the Hospital Natal Rio Grande, Natal, Brazil, a reference hospital in the state of Rio Grande do Norte, from December 2021 to June 2022 to undergo hematopoietic stem cell transplantation. Patients under 18 years of age and those with clinical conditions that did not allow a physical dental examination for this research were excluded. Data collection was carried out through physical examination of the mouth of the patients, at regular intervals of three days, from the beginning of the chemotherapy regimen until the day of bone marrow attachment. The initial examination of the patients was performed on the first day of hospitalization in the bone marrow transplant sector of the reference hospital, which corresponded to the first day of the chemotherapy conditioning protocol. From this initial clinical examination, the patient was followed up by the dentist with an interval of three days between each visit. The follow-up of the patient ended upon successful bone marrow engraftment. Thus, there was variation in the follow-up time among the participants. In detail, the physical examination was performed in the hospital bed with the aid of a flashlight, wooden spatula, and gauze, by a previously trained and calibrated dental surgeon. Visual inspection and palpation of the oral structures were conducted, evaluating the appearance of the oral mucosa (upper and lower lip, bilateral buccal mucosa, gums, upper and lower ridges, hard palate, soft palate, dorsal and ventral tongue, lateral borders of the tongue, floor of mouth, vestibular sulcus). The features found within the normal range and deviations from this standard, as well as oral hygiene conditions (presence or absence of visible biofilm), were recorded. Possible predisposing local risk factors (absence or presence) were analyzed on the first day of the hospitalization (at the beginning of the chemotherapy conditioning protocol) through tactile and visual examination. The following factors were considered: root remnants, caries, gingival bleeding, visible dental and tongue biofilm, dental calculus, and traumatic ulcer. Oral alterations were described according to location, number, size (mm and cm), shape (regular or irregular), type of fundamental lesion (spot, macula, plaque, ulcer, vesicle, blister, papules, and nodules), implantation (sessile or pedunculated), color (red, white, brown, black, yellow), surface (rough, smooth, verrucous), consistency (normal, fibrous, soft, rubbery), whether edematous or not, and the time of onset/evolution (in days), in addition to the clinical diagnosis. Mucosal dryness was analyzed according to the visual and tactile examination and classified as dry or not dry, as well as intraoral and/or labial. Symptomatology was recorded as absent or present and according to type (stinging, burning, pain, or discomfort). After examination, the data obtained were analyzed and diagnosed according to the nomenclature of the lesions. Oral mucositis was classified according to the WHO classification proposal [ 10 ]. During this exam, any detected alteration was treated according to the service alteration-specific protocols, which are already routinely performed by the dental surgeon responsible for the sector. Data on age, sex, underlying disease (diagnosis), comorbidities, conditioning protocol, and its schedule, graft-versus-host disease (GVHD) prevention protocol, medications, and complementary tests were obtained from the medical records of the patients. The study was carried out in accordance with the Declaration of Helsinki and was approved by the Ethics and Research Committee of the Federal University of Rio Grande do Norte (Protocol No. 5,186,340). Patients were informed about the study (methods, objectives, risks, and benefits) and signed the Free and Informed Consent Form. Bias In lux calibration was adopted and performed using 12 projected images that ranged from normal oral conditions to more severe conditions with various oral alterations. In the end, the responses were collected, and the inter-examiner agreement was calculated using the Kappa test [ 11 ]. The kappa index (ĸ) was above the recommended value (ĸ > 0.83; 95% CI: 0.51-1.00). Statistical analysis Data were organized and compiled in Microsoft Excel® spreadsheets (Microsoft Corporation, USA), in which descriptive analysis was performed to characterize the sample. Subsequently, data were statistically analyzed using SPSS® for Windows 25.0 software (Statistical Package for Social Sciences; Inc., Chicago, USA). Quantitative variables were described by measures of central tendency (mean and median) and variability. Categorical variables were represented by frequency distribution. The Kaplan-Meier method was used to estimate the probability of survival at various time intervals and to graphically illustrate survival over time, represented by the time of development of the oral alteration. Log-rank test and univariate COX regression were used to compare survival distributions between samples to investigate associations between risk factors and the time of onset of oral alterations. For all tests, the adopted significance level was 5%. Results A total of 39 patients elected to undergo HSCT were selected, nine of them (23%) were excluded due to systemic problems and the impossibility of clinical follow-up. Among the 30 patients, most were male (56.7%), and the median age was 35 years, ranging from 19 to 72 years. Patient profile, disease characteristics, and chemotherapy conditioning protocols are described in Table 1 . Table 1 Characterization of the sample (n = 30) regarding sex, age, diagnosis of the hematological disorder, type of transplant, type of chemotherapy conditioning, presence of local risk factors and oral alterations. Variables n (%) Sex Female 13 (43.3) Male 17 (56.7) Age group < 35 years 15 (50) ≥ 35 years 15 (50) Diagnosis Myeloid leukemia 7 (23.3) Lymphoid leukemia 7 (23.3) Multiple myeloma 7 (23.3) Hodgkin's lymphoma 4 (13.3) Aplastic aplasia 2 (6.7) Myelodysplastic syndrome 2 (6.7) Non-Hodgkin's lymphoma 1 (3.3) Transplant Related allogeneic 19 (63.3) Autologous 8 (26.7) Unrelated allogeneic 3 (10) Chemotherapy conditioning regimen FluBuMel a 14 (46.7) Mel 200 b 6 (20) FluMel c 2 (6.7) Leam d 2 (6.7) FluCyThy e 2 (6.7) FluMelThy f 2 (6.7) FluBu g 1 (3.3) FluCy h 1 (3.3) Local risk factor Presence 16 (53.3) Absence 14 (46.7) Oral alteration Presence 28 (93.3) Absence 2 (6.7) a Fludarabine, Busulfan and Melphalan. b Melphalan at a dose of 200 mg/m2. c Fludarabine–melphalan. d Lomustine, etoposide, cytarabine, and melphalan. e Fludarabine, cyclophosphamide and thymoglobulin. f Fludarabine, Melphalan and Thymoglobulin. g Fludarabine and Busulfan. h Fludarabine and cyclophosphamide. The distribution of hematological disorders according to the type of transplant and chemotherapy used is shown in Table 2 . The most prevalent hematological diseases were leukemia (myeloid and lymphoid) and myeloma (23.3%). Among the various types of transplants, allogeneic related transplantation emerged as the prevailing choice, constituting 63.3% of the cases. FluBuMel conditioning regimen was predominant (40%), citing Melphalan as the most used chemotherapeutic. Table 2 Distribution of hematological disorders according to the type of transplant and chemotherapy conditioning. Hematological disorder n (%) Transplant n (%) Chemotherapy conditioning N (%) Myeloid leukemia 7 (23.3) Related allogeneic 5 (71.4) FluBuMel a FluBu g 4 (80) 1 (20) Unrelated allogeneic 2 (28.6) FluBuMel a FluMelThy f 1 (50) 1 (50) Autologous - - - Lymphoid leukemia 7 (23.3) Related allogeneic 7 (100) FluBuMel a 7 (100) Unrelated allogeneic - - - Autologous - - - Multiple myeloma 7 (23.3) Related allogeneic 1 (14.3) FluMel c 1 (100) - 6 (100) Unrelated allogeneic 0 (0) - Autologous 6 (85.7) Mel200 b Hodgkin's lymphoma 4 (13.3) Related allogeneic 3 (75) FluBuMel a FluMel c FluCy h 1 (33.3) 1 (33.3) 1 (33.3) Unrelated allogeneic - - - Autologous 1 (25) FluMel c 1 (100) Aplastic aplasia 2 (6.7) Related allogeneic 2 (100) FluCyThy e 2 (100) Unrelated allogeneic - - - Autologous - - - Myelodysplastic syndrome 2 (6.7) Related allogeneic 1 (50) FluBuMel a 1 (100) Unrelated allogeneic 1 (50) FluMelThy f 1 (100) Autologous - - - Non-Hodgkin's lymphoma 1 (3.3) Related allogeneic - - - Unrelated allogeneic - - - Autologous 1 (100) Leam d 1 (100) a Fludarabine, Busulfan and Melphalan. b Melphalan at a dose of 200 mg/m2. c Fludarabine–melphalan. d Lomustine, etoposide, cytarabine, and melphalan. e Fludarabine, cyclophosphamide and thymoglobulin. f Fludarabine, Melphalan and Thymoglobulin. g Fludarabine and Busulfan. h Fludarabine and cyclophosphamide. The average follow-up time for patients in the study was 23 days (± 5.5). Most patients (n = 28; 93.3%) developed some oral alteration during the HSCT hospitalization period (Fig. 2 ). There was a higher prevalence of oral alterations in men (53.7%), and the most frequent oral alteration was edema in the buccal mucosa (n = 25; 83.3%), followed by oral mucositis, which affected 24 (80%) patients (Fig. 1 ). Oral mucositis of grade 1 developed in 13 patients (43.3%), with a remarkable male preference (n = 9; 69.2%). Grade 2 was observed in 11 patients (36.6%), with a higher frequency in women (n = 6; 54.5%). Only six patients presented oral mucositis of grade 0, and none of the cases were graded as 3 or 4 (Fig. 2 ). Even with the oral care adopted before the transplant procedures, many patients (53.3%) initiated the treatment with at least one predisposing oral risk factor. The frequency of local risk factors in the sample is illustrated in Fig. 3 . Visible dental biofilm emerged as the most common factor, observed in 26.7% of the patients, while dental caries and root remnants were not frequently identified (6.7%). Patients diagnosed with myeloid leukemia developed the oral changes with a median time of 9 days (ranging from 5 to 13 days), those diagnosed with lymphoid leukemia and multiple myeloma with a median time of 8.5 days (ranging from 6 to 13 days), patients with non-Hodgkin lymphoma and myelodysplastic syndrome developed oral changes with median times of 11.5 and 13.5 days, respectively (ranging from 9 to 11 days). Patients with Aplastic Anemia did not develop oral changes. In the follow-up period, on the 5th day of hospitalization, the probability of the patient being free from oral alterations (survival rate) was 93.3% (CI 0.75–0.98) and at 28 days, 6.7% (CI 0.01–0.19) were free of oral changes (Table 3 ). Table 3 Survival function estimation and 95% confidence interval (95% CI). Time (days) Total Event Survival function 95% CI 05 30 2 0.9333 0.7559 0.9829 06 28 5 0.7667 0.5720 0.8813 07 23 5 0.6000 0.4045 0.7495 09 18 5 0.4333 0.2556 0.5989 10 13 2 0.3670 0.2012 0.5337 11 11 5 0.2000 0.0812 0.3564 13 6 2 0.1333 0.0421 0.2777 17 4 2 0.6670 0.0118 0.1917 21 2 0 0.6670 0.0118 0.1917 28 1 0 0.6670 0.0118 0.1917 Kaplan-Meier survival curves for oral alterations concerning sex, age group, and comorbidity are shown in Fig. 4 A-F. No statistically significant differences were verified in the time of development of oral changes according to the sex ( p = 0.290), age group ( p = 0.890), or type of hematological disorder ( p = 0.100) of the patients. Despite the presence of some type of comorbidity in 61% of the patients with oral alterations, there was no significant influence on the development time of the alterations (HR 0.97; CI 0.45–2.09; p = 0.940). As for the type of transplant, the autologous transplant emerged was significantly associated with the earlier development of oral alterations (HR 3.41; CI 1.28–9.07; p = 0.004). In addition, the allogenic related transplant proved to be a possible protective factor, as it was associated with a later appearance of oral changes to the detriment of others (HR 0.48; CI 0.22–1.07; p = 0.040). Concerning chemotherapeutic conditioning protocol, patients under the Mel200 protocol were found to have a significantly higher risk of developing oral alterations earlier (HR 2.89; CI 0.04–1.02; p = 0.020). Discussion The results of the present study showed a high prevalence of oral alterations among hemato-oncologic patients during HSCT hospitalization, emphasizing the relevance of comprehensive oral care to the healthcare team in this vulnerable population, including dental professionals, particularly dentists. The HSCT is a potentially curative strategy for hematological diseases, involving the infusion of either autologous or allogeneic stem cells. This treatment encompasses an extensive treatment duration and chemotherapy conditioning phase, which can induce the development of complications resulting from direct or indirect immunosuppressive activity of the chemotherapy agents [ 1 , 12 , 13 ]. The cytotoxic effects of these pharmaceutical agents extend to the oral environment, causing a series of complications that can directly interfere with the patient's response to treatment and survival [ 14 ]. In this research, most patients were diagnosed with myeloid leukemia and lymphoid leukemia, with a predominance of males, a median age of 35 years, and allogeneic related was the most performed transplantation. Similar results were reported by Souza et al. [ 15 ], who performed an epidemiological characterization of patients undergoing HSCT in a Brazilian reference center. We found a high prevalence of the development of oral alterations in the patients during the procedures for HSCT, with swelling of the buccal mucosa being the most frequent. Oral mucositis was the second most observed oral alteration, accounting for 80% of the sample. However, all oral mucositis cases were limited to grades 1 and 2 (mild to moderate), and because these alterations were under constant monitoring by the dentist of the healthcare team, they did not lead to any disruptions to the treatment process. Oral mucositis may affect up to 80% of patients undergoing chemotherapy conditioning for HSCT and is considered a major complication for these individuals [ 16 ]. This high prevalence has been consistently reported in previous studies on this population [ 3 , 17 , 18 ], for instance, Radochová et al. [ 3 ] evaluated a sample of 496 HSTC patients and identified that a significant proportion (63.3%) experienced this complication. Edema in the oral mucosa is an acute effect of oncological therapy in the head and neck, without necessarily inducing pain or affecting the patient's functionality [ 19 ]. Oral mucosa edema is described as part of the early manifestations of the adverse effects of chemotherapy and can be reversible, not necessarily progressing to oral mucositis [ 3 , 20 ]. In this study, edema was regarded as an oral alteration distinct from oral mucositis, as the grading of the latter was based on the WHO classification. Oral mucositis is characterized initially as an erythema in the oral mucosa that can progress to atrophy, ulceration, and the formation of pseudomembranes [ 21 ]. The development of oral mucositis is associated with the formation of diffuse ulcers, with imprecise and generally non-delimited limits, often not surrounded by an erythematous halo [ 10 , 22 ]. These characteristics were used to differentiate oral mucositis from changes not associated with it in the present research. Ulcerations not associated with oral mucositis were detected in 26.7% of the patients analyzed. Other oral changes, such as pallor in mucous membranes and edema in the tongue, also exhibited high prevalence in HSCT recipients. However, despite the high prevalence of oral changes during HSCT procedures in the patients in this study, they were considered mild and often without clinical implications for the patient or the course of HSCT. An important factor justifying the low severity of the oral changes revealed here is the presence of a dentist in the healthcare team, as well as adopted prevention and treatment protocols, highlighting the use of photobiomodulation therapy and guidance on oral hygiene. Half of the HSCT patients in our study (53.3%) initiated the treatment with at least one predisposing oral risk factor. In a recent prospective study, that analyzed the oral health of 272 patients (≥ 18 years old) planned for HSCT, a substantial prevalence of oral disease was also found, including dental caries, deep periodontal pockets, oral mucosal lesions and visible biofilm [ 26 ]. In our sample, visible biofilm and ulcers were frequently observed before treatment. Despite the high prevalence of oral risk factors observed in HSCT patients, statistical analysis did not reveal a significant association with the early onset of oral alterations. This might be a consequence of closer monitoring by the dentist, optimizing oral hygiene, oral care and providing necessary treatment, to reduce and/or mitigate the repercussions of these risk factors, which are known contributors to the development of oral mucositis and other complications linked to HSCT. Oral care is defined as the activities that must be part of the routine of the patient submitted to anticancer therapy to maintain oral health and reduce the risk of local inflammation and/or infection, as well as systemic infections associated with oral complications [ 23 ]. In the present sample, the onset time of oral changes was influenced by the chemotherapy protocol employed, where patients under the Mel200 protocol (200 to 140mg/mm² of melphalan) exhibited oral changes earlier. The influence of the transplant type on the time of development of oral changes was also observed, where patients undergoing autologous transplants experienced an earlier onset of alterations. Autologous transplantation is the standard therapeutic choice for patients affected by multiple myeloma and the most used chemotherapy conditioning for myeloma cases is Mel200, where patients receive around 140 to 200mg/mm² of melphalan [ 29 ]. Melphalan is an alkylating-type chemotherapy agent, known as capable of forming interfilamentous bonds with DNA, which are the most cytotoxic since DNA alkylation requires more complex repair mechanisms and can even inhibit its replication [ 18 , 29 , 20 ]. Given the evidence of greater toxicity, the dentist at the HSCT team can increase surveillance and reinforce oral mucositis prevention strategies for patients treated with this protocol. Elad et al. [ 21 ] also demonstrated that the development of oral mucositis in patients undergoing HSCT depends on the type of transplant and the conditioning regimen. The direct influence of chemotherapy protocols on the development of oral mucositis in patients undergoing HSCT and who are at high risk for the occurrence of this complication was also reported by Curra et al. [ 18 ]. The authors highlighted that, among other chemotherapy agents, alkylating agents are commonly more associated with the development of oral mucositis. The survival analysis revealed a significant decrease in the probability of HSCT recipients being free of oral alterations over the hospitalization period, reinforcing the dynamic nature of oral health during this critical treatment phase and the relevance of continuous monitoring of the oral conditions of the patients by a dentist. Despite the significant evidence from this research, some limitations must be addressed such as the small sample size and the single-center setting. The period of data collection may have influenced the sample size due to the COVID-19 pandemic, as changes in protocols aiming at the maintenance of social distancing for preventing the spread of COVID-19 may contributed to the decrease in the number of transplants. Additionally, the evaluation of changes in saliva production was not possible, as several patients declined to provide saliva in a designated container due to discomfort in the oral and throat regions. Consequently, this aspect of the analysis was excluded from the study. Conclusions Our results indicate a high prevalence of mild oral alterations in patients undergoing HSCT. The time of development of these alterations was influenced by the transplant type and chemotherapy protocol. As the transplant procedures progressed, the likelihood of patients being free from oral alterations decreased. Having a dentist on the multidisciplinary team during HSCT is crucial for monitoring the oral health of the patients throughout hospitalization. Declarations CRediT author statement Conceptualization: Éricka Janine Dantas da Silveira, Tatiana Bernardo Farias Pereira; Methodology: Éricka Janine Dantas da Silveira, Tatiana Bernardo Farias Pereira; Formal analysis and investigation: Tatiana Bernardo Farias Pereira, Gleidston Silva Potter, Beatriz Maria Falcão Lima, Ana Rafaela Luz de Aquino Martins, Maria Luiza Diniz de Sousa Lopes, Kenio Costa de Lima, Éricka Janine Dantas da Silveira; Writing - original draft preparation: Tatiana Bernardo Farias Pereira, Éricka Janine Dantas da Silveira; Writing - review and editing: Tatiana Bernardo Farias Pereira, Maria Luiza Diniz de Sousa Lopes, Éricka Janine Dantas da Silveira; Supervision: Éricka Janine Dantas da Silveira. Acknowledgments All professionals involved in Bone marrow transplantation service, Rio Grande Hospital, Natal Rio Grande do Norte, Brazil. Compliance with Ethical Standards The study was carried out in accordance with the Declaration of Helsinki and was approved by the Ethics and Research Committee of the Federal University of Rio Grande do Norte (Protocol No. 5,186,340). All patients signed the Free and Informed Consent Form. Funding None Conflicts of interest The authors have no relevant financial or non-financial interests to disclose. Data availability The research data are available at any time from the corresponding author, upon reasonable request. Code availability N/A References Auberger P, Tamburini-Bonnefoy J, Puissant A (2020). Drug Resistance in Hematological Malignancies. Int J Mol Sci 21:6091. https://doi.org/10.3390/ijms21176091 Brennan MT, Hasséus B, Hovan AJ, et al (2018). Impact of Oral Side Effects from Conditioning Therapy Before Hematopoietic Stem Cell Transplantation: Protocol for a Multicenter Study. 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Dental status and risk of odontogenic complication in patients undergoing hematopoietic stem cell transplant. Support Care Cancer 29:2231–2238. https://doi.org/10.1007/s00520-020-05733-1 Skallsjö K, Von Bültzingslöwen I, Hasséus B, et al (2023). Oral health in patients scheduled for hematopoietic stem cell transplantation in the Orastem study. PLOS ONE 18:e0285615. https://doi.org/10.1371/journal.pone.0285615 Spijkervet FKL, Schuurhuis JM, Stokman MA, et al (2021). Should oral foci of infection be removed before the onset of radiotherapy or chemotherapy? Oral Dis 27:7–13. https://doi.org/10.1111/odi.13329 Jasiński M, Maciejewska M, Brodziak A, et al (2021). Ice-cream used as cryotherapy during high-dose melphalan conditioning reduces oral mucositis after autologous hematopoietic stem cell transplantation. Sci Rep 11:22507. https://doi.org/10.1038/s41598-021-02002-x Muniz AB, Bessa ERL, Lança MLA, et al (2021). Oral mucosites in children with cancer: difficulties of evaluation and effective therapy. Research, Society and Development. http://dx.doi.org/10.33448/rsd-v10i11.20018 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4031711","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":277257990,"identity":"5cc36254-f5a4-4621-ae8c-21a14889a385","order_by":0,"name":"Tatiana Bernardo Farias Pereira","email":"","orcid":"","institution":"Federal University of Rio Grande do Norte","correspondingAuthor":false,"prefix":"","firstName":"Tatiana","middleName":"Bernardo Farias","lastName":"Pereira","suffix":""},{"id":277257991,"identity":"d2919a80-a400-48b7-9b84-61fc88b1d1f9","order_by":1,"name":"Gleidston Silva Potter","email":"","orcid":"","institution":"Rio Grande Hospital, Natal Rio Grande do Norte","correspondingAuthor":false,"prefix":"","firstName":"Gleidston","middleName":"Silva","lastName":"Potter","suffix":""},{"id":277257992,"identity":"5ba0ab4c-2829-494e-8986-6306903e5c9d","order_by":2,"name":"Beatriz Maria Falcão Lima","email":"","orcid":"","institution":"Federal University of Rio Grande do Norte","correspondingAuthor":false,"prefix":"","firstName":"Beatriz","middleName":"Maria Falcão","lastName":"Lima","suffix":""},{"id":277257993,"identity":"45941697-5a91-4a92-b185-2cfa9498606d","order_by":3,"name":"Ana Rafaela Luz Aquino Martins","email":"","orcid":"","institution":"Federal University of Rio Grande do Norte","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"Rafaela Luz Aquino","lastName":"Martins","suffix":""},{"id":277257994,"identity":"363b8f96-b739-4e2b-b27d-31f875cb47be","order_by":4,"name":"Maria Luiza Diniz Sousa Lopes","email":"","orcid":"","institution":"Federal University of Rio Grande do Norte","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"Luiza Diniz Sousa","lastName":"Lopes","suffix":""},{"id":277257995,"identity":"49a64afe-3814-426e-b9dd-60f2e30ebc96","order_by":5,"name":"Kenio Costa Lima","email":"","orcid":"","institution":"Federal University of Rio Grande do Norte","correspondingAuthor":false,"prefix":"","firstName":"Kenio","middleName":"Costa","lastName":"Lima","suffix":""},{"id":277257996,"identity":"e655628f-3a4b-4051-923c-4c70179e51fd","order_by":6,"name":"Ericka Janine Dantas da Silveira","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIiWNgGAWjYFACxgbGBgYGZhCDgaGCgcEAJmFAnJYzRGmBqIWy2ojQwi99uPHjjBoGdv7ZzW0PPs47LG/O3nyA4UfFNgZz6QNYtUj2JTZLbjjGwCxx52C74cxthw139hxLYOw5c5vBsi8BqxaDM4xtjA/YgH65kdgmzbvtMOOGGzkGzIxtt4FS2B1mD9byj4FZHqTl75zD9gS1GPAAtWxsY2A2AGlhbDicSFCLxBnGZsmZfQzMhkAtkj3H0pM3nDmWcBDoFx7LHhwh1sP+8GPPN4ZkuRvpzyR+1FjbbjjefPDBj4rbcuY82LVAwf9kKKMZTB4AYvwagMAOStcRUjgKRsEoGAUjEAAANGFh4GqYQ5UAAAAASUVORK5CYII=","orcid":"","institution":"Federal University of Rio Grande do Norte","correspondingAuthor":true,"prefix":"","firstName":"Ericka","middleName":"Janine Dantas da","lastName":"Silveira","suffix":""}],"badges":[],"createdAt":"2024-03-07 20:05:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4031711/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4031711/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":52537506,"identity":"8a150be3-fdce-4602-abe2-bfd3718680aa","added_by":"auto","created_at":"2024-03-12 16:45:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":150148,"visible":true,"origin":"","legend":"\u003cp\u003eOral alterations related to hematopoietic stem cell transplantation procedures. (A) Petechiae on the dorsum of the tongue. (B) Ulcer not associated with oral mucositis on the lateral border of the tongue. (C) Oral mucositis - Grade 2. (D) Oral mucositis - Grade 1. (E) Edema in lhe buccal mucosa. (F) Gingival paleness. (G) \u0026nbsp;Oral alterations are rendered on a 100% stacked bar chart that indicates the proportion of female and male patients affected by each alteration. Rio Grande Hospital, Natal, RN, 2021-2022.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4031711/v1/092c5741725a3c5f89acf932.png"},{"id":52537505,"identity":"16b3e285-72fa-4f06-b0c1-d3947ca644f7","added_by":"auto","created_at":"2024-03-12 16:45:39","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":841858,"visible":true,"origin":"","legend":"\u003cp\u003eBar chart (100% stacked) illustrating the distribution of the patients according to the grade of oral mucositis. Rio Grande Hospital, Natal, RN, 2021-2022.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4031711/v1/0a0f9bc226cfa0bb8db776e6.png"},{"id":52538017,"identity":"b9253659-2802-47c3-8a8a-65e26b3fcb24","added_by":"auto","created_at":"2024-03-12 16:53:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":58125,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution (%) of local risk factors in the sample (n = 30). Rio Grande Hospital, RN, 2021-2022.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4031711/v1/887c01faf2406e9fe18b054d.png"},{"id":52537508,"identity":"392dad17-b877-4735-820d-f85bb1b7b19f","added_by":"auto","created_at":"2024-03-12 16:45:39","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":372884,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves showing the estimated survival probability of the development of oral alterations according to (A) sex, (B) age group, (C) comorbidity, (D) autologous transplant, (E) allogeneic related transplant, and (F) Mel200 conditioning protocol. Log-rank test. \u003csup\u003e*\u003c/sup\u003eStatistical significance. Rio Grande Hospital, Natal, RN, 2021-2022.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4031711/v1/c56ae5e26b625163d4e14f61.png"},{"id":56058776,"identity":"764ec919-1282-49b0-9029-827ce8047664","added_by":"auto","created_at":"2024-05-08 04:04:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2197760,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4031711/v1/515d1d30-04cf-4016-a2d1-a66ba557f2b6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Oral changes in patients undergoing hematopoietic stem cell transplantation and their risk factors: a cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHematologic malignancies comprise a heterogeneous group of diseases originating from the malignant transformation of hematopoietic progenitor cells [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Therapeutic modalities for these malignancies are varied and include surgical resections, chemotherapy, radiotherapy, hematopoietic stem cell transplantation (HSCT), and, sometimes, a combination of multiple treatment regimens [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The treatment's choice will depend on genetic factors, molecular alterations, and clinical characteristics of the affected patients [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHSCT is an important and potentially curative treatment for some hematological disorders, consisting of the infusion of stem cells from the patient himself or a compatible donor [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. It is considered a complex, long procedure, performed in stages, preceded by preconditioning with high doses of chemotherapy drugs [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], which may result in significant failures of the immune system of the patients. HSCT is indicated for various hematological disorders, whether malignant, such as leukemias, lymphomas, myelomas, and myelodysplastic syndrome, or non-malignant, such as aplastic anemia [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eChemotherapeutic preconditioning can lead to complications arising from the direct or indirect toxicities of the administered drugs [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Among the adverse effects that can occur in the oral environment, opportunistic infections, bleeding, disruptions in saliva production, gingival hyperplasia, and, primarily, oral mucositis are mentioned [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Therefore, the importance of understanding and accurate diagnosis reinforces the need for establishing oral care during HSCT to maintain the patient's oral health and prevent complications that could potentially interfere with the success of the treatment.\u003c/p\u003e \u003cp\u003eIn addition to the influence of the chemotherapeutic agents selected for the pre-transplantation conditioning protocol, oral factors linked to the patient, including saliva composition and quality, oral hygiene, microbial biofilm, and pre-existing conditions, are considered individual risks. These risks may contribute to the occurrence and/or aggravation of oral alterations associated with hematopoietic stem cell transplantation [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eGiven the above, this research aimed to identify the most prevalent oral alterations in patients with hematological disorders during hospitalization for hematopoietic stem cell transplantation. Additionally, we analyzed the time of development of these alterations during the hospitalization period, and we explored the factors inherent to the patient and the HSCT procedure that may contribute to the development of these oral alterations.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and sample\u003c/h2\u003e \u003cp\u003eIn this observational, longitudinal, prospective study, we evaluated the occurrence of oral alterations (time of onset, treatment, and follow-up) in patients with hematological disorders, admitted to the Bone Marrow Transplantation sector of the Hospital Natal Rio Grande, Natal, Brazil, a reference hospital in the state of Rio Grande do Norte, from December 2021 to June 2022 to undergo hematopoietic stem cell transplantation. Patients under 18 years of age and those with clinical conditions that did not allow a physical dental examination for this research were excluded.\u003c/p\u003e \u003cp\u003eData collection was carried out through physical examination of the mouth of the patients, at regular intervals of three days, from the beginning of the chemotherapy regimen until the day of bone marrow attachment. The initial examination of the patients was performed on the first day of hospitalization in the bone marrow transplant sector of the reference hospital, which corresponded to the first day of the chemotherapy conditioning protocol. From this initial clinical examination, the patient was followed up by the dentist with an interval of three days between each visit. The follow-up of the patient ended upon successful bone marrow engraftment. Thus, there was variation in the follow-up time among the participants.\u003c/p\u003e \u003cp\u003eIn detail, the physical examination was performed in the hospital bed with the aid of a flashlight, wooden spatula, and gauze, by a previously trained and calibrated dental surgeon. Visual inspection and palpation of the oral structures were conducted, evaluating the appearance of the oral mucosa (upper and lower lip, bilateral buccal mucosa, gums, upper and lower ridges, hard palate, soft palate, dorsal and ventral tongue, lateral borders of the tongue, floor of mouth, vestibular sulcus). The features found within the normal range and deviations from this standard, as well as oral hygiene conditions (presence or absence of visible biofilm), were recorded.\u003c/p\u003e \u003cp\u003ePossible predisposing local risk factors (absence or presence) were analyzed on the first day of the hospitalization (at the beginning of the chemotherapy conditioning protocol) through tactile and visual examination. The following factors were considered: root remnants, caries, gingival bleeding, visible dental and tongue biofilm, dental calculus, and traumatic ulcer.\u003c/p\u003e \u003cp\u003eOral alterations were described according to location, number, size (mm and cm), shape (regular or irregular), type of fundamental lesion (spot, macula, plaque, ulcer, vesicle, blister, papules, and nodules), implantation (sessile or pedunculated), color (red, white, brown, black, yellow), surface (rough, smooth, verrucous), consistency (normal, fibrous, soft, rubbery), whether edematous or not, and the time of onset/evolution (in days), in addition to the clinical diagnosis. Mucosal dryness was analyzed according to the visual and tactile examination and classified as dry or not dry, as well as intraoral and/or labial. Symptomatology was recorded as absent or present and according to type (stinging, burning, pain, or discomfort). After examination, the data obtained were analyzed and diagnosed according to the nomenclature of the lesions. Oral mucositis was classified according to the WHO classification proposal [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. During this exam, any detected alteration was treated according to the service alteration-specific protocols, which are already routinely performed by the dental surgeon responsible for the sector.\u003c/p\u003e \u003cp\u003eData on age, sex, underlying disease (diagnosis), comorbidities, conditioning protocol, and its schedule, graft-versus-host disease (GVHD) prevention protocol, medications, and complementary tests were obtained from the medical records of the patients.\u003c/p\u003e \u003cp\u003e The study was carried out in accordance with the Declaration of Helsinki and was approved by the Ethics and Research Committee of the Federal University of Rio Grande do Norte (Protocol No. 5,186,340). Patients were informed about the study (methods, objectives, risks, and benefits) and signed the Free and Informed Consent Form.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eBias\u003c/h2\u003e \u003cp\u003e\u003cem\u003eIn lux\u003c/em\u003e calibration was adopted and performed using 12 projected images that ranged from normal oral conditions to more severe conditions with various oral alterations. In the end, the responses were collected, and the inter-examiner agreement was calculated using the Kappa test [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The kappa index (ĸ) was above the recommended value (ĸ \u0026gt; 0.83; 95% CI: 0.51-1.00).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData were organized and compiled in Microsoft Excel\u0026reg; spreadsheets (Microsoft Corporation, USA), in which descriptive analysis was performed to characterize the sample. Subsequently, data were statistically analyzed using SPSS\u0026reg; for Windows 25.0 software (Statistical Package for Social Sciences; Inc., Chicago, USA). Quantitative variables were described by measures of central tendency (mean and median) and variability. Categorical variables were represented by frequency distribution.\u003c/p\u003e \u003cp\u003eThe Kaplan-Meier method was used to estimate the probability of survival at various time intervals and to graphically illustrate survival over time, represented by the time of development of the oral alteration. Log-rank test and univariate COX regression were used to compare survival distributions between samples to investigate associations between risk factors and the time of onset of oral alterations. For all tests, the adopted significance level was 5%.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 39 patients elected to undergo HSCT were selected, nine of them (23%) were excluded due to systemic problems and the impossibility of clinical follow-up. Among the 30 patients, most were male (56.7%), and the median age was 35 years, ranging from 19 to 72 years. Patient profile, disease characteristics, and chemotherapy conditioning protocols are described in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacterization of the sample (n\u0026thinsp;=\u0026thinsp;30) regarding sex, age, diagnosis of the hematological disorder, type of transplant, type of chemotherapy conditioning, presence of local risk factors and oral alterations.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (43.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (56.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;35 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;35 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiagnosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMyeloid leukemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (23.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphoid leukemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (23.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple myeloma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (23.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHodgkin's lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (13.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAplastic aplasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMyelodysplastic syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hodgkin's lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTransplant\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (63.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutologous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (26.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnrelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChemotherapy conditioning regimen\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFluBuMel\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (46.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMel 200\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFluMel\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeam\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFluCyThy\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFluMelThy\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFluBu\u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFluCy\u003csup\u003eh\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLocal risk factor\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (53.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (46.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOral alteration\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (93.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003csup\u003ea\u003c/sup\u003eFludarabine, Busulfan and Melphalan. \u003csup\u003eb\u003c/sup\u003eMelphalan at a dose of 200 mg/m2. \u003csup\u003ec\u003c/sup\u003eFludarabine\u0026ndash;melphalan. \u003csup\u003ed\u003c/sup\u003eLomustine, etoposide, cytarabine, and melphalan. \u003csup\u003ee\u003c/sup\u003eFludarabine, cyclophosphamide and thymoglobulin. \u003csup\u003ef\u003c/sup\u003eFludarabine, Melphalan and Thymoglobulin. \u003csup\u003eg\u003c/sup\u003eFludarabine and Busulfan. \u003csup\u003eh\u003c/sup\u003eFludarabine and cyclophosphamide.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe distribution of hematological disorders according to the type of transplant and chemotherapy used is shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The most prevalent hematological diseases were leukemia (myeloid and lymphoid) and myeloma (23.3%). Among the various types of transplants, allogeneic related transplantation emerged as the prevailing choice, constituting 63.3% of the cases. FluBuMel conditioning regimen was predominant (40%), citing Melphalan as the most used chemotherapeutic.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of hematological disorders according to the type of transplant and chemotherapy conditioning.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematological disorder\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTransplant\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eChemotherapy conditioning\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eMyeloid leukemia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e7 (23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (71.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFluBuMel\u003csup\u003ea\u003c/sup\u003e FluBu\u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (80)\u003c/p\u003e \u003cp\u003e1 (20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnrelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFluBuMel\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eFluMelThy\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (50)\u003c/p\u003e \u003cp\u003e1 (50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAutologous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eLymphoid leukemia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e7 (23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFluBuMel\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnrelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAutologous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eMultiple myeloma\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e7 (23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFluMel\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e1 (100)\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003cp\u003e6 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnrelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAutologous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (85.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMel200\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eHodgkin's lymphoma\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e4 (13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFluBuMel\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eFluMel\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eFluCy\u003csup\u003eh\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnrelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAutologous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFluMel\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eAplastic aplasia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFluCyThy\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnrelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAutologous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eMyelodysplastic syndrome\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFluBuMel\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnrelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFluMelThy\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAutologous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eNon-Hodgkin's lymphoma\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e1 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnrelated allogeneic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAutologous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLeam\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003ea\u003c/sup\u003eFludarabine, Busulfan and Melphalan. \u003csup\u003eb\u003c/sup\u003eMelphalan at a dose of 200 mg/m2. \u003csup\u003ec\u003c/sup\u003eFludarabine\u0026ndash;melphalan. \u003csup\u003ed\u003c/sup\u003eLomustine, etoposide, cytarabine, and melphalan. \u003csup\u003ee\u003c/sup\u003eFludarabine, cyclophosphamide and thymoglobulin. \u003csup\u003ef\u003c/sup\u003eFludarabine, Melphalan and Thymoglobulin. \u003csup\u003eg\u003c/sup\u003eFludarabine and Busulfan. \u003csup\u003eh\u003c/sup\u003eFludarabine and cyclophosphamide.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe average follow-up time for patients in the study was 23 days (\u0026plusmn;\u0026thinsp;5.5). Most patients (n\u0026thinsp;=\u0026thinsp;28; 93.3%) developed some oral alteration during the HSCT hospitalization period (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). There was a higher prevalence of oral alterations in men (53.7%), and the most frequent oral alteration was edema in the buccal mucosa (n\u0026thinsp;=\u0026thinsp;25; 83.3%), followed by oral mucositis, which affected 24 (80%) patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOral mucositis of grade 1 developed in 13 patients (43.3%), with a remarkable male preference (n\u0026thinsp;=\u0026thinsp;9; 69.2%). Grade 2 was observed in 11 patients (36.6%), with a higher frequency in women (n\u0026thinsp;=\u0026thinsp;6; 54.5%). Only six patients presented oral mucositis of grade 0, and none of the cases were graded as 3 or 4 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEven with the oral care adopted before the transplant procedures, many patients (53.3%) initiated the treatment with at least one predisposing oral risk factor. The frequency of local risk factors in the sample is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Visible dental biofilm emerged as the most common factor, observed in 26.7% of the patients, while dental caries and root remnants were not frequently identified (6.7%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatients diagnosed with myeloid leukemia developed the oral changes with a median time of 9 days (ranging from 5 to 13 days), those diagnosed with lymphoid leukemia and multiple myeloma with a median time of 8.5 days (ranging from 6 to 13 days), patients with non-Hodgkin lymphoma and myelodysplastic syndrome developed oral changes with median times of 11.5 and 13.5 days, respectively (ranging from 9 to 11 days). Patients with Aplastic Anemia did not develop oral changes.\u003c/p\u003e \u003cp\u003eIn the follow-up period, on the 5th day of hospitalization, the probability of the patient being free from oral alterations (survival rate) was 93.3% (CI 0.75\u0026ndash;0.98) and at 28 days, 6.7% (CI 0.01\u0026ndash;0.19) were free of oral changes (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSurvival function estimation and 95% confidence interval (95% CI).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime (days)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEvent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSurvival function\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.7559\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.9829\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7667\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.5720\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.8813\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.6000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.4045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.7495\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.4333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.2556\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.5989\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3670\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.5337\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.0812\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.3564\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.0421\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.2777\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.6670\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.0118\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.1917\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.6670\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.0118\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.1917\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.6670\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.0118\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.1917\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eKaplan-Meier survival curves for oral alterations concerning sex, age group, and comorbidity are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA-F. No statistically significant differences were verified in the time of development of oral changes according to the sex (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.290), age group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.890), or type of hematological disorder (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.100) of the patients. Despite the presence of some type of comorbidity in 61% of the patients with oral alterations, there was no significant influence on the development time of the alterations (HR 0.97; CI 0.45\u0026ndash;2.09; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.940).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAs for the type of transplant, the autologous transplant emerged was significantly associated with the earlier development of oral alterations (HR 3.41; CI 1.28\u0026ndash;9.07; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004). In addition, the allogenic related transplant proved to be a possible protective factor, as it was associated with a later appearance of oral changes to the detriment of others (HR 0.48; CI 0.22\u0026ndash;1.07; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.040).\u003c/p\u003e \u003cp\u003eConcerning chemotherapeutic conditioning protocol, patients under the Mel200 protocol were found to have a significantly higher risk of developing oral alterations earlier (HR 2.89; CI 0.04\u0026ndash;1.02; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe results of the present study showed a high prevalence of oral alterations among hemato-oncologic patients during HSCT hospitalization, emphasizing the relevance of comprehensive oral care to the healthcare team in this vulnerable population, including dental professionals, particularly dentists.\u003c/p\u003e \u003cp\u003eThe HSCT is a potentially curative strategy for hematological diseases, involving the infusion of either autologous or allogeneic stem cells. This treatment encompasses an extensive treatment duration and chemotherapy conditioning phase, which can induce the development of complications resulting from direct or indirect immunosuppressive activity of the chemotherapy agents [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The cytotoxic effects of these pharmaceutical agents extend to the oral environment, causing a series of complications that can directly interfere with the patient's response to treatment and survival [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this research, most patients were diagnosed with myeloid leukemia and lymphoid leukemia, with a predominance of males, a median age of 35 years, and allogeneic related was the most performed transplantation. Similar results were reported by Souza et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], who performed an epidemiological characterization of patients undergoing HSCT in a Brazilian reference center.\u003c/p\u003e \u003cp\u003eWe found a high prevalence of the development of oral alterations in the patients during the procedures for HSCT, with swelling of the buccal mucosa being the most frequent. Oral mucositis was the second most observed oral alteration, accounting for 80% of the sample. However, all oral mucositis cases were limited to grades 1 and 2 (mild to moderate), and because these alterations were under constant monitoring by the dentist of the healthcare team, they did not lead to any disruptions to the treatment process.\u003c/p\u003e \u003cp\u003eOral mucositis may affect up to 80% of patients undergoing chemotherapy conditioning for HSCT and is considered a major complication for these individuals [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. This high prevalence has been consistently reported in previous studies on this population [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], for instance, Radochov\u0026aacute; et al. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] evaluated a sample of 496 HSTC patients and identified that a significant proportion (63.3%) experienced this complication.\u003c/p\u003e \u003cp\u003eEdema in the oral mucosa is an acute effect of oncological therapy in the head and neck, without necessarily inducing pain or affecting the patient's functionality [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Oral mucosa edema is described as part of the early manifestations of the adverse effects of chemotherapy and can be reversible, not necessarily progressing to oral mucositis [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In this study, edema was regarded as an oral alteration distinct from oral mucositis, as the grading of the latter was based on the WHO classification.\u003c/p\u003e \u003cp\u003eOral mucositis is characterized initially as an erythema in the oral mucosa that can progress to atrophy, ulceration, and the formation of pseudomembranes [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The development of oral mucositis is associated with the formation of diffuse ulcers, with imprecise and generally non-delimited limits, often not surrounded by an erythematous halo [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. These characteristics were used to differentiate oral mucositis from changes not associated with it in the present research. Ulcerations not associated with oral mucositis were detected in 26.7% of the patients analyzed.\u003c/p\u003e \u003cp\u003e Other oral changes, such as pallor in mucous membranes and edema in the tongue, also exhibited high prevalence in HSCT recipients. However, despite the high prevalence of oral changes during HSCT procedures in the patients in this study, they were considered mild and often without clinical implications for the patient or the course of HSCT. An important factor justifying the low severity of the oral changes revealed here is the presence of a dentist in the healthcare team, as well as adopted prevention and treatment protocols, highlighting the use of photobiomodulation therapy and guidance on oral hygiene.\u003c/p\u003e \u003cp\u003eHalf of the HSCT patients in our study (53.3%) initiated the treatment with at least one predisposing oral risk factor. In a recent prospective study, that analyzed the oral health of 272 patients (\u0026ge;\u0026thinsp;18 years old) planned for HSCT, a substantial prevalence of oral disease was also found, including dental caries, deep periodontal pockets, oral mucosal lesions and visible biofilm [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In our sample, visible biofilm and ulcers were frequently observed before treatment.\u003c/p\u003e \u003cp\u003e Despite the high prevalence of oral risk factors observed in HSCT patients, statistical analysis did not reveal a significant association with the early onset of oral alterations. This might be a consequence of closer monitoring by the dentist, optimizing oral hygiene, oral care and providing necessary treatment, to reduce and/or mitigate the repercussions of these risk factors, which are known contributors to the development of oral mucositis and other complications linked to HSCT. Oral care is defined as the activities that must be part of the routine of the patient submitted to anticancer therapy to maintain oral health and reduce the risk of local inflammation and/or infection, as well as systemic infections associated with oral complications [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the present sample, the onset time of oral changes was influenced by the chemotherapy protocol employed, where patients under the Mel200 protocol (200 to 140mg/mm\u0026sup2; of melphalan) exhibited oral changes earlier. The influence of the transplant type on the time of development of oral changes was also observed, where patients undergoing autologous transplants experienced an earlier onset of alterations.\u003c/p\u003e \u003cp\u003eAutologous transplantation is the standard therapeutic choice for patients affected by multiple myeloma and the most used chemotherapy conditioning for myeloma cases is Mel200, where patients receive around 140 to 200mg/mm\u0026sup2; of melphalan [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Melphalan is an alkylating-type chemotherapy agent, known as capable of forming interfilamentous bonds with DNA, which are the most cytotoxic since DNA alkylation requires more complex repair mechanisms and can even inhibit its replication [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Given the evidence of greater toxicity, the dentist at the HSCT team can increase surveillance and reinforce oral mucositis prevention strategies for patients treated with this protocol.\u003c/p\u003e \u003cp\u003eElad et al. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] also demonstrated that the development of oral mucositis in patients undergoing HSCT depends on the type of transplant and the conditioning regimen. The direct influence of chemotherapy protocols on the development of oral mucositis in patients undergoing HSCT and who are at high risk for the occurrence of this complication was also reported by Curra et al. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The authors highlighted that, among other chemotherapy agents, alkylating agents are commonly more associated with the development of oral mucositis.\u003c/p\u003e \u003cp\u003eThe survival analysis revealed a significant decrease in the probability of HSCT recipients being free of oral alterations over the hospitalization period, reinforcing the dynamic nature of oral health during this critical treatment phase and the relevance of continuous monitoring of the oral conditions of the patients by a dentist.\u003c/p\u003e \u003cp\u003eDespite the significant evidence from this research, some limitations must be addressed such as the small sample size and the single-center setting. The period of data collection may have influenced the sample size due to the COVID-19 pandemic, as changes in protocols aiming at the maintenance of social distancing for preventing the spread of COVID-19 may contributed to the decrease in the number of transplants. Additionally, the evaluation of changes in saliva production was not possible, as several patients declined to provide saliva in a designated container due to discomfort in the oral and throat regions. Consequently, this aspect of the analysis was excluded from the study.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur results indicate a high prevalence of mild oral alterations in patients undergoing HSCT. The time of development of these alterations was influenced by the transplant type and chemotherapy protocol. As the transplant procedures progressed, the likelihood of patients being free from oral alterations decreased. Having a dentist on the multidisciplinary team during HSCT is crucial for monitoring the oral health of the patients throughout hospitalization.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCRediT author statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: \u0026Eacute;ricka Janine Dantas da Silveira, Tatiana Bernardo Farias Pereira; Methodology: \u0026Eacute;ricka Janine Dantas da Silveira, Tatiana Bernardo Farias Pereira; Formal analysis and investigation: Tatiana Bernardo Farias Pereira, Gleidston Silva Potter, Beatriz Maria Falc\u0026atilde;o Lima, Ana Rafaela Luz de Aquino Martins, Maria Luiza Diniz de Sousa Lopes, Kenio Costa de Lima, \u0026Eacute;ricka Janine Dantas da Silveira; Writing - original draft preparation: Tatiana Bernardo Farias Pereira, \u0026Eacute;ricka Janine Dantas da Silveira; Writing - review and editing: Tatiana Bernardo Farias Pereira, Maria Luiza Diniz de Sousa Lopes, \u0026Eacute;ricka Janine Dantas da Silveira; Supervision: \u0026Eacute;ricka Janine Dantas da Silveira.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll professionals involved in Bone marrow transplantation service, Rio Grande Hospital, Natal Rio Grande do Norte, Brazil.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompliance with Ethical Standards\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was carried out in accordance with the Declaration of Helsinki and was approved by the Ethics and Research Committee of the Federal University of Rio Grande do Norte (Protocol No. 5,186,340). All patients signed the Free and Informed Consent Form.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research data are available at any time from the corresponding author, upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eN/A\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAuberger P, Tamburini-Bonnefoy J, Puissant A (2020). Drug Resistance in Hematological Malignancies. Int J Mol Sci 21:6091. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/ijms21176091\u003c/span\u003e\u003cspan address=\"10.3390/ijms21176091\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrennan MT, Hass\u0026eacute;us B, Hovan AJ, et al (2018). Impact of Oral Side Effects from Conditioning Therapy Before Hematopoietic Stem Cell Transplantation: Protocol for a Multicenter Study. JMIR Res Protoc 7:e103. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2196/resprot.8982\u003c/span\u003e\u003cspan address=\"10.2196/resprot.8982\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRadochov\u0026aacute; V, Šembera M, Slez\u0026aacute;k R, et al (2021). 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Ice-cream used as cryotherapy during high-dose melphalan conditioning reduces oral mucositis after autologous hematopoietic stem cell transplantation. Sci Rep 11:22507. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41598-021-02002-x\u003c/span\u003e\u003cspan address=\"10.1038/s41598-021-02002-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMuniz AB, Bessa ERL, Lan\u0026ccedil;a MLA, et al (2021). Oral mucosites in children with cancer: difficulties of evaluation and effective therapy. Research, Society and Development. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.33448/rsd-v10i11.20018\u003c/span\u003e\u003cspan address=\"10.33448/rsd-v10i11.20018\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hematologic neoplasms, Hematopoietic stem cell transplantation, Bone marrow, Oral alterations","lastPublishedDoi":"10.21203/rs.3.rs-4031711/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4031711/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose\u003c/b\u003e\u003c/p\u003e \u003cp\u003eto investigate the occurrence, time of onset, and associated factors of oral alterations in hemato-oncologic patients throughout their hospitalization for hematopoietic stem cell transplantation (HSCT).\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis longitudinal cohort study involved 30 patients receiving care at a bone marrow transplantation service in a Brazilian hospital. Data about oral physical examination, diagnosis of hematological disorder, transplant type, comorbidities, chemotherapy protocols, and oral risk factors were collected. Survival analysis was performed to estimate the onset time of oral alterations and investigate possible associations with risk factors. The significance level adopted was 5%.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMost patients were male (57.7%), with a median age of 35 years, 93.3% developed oral alterations, and 53.3% presented local risk factors. Leukemias and multiple myeloma were the most common hematologic disorders (23.3%). FluBuMel was the most frequent conditioning protocol (46.7%). Buccal mucosa edema (83.3%) was the most common oral alteration, followed by oral mucositis (80%; grade 1: 54.2%). The mean follow-up time was 23 days, with the probability of the patient being free of oral alterations decreasing as time progressed. Mel200 protocol (HR 2.89; IC 0.04\u0026ndash;1.02; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020), and autologous transplant (HR 3.41; CI 1.28\u0026ndash;9.07; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004) were associated with an earlier occurrence of oral alterations, while allogenic related transplant was a protective factor (HR 0.48; CI 0.22\u0026ndash;1.07; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.040).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eresults indicate that the time of onset of oral alterations is affected by transplant type and conditioning protocol and suggest that the severity of the alterations is positively affected by the presence of dentists in the HSCT team.\u003c/p\u003e","manuscriptTitle":"Oral changes in patients undergoing hematopoietic stem cell transplantation and their risk factors: a cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-12 16:45:34","doi":"10.21203/rs.3.rs-4031711/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"194fcd4a-6cf7-4377-be97-1a587f710941","owner":[],"postedDate":"March 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-08T04:02:14+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-12 16:45:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4031711","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4031711","identity":"rs-4031711","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}