Lic. -avh. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 3 uppsatser.

Source: Dissertation Abstracts International, Volume: 70-07, Section: B, page: 4063. Adviser: David R. Lairson. Includes bibliographical references.

Thesis (Ph. D.)--Florida State University, 2005. / Advisor: Bruce R. Locke, Florida State University, FAMU-FSU College of Engineering, Dept. of Chemical and Biomedical Engineering. Title and description from dissertation home page (viewed Jan. 12, 2006). Document formatted into pages; contains xix, 250 pages. Includes bibliographical references.

Η Οξεία λευχαιμία (ΟΛ) αποτελεί νεοπλασματικό, αιμοποιητικό νόσημα, που οφείλεται στον πολλαπλασιασμό και την επέκταση κυττάρων, που προέρχονται από τους λευχαιμικούς βλάστες. Η φυσική εξέλιξη του νοσήματος είναι η αντικατάσταση των φυσιολογικών κυττάρων του αιμοποιητικού ιστού από τους απόγονους των λευχαιμικών βλαστών και θάνατος, λόγω των επιπλοκών της έλλειψης των ώριμων αιμοποιητικών κυττάρων, όπως λοιμώξεις, αναιμία και αιμορραγία. Θεραπευτικά για την αντιμετώπιση της ΟΛ χρησιμοποιούνται σχήματα χημειοθεραπείας και ακτινοθεραπείας, που έχουν σαν σκοπό την καταστροφή των λευχαιμικών βλαστών και την αποκατάσταση της φυσιολογικής αιμοποίησης. Συχνά η ΟΛ, ιδιαίτερα σε ασθενείς μεγάλης ηλικίας, εμφανίζεται ταυτόχρονα με δυσπλαστικές διαταραχές των αιμοποιητικών κυττάρων που ωριμάζουν ή εξελίσσεται σε μυελοδυσπλαστικό σύνδρομο μετά από χημειοθεραπεία. Από την βιβλιογραφία είναι γνωστό ότι, τόσο η ΟΛ μπορεί να είναι στάδιο εξέλιξης των μυελοδυσπλαστικών συνδρόμων και κατά συνέπεια μετά τη θεραπεία της ΟΛ επανέρχεται η δυσπλαστική κατάσταση της αιμοποίησης, όσο ότι η χημειοθεραπεία καθαυτή μπορεί να προκαλέσει μυελοδυσπλασία. Είναι σημαντική η διάγνωση των πρωτοπαθών μυελοδυσπλαστικών συνδρόμων που εξελίσσονται σε ΟΛ, ως προς την πρόγνωση των ασθενών, αλλά και τη θεραπευτική τους αντιμετώπιση. Επίσης, είναι σημαντική η διάκριση ομάδων ασθενών που θα αναπτύξουν δυσπλασία μετά από χημειοθεραπεία, σε σχέση με αυτούς που δεν θα αναπτύξουν και ως προς την πρόγνωση και ως προς τη θεραπευτική αντιμετώπιση. Μέχρι σήμερα, κατά την εμφάνιση της ΟΛ η διάγνωση υποκείμενης μυελοδυσπλασίας είναι δύσκολη και στηρίζεται σε μορφολογικά χαρακτηριστικά των ώριμων κυττάρων και στην παρουσία ορισμένων κυτταρογενετικών διαταραχών. Η διάκριση ομάδων που θα αναπτύξουν δυσπλασία μετά από χημειοθεραπεία είναι αδύνατη. Σκοπός της μελέτης ήταν να συμβάλλει στην ανάπτυξη νέων πρωτοκόλλων στο λογισμικό της κυτταρομετρίας ροής, που θα διευκολύνουν τη διάγνωση πρωτοπαθών δυσπλαστικών συνδρόμων κατά την εμφάνιση της ΟΛ, αλλά και θα διακρίνουν τις ομάδες που μπορούν να αναπτύξουν δυσπλασία μετά από θεραπεία. Για τον σκοπό αυτό, παρακολουθήσαμε την έκφραση χαρακτηριστικών αντιγονικών συνδυασμών, που εκφράζονται σε διαφορετικά στάδια ωρίμανσης των φυσιολογικών κυττάρων, παράλληλα με την έκφραση των αντιγόνων των βλαστών. Τα δεδομένα αυτά μελετήθηκαν, τόσο κατά την εμφάνιση της ΟΛ, όσο και κατά τη παρακολούθηση της. Τα δεδομένα αναλύθηκαν με συστήματα ταυτόχρονης ανάλυσης και συσχέτισης 15-20 παραμέτρων, με σκοπό τον καθορισμό συσχετισμών που θα έχουν διαγνωστική και προγνωστική σημασία για τους ασθενείς με ΟΛ. Τα αποτελέσματα του ανοσοφαινοτύπου αναλύθηκαν, επιπλέον, με το λογισμικό πακέτο στατιστικής ανάλυσης SPSS 16.0. Για τους σκοπούς της μελέτης αναλύθηκαν αναδρομικά τα αποτελέσματα της κυτταρομετρίας ροής στο μυελό των οστών 148 ασθενών με ΟΜΛ κατά την εμφάνιση της νόσου, κατά την διάρκεια και μετά από θεραπεία. Αναλύθηκε η έκφραση των αντιγόνων CD11b/CD16/CD13 σε όλα τα στάδια ωρίμανσης της μυελικής σειράς, ενώ η έκφραση των αντιγόνων CD34/CD117 μόνο στα άωρα κύτταρα. Τα ευρήματα του ανοσοφαινοτύπου συγκρίθηκαν με τα μορφολογικά χαρακτηριστικά των αντίστοιχων μυελών των οστών. Συμπερασματικά, τα αποτελέσματα έδειξαν ότι, η έκφραση των αντιγόνων CD11b και CD13 στα μεταμυελοκύτταρα και ουδετερόφιλα των ασθενών διακρίνει αποτελεσματικά τους ασθενείς με de novo ΟΜΛ σε σχέση με αυτούς που εμφάνισαν ΟΜΛ μετά από ΜΔΣ. Στους ασθενείς με de novo ΟΜΛ η έκφραση των αντιγόνων CD11b, CD13, CD16 δεν διέφερε κατά την εμφάνιση της ΟΛ στους υποπληθυσμούς των προμυελοκυττάρων, μυελοκυττάρων, μεταμυελοκυττάρων και ουδετερόφιλων μεταξύ των ασθενών που κατά ή μετά την θεραπεία εμφάνισαν μυελοδυσπλασία, σε σχέση με αυτούς που δεν εμφάνισαν. Επίσης, η θετική συν- έκφραση των αντιγόνων CD34/CD117 στους λευχαιμικούς βλάστες κατά την εμφάνιση δεν συσχετίζονταν με την εμφάνιση ΜΔΣ μετά την θεραπεία. Αντίθετα, η υψηλή έκφραση του λευχαιμικού φαινοτύπου CD34+/CD117- στα άωρα κύτταρα της μυελικής σειράς κατά την εμφάνιση της ΟΜΛ, έδειξε ότι σχετίζεται με την εμφάνιση μυελοδυσπλαστικών χαρακτηριστικών μετά τη θεραπεία. Η ανάλυση των ανοσοφαινοτύπων του μυελού των οστών κατά ή μετά την θεραπεία έδειξε παθολογική έκφραση CD11b, CD13, CD16 στα μεταμυελοκύτταρα και ουδετερόφιλα των ασθενών που εμφάνισαν ΜΔΣ μετά θεραπεία για de novo ΟΜΛ και ασθενών (5/17) που δεν εμφάνισαν ΜΔΣ. Συμπερασματικά, η έκφραση των αντιγόνων CD11b, CD16 και CD13 στα ώριμα κύτταρα της μυελικής σειράς κατά την εμφάνιση της ΟΜΛ διαχωρίζει αποτελεσματικά την de novo ΟΜΛ από την δευτεροπαθή μετά ΜΔΣ. Η έκφραση αυτών των αντιγόνων κατά την εμφάνιση της ΟΜΛ δεν μπορεί, όμως, να προβλέψει την εξέλιξη της de novo ΟΜΛ και την εμφάνιση δυσπλαστικών χαρακτηριστικών μετά τη θεραπεία. Αντιθέτως, η μελέτη των λευχαιμικών φαινοτύπων CD34+/CD117- και CD34+/CD117+ μπορεί να παίξει καθοριστικό ρόλο στην πρόγνωση της εμφάνισης μυελοδυσπλαστικών χαρακτηριστικών κατά τη διάρκεια ή μετά τη θεραπεία του ασθενούς. / --

No description available.

A mucosite bucal (MB) é uma complicação comum no tratamento do câncer e o desenvolvimento de intervenções efetivas para sua prevenção e tratamento são vistos como prioridade nos cuidados de suporte ao paciente oncológico. O objetivo do presente estudo foi investigar fatores de risco relacionados à incidência de mucosite bucal em pacientes submetidos a transplante de células progenitoras hematopoiéticas (TCPH) e em pacientes oncológicos pediátricos. Foram realizados dois estudos: o primeiro analisando a relação entre a incidência de mucosite bucal e o estado de saúde bucal, neutropenia, leucopenia e níveis de IL-1β em pacientes submetidos ao TCPH; e, o segundo, avaliando a incidência de mucosite bucal em pacientes oncopediátricos submetidos a diferentes protocolos quimioterápicos e sua relação com toxicidade hematológica, hepática e renal. Estudo 1: Foram avaliados 54 pacientes submetidos ao TCPH coletados dados demográficos e de à história médica foram coletados. Todos os pacientes foram avaliados quanto a saúde bucal através da análise do índice de placa (IP), índice gengival (IG), número de dentes cariados, perdidos e obturados (CPOD) e exame da mucosa bucal. Todos os pacientes receberam tratamento dentário e orientações de higiene bucal prévio bem como, fotobiomodulação (FBM) com laser de diodo InGaAlP como protocolo preventivo para mucosite bucal. Os pacientes foram avaliados diariamente desde o condicionamento ate o final do transplante. Avaliações de mucosite bucal, níveis de neutrófilos e leucócitos e análise de IL-1β foram realizados nos períodos de condicionamento, D+3 e D+8. Os pacientes que apresentaram gengivite severa anterior ao condicionamento para o transplante e que apresentaram neutropenia grave e leucopenia mostraram associação com o desenvolvimento OM. Os pacientes com mucosite bucal apresentaram níveis mais baixos de IL-1β. Estudo 2: Foram acompanhados 172 ciclos de quimioterapia realizados em 40 pacientes pediátricos. Dados de toxicidade hematológica (níveis de plaquetas, leucócitos, neutrófilos e hemoglobina), hepática (níveis de bilirrubina, TGO, TGP) e renal (creatinina e uréia) nos períodos D1, D5, D10 e D15 foram coletados. Avaliação do grau de mucosite bucal foi realizado diariamente a partir de D1 até D15. Os pacientes que desenvolveram mucosite receberam FBM 3 vezes por semana como tratamento. Os resultados mostraram que a mucosite bucal em pacientes oncológicos pediátricos tem relação com o tipo de protocolo quimioterápico utilizado, com a diminuição nos níveis de plaquetas, leucócitos e hemoglobina bem como, com o aumento dos níveis de bilirrubina. Os níveis de plaquetas e de bilirrubina podem ser considerados como fatores de risco para predizer o desenvolvimento de mucosite bucal. Conclui-se que ambos os trabalhos vieram a contribuir para a elucidação de fatores envolvidos no desenvolvimiento de mucosite bucal em pacientes submetidos ao TCPH e em pacientes oncopediátricos. / Oral mucositis (OM) is a common complication in cancer treatment. The development of effective interventions for prevention and treatment are seen as priority in supportive care cancer patients. The aim of this study was to investigate risk factors related to the incidence of oral mucositis in patients undergoing to hematopoietic stem cells transplantation (HSCT) and in pediatric oncology patients. Two studies were performed: the first analyzing the relationship between oral mucositis incidence with oral health status, neutropenia, leukopenia, and IL-1β levels in patients undergoing to HPCT; and the second, evaluating the incidence of oral mucositis in pediatric oncological patients undergoing to different chemotherapy protocols and their relationship with toxicity haematological, of liver and of kidney. Study 1: A total of 54 patients undergoing to HSCT were collected demographic data and medical history. All patients were evaluated for the oral health through plaque index (PI), gingival index (GI), number of decayed, missing and filled (DMF) and oral mucosa examination. All patients received prior dental and oral hygiene as well as photobiomodulation (PBM) InGaAlP diode laser as a preventive protocol for oral mucositis. Patients were evaluated daily from the conditioning until the end of transplantation. Reviews of oral mucositis, neutrophil ans leukocytes levels and IL- 1β analysis were performed in periods of conditioning, D+3 and D+8. Patients with previous severe gingivitis to conditioning for transplantation and who had severe neutropenia and leukopenia showed association with OM development. The oral mucositis patients had lower levels of IL-1β. Study 2: Wewre analyzed a total of 172 cycles of chemotherapy conducted in 40 oncological pediatric patients. Haematological toxicity data (levels of platelets, leukocytes, neutrophils, and hemoglobin), liver (bilirubin, GOT, GPT) and renal (creatinine and urea) in the periods D1, D5, D10 and D15 were collected. oral mucositis grade evaluation was performed daily from D1 to D15. Patients who developed oral mucositis received three times a week PBM as treatment. The results showed that oral mucositis in pediatric oncology patients is related to the type of chemotherapy protocol used with the decrease in the levels of platelets, leucocytes and hemoglobin as well as with the increase of the bilirubin level. The levels of platelets and bilirubin may be considered as risk factors to predict the development of oral mucositis. We conclude that both studies contributed to the elucidation of factors involved in the development of oral mucositis in patients undergoing HSCT and pediatric oncology patients.

Introdução: O transplante de células‐tronco hematopoéticas (TCTH) é um procedimento complexo, que envolve diferentes fatores e condições biopsicossociais. O acompanhamento dos dados desses pacientes é fundamental para a obtenção de informações que possam auxiliar a gestão, aperfeiçoar a assistência prestada e subsidiar novas pesquisas sobre o assunto. Objetivos: desenvolver um modelo de banco de dados (BD) de pacientes submetidos a TCTH, contemplando as principais variáveis de interesse na área. Métodos: Trata‐se de um estudo aplicado, onde utilizou‐se a metodologia de desenvolvimento de um BD relacional, seguindo três etapas principais (modelo conceitual, modelo relacional, modelo físico). O modelo físico proposto foi desenvolvido na plataforma Research Electronic Data Capture (REDCap). Um teste piloto foi realizado com dados de três pacientes submetidos a TCTH no Hospital Moinhos de Vento no ano de 2016/2017, a fim de avaliar a utilização das ferramentas e sua aplicabilidade. Resultados: Foram desenvolvidos nove formulários no REDCap: dados sociodemográficos; dados diagnósticos; histórico, dados clínicos prévios; avaliação prétransplante; procedimento; acompanhamento pós‐imediato; acompanhamento pós‐tardio; reinternações; óbito. Adicionalmente foram desenvolvidos três modelos de relatórios, com as variáveis contidas nos formulários para auxiliar na exportação de dados para as instituições envolvidas com o TCTH. Após o teste piloto foram realizados pequenos ajustes na nomenclatura de algumas variáveis e exclusão de outras devido à complexidade na sua obtenção. Conclusão: Espera‐se que com a sua utilização, o modelo de BD proposto possa servir como subsídio para qualificar a assistência prestada ao paciente, auxiliar a gestão e facilitar futuras pesquisas na área. / Introduction: hematopoietic stem cell transplantation (HSCT) is a complex procedure involving different biopsychosocial factors and conditions. Monitoring the data of these patients is fundamental for obtaining information that can help the management, improve the assistance provided and subsidize new research on the subject. Objectives: to develop a database model (DB) of patients submitted to HSCT, considering the main variables of interest in the area. Methods: it is an applied study, where the methodology of development of a relational DB was used, following three main steps (conceptual model, relational model, physical model). The proposed physical model was developed in the research electronic data capture (Redcap) platform. A pilot test was performed with data from three patients submitted to HSCT at Moinhos de Vento Hospital in 2016, in order to evaluate the use of the tools and their applicability. Results: nine forms were developed in redcap: demographic data; diagnostic data; previous clinical data; pre‐transplant evaluation; procedure; post‐immediate follow‐up; post‐late follow‐up; readmissions; death. In addition, three reporting models were developed, with the variables contained in the forms to assist in the export of data to the institutions involved with the TCTH. After the pilot test small adjustments were made in the nomenclature of some variables and others were excluded due to the complexity in obtaining them. Conclusion: it is hoped that with its use, the proposed BD model can serve as a subsidy to qualify the care provided to the patient, assist the management and facilitate research in the area.

Les mutations du gène codant pour la protéine XIAP (X-Linked Inhibitor of Apoptosis Protein) sont à l’origine du syndrome lymphoprolifératif lié à l’X de type 2 (XLP-2). Il s’agit d’un déficit immunitaire rare caractérisé par une susceptibilité anormale à l’infection par le virus d’Epstein Barr (EBV). De plus, certains patients déficients en XIAP peuvent souffrir d’une pathologie intestinale parfois sévère. XIAP est molécule anti-apoptique qui a aussi été impliquée dans la signalisation et les fonctions de récepteurs de l’immunité innée, les récepteurs NOD1 et NOD2. Mon travail de thèse a eu pour objectif de caractériser cette pathologie intestinale et ses mécanismes physiopathologiques. Pour cela, nous avons étudié une cohorte de patients déficients en XIAP présentant une pathologie inflammatoire intestinale. Nous avons également recherché des mutations de XIAP dans une cohorte d’enfants ayant présenté comme unique signe clinique une pathologie intestinale précoce. Sur 83 patients testés, 3 patients porteurs de mutations de XIAP ont été identifiés. Nous avons ensuite montré que cette pathologie intestinale est très proche sur les plans clinique et histologique de la maladie de Crohn, qui est une des principales affections inflammatoires de l’intestin chez l’adulte. La maladie de Crohn est associée à des facteurs environnementaux et une susceptibilité génétique, dont les polymorphismes dans le gène NOD2 qui représentent le facteur plus important identifié à ce jour. Nous avons ensuite montré que les monocytes des patients déficients en XIAP ont un défaut de production d’IL-8, de MCP-1 et d’IL-10 en réponse à la stimulation de la voie NOD2. Par contre, nous n’avons pas mis en évidence d’excès d’apoptose des cellules épithéliales digestives chez les patients. En revanche, ils présentaient un nombre diminué de leur lymphocytes T innés circulants, Enfin, au cours de cette étude, nous avons identifié pour la première fois des femmes vectrices d’une mutation de XIAP à l’état hétérozygote, ayant développé des manifestations inflammatoires intestinales. Chez ces patientes, l’inactivation du chromosome X, qui normalement est biaisée en faveur de l’allèle sain chez les vectrices asymptomatiques, est de façon inhabituelle biaisée vers l’allèle muté contribuant à une diminution de l’expression de XIAP dans les monocytes et une altération de la voie NOD2. Ce travail a permis de montrer que le déficit en XIAP est responsable d’une forme monogénique de la maladie de Crohn. Nos résultats suggèrent que le défaut d’activation des monocytes par NOD2 est un mécanisme important de la pathogénèse de la maladie. Sur le plan thérapeutique, la greffe de moelle osseuse semble indiquée dans les formes sévères, puisque le principal défaut identifié est une anomalie du compartiment hématopoïétique, et chez deux de nos patients, elle a permis en effet une amélioration franche de la pathologie digestive qui était très sévère. / Mutations in the gene encoding for XIAP (X-Linked Inhibitor of Apoptosis Protein) are causing the X-linked lymphoproliferative syndrome type 2 (XLP-2). It is a rare immunodeficiency characterized by an abnormal susceptibility to infection with Epstein Barr virus (EBV). In addition, some XIAP-deficient patients may suffer from an intestinal disease that can be severe. XIAP is an anti-apoptotic molecule which has also been involved in the signaling and the functions of receptors of the innate immunity, NOD1 and NOD2. My thesis work aimed to characterize this intestinal pathology and its pathophysiology. For this, we studied a cohort of known XIAP-deficient patients with inflammatory bowel disease. We also looked for mutations of XIAP in a cohort of children who presented as the only clinical sign an early intestinal pathology. In 83 patients tested, three were identified as carrier of a XIAP mutation. We then showed that this intestinal pathology is clinically and histologically very close to Crohn’s disease, which is a major inflammatory bowel disease in adults. Crohn's disease is associated with environmental factors and genetic susceptibility, including polymorphisms in the NOD2 gene that represent the most important factor identified to date. We then showed that the monocytes from XIAP-deficient patients have a defect in production of IL-8, MCP-1 and IL-10 in response to stimulation of the NOD2 pathway. However, we did not reveal any excess of apoptosis in intestinal epithelial cells from XIAP-deficient patients. On the other hand, they showed a decreased number of their circulating innate T cells. Finally, during this study, we identified for the first time, female carriers of a mutation of XIAP in the heterozygous state, who developed intestinal inflammatory manifestations. In these patients, the inactivation of the X chromosome, which is normally biased toward the healthy allele in asymptomatic vectors, is biased to the unusually mutated allele contributing to a decrease of the expression of XIAP in monocytes and an alteration of the NOD2 pathway. This work showed that XIAP deficiency is responsible for a monogenic form of Crohn's disease. Our results suggest that the lack of monocyte activation by NOD2 is an important mechanism in the pathogenesis of the disease. Therapeutically, the bone marrow transplant seems indicated in severe cases, since the main identified defect is an abnormality of the hematopoietic compartment and in two of our patients, it allowed a clear improvement of the digestive pathology that was very severe.

Introdução: Cistite Hemorrágica (CH) é uma grave complicação do Transplante de Células-Tronco Hematopoiéticas (TCTH) Alogênico. Sua incidência varia de 12 a 25,5%. A forma precoce desenvolve-se devido aos efeitos tóxicos de certos quimioterápicos usados no regime de condicionamento, especialmente Ciclofosfamida. Já a CH tardia ocorre a partir do terceiro dia após o TCTH e sua etiologia é multifatorial. Vários fatores de risco para o desenvolvimento de CH tardia foram descritos, incluindo Doença do Enxerto Contra o Hospedeiro (DECH) aguda, doador não relacionado, infecções por vírus urotrópicos, sexo masculino e condicionamento mieloablativo. Materiais e Métodos: O presente estudo tem como objetivos descrever a incidência de CH em pacientes adultos e pediátricos submetidos a TCTH alogênico e identificar fatores de risco associados ao desenvolvimento de CH nesta população. Foram analisados dados de prontuário de 347 pacientes submetidos a TCTH Alogênico no Hospital de Clínicas de Porto Alegre no período de Janeiro de 2001 a Dezembro de 2014. Resultados: CH ocorreu em 42 pacientes (12,1%, IC: 8,9 - 16%), em uma média de 53.4 dias após o procedimento (desvio padrão: 28.1 dias). Apenas 1 paciente (2,4%) desenvolveu CH precoce, com início dos sintomas no D+1. Entre os 41 pacientes que desenvolveram CH tardia, BK vírus foi o principal agente viral identificado. CH ocorreu em 12.8% dos pacientes que receberam condicionamento mieloablativo e em 10.5% dos restantes (P = 0,704). Dos 197 pacientes que apresentaram DECH aguda, 35 (17,8%) desenvolveram CH e somente 7 (4,9%) apresentaram CH na ausência de DECH aguda (P < 0,001). CH foi mais frequente também em pacientes do sexo masculino (P = 0,027). Conclusão: A incidência de CH em nossa amostra foi semelhante à encontrada em outros trabalhos. DECH aguda e sexo masculino estiveram associados a um maior risco de desenvolvimento de CH. / Introduction: Hemorrhagic cystitis (HC) is a serious complication of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) afecting 12 to 25.5% of the patients. The early-onset form of HC develops during or until 72 hours after the conditioning regimen containing high doses of certain chemotherapy drugs such as Busulfan and especially Cyclophosphamide. Late-onset HC occurs from the third day on after HSCT and its etiology is multifactorial. Several risk factors for the late-onset form have been reported including graft-versus-host disease (GVHD), unrelated donor, urotropic infections, male gender and myeloblative conditioning regimen. Methods: This study aims to evaluate the incidence of HC in adult and pediatric patients undergoing Allogeneic HSCT and to identify risk factors associated with the development of HC in this population. Medical records of 347 patients who underwent Allogeneic HSCT at Hospital de Clínicas, Porto Alegre, Brazil, from January 2001 to December 2014 were analyzed. Results: HC occurred in 42 patients (12.1% CI: 8.9 - 16%) at an average of 53.4 days after the procedure (standard deviation: 28.1 days). Only one of them developed early-onset HC, with onset of symptoms on D+1. Among the 41 patients who developed late-onset HC, BKV was the main identified viral agent. HC developed in 12.8% of the patients treated with myeloablative conditioning and in 10.5% of the remaining patients (P = 0.704). Of the 197 patients with acute GVHD, 35 (17.8%) developed HC and only 7 (4.9%) showed HC in the absence of GVHD (P<0.001). HC was also more frequent in males than females (P = 0.027). Conclusion: The incidence of HC in our sample was similar to that found in other studies. In our cohort of patients being male and having acute GVHD increased the risk of developing HC.

A mucosite bucal (MB) é uma complicação comum no tratamento do câncer e o desenvolvimento de intervenções efetivas para sua prevenção e tratamento são vistos como prioridade nos cuidados de suporte ao paciente oncológico. O objetivo do presente estudo foi investigar fatores de risco relacionados à incidência de mucosite bucal em pacientes submetidos a transplante de células progenitoras hematopoiéticas (TCPH) e em pacientes oncológicos pediátricos. Foram realizados dois estudos: o primeiro analisando a relação entre a incidência de mucosite bucal e o estado de saúde bucal, neutropenia, leucopenia e níveis de IL-1β em pacientes submetidos ao TCPH; e, o segundo, avaliando a incidência de mucosite bucal em pacientes oncopediátricos submetidos a diferentes protocolos quimioterápicos e sua relação com toxicidade hematológica, hepática e renal. Estudo 1: Foram avaliados 54 pacientes submetidos ao TCPH coletados dados demográficos e de à história médica foram coletados. Todos os pacientes foram avaliados quanto a saúde bucal através da análise do índice de placa (IP), índice gengival (IG), número de dentes cariados, perdidos e obturados (CPOD) e exame da mucosa bucal. Todos os pacientes receberam tratamento dentário e orientações de higiene bucal prévio bem como, fotobiomodulação (FBM) com laser de diodo InGaAlP como protocolo preventivo para mucosite bucal. Os pacientes foram avaliados diariamente desde o condicionamento ate o final do transplante. Avaliações de mucosite bucal, níveis de neutrófilos e leucócitos e análise de IL-1β foram realizados nos períodos de condicionamento, D+3 e D+8. Os pacientes que apresentaram gengivite severa anterior ao condicionamento para o transplante e que apresentaram neutropenia grave e leucopenia mostraram associação com o desenvolvimento OM. Os pacientes com mucosite bucal apresentaram níveis mais baixos de IL-1β. Estudo 2: Foram acompanhados 172 ciclos de quimioterapia realizados em 40 pacientes pediátricos. Dados de toxicidade hematológica (níveis de plaquetas, leucócitos, neutrófilos e hemoglobina), hepática (níveis de bilirrubina, TGO, TGP) e renal (creatinina e uréia) nos períodos D1, D5, D10 e D15 foram coletados. Avaliação do grau de mucosite bucal foi realizado diariamente a partir de D1 até D15. Os pacientes que desenvolveram mucosite receberam FBM 3 vezes por semana como tratamento. Os resultados mostraram que a mucosite bucal em pacientes oncológicos pediátricos tem relação com o tipo de protocolo quimioterápico utilizado, com a diminuição nos níveis de plaquetas, leucócitos e hemoglobina bem como, com o aumento dos níveis de bilirrubina. Os níveis de plaquetas e de bilirrubina podem ser considerados como fatores de risco para predizer o desenvolvimento de mucosite bucal. Conclui-se que ambos os trabalhos vieram a contribuir para a elucidação de fatores envolvidos no desenvolvimiento de mucosite bucal em pacientes submetidos ao TCPH e em pacientes oncopediátricos. / Oral mucositis (OM) is a common complication in cancer treatment. The development of effective interventions for prevention and treatment are seen as priority in supportive care cancer patients. The aim of this study was to investigate risk factors related to the incidence of oral mucositis in patients undergoing to hematopoietic stem cells transplantation (HSCT) and in pediatric oncology patients. Two studies were performed: the first analyzing the relationship between oral mucositis incidence with oral health status, neutropenia, leukopenia, and IL-1β levels in patients undergoing to HPCT; and the second, evaluating the incidence of oral mucositis in pediatric oncological patients undergoing to different chemotherapy protocols and their relationship with toxicity haematological, of liver and of kidney. Study 1: A total of 54 patients undergoing to HSCT were collected demographic data and medical history. All patients were evaluated for the oral health through plaque index (PI), gingival index (GI), number of decayed, missing and filled (DMF) and oral mucosa examination. All patients received prior dental and oral hygiene as well as photobiomodulation (PBM) InGaAlP diode laser as a preventive protocol for oral mucositis. Patients were evaluated daily from the conditioning until the end of transplantation. Reviews of oral mucositis, neutrophil ans leukocytes levels and IL- 1β analysis were performed in periods of conditioning, D+3 and D+8. Patients with previous severe gingivitis to conditioning for transplantation and who had severe neutropenia and leukopenia showed association with OM development. The oral mucositis patients had lower levels of IL-1β. Study 2: Wewre analyzed a total of 172 cycles of chemotherapy conducted in 40 oncological pediatric patients. Haematological toxicity data (levels of platelets, leukocytes, neutrophils, and hemoglobin), liver (bilirubin, GOT, GPT) and renal (creatinine and urea) in the periods D1, D5, D10 and D15 were collected. oral mucositis grade evaluation was performed daily from D1 to D15. Patients who developed oral mucositis received three times a week PBM as treatment. The results showed that oral mucositis in pediatric oncology patients is related to the type of chemotherapy protocol used with the decrease in the levels of platelets, leucocytes and hemoglobin as well as with the increase of the bilirubin level. The levels of platelets and bilirubin may be considered as risk factors to predict the development of oral mucositis. We conclude that both studies contributed to the elucidation of factors involved in the development of oral mucositis in patients undergoing HSCT and pediatric oncology patients.