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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
61

Impacto do loco HLA-DPB1* em pacientes consanguíneos submetidos a transplantes de células tronco hematopoiéticas / Impact of HLA-DPB1* loco in consanguineous patients submitted hematopoietic stem cell transplantation

Jordana Braga 21 May 2014 (has links)
O requisito fundamental na seleção do par doador-receptor em Transplantes de Medula Óssea (TMO) é regido pelo sistema do Complexo Principal de Histocompatibilidade, ou seja, pelos mecanismos imunológicos mediados pelas moléculas dos Antígenos Leucocitários Humanos (HLA). No entanto as incompatibilidades HLA, podem influenciar de forma negativa ou positiva os resultados dos transplantes, através da Doença do Enxerto versus Hospedeiro e o efeito do enxerto versus Leucemia (EvL) respectivamente. Ainda é desconhecido o impacto do locus HLA-DPB1* neste contexto. Assim o presente projeto tem como objetivo a avaliação do impacto do HLA-DPB1* em transplantes de pacientes consanguíneos e a ocorrência de DECH. Para a tal finalidade, tipificamos o locus em questão utilizando a metodologia PCR-SSO, onde após a reação de amplificação da cadeia pela polimerase, realizamos a hibridização com uma sequência específica de oligonucleotídeos para tipificação do Loco HLA-DPB1*. Foram analisadas 826 amostras, sendo 413 pares de receptores e seus respectivos doadores familiares, submetidos a Transplantes de Células Tronco Hematopoiéticas, realizados na Unidade de Transplante de Medula Óssea de Curitiba da Universidade Federal do Paraná e da Faculdade de Medicina de Ribeirão Preto- USP. Observou-se que a presença de incompatibilidades HLA-DPB1* aumentam a chance dos receptores desenvolverem a doença do enxerto versus hospedeiro aguda, em graus mais graves. Assim, concluímos que a avaliação deste loco pode prevenir esta doença, e caso não haja outro doador, alerta o clínico quanto à utilização de medidas profiláticas. / The key requirement in the selection of the receptor-donor pair for bone marrow transplant is is defined by the Major Histocompatibility Complex, or by immunologic mechanisms mediated by molecules of the Human Leukocyte Antigens (HLA). However the post transplant complications due to HLA mismatches, as Graft versus Host Disease (GVHD) and graft failure are fundamental to the success of these transplants. Still unknown is the impact of loci HLA DPB1*, so this project aims to assess the impact of HLA - DPB1* in transplant patients consanguineous and assessing the impact of incompatibilities in HLA - DPB1 * GVHD. For this purpose, analyzed the loco in question using the PCR-SSO method, where after the amplification reaction polymerase chain, we performed hybridization with a sequence -specific primers for typing of HLA - DPB1* Loco. We analyzed 826 samples, 413 pairs of recipients and their respective donors, patients undergoing Hematopoietic Stem Cell Transplants performed in the Unit for Bone Marrow Transplantation in Curitiba, Federal University of Paraná and the Faculty of Medicine of Ribeirão Preto - USP. It was observed that the presence of mismatches HLA- DPB1* increase the chance of recipients develop chronic graft versus host disease, in more severe degrees. Thus, we conclude that the evaluation of this loci can prevent this disease and if no other donors alert the clinician to the use of prophylactic measures.
62

Immunobiology and Novel Therapeutics in Acute Graft-versus-Host Disease

Zitzer, Nina Celia 08 October 2018 (has links)
No description available.
63

Le bortezomib après l’allogreffe diminue l’incidence et la sévérité de la maladie du greffon contre l’hôte chronique chez les patients avec un myélome multiple

Claveau, Jean-Sébastien 09 1900 (has links)
Introduction L’allogreffe de cellules souches hématopoïétiques est un traitement avec un potentiel curatif chez une minorité de patients ayant un diagnostic myélome multiple. Malheureusement, ce traitement est associé à un taux élevé de complications, incluant une probabilité élevée de rechute et/ou de GVH chronique limitant. L’objectif principal de cette étude est de déterminer si un entretien au bortezomib (BTZ) post-allogreffe permet de diminuer l’incidence et la sévérité de la maladie du greffon contre l’hôte (GVH) chronique. Les objectifs secondaires étaient d’évaluer la prise d’immunosuppresseur, de déterminer l’atteinte d’organe et la survie (OS et PFS) chez les patients ayant reçu ou pas du BTZ en entretien. Méthodes Dans cette étude rétrospective, nous avons comparé 46 patients ayant reçu du BTZ en entretien post-allogreffe à 61 patients n’ayant pas reçu d’entretien. Nous avons étudié l’impact du BTZ sur l’incidence et la sévérité de la GVH chronique en utilisant les critères du NIH de 2014. Résultats À 2 ans, l’incidence globale (61.2% vs 83.6%, p=0.001) et modérée/sévère (44.5% vs 77.0%, p=0.001) de GVH chronique était significativement inférieure chez les patients ayant reçu du BTZ en entretien. Les atteintes buccale (43% vs 67%, p=0.018) et ophtalmique (9% vs 41%, p=0.001) étaient diminuées de manière significative lors du diagnostic initial de la GVH chronique chez ces patients ayant reçu un entretien post-allogreffe. Une diminution de l’usage des immunosuppresseurs, dont les corticostéroïdes systémiques (45.1% vs 76.4%, p<0.001), du mycophenolate mofetil (15.5% vs 28.2%, p=0.031) et du tacrolimus (34.5% vs 70.6%, p<0.001) a été observée chez les patients ayant reçu le BTZ. La probabilité d’être vivant et sans immunosuppresseur à 3 ans post-allogreffe était de 77% chez les patients de la cohorte BTZ et 56% dans la cohorte contrôle (p=0.046). Conclusion En conclusion, un entretien avec du BTZ post-allogreffe permet de diminuer l’incidence et la sévérité de la GVH chronique. Ceci devrait donc être considéré comme une option valide chez les patients avec un myélome multiple traités avec une allogreffe. / Background Allogeneic hematopoietic cell transplant (HCT) has curative potential in myeloma but remains hampered by high rates of relapse and chronic GVHD. The primary endpoint of this study was to determine if BTZ maintenance decreases the incidence and severity of chronic GVHD using NIH criteria. The secondary endpoints were to determine the immunosuppression burden, organ involvement and survival (OS, PFS) in patients receiving or not BTZ. Study Design In this retrospective study, we compared the outcome of 46 myeloma patients who received BTZ after upfront tandem auto-allo HCT to 61 patients without maintenance. We explored the impact of bortezomib (BTZ) maintenance on incidence and severity of chronic GVHD using the 2014 NIH criteria. Results At 2 years, incidences of overall (61.2% vs 83.6%, p=0.001) and moderate/severe chronic GVHD (44.5% vs 77.0%, p=0.001) were significantly lower in BTZ recipients who had less mouth (43% vs 67%, p=0.018) and eyes (9% vs 41%, p=0.001) involvement at initial diagnosis. We report a lower use of systemic steroids (45.1% vs 76.4%, p<0.001), mycophenolate mofetil (15.5% vs 28.2%, p=0.031) and tacrolimus (34.5% vs 70.6%, p<0.001) in BTZ recipients. Probability of being alive and off systemic immunosuppressants at 3 years was 77% in BTZ recipients and 56% in controls (p=0.046). Conclusion In summary, BTZ maintenance improved incidence and severity of chronic GVHD and should be considered as a valid option in myeloma patients receiving upfront tandem auto-allo HCT.
64

Potential of TCR sequencing in graft-versus-host disease

Goel, Manisha, Eugster, Anne, Bonifacio, Ezio, Schetelig, Johannes, Bornhäuser, Martin, Link-Rachner, Cornelia S. 19 March 2024 (has links)
Graft-versus-host disease (GvHD) remains one of the major complications following allogeneic haematopoietic stem cell transplantation (allo-HSCT). GvHD can occur in almost every tissue, with the skin, liver, and intestines being the mainly affected organs. T cells are implicated in initiating GvHD. T cells identify a broad range of antigens and mediate the immune response through receptors on their surfaces (T cell receptors, TCRs). The composition of TCRs within a T cell population defines the TCR repertoire of an individual, and this repertoire represents exposure to self and non-self proteins. Monitoring the changes in the TCR repertoire using TCR sequencing can provide an indication of the dynamics of a T cell population. Monitoring the frequency and specificities of specific TCR clonotypes longitudinally in different conditions and specimens (peripheral blood, GvHD-affected tissue samples) can provide insights into factors modulating immune reactions following allogeneic transplantation and will help to understand the underlying mechanisms mediating GvHD. This review provides insights into current studies of the TCR repertoire in GvHD and potential future clinical implications of TCR sequencing.
65

Burden and Needs of Patients with Severe GvHD from the Supportive and Palliative Care Perspective—A Literature Review

Wenzel, Freya, Pralong, Anne, Holtick, Udo, Scheid, Christoph, Herling, Marco, Simon, Steffen T. 26 April 2023 (has links)
Graft-versus-host disease (GvHD) is a frequent, and often life-threatening, complication after an allogeneic, hematopoietic stem cell transplantation (allo-SCT). It can appear in an acute or a chronic form and presents different grades of severity. Particularly, the severe forms of GvHD are often responsible for a change of the curative intent for allo-SCT into a palliative goal of care. For this non-systematic review, we conducted a focused literature search in the MEDLINE database via PubMed to examine whether patients with severe forms of GvHD might have special needs and burdens from a supportive and palliative care perspective. To draw a comprehensive picture of this patient group, we included findings on quality of life (QoL) and physical symptoms and function as well as psychological and spiritual well-being. In most domains, patients with severe forms of GvHD showed greater impairment and a higher symptom burden compared to patients with milder forms of GvHD. However, we could not identify any studies that specifically investigated patients with severe forms of GvHD. Further research in this field is necessary to guarantee the highest standard of care for this very special patient group.
66

Role of CD2 and its ligands in T cell activation

Li, Bin 08 1900 (has links)
CD2 is a transmembrane molecule and a “non-canonical” member of the signaling lymphocyte activation molecule (SLAM) family of receptors that is expressed on T cells and NK cells. Its ligands, mouse CD48 and human CD58, are widely expressed on hematopoietic cells including antigen-presenting cells (APCs) and T cells. Previous studies indicated that CD2 promotes T-cell receptor (TCR) signaling when it is engaged by its ligands displayed on APCs. However, the supporting experimental data were rather controversial, and there is no general agreement about the role of CD2 in T cell activation. To study the function of CD2 and its ligands in T cells, we examined T cell functions in newly generated mouse strains lacking CD2 or CD48 in the C57BL/6 background. Compared to wild-type (WT) mice, T cells from CD2-deficient (“knock-out”; KO) mice had severe activation defects. Surprisingly, expression of CD48 on T cells, not on APCs, was also necessary for optimal T cell responses. We found evidence of CD2 interacted with CD48 in cis on T cells and observed their co-localization by confocal microscopy and fluorescence resonance energy transfer (FRET). The only exception was CD2-dependent cytotoxicity, which required CD48 both on T cells and on APCs. Mechanistic studies using mass spectrometry and structure-function analyses revealed that the cis interactions between CD2 and CD48 on T cells boosted TCR signaling, an effect that correlated with the capacity of CD2 to recruit the kinase Lck. Similarly, our further study revealed that the cis interactions between CD2 and CD58 on human T cells were also necessary for maximal TCR signaling and T cell activation. Taken together, our studies provide clear evidence that cis interactions between CD2 and its ligands on T cells are important in TCR signaling and T cell activation. Modulation of these cis interactions can be a promising approach to suppress or enhance T cell activation in a therapeutic setting. / CD2 est une molécule transmembranaire et un membre “ non-canonique ” de la famille de la famille SLAM (« signaling lymphocyte activation molecule ») exprimée à la surface des lymphocytes T et des cellules NK (« natural killer »). Les ligands de CD2, CD48 chez la souris et CD58 chez l’humain, sont exprimés de manière ubiquitaire sur les cellules hématopoïétiques, y compris sur les cellules présentatrices d’antigène (CPA) et lymphocytes T. Des études antérieures ont indiqué que CD2 est impliqué dans la signalisation des récepteurs TCR (« T-cell receptor ») en réponse à son engagement par CD48 sur le CPA; cependant, les données expérimentales qui supportent ce modèle sont plutôt contradictoires et aucun accord n’a été trouvé sur les rôle de CD2 dans l’activation de lymphocytes T. Pour étudier la fonction de CD2 et ses ligands, nous avons examiné les fonctions des lymphocytes T chez des souches de souris dépourvues de CD2 ou CD48 nouvellement générées à partir du “fond génétique” C57BL/6. Par rapport aux souris de type sauvage (WT; « wild-type »), les lymphocytes T de souris CD2-déficientes (« knock-out »; KO) présentent des sévères défauts d’activation. Il est intéressant de noter que l’expression de CD48 sur les lymphocytes T, mais non sur les CPA, était aussi nécessaire pour les réponses des lymphocytes T. Nous avons également démontré que CD2 interagit en cis avec CD48 sur les cellules T et avons observé leur co-localisation par microscopie confocale et FRET (« fluorescence resonance energy transfer) ». La seule exception était la cytotoxicité CD2- dépendante, qui nécessitait l’expression de CD48 à la fois sur les lymphocytes T et sur les CPA. L’étude des mécanismes par la spectrométrie de masse et les analyses structurefonction ont démontré que les interactions en cis entre CD2 et CD48 permettent de stimuler la signalisation du TCR, ce qui corrèle avec la capacité de CD2 à recruter la kinase Lck. De manière similaire, notre étude plus approfondie a démontré que les interactions en cis entre CD2 et CD58 sur les lymphocytes T humains sont nécessaires pour la signalisation maximale du TCR et l’activation cellulaire T. L’ensemble de nos études ont mis en évidence que les interactions en cis entre CD2 et ses ligands sur les lymphocytes T jouent un rôle important dans la signalisation du TCR et l’activation de ces cellules. La modulation de ces interaction en cis pourrait être une approche potentielle pour augmenter ou interférer avec l’activation des lymphocytes T dans un contexte thérapeutique.
67

Addition of Rituximab in Reduced Intensity Conditioning Regimens for B-Cell Malignancies Does Not Influence Transplant Outcomes: EBMT Registry Analyses Following Allogeneic Stem Cell Transplantation for B-Cell Malignancies

Tomaszewska, Agnieszka, Jagasia, Madan, Beohou, Eric, van der Werf, Steffie, Blaise, Didier, Kanfer, Edward, Milpied, Noel, Reményi, Péter, Ciceri, Fabio, Bourhis, Jean H., Chevallier, Patrice, Solano, Carlos, Socié, Gerard, Bruno, Benedetto, Rambaldi, Alessandro, Castagna, Luca, Kröger, Nicolaus, Corradini, Paolo, Afanasyev, Boris, Ladetto, Marco, Niederwieser, Dietger, Scheid, Christof, Sengeloev, Henrik, Kroschinsky, Frank, Yakoub-Agha, Ibrahim, Schoemans, Helene, Koenecke, Christian, Penack, Olaf, Peri´c, Zinaida, Greinix, Hildegard, Duarte, Rafael L., Basak, Grzegorz W. 24 March 2023 (has links)
Rituximab (R) is increasingly incorporated in reduced intensity conditioning (RIC) regimens for allogeneic hematopoietic cell transplantation (alloHCT) in patients with B-cell malignancies, not only to improve disease control, but also to prevent graft-versus-host disease (GVHD). There are no randomized prospective data to validate this practice, although single center data and the CIBMTR analysis have shown promising results. We aimed at validation of these findings in a large registry study. We conducted a retrospective analysis using the EBMT registry of 3,803 adult patients with B-cell malignancies undergoing alloHCT (2001–2013) with either rituximab (R-RIC-9%) or nonrituximab (RIC-91%) reduced intensity regimens respectively. Median age and median follow up were 55 years (range 19.1–77.3) and 43.2 months (range 0.3–179.8), respectively. There was no difference in transplant outcomes (R-RIC vs RIC), including 1-year overall survival (69.9% vs 70.7%), 1-year disease-free survival (64.4% vs 62.2%), 1-year non-relapse mortality (21% vs 22%), and day-100 incidence of acute GVHD 2-4° (12% vs 12%). In summary, we found that addition of rituximab in RIC regimens for B-cell malignancies had no significant impact on major transplant outcome variables. Of note, data on chronic GVHD was not available, limiting the conclusions that can be drawn from the present study.
68

Alterações bucais em pacientes submetidos ao transplante de células tronco hematopoiéticas: estudo longitudinal / Oral complications in patients undergoing hematopoietic stem cell transplantation: a longitudinal study

Luiz, Ana Cláudia 03 May 2012 (has links)
A boca é local de frequentes complicações relacionadas ao transplante de células tronco hematopoiéticas (TCTH) tais como xerostomia, disgeusia, disfagia, mucosite, infecções oportunistas e doença do enxerto contra hospedeiro (DECH). Sabe-se que estas complicações podem comprometer a qualidade de vida do paciente e interferir na morbidade pós-TCTH. O dentista é o profissional da saúde que deverá intervir no momento correto para tratar e minimizar esses efeitos secundários do TCTH. Para tanto é importante conhecermos o momento em que cada complicação ocorre para que a intervenção seja pronta e eficiente. O objetivo principal deste estudo foi identificar e quantificar as alterações bucais em indivíduos submetidos ao TCTH em cinco momentos consecutivos desde antes do início do condicionamento pré-TCTH até o dia 100 pós-TCTH. Como objetivos secundários buscamos investigar possíveis relações entre a severidade da mucosite oral e a manifestação da DECH com dados demograficos (sexo, idade), com o status de saude bucal (por meio dos índices IHO-S, CPOD, número de dentes cariados) e com a realização de adequação bucal pré-TCTH, e ainda, somente para a DECH, também foi investigada a possível relação entre esta doença com infecção sistêmica por citomegalovírus e com a manifestação de mucosite oral severa. Foram incluídos no estudo 27 indivíduos com doenças hematológicas do Serviço de Transplante de Medula Óssea do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), com idade 12 anos que receberam TCTH alogênico. Os indivíduos foram examinados em cinco momentos consecutivos. No primeiro momento, pré-TCTH, foi realizada a coleta de índices de saúde bucal e aplicação de questionário sobre o histórico de tratamentos odontológico prévios. Nos momentos de 10, 20, 60 e 100 dias pós-TCTH foram avaliadas as manifestações bucais presentes. A incidência de mucosite oral foi de 82,6% considerando todos os momentos avaliados. Mucosite oral severa, ou seja, graus 3 e 4 (OMS) foi observada em 57,9% dos pacientes avaliados nos momentos 2 e 3. Dez (37%) pacientes apresentaram GVHD em algum órgão, e destes, 8 (80%) apresentaram GVHD de boca. Infecção sistêmica por CMV foi diagnosticada em 6 (22,2%) pacientes. Concluímos que entre as queixas levantadas, dor bucal e disfagia foram as mais referidas. O período de maior incidência das complicações bucais foi nos segundo e terceiro momentos, ou seja, D+10 e D+20, representando deste forma, o período de maior morbidade do tratamento. Não houve associação entre a severidade de mucosite oral e idade, sexo, fonte de células, regime de condicionamento, número de dentes cariados, IHO-S, CPOD e preparo bucal pré-TCTH. Para a DECH a única relação encontrada foi para fonte de células, tendo sido observada menor chance de ocorrer DECH quando a fonte de células foi o sangue periférico. / The mouth is a well-known site of complications of the hematopoietic stem cell transplantation (HSCT) such as dry mouth, dysgeusia, dysphagia, mucositis, opportunistic infections and graft versus host disease (GVDH). It is known that these complications can compromise the patients quality of life and morbidity post-HSCT. The dentist is the health professional who should interfere at the right time to treat and minimize these side effects of HSCT. Thus, it is important to know the time at which each complication occurs to be dynamic and efficient. The main objective of this study was to identify and quantify the oral complications in patients treated with HSCT in five consecutive moments starting before conditioning chemotherapy until day 100 post-HSTC. As secondary objectives we seek to investigate possible relationships between the severity of oral mucositis and the manifestation of GVHD with demographic data (gender, age), with the oral health status (IHO-S, CPOD, number of decayed teeth) and dental treatment previously HSCT, and, only for GVHD, was also investigated the possible relationship between this disease with systemic cytomegalovirus infection and the manifestation of severe oral mucositis. It was included in the study 27 patients with hematologic diseases who were admitted in the Unit of Bone Marrow Transplantation, Hospital of Clinics, Faculty of Medicine, University of Sao Paulo (HC-FMUSP), 12 years old whom received allogeneic HSCT. The subjects were examined in five consecutive moments. At the first moment, before HSCT, the oral health índex evaluation and a questionnaire about history of previous dental treatments were performed. Besides that, 10, 20, 60 and 100 days after HSCT they were evaluated for oral manifestations. Oral mucositis incidence was 82,6% and 57,9% of these patients presented severe mucositis. Ten (37%) patients had GVHD in any organ, and of these, 8 (80%) had oral GVHD. Infection by CMV was diagnosed in 6 (22.2%) patients. We conclude that among the complaints raised, mouth pain and dysphagia were the most mentioned. The period of increased incidence of oral complications was the second and third times (D +10 and +20), representing the increased morbidity period. There was no association between the severity of oral mucositis and age, sex, cell source, conditioning regimen, number of decayed teeth, IHO-S, CPOD and dental treatment pre-HSCT. For GVHD the only relation found was with source of cells, in which, GVHD was less likely to occur when the source of cells was peripheral blood.
69

Caracterização e adaptação do dosímetro Fricke para dosimetria em irradiação de sangue / Characterization and Adaptation of Fricke Dosimeter for Blood Irradiation Dosimetry

Del Lama, Lucas Sacchini 31 October 2013 (has links)
A Doença Enxerto Contra Hospedeiro Associada à Transfusão (DECH-AT) é uma reação transfusional rara, porém fatal, que ocorre devido à presença de células T no sangue doado e que pode ser prevenida por meio da irradiação do sangue do doador e de seus componentes antes da transfusão. Assim, o controle de qualidade associado à irradiação do sangue é necessário para se garantir a qualidade do produto transfundido. Neste trabalho é proposta a caracterização e a adaptação da resposta do dosímetro Fricke para uso na dosimetria da irradiação de sangue, mais especificamente o Fricke Xilenol Gel (FXG). Este é um dosímetro químico radiocrômico, que apresenta as vantagens de ser tecido equivalente e de permitir a inferência espacial da dose absorvida dentro da faixa de doses usados na prevenção DECH-AT. Dessa maneira, de modo a possibilitar a inferência de dose absorvida em todo o intervalo utilizado na prevenção da DECH-AT (25 a 50 Gy), o FXG foi caracterizado e adaptado para aplicações dosimétricas envolvendo a irradiação de sangue e derivados. Os resultados com o novo dosímetro apontaram adequabilidade para toda a faixa necessária de doses absorvidas, com sensibilidade e desvanecimento temporal satisfatórios para aplicações rotineiras. Além disso, pela metodologia proposta neste trabalho, foi possível determinar as distribuições espaciais das doses absorvidas com o dosímetro proposto de uma maneira rápida e simples, mostrando assim que este dosímetro apresenta características convenientes para o controle de qualidade para a dosimetria da irradiação de sangue e de hemocomponentes. / The Transfusion Associated Graft Versus Host Disease (TA-GVHD) is a rare transfusion reaction, however fatal, which develops due to the presence of donor T lymphocytes in the donated blood and that can be avoided by the irradiation of the donated blood blood and blood components prior to transfusion. Thus, the associated quality control of blood irradiation is necessary to guarantee the quality of the transfused product. In this work it is proposed the characterization and adaptation of the response of a Fricke dosimeter to be used for dosimetry of blood irradiation, more especiafically the Fricke Xylenol Gel (FXG). This is a radiochromic chemical dosimeter, which presents advantages to be tissue equivalent and allows the spatial absorbed dose inference. In this manner, in a way to possibilitate the absorbed dose inference in the full interval used for the prevention of the TA-GVHD (25 to 50 Gy) the FXG was characterized and adapted for dosimetry applications involving blood and blood components irradiation. The results with the new dosimeter showed adequability for the necessary absorbed doses, with satisfactory sensibility and time fading for routine applications. Furthermore, according to the methodology proposed in this work, it was possible to determine the spatial absorbed dose distributions with the new dosimeter in an fast and simple way, showing that this dosimeter presents convenient characteristics for dosimetry quality control of irradiated the blood and blood components.
70

Alterações bucais em pacientes submetidos ao transplante de células tronco hematopoiéticas: estudo longitudinal / Oral complications in patients undergoing hematopoietic stem cell transplantation: a longitudinal study

Ana Cláudia Luiz 03 May 2012 (has links)
A boca é local de frequentes complicações relacionadas ao transplante de células tronco hematopoiéticas (TCTH) tais como xerostomia, disgeusia, disfagia, mucosite, infecções oportunistas e doença do enxerto contra hospedeiro (DECH). Sabe-se que estas complicações podem comprometer a qualidade de vida do paciente e interferir na morbidade pós-TCTH. O dentista é o profissional da saúde que deverá intervir no momento correto para tratar e minimizar esses efeitos secundários do TCTH. Para tanto é importante conhecermos o momento em que cada complicação ocorre para que a intervenção seja pronta e eficiente. O objetivo principal deste estudo foi identificar e quantificar as alterações bucais em indivíduos submetidos ao TCTH em cinco momentos consecutivos desde antes do início do condicionamento pré-TCTH até o dia 100 pós-TCTH. Como objetivos secundários buscamos investigar possíveis relações entre a severidade da mucosite oral e a manifestação da DECH com dados demograficos (sexo, idade), com o status de saude bucal (por meio dos índices IHO-S, CPOD, número de dentes cariados) e com a realização de adequação bucal pré-TCTH, e ainda, somente para a DECH, também foi investigada a possível relação entre esta doença com infecção sistêmica por citomegalovírus e com a manifestação de mucosite oral severa. Foram incluídos no estudo 27 indivíduos com doenças hematológicas do Serviço de Transplante de Medula Óssea do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), com idade 12 anos que receberam TCTH alogênico. Os indivíduos foram examinados em cinco momentos consecutivos. No primeiro momento, pré-TCTH, foi realizada a coleta de índices de saúde bucal e aplicação de questionário sobre o histórico de tratamentos odontológico prévios. Nos momentos de 10, 20, 60 e 100 dias pós-TCTH foram avaliadas as manifestações bucais presentes. A incidência de mucosite oral foi de 82,6% considerando todos os momentos avaliados. Mucosite oral severa, ou seja, graus 3 e 4 (OMS) foi observada em 57,9% dos pacientes avaliados nos momentos 2 e 3. Dez (37%) pacientes apresentaram GVHD em algum órgão, e destes, 8 (80%) apresentaram GVHD de boca. Infecção sistêmica por CMV foi diagnosticada em 6 (22,2%) pacientes. Concluímos que entre as queixas levantadas, dor bucal e disfagia foram as mais referidas. O período de maior incidência das complicações bucais foi nos segundo e terceiro momentos, ou seja, D+10 e D+20, representando deste forma, o período de maior morbidade do tratamento. Não houve associação entre a severidade de mucosite oral e idade, sexo, fonte de células, regime de condicionamento, número de dentes cariados, IHO-S, CPOD e preparo bucal pré-TCTH. Para a DECH a única relação encontrada foi para fonte de células, tendo sido observada menor chance de ocorrer DECH quando a fonte de células foi o sangue periférico. / The mouth is a well-known site of complications of the hematopoietic stem cell transplantation (HSCT) such as dry mouth, dysgeusia, dysphagia, mucositis, opportunistic infections and graft versus host disease (GVDH). It is known that these complications can compromise the patients quality of life and morbidity post-HSCT. The dentist is the health professional who should interfere at the right time to treat and minimize these side effects of HSCT. Thus, it is important to know the time at which each complication occurs to be dynamic and efficient. The main objective of this study was to identify and quantify the oral complications in patients treated with HSCT in five consecutive moments starting before conditioning chemotherapy until day 100 post-HSTC. As secondary objectives we seek to investigate possible relationships between the severity of oral mucositis and the manifestation of GVHD with demographic data (gender, age), with the oral health status (IHO-S, CPOD, number of decayed teeth) and dental treatment previously HSCT, and, only for GVHD, was also investigated the possible relationship between this disease with systemic cytomegalovirus infection and the manifestation of severe oral mucositis. It was included in the study 27 patients with hematologic diseases who were admitted in the Unit of Bone Marrow Transplantation, Hospital of Clinics, Faculty of Medicine, University of Sao Paulo (HC-FMUSP), 12 years old whom received allogeneic HSCT. The subjects were examined in five consecutive moments. At the first moment, before HSCT, the oral health índex evaluation and a questionnaire about history of previous dental treatments were performed. Besides that, 10, 20, 60 and 100 days after HSCT they were evaluated for oral manifestations. Oral mucositis incidence was 82,6% and 57,9% of these patients presented severe mucositis. Ten (37%) patients had GVHD in any organ, and of these, 8 (80%) had oral GVHD. Infection by CMV was diagnosed in 6 (22.2%) patients. We conclude that among the complaints raised, mouth pain and dysphagia were the most mentioned. The period of increased incidence of oral complications was the second and third times (D +10 and +20), representing the increased morbidity period. There was no association between the severity of oral mucositis and age, sex, cell source, conditioning regimen, number of decayed teeth, IHO-S, CPOD and dental treatment pre-HSCT. For GVHD the only relation found was with source of cells, in which, GVHD was less likely to occur when the source of cells was peripheral blood.

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