رسالة جامعية
Estudio de polimorfismos genéticos en la evolución clínica de pacientes sometidos a trasplante alogenico de progenitores hematopoyéticos
| العنوان: | Estudio de polimorfismos genéticos en la evolución clínica de pacientes sometidos a trasplante alogenico de progenitores hematopoyéticos |
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| المؤلفون: | Alcoceba Sánchez, Miguel |
| مرشدي الرسالة: | González Díaz, Marcos, García Sanz, Ramón |
| مصطلحات موضوعية: | Tesis y disertaciones académicas, Universidad de Salamanca (España), Academic dissertations, Polimorfismo genético, Genetic polymorphism, Pacientes, Patients, Hematopoietic Stem Cells, Células Madre Hematopoyéticas, Homologous Transplantation, Trasplante Homólogo, Materias::Investigación::32 Ciencias médicas::3201 Ciencias clínicas |
| الوصف: | [ES]En el presente trabajo de tesis doctoral se ha analizado el valor de algunossistemas polimórficos (sistema HLA, regiones microsatélite y polimorfismos en dosgenes codificantes de moléculas de adhesión) en un grupo de pacientes receptores de untrasplante alogénico de progenitores hematopoyéticos de sangre periférica de undonante emparentado HLA idéntico. Igualmente se analiza la influencia del sistemaHLA en el desarrollo y evolución clínica de pacientes con mieloma múltiple sometido adiferentes esquemas terapéuticos incluido el trasplante alogénico. |
| الوصف (مترجم): | [EN]Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a wellestablished treatment procedure that can potentially cure patients with hematologic malignancies and inherited or acquired non-malignant diseases. An interaction between recipient immunocompetent cells with the donor cells takes place, triggering a series of alloreactive phenomena which will determine the success or failure of the transplant. The most important events are the immune recognition, resulting in graftversus- host disease (GvHD) and graft-versus-tumor (GvT) effect, the graft rejection and relapse. These phenomena are related to the chimerism establishment and posttransplanttolerance, conditioned by genetic and clinical factors [i.e. stem cell source ormyeloablative vs. non-myeloablative regimen].Contributions like the development of conditioning regimens with lower toxicity, the better management of GvHD, the development of more effective tools for monitoring the engraftment and the better knowledge of GvHD and GvT effects are leading to improvement in the allo-HSCT outcome, with an increased survival reducing allo-HSCT derived complications. Therefore, there is a remarkable increase in the number of indications and patients that could be beneficed by this procedure. However, despite the increasing knowledge in this area, about 20-30% of patients undergoing allo-HSCT die due to procedure-derived complications, mainly GvHD and disease relapse,the major complications of allogeneic HSCT.The HLA system is the most important genetic factor in that processes due to its antigen presentation ability. However, even in the setting of identical HLA allo-HSCT in which disease relapse rate is relatively low (about 20%), up to 40% of the patients present acute and/or chronic GvHD4. This GvHD is a major cause of morbidity and mortality, thereby limiting the use of the procedure. Thus, in these processes there are other factors implicated, such us genetic differences out of HLA loci, the minor histocompatibility antigens (mHLA), cytokine gene polymorphisms implicated in the cytokine storm of the GvHD8 or polymorphisms in proteins related to innate immune response.Finally, a better knowledge of the immunogenetics together with the clinical risk factors will allow a more accurate assessment of the risk of transplant-related complications. This fact could lead to the generation of a clinicprognostic index that would help to select the most appropiate donor, to modify the conditioning regimen and to develope individualized immunosuppressive therapy, GvHD prophylaxis and the graft and post-transplant immunotherapy manipulation11. Moreover, a more exhaustive knowledge on the role of donor and recipient genotypes in GvHD triggering or maintainance, could help to include new clinical assays using new drugs.On the other side, HLA system, as antigen presenting system, could have a role in the development and/or control of some neoplasias. With this premise, its role will be analyzed in multiple myeloma patients, a representative disease from our center.In this thesis, we aim to analyze the influence of three groups of genetic polymorphisms in the allo-HSCT setting (HLA, microsatellites and two adhesion molecules). The obtained results will be discussed below. |
| نوع الوثيقة: | Dissertation/Thesis |
| اللغة: | Spanish; Castilian |
| URL الوصول: | http://hdl.handle.net/10366/76378 |
| حقوق: | Acceso abierto / Open Access CC Reconocimiento - No comercial - Sin obras derivadas 3.0 España |
| رقم الأكسشن: | edstdx.10803.21206 |
| قاعدة البيانات: | TDX |
| الوصف غير متاح. |