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Validação do escore de risco do EBMT (European Group for Blood and Marrow Transplantation) na população de pacientes submetidos ao transplante de células-tronco hematopoéticas no Hospital de Clínicas de Porto AlegreAraújo, Beatriz Stela Gomes de Souza Pitombeira January 2012 (has links)
INTRODUÇÃO: O Transplante de Células-tronco Hematopoéticas (TCTH) alogênico é uma modalidade de tratamento com capacidade de curar várias doenças hematológicas benignas e malignas. Os progressos nesta área aumentaram o número e melhoraram os desfechos dos procedimentos realizados, porém sua morbimortalidade permanece elevada. Em 2009, o escore de risco do EBMT foi validado como um método simples para predizer, com dados pré-transplante, os desfechos de um paciente após o TCTH alogênico. OBJETIVOS: O objetivo deste estudo foi validar a aplicabilidade do escore de risco do EBMT em pacientes brasileiros do Hospital de Cínicas de Porto Alegre (HCPA), submetidos a TCTH alogênico. MÉTODOS: Foi realizado um estudo retrospectivo, observacional, com dados coletados de prontuários de 278 pacientes (156 homens (56%) com mediana de idade de 32 anos) submetidos ao TCTH alogênico no HCPA para doenças malignas e anemia aplástica severa, entre 1994 e 2010. Foi aplicado o escore de risco do EBMT e analisados os desfechos sobrevida global (OS), mortalidade não relacionada à recaída (NRM) e taxa de recaída (RR). RESULTADOS: OS, NRM e RR em cinco anos foram de 53,4%, 39% e 30,7%, respectivamente. A OS em pacientes com risco 0 foi significativamente maior (81,8%) do que os de risco 6 (20%) (p<0,001). Da mesma forma, pacientes com risco 0 tiveram menor NRM (13,6%) do que os com risco 6 (80%) (p=0,001). O estágio avançado da doença foi associado com aumento de RR em todas as patologias neoplásicas avaliadas. CONCLUSÃO: O escore de risco do EBMT pode ser utilizado como um dado adicional na avaliação de pacientes com doenças malignas e anemia aplástica severa com indicação de TCTH alogênico no nosso centro. / BACKGROUND: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is a treatment modality able to cure many hematological disorders. Although utilized with increasing frequency and success, it is still associated with a high transplant related mortality rate. In 2009, the EBMT risk score was validated as a simple tool to predict outcome after allogeneic HSCT for acquired hematological disorders. OBJECTIVES: The aim of this study was to validate the applicability of the EBMT risk score for allogeneic HSCT on south Brazilian patients, from a single center. METHODS: A retrospective observational study was performed based on patients’ records and data base of Hematology and Bone Marrow Transplantation Department at Hospital de Clínicas de Porto Alegre, including all allogeneic transplants for malignant and severe aplastic anemia from 1994 to 2010. Patients were categorized according to EBMT risk score and overall survival (OS), non-relapse mortality (NRM) and relapse rate (RR) were analyzed. RESULTS: There were 278 evaluable patients, of whom 56% were male, and the median age was 32 years. OS, NRM, and RR at five years median follow up, were 53,4%, 39%, and 30,7%, respectively. The OS was 81,8% for risk score 0 and 20% for score 6 (p<0,001), and NRM 13,6% and 80% for risk score 0 and 6, respectively (p=0,001). Advanced disease stage was associated with an increased RR in all evaluated neoplastic disorders. CONCLUSION: The EBMT risk score can be utilized as a tool for clinical decision-making before allogeneic HSTC for malignant hematological diseases and severe aplastic anemia at a single center, in Brazil.
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Impacto clínico da recuperação linfocitária precoce na reconstituição imunológica pós transplante alogênico de células tronco hematopoiéticasCosta, Lisandra Della January 2012 (has links)
Introdução: O transplante de células tronco hematopoiéticas é capaz de curar as doenças hematológicas. O papel da repopulação linfocitária precoce no período pós transplan te visa combater a células neoplásicas que resistiram ao regime de condicionamento e prevenir as infecções oportunistas graves. Sendo assim, uma contagem elevada de linfócitos no período pós transplante é capaz de reduzir a mortalidade relacionada ao transplante (TRM), melhorar a sobrevida livre de doença e reduzir a taxa de recidiva. Objetivos: Avaliar a recuperação linfocitária precoce no D+21 e D+30 pós transplante correlacionado com a taxa de recidiva da doença de base, mortalidade, sobrevida global e livre de doença. Analisar a freqüência das complicações infecciosas neste período. Métodos: Analisado o número absoluto de linfócitos no D+21 e D+30 pós transplante de células tronco hematopoiéticas. Conforme dados da literatura definiu-se no D+21 e no D+30 aqueles com número absoluto de linfócitos abaixo e acima de 300 e se correlacionou os dados obtidos com a taxa de óbito, taxa de recidiva, sobrevida global em 5 anos, sobrevida livre de doença, em 5 anos, TRM em 100 dias. e mortalidade não relacionada a recaída (NRM). Resultados: Neste estudo foram incluídos 100 pacientes portadores das seguintes neoplasias hematológicas: leucemia mielóide aguda, leucemia linfocítica aguda, leucemias secundárias e síndrome mielodisplásica. Destes, 55 pacientes eram do sexo masculino e 45 do sexo feminino. A média de idade foi de 27,9 anos (mínima 9 meses e máxima 55 anos). A mediana do tempo de seguimento foi de 601 dias (IC 95% 106-1845). A mediana de CD 34 infundidos foi de 4,0 (IC 95% 2,4-5,7) e quanto a origem destas células CD 34 infundidas 85% foram de medula óssea (MO), 12% periférica (PBSC) e 3% sangue de cordão umbilical (SCU). Quanto ao tipo de condicionamento realizado 22% foram não mieloablativos e 78% mieloablativos.A mediana de linfócitos no D+21 foi de 460 (IC 95% 0 - 6250) e no D+30 foi de 760 (IC 95% 40-6370). Com relação a taxa de infecções observou-se que 19% das infecções foram de etiologia viral, 65 % bacteriana e 17% fúngicas. A sobrevida global (OS) em 5 anos foi de 44 % , sobrevida livre de doença (DFS) foi de 37,7% , a mortalidade relacionada ao transplante (TRM) em 100 dias foi de 32,5%. E a mortalidade não relacionada a recidiva (NRM) em 5 anos foi de 40,2%. No desfecho óbito observamos que 69% dos pacientes que foram a óbito no D+21 tinham linfócitos abaixo de 300, e 43,9% tinham linfócitos acima de 300 (p<0,05). Pacientes com valores menores que 300 no dia 30 tem 2,20 vezes o risco de irem a óbito quando comparados com aqueles com valores acima de 300 (IC 95% 1,03-4,69) ajustado para DECH e CD34. Pacientes com valores menores que 300 no dia 30 tem 3,76 vezes o risco de irem a óbito em menos de 100 dias quando comparados com aqueles com valores acima de 300 (IC 95% 1,23-11,46) Conclusões: A reconstituição linfocitária precoce (> 300) no D+21 e no D+30 melhora a sobrevida global e livre de doença, bem como reduz a taxa de recidiva da doença de base e reduz a mortalidade. / Background: The role of repopulating lymphocyte after allogenic stem cell transplantation (SCT) includes the prevention of serious infections and attacking residual tumor cells in the early post transplant phase. Therefore, the current study analysed the role of the absolute lymphocyte count (ALC) on day 21 and 30 after SCT in predicting transplant outcomes of patients in terms of the risk of transplant related mortality (TRM) recurrence of original disease and risk of opportunistic infections. Objective: Evaluate early lymphocyte recovery on D +21 and D +30 posttransplant correlated with the rate of recurrence of the underlying disease, mortality, overall survival and disease free survival. Analyzed the frequency of infectious complications in this period. Methods: Analyzed the absolute lymphocyte count in the D +21 and D +30 after hematopoietic stem cell transplantation. According to literature data set the we correlate the absolute lymphocyte count in the D +21D +30 below and above 300 these data with the rate of death, relapse rate, overall survival in 5 years, disease-free survival in 5 years , TRM in 100 days and mortality unrelated to relapse (NRM). Results : Included in the study 100 patients with the following hematologic malignancies: acute myeloid leukemia, acute lymphocytic leukemia, secondary leukemia and myelodysplastic syndrome. Of these, 55 patients were male and 45 female. The average age was 27.9 years (minimum 9 months and maximum 55 years). The median follow-up was 601 days (95% CI 106-1845). The CD 34 median that was infused was 4.0 (95% CI 2.4 to 5.7).The source of stem cells infused was 85% of bone marrow (BM), peripheral 12% (PBSC) and 3 % of umbilical cord blood (UCB). Regarding the type of conditioning performed 22% were non myeloablative and 78% of lymphocytes were mieloablativos. The median of absolute lymphocyte count in the D +21 was 460 (95% CI 0 to 6250) and D +30 was 760 (95% CI 40- 6370 ). Regarding the rate of infections were observed 19% viral infections , bacterial in 65% and fungal in 17%. Overall survival (OS) at 5 years was 44%, disease-free survival (DFS) was 37.7%, transplant related mortality (TRM) in 100 days was 32.5%. Non relapsed mortality (NRM) at 5 years was 40.2%. The death rate found that 69% of patients who died at the D +21 had presented lymphocytes count below 300, and 43.9% were above 300 lymphocytes (p <0.05). Patients with counts less than 300 in D+30 presented 2.20 times risk of death when compared with those who presented values above 300 (95% CI 1.03 to 4.69) adjusted for GVHD and CD34. Patients presenting values less than 300 in 30 days have 3.76 times more risk of death in less than 100 days compared with those with values above 300 (95% CI 1.23 to 11.46). Conclusions: The early lymphocyte reconstitution (> 300) in D +21 D +30 improves overall survival and disease-free and reduces the relapse rate of the underlying disease and reduces mortality.
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Implementation of a blood conservation program in the private hospital setting in South AfricaDu Preez, Monique 22 May 2012 (has links)
Although blood products are a great deal safer these days than in the past, patients receiving allogeneic blood transfusions are still exposed to potential hazards such as infectious diseases and immunomodulatory reactions. Therefore it is important to consider alternatives to allogeneic blood use. This can be done by means of blood conservation alternatives. A successful blood conservation program consists of three integrated phases, namely pre-operative, intra-operative and post-operative stages of patient care. The main objective of this study was to create a transfusion medicine database in order to evaluate the effect of a blood conservation program on the length of hospital stay of patients and the costs incurred in such a program. Five pilot hospitals who had implemented a blood conservation program were compared to five non-pilot hospitals (no blood conservation program). The results show that the average cost related to allogeneic blood usage in pilot hospitals amounted to R 473 274.13, compared to R 777 646.22 for the non-pilot hospitals. Length of hospital stay was also significantly lower in patients receiving blood conservation alternatives compared to patients receiving allogeneic blood. The total costs related to patients of blood conservation was lower, although not significantly, than the total costs of patients using allogeneic blood or both. In this study it was seen that the outcomes were positively associated with the implementation of blood conservation techniques. The efficacy of two leukodepletion methods for allogeneic blood products namely pre-storage and post-storage filtration, were evaluated. The results revealed that the mean leukocyte count of pre-storage leukodepleted blood samples (n = 30) was 0.12 cells/μl. The mean leukocyte count of the post-storage filtered blood samples (n = 20) was 0.05 cells/μl. Both methods were shown to be successful in the efficient removal of leukocytes. Copyright / Dissertation (MSc)--University of Pretoria, 2011. / Immunology / unrestricted
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Serum Neutrophil Extracellular Trap Levels Predict Thrombotic Microangiopathy after Allogeneic Stem Cell Transplantation / 血清中の好中球細胞外トラップ増加は、同種造血幹細胞移植後の血栓性微小血管障害の発症を予測するArai, Yasuyuki 23 March 2015 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18857号 / 医博第3968号 / 新制||医||1008(附属図書館) / 31808 / 京都大学大学院医学研究科医学専攻 / (主査)教授 前川 平, 教授 江藤 浩之, 教授 河本 宏 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
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Storage and allogeneic transplantation of peripheral nerve using a green tea polyphenol solution in a canine model / ポリフェノール処理による末梢神経の保存と同種移植に関する犬モデルの研究Nakayama, Ken 25 January 2016 (has links)
京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12980号 / 論医博第2106号 / 新制||医||1012(附属図書館) / 32450 / (主査)教授 髙橋 良輔, 教授 鈴木 茂彦, 教授 高橋 淳 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM
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Risk Stratification, Measurable Residual Disease, and Outcomes of AML Patients with a Trisomy 8 Undergoing Allogeneic Hematopoietic Stem Cell TransplantationBackhaus, Donata, Jentzsch, Madlen, Bischof, Lara, Brauer, Dominic, Wilhelm, Christina, Schulz, Julia, Franke, Georg-Nikolaus, Pönisch, Wolfram, Vucinic, Vladan, Platzbecker, Uwe, Schwind, Sebastian 26 April 2023 (has links)
Background: For most patients with acute myeloid leukemia (AML) harboring a trisomy 8 an allogeneic hematopoietic stem cell transplantation (HSCT) is a suitable and recommended consolidation therapy. However, comparative outcome analyses between patients with and without trisomy 8 undergoing allogeneic HSCT have not been performed so far. Methods: We retrospectively analyzed clinical features, outcomes, and measurable residual disease (MRD) of 659 AML (12%, n = 81, with a trisomy 8) patients subjected to allogeneic HSCT as a consolidation therapy. Results: The presence of a trisomy 8 associated with a trend for higher age at diagnosis, AML of secondary origin, lower white blood cell counts at diagnosis, worse ELN2017 genetic risk, wild-type NPM1, and mutated IDH1/2 and JAK2. Outcomes after allogeneic HSCT in the entire cohort did not differ between patients with a sole trisomy 8, trisomy 8 with additional cytogenetic aberrations or without a trisomy 8. A trisomy 8 did not affect outcomes within the three ELN2017 risk groups. In accordance with findings in unselected patient cohorts, persistent MRD at allogeneic HSCT in patients with a trisomy 8 identified individuals with a higher risk of relapse following allogeneic HSCT. Conclusions: Outcomes of trisomy 8 patients after allogeneic HSCT did not compare unfavorably to that of other AML patients following allogeneic HSCT. Rather than the presence or absence of a trisomy 8, additional genetic aberrations and MRD at HSCT define outcome differences and aid in informed treatment decisions.
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Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect / 霊長類モデルにおける同種iPS細胞由来軟骨の関節軟骨欠損への生着Abe, Kengo 24 July 2023 (has links)
京都大学 / 新制・課程博士 / 博士(医学) / 甲第24830号 / 医博第4998号 / 新制||医||1067(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 後藤, 慎平, 教授 河本, 宏, 教授 羽賀, 博典 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
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The Effects of Pre-Transplant Music Therapy on Distress, Quality of Life, Pain, Anxiety, Mood, and Pain Medication Use for Patients Undergoing Hematopoietic Stem Cell TransplantBates, Deborah January 2019 (has links)
The purpose of this randomized controlled trial was to determine the effects of pre-transplant music therapy on distress, pain, anxiety, mood, quality of life (QOL), and pain medication use during the preparation period for hematopoietic stem cell transplant (HSCT). Distress, the primary outcome, was measured via the Distress Thermometer. QOL was assessed with the Functional Assessment of Cancer Therapy – General 7 (FACT-G7). Participants self-rated pain and anxiety on Numeric Rating Scales (NRS) and mood on the Rogers Happy/Sad Faces Scale. Participants randomized to the experimental group received three music therapy sessions prior to stem cell infusion day. Repeated measures analysis of variance (RMANOVA) was employed to detect differences between groups for distress and QOL, and t-tests were used to detect differences between groups for pain, anxiety, and mood. Data collection is ongoing and will conclude when 50 patients have been accrued. This report presents interim data analysis, with complete data available for 23 participants. The experimental group had higher distress that was statistically significant at baseline and on Day -1. Music therapy did not affect distress but showed other limited beneficial effects. There were no differences between groups at any individual time point for pain, anxiety, or mood. At all three time points, decreases in anxiety from pre-session to post-session assessment were statistically significant in the experimental group. In the first and third music therapy session, differences between pre- and post-session mood scores were statistically significant in a positive direction. Differences in pain medication use could not be calculated because too few participants required pain medication. Although music therapy did not affect the primary outcome of distress, the positive short-term effects on anxiety and limited positive effects on mood are important to acknowledge. The small sample size likely contributed to the lack of findings on distress, although the longitudinal assessment of this outcome may have also been a factor. This study provides an initial understanding of how music therapy may be effective on distress and other variables during the pre-transplant hospitalization period for patients undergoing allogeneic HSCT, as it is the first research study to examine this treatment phase. There are few music therapy research studies with patients undergoing HSCT, which leaves many options for future research. It would be worthwhile to explore any short-term effects of music therapy on distress and QOL, as well as longitudinal effects on anxiety and mood. Optimal music therapy session duration and frequency during the pre-transplant hospitalization period remains unknown. Research opportunities exist during other phases of HSCT treatment, such as the out-patient pre-transplant period, duration of hospitalization, or post-transplant follow up. Understanding the effects of music therapy for patients suffering from Graft-Versus-Host Disease could also be beneficial as this is often debilitating and can be life-threatening. Finally, there is a need for qualitative music therapy studies with this patient population, as none currently exist but could provide additional insight for future research studies as well as clinical practice. / Music Therapy
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Improvement of adoptive T-cell therapy for CancerJin, Chuan January 2016 (has links)
Cancer immunotherapy has recently made remarkable clinical progress. Adoptive transfer of T-cells engineered with a chimeric antigen receptor (CAR) against CD19 has been successful in treatment of B-cell leukemia. Patient’s T-cells are isolated, activated, transduced with a vector encoding the CAR molecule and then expanded before being transferred back to the patient. However some obstacles restrict its success in solid tumors. This thesis explores different aspects to improve CAR T-cells therapy of cancer. Ex vivo expanded T-cells are usually sensitive to the harsh tumor microenvironment after reinfusion. We developed a novel expansion method for T-cells, named AEP, by using irradiated and preactivated allo-sensitized allogeneic lymphocytes (ASALs) and allogeneic mature dendritic cells (DCs). AEP-expanded T-cells exhibited better survival and cytotoxic efficacy under oxidative and immunosuppressive stress, compared to T-cells expanded with established procedures. Integrating retro/lentivirus (RV/LV) used for CAR expressions randomly integrate in the T-cell genome and has the potential risk of causing insertional mutagenesis. We developed a non-integrating lentiviral (NILV) vector containing a scaffold matrix attachment region (S/MAR) element (NILV-S/MAR) for T-cells transduction. NILV-S/MAR-engineered CAR T-cells display similar cytotoxicity to LV-engineered CAR T-cells with undetectable level of insertional event, which makes them safer than CAR T-cells used in the clinic today. CD19-CAR T-cells have so far been successful for B-cell leukemia but less successful for B-cell lymphomas, which present semi-solid structure with an immunosuppressive microenvironment. We have developed CAR T-cells armed with H. pylorineutrophil-activating protein (HP-NAP). HP-NAP is a major virulence factor and plays important role in T-helper type 1 (Th1) polarizing. NAP-CAR T-cells showed the ability to mature DCs, attract innate immune cells and increase secretion of Th1 cytokines and chemokines, which presumably leads to better CAR T-cell therapy for B-cell lymphoma. Allogeneic-DCs (alloDCs) were used to further alter tumor microenvironment. The premise relies on initiation of an allo-reactive immune response for cytokine and chemokines secretion, as well as stimulation of T-cell response by bringing in tumor-associated antigen. We demonstrated that alloDCs promote migration and activation of immune cells and prolong the survival of tumor-bearing mice by attracting T-cells to tumors and reverse the immune suppressive tumor microenvironment.
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Genotypová analýza lidského cytomegaloviru u pacientů po allogenní transplantaci kmenových buněk krvetvorby. / Genotypic analysis of human cytomegalovirus in the patients after allogeneic haematopoietic stem cell transplatation.Javornická, Tereza January 2014 (has links)
In patients after allogeneic haematopoietic stem cell transplantation (HSCT) is a human cytomegalovirus (CMV) one of the most important viral pathogens. Its detailed characteristic could provide information about the impact of each CMV genotype on overall survival of the patient, and some serious complications, such as graft versus host disease (GvHD). This thesis deals with retrospective genetic analysis of samples from 1877 patients transplanted at the Clinic of Pediatric Hematology and Oncology, University Hospital Motol and the Institute of Hematology and Blood Transfusion since 2002. DNA from biological samples (especially whole blood) was isolated kit Qiagen DNA Blood Mini or Qiagen DNA Mini and samples were prospectively detected presence of CMV DNA. Samples were subsequently stored at -20 řC. Genotyping was performed using real-time PCR technologies to the genes of 2 structural proteins glycoprotein B, glycoprotein H and using sequence specific primers and probes. In 1343 samples (71.6%) from 390 patients there was only one strain of CMV; in 256 (13.6%) samples from 113 patients have detected mixed infection caused by two or more strains of CMV. The most common genotype demonstrated in "single" infection was in pediatric and adult patients gB1/gH2 detected in 118 (28.4%) patients. Most...
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