Assuntos
COVID-19 , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva , Linfócitos TRESUMO
Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1-5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1-10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23-67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63-89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Aguda , Doença Crônica , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Nitrilas , Pirazóis/uso terapêutico , Pirimidinas , Estudos RetrospectivosRESUMO
Clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-SCT) from unrelated donors (URDs) approach those of matched related donor (MRD) transplants in patients with acute myeloid leukemia (AML). Yet, available data fail to account for differences in pretransplantation outcomes between these donor selection strategies. In this regard, URD allo-HSCT is associated with longer waiting times to transplantation, potentially resulting in higher probabilities of failure to reach transplant. We retrospectively analyzed 108 AML patients accepted for first allo-HSCT from the time of approval to proceed to transplant. Fifty-eight (54%) patients were initially allocated to MRD, while URD search was initiated in 50 (46%) patients. Time to transplant was longer in patients allocated to a URD when compared with patients assigned to an MRD (median 142 days versus 100 days; p < .001). Forty-three of 58 (74%) patients in the MRD group and 35 of 50 (70%) patients in the URD group underwent transplantation (odds ratio [OR], 1.22; pâ¯=â¯.63). Advanced disease status at the time of allo-HSCT approval was the only predictor of failure to reach transplantation in the multivariate analysis (OR, 4.78; pâ¯=â¯.001). Disease progression was the most common cause of failure to reach allo-HSCT (66.7%) in both the MRD and URD groups. With a median follow-up from transplantation of 14.5 (interquartile range, 5 to 29) months, the 2-year estimate of overall survival (OS) from allo-HSCT was 46% in the MRD group and 57% in the URD group (pâ¯=â¯.54). There were no differences in OS according to donor type allocation in the multivariate analysis (hazard ratio, 1.01; pâ¯=â¯.83). When including patients from the time of transplant approval, 2-year OS was 39% in the MRD group versus 42% in the URD group. Our study suggests that allocation of AML patients to URDs may result in comparable clinical outcomes to MRD assignment without a significant increase in the risk of failure to reach transplant.
Assuntos
Seleção do Doador , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Doadores não Relacionados , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Transplante HomólogoRESUMO
Introduction: Stem cell transplantation has been used for many years to treat haematological malignancies that could not be cured by other treatments. Despite this medical breakthrough, mortality rates remain high. Our purpose was to evaluate labour productivity losses associated with premature mortality due to blood cancer in recipients of stem cell transplantations. Methods: We collected primary data from the clinical histories of blood cancer patients who had undergone stem cell transplantation between 2006 and 2011 in two Spanish hospitals. We carried out a descriptive analysis and calculated the years of potential life lost and years of potential productive life lost. Labour productivity losses due to premature mortality were estimated using the Human Capital method. An alternative approach, the Friction Cost method, was used as part of the sensitivity analysis. Results: Our findings suggest that, in a population of 179 transplanted and deceased patients, males and people who die between the ages of 30 and 49 years generate higher labour productivity losses. The estimated loss amounts to over 31.4 million using the Human Capital method (480,152 using the Friction Cost method), which means an average of 185,855 per death. The highest labour productivity losses are produced by leukaemia. However, lymphoma generates the highest loss per death. Conclusions: Further efforts are needed to reduce premature mortality in blood cancer patients undergoing transplantations and reduce economic losses (AU)
Introducción: Durante muchos años el trasplante de células madre se ha usado para tratar neoplasias hematológicas que no podrían haber sido curadas mediante otras terapias. A pesar de este avance médico, la ratio de mortalidad es aún elevada. Nuestro objetivo es evaluar las pérdidas de productividad laboral por mortalidad prematura debido a una neoplasia hematológica en receptores de trasplante de células madre. Métodos: Se recogieron datos primarios de las historias clínicas de pacientes con neoplasia hematológica, trasplantados durante los años 2006 y 2011 en dos hospitales españoles. Se realizó un análisis descriptivo y se calcularon los años potenciales de vida y los años potenciales de vida laboral perdidos. Las pérdidas de productividad laboral se estimaron usando el método del Capital Humano. El método de los Costes de Fricción se empleó como parte del análisis de sensibilidad. Resultados: En una población de 179 pacientes trasplantados y fallecidos, se dan mayores pérdidas de productividad laboral en varones y en personas de edades comprendidas entre los 30 y 49 años. La pérdida estimada está por encima de 31.4 millones usando el método del Capital Humano (480,152 usando el método Costes Fricción), lo que significa una pérdida media de 185,855 por persona fallecida. Las mayores pérdidas globales son generadas por la leucemia. Sin embargo, el linfoma genera las mayores pérdidas por fallecimiento. Conclusiones: Mayores esfuerzos son necesarios para reducir la mortalidad prematura de pacientes trasplantados por neoplasia hematológica y reducir el impacto económico y social asociado a la misma (AU)
Assuntos
Humanos , Neoplasias Hematológicas/mortalidade , Mortalidade Prematura/tendências , Transplante de Células-Tronco , 33955 , Valor da VidaRESUMO
INTRODUCTION: Stem cell transplantation has been used for many years to treat haematological malignancies that could not be cured by other treatments. Despite this medical breakthrough, mortality rates remain high. Our purpose was to evaluate labour productivity losses associated with premature mortality due to blood cancer in recipients of stem cell transplantations. METHODS: We collected primary data from the clinical histories of blood cancer patients who had undergone stem cell transplantation between 2006 and 2011 in two Spanish hospitals. We carried out a descriptive analysis and calculated the years of potential life lost and years of potential productive life lost. Labour productivity losses due to premature mortality were estimated using the Human Capital method. An alternative approach, the Friction Cost method, was used as part of the sensitivity analysis. RESULTS: Our findings suggest that, in a population of 179 transplanted and deceased patients, males and people who die between the ages of 30 and 49 years generate higher labour productivity losses. The estimated loss amounts to over 31.4 million using the Human Capital method (480,152 using the Friction Cost method), which means an average of 185,855 per death. The highest labour productivity losses are produced by leukaemia. However, lymphoma generates the highest loss per death. CONCLUSIONS: Further efforts are needed to reduce premature mortality in blood cancer patients undergoing transplantations and reduce economic losses.
Assuntos
Eficiência , Neoplasias Hematológicas/mortalidade , Mortalidade Prematura , Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Efeitos Psicossociais da Doença , Feminino , Neoplasias Hematológicas/economia , Neoplasias Hematológicas/terapia , Humanos , Leucemia/economia , Leucemia/mortalidade , Leucemia/terapia , Expectativa de Vida , Linfoma/economia , Linfoma/mortalidade , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Espanha , Adulto JovemRESUMO
UNLABELLED: Burkitt lymphoma (BL) is highly FDG-avid even though its usefulness in the management of these patients is still controversial. AIM: We analyzed the role of positron emission tomography/computerized tomography (PET/CT) in staging newly diagnosed patients with BL and evaluating disease after first-line chemotherapy. METHODS: Fifty-two PET/CTs were performed in 32 patients (20 at diagnosis, 27 after treatment, five to monitor residual disease). Involved areas were retrospectively compared with those observed in contrast-enhanced CT. RESULTS: Discrepancies were found in 64.7% of patients for whom results of both tests at diagnosis were available (n = 17), most of them involving extranodal sites. Regarding response assessment, discrepancies were observed in 38% of patients with both tests (5/13): residual masses detected by CT with negative PET/CT. Of 27 patients with post-treatment PET/CT, 22 were in complete remission whereas one true-positive and four false-positive lesions (two nodal and two extranodal) were detected. With a median follow-up of 27 months, 22 patients with negative PET/CT did not relapse. Thus, negative predictive value (NPV) was 100%. With respect to positive predictive value (PPV), one of five patients with positive assays after treatment died due to progression while the remaining four had false-positive lesions. Nevertheless, for these four patients, mean SUVmax at nodal sites was 4.1 vs. 14.9 at diagnosis, while mean SUVmax at extranodal sites was 3.8 vs. 12.1. Thus, with a cutoff value for SUVmax < 66% of that observed at diagnosis, PPV was also 100%. CONCLUSION: More accurate staging can be achieved using PET/CT. NPV reaches 100%, and using a ΔSUV < 66%, a high PPV is also observed.
Assuntos
Linfoma de Burkitt/diagnóstico , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/mortalidade , Criança , Pré-Escolar , Gerenciamento Clínico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
The use of PET in patients with marginal zone B cell lymphoma (MZL) is controversial because of variability of fluorodeoxyglucose (FDG) avidity. We analyzed 40 PET/CT in 25 consecutive patients to compare its performance with CT at staging and as a first-line response assessment. Sensitivity of PET/CT and CT was 96 and 76%. Mean standard uptake value was 6.1, 6.9 and 3.4 (p = 0.3) in nodal, extranodal and splenic subtypes, respectively. Of 17 patients (extranodal: n = 9; nodal: n = 6; splenic subtype: n = 2) with both imaging tests available at diagnosis, 8 (47%) had more involved areas with PET/CT than with CT, 75% of which were extranodal lesions. PET/CT resulted in upstaging of five patients although treatment of only two of them was changed. Responses of 15 patients with post-treatment PET/CT were the following: 9 negative and 6 positive of which 3 were isolated residual lesions. Progression was documented in two of these three patients. Response was also assessed by CT in 11 patients. Discrepancies were found in three: Two were in complete remission by CT while PET/CT detected localized residual disease; another patient was in partial remission by CT, whereas PET/CT showed only one positive lesion. Two of these three patients relapsed. Patients with negative post-treatment PET/CT did not relapse. With a median follow-up of 50 months (10-152 months), 3-year overall survival was 100 and 80% for patients with negative and positive post-treatment PET/CT (p = 0.2). Three-year disease-free survival was 86%; the negative predictive value (NPV) was 100%, and the positive predictive value (PPV) was 83.3%. Although a larger number of patients will be required to further confirm these data, we can conclude that PET/CT is a useful imaging tool for both staging and response assessment in patients with nodal and extranodal MZL as a result of its high sensitivity, NPV and PPV.
Assuntos
Fluordesoxiglucose F18/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Micose Fungoide/tratamento farmacológico , Síndrome de Sézary/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bexaroteno , Ciclofosfamida/administração & dosagem , Humanos , Pentostatina/administração & dosagem , Tetra-Hidronaftalenos/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: Recombinant human granulocyte-colony-stimulating factor (G-CSF) is used to mobilize hematopoietic stem cells for both autologous and allogeneic hematopoietic stem cell transplantation. The recombinant products clinically available are lenograstim and filgrastim, which differ from a biologic point of view as well as from their economical impact. In this regard, some studies have shown different in vitro activities although clinical studies comparing both drugs in the allogeneic transplant setting are scanty. STUDY DESIGN AND METHODS: In the current study we compare the efficacy of lenograstim and filgrastim in terms of number of circulating CD34+ cells/µL during the fifth day of G-CSF administration, the number of days of apheresis required to obtain the target cell dose, the median of CD34+ cells collected on the first day of apheresis, or the median number of total CD34+ cells collected at the end of the procedure, in a series of 146 healthy donors undergoing hematopoietic stem cell mobilization for allogeneic transplantation. RESULTS: We observed that, using a comparable dose for the two products, no significant differences were observed between the two groups. CONCLUSION: In conclusion, the current retrospective study shows that lenograstim and filgrastim are similar in terms of efficacy for the mobilization of hematopoietic stem cells in healthy donors.
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Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Adolescente , Adulto , Idoso , Antígenos CD34/metabolismo , Criança , Feminino , Filgrastim , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lenograstim , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/farmacologia , Estudos Retrospectivos , Adulto JovemRESUMO
La prática del trasplante de células progenitoras para las enfermedades autoinmunitarias severas refractarias a terapia convencional parte de dos descubrimientos: los excelentes resultados de los experimentos animales, y las observaciones descubiertas en humanos con enfermedades coincidentes. Los datos de los estudios experimentales y en fase temprana I-II en algunos pacientes altamente seleccionados sugieren que la quimioterapia a dosis elevadas seguidas por trasplante autólogo de progenitores hematopoyéticos (TPH) puede detener la progresión de enfermedades autoinmunitarias (EAI) severas con un aceptable riesgo/beneficio. En este artículo revisamos los ensayos en fase II-III prospectivos, multicéntricos, aleatorizados en diferentes EAI. Por otra parte, el trasplante alogénico de células progenitoras para EAI está siendo cautelosamente explorado en protocolos actuales(AU)
The use of stem cell transplantation for severe autoimmune diseases refractory to conventional therapy arose from two discoveries: the excellent results of animal experiments, and serendipitous observations in human coincidental diseases. Experimental data and early phase I-II trials in highly selected patients suggest that highdose chemotherapy followed by autologous hematopoietic stem cell transplantation can arrest progression of severe autoimmune diseases with an acceptable risk/benefit ratio. The present article reviews the phase II-III prospective, multicenter, randomized trials that have been performed in distinct autoimmune diseases. In addition, allogeneic stem cell transplantation for autoimmune diseases is being cautiously explored in current protocols(AU)
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Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Doenças Autoimunes/terapia , Transplante Homólogo , Autoantígenos/análiseRESUMO
The use of stem cell transplantation for severe autoimmune diseases refractory to conventional therapy arose from two discoveries: the excellent results of animal experiments, and serendipitous observations in human coincidental diseases. Experimental data and early phase I-II trials in highly selected patients suggest that highdose chemotherapy followed by autologous hematopoietic stem cell transplantation can arrest progression of severe autoimmune diseases with an acceptable risk/benefit ratio. The present article reviews the phase II-III prospective, multicenter, randomized trials that have been performed in distinct autoimmunediseases. In addition, allogeneic stem cell transplantation for autoimmune diseases is being cautiously explored in current protocols.
RESUMO
No disponible
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Adulto , Feminino , Humanos , Transplante de Células-Tronco Hematopoéticas , Transplante Autólogo , Artrite ReumatoideRESUMO
No disponible