RESUMEN
INTRODUCTION:: Allogeneic hematopoietic stem cell transplantation (ASCT) representes a potentially curative approach for patients with relapsed or refractory acute myeloid leukemia (AML). We report the outcome of relapsed/refractory AML patients treated with ASCT. METHOD:: A retrospective cohort from 1994 to 2013 that included 61 patients with diagnosis of relapsed/refractory AML. Outcomes of interest were transplant-related mortality (TRM), incidence of acute and chronic graft-versus-host disease (GVHD), relapse incidence, progression-free survival (PFS) and overall survival (OS). Statistical significance was set at p<0.05. RESULTS:: The median age was 61 years (range 1 to 65). The cumulative incidence of 90 days, 1 year, and 3 years TRM were 60%, 26.7%, and 13.3%, respectively (p<0.001). The incidence of relapse was 21.7% at 1 year, 13% at 3 years, and 8.7% at 5 years. Median OS was estimated to be 8 months (95CI 3.266-12.734) and median PFS, 3 months (95CI 1.835-4.165). CONCLUSION:: In our cohort, TRM in first years after ASCT remains considerable, but ASCT in this setting seems to be a good choice for AML patients with active disease. However, novel approaches are needed to reduce TRM and relapse in this set of patients.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/mortalidad , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/cirugía , Adolescente , Adulto , Anciano , Niño , Preescolar , Enfermedad Crónica , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Determinación de Punto Final , Femenino , Enfermedad Injerto contra Huésped , Humanos , Lactante , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Estadísticas no Paramétricas , Factores de Tiempo , Trasplante Homólogo/métodos , Trasplante Homólogo/mortalidad , Resultado del Tratamiento , Adulto JovenRESUMEN
Summary Introduction: Allogeneic hematopoietic stem cell transplantation (ASCT) representes a potentially curative approach for patients with relapsed or refractory acute myeloid leukemia (AML). We report the outcome of relapsed/refractory AML patients treated with ASCT. Method: A retrospective cohort from 1994 to 2013 that included 61 patients with diagnosis of relapsed/refractory AML. Outcomes of interest were transplant-related mortality (TRM), incidence of acute and chronic graft-versus-host disease (GVHD), relapse incidence, progression-free survival (PFS) and overall survival (OS). Statistical significance was set at p<0.05. Results: The median age was 61 years (range 1 to 65). The cumulative incidence of 90 days, 1 year, and 3 years TRM were 60%, 26.7%, and 13.3%, respectively (p<0.001). The incidence of relapse was 21.7% at 1 year, 13% at 3 years, and 8.7% at 5 years. Median OS was estimated to be 8 months (95CI 3.266-12.734) and median PFS, 3 months (95CI 1.835-4.165). Conclusion: In our cohort, TRM in first years after ASCT remains considerable, but ASCT in this setting seems to be a good choice for AML patients with active disease. However, novel approaches are needed to reduce TRM and relapse in this set of patients.
Resumo Introdução: o transplante alogênico de células-tronco hematopoiéticas (TCTH-alo) representa uma abordagem potencialmente curativa para pacientes com leucemia mieloide aguda (LMA) recorrente ou refratária. Nosso trabalho apresenta o resultado de pacientes com recaída ou doença refratária tratados com TCTH-alo. Método: coorte retrospectiva incluindo 61 pacientes de 1994 a 2013 com diagnóstico de recidiva/LMA refratária. Os desfechos de interesse foram mortalidade relacionada ao transplante (MRT), incidência da doença aguda e crônica do enxerto contra hospedeiro (DECH), incidência de recaídas, sobrevida livre de progressão (PFS - progression-free survival) e sobrevida global (SG). A significância estatística foi considerada para p<0,05. Resultados: a média de idade foi de 61 anos (variação de 1 a 65). A incidência cumulativa de 90 dias, 1 ano e 3 anos de MRT foram de 60%, 26,7% e 13,3%, respectivamente (p<0,001). A incidência de recaída foi de 21,7% em 1 ano, 13% em 3 anos e 8,7% em 5 anos. A SG mediana foi estimada em 8 meses (IC 95% 3,266-12,734) e a mediana de PFS, em 3 meses (IC 95% 1,835-4,165). Conclusão: em nossa coorte, MRT no primeiro ano após o transplante permanece considerável, mas TCTH-alo nesse cenário parece ser uma boa opção para pacientes com LMA ativa. No entanto, novas abordagens são necessárias para reduzir MRT e recaída nesse conjunto de pacientes.
Asunto(s)
Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Adulto , Anciano , Adulto Joven , Leucemia Mieloide Aguda/cirugía , Leucemia Mieloide Aguda/mortalidad , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Recurrencia , Factores de Tiempo , Trasplante Homólogo/métodos , Trasplante Homólogo/mortalidad , Enfermedad Crónica , Estudios Retrospectivos , Resultado del Tratamiento , Estadísticas no Paramétricas , Supervivencia sin Enfermedad , Progresión de la Enfermedad , Determinación de Punto Final , Estimación de Kaplan-Meier , Enfermedad Injerto contra Huésped , Persona de Mediana EdadRESUMEN
Background: The intensity of conditioning chemotherapy and radiotherapy in hematopoietic stem cell transplantation (HSCT) varies according to several factors including the patients age, pre-existing conditions and performance status. Myeloablative conditioning (MA) increases transplant related mortality and reduces survival in older patients. Reduced intensity conditioning (RIC) is a good option for these patients. Aim: To report our experience with HSCT in patients of different ages with acute leukemia. Material and Methods: Retrospective analysis of 115 allogeneic HSCT performed in patients with acute myeloid or lymphoblastic leukemia. Results: We analyzed the cohort of patients in groups according to age at transplantation: younger than 40 years (n = 74), 41 to 50 years (n = 25) and older than 51 years of age (n = 16). Overall survival (OS), Disease free survival (DFS) and relapse at five years were similar in both groups of patients younger than 50 years (OS 40 and 44% respectively, DFS 38 and 42% respectively and relapse 40% and 34% respectively, p = NS). Patients over 51 years had a five years OS of 12%. However when we analyzed those patients by date and conditioning we found that patients who were treated with MA regimens in the first decade of the transplant program (before 2000) had lower OS compared to those treated after 2000 with RIC (five years OS 49% and 12% respectively, p < 0.01). No significant differences in terms of OS, recurrence or incidence of graft-versus-host disease were found when comparing groups under 40 years, between 41 and 50 years and older than 51 years treated only with RIC. Conclusions: RIC provides the possibility of HSCT in older patients with rates comparable to those obtained in younger patients successfully treated with MA conditioning.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Leucemia Mielomonocítica Aguda/cirugía , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Recurrencia , Trasplante Homólogo/métodos , Trasplante Homólogo/mortalidad , Análisis de Supervivencia , Estudios Retrospectivos , Factores de Edad , Trasplante de Células Madre Hematopoyéticas/mortalidad , Supervivencia sin Enfermedad , Acondicionamiento Pretrasplante/mortalidadRESUMEN
BACKGROUND: The intensity of conditioning chemotherapy and radiotherapy in hematopoietic stem cell transplantation (HSCT) varies according to several factors including the patients age, pre-existing conditions and performance status. Myeloablative conditioning (MA) increases transplant related mortality and reduces survival in older patients. Reduced intensity conditioning (RIC) is a good option for these patients. AIM: To report our experience with HSCT in patients of different ages with acute leukemia. MATERIAL AND METHODS: Retrospective analysis of 115 allogeneic HSCT performed in patients with acute myeloid or lymphoblastic leukemia. RESULTS: We analyzed the cohort of patients in groups according to age at transplantation: younger than 40 years (n = 74), 41 to 50 years (n = 25) and older than 51 years of age (n = 16). Overall survival (OS), Disease free survival (DFS) and relapse at five years were similar in both groups of patients younger than 50 years (OS 40 and 44% respectively, DFS 38 and 42% respectively and relapse 40% and 34% respectively, p = NS). Patients over 51 years had a five years OS of 12%. However when we analyzed those patients by date and conditioning we found that patients who were treated with MA regimens in the first decade of the transplant program (before 2000) had lower OS compared to those treated after 2000 with RIC (five years OS 49% and 12% respectively, p < 0.01). No significant differences in terms of OS, recurrence or incidence of graft-versus-host disease were found when comparing groups under 40 years, between 41 and 50 years and older than 51 years treated only with RIC. CONCLUSIONS: RIC provides the possibility of HSCT in older patients with rates comparable to those obtained in younger patients successfully treated with MA conditioning.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/cirugía , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Factores de Edad , Supervivencia sin Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Acondicionamiento Pretrasplante/mortalidad , Trasplante Homólogo/métodos , Trasplante Homólogo/mortalidad , Adulto JovenRESUMEN
OBJECTIVE: We analyzed the clinical evolution of pancreas allografts in simultaneous pancreas-kidney transplantation (SPKT) cases after asynchronous kidney allograft loss and kidney retransplantation at a single non-United States center. PATIENTS AND METHODS: We performed a retrospective analysis of 168 SPKT from December 2000 to June 2007. RESULTS: The 5-year kidney allograft survival rate was 71%. Excluding cases of death with a functioning graft after SPKT (n = 35; 74.4%), 12 kidney allografts were lost due to acute rejection (n = 7; 15%) or chronic allograft nephropathy (n = 5; 10.6%). Delayed graft function contributed to kidney allograft loss. Five of 12 patients underwent kidney retransplantation. Sixty percent of pancreas allografts were lost after this procedure, which was attributed to either the diabetogenic effects of the immunosuppressive regimen or to the perioperative stress. Oral glucose tolerance tests performed before kidney retransplantation identified patients with good pancreas allograft function versus those with intolerance on glucose tests who received reduced glucocorticoid doses. CONCLUSIONS: In SPKT, pancreas allograft function was seriously affected by kidney retransplantation. Oral glucose tolerance tests performed before kidney retransplantation were helpful to assess beta-cell function and suggest prescription of lower steroid doses to decrease the pancreas allograft dysfunction.
Asunto(s)
Trasplante de Riñón/patología , Trasplante de Páncreas/patología , Trasplante Homólogo/patología , Adolescente , Adulto , Brasil , Diabetes Mellitus/cirugía , Nefropatías Diabéticas/cirugía , Femenino , Hemoglobina Glucada/análisis , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Trasplante de Páncreas/inmunología , Reoperación , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante Homólogo/mortalidad , Insuficiencia del Tratamiento , Resultado del Tratamiento , Adulto JovenRESUMEN
CONTEXT AND OBJECTIVE: The increasing number of patients waiting for bone marrow transplantation in our service led to the implement of an early hospital discharge program with the intention of reducing the interval between diagnosis and transplantation. In this study we analyzed the results from early discharge, with outpatient care for patients with chronic myeloid leukemia who underwent allogeneic bone marrow transplantation. DESIGN AND SETTING: Retrospective study at the Bone Marrow Transplantation Unit of Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. METHODS: We compared clinical outcomes within 100 days post-transplantation, for 51 patients with chronic myeloid leukemia (CML) who received partially outpatient-based allogeneic hematopoietic stem cell transplantation, and the results were compared with a historical control group of 49 patients who received inpatient-based hematopoietic stem cell transplantation. RESULTS: There were significantly fewer days of hospitalization (p = 0.004), Pseudomonas-positive cultures (p = 0.006) and nausea and vomiting of grade 2-3 (p < 0.001) in the outpatient group. There were no significant differences in mortality between the groups and no deaths occurred within the first 48 days post-transplantation in the outpatient group. CONCLUSIONS: This partially outpatient-based hematopoietic stem cell transplantation program allowed an increased number of transplantations in our institution, in cases of CML and other diseases, since it reduced the median length of hospital stay without increasing morbidity and mortality.
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Trasplante de Médula Ósea , Leucemia Mieloide de Fase Crónica/cirugía , Alta del Paciente , Adolescente , Adulto , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/mortalidad , Trasplante de Médula Ósea/rehabilitación , Niño , Preescolar , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Pseudomonas aeruginosa/aislamiento & purificación , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/mortalidad , Resultado del Tratamiento , Vómitos/etiologíaRESUMEN
CONTEXT AND OBJECTIVE: The increasing number of patients waiting for bone marrow transplantation in our service led to the implement of an early hospital discharge program with the intention of reducing the interval between diagnosis and transplantation. In this study we analyzed the results from early discharge, with outpatient care for patients with chronic myeloid leukemia who underwent allogeneic bone marrow transplantation. DESIGN AND SETTING: Retrospective study at the Bone Marrow Transplantation Unit of Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. METHODS: We compared clinical outcomes within 100 days post-transplantation, for 51 patients with chronic myeloid leukemia (CML) who received partially outpatient-based allogeneic hematopoietic stem cell transplantation, and the results were compared with a historical control group of 49 patients who received inpatient-based hematopoietic stem cell transplantation. RESULTS: There were significantly fewer days of hospitalization (p = 0.004), Pseudomonas-positive cultures (p = 0.006) and nausea and vomiting of grade 2-3 (p < 0.001) in the outpatient group. There were no significant differences in mortality between the groups and no deaths occurred within the first 48 days post-transplantation in the outpatient group. CONCLUSIONS: This partially outpatient-based hematopoietic stem cell transplantation program allowed an increased number of transplantations in our institution, in cases of CML and other diseases, since it reduced the median length of hospital stay without increasing morbidity and mortality.
CONTEXTO E OBJETIVO: O número crescente de pacientes com indicação de transplante de medula óssea levou à implantação da alta hospitalar precoce em nosso serviço, com o intuito de reduzir o intervalo entre o diagnóstico e o transplante. Neste trabalho, avaliamos os resultados da alta precoce, com acompanhamento ambulatorial dos pacientes submetidos ao transplante de medula óssea alogênico portadores de leucemia mielóide crônica. TIPO E ESTUDO E LOCAL: Estudo retrospectivo, realizado no Serviço de Transplante de Medula Ossea do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Foram avaliados os resultados do transplante de medula óssea alogênico, de doadores aparentados, até o dia 100 pós-transplante, de 51 pacientes portadores de leucemia mielóide crônica que receberam alta precoce, antes da pega medular. Os resultados foram comparados com o controle histórico constituído por 49 pacientes que receberam alta somente após a pega medular. RESULTADOS: Houve significativamente menos dias de hospitalização (p = 0,004), culturas positivas para Pseudomonas sp. (p = 0,006) e náusea e vômitos graus 2-3 (p < 0,001) no grupo de alta precoce. Não houve diferença significativa entre os grupos quanto à mortalidade e não ocorreu nenhum óbito até o dia 48 pós-transplante no grupo de alta precoce. CONCLUSÕES: O programa de alta precoce permitiu aumento do número de transplantes em leucemia mielóide crônica e outras doenças em nosso serviço, com redução do número de dias de internação hospitalar sem aumento da morbidade ou da mortalidade.
Asunto(s)
Adolescente , Adulto , Niño , Preescolar , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Médula Ósea , Leucemia Mieloide de Fase Crónica/cirugía , Alta del Paciente , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/mortalidad , Trasplante de Médula Ósea/rehabilitación , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Tiempo de Internación/estadística & datos numéricos , Pseudomonas aeruginosa/aislamiento & purificación , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/mortalidad , Resultado del Tratamiento , Vómitos/etiologíaRESUMEN
Foi realizado o estudo comparativo do efeito imunossupressor de três tratamentos, utilizando-se a combinação de ciclosporina A e metilprednisolona, um ciclo curto e um ciclo longo de FK506 por 12 semanas no transplante de membro inferior entre ratos Sprague-Dawley e Wistar. O tempo médio de instalação da rejeição foi de 6,6 dias nos animais que não receberam imunossupressão, 34 dias nos que receberam ciclosporina A e metilprednisolona, 58 dias para os que receberam FK506 em ciclo curto e 77.75 para os que receberam FK506 em ciclo longo. Os grupos que receberam FK506 apresentaram tempo prolongado de sobrevivência do transplante. /The immunosuppressive effect of combined therapy using cyclosporine A and metilprednisolone, a short course and a long course of FK506 for 12 weeks in a Sprague-Dawley/Wistar rat limb allotransplantation model was tested. 36 right hindlimb transplantations were performed. Median time for onset of rejection was 6,6 days in animals without immunosuppression, 34 days receiving cyclosporine A and metilprednisolone, 58 days receiving FK506 short course and 77.75 days in the long course group. The FK506 groups presented survival time of the allograft longer than the cyclosporine A and metilprednisolone, and the FK506 long course was the most efficient among the three treatments preventing rejection. The mortality of the animal was increased in the cyclosporine A and metilprednisolone compared to the FK506 groups...
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Animales , Masculino , Adulto , Miembro Posterior/trasplante , Trasplante Homólogo/estadística & datos numéricos , Ciclosporina/efectos adversos , Ciclosporina/uso terapéutico , Modelos Animales de Enfermedad , Hemisuccinato de Metilprednisolona/uso terapéutico , Ratas Sprague-Dawley , Ratas Wistar , Rechazo de Injerto/tratamiento farmacológico , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/mortalidadRESUMEN
Using nonmyeloablative, immunosuppressive, fludarabine (FLU)-based conditioning regimens, we have performed allogeneic peripheral blood stem cell transplants in 26 patients (8 with chronic myelogenous leukemia, 6 with acute myelogenous leukemia, 10 with acute lymphoblastic leukemia, 1 with myelodysplasia, and 1 with thalassemia major). Conditioning consisted of FLU/busulphan/cyclophosphamide/cyclosporin-A (CyA)/methotrexate, or FLU/melphalan/CyA/methotrexate. The median granulocyte recovery time to 0.5 x 10(9)/l was 11 days, whereas the median platelet recovery time to 20 x 10(9)/l was 12 days. Twelve patients did not need red blood cell transfusions, and 8 did not need platelet transfusions. In 21 individuals (81%), the procedure could be completed fully on an outpatient basis. Follow-up times range between 30 and 600 days: one patient failed to engraft and recovered endogenous hemopoiesis; six out of 26 patients developed acute graft-versus-host disease (GVHD) whereas 7/22 developed chronic GVHD. Twelve patients (46%) have died, nine of them with a relapsing disease and three with GVHD; median post-transplant survival (SV) was 300 days, whereas the 12-month SV was 42%. The 100-day mortality was 3.8% and the transplant-related mortality was 11.5%. This procedure is substantially less costly than its counterpart, using in-hospital myeloablative conditioning regimens, and it may represent another approach in the management of patients requiring an allogeneic stem cell transplant.
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Atención Ambulatoria/estadística & datos numéricos , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Inmunosupresores/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/estadística & datos numéricos , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico , Adolescente , Adulto , Atención Ambulatoria/economía , Busulfano/uso terapéutico , Niño , Ciclofosfamida/uso terapéutico , Ciclosporina/uso terapéutico , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/economía , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Leucemia/mortalidad , Leucemia/terapia , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Defectos del Tubo Neural/terapia , Evaluación de Programas y Proyectos de Salud , Recurrencia , Análisis de Supervivencia , Talasemia/terapia , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/economía , Trasplante Homólogo/economía , Trasplante Homólogo/métodos , Trasplante Homólogo/mortalidad , Resultado del TratamientoRESUMEN
The rejection of allotransplantation of epigastric microsurgical flaps and the effect of immunosuppression have been studied in 58 rats. Three sets of experiments were planned: (1) Wistar Furth isogenic donors and receptors (control set); (2) Brown Norway donors and Wistar Furth receptors (rejection set); and (3) Brown Norway donors and Wistar Furth immunosuppressed receptors (cyclosporin A set). Cyclosporin A (10 mg/kg/d) treated rats had a transplantation survival rate of up to 30 days: 83.3% among isogenic animals and 60% among allogeneic. There was 100% rejection by the 9th day after the transplantation in allogeneic non-immunosuppressed rats. Biopsies embedded with historesin were taken from the flap and normal contralateral skin (used as control) on the 3rd, 7th, 15th, and 30th days after the surgery. A quantitative study of infiltrating lymphocytes in the flaps, with and without cyclosporin A, was done by evaluating the local inflammatory infiltrate. A significant increase in the number of lymphocytes among the rejection and immunosuppressed groups was seen, as compared to the isogenic set. Local lymphocytosis in allogeneic non-immunosuppressed transplantations reached its highest level on the 3rd day after surgery, before gross findings of rejection, which could only be seen by naked eye on the 5th or 6th day. Therefore, we conclude that cyclosporin A is effective in preserving allogenic transplantation in rats. Biopsies of transplanted areas may contribute to earlier diagnosis of the need for immunosuppressive therapy.
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Ciclosporina/uso terapéutico , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Colgajos Quirúrgicos , Trasplante Homólogo/métodos , Animales , Método Doble Ciego , Arterias Epigástricas/trasplante , Rechazo de Injerto/patología , Ratas , Ratas Endogámicas BN , Ratas Endogámicas WF , Colgajos Quirúrgicos/irrigación sanguínea , Trasplante Homólogo/mortalidadRESUMEN
The rejection of allotransplantation of epigastric microsurgical flaps and the effect of immunosuppression have been studied in 58 rats. Three sets of experiments were planned: (1) Wistar Furth isogenic donors and receptors (control set); (2) Brown Norway donors and Wistar Furth receptors (rejection set); and (3) Brown Norway donors and Wistar Furth immunosuppressed receptors (cyclosporin A set). Cyclosporin A (10 mg/kg/d) treated rats had a transplantation survival rate of up to 30 days: 83.3 percent among isogenic animals and 60 percent among allogeneic. There was 100 percent rejection by the 9th day after the transplantation in allogeneic non-immunosuppressed rats. Biopsies embedded with historesin were taken from the flap and normal contralateral skin (used as control) on the 3rd, 7th, 15th, and 30th days after the surgery. A quantitative study of infiltrating lymphocytes in the flaps, with and without cyclosporin A, was done by evaluating the local inflammatory infiltrate. A significant increase in the number of lymphocytes among the rejection and immunosuppressed groups was seen, as compared to the isogenic set. Local lymphocytosis in allogeneic non-immunosuppressed transplantations reached its highest level on the 3rd day after surgery, before gross findings of rejection, which could only be seen by naked eye on the 5th or 6th day. Therefore, we conclude that cyclosporin A is effective in preserving allogenic transplantation in rats. Biopsies of transplanted areas may contribute to earlier diagnosis of the need for immunosuppressive therapy.
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Animales , Ratas , Ciclosporina/uso terapéutico , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Colgajos Quirúrgicos/irrigación sanguínea , Trasplante Homólogo/métodos , Biopsia , Método Doble Ciego , Arterias Epigástricas/trasplante , Rechazo de Injerto/patología , Microcirugia , Periodo Posoperatorio , Ratas Endogámicas BN , Ratas Endogámicas WF , Estadísticas no Paramétricas , Tasa de Supervivencia , Trasplante Homólogo/mortalidad , Trasplante IsogénicoRESUMEN
OBJETIVO: Analisar as complicaçöes pós-operatórias dos transplantes microcirúrgicos alógenos de membro, bem como determinar fatores associados à toxicidade das drogas. MÉTODO. O estudo foi realizado entre combinaçöes de maior histocompatibilidade, utilizando 39 ratos Brown-Norway (doadores) e 78 ratos Fischer 344 (receptores), submetidos ao transplante microcirúrgico alógenode membro e ao tratamento imunossupressor com ciclosporina e RS-61443. RESULTADOS. Um (1/78: 1,28 por cento) foi sacrificado devido à trombose; dois (2/78:2,56 por cento) por enterite; um (1/78:1,28 por cento) devido à autofagia e oito (8/78:10,42 por cento) morreram por causa indeterminada. CONCLUSÄO. Dentre os 78 (78/78:100 por cento) ratos submetidos ao transplante alógeno microcirúrgico de membro, 12 (15,5 por cento) ratos morreram ou foram sacrificados devido às complicaçöes pós-operatórias agudas näo relacionadas à rejeiçäo, toxicidade dos agentes imunossupressores ou infecçäo oportunista
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Animales , Masculino , Ratas , Ciclosporina/administración & dosificación , Miembro Posterior/trasplante , Inmunosupresores/administración & dosificación , Ácido Micofenólico/análogos & derivados , Histocompatibilidad , Microcirugia , Ácido Micofenólico/administración & dosificación , Complicaciones Posoperatorias , Ratas Endogámicas BN , Trasplante Autólogo , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/mortalidadRESUMEN
PURPOSE: To analyze the composite tissue vascularized allotransplantation post operative complications and to identify factors associated with agents toxicity. METHOD: The study was done across a strong histocompatibility barrier using 39 Brown-Norway rats as donors and 78 Fischer 344 as hindlimb allotransplantation recipients treated with cyclosporine and RS-61443. RESULTS: 1 (1/78: 1.28%) was eliminated owing to thrombosis; 2 (2/78: 2.56%) owing to enteritis; 1 (1/78: 1.28%) owing to autophagia and 8 (8/78: 10.42%) died owing to undiscovered cause. CONCLUSION: Among 78 (78/78: 100%) rat limb vascularized allotransplantations, 12 (15.5%) rats died or were eliminated because of acute postoperative complications that were not related to rejection, to immunosuppressive toxicity or to opportunistic infection.
Asunto(s)
Ciclosporina/administración & dosificación , Miembro Posterior/trasplante , Inmunosupresores/administración & dosificación , Ácido Micofenólico/análogos & derivados , Complicaciones Posoperatorias/etiología , Animales , Masculino , Microcirugia , Ácido Micofenólico/administración & dosificación , Ratas , Ratas Endogámicas BN , Ratas Endogámicas F344 , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/mortalidadRESUMEN
We have treated 28 patients (pts) with malignant hematological diseases with allogenic bone marrow transplantation (BMT). 18 pts had acute lymphoblastic (ALL) and non lymphoblastic leukemia (ANLL), 5 chronic myeloid leukemia (CML), 2 severe aplastic anemia (SAA), 1 myelodisplasia, 1 Fanconi's anemia and 1 advanced Non Hodgkin's lymphoma. All but three received the graft from HLA identical sibling donors. We used conditioning with total body irradiation and chemotherapy (cyclophosphamide, cytarabine and etoposide) in 17 pts and chemotherapy alone in 11.24 pts had a full hematological recovery 18 to 25 days post BMT. 15 pts died after BMT as a consequence of toxicity or early infection (4), graft failure (2), graft vesus host disease (4) or relapse (5). Actuarial event free survival for the group with favorable prognosis (SAA, ALL and ANLL in first or second remission and CML in chronic phase) is 57 percent at 36 months. Allogeneic BMT is an effective and feasing therapeutic procedure for selected patients with hematological malignancies
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Adolescente , Adulto , Trasplante de Médula Ósea , Enfermedades Hematológicas/cirugía , Aislamiento de Pacientes , Complicaciones Posoperatorias/tratamiento farmacológico , Trasplante Homólogo , Trasplante Homólogo/mortalidad , Leucemia/terapia , Defectos del Tubo Neural/terapia , Anemia Aplásica/terapia , Premedicación/métodos , Reacción Huésped-Injerto/inmunología , Sistema Hematopoyético/fisiopatología , Transfusión Sanguínea/métodosRESUMEN
No período de setembro de 1984 a dezembro de 1992, 145 pacientes selecionados foram submetidos a substituiçao isolada de valva mitral, utilizando-se valvas aórticas de cadáver obtidas durante autopsia, processadas em glutaraldeído e montadas em suporte flexível de Celcon recoberto com Dacron. Os pacientes apresentavam idade média de 22,5 anos, variando de 5 a 77 anos e 79 (54,5 por cento) pacientes tinham idade igual ou inferior a 15 anos. Operaçoes cardíacas prévias haviam sido realizadas em 26 (18 por cento) pacientes e 20 (13,8 por cento) deles eram portadores de biopróteses de porco, pericárdio bovino ou dura-máter calcificadas. A mortalidade hospitalar (30 dias) foi de 3 (2,1 por cento) pacientes. A evoluçao tardia coletou 709 pacientes-ano de seguimento total, correspondendo a um seguimento médio de 5 anos por paciente e máximo de 9 anos e 5 meses. Segmento completo foi obtido em 130 (91,5 por cento) pacientes e parcial nos 12 pacientes restantes. Complicaçoes relacionadas ao aloenxerto ocorreram em 48 pacientes, incluindo a fibrocalcificaçao, tromboembolismo, endocardite e escape para-valvar, correspondendo a uma incidência de 6,8 mais ou menos 0,9 por cento por paciente-ano. A fibrocalcificaçao levando a disfunçao valvar representou a principal complicaçao, presente em 37 pacientes com incidência de 5, 2 por cento mais ou menos 0,8 por cento por paciente-ano. Todos os casos de calcificaçao ocorreram em pacientes com idade igual ou inferior a 15 anos, com um intervalo médio entre o implante valvar e a calcificaçao de 46 meses, variando de 14 a 100 meses. Reoperaçoes foram realizadas em 44 pacientes com substituiçao da alobioprótese em 39, representando uma incidência de reoperaçoes de 6,3 por cento mais ou menos 0,9 por cento por paciente-ano e uma incidência de substituiçao da alobioprótese de 5,5 por cento mais ou menos 0,9 por cento por paciente-ano. A principal causa da reoperaçao foi a calcificaçao, presente em 36 aloenxertos, sendo as outras caudas representadas pela endocardite, escape para-valvar e insuficiência aórtica em valva natural. Ocorreram 15 óbitos tardios, representando uma mortalidade tardia de 2,1 por cento mais ou menos 0,5 por cento por paciente-ano, porém apenas 3 óbitos estavam relacionados diretamente à alobioprótese, 10 à doença cardíaca (ICC, miocardiopatia e morte súbita) e 2 a outras causas (tuberculose e diabetes). A sobrevida atuarial em 10 anos foi de 82,9 por cento mais ou menos 4,8 por cento. A sobrevida atuarial em 10 anos livre de disfunçao valvar devido a fibrocalcificaçao foi de 62,1 por cento mias ou menos 8,4 por cento sendo de 100 por cento para pacientes acima de 15 anos e 34,2 por cento mais ou menos 11,2 para pacientes com idade igual ou inferior a 15 anos. Embora a fibrocalcificaçao tenha representado a principal complicaçao tardia ocorrida com as alobiopróteses levando a disfunçao valvar e representando a principal indicaçao para reoperaçoes no grupo pediátrico, sua incidência foi significativamente menor que a incidência relatada na literatura para pacientes pediátricos portadores de xenobiopróteses.
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Bioprótesis/mortalidad , Prótesis Valvulares Cardíacas/mortalidad , Insuficiencia de la Válvula Mitral/mortalidad , Trasplante Homólogo/mortalidad , Brasil/epidemiología , Insuficiencia de la Válvula Mitral/cirugía , Complicaciones Posoperatorias , Reoperación , Sobrevivientes , Tasa de SupervivenciaRESUMEN
Se realizaron 21 transplantes pulmonares unilaterales en perros, divididos en tres grupos: 1) autotransplante sin sobrevida, 2) autotransplante y 3) homotransplante. Se anastomosaron la arteria pulmonar, una porción de pared de aurícula izquierda con las venas pulmonares y el bronquio, cuya sutura fue cubierta con epiplón en 4 animales, con grasa pericárdica en 2 y no fue cubierta en 3. Los hallasgos post-operatorios se corresponden en general con los mencionados en la literatura. No se observó relación entre la cicatrización de la sutura bronquial y el uso o tipo de cobertura utilizada para la misma
Asunto(s)
Animales de Laboratorio , Perros , Trasplante de Pulmón/veterinaria , Anestesia Endotraqueal , Ketamina , Trasplante de Pulmón/efectos adversos , Trasplante Autólogo/efectos adversos , Trasplante Autólogo/mortalidad , Trasplante Autólogo/veterinaria , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/mortalidad , Trasplante Homólogo/veterinariaRESUMEN
Se realizaron 21 transplantes pulmonares unilaterales en perros, divididos en tres grupos: 1) autotransplante sin sobrevida, 2) autotransplante y 3) homotransplante. Se anastomosaron la arteria pulmonar, una porción de pared de aurícula izquierda con las venas pulmonares y el bronquio, cuya sutura fue cubierta con epiplón en 4 animales, con grasa pericárdica en 2 y no fue cubierta en 3. Los hallasgos post-operatorios se corresponden en general con los mencionados en la literatura. No se observó relación entre la cicatrización de la sutura bronquial y el uso o tipo de cobertura utilizada para la misma
Asunto(s)
Trasplante de Pulmón/veterinaria , Animales de Laboratorio , Perros , Trasplante de Pulmón/efectos adversos , Trasplante Autólogo/efectos adversos , Trasplante Autólogo/mortalidad , Trasplante Autólogo/veterinaria , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/mortalidad , Trasplante Homólogo/veterinaria , Anestesia Endotraqueal , KetaminaRESUMEN
We analyzed data from 93 patients who received a kidney graft from their parents; 55 were transplanted with a kidney from their mothers (Mat.) and thirty-eight from their fathers (Pat.) The Pat. group has shown a better graft and patient survival as well as long-term renal function when compared with the Mat. group. This pattern was more evident with time. Long-term graft function assessed by creatinine levels also showed differences between the groups, favoring the Pat. group. The results are interesting since recent reports have claimed a tolerance developed by the individual to noninherited HLA antigens of their mother.
Asunto(s)
Intercambio Materno-Fetal/inmunología , Trasplante Homólogo/inmunología , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Supervivencia de Injerto/inmunología , Humanos , Tolerancia Inmunológica , Trasplante de Riñón/inmunología , Persona de Mediana Edad , Embarazo , Tasa de Supervivencia , Donantes de Tejidos , Trasplante Homólogo/mortalidadAsunto(s)
Corticoesteroides/uso terapéutico , Ciclosporinas/uso terapéutico , Trasplante de Hígado , Adolescente , Corticoesteroides/administración & dosificación , Adulto , Anciano , Neoplasias de los Conductos Biliares/cirugía , Niño , Preescolar , Colorado , Ciclosporinas/administración & dosificación , Quimioterapia Combinada , Humanos , Lactante , Recién Nacido , Hepatopatías/cirugía , Neoplasias Hepáticas/cirugía , Persona de Mediana Edad , Pennsylvania , Complicaciones Posoperatorias/mortalidad , Texas , Trasplante Homólogo/mortalidadRESUMEN
Se presenta la experiencia con los primeros 4 pacientes sometidos a trasplante cardiaco en Colombia y se hace una revision somera de la historia, indicaciones y manejo de la inmunosupresion de las infecciones (citomegalovirus y aspergilosis pulmonar) que fueron causa de la muerte del segundo paciente y que son consecuencia directa del tratamiento inmunosupresor, que inicialmente es intenso para evitar el rechazo. El cuarto paciente murio en forma sorpresiva al 9o dia post operatorio, posiblemente por efecto neurotoxico asociado a la administracion de ciclosporina. Los otros dos pacientes con 10 y 2 meses de trasplante, estan en perfectas condiciones. El primero goza de vida activa y utiliza la ciclosporina A y prednisona, como regimen inmunosupresivo. El tercero toma ciclosporina A, azatioprina y prednisona y se encuentra en un proceso normal de recuperacion y rehabilitacion.