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1.
Lancet Haematol ; 7(2): e100-e111, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31958417

RESUMO

BACKGROUND: Previous trials testing prevention strategies for chronic graft versus host disease (GVHD) have measured its cumulative incidence. In this trial of anti-thymocyte globulin, we measured treatment-independence at a long-term timepoint as the primary endpoint. METHODS: This was a randomised, open-label, multicentre, phase 3 trial done at ten centres in Canada and one in Australia. Eligible patients had a haematological malignancy (leukaemia, myelodysplastic syndrome, or lymphoma), were between 16 and 70 years of age, eligible for transplantation with a Karnofsky score of at least 60, and received an unrelated donor (fully matched or one-locus mismatched at HLA-A, HLA-B, HLA-C, or DRB1 loci) graft following myeloablative or non-myeloablative-reduced intensity conditioning. Patients were randomly assigned to receive anti-thymocyte globulin 4·5 mg/kg plus standard GVHD prophylaxis (cyclosporine or tacrolimus plus methotrexate or mycophenolate) or standard GVHD prophylaxis alone. The primary endpoint, freedom from immunosuppressive therapy without resumption at 12 months, was previously reported. Here we report on the prespecified 24-month analysis. Analyses were per-protocol, excluding those patients who did not proceed to transplantation. This trial is registered as ISRCTN 29899028 and NCT01217723, status completed. FINDINGS: Between June 9, 2010, and July 8, 2013, we recruited and randomly assigned 203 eligible patients to receive anti-thymocyte globulin (n=101) or no additional treatment (n=102) along with standard GVHD prophylaxis. 7 (3%) patients did not receive a transplant and were excluded from the analysis. 38 (38%) of 99 evaluable patients in the anti-thymocyte globulin plus GVHD prophylaxis group were free from immunosuppressive therapy at 24 months compared with 18 (19%) of 97 patients in the standard GVHD prophylaxis group (adjusted odds ratio [OR] 3·49 [95% CI 1·60­7·60]; p=0·0016). At 24 months, the cumulative incidence of relapse was 16·3% (95% CI 8·9­23·7) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 17·5 (9·9­25·1) in the standard GVHD prophylaxis group (p=0·73) and non-relapse mortality was 21·2% (95% CI 13·2­29·2) versus 31·3% (21·9­40·7; p=0·15). The cumulative incidence of chronic GVHD at 24 months was 26·3% (95% CI 17·5­35·1) in the anti-thymocyte globulin group and 41·3% (31·3­51·3) in the standard GVHD prophylaxis group (p=0·032). Overall survival at 24 months was 70·6% (95% CI 60·6­78·6) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 53·3% (42·8­62·8) in the standard GVHD prophylaxis group (adjusted hazard ratio [HR] 0·56, 95% CI [0·35­0·90]; p=0·017). Symptoms of chronic GVHD by the Lee Scale were more prevalent in the standard GVHD prophylaxis group, with scores of 13·27 (SD 10·94) in the anti-thymocyte globulin plus GVHD prophylaxis group and 20·38 (SD 14·68) in the standard GVHD prophylaxis group (p=0·040). Depressive symptoms were more prominent in the standard GVHD prophylaxis group, the mean Center for Epidemiological Studies Depression scale (CES-D) scores were 10·40 (SD 9·88) in the anti-thymocyte globulin group and 14·62 (SD 12·26) in the standard GVHD prophylaxis group (p=0·034). Serious adverse events (CTCAE grade 4 or 5) occurred in 38 (38%) patients in the anti-thymocyte globulin group and in 49 (51%) in the standard GVHD prophylaxis group, the most common being infection and GVHD. One patient in the anti-thymocyte globulin plus GVHD prophylaxis group died of Epstein-Barr virus hepatitis, but no deaths were attributable to anti-thymocyte globulin. INTERPRETATION: The results of this prespecified 24-month analysis suggest that pretreatment with anti-thymocyte globulin provides clinically meaningful benefits when added to standard GVHD prophylaxis in patients undergoing unrelated donor transplantation, including decreases in use of immunosuppressive therapy, chronic GVHD and its symptoms, depressive symptoms, and improved overall survival. Anti-thymocyte globulin should be included in the preparative regimens of patients with haematological malignancies selected for unrelated donor transplantation. FUNDING: Canadian Institutes of Health Research and Sanofi.


Assuntos
Soro Antilinfocitário/uso terapêutico , Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Imunossupressores/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Adolescente , Adulto , Idoso , Ciclosporina/administração & dosagem , Ciclosporina/uso terapêutico , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressores/administração & dosagem , Estimativa de Kaplan-Meier , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Linfócitos T/imunologia , Tacrolimo/administração & dosagem , Tacrolimo/uso terapêutico , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Doadores não Relacionados , Adulto Jovem
2.
Chemotherapy ; 64(2): 57-61, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31484176

RESUMO

Invasive fungal infections are one of the main infectious complications in allogeneic stem cell transplantation (SCT). Triazoles (voriconazole, posaconazole) are the main prophylactic and therapeutic options for the treatment of invasive aspergillosis. However, pharmacological interactions and hepatotoxicity limit its use. Isavuconazole (ISV) is a recently approved azole with a promising interaction and safety profile. We present a case with invasive aspergillosis in the post-allogeneic SCT setting in a critically ill patient with severe multiorgan failure due to veno-occlusive disease. The patient was treated with ISV and B amphotericin during severe kidney and liver failure and multiple immunosuppressants, without significant drug-related toxicity and with favorable outcome. The interaction and safety profile of ISV is discussed along the reported experience. ISV can be an effective salvage therapy even in complex clinical situations with multiple potential interactions.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/terapia , Transplante de Células-Tronco Hematopoéticas , Nitrilos/uso terapêutico , Piridinas/uso terapêutico , Triazóis/uso terapêutico , Adulto , Aspergilose/tratamento farmacológico , Aspergillus fumigatus/genética , Aspergillus fumigatus/isolamento & purificação , DNA Fúngico/metabolismo , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Tórax/diagnóstico por imagem , Transplante Homólogo/efeitos adversos
3.
Transplant Proc ; 51(8): 2845-2847, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31471013

RESUMO

BACKGROUND: Several surgical strategies have been introduced for spontaneous kidney rupture. Herein, we report on a case in which temporary artery clamping with hemostatic materials was performed. CASE PRESENTATION: A 52-year-old man underwent renal transplant from a living donor (his 20-year-old son). Spontaneous allograft rupture occurred 6 days after transplant. He developed severe abdominal pain, hypotension, and mental changes. His blood hemoglobin level was 3.6 g/dL, which was indicative of severe hemorrhage. Immediate re-exploration revealed a large hematoma in the iliac fossa and that the renal allograft had ruptured, with multiple fracture lines on the entire surface. Because of diffuse surface rupture, surgical suture was not attempted. For manual compressive hemostasis, temporary artery clamping with hemostatic materials was performed. First, we identified the graft artery for temporary clamping, similar to the method in partial nephrectomy. Second, at the time of temporary clamping, the hemostatic matrix was sprayed on the surface of the renal graft. Third, we compressed the whole renal parenchyma with both hands and a dry pad for 5 minutes. After removing the clamp, successful bleeding control was confirmed. Finally, the graft was wrapped with oxidized cellulose. Renal biopsy in the operating room revealed the cause of rupture as acute rejection type IIB. CONCLUSION: Spontaneous renal allograft rupture is a rare but serious complication. When surgical suture is not appropriate for the repair of the ruptured allograft, temporary artery clamping with hemostatic materials can be considered an alternative.


Assuntos
Hematoma/tratamento farmacológico , Hemostáticos/uso terapêutico , Nefropatias/cirurgia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/cirurgia , Ruptura Espontânea/cirurgia , Constrição , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo/efeitos adversos
4.
Transplant Proc ; 51(9): 3067-3069, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31371216

RESUMO

Post-transplant lymphoproliferative disorder (PTLD) can be Epstein-Barr virus (EBV)-positive lymphoproliferations occurring in the first year after transplantation or EBV-negative lymphoma occurring many years after transplantation. Both B-cell and T-cell type of PTLD are described in the literature. In the gastrointestinal tract, the small and large intestine are the common sites of involvement. PTLD of the appendix is a lesser-known entity and cases described previously presented clinically as acute appendicitis. We report a case of EBV-negative B-cell PTLD of the appendix mimicking acute appendicitis in a live young renal allograft recipient 7 years after transplantation.


Assuntos
Neoplasias do Apêndice/imunologia , Transplante de Rim/efeitos adversos , Linfoma Difuso de Grandes Células B/imunologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/imunologia , Adulto , Neoplasias do Apêndice/diagnóstico , Apendicite/diagnóstico , Diagnóstico Diferencial , Humanos , Hospedeiro Imunocomprometido , Masculino , Transplante Homólogo/efeitos adversos
5.
Nat Commun ; 10(1): 3495, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375697

RESUMO

Immune tolerance to allografts has been pursued for decades as an important goal in transplantation. Administration of apoptotic donor splenocytes effectively induces antigen-specific tolerance to allografts in murine studies. Here we show that two peritransplant infusions of apoptotic donor leukocytes under short-term immunotherapy with antagonistic anti-CD40 antibody 2C10R4, rapamycin, soluble tumor necrosis factor receptor and anti-interleukin 6 receptor antibody induce long-term (≥1 year) tolerance to islet allografts in 5 of 5 nonsensitized, MHC class I-disparate, and one MHC class II DRB allele-matched rhesus macaques. Tolerance in our preclinical model is associated with a regulatory network, involving antigen-specific Tr1 cells exhibiting a distinct transcriptome and indirect specificity for matched MHC class II and mismatched class I peptides. Apoptotic donor leukocyte infusions warrant continued investigation as a cellular, nonchimeric and translatable method for inducing antigen-specific tolerance in transplantation.


Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Tolerância Imunológica , Transplante das Ilhotas Pancreáticas/efeitos adversos , Linfócitos T Reguladores/transplante , Transferência Adotiva , Aloenxertos/imunologia , Animais , Apoptose/imunologia , Modelos Animais de Doenças , Feminino , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/uso terapêutico , Ilhotas Pancreáticas/imunologia , Macaca mulatta , Masculino , Linfócitos T Reguladores/imunologia , Doadores de Tecidos , Transplante Homólogo/efeitos adversos
6.
World J Gastroenterol ; 25(25): 3123-3135, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31333306

RESUMO

The transplanted liver can modulate the recipient immune system to induce tolerance after transplantation. This phenomenon was observed nearly five decades ago. Subsequently, the liver's role in multivisceral transplantation was recognized, as it has a protective role in preventing rejection of simultaneously transplanted solid organs such as kidney and heart. The liver has a unique architecture and is home to many cells involved in immunity and inflammation. After transplantation, these cells migrate from the liver into the recipient. Early studies identified chimerism as an important mechanism by which the liver modulates the human immune system. Recent studies on human T-cell subtypes, cytokine expression, and gene expression in the allograft have expanded our knowledge on the potential mechanisms underlying immunomodulation. In this article, we discuss the privileged state of liver transplantation compared to other solid organ transplantation, the liver allograft's role in multivisceral transplantation, various cells in the liver involved in immune responses, and the potential mechanisms underlying immunomodulation of host alloresponses.


Assuntos
Aloenxertos/imunologia , Rejeição de Enxerto/imunologia , Tolerância Imunológica , Fígado/imunologia , Transplante de Órgãos/efeitos adversos , Sobrevivência de Enxerto/imunologia , Humanos , Transplante Homólogo/efeitos adversos
7.
BioDrugs ; 33(4): 401-409, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31302863

RESUMO

Three prospective controlled clinical trials and numerous small series and case reports have confirmed that durable, drug-free remission in systemic sclerosis is possible via an autologous hematopoietic stem cell transplantation. Similar results have been seen in other autoimmune diseases. The exact mechanism by which this immune "reset" was achieved in some but not all cases remains elusive, but includes major reduction of autoreactive immune competent cells, re-establishment of T- and B cell regulatory networks and normalization of tissue niche function, particularly vascular. Some aspects regarding mobilization, conditioning and graft manipulation still remain open, but clearly a significant toxicity is associated with all effective regimens at present, and therefore patient selection remains a key issue. In the hematology/oncology arena, major efforts are being made to reduce genotoxic and other collateral toxicity induced by current mobilization and conditioning protocols, which may also translate to autoimmune disease. These include developments in rapid mobilization and antibody drug conjugate conditioning technology. If effective, such low-toxicity regimens might be applied to autoimmune disease at an earlier stage before chronicity of autoimmunity has been established, thus changing the therapeutic paradigm.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Imunoconjugados/uso terapêutico , Escleroderma Sistêmico/terapia , Condicionamento Pré-Transplante/métodos , Ensaios Clínicos Controlados como Assunto , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Prospectivos , Escleroderma Sistêmico/imunologia , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos , Resultado do Tratamento
8.
Metas enferm ; 22(6): 28-32, jul. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-184045

RESUMO

Objetivo: conocer los problemas en salud que presentan estos pacientes a los 10 años de haber recibido un trasplante alogénico de progenitores hematopoyéticos (alo-TPH). Método: estudio descriptivo transversal de aquellos pacientes pediátricos (0 a 18 años) que recibieron un alo-TPH durante el periodo 2006-2007 en la unidad de trasplante de progenitores hematopoyéticos del Hospital Universitario Vall d'Hebron (Barcelona). Los datos clínicos se recogieron a través de las historias clínicas. Se realizó estadística descriptiva. Resultados: la muestra fue de 28 pacientes con una media de edad de 16 años y rango de edad de 11 a 26 años. Hubo la misma proporción de hombres y mujeres, un 50% (n= 14). El 96,5% (n= 27) vive con sus padres, el 92,8% (n=20) es estudiante. Las principales complicaciones fueron las endocrinas con un 53,5% (n= 15), seguidas de un 28,5% (n= 8) de problemas circulatorios. Un 57% (n= 16) presentó alteraciones en la piel, musculoesqueléticas y enfermedades no malignas, principalmente anemias hemolíticas. En la muestra de estudio únicamente tres (10,7%) casos sufrieron enfermedad injerto contra huésped. Conclusión: la identificación de los problemas de salud más prevalentes en los alo-TPH (endocrinas, circulatorias, piel, musculoesqueléticas) permitirá diseñar recomendaciones específicas a estos pacientes y sus familias para minimizar los riesgos y mejorar el manejo de las mismas


Objective: to understand the health problems presented by these patients 10 years after receiving an allogeneic stem cell transplant (allo-SCT). Method: a descriptive cross-sectional study of those pediatric patients (from 0 to 18-year-old) who received an allo-SCT during the 2006-2007 period at the Stem Cell Transplant Unit of the Hospital Universitario Vall d'Hebron (Barcelona). Clinical data were collected through clinical records. Descriptive statistics was conducted. Results: the sample included 28 patients with 16 years as mean age, and an age range from 11 to 26-year-old. There was an equal proportion of men and women: 50% (n= 14); 96.5% (n= 27) lived with their parents, and 92.8% (n=20) were students. The main complications were endocrinological, with 53.5% (n= 15), followed by circulatory problems with 28.5% (n= 8); 57% (n= 16) presented skin alterations, musculoskeletal alterations, and non-malignant conditions, mainly hemolytic anemia. Only 3 cases (10.7%) from the sample suffered graft versus host disease. Conclusion: the detection of the most prevalent health conditions in allo-SCT (endocrinological, circulatory, skin, and musculoskeletal) will allow to design specific recommendations for these patients and their families, in order to minimize risks and improve their management


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Transplante Homólogo/métodos , Hematínicos/administração & dosagem , Transplante Homólogo/efeitos adversos , Estudos Transversais , Epidemiologia Descritiva
9.
Zhonghua Nei Ke Za Zhi ; 58(6): 423-427, 2019 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-31159520

RESUMO

Objective: To analyze the clinical features, efficacy and outcomes in patients with transplantation associated thrombotic microangiopathy (TA-TMA). Methods: The clinical data of 9 patients who developed TA-TMA after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were retrospectively analyzed from January 2011 to August 2018 in Affiliated Tumor Hospital of Zhengzhou University. Results: There were 6 male and 3 female patiens with a median age of 31 (12-38) years. The median time from transplantation to TA-TMA was 76 (24-155) days. The baseline blood and biochemical parameters at diagnosis of TA-TMA included median hemoglobin (Hb) 66 (58-77) g/L,platelet (PLT) count 22 (4-38) × 10(9)/L,serum lactic dehydrogenase (LDH) 655 (305-4 238) U/L,blood urine nitrogen (BUN) level 15.9 (4.8-26.2) mmol/L,blood creatinine (Cr) level 118 (24-380) µmol/L. The proportion of median peripheral blood schistocytes was 2.6%(1.2%-9%). All patients had positive urinary occult blood tests,and urinary protein was seen in 4 patients. Three patients had mental symptoms. Coombs tests were all negative. The main treatments of TA-TMA composed of reduction and withdrawal of calcineurin inhibitor,steroids and plasma exchange. Response was seen in 4 patients. Patients who did not response to the treatment had a higher proportion of schistocytes,more severe acute graft-versus-host disease (aGVHD),more elevated serum LDH and other transplant-related complications. Conclusions: TA-TMA after allo-HSCT is a serious complication with high mortality rate. The proportion of schistocytes in peripheral blood, serum LDH level and comorbidities are prognostic factors of clinical outcome.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Microangiopatias Trombóticas/etiologia , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Troca Plasmática , Estudos Retrospectivos , Microangiopatias Trombóticas/patologia
10.
Transplant Proc ; 51(5): 1568-1570, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31155194

RESUMO

BACKGROUND: The risk factors associated with delayed graft function (DGF) and its impact in kidney transplant (KTx) outcomes remains controversial; it is possible that donor renal characteristics influence the initial graft function in KTx. OBJECTIVE: Evaluate risk factors associated with DGF and its impact in KTx outcomes. METHODS: One hundred six mate KTx mate recipients performed in a single center were grouped according to the presence or absence of DGF. RESULTS: Donors were predominantly men (58%); 70% were standard criteria type, with a mean Kidney Donor Profile Index (KDPI) of 62% ± 28%, median age of 42 ± 15 and presenting hospitalization time of 6 ± 5 days. KTx recipients presented an overall DGF rate of 82%, lasting 12 ± 7 days. Pairs presenting DGF were older than pairs without DGF (P = .008), while cold ischemia time (CIT) was significantly shorter in the group without DGF compared to those presenting DGF (P = .003). The KDPI of the KTx pairs was significantly higher in pairs with DGF versus without DGF (P = .04). No statistically significant differences in 1 year allograft and patient survival were observed. Recipient age (odds ratio = 6.3, confidence interval = 1.5-25.8; P = .009) and CIT (odds ratio = 4.6, confidence interval = 1.2-17.7; P = .002) were significantly associated with DGF. CONCLUSION: This study suggests that recipient age, cold ischemic time, and KDPI are factors associated with DGF. In addition, DGF had no impact on 1-year renal function, allograft, and patient survival. In the transplant conditions of our country, Brazil, CIT seems to represent an important variable to be managed, and the aim should be to reduce this factor as much as possible.


Assuntos
Função Retardada do Enxerto/etiologia , Transplante de Rim/efeitos adversos , Adulto , Fatores Etários , Brasil , Isquemia Fria/efeitos adversos , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Doadores de Tecidos , Transplante Homólogo/efeitos adversos
11.
World J Gastroenterol ; 25(22): 2743-2751, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31235997

RESUMO

Gastrectomy with radical lymph node dissection is the most promising treatment avenue for patients with gastric cancer. However, this procedure sometimes induces excessive intraoperative blood loss and requires perioperative allogeneic blood transfusion. There are lasting discussions and controversies about whether intraoperative blood loss or perioperative blood transfusion has adverse effects on the prognosis in patients with gastric cancer. We reviewed laboratory and clinical evidence of these associations in patients with gastric cancer. A large amount of clinical evidence supports the correlation between excessive intraoperative blood loss and adverse effects on the prognosis. The laboratory evidence revealed three possible causes of such adverse effects: anti-tumor immunosuppression, unfavorable postoperative conditions, and peritoneal recurrence by spillage of cancer cells into the pelvis. Several systematic reviews and meta-analyses have suggested the adverse effects of perioperative blood transfusions on prognostic parameters such as all-cause mortality, recurrence, and postoperative complications. There are two possible causes of adverse effects of blood transfusions on the prognosis: Anti-tumor immunosuppression and patient-related confounding factors (e.g., preoperative anemia). These factors are associated with a worse prognosis and higher requirement for perioperative blood transfusions. Surgeons should make efforts to minimize intraoperative blood loss and transfusions during gastric cancer surgery to improve patients' prognosis.


Assuntos
Perda Sanguínea Cirúrgica , Gastrectomia/efeitos adversos , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Gástricas/cirurgia , Reação Transfusional/imunologia , Transfusão de Sangue/estatística & dados numéricos , Gastrectomia/métodos , Humanos , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Recidiva Local de Neoplasia/imunologia , Assistência Perioperatória/estatística & dados numéricos , Prognóstico , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/mortalidade , Transplante Homólogo/efeitos adversos , Evasão Tumoral/imunologia , Microambiente Tumoral/imunologia
12.
Transplant Proc ; 51(5): 1472-1474, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31084921

RESUMO

INTRODUCTION: The immunosuppressant agents in kidney transplantation (KT) may lead to various complications such as opportunistic infections and malignancies. BK virus associated nephropathy is a significant complication following KT, and it can result in graft failure. BK virus causes tubulointerstitial nephritis, ureter stenosis, and even graft failure in KT recipients with impaired immune system. We described a 63-year-old woman, who was a hepatitis C carrier and on dialysis for 22 years before KT, who received cadaveric-donor KT 2 years previously. She reported decreasing urine output and general weakness. The serum creatinine level was slightly increased from 2.94 to 4.38 mg/dL. METHODS: Immunosuppressant medications including prednisolone, everolimus, cyclosporin, and mycophenolate sodium were continued as maintenance therapy post KT. Kidney biopsy was performed due to deterioration of graft function. RESULTS: The kidney biopsy showed consistent results with early-stage polyomavirus nephropathy, characterized by focal viral cytopathic changes with positive immunohistochemical signals and mesangial proliferative glomerulonephritis, immune-complex-mediated (Fig 1 and Fig 2). Negative C4d staining at peritubular capillary was reported. The dosage of mycophenolate sodium was tapered from 720 to 360 mg daily and that of everolimus increased from 0.5 to 1.0 mg daily due to BK viral infection with BK nephropathy. The serum creatinine level was 2.75 mg/dL after treatment. CONCLUSION: Early detection of BK nephropathy and decreasing immunosuppressant agents are the mainstay of treatment. Substituting leflunomide for mycophenolate sodium and increasing dosage of everolimus has been proposed to solve BK nephropathy. We presented that the use of leflunomide in such situation is in a timely manner.


Assuntos
Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Rim , Infecções por Polyomavirus/imunologia , Infecções Tumorais por Vírus/imunologia , Vírus BK , Everolimo/uso terapêutico , Feminino , Humanos , Transplante de Rim/efeitos adversos , Leflunomida/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Nefrite Intersticial/imunologia , Nefrite Intersticial/virologia , Infecções Oportunistas/imunologia , Transplante Homólogo/efeitos adversos
13.
Lab Med ; 50(4): 426-431, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31065690

RESUMO

Hormographiella is a rare fungal pathogen in humans; however, case reports have described disseminated infection in immunocompromised hosts. This pathogen has been described to yield poor prognosis in patients who harbor it. Herein, we present a case report of autopsy-proven disseminated Hormographiella aspergillata infection, confirmed by DNA sequencing, in a patient experiencing a relapse of leukemia. This 54-year-old Caucasian man with chronic myelogenous leukemia (CML) that had been diagnosed in 1989, after having received a hematopoietic cell allotransplant from a compatible sibling donor, had B-cell lymphoid-blast phase of CML in April of 2013, with multiple relapses. His most recent relapse was in September of 2016, when bone marrow biopsy showed 90% blasts. The results of bronchoalveolar lavage (BAL) cultures were positive for filamentous fungus infection. The patient developed encephalopathy and worsening respiratory statusand tachycardia with flutter and hypotension, which resulted in his death. At autopsy, bilateral pleural effusions, multiple right pleural nodules, and subarachnoid hemorrhage were noted. Angioinvasive hyphal fungi were found in the right frontal lobe of the brain and the right upper lobe of the lung. Morphologically, the fungi had multiseptate, branching hyphae. The bronchoalveolar lavage specimen grew a fungus for which the colony morphologic characteristics and microscopic features were compatible with a Hormographiella species. H. aspergillata from the bronchoalveolar lavage was further identified by sequencing the D2 hypervariable region of the large-subunit (LSU) ribosomal DNA gene and the full internal transcribed spacer (ITS) regions.


Assuntos
Agaricales/isolamento & purificação , Infecções Fúngicas do Sistema Nervoso Central/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções Fúngicas Invasivas/diagnóstico , Pneumopatias Fúngicas/diagnóstico , Transplante Homólogo/efeitos adversos , Agaricales/classificação , Agaricales/genética , Autopsia , Encéfalo/microbiologia , Encéfalo/patologia , Líquido da Lavagem Broncoalveolar/microbiologia , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Infecções Fúngicas do Sistema Nervoso Central/patologia , Evolução Fatal , Histocitoquímica , Humanos , Infecções Fúngicas Invasivas/microbiologia , Infecções Fúngicas Invasivas/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Pulmão/microbiologia , Pulmão/patologia , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/patologia , Masculino , Pessoa de Meia-Idade
14.
J Neurol ; 266(8): 1960-1972, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31087160

RESUMO

BACKGROUND: Despite advances in the field, diagnosis and management of the wide spectrum of neurological events post allogeneic hematopoietic cell transplantation (alloHCT) remain challenging. Therefore, we investigated their incidence, diagnosis, management and long-term prognosis in alloHCT recipients. METHODS: We retrospectively recorded data from consecutive alloHCT recipients with or without neurological complications in our center. RESULTS: Among 758 alloHCT recipients, 127 (16.8%) presented with neurological complications. Complications developed in central nervous system (89.7%) during the late post-transplant period. Neurological adverse events included a wide spectrum of infectious and non-infectious etiologies. With a median follow-up of 11.4 months, incidence of chronic graft-versus-host disease (GVHD) was 52.8%, relapse mortality 48.6%, transplant-related mortality 39.1% and 5-year overall survival (OS) 25.8% in patients with neurological complications. Timing of appearance of neurological complications, early or late, was associated only with acute and chronic graft-versus-host-disease/GVHD. Independent pre-transplant risk factors of neurological complications in the multivariate model were unrelated or alternative donors, ALL diagnosis and non-myeloablative conditioning. In multivariate analysis of post-alloHCT events, favorable OS was independently associated with resolution of neurological syndromes, absence of chronic GVHD and sibling transplantation. In our cohort, 10-year OS was significantly lower in patients with neurological complications and independently associated with acute and chronic GVHD, relapse, fungal and bacterial infections and neurological complications. CONCLUSIONS: Our large study with long-term follow-up highlights the wide spectrum of neurological complications in alloHCT. Accurate recognition is required for adequate management, a major determinant of survival. Thus, long-term increased awareness and collaboration between expert physicians is warranted.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/mortalidade , Adulto , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Mortalidade/tendências , Doenças do Sistema Nervoso/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/tendências , Adulto Jovem
15.
Transplant Proc ; 51(4): 1296-1298, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31101218

RESUMO

Lung transplant is an effective way to treat many end-stage lung diseases. However, one of the main barriers of allograft organ transplant is still the immunologic rejection of transplanted tissue, which is a response of the HLA molecules. Rejection is a complex process involving both T-cell-mediated delayed-type hypersensitivity reactions and antibody-mediated hypersensitivity reactions to histocompatibility molecules on foreign grafts. We report the case of a 25-year-old female patient with cystic fibrosis who underwent 2 lung transplants because of her initial diagnosis and appearance of bronchiolitis obliterans syndrome after the first transplant. Only 13 months after the second transplant, despite the therapies applied, a new rejection occurred associated with high mean fluorescent intensity donor-specific antibody levels, which resulted later in the death of the patient. The present case draws attention to the importance of matching HLA molecules between donor and recipient in addition to immunosuppressive therapy.


Assuntos
Fibrose Cística/cirurgia , Rejeição de Enxerto/imunologia , Transplante de Pulmão/efeitos adversos , Reoperação/efeitos adversos , Adulto , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/cirurgia , Feminino , Antígenos HLA/imunologia , Humanos , Transplante Homólogo/efeitos adversos
16.
Arch Immunol Ther Exp (Warsz) ; 67(3): 171-177, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31028405

RESUMO

The complement system is one of the crucial pathophysiological mechanisms that directly influence the function of a transplanted kidney. Since the complement pathways' activation potential can be easily determined via their functional activity measurement, we focused on fluctuation in the cascade activity in the early post-transplant period. The aim of the study was to relate the kidney transplantation-induced complement system response to allograft outcome. Forty-two kidney recipients (aged: 53.5 [37-52], 17 females/25 males) and 24 healthy controls (aged: 40.5 [34-51], 13 females/11 males) were enrolled in the study. The functional activities of alternative, classical, and lectin pathways were determined before and in the first week after transplantation using Wielisa®-kit. We observed that the baseline functional activity of the alternative pathway (AP) was higher in chronic kidney disease patients awaiting transplantation compared to healthy controls and that its level depended on the type of dialysis. AP-functional activity was decreased following transplantation procedure and its post-transplant level was related to allograft function. The baseline and transplantation-induced functional activities of the classical and lectin pathways were not influenced by dialysis type and were not associated with transplant outcome. Moreover, our study showed that intraoperative graft surface cooling had a protective effect on AP activation. Our study confirms the influence of dialysis modality on persistent AP complement activation and supports the role of AP in an early phase after kidney transplantation and allograft outcome.


Assuntos
Via Alternativa do Complemento/imunologia , Rejeição de Enxerto/imunologia , Falência Renal Crônica/terapia , Transplante de Rim/efeitos adversos , Diálise Renal/efeitos adversos , Adulto , Idoso , Aloenxertos/imunologia , Aloenxertos/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/fisiopatologia , Humanos , Rim/imunologia , Rim/fisiopatologia , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo/efeitos adversos , Resultado do Tratamento
17.
Transpl Infect Dis ; 21(4): e13095, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30993823

RESUMO

BACKGROUND: Viral infections are a significant cause of morbidity and mortality in pediatric transplant populations. We analyzed the epidemiology of viral infections in pediatric hematopoietic stem cell transplant (HSCT) patients, including their incidence, associated risk factors, and outcome. METHODS: In a prospective study from September 2011 to September 2015, blood, urine, and stool specimens were monitored weekly from transplantation to day 100 or after if clinically suspected, by use of real-time polymerase chain reaction. Cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK polyomavirus (BKV), Herpes simplex virus-1,2, Varicella zoster virus, Human herpes virus-6,7, and Adenovirus infections were monitored. All children and adolescents who underwent HSCT received long-term follow up in the regular outpatient clinics (range 2-48 months). RESULTS: A total of 192 HSCTs (autologous/allogeneic: 53/139) were performed in 165 subjects (median age: 5.6 years). Viruses most commonly isolated were CMV (46.1%), BKV (25.9%) and EBV (22.6%) and were more frequent in allogeneic versus autologous transplants (P < 0.05). Almost all high-risk allogeneic recipients developed EBV infections post-HSCT. EBV-PTLD was the only cause of death among those who developed viral disease. The factors significantly associated with the development of viral infections were recipient's advanced age, unrelated donor, mismatched graft and use of peripheral blood stem cells grafts. CONCLUSIONS: Viral infections were common among our pediatric recipients. Data suggest that monitoring of viral load may be significant to the prevention of viral disease. Particular demographic and transplantation characteristics were associated with the development of viral infections post-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Viroses/epidemiologia , Infecções por Adenoviridae/epidemiologia , Adolescente , Criança , Pré-Escolar , Infecções por Citomegalovirus/epidemiologia , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/epidemiologia , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Fatores de Risco , Transplante Homólogo/efeitos adversos , Carga Viral , Ativação Viral
18.
Infect Dis (Lond) ; 51(7): 479-484, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31012777

RESUMO

BK-virus (BKV) associated nephropathy (BKVAN) and BKV associated haemorrhagic cystitis (HC) are complications of BKV infection/reactivation in renal and allogeneic haematopoietic stem cell transplantation (HSCT) patients, respectively. The task of how to manage these diseases was given to the chair by the Swedish Reference Group for Antiviral Therapy (RAV). After individual contributions by members of the working group, consensus discussions were held in a meeting on 23 January 2018 arranged by RAV. Thereafter, the recommendations were published in Swedish on November 2018. The current translation to English has been approved by all co-authors. High BKV serum levels suggest an increased risk for BKVAN and potential graft failure. For detection of BKVAN, careful monitoring of BKV DNA levels in serum or plasma is recommended the first year after renal transplantation and when increased creatinine serum levels of unknown cause are observed. Notably, a renal biopsy is mandatory for diagnosis. To reduce the risk for progression of BKVAN, there is no specific treatment, and tailored individual decrease of immunosuppression is recommended. For BKV-HC, BKV monitoring is not recommended, since BK-viruria frequently occurs in HSCT patients and the predictive value of BKV in plasma/serum has not been determined. However, the risk for BKV-HC is higher for patients undergoing myeloablative conditioning, having an unrelated, HLA-mismatched, or a cord blood donor, and awareness of the increased risk and early intervention may benefit the patients. Also for BKV-HC, no specific therapy is available. Symptomatic treatment, e.g. forced diuresis and analgesics could be of use.


Assuntos
Antivirais/uso terapêutico , Vírus BK/isolamento & purificação , Testes Diagnósticos de Rotina/métodos , Gerenciamento Clínico , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Transplante Homólogo/efeitos adversos
19.
Mycoses ; 62(7): 576-583, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31034703

RESUMO

False positivity of antigen immunoassays used as an early diagnostic tool to detect invasive fungal infections is known. Interpretation of the assay needs the identification of sources which could affect the specificity of the test. We focused on the influence of parenteral nutrition (PN) and piperacillin-tazobactam (TZP) on fungal immunoassays. Measurable amounts of Candida antigen mannan were detected in several compounds of PN and TZP in a previous in vitro study. In the current study, 84 patients undergoing allogeneic haematopoietic cell transplantation receiving either TZP, PN or both were monitored with Aspergillus and Candida antigen assay. Six patients were analysed closer in a kinetic analysis with more frequent blood sampling to detect mannan. PN in diverse compositions as well as TZP did not increase significantly the amount of mannan and the Aspergillus antigen in serum. We could not confirm the positive results of the in vitro study. Physicians should be aware that mannan antigenemia due to drug infusion could be a transient issue and should be considered in the interpretation of fungal immunoassays, although we could not find clinically relevant effects on mannan levels.


Assuntos
Antibacterianos/administração & dosagem , Antígenos de Fungos/sangue , Candidíase Invasiva/diagnóstico , Reações Falso-Positivas , Aspergilose Pulmonar Invasiva/diagnóstico , Nutrição Parenteral , Combinação Piperacilina e Tazobactam/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Homólogo/efeitos adversos , Adulto Jovem , Inibidores de beta-Lactamases/administração & dosagem
20.
J Pediatr Hematol Oncol ; 41(5): e296-e301, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30933028

RESUMO

Thalassemia is a major public health problem in developing countries. Sibling matched hematopoietic stem cell transplantation (HCT) is the recommended treatment for thalassemia major (TM). We retrospectively analyzed our data of thalassemia major patients who underwent HCT at a tertiary care center in Northern India from January 2008 to September 2017. The primary end points were overall survival (OS) and thalassemia-free survival (TFS), and secondary end points were complications post HCT (graft-versus-host-disease [GVHD], hemorrhagic cystitis [HC], and sinusoidal obstruction syndrome [SOS]). Data of 203 transplants for 200 patients (3 s transplants) were evaluated. Median follow-up period was 29.1 months (range, 0.3 to 116.7 mo). The overall survival (OS) was 88.5% and TFS was 82%. Class risk analysis showed a significantly higher OS and TFS in class I and class II compared to class III high risk group (OS: P=0.0017; TFS: P=0.0005) and (OS: P=0.0134; TFS: P=0.0027) respectively. Acute and chronic GVHD was seen in 59 (29.5%) and 18 (9%) patients, respectively, and SOS and HC were seen in 23 (11.5%) and 11 (5.5%) patients, respectively. This study reconfirms that allogenic HCT is feasible in developing world with the overall survival and TFS comparable to that reported in Western literature and should be considered early in all TM patients with available matched sibling donors.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Talassemia beta/terapia , Adulto , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/etiologia , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Irmãos , Análise de Sobrevida , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos , Talassemia beta/complicações , Talassemia beta/mortalidade
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