RESUMEN
BACKGROUND: Chronic immunosuppression following pancreas transplantation carries significant risk, including posttransplant lymphoproliferative disease (PTLD). We sought to define the incidence, risk factors, and long-term outcomes of PTLD following pancreas transplantation at a single center. METHODS: All adult pancreas transplants between February 1, 1983 and December 31, 2023 at the University of Minnesota were reviewed, including pancreas transplant alone (PTA), simultaneous pancreas-kidney transplants (SPK), and pancreas after kidney transplants (PAK). RESULTS: Among 2353 transplants, 110 cases of PTLD were identified, with an overall incidence of 4.8%. 17.3% were diagnosed within 1 year of transplant, 32.7% were diagnosed within 5 years, and 74 (67.3%) were diagnosed after 5 years. The overall 30-year incidence of PTLD did not differ by transplant type-7.4% for PTA, 14.2% for SPK, and 19.4% for PAK (p = 0.3). In multivariable analyses, older age and Epstein-Barr virus seronegativity were risk factors for PTLD, and PTLD was a risk factor for patient death. PTLD-specific mortality was 32.7%, although recipients with PTLD had similar median posttransplant survival compared to those without PTLD (14.9 year vs. 15.6 year, p = 0.9). CONCLUSIONS: PTLD following pancreas transplantation is associated with significant mortality. Although the incidence of PTLD has decreased over time, a high index of suspicion for PTLD following PTx should remain in EBV-negative recipients.
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Supervivencia de Injerto , Trastornos Linfoproliferativos , Trasplante de Páncreas , Complicaciones Posoperatorias , Humanos , Trasplante de Páncreas/efectos adversos , Masculino , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/epidemiología , Femenino , Adulto , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios de Seguimiento , Factores de Riesgo , Pronóstico , Persona de Mediana Edad , Incidencia , Tasa de Supervivencia , Estudios Retrospectivos , Rechazo de Injerto/etiología , Rechazo de Injerto/mortalidad , Trasplante de Riñón/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Epstein-Barr virus-associated lymphoproliferative disorders (EBV-LPDs) are a group of disorders involving lymphoid tissues or lymphocytes. The epidemiology and economic burden of hospitalized children with EBV-LPDs in China have not been well studied. This study aimed to reveal the epidemic characteristics and disease burden of EBV-LPDs among the Chinese hospitalized children, providing strategies for the prevention and management. METHODS: This study was based on the FUTang Updating medical REcords (FUTURE) database of China and collected the medical records from 27 tertiary children's hospitals between January 2016 and December 2021 in China, counting five types of EBV-LPDs, namely EBV-positive T-cell lymphoproliferative disease, NK/T cell lymphoma, extranodal NK/T-cell lymphoma (nasal type), systemic EBV-positive T-cell lymphoproliferative disease of childhood and posttransplant lymphoproliferative disorders. We conducted a retrospective syhthesis and analysis of the epidemiological characteristics, expenses, length of stay (LOS), as well as complications among hospitalized children diagnosed with five types of EBV-LPDs and compared parameters using appropriate statistical tests. RESULTS: The study described 153 children aged 0-18 years hospitalized with EBV-LPDs from 2016 to 2021 in the FUTURE database. The male-to-female ratio was 1.10:1, and more than half of the age distribution was in the 6-12 y group. Among EBV-LPDs cases, EBV+ T-LPD accounted for the largest proportion (65.36%). Complications were presented in 93 children with EBV-LPDs, mainly hemophagocytic lymphohistiocytosis (HLH). The median LOS of NKTL was 26.5 days [interquartile range (IQR) = 3-42], which was the longest among EBV-LPDs. The median hospitalization cost of PTLD was 10 785.74 United States dollars (IQR = 7 329.38-16 531.18), which was the heaviest among EBV-LPDs. CONCLUSIONS: Compared with the total number of hospitalized children in China during the same period and in the same age group, the proportion of EBV-LPD is very low. EBV-LPD can develop in all age groups, but it is more common in school-age children. Among 5 EBV-LPDs, the disease with the highest proportion is EBV+ T-LPD. The overall disease burden of EBV-LPD was heavy, especially the economic burden. HLH was one of the most common complications, which could directly affect the burden of patients because of prolonged hospitalization. These data are taken from a very large database, illustrating the epidemiological and economic burden of EBV-LPDs hospitalized children in China, which enriched the existing epidemiological and disease burden content of EBV-LPDs.
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Infecciones por Virus de Epstein-Barr , Trastornos Linfoproliferativos , Humanos , China/epidemiología , Niño , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/virología , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/complicaciones , Masculino , Femenino , Preescolar , Lactante , Adolescente , Estudios Retrospectivos , Recién Nacido , Hospitalización/estadística & datos numéricos , Herpesvirus Humano 4/aislamiento & purificación , Niño HospitalizadoRESUMEN
Children with end-stage kidney disease (ESKD) face a lifetime of complex medical care, alternating between maintenance chronic dialysis and kidney transplantation. Kidney transplantation has emerged as the optimal treatment of ESKD for children and provides important quality of life and survival advantages. Although transplantation is the preferred therapy, lifetime exposure to immunosuppression among children with ESKD is associated with increased morbidity, including an increased risk of cancer. Following pediatric kidney transplantation, cancer events occurring during childhood or young adulthood can be divided into two broad categories: post-transplant lymphoproliferative disorders and non-lymphoproliferative solid tumors. This review provides an overview of cancer incidence, types, outcomes, and preventive strategies in this population.
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Fallo Renal Crónico , Trasplante de Riñón , Trastornos Linfoproliferativos , Neoplasias , Humanos , Trasplante de Riñón/efectos adversos , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/epidemiología , Niño , Neoplasias/epidemiología , Neoplasias/etiología , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/epidemiología , Factores de Riesgo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Incidencia , Terapia de Inmunosupresión/efectos adversosRESUMEN
BACKGROUND: Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, difficulties for early detection may worsen the prognosis. METHODS: The prospective, multicenter, study enrolled 944 children (≤21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in seven US centers between 2014 and 2019 (NCT02182986). In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Variables included sex, age, race, ethnicity, transplanted organ, EBV viral load, pre-transplant EBV serology, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis. RESULTS: The uni-/multivariable competing risk analyses revealed the combination of EBV-seropositive donor and EBV-naïve recipient (D+R-) was a significant risk factor for PTLD development (sub-hazard ratio: 2.79 [1.34-5.78], p = .006) and EBV DNAemia (2.65 [1.72-4.09], p < .001). Patients with D+R- were significantly more associated with monomorphic/polymorphic PTLD than those with the other combinations (p = .02). Patients with monomorphic/polymorphic PTLD (n = 21) had significantly more EBV DNAemia than non-PTLD patients (p < .001) and an earlier clinical presentation of PTLD than patients with hyperplasias (p < .001), within 6-month post-transplant. Among non-liver transplant recipients, monomorphic/polymorphic PTLD were significantly more frequent than hyperplasias in patients ≥5 years of age at transplant (p = .01). CONCLUSIONS: D+R- is a risk factor for PTLD and EBV DNAemia and associated with the incidence of monomorphic/polymorphic PTLD. Intensive follow-up of EBV viral load within 6-month post-transplant, especially for patients with D+R- and/or non-liver transplant recipients ≥5 years of age at transplant, may help detect monomorphic/polymorphic PTLD early in pediatric transplant.
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Infecciones por Virus de Epstein-Barr , Trastornos Linfoproliferativos , Trasplante de Órganos , Complicaciones Posoperatorias , Humanos , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/virología , Infecciones por Virus de Epstein-Barr/epidemiología , Masculino , Estudios Prospectivos , Niño , Femenino , Estados Unidos/epidemiología , Preescolar , Adolescente , Lactante , Trasplante de Órganos/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/virología , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Herpesvirus Humano 4 , Adulto JovenRESUMEN
Kidney transplantation is the ideal treatment modality for patients with end-stage kidney disease, with excellent outcomes post-transplant compared with dialysis. However, kidney transplant recipients are at increased risk of infections and cancer because of the need for immunosuppression. Kidney transplant recipients have approximately two to three times greater risk of developing cancer than the general population, and cancer is a major contributor to morbidity and mortality. Most of the increased risk is driven by viral-mediated cancers such as post-transplant lymphoproliferative disorder, anogenital cancers, and Kaposi sarcoma. Nonmelanoma skin cancer is the most frequent type of cancer in kidney transplant recipients, likely due to an interaction between ultraviolet radiation exposure and decreased immune surveillance. Occurrence of the more common types of solid organ cancers seen in the general population, such as breast, prostate, lung, and colorectal cancers, is not, or is only mildly, increased post-transplant. Clinical care and future research should focus on prevention and on improving outcomes for important immunosuppression-related malignancies, and treatment options for other cancers occurring in the transplant setting.
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Trasplante de Riñón , Neoplasias , Neoplasias Cutáneas , Humanos , Trasplante de Riñón/efectos adversos , Neoplasias/epidemiología , Neoplasias/etiología , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/etiología , Sarcoma de Kaposi/epidemiología , Sarcoma de Kaposi/etiología , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/etiología , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/cirugía , Terapia de Inmunosupresión/efectos adversos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/etiología , Neoplasias del Ano/epidemiología , Neoplasias del Ano/etiología , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/etiología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Factores de Riesgo , Receptores de TrasplantesAsunto(s)
Antígeno Ki-1 , Neoplasias Cutáneas , Humanos , Estudios Retrospectivos , Masculino , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/epidemiología , Femenino , Persona de Mediana Edad , Antígeno Ki-1/análisis , Antígeno Ki-1/metabolismo , Anciano , Adulto , Trastornos Linfoproliferativos/epidemiología , Medición de Riesgo , Anciano de 80 o más Años , Linfoma/epidemiología , Estudios de CohortesRESUMEN
BACKGROUND AND OBJECTIVE: Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) are rare but well-known diseases that manifest during or after methotrexate (MTX) administration. Limited information is available on the clinical characteristics of OIIA-LPD of the lung because only a few cases have been reported. Thus, we aimed to assess the incidence and prognosis of patients with OIIA-LPD of the lung. METHODS: Patients with OIIA-LPD of the lung treated at our institution between January 2008 and July 2020 were retrospectively analysed. RESULTS: Among the 51 patients with OIIA-LPD, 16 (31.3%, 7 men, 9 women) had OIIA-LPD of the lung (median age, 69 [range, 63-82] years). Peripheral lesions were observed in 10 (62.5%), central lesions in two (12.5%), and both lesions in four (25.0%) patients. Nine of the 16 patients underwent bronchoscopic biopsy, seven were diagnosed (diagnostic yield, 77.8%) and, re-biopsy was performed in 2 patients. Eight (50.0%) patients had LPD and six (37.5%) had diffuse large B-cell lymphoma. In the 14 patients with confirmed treatment efficacy, the overall response rate to MTX withdrawal was 71.4%. However, chemotherapy was required in case of larger lesions (three patients). Death related to OIIA-LPD occurred in only one patient, and 11 of the 14 patients were alive during the study period (median follow-up time, 53.7 [range, 4.3-84.2] months). CONCLUSION: The incidence of OIIA-LPD of the lung is 31.3% and higher than that reported previously. The treatment effect of MTX withdrawal seems to be sufficient; however, in some cases, chemotherapy may be required from the beginning.
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Enfermedad Iatrogénica , Trastornos Linfoproliferativos , Metotrexato , Humanos , Metotrexato/efectos adversos , Metotrexato/administración & dosificación , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Anciano , Trastornos Linfoproliferativos/inducido químicamente , Trastornos Linfoproliferativos/epidemiología , Incidencia , Pronóstico , Anciano de 80 o más Años , Enfermedad Iatrogénica/epidemiología , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/epidemiología , Síndromes de Inmunodeficiencia/inducido químicamente , Síndromes de Inmunodeficiencia/epidemiología , Pulmón/patología , Pulmón/efectos de los fármacosRESUMEN
BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is an important cause of morbidity and mortality in heart transplant (HTx) recipients. However, previous studies of PTLD after HTx are limited to single-center analyses or extrapolated from all solid organ transplantations. OBJECTIVES: The authors analyzed the temporal trends, risk factors, and clinical outcome of de novo PTLD specifically after HTx. METHODS: Using multi-institutional, multinational data from the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry, the authors evaluated the real-world data of PTLD after HTx, transplanted between January 2000 and June 2015. Multivariable analysis was done to identify risk factors for PTLD development after HTx. RESULTS: Among 28,136 HTx recipients, 1,069 (3.8%) developed PTLD within 10 years of transplantation. PTLD showed a bimodal age pattern with peak incidence in patients of pediatric age and late adulthood at transplantation. The early transplant era (2000-2007 vs 2008-2015), male recipient, and EBV donor-positive-recipient-negative match were independent risk factors of PTLD development within 3 years of transplantation, whereas maintenance therapy with cyclosporine vs tacrolimus at initial discharge was associated with a lower incidence. PTLD development within 3 years of transplantation was significantly associated with mortality (HR: 2.42 [95% CI: 2.01-2.91]; P < 0.001). Survival after PTLD diagnosis was higher in the recent transplant era. CONCLUSIONS: PTLD is relatively rare, but potentially fatal, post-transplant malignancy. PTLD incidence and mortality after HTx have decreased in the recent era. Strategies to minimize the risk of PTLD, and ensure early diagnosis and effective treatment are likely to improve outcomes in HTx.
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Trasplante de Corazón , Trastornos Linfoproliferativos , Adulto , Niño , Humanos , Masculino , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón/efectos adversos , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/diagnóstico , Estudios Multicéntricos como Asunto , Factores de Riesgo , FemeninoAsunto(s)
Colangitis Esclerosante , Trasplante de Hígado , Trastornos Linfoproliferativos , Humanos , Colangitis Esclerosante/cirugía , Colangitis Esclerosante/complicaciones , Colangitis Esclerosante/etiología , Colangitis Esclerosante/inmunología , Trasplante de Hígado/efectos adversos , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/diagnóstico , Factores de Riesgo , Masculino , Femenino , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Persona de Mediana Edad , Adulto , Inmunosupresores/efectos adversosRESUMEN
PURPOSE: Post-transplantation lymphoproliferative disorders (PTLDs) after hematopoietic stem transplantation (HCT) or solid organ transplantation (SOT) result in poorer outcomes, including death. There are limited large cohort data on the incidence and natural course of PTLD in Asians. MATERIALS AND METHODS: We investigated PTLD using Korean national health insurance claims data of 47,518 patients who underwent HCT or SOT in 2008-2020. Patient demographics, time and type of PTLD diagnosis, type of PTLD treatment, and death data were collected. We used Fine and Gray subdistribution hazard models to calculate the cumulative incidence and risk factors for PTLD. RESULTS: During median follow-up of 5.32 years, PTLD occurred in 294 of 36,945 SOT patients (0.79%) and 235 of 10,573 HCT patients (2.22%). Cumulative incidence of PTLD were 0.49% at 1 year, 1.02% at 5 years, and 1.50% at 10 years post-transplantation. Age < 20 years (subdistribution hazard ratio [SHR] of 1.67 in age 10-19, SHR 1.51 in age 0-9), HCT (SHR 3.02), heart transplantation (SHR 2.27), and liver transplantation (SHR 1.47) were significant risk factors for PTLD. The presence of PTLD was associated with an increased risk of death (hazard ratio of 2.84). Overall, 5-year survival of PTLD patients was 68.9% (95% confidence interval, 64.9 to 73.2). CONCLUSION: We observed a steady increase in PTLD over 10 years after HCT or SOT in this large cohort study. Pediatric age group, HCT, liver transplantation, and heart transplantation were suggested to be risk factors for PTLD, and PTLD was associated with a higher risk of death.
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Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Linfoma , Trastornos Linfoproliferativos , Humanos , Niño , Adulto Joven , Adulto , Adolescente , Recién Nacido , Lactante , Preescolar , Incidencia , Estudios de Cohortes , Infecciones por Virus de Epstein-Barr/complicaciones , Linfoma/epidemiología , Linfoma/etiología , Linfoma/terapia , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/diagnóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Proliferación Celular , Estudios RetrospectivosRESUMEN
INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is a clinically heterogeneous potentially fatal complication of pediatric liver transplantation (PLT). We determined the prevalence, complications, and associated factors for PTLD in PLT recipients from Wits Donald Gordon Medical Centre, South Africa from January 2012 to August 2019. METHODS: We performed a retrospective record review of 150 PLT recipients. RESULTS: Histologically proven PTLD occurred in 17/150 PLT recipients (11.3%). Children with PTLD were significantly younger at transplant (17.9 vs. 32.7 months, p = 0.001) with a significantly higher prevalence of obstructive etiology (17/17 vs. 81/133, p = 0.001). Fifteen (88.2%) children with PTLD were Epstein-Barr virus (EBV) seronegative at transplant. High post-transplant EBV viral load at a threshold value of 4.8 log10 DNA copies/mL (sensitivity: 80.0% [95% confidence interval {CI}, 46.7%-100.0%]; specificity: 73.1% [95% CI 42.3%-93.3%; area under the curve {AUC} 75.8%]) and low post-transplant albumin levels at a threshold value of 21.5 g/L (sensitivity: 70.6% [95% CI, 41.2%-94.1%]; specificity: 85.7% [95% CI, 60.4%-94.5%; {AUC} 74.8%]) were associated with PTLD. The prevalence of cytomegalovirus (CMV) disease was significantly higher in children who developed PTLD versus non-PTLD (12/17 vs. 18/133; p < 0.001). CMV disease and the combination of post-transplant high EBV viral load and low albumin were independently associated with an increased risk of developing PTLD. Four (23.5%) children with PTLD died, however, survival was equivalent to non-PTLD PLT (p = 0.580). CONCLUSION: The prevalence of PTLD in our cohort mirrors international cohorts, with mortality similar to non-PTLD PLT recipients.
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Infecciones por Citomegalovirus , Infecciones por Virus de Epstein-Barr , Trasplante de Hígado , Trastornos Linfoproliferativos , Niño , Humanos , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/epidemiología , Sudáfrica/epidemiología , Herpesvirus Humano 4 , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/etiología , Infecciones por Citomegalovirus/complicaciones , Receptores de Trasplantes , Albúminas , Carga Viral , ADN ViralRESUMEN
Objectives: To assess the spectrum and clinico-haematological profile of chronic lymphoproliferative disorders in patients presenting with lymphocytosis. METHODS: The cross-sectional, retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data related to cases of bone marrow aspirate and trephine from January to November 2020. Patients for whom the bone marrow was done for lymphocytosis were studied for the presence of lymphoproliferative disorders, sub-types and patients'characteristics. The diagnosis and classification were based on the World Health Organisation criteria for tumours of haematopoietic and lymphoid tissues. Data was analysed using SPSS 21. RESULTS: Of the 3,334 bone marrow specimenstested, 103(3%) were related to lymphocytosis. Of these, 84(82%) were diagnosed with lymphoproliferative disorders, while diagnosisremained undetermined in 19(18%) cases. Male:female ratio was 3.6:1 and median age was 60 years (range: 21-85 years). Constitutional symptoms were found in 61(73%) patients. Median absolute lymphocyte count was 45x109/L (range: 5.3-480). All 84(100%) patients were classified as B-cell lymphoproliferative disorder. Chronic lymphocytic leukaemia wasthe most common form, 61(73%), and 31(51%) of them presented with advanced stage disease. CONCLUSIONS: A huge majority of patients presenting with lymphocytosis had underlying lymphoproliferative disorders of which B-cell chronic lymphocytic leukaemia was found to be the most common.
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Leucemia Linfocítica Crónica de Células B , Linfocitosis , Trastornos Linfoproliferativos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Linfocitosis/epidemiología , Linfocitosis/diagnóstico , Linfocitosis/patología , Linfocitos B/patología , Estudios Retrospectivos , Estudios Transversales , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/patología , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/patologíaRESUMEN
INTRODUCTION: Post transplant lymphoproliferative disorders (PTLD) are heterogeneous lymphoid proliferations in recipients of solid organs which seem to be related to Epstein Barr Virus (EBV). The use of antilymphocyte antibodies, EBV seronegativity in the recipient,acute rejection and CMV infection have been identified as classical risk factors. MATERIAL Y METHODS: We have studied in a retrospective observational study, the incidence of PTLD in a period of 22 years, its relationship with EBV, presence of classical risk factors and outcome in 21546 simple adult renal transplant recipients from cadaveric and living donors, transplanted in 21 hospitals from 1990 to 2009. RESULTS: A total of 275 recipients developed PTLD (1,2%),195 males (70,9%), 80 females (29,1%) aged 59.2 (p25 44.7 p75 68)years. Two hundred forty-five (89.0%) were 1st transplant recipients and 269 (97,8%) from cadaveric donors. EBV in the tissue was reported in 94 out of the 155 studied recipients (60.6%) and 86.0% of the proliferations were due to B lymphocytes. PTLD median appearance after transplant were 42.months (p25, 75, 12, 77, 5). One hundred eighty-eight recipients out of 275 patients (68.3%) had any classical risk factor and the use of antilymphocyte antibodies was the most frequent. During the follow-up, 172 patients died (62,5%) and 103 (37,5%) had a complete remission. The main cause of death was PTLD progression (nâ¯=â¯91, 52,9%), followed by sepsis (nâ¯=â¯24, 13,9%). The follow-up period post-transplant of the recipients was between 3 and 22 years. The incidence was 0,14% during the first year post-trasplant and 0.98% the cumulative incidence at 10 years. Patient survival after diagnosis was 51%, 44% and 39% after 1, 2 and 5 years, respectively. Finally, overall graft survival was 48%, 39% and 33% at the same periods. CONCLUSION: PTLD has a low incidence in renal transplant recipients. Most of the proliferations are due to B lymphocytes and seem to have a close relationship with EBV. PTLD can develop in the absence of classical risk factors. The prognosis is poor, mainly due to PTLD progression, but the survivors can even maintain their grafts.
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Infecciones por Virus de Epstein-Barr , Trasplante de Riñón , Trastornos Linfoproliferativos , Masculino , Adulto , Femenino , Humanos , Trasplante de Riñón/efectos adversos , Infecciones por Virus de Epstein-Barr/epidemiología , Herpesvirus Humano 4 , Suero Antilinfocítico , Estudios Longitudinales , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/etiología , CadáverRESUMEN
Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a troublesome problem in patients receiving MTX for rheumatoid arthritis (RA). However, its incidence, prognosis, and risk factors remain unclear. In this retrospective study, we evaluated the actual incidence, prognostic impact, and risk factors of MTX-LPD. Of the 986 patients with RA treated with MTX, 90 patients experienced 95 new malignancies (NMs), with LPD as the most frequent in 26 patients. The cumulative LPD incidences were 1.3% and 4.7% at 5 and 10 years after MTX initiation, respectively. Among the 24 patients who discontinued MTX after developing LPD, 15 showed sustained regression, without difference in overall survival between patients with LPD and without NM. Inflammatory markers and absolute lymphocyte counts were not useful for early LPD development detection, but most of the patients with LPD had persistently elevated erythrocyte sedimentation ratios. Regarding concomitant drugs, tacrolimus increased the risk only if patients were not receiving biological disease-modifying antirheumatic drugs (bDMARDs). bDMARDs did not increase the risk for any of the drugs or the number of classes used. The number of LPD cases was lower in patients with IL-6A even after a long period after MTX, although with no statistically significant difference. Thus, approximately 1 in 20 patients with RA developed MTX-LPD over the 10 years of MTX treatment, but it did not affect the survival of patients with RA. Tacrolimus increased the risk of developing LPD for certain patients and should be used with caution.
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Antirreumáticos , Artritis Reumatoide , Trastornos Linfoproliferativos , Humanos , Metotrexato/efectos adversos , Estudios Retrospectivos , Tacrolimus/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/complicaciones , Antirreumáticos/efectos adversos , Trastornos Linfoproliferativos/inducido químicamente , Trastornos Linfoproliferativos/epidemiologíaRESUMEN
Post-transplant lymphoproliferative disease (PTLD) remains a major complication of transplantation. PTLD is a rare entity and very heterogenous making consensus on diagnosis and treatment very challenging. The majority are Epstein-Barr virus (EBV) driven, CD20+ B-cell proliferations. PTLD does occur following hematopoietic stem cell transplant (HSCT), but due to the relative short risk period and efficacy of pre-emptive therapy, PTLD following HSCT will not be discussed in this review. This review will focus on the epidemiology, role of EBV, clinical presentation, diagnosis and evaluation and the current and emerging treatment strategies for pediatric PTLD following solid organ transplantation.
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Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Trastornos Linfoproliferativos , Humanos , Niño , Adolescente , Adulto Joven , Herpesvirus Humano 4 , Infecciones por Virus de Epstein-Barr/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante Homólogo/efectos adversos , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/etiologíaRESUMEN
Post-transplant lymphoproliferative disorders (PTLD) represent a typical complication of transplant recipients. Their incidence varies according to the recipient's characteristics and the type of transplanted organ. Their pathogenesis is strongly related to a disbalance between reduced T-cell immune surveillance to avoid graft rejection, and the reactivation of the oncogenic Epstein-Barr virus (EBV) within B lymphocytes, leading to uncontrolled B-cell proliferation and malignant transformation. PTLD represent a spectrum of various histological entities with distinct prognosis. Clinical management mainly focuses on their surveillance and therapeutic strategy is risk-adapted. This review aims to shed light on these rare pathologies whose early detection could greatly improve the prognosis of transplant patients.
Les maladies lymphoprolifératives post-transplantation (PTLD) représentent une complication classique des receveurs d'organe. Leur incidence varie selon le profil du receveur et le type d'organe transplanté. La pathogenèse est fortement associée à un déséquilibre entre la diminution de la surveillance immunitaire T requise pour éviter le rejet du greffon et la réactivation du virus oncogénique Epstein-Barr (EBV) au sein des lymphocytes B, amenant à leur prolifération incontrôlée et à la transformation maligne. Elles représentent un spectre d'entités histologiques au pronostic variable, dont la prise en charge se concentre sur la surveillance ; la stratégie thérapeutique étant dictée par le risque. Cet article vise à mettre en lumière ces pathologies rares dont la détection précoce pourrait améliorer le pronostic des patients transplantés.
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Infecciones por Virus de Epstein-Barr , Trasplante de Riñón , Trastornos Linfoproliferativos , Trasplante de Órganos , Humanos , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/epidemiología , Herpesvirus Humano 4/fisiología , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/etiología , Trasplante de Órganos/efectos adversos , Trasplante de Riñón/efectos adversosRESUMEN
BACKGROUND: The incidence of post-transplant lymphoproliferative disorder (PTLD) in adult kidney transplant (KTx) recipients is less common in Taiwan. In our institute, we observed that brain lymphoma was the most notorious type. METHODS: The study describes the clinical, histologic, and radiological features of primary central nervous lymphoma (PCNSL) and the outcomes and associations with Epstein-Barr virus (EBV) infection in our center. RESULTS: Among 1470 KTx recipients, 5 patients had tissue-proven brain lymphoma (0.34%). The brain pathology disclosed diffuse large B-cell lymphoma in all patients. EBV was detected through in situ hybridization for Epstein-Barr encoding region (EBER) to disclose the EBV inclusion in the nuclei of lymphoma cells. The first treatment step was the reduction of immunosuppressants; 4 patients received whole-brain radiotherapy after complete resection of PCNSL, and 1 received concurrent chemoradiotherapy. Only one patient had poor performance status at the time of diagnosis and had a poor response to treatment with steroids. Four patients survived (mean 36.5 months, range 8.6 to 57.6 months), but one died after rapid neurologic deterioration. CONCLUSION: Epstein-Barr virus inclusion was found in PCNSL in our patients; however, the role of EBV in PCNSL remains to be clarified. Post-transplant lymphoproliferative disorder is a rare malignancy after KTx with a predilection of brain involvement in Taiwan. We report a successful care experience in a patient with primary CNS lymphoma with better survival.
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Infecciones por Virus de Epstein-Barr , Trasplante de Riñón , Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Trastornos Linfoproliferativos , Adulto , Humanos , Herpesvirus Humano 4/genética , Trasplante de Riñón/efectos adversos , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/epidemiología , Prevalencia , Linfoma de Células B Grandes Difuso/etiología , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/etiología , Encéfalo/patologíaRESUMEN
Data on the potential benefits and risks of induction therapy in pediatric liver transplantation (LT) are limited. This was a retrospective cohort study of 2748 pediatric LT recipients at 26 children's hospitals between January 1, 2006 to May 31, 2017 using data from the pediatric health information system linked to the United Network for Organ Sharing database. The induction regimen was obtained from the pediatric health information system day-by-day pharmacy resource utilization. Cox proportional hazards evaluated the association of induction regimen (none/corticosteroid-only, nondepleting, and depleting) on patient and graft survival. Additional outcomes, including opportunistic infections and posttransplant lymphoproliferative disorder, were studied using multivariable logistic regression. Overall, 64.9% received none/corticosteroid-only induction, whereas 28.1% received nondepleting, 8.3% received depleting, and 2.5% other antibody regimens. Differences in patient characteristics were small, but center practices were heterogeneous. Compared with none/corticosteroid-only induction, nondepleting induction was associated with reduced acute rejection (odd ratio [OR], 0.53; P <.001) but with the increased posttransplant lymphoproliferative disorder (OR, 1.75; P =.021). Depleting induction was associated with improved graft survival (hazard ratio [HR], 0.64; P =.028) but with increased noncytomegalovirus opportunistic infections (OR, 1.46; P =.046). Depleting induction is underused yet may offer long-term benefits in this large multicenter cohort. Greater consensus guidance in this aspect of pediatric LT care is warranted.
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Trasplante de Hígado , Trastornos Linfoproliferativos , Humanos , Niño , Estados Unidos/epidemiología , Inmunosupresores/uso terapéutico , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Terapia de Inmunosupresión/métodos , Anticuerpos Monoclonales , Corticoesteroides , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/etiología , Rechazo de Injerto , Supervivencia de InjertoRESUMEN
OBJECTIVE: Solid-organ transplantation (SOT) has become the standard of care for children with terminal organ failure. Long-term immunosuppression has improved survival substantially but is associated with secondary malignancies and impaired wound healing. Our goal was to review the incidence, outcomes, complications, and rate of posttransplant lymphoproliferative disorder on pathologic examination following tonsillectomy/adenotonsillectomy (T/AT) in children after SOT. STUDY DESIGN: A retrospective cohort study. SETTING: Tertiary care children's hospital. METHODS: Data were extracted from charts of children with a history of kidney, heart, or liver transplantation, who underwent T/AT between 2006 and 2021. RESULTS: A total of 110 patients met the inclusion criteria, including 46 hearts, 41 kidneys, 19 livers, and 4 liver-and-kidney transplants. The mean age at transplantation was 4.2 years, and the mean transplantation-to-T/AT time interval was 28.8 months. The posttransplant lymphoproliferative disorder was diagnosed in 52 (47.3%) patients, and 25% of these had no tonsillar hypertrophy. There was no difference in age at transplantation, organ received, transplantation-to-T/AT time interval, immunosuppressive medications, tonsil size, or tonsillar asymmetry between patients diagnosed with the posttransplant lymphoproliferative disorder and patients with benign tonsillar/adenotonsillar hypertrophy. Posttonsillectomy complications were similar between the groups. CONCLUSION: The incidence of posttransplant lymphoproliferative disorder undergoing tonsillectomy for any indication was 47.3%. There was no association between preoperative signs and symptoms and the histopathological diagnosis of posttransplant lymphoproliferative disorder. Stratification by organ received and immunosuppressive medications did not identify differences among the groups relative to the incidence of posttransplant lymphoproliferative disorder and other postoperative complications.
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Trastornos Linfoproliferativos , Trasplante de Órganos , Tonsilectomía , Niño , Humanos , Tonsilectomía/efectos adversos , Estudios Retrospectivos , Trasplante de Órganos/efectos adversos , Hipertrofia , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/patologíaRESUMEN
INTRODUCTION: Post-transplant lymphoproliferative disorders (PTLD) represent a diverse group of diseases. They develop as a consequence of uncontrolled proliferation of lymphoid or plasmacytic cells resulting from T-cell immunosuppression after transplantation of either hematopoietic cells (HCT) or solid organs (SOT), caused mainly by latent Epstein-Barr virus (EBV). The risk for EBV recurrence is dependent on the level of incompetency of the immune system, presented as an impairment of T-cell immunity. AREAS COVERED: This review summarizes the data on incidence and risk factors of EBV infection in patients after HCT. The median rate of EBV infection in HCT recipients was estimated at 30% after allogeneic and<1% after autologous transplant; 5% in non-transplant hematological malignancies; 30% in SOT recipients. The median rate of PTLD after HCT is estimated at 3%. The most frequently reported risk factors for EBV infection and disease include: donor EBV-seropositivity, use of T-cell depletion, especially with ATG; reduced-intensity conditioning; mismatched family or unrelated donor transplants; and acute or chronic graft-versus-host-disease. EXPERT OPINION: The major risk factors for EBV infection and EBV-PTLD can be easily identified: EBV-seropositive donor, depletion of T-cells, and the use of immunosuppressive therapy. Strategies for avoiding risk factors include elimination EBV from the graft and improving T-cell function.