Age and Epstein-Barr viral load at diagnosis of post-transplant lymphoproliferative disease are associated with patient survival in kidney transplant recipients.

INTRODUCTION: This study investigated variables associated with mortality in kidney transplant recipients (KTRs) diagnosed with post-transplant lymphoproliferative disease (PTLD) and a simultaneous Epstein-Barr virus (EBV) viremia. METHODS: This was a retrospective cohort study enrolling KTRs diagnosed with PTLD between 2018 and 2020. Outcome: death within two years after diagnosis. RESULTS: Among 1,625 KTRs who collected EBV viremia (by PCR, 2018-2020) for any reason, 238 (14.6%) had a positive viral load and 41 (17.2%) simultaneous PTLD. These 41 patients were 40.1 years old at diagnosis and 8.6 years after transplantation; 26.8% were induced with rATG and 92.7% were maintained on tacrolimus and azathioprine (TAC/AZA) as immunosuppressive regimen. Lymph nodes (75.6%) was the most common site of PTLD, followed by the gastrointestinal tract (48.8%), with 61.0% at Lugano stage IV and 80.5% monomorphic PTLD. The mean EBV viral load was 12,198 IU/mL. One- and two-year patient survival post-diagnosis was 60.4% and 46.8%, respectively. In the Cox regression analysis, age at PTLD diagnosis (HR for each year = 1.039; p < 0.001) and EBV viral load (HR for each log = 1.695; p = 0.026) were associated with risk of death. CONCLUSION: This study suggests that in patients predominantly on TAC/AZA, PTLD with simultaneous EBV positive viral load is a late event, and worse survival is associated with older age and EBV viral load at diagnosis.

Post-transplant lymphoproliferative disorders in a cohort of adult patients with a liver transplant from a reference hospital in Bogotá, Colombia / Trastornos linfoproliferativos en una cohorte de pacientes adultos con trasplante hepático atendidos en un hospital de referencia en Bogotá, Colombia.

Introduction: The post-transplant lymphoproliferative disorders (PTLD) are characterized by an uncontrolled pathological lymphoid proliferation as a consequence of transplant immunosuppression therapy. Objective: To characterize the clinical and pathological characteristics of PTLD in a cohort of adult patients with liver transplant during a 15 year period at the Hospital Universitario Fundación Santa Fe de Bogota. Materials and methods: We conducted an observational retrospective study by searching for the PTLD cases diagnosed during the study period in the databases of the Liver Transplantation Unit and the Pathology Department. We collected the epidemiological, clinical, and pathological information and performed the corresponding statistics analyses. Results: During the research period, 572 patients were transplanted; the incidence of PTDL was 2.44%; 79% of them were man and the average age at the time of diagnosis was 62.5 years; 71% of the cases were diagnosed during the first year after the transplant and the same percentage EBV-seropositive patients. The most frequent pathological phenotype was monomorphic and the majority of tumors was detected in the hepatic hilum. The one-year survival was 50%. Conclusion: The high proportion of early cases and the high frequency of Epstein-Barr virus seropositivity both in donors and receptors drewour attention. More studies are necessary to have a better understanding of this condition in Colombia. This is the first PTLD clinical and pathological analysis in liver-transplant patients from Colombia to date.

Introducción. Los trastornos linfoproliferativos después de un trasplante se caracterizan por la proliferación descontrolada de linfocitos como consecuencia del tratamiento inmunosupresor posterior a este. Objetivo. Caracterizar clínica y patológicamente los casos de trastornos linfoproliferativos después de trasplante (Post-Transplant Lymphoproliferative Disorders, PTLD) en una cohorte de pacientes adultos con trasplante de hígado atendidos a lo largo de 15 años en el Hospital Universitario Fundación Santa Fe de Bogotá. Materiales y métodos. Se hizo un estudio observacional retrospectivo a partir de la revisión de las bases de datos de la Unidad de Trasplante Hepático y del Departamento de Patología del Hospital en busca de los casos de PTLD diagnosticados durante el periodo de estudio. Se recolectó la información epidemiológica, clínica y patológica, y se adelantaron los análisis estadísticos. Resultados. Durante el periodo de estudio, hubo 572 pacientes con trasplante de hígado, la incidencia de trastornos linfoproliferativos fue de 2,44 %, el 79 % en hombres, y la edad promedio en el momento del diagnóstico fue de 62,5 años. El 71 % de los casos se presentó durante los primeros 12 meses después del trasplante y el mismo porcentaje fue seropositivo para el virus de Epstein-Barr (EBV). El fenotipo patológico más frecuente fue el monomorfo y la mayoría de los tumores se detectaron en el hilio hepático. La supervivencia al año fue del 50 %. Conclusiones. Llamó la atención el alto porcentaje de casos de presentación temprana, así como la gran frecuencia de seropositividad para el EBV tanto en los donantes como en los receptores. Deben adelantarse estudios más detallados para una mejor comprensión de esta enfermedad en el país. Este es el primer análisis clínico y patológico de PTLD en pacientes con trasplante de hígado adelantado en Colombia hasta la fecha.

Epstein-Barr Virus-Positive Mucocutaneous Ulcer in a Pediatric Patient-Case Report.

The Epstein-Barr virus (EBV)-positive mucocutaneous ulcer is a rare entity in the spectrum of lymphoproliferative diseases associated with the EBV. It occurs typically in patients with immunosuppression associated with immunosenescence, as well as due to iatrogenic causes, posttransplant patients and primary immunodeficiency disorders. It is often a benign and self-limited disease that recedes by stopping or reducing the immunosuppressive agents in most of the cases. Histologically, it is characterized by a population of EBV-positive atypical lymphoid cells. Here, we present a rare case of a 5-month-old pediatric patient, born preterm at 24 weeks of gestational age, presenting a lump on the right shoulder, later evolving to EBV-positive mucocutaneous ulcer.

Extrahepatic manifestations of HCV: the role of direct acting antivirals.

INTRODUCTION: Hepatitis C virus (HCV) represents a major health concern, as nearly 3 million people become newly infected by this pathogen annually. The majority of infected individuals fail to clear the virus, and chronicity is established. Chronic HCV patients are at high risk for liver disease, ranging from mild fibrosis to cirrhosis and severe hepatocellular carcinoma. Over the last few years, the development of multiple direct acting antivirals (DAA) have revolutionized the HCV infection treatment, demonstrating cure rates higher than 90%, and showing less side effects than previous interferon-based regimens. Areas covered: Besides liver, HCV infection affects a variety of organs, therefore inducing diverse extrahepatic manifestations. This review covers clinical, experimental, and epidemiological publications regarding systemic manifestations of HCV, as well as recent studies focused on the effect of DAA in such conditions. Expert commentary: Though further research is needed; available data suggest that HCV eradication is often associated with the improvement of extrahepatic symptoms. Therefore, the emergence of DAA would offer the opportunity to treat both HCV infection and its systemic manifestations, requiring shorter treatment duration and driving minor adverse effects.

Epstein-Barr virus load in transplant patients: Early detection of post-transplant lymphoproliferative disorders / Carga de virus Epstein-Barr en pacientes trasplantados: detección temprana de desórdenes linfoproliferativos postrasplante

High levels of circulating EBV load are used as a marker of post-transplant lymphoproliferative disorders (PTLD). There is no consensus regarding the threshold level indicative of an increase in peripheral EBV DNA. The aim of the study was to clinically validate a developed EBV quantification assay for early PTLD detection. Transversal study: paired peripheral blood mononuclear cells (PBMC), plasma and oropharyngeal lymphoid tissue (OLT) from children undergoing a solid organ transplant with (n = 58) and without (n = 47) PTLD. Retrospective follow-up: 71 paired PBMC and plasma from recipients with (n = 6) and without (n = 6) PTLD history. EBV load was determined by real-time PCR. The diagnostic ability to detect all PTLD (categories 1-4), advanced PTLD (categories 2-4) or neoplastic PTLD (categories 3 and 4) was estimated by analyzing the test performance at different cut-off values or with a load variation greater than 0.5 log units. The higher diagnostic performance for identifying all, advanced or neoplastic PTLD, was achieved with cut-off values of 1.08; 1.60 and 2.47 log EBV gEq/10(5) PBMC or 2.30; 2.60; 4.47 log gEq/10(5) OLT cells, respectively. EBV DNA detection in plasma showed high specificity but low (all categories) or high (advanced/neoplastic categories) sensitivity for PTLD identification. Diagnostic performance was greater when: (1) a load variation in PBMC or plasma was identified; (2) combining the measure of EBV load in PBMC and plasma. The best diagnostic ability to identify early PTLD stages was achieved by monitoring EBV load in PBMC and plasma simultaneously; an algorithm was proposed.

La carga alta del virus Epstein-Barr se utiliza como un marcador de desórdenes linfoproliferativos postrasplante (post-transplant lymphoproliferative disorders [PTLD]). El objetivo de este estudio fue validar clínicamente un ensayo de cuantificación del virus Epstein-Barr para la detección temprana de PTLD. Se efectuó un estudio transversal en el que se analizaron muestras pareadas de células mononucleares periféricas (CMP), de plasma y de tejido linfoide orofaríngeo de niños con trasplante de órgano sólido, con PTLD (n = 58) y sin PTLD (n = 47). En el seguimiento retrospectivo se incluyeron 71 muestras pareadas de CMP y de plasma de trasplantados, con PTLD (n = 6) y sin PTLD (n = 6). La carga viral se determinó por PCR en tiempo real. Se estimó la capacidad diagnóstica para detectar PTLD (categorías: todas vs. avanzadas vs. neoplásicas) analizando diferentes valores de corte o una variación de carga mayor de 0,5 logaritmos. El mayor desempeño diagnóstico para identificar todos los PTLD, los avanzados y los neoplásicos, se obtuvo con valores de corte de 1,08; 1,60 y 2,47 log copias/10(5) en CMP y de 2,30; 2,60 y 4,48 log copias/10(5) en células de tejido linfoide orofaríngeo, respectivamente. La detección del ADN del virus Epstein-Barr en el plasma mostró una especificidad alta, pero una sensibilidad baja (todas las categorías) o alta (categorías avanzadas o neoplásicas) para identificar PTLD. Se observó el desempeño diagnóstico más alto en las siguientes condiciones: 1) al identificar una variación de carga en CMP o en plasma; 2) combinando la medición de la carga viral en CMP y en plasma. La mejor capacidad diagnóstica para identificar las etapas tempranas de los PTLD se logró mediante el seguimiento simultáneo de la carga viral en CMP y en plasma; se propone un algoritmo.

Epstein-Barr virus load in transplant patients: Early detection of post-transplant lymphoproliferative disorders.

High levels of circulating EBV load are used as a marker of post-transplant lymphoproliferative disorders (PTLD). There is no consensus regarding the threshold level indicative of an increase in peripheral EBV DNA. The aim of the study was to clinically validate a developed EBV quantification assay for early PTLD detection. Transversal study: paired peripheral blood mononuclear cells (PBMC), plasma and oropharyngeal lymphoid tissue (OLT) from children undergoing a solid organ transplant with (n=58) and without (n=47) PTLD. Retrospective follow-up: 71 paired PBMC and plasma from recipients with (n=6) and without (n=6) PTLD history. EBV load was determined by real-time PCR. The diagnostic ability to detect all PTLD (categories 1-4), advanced PTLD (categories 2-4) or neoplastic PTLD (categories 3 and 4) was estimated by analyzing the test performance at different cut-off values or with a load variation greater than 0.5log units. The higher diagnostic performance for identifying all, advanced or neoplastic PTLD, was achieved with cut-off values of 1.08; 1.60 and 2.47log EBVgEq/10(5) PBMC or 2.30; 2.60; 4.47loggEq/10(5) OLT cells, respectively. EBV DNA detection in plasma showed high specificity but low (all categories) or high (advanced/neoplastic categories) sensitivity for PTLD identification. Diagnostic performance was greater when: (1) a load variation in PBMC or plasma was identified; (2) combining the measure of EBV load in PBMC and plasma. The best diagnostic ability to identify early PTLD stages was achieved by monitoring EBV load in PBMC and plasma simultaneously; an algorithm was proposed.

Epstein-Barr virus (EBV)--associated posttransplant lymphoproliferative disorder appearing as mandibular gingival ulcers.

Posttransplant lymphoproliferative disorders (PTLDs) comprise a spectrum of complications that affect immunocompromised patients following hematopoietic stem cell transplantation or solid organ transplantation. Its incidence varies depending on the transplanted organ, occurring in approximately 2.3% of kidney transplantations. A 31-year-old woman was referred to the Dental Clinic of the State University of Western Paraná for evaluation of an oral lesion. Her medical history revealed a previous diagnosis of hypertension, Epstein-Barr virus (EBV) seropositivity, and kidney transplantation 12 years prior. She was under standard immunosuppressive therapy. Intraoral examination identified a gingival necrotic lesion with extension to the posterior right lower alveolar bone. An incisional biopsy was performed. Histologic examination showed lymphocytic proliferation of cells with small and hyperchromatic nuclei, atypical mitosis, and cells with large and pale nuclei showing prominent nucleoli permeating connective tissue, muscle fibers, and adipocytes. Correlation of clinical, histologic, and immunohistochemical findings led to a diagnosis of polymorphic EBV-associated PTLD rich in B and T cells.

The Impact of EBV Status on Characteristics and Outcomes of Posttransplantation Lymphoproliferative Disorder.

We examined the associations of Epstein-Barr virus (EBV) status with characteristics and outcomes of posttransplantation lymphoproliferative disorder (PTLD) by studying 176 adult solid organ transplant recipients diagnosed with PTLD between 1990 and 2013 (58 [33%] EBV-negative; 118 [67%] EBV-positive). The proportion of EBV-negative cases increased over time from 10% (1990-1995) to 48% (2008-2013) (p < 0.001). EBV-negative PTLD had distinct characteristics (monomorphic histology, longer latency) though high-risk features (advanced stage, older age, high lactate dehydrogenase, central nervous system involvement) were not more common compared to EBV-positive PTLD. In multivariable analysis, EBV negativity was not significantly associated with worse response to initial therapy (adjusted odds ratio, 0.84; p = 0.75). The likelihood of achieving a complete remission (CR) was not significantly different for EBV-negative versus EBV-positive PTLD including when therapy was reduction of immunosuppression alone (35% vs. 43%, respectively, p = 0.60) or rituximab (43% vs. 47%, p = 1.0). EBV negativity was also not associated with worse overall survival (adjusted hazard ratio, 0.91; p = 0.71). Our findings indicate that EBV status is not prognostic or predictive of treatment response in adults with PTLD. The high proportion of EBV-negative disease diagnosed in recent years highlights the need for new strategies for prevention and management of EBV-negative PTLD.

Management of post-transplant Epstein-Barr virus-related lymphoproliferative disease in solid organ and hematopoietic stem cell recipients.

Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) is one of the most serious complications associated with solid organ and hematopoietic stem cell transplantation. PTLD is most frequently seen with primary EBV infection post-transplant, a common scenario for pediatric solid organ recipients. Risk factors for infection or reactivation of EBV following solid organ transplant are stronger immunosuppressive therapy regimens, and being seronegative for receptor. For hematopoietic stem cell transplantation, the risk factors relate to the type of transplant, human leukocyte antigen disparity, the use of stronger immunosuppressants, T-cell depletion, and severe graft-versus-host disease. Mortality is high, and most frequent in patients who develop PTLD in the first six months post-transplant. The primary goal of this article is to provide an overview of the clinical manifestations, diagnosis, accepted therapies, and management of EBV infection in transplant recipients, and to suggest that the adoption of monitoring protocols could contribute to a reduction in related complications.

Management of post-transplant Epstein-Barr virus-related lymphoproliferative disease in solid organ and hematopoietic stem cell recipients

Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) is one of the most serious complications associated with solid organ and hematopoietic stem cell transplantation. PTLD is most frequently seen with primary EBV infection post-transplant, a common scenario for pediatric solid organ recipients. Risk factors for infection or reactivation of EBV following solid organ transplant are stronger immunosuppressive therapy regimens, and being seronegative for receptor. For hematopoietic stem cell transplantation, the risk factors relate to the type of transplant, human leukocyte antigen disparity, the use of stronger immunosuppressants, T-cell depletion, and severe graft-versus-host disease. Mortality is high, and most frequent in patients who develop PTLD in the first six months post-transplant. The primary goal of this article is to provide an overview of the clinical manifestations, diagnosis, accepted therapies, and management of EBV infection in transplant recipients, and to suggest that the adoption of monitoring protocols could contribute to a reduction in related complications.

Duplex realtime PCR method for Epstein-Barr virus and human DNA quantification: its application for post-transplant lymphoproliferative disorders detection

INTRODUCTION: The quantification of circulating Epstein-Barr virus (EBV) DNA is used to monitor transplant patients as an early marker of Post-Transplant Lymphoproliferative Disorders (PTLD). So far no standardized methodology exists for such determination. OBJECTIVE: Our purpose was to develop and validate a real-time PCR assay to quantify EBV DNA in clinical samples from transplant recipients. METHODS: A duplex real-time PCR method was developed to amplify DNA from EBV and from a human gene. The EBV load was determined in peripheral blood mononuclear cells (PBMC), plasma and oropharyngeal tissue from 64 non-transplanted patients with lymphoid-hypertrophy (Non-Tx), 47 transplant recipients without PTLD (Tx), 54 recipients with PTLD (Tx-PTLD), and 66 blood donors (BD). WinPEPI, version 11.14 software was used for statistical analysis. RESULTS: Analytical validation: the intra and inter-assays variation coefficients were less than 4.5% (EBV-reaction) and 3% (glyceraldehyde 3-phosphate dehydrogenase - GAPDH reaction). Linear ranges comprised 107-10 EBV genome equivalents (gEq) (EBV-reaction) and 500,000-32 human gEq (GAPDH-reaction). The detection limit was 2.9 EBV gEq (EBV-reaction). Both reactions showed specificity. Application to clinical samples: higher levels of EBV were found in oropharyngeal tissue from transplanted groups with and without PTLD, compared to Non-Tx (p < 0.05). The EBV load in PBMC from the groups of BD, Non-Tx, Tx and Tx-PTLD exhibited increasing levels (p < 0.05). In BD, PBMC and plasma, EBV loads were undetectable. CONCLUSIONS: The performance of the assay was suitable for the required clinical application. The assay may be useful to monitor EBV infection in transplant patients, in particular in laboratories from low-income regions that cannot afford to use commercial assays. .

Duplex realtime PCR method for Epstein-Barr virus and human DNA quantification: its application for post-transplant lymphoproliferative disorders detection.

INTRODUCTION: The quantification of circulating Epstein-Barr virus (EBV) DNA is used to monitor transplant patients as an early marker of Post-Transplant Lymphoproliferative Disorders (PTLD). So far no standardized methodology exists for such determination. OBJECTIVE: Our purpose was to develop and validate a real-time PCR assay to quantify EBV DNA in clinical samples from transplant recipients. METHODS: A duplex real-time PCR method was developed to amplify DNA from EBV and from a human gene. The EBV load was determined in peripheral blood mononuclear cells (PBMC), plasma and oropharyngeal tissue from 64 non-transplanted patients with lymphoid-hypertrophy (Non-Tx), 47 transplant recipients without PTLD (Tx), 54 recipients with PTLD (Tx-PTLD), and 66 blood donors (BD). WinPEPI, version 11.14 software was used for statistical analysis. RESULTS: Analytical validation: the intra and inter-assays variation coefficients were less than 4.5% (EBV-reaction) and 3% (glyceraldehyde 3-phosphate dehydrogenase - GAPDH reaction). Linear ranges comprised 10(7)-10 EBV genome equivalents (gEq) (EBV-reaction) and 500,000-32 human gEq (GAPDH-reaction). The detection limit was 2.9 EBV gEq (EBV-reaction). Both reactions showed specificity. Application to clinical samples: higher levels of EBV were found in oropharyngeal tissue from transplanted groups with and without PTLD, compared to Non-Tx (p<0.05). The EBV load in PBMC from the groups of BD, Non-Tx, Tx and Tx-PTLD exhibited increasing levels (p<0.05). In BD, PBMC and plasma, EBV loads were undetectable. CONCLUSIONS: The performance of the assay was suitable for the required clinical application. The assay may be useful to monitor EBV infection in transplant patients, in particular in laboratories from low-income regions that cannot afford to use commercial assays.

[Viruses as agents inducing cutaneous neoplasms]. / Virus como inductores de neoplasias cutáneas.

The oncogenic role of viruses in cutaneous neoplasms has been known by humankind for more than a century, when the origin of the common wart, or verruca vulgaris, was attributed to the human papilloma virus (HPV). Currently, virus-induced cutaneous neoplasms may be grouped into solid tumors and lymphoproliferative disorders. HPV, from which various serotypes are now known, each being linked to a specific neoplasm, the human herpes virus type 8 producing Kaposi sarcoma, and the Merkel cell polyomavirus, highlight among the first group. Regarding the lymphoproliferative disorders, we should mention the human T-lymphotropic virus type I (HTLV-1), which is responsible for the T-cell lymphomas, in which the cutaneous manifestations are non-specific and have a wide spectrum, thus posing a challenge for differential diagnosis. The Epstein Barr virus, linked to nasal lymphomas of NK/T-cells and Hydroa-like cutaneous lymphomas, is also part of this group. In an era in which the genetic and molecular aspects of cancer research prevail, we may not leave behind the concept of neoplasms as a result an infection with a viral agent, which opens a wide array of new possibilities for cancer treatment based on antiviral drugs.

Virus como inductores de neoplasias cutáneas / Viruses as agents inducing cutaneous neoplasms

El rol oncogénico de los virus en las neoplasias cutáneas es conocido por el hombre desde hace más de un siglo, cuando se atribuía el origen de la verruga vulgar al virus papiloma humano (VPH). En la actualidad, las neoplasias inducidas por virus pueden agruparse en tumores sólidos y procesos linfoproliferativos. Destacan entre los primeros el VPH, del cual ahora conocemos numerosos serotipos, cada uno vinculado a una neoplasia específica, el herpesvirus humano tipo 8 que produce el sarcoma de Kaposi y el poliomavirus vinculado al carcinoma de Merkel. Entre los procesos linfoproliferativos debemos mencionar al virus linfotrópico de células T humanas tipo 1 (HTLV-1) responsable de los linfomas de células T, en los cuales el compromiso cutáneo es inespecífico, con un amplio espectro de presentaciones clínicas y, que por consiguiente, plantean un reto para el diagnóstico diferencial. En este grupo también se encuentra el virus Epstein Barr vinculado a los linfomas nasales de Células NK/T y a los linfomas tipo Hidroa, de reciente descripción. En esta era en la que lo genético y lo molecular priman en las investigaciones en cáncer, no podemos dejar de lado el concepto de neoplasia como resultado de la infección por un agente viral, lo que abre una nueva veta de posibilidades de tratamiento anticanceroso basado en medicamentos antivirales.

The oncogenic role of viruses in cutaneous neoplasms has been known by humankind for more than a century, when the origin of the common wart, or verruca vulgaris, was attributed to the human papilloma virus (HPV). Currently, virus-induced cutaneous neoplasms may be grouped into solid tumors and lymphoproliferative disorders. HPV, from which various serotypes are now known, each being linked to a specific neoplasm, the human herpes virus type 8 producing Kaposi sarcoma, and the Merkel cell polyomavirus, highlight among the first group. Regarding the lymphoproliferative disorders, we should mention the human T-lymphotropic virus type I (HTLV-1), which is responsible for the T-cell lymphomas, in which the cutaneous manifestations are non-specific and have a wide spectrum, thus posing a challenge for differential diagnosis. The Epstein Barr virus, linked to nasal lymphomas of NK/T-cells and Hydroa-like cutaneous lymphomas, is also part of this group. In an era in which the genetic and molecular aspects of cancer research prevail, we may not leave behind the concept of neoplasms as a result an infection with a viral agent, which opens a wide array of new possibilities for cancer treatment based on antiviral drugs.

Profilaxis de enfermedad por virus de Epstein Barr en niños y adultos receptores de trasplante de órganos sólidos y de precursores hematopoyéticos / Prophylaxis against Epstein Barr disease in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation

Post transplant lymphoproliferative disease (PTLD) associated with EBV infection is one of the most life-threatening complications in SOT and HSCT. Risk factors for infection or reactivation of EBV in SOT are the use of greater immunosuppression, seronegative receptor and CMV infection. In HSCT, the risk factors are related to type of transplant, HLA disparity, the greater immunosuppression, T-cell depletion and severe GVHD. There is no scientific evidence to support the use of specific therapy for prophylaxis of EBV infection. Prophylaxis recommendations focus on avoid exposure of transplant recipients to sources of virus, through hygiene practices such as hand washing (A3), avoid sharing utensils (B3) and avoid contact with potentially infected secretions (respiratory or saliva) (A2). For PTLD prevention, the recommendation is regular EBV viral load monitoring by rtPCR. In SOT with logarithmic rising of EBV loads, it is recommended to reduce immunosuppression and periodically perform exams to diagnose PTLD. In HSCT, it is recommended to reduce immunosuppression whenever possible, and use rituximab according to speciic protocol. Acyclovir or gancyclovir have not proven to be of any eficacy in PTLD prophylaxis in SOT (C3) or HSCT (D2), so their administration as preemptive therapy is no recommended.

El síndrome linfoproliferativo (SLP) asociado a VEB constituye una grave complicación en TOS y en TPH. Los factores de riesgo de infección o reactivación de VEB en TOS son el uso de mayor inmunosupresión, la seronegatividad del receptor previa al trasplante y la infección por CMV. En TPH se consideran factores de riesgo el tipo de trasplante, disparidad HLA, mayor inmunosupresión, depleción linfocitaria y enfermedad injerto contra hospedero (EICH) grave. No hay evidencia cientíica que apoye el uso de medidas especíicas de proilaxis en prevención de infección por VEB. Se recomienda evitar la exposición a fuentes del virus de los candidatos a trasplantes a través de prácticas de higiene tales como lavado de manos (A3), evitar el compartir utensilios (B3) y evitar el contacto con potenciales secreciones infectadas (respiratorias o saliva) (A2). Para la prevención de SLP, se recomienda un esquema de monitoreo periódico de carga viral de VEB por RPC-TR. En el caso de TOS con cargas de VEB en ascenso logarítmico, se recomienda disminuir inmuno-supresión y buscar activa y periódicamente la aparición de SLP. En TPH, se recomienda, en lo posible, disminuir la inmunosupresión y se reserva el uso de rituximab para casos especíicos según protocolo. El uso de aciclovir o ganciclovir no han demostrado constituir medidas profilácticas efectivas en TOS (C3) ni en TPH (D2), no siendo recomendada su administración en esquemas de terapia anticipada.

[Prophylaxis against Epstein Barr disease in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation]. / Profilaxis de enfermedad por virus de Epstein Barr en niños y adultos receptores de trasplante de órganos sólidos y de precursores hematopoyéticos.

Post transplant lymphoproliferative disease (PTLD) associated with EBV infection is one of the most life-threatening complications in SOT and HSCT. Risk factors for infection or reactivation of EBV in SOT are the use of greater immunosuppression, seronegative receptor and CMV infection. In HSCT, the risk factors are related to type of transplant, HLA disparity, the greater immunosuppression, T-cell depletion and severe GVHD. There is no scientific evidence to support the use of specific therapy for prophylaxis of EBV infection. Prophylaxis recommendations focus on avoid exposure of transplant recipients to sources of virus, through hygiene practices such as hand washing (A3), avoid sharing utensils (B3) and avoid contact with potentially infected secretions (respiratory or saliva) (A2). For PTLD prevention, the recommendation is regular EBV viral load monitoring by rtPCR. In SOT with logarithmic rising of EBV loads, it is recommended to reduce immunosuppression and periodically perform exams to diagnose PTLD. In HSCT, it is recommended to reduce immunosuppression whenever possible, and use rituximab according to speciic protocol. Acyclovir or gancyclovir have not proven to be of any eficacy in PTLD prophylaxis in SOT (C3) or HSCT (D2), so their administration as preemptive therapy is no recommended.

Hepatitis B virus infection has no significant role on lymphoproliferative disorders post liver transplantation: PTLD. int survey.

INTRODUCTION: Based on very limited data, it has been recently suggested that hepatitis B virus infection can play significant roles in post transplantation lymphoproliferative disorders. In the current study pooling data of PTLD in HBV positive liver recipients gathered from the existing literature, we sought to analyze and compare characteristics, behavior and prognosis of PTLD arising in HBV positive liver graft recipients. METHODS: A comprehensive search for the available data though PubMed and Google Scholar for reports of PTLD and HBV infection in liver recipients was conducted. Data of 18 different studies were pooled and analyzed. RESULTS: Liver recipients with HBV positive-PTLD were comparable to their HBV negative counterparts in gender, age at transplantation, time from transplantation to PTLD development, lymphoma cell type, histopathology of lesions, remission episodes, mortality rate, multi-organ involvement, and disseminated PTLD (p > 0.1 for all). HBV positive PTLD patients were significantly less likely to complicate spleen (0 vs. 23%, respectively; p = 0.015). Survival of the two patient groups were comparable (p = 0.8). CONCLUSION: HBV infection has no significant impact on inducing some distinct types of PTLD and represents no survival effect in PTLD setting. Future prospective studies are needed for confirming our findings.

[Human T-cell lymphotropic virus type I infection in patients with lymphoproliferative disorders at two sentinel sites in Cuba]. / Infección por el HTLV-I en pacientes con síndromes linfoproliferativos en dos sitios centinela de Cuba.

OBJECTIVE: To determine the prevalence of human T-cell lymphotropic virus type I (HTLV-I) infection among patients with lymphoproliferative disorders, as well as among their family members and sexual contacts, at two sentinel sites in Cuba. METHODS: An analysis was conducted of all the patients with a presumptive diagnosis of hematological malignancies seen by the hematology departments of the Hospital Hermanos Ameijeiras (HHA), City of Havana, and the Hospital Provincial Comandante Faustino Pérez (HPCFP), Matanza, Cuba, in January 1996-January 1997. HTLV-I seropositivity was determined by ELISA and Western Blot, and infection was confirmed by polymerase chain reaction. The positive patients' family members and sexual contacts were also assessed. The Z-test was used to compare proportions. RESULTS: Seroprevalence of HTLV-I infection in patients with lymphoproliferative disorders was 0.4% higher at the HPCFP than at the HHA (6.1% versus 0.2%, P<0.001). There were no significant differences in prevalence by age, sex, or skin color. Of the 53 family members and sexual contacts studied, 8 (15.1%) were positive for HTLV-I infection. CONCLUSION: The prevalence of HTLV-I in the study group was higher than previously found in Cuba. The value of seroepidemiological surveillance through sentinel sites was confirmed.

Infección por el HTLV-I en pacientes con síndromes linfoproliferativos en dos sitios centinela de Cuba / Human T-cell lymphotropic virus type I infection in patients with lymphoproliferative disorders at two sentinel sites in Cuba

OBJETIVO: Determinar la frecuencia de la infección por el HTLV-I en pacientes con síndromes linfoproliferativos, así como en sus familiares y contactos sexuales, en dos sitios de vigilancia centinela en Cuba. MÉTODOS: Se analizaron todos los pacientes que tenían un diagnóstico presuntivo de neoplasias hematológicas entre enero de 1996 y enero de 2007 atendidos en los servicios de hematología del Hospital Hermanos Ameijeiras (HHA), de Ciudad de La Habana, y el Hospital Provincial Comandante Faustino Pérez (HPCFP), de Matanzas, Cuba. Se determinó la seropositividad al HTLV-I por ELISA y western blot y se confirmó la infección mediante la reacción en cadena de la polimerasa. Se estudiaron también los familiares y los contactos sexuales de los pacientes positivos. Se utilizó la prueba de la Z para la comparación de proporciones. RESULTADOS: La seroprevalencia de la infección por el HTLV-I en pacientes con síndromes linfoproliferativos fue de 0,4 por ciento, mayor en el HPCFP que en el HHA (6,1 por ciento frente a 0,2 por ciento; P < 0,001). No se encontraron diferencias significativas en la frecuencia de la infección según la edad, el sexo y el color de la piel. De los 53 familiares y contactos sexuales estudiados, 8 (15,1 por ciento) tuvieron diagnóstico positivo de infección por el HTLV-I. CONCLUSIÓN: La frecuencia de la infección por el HTLV-I en el grupo estudiado fue superior a la encontrada con anterioridad en Cuba. Se confirmó la utilidad de la vigilancia seroepidemiológica mediante centros centinela.

OBJECTIVE: To determine the prevalence of human T-cell lymphotropic virus type I (HTLV-I) infection among patients with lymphoproliferative disorders, as well as among their family members and sexual contacts, at two sentinel sites in Cuba. METHODS: An analysis was conducted of all the patients with a presumptive diagnosis of hematological malignancies seen by the hematology departments of the Hospital Hermanos Ameijeiras (HHA), City of Havana, and the Hospital Provincial Comandante Faustino Pérez (HPCFP), Matanza, Cuba, in January 1996-January 1997. HTLV-I seropositivity was determined by ELISA and Western Blot, and infection was confirmed by polymerase chain reaction. The positive patients' family members and sexual contacts were also assessed. The Z-test was used to compare proportions. RESULTS: Seroprevalence of HTLV-I infection in patients with lymphoproliferative disorders was 0.4 percent higher at the HPCFP than at the HHA (6.1 percent versus 0.2 percent, P < 0.001). There were no significant differences in prevalence by age, sex, or skin color. Of the 53 family members and sexual contacts studied, 8 (15.1 percent) were positive for HTLV-I infection. CONCLUSION: The prevalence of HTLV-I in the study group was higher than previously found in Cuba. The value of seroepidemiological surveillance through sentinel sites was confirmed.