Trasplante Renal en un paciente con Síndrome de Down, Seudo Prune Belly y un trastorno linfoproliferativo post-trasplante: Primer reporte de un caso en Argentina / Kidney trasplantation in a female infant with Down syndrome, Pseudo Prune Belly Syndrome, and a post-transplant lymphoproliferative disorder. First case report in Argentina

RESUMEN Introducción: Los pacientes con trisomía 21 tienen un mayor riesgo de anomalías congénitas, incluidas las anomalías renales y de vías urinarias. La ocurrencia del Síndrome de Prune Belly y el Síndrome de Down ha sido descrita, pero representaría una coincidencia. Existen escasos reportes que describan estos pacientes y que fueran trasplantados. Caso Clínico: Paciente de 5 años con diagnóstico prenatal de trisomía 21. La ecografía postnatal reveló megavejiga y riñones displásicos. Comenzó con diálisis peritoneal a los 5 meses de vida. Se realizó el trasplante renal a los 3 años de edad, complicando con trombosis aguda de la arteria y pérdida del injerto. Cuatro meses después del segundo trasplante, la paciente fue diagnosticada con un trastorno linfoproliferativo post-trasplante.Conclusión: Se describe la evolución y el manejo de un único paciente que presentó múltiples complicaciones, con la esperanza de contribuir al conocimiento existente en relación con los pacientes trasplantados renales con síndrome de Down.

ABSTRACT Introduction: Patients with trisomy 21 have a higher risk for congenital anomalies including congenital anomalies of the kidney and urinary tract. The association between Prune Belly Syndrome and Down Syndrome has been described but the occurrence of both conditions would likely represent a coincidence. There are few published reports on renal transplantation in patients with this syndromes. Clinical Case: We reporte a 5-year-old female patient with antenal diagnosis of down syndrome. Post-natal abdominal ultrasound revealed megabladder and dysplastic kidneys. At five months of age, she was commenced on peritoneal dialysis. The patient underwent renal transplantation at age of 3. Acute thrombosis of transplanted renal artery was diagnosed, resulting in graft loss. Four months after second transplantation, the patient presented bilateral tonsillar enlargement and a post-transplant lymphoproliferative disorder was diagnosed. Conclusion: We describe the existence of these conditions in a single patient who underwent kidney transplantation, it's clinical manement and follow up. This case has been reported with the hope of contributing to the existing knowledge which pertains to kidney transplantation patients with Down syndrome.

Central nervous system post-transplant lymphoproliferative disorder: a case report / 中华神经科杂志

Post-transplant lymphoproliferative disorder (PTLD) is a solid organ or hematopoietic stem cells transplant associated syndrome, and central nervous system PTLD(CNS-PTLD) is extremely rare. A case of CNS-PTLD occurring after 24 years of kidney transplant was reported, and pathological examination proved it to be diffuse large B cell lymphoma. Cerebrospinal fluid next generation sequencing and pathological examination supported that Epstein-Barr virus infection was associated with it.

Significance of Epstein-Barr virus-infected lymphocyte cell types in peripheral blood mononuclear cells in post-transplant lymphoproliferative disorder after pediatric liver transplantation / 中华器官移植杂志

Objective:To explore the characteristics and significance of Epstein-Barr virus-infected lymphocyte cell types in peripheral blood mononuclear cells(PBMC)in post-transplant lymphoproliferative disorder(PTLD)after pediatric liver transplantation.Methods:From June 2013 to March 2021, retrospective data analysis was performed for 14 pediatric liver transplant recipients with PTLD.The determination of EBV-DNA in PBMC, plasma and TBNK lymphocyte cells was analyzed.Results:EBV-DNA in PBMC showed a high viral load(>10 4 copies/ml)and plasma EBV-DNA was >10 3 copies/ml( n=8). There were dominant B-cell-type infection( n=12)and T/NK-cell-type infection( n=2). After treatment, EBV-DNA in PBMC and plasma turned negative in 7 patients with a decline( n=6)and an increase( n=1). EBV-DNA in B lymphocyte became negative( n=10)with a decline( n=3). In one case, EBV-DNA increased in T, B and NK cells with a high viral load.The remainders recovered after treatment.One case of hemophagocytic syndrome died from a progression of PTLD. Conclusions:A large majority of EBV-related PTLD are dominated by B-cell-type infection and a few belong to T or NK-cell-type infection.Patients with T/NK-cell-type infection have a worse response to therapy and poorer prognosis than those with B-cell-type infection.Determination of EBV-infected lymphocyte cell types is of vital research value for treatment and prognosis.

Expression of programmed death-1 and programmed death-ligand 1 in post-transplant lymphoproliferative disorders after allogeneic hematopoietic stem cell transplantation in children / 中华实用儿科临床杂志

Objective:To explore the expressions of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) and clinicopathological characteristics in post-transplant lymphoproliferative disorder (PTLD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, with the aim of clarifying whether checkpoint inhibition of PD-1/PD-L1 inhibitors may serve as a therapy option.Methods:The clinical data of 13 cases of PTLD after allo-HSCT pathologically confirmed in Shenzhen Children′s Hospital from January 1, 2012 to December 30, 2019 were retrospectively analyzed.The detection was performed by immunohistochemical staining by MaxVision? method, Epstein-Barr virus(EBV) in situ hybridization and lymphoma gene rearrangement.The relationship between the expression of PD-1 and PD-L1 and the clinicopathological characteristics of PTLD were analyzed.Results:The expression of PD-1 was not correlated with gender, age, primary diseases, histopathological types, transplantation mode and the expression of EBV in situ hybridization (all P>0.05). The expression of PD-L1 was correlated with histopathological types ( P<0.05). Furthermore, the expression rate of PD-L1 on severe β-thalassemia was significantly higher than that of severe aplastic anemia [90.0%(9/10 cases) vs. 66.7%(2/3 cases)] and monomorphic PTLD was higher than that of polymorphic PTLD [100.0%(2/2 cases) vs. 83.3%(5/6 cases)]. Moreover, the positive PTLD in EBV was higher than the negative PTLD in EBV [90.9%(10/11 cases) vs. 50.0%(1/2 cases)]. The positive rates of PD-1 and PD-L1 in 13 cases with PTLD were 46.2%(6/13 cases) and 61.5%(8/13 cases) in tumor cells, 92.3% (12/13 cases) and 76.9% (10/13 cases) in microenvironmental cells, and 84.6%(11/13 cases) in EBV, respectively. Conclusions:PD-L1 has a higher positive rate in tumor cells with monomorphic PTLD; and routine staining for PD-1 and PD-L1 can be performed in all types of PTLD when standard immunotherapy and chemotherapy are ineffective.

Various Clinical Presentation of Post-Transplant Lymphoproliferative Disorder in Head and Neck: A Case Series of 3 Patients / 대한이비인후과학회지

The outcome of solid organ and bone marrow transplantation has been dramatically improved with the development of immunosuppressive agent. However, the use of immunosuppressive agents could increase the risk of malignancies such as post-transplant lymphoproliferative disorder (PTLD). PTLD is regarded as the lymphoid malignancy of patients using immunosuppressive agents, and it could present diverse and non-specific symptoms. It involves various organs including the tonsil, adenoid, lymph node, and the brain. Because of its poor prognosis, an early suspicion of pathologic diagnosis is crucial for the treatment of PTLD. In this report, we demonstrate the case of three pediatric patients who had been treated for PTLD of various clinical presentations by early suspicion and pathologic diagnosis.

Progress of EB virus related post-transplantation lymphoproliferative diseases / 白血病·淋巴瘤

Epstein-Barr virus (EBV) related post-transplant lymphoproliferative diseases (EBV-PTLD) is a rare and deadly complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical manifestations often show the unexplained fever, swollen lymph nodes, hepatosplenomegaly, pharyngitis, and central nervous system symptoms, with rapid disease progression and high fatality rate. As allo-HSCT for treatment of complex and refractory hemopathy has made a great progress, the prevention of graft versus host disease (GVHD) requires more application of immune inhibitors, resulting in an increasing incidence rate of PTLD. In addition to conventional treatments, such as antiviral therapy, reduction of immune suppression , local surgery and traditional chemotherapy, monoclonal antibodies and adoptive immunotherapy with T-cells for treatment of PTLD have brought a profound influence. This paper reviews the latest progress of treatment of EBV-PTLD.

Genotypic Detection of Epstein-Barr Virus in Pediatric Transplant Recipients From India.

Objective: To determine the rate of occurrence and genotypes of Epstein-Barr Virus (EBV) among pediatric renal and liver transplants recipients. Design: Observational study. Setting: Vision Research Foundation referral center and Institute of Liver Disease and Transplantation, Chennai, India. Participants: 70 pediatric solid organ transplant recipients and 60 voluntary healthy donors. Methods: Polymerase chain reaction (PCR) for detection and genotyping of EBV were carried out using genes targeting Viral capsid antigen, Nuclear antigen 1, 2 and 3, followed by real time PCR for viral load determination and further confirmed by phylogenetic analysis. Results: EBV was detected in 35 (51.4%) samples (32 liver and 4 renal transplants) with high viral load. Type A was detected in 33 samples, Type B in 2 liver transplant patients, and co-infection in one liver transplant patient who developed Post-transplant Lymphoproliferative Disorder (PTLD). Real time PCR results correlated with conventional PCR. The mean viral load for patients who did not develop PTLD was 50,424 copies/mL. Overall EBV load in patient with PTLD ranged from 1,40,392 copies/mL prior to PTLD diagnosis to 62,124 copies /mL post treatment. Conclusion: EBV infection is the high risk factor for PTLD after liver transplantation. PCR targeting of EBV can be applied to diagnose EBV infections and monitor treatment for EBV in pediatric solid organ transplant recipients.

Livedo Racemosa Associated with Epstein-Barr Virus-induced Post-transplant Lymphoproliferative Disorder / 대한피부과학회지

Livedo racemosa (LR) is characterized by a striking violaceous netlike patterning of the skin similar to the livedo reticularis, from which it differs by its localization (more generalized), and shape (irregular, broken circular segments). LR is probably caused by patchy impairment of cutaneous arteriolar circulation, resulting in venous dilatation and stasis of blood. LR is always associated with a pathological condition, including hematologic/hypercoagulable disease, vasculitis, connective tissue diseases, neoplasm, lymphoma, infection, cerebrovascular disease, adverse response to a drug, and etc. Hence, clinical, pathological and laboratory examinations are important for excluding these underlying diseases. To date, there have been few reports of LR secondary to posttransplant lymphoproliferative disease (PTLD) in dermatologic literatures. Herein, we report a case of LR associated with Epstein-Barr virus-induced PTLD of cervical lymph node in a 19-year-old female, who had generalized reticular erythematous to violaceous patch on the entire body after allogenic peripheral blood stem cell transplantation.

Enfermedad linfoproliferativa difusa postrasplante en adultos: comunicación de un caso y revisión de la literatura / Post-transplant lymphoproliferative disorder in adults: case report and review of the literature

The post-transplant lymphoproliferative disorder (PTLD) corresponds to a heterogeneous group of lymphoproliferative diseases that develop in solid organ and bone marrow transplant recipients. It occurs in 3-10 percent of patients receiving solid organ transplants, mostly children. It is called early PTLD if it occurs in the first year after transplantation, if it affects B-cell lymphocytes and is associated with infection by Epstein-Barr virus. Late presentation occurs after the first year of transplantation and its pathogenesis is less clear. Clinical manifestations vary from a benign mononucleosis-like clinical setting to high-grade tumors with high mortality (40-60 percent). Treatment depends on the extent of the disease, including reduction of immunosuppressive therapy, radiotherapy, surgery and, more recently, the use of anti-CD20 monoclonal antibody. We report the case of a 67 year-old woman presenting with PTLD on the eighth month after receiving a liver graft.

La enfermedad linfoproliferativa difusa postrasplante (ELDP), corresponde a un grupo heterogéneo de desórdenes linfoproliferativos que se desarrollan en receptores de órganos sólidos y médula ósea. Ocurre en 3 a 10 por ciento de los pacientes receptores de órganos sólidos, fundamentalmente pediátricos. Se denomina ELDP precoz si se presenta en el primer año posterior al trasplante, afecta a los linfocitos de estirpe B y se asocia a la infección por virus Epstein-Barr. La presentación tardía ocurre luego del primer año de trasplante y su etiopatogenia es menos clara. Las manifestaciones clínicas varían desde un cuadro benigno similar a la mononucleosis a neoplasias de alto grade, con elevada mortalidad (40-60 por ciento). El tratamiento dependerá de la extensión de la enfermedad, incluyendo reducción del tratamiento inmunosupresor, radioterapia, cirugía y más recientemente el uso de anticuerpos monoclonales anti CD20. Presentamos el caso clínico de una mujer de 67 años, que al octavo mes de recibir un injerto hepático presenta ELDP.

The efficacy and safety of donor lymphocyte infusion to treat Epstein-Barr virus associated lymphoproliferative diseases after allogeneic hematopoietic stem cell transplantation / 中华内科杂志

Objective To analyse our series patients' data to assess its efficacy and safety of donor lymphocyte infusion (DLI) for Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) after allogeneic hematopoietic stem cell transplantation (HSCT). Methods Patients received HSCT from November 2006 to November 2009 and diagnosed as EBV associated PTLD by pathological or clinical methods were enrolled in this study. Lymphocyte was prepared by COBE collector.Related haplo-donors were the alternative if the original donors was unavailable. A range of mononuclear cell (MNC) dose of (0.5-1.0) × 108/kg was designed and the expected number of T lymphocyte included was at level of 107/kg. Cyclosporine (CsA) trough concentration was kept in a therapeutic level. Results Nine patients with PTLD received DLI 13 times, the median number of PBMC infused was 0.8 (0.16-1.03) ×108/kg, CD3+T cell number was 4.2 (1.6-5.7) × 107/kg. Seven patients received peripheral blood mononuclear cells (PBMC) from original haplo-identical donors, with 7 response and 6 complete remission.Defervescence occurred after 2 ( 1-5 ) d, and adenopathy began to recover in 6 ( 1-14 ) d after the initial infusion of leukocytes. Graft versus host diseases (GVHD) occurred in 6 recipients out of 7 evaluable patients, and all were controlled successfully. Three patients survived for 38, 23 and 3 months after PTLD.Conclusion In this small series cases, infusion of controlled dose of lymphocyte from primary donor is an effective and safe therapy for EBV associated PTLD after mismatched/haploidentical HSCT while the optimal regimen needs to be further studied.

The Post-transplant Lymphoproliferative Disorder after Renal Transplantation / 대한이식학회지

Post-transplant lymphoproliferative disorder (PTLD) is a B cell proliferative disorder that is associated with Eptstein-Bar (EBV). This is a heterogeneous group of conditions characterized by EBV-driven proliferation of B-lymphocytes in the face of impaired T-cell immune surveillance. While new treatment modalities are being tried with variable success, regular EBV surveillance and carefully monitored reduction of immunosuppression remain the mainstay of treatment. This paper reviews the current knowledge of this increasingly common complications in renal transplant recipients.

Epstein-Barr virus-associated Hodgkin's disease following renal transplantation

Post-transplant lymphoproliferative disorders (PTLD) have been recognized as a complication of immunosuppression and occur with a reported incidence of 1 to 8% of recipients receiving solid organ transplantation. PTLD are classified into two major categories, polymorphic and monomorphic PTLD. The majority of the monomorphic PTLD cases are non-Hodgkin's lymphoma of B-cell origin. Hodgkin's disease is not part of the typical spectrum of PTLD; however, it has been rarely reported. We describe a case of Hodgkin's disease following renal transplantation. A 41-year-old man developed right cervical lymphadenopathy following renal transplantation 116 months previously for chronic renal failure of unknown origin. He had been taking cyclosporine, mycophenolate mofetil and prednisone. A lymph node biopsy revealed mixed cellularity Hodgkin's disease. Immunohistochemical staining was positive for CD30 and EBV-latent membrane protein-1. No other site of disease was identified. The immunosuppressive agents were reduced (mycophenolate mofetil was discontinued, cyclosporine dose reduced from 200 mg to 150 mg and prednisone continued at 5 mg). After 2 cycles of ABVD followed by radiation therapy (3600 cGy), he achieved complete remission.

Clinical Manifestations of Posttransplantation Lymphoproliferative Disorder (PTLD) after Liver Transplantation / 감염과화학요법

BACKGROUND: Post-transplantation lymphoproliferative disorder (PTLD) after liver transplantation is a rare but potentially fatal disease. Clinical manifestations and prevalence of PTLD after liver transplantation in Korea have not been investigated thoroughly. MATERIALS AND METHODS: A retrospective chart review was done for 284 liver transplant recipients at Samsung Medical Center, Seoul, Korea during the period from 1996 to 2003. RESULTS: The incidence of PTLD after liver transplantation was 3.9% (11/284). PTLDs were more prevalent in children (9/55, 16.4%) than in adults (2/237, 0.9%; P<0.01). Among the PTLD patients, four cases were male (36.3%) and seven were female (63.7%). Median time from the transplantation to PTLD diagnosis was 9 months. The type of PTLD was as follows:early lesion (6 cases, 54.5%), polymorphic PTLD (3 cases, 27.3%), and B cell lymphoma (2 cases, 18.2%). PTLDs were more prevalent in the patients with cyclosporine use (OR 13.28, 95% CI:1.29-136.31, P=0.03), acute rejection (OR 5.63, 95% CI:1.03-30.62, P=0.04), and negative serology for EBV VCA IgG (OR 19.15, 95% CI:1.99-183.98, P=0.01) by multivariate logistic regression. Three patients (27.3%) died of B cell lymphoma (2 cases) and polymorphic PTLD (1 case). The remaining patients were improved with reduction of immunosuppression and treatment with acyclovir. CONCLUSION: The incidence of PTLD was high in children. The risk factors of PTLD were negative serology for EBV VCA IgG, history of acute rejection, and cyclosporine use. Considering the poor prognosis of PTLD, effective strategies for prevention and early diagnosis for early treatment should be emphasized.

Clinical Manifestations of Posttransplantation Lymphoproliferative Disorder (PTLD) after Liver Transplantation / 감염과화학요법

BACKGROUND: Post-transplantation lymphoproliferative disorder (PTLD) after liver transplantation is a rare but potentially fatal disease. Clinical manifestations and prevalence of PTLD after liver transplantation in Korea have not been investigated thoroughly. MATERIALS AND METHODS: A retrospective chart review was done for 284 liver transplant recipients at Samsung Medical Center, Seoul, Korea during the period from 1996 to 2003. RESULTS: The incidence of PTLD after liver transplantation was 3.9% (11/284). PTLDs were more prevalent in children (9/55, 16.4%) than in adults (2/237, 0.9%; P<0.01). Among the PTLD patients, four cases were male (36.3%) and seven were female (63.7%). Median time from the transplantation to PTLD diagnosis was 9 months. The type of PTLD was as follows:early lesion (6 cases, 54.5%), polymorphic PTLD (3 cases, 27.3%), and B cell lymphoma (2 cases, 18.2%). PTLDs were more prevalent in the patients with cyclosporine use (OR 13.28, 95% CI:1.29-136.31, P=0.03), acute rejection (OR 5.63, 95% CI:1.03-30.62, P=0.04), and negative serology for EBV VCA IgG (OR 19.15, 95% CI:1.99-183.98, P=0.01) by multivariate logistic regression. Three patients (27.3%) died of B cell lymphoma (2 cases) and polymorphic PTLD (1 case). The remaining patients were improved with reduction of immunosuppression and treatment with acyclovir. CONCLUSION: The incidence of PTLD was high in children. The risk factors of PTLD were negative serology for EBV VCA IgG, history of acute rejection, and cyclosporine use. Considering the poor prognosis of PTLD, effective strategies for prevention and early diagnosis for early treatment should be emphasized.

Post-Transplant Lymphoproliferative Disorder / 대한이식학회지

Post-transplant lymphoproliferative disorder (PTLD) is a heterogeneous group of conditions characterized by Epstein-Barr virus (EBV)-driven lymphoid proliferation in the face of impaired T-cell immune surveillance. Most of PTLD are of B- cell origin. Sero-negative recipients of sero-positive organs, and recipients receiving OKT3 are at increased risk. The clinical features are multiple and varied and can range from a benign mononucleosis-like illness to a fulminant non- Hodgkin's lymphoma. Frequently, an extranodal presentation is found with a predilection for brain and allograft. The presentation of forms localized to the renal graft may be incidentally discovered during imaging of the kidney; because the masses may also produce a pressure effect on the collecting system, the patient may present with renal obstruction. To establish diagnosis of PTLD, tissue biopsy is necessary. The mainstay of treatment is immunosuppressive dose reduction. For patients failing to respond to a reduction in immunousppression, a second step of treatment can be used such as interferon alpha, chemotherapy, anti-CD20 antibody (rituximab), and EBV-specific cytotoxic T-cells. Chemotherapy is currently the most commonly used therapeutic alternative. Anti-viral drug therapy has been shown to be of very limited benefit and there are theoretical reasons why it may be ineffective. There appears to be a correlation between PTLD and EBV viral load measured by polymerase chain reaction (PCR) of the peripheral blood, and quantitative PCR may be a useful guide in the management of PTLD. Multicenter randomized trials and standardized diagnostic and therapeutic strategies are required to improve our understanding of PTLD.