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Recent insights in the pathogenesis of post-transplantation lymphoproliferative disorders

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World Journal of Transplantation 2016年第3期6卷 505-516页

作者： Julie Morscio Thomas Tousseyn Department for Imaging and Pathology Translational Cell and Tissue Research Department of Pathology University Hospitals Leuven

Post-transplant lymphoproliferative disorder(PTLD) is an aggressive complication of solid organ and hematopoietic stem cell transplantation that arises in up to 20% of transplant recipients. Infection or reactivation of the Epstein-Barr virus(EBV), a ubiquitous human herpesvirus, in combination with chronic immunosuppression are considered as the main predisposing factors, however insight in PTLD biology is fragmentary. The study of PTLD is complicated by its morphological heterogeneity and the lack of prospective trials, which also impede treatment optimization. Furthermore, the broad spectrum of underlying disorders and the graft type represent important confounding factors. PTLD encompasses different malignant subtypes that resemble histologically similar lymphomas in the general population. Post-transplant diffuse large B-cell lymphoma(PT-DLBCL), Burkitt lymphoma(PTBL) and plasmablastic lymphoma(PT-PBL) occur most frequently. However, in many studies various EBV+ and EBV- PTLD subtypes are pooled, complicating the interpretation of the results. In this review, studies of the gene expression pattern, the microenvironment and the genetic profile of PT-DLBCL, PT-BL and PT-PBL are summarized to better understand the mechanisms underlying post-transplantation lymphomagenesis. Based on the available findings we propose stratification of PTLD according to the histological subtype and the EBV status to facilitate the interpretation of future studies and the establishment of clinical trials.

关键词： Epstein-Barr virus Post-transplant lymphoproliferative disorder Immunodeficiency Diffuse large B-cell lymphoma Burkitt lymphoma Plasmablastic lymphoma

Atypical Cutaneous lymphoproliferative Disorder: A Fatal Mimic of Cutaneous T-Cell Lymphoma in a Patient with HIV Infection

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World Journal of AIDS 2013年第1期3卷 10-15页

作者： Veronica Nguyen Russell Dorer David M. Aboulafia Albany Medical College Albany USA Division of Hematology and Oncology Virginia Mason Medical Center Seattle USA Division of Hematology University of Washington Seattle USA. Division of Pathology Virginia Mason Medical Center Seattle USA

Atypical cutaneous lymphoproliferative disorder (ACLD) is a rare condition that has been associated with HIV infection. Patients with ACLD present with diffuse, erythematous and pruritic skin lesions accompanied by generalized lymphadenopathy. The clinical characteristics of ACLD overlap most notably with several other conditions including Mycosis Fungoides/Sézary Syndrome (MF/SS), a cutaneous lymphoma of T-cell lineage. Unlike Mycosis Fungoides, the noxious infiltrates of ACLD are not monoclonal but polyclonal and consist of cytotoxic CD8+ T-cells instead of CD4+ T-cells or B-cells. Highly active antiretroviral therapy (HAART) has been reported to improve ACLD. We describe the case of a Caucasian man with longstanding HIV infection who presented with severe erythroderma. Skin and lymph node biopsies showed polyclonal CD8+ T-cell infiltrates. Gene rearrangement studies did not reveal an obvious clonal disorder. Hallmark peripheral blood findings consisting of a severe depletion of CD4+ T-lymphocytes and markedly elevated CD8+ cells provided an important diagnostic clue. Despite the purported benefits of HAART in ameliorating this disorder, erythroderma and extreme pruritus improved only after the patient began taking mycophenolate mofetil and hydroxyurea. Unfortunately, he succumbed to complications of methicillin-resistant Staphylococcus aureus septicemia. We alert readers to this rare HIV-associated condition which may mimic other benign and malignant skin conditions and briefly discuss diagnostic and therapeutic options.

关键词： Atypical Cutaneous lymphoproliferative Disorder Mimic Fatal Cutaneous T-Cell Lymphoma HIV Infection

Persistent Epstein-Barr viral load in Epstein-Barr viral na?ve pediatric heart transplant recipients:Risk of late-onset post-transplant lymphoproliferative disease

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World Journal of Transplantation 2016年第4期6卷 729-735页

作者： Bibhuti Das Robert Morrow Rong Huang David Fixler Deptartment of Pediatrics Children’s Medical Center University of Texas Southwestern Medical Center Children’s Medical Center

AIM To examine the risk of late-onset post-transplant lymphoproliferative disorder(PTLD) in the presence of persisting high Epstein-Barr virus(EBV) in EBV na?ve pediatric heart transplant(HT) recipients. METHODS A retrospective review of the medical records of the 145 pediatric HT recipients who had serial EBV viral load monitoring at our center was performed. We defined EBV naive patients whose EBV serology either IgM or IgG in the blood were negative at the time of HT and excluded passive transmission from mother to child in subjects less than 6 mo of age. RESULTS PTLD was diagnosed in 8 out of 145 patients(5.5%); 6/91(6.5%) in those who were EBV seropositive and 2/54(3.7%) in the EBV na?ve group at the time of HT(P = 0.71). We found 32/145(22%) patients with persistently high EBV load during continuing follow-up; 20/91(22%) in EBV seropositive group vs 12/54(22%) in EBV na?ve group(P = 0.97). There was no significant association between pre-HT serostatus and EBV load after transplant(P > 0.05). In the EBV seropositive group, PTLD was diagnosed in 15%(3/20) of patients with high EBV vs 4.2%(3/71) of patients with low or undetectable EBV load(P = 0.14) whereas in EBV na?ve patients 8.3%(1/12) of those withhigh EBV load and 2.3%(1/42) with low or undetectable EBV load(P = 0.41). There was a highly significant association between occurrence of PTLD in those with high EBV load and duration of follow up(4.3 ± 3.9 years) after HT by Cochran-Armitage test for the entire cohort(P = 0.005). At least one episode of acute rejection occurred in 72%(23/32) of patients with high EBV vs 36%(41/113) patients with low or undetectable EBV after HT(P < 0.05). CONCLUSION There is an association between persistently high EBV load during post-HT follow up and the occurrence of late-onset PTLD in pediatric HT recipients irrespective of serostatus at the time of transplant. The occurrence of allograft rejection increased in patients with high EBV load presumably due to reduction in immun

关键词： Pediatric heart transplantation Epstein-Barr virus Post-transplant lymphoproliferative disorder Immunosuppression Allograft rejection

EBV-Associated Post-Transplantation B-Cell lymphoproliferative Disorder in Patient after Allogenic Stem Cell Transplantation

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Journal of Biosciences and Medicines 2019年第5期7卷 11-15页

作者： Li Tang Yu Li Department of Pathophysiology Chongqing Medical University Chongqing China Department of Pathology Institute of Neuroscience Chongqing Medical University Chongqing China

Epstein-Barr virus (EBV)-associated B-cell post-transplantation lymphoproliferative disorder (PTLD) is a severe complication following solid-organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (HSCT). We present a case of a 15-year-old male developing a monomorphic B-cell PTLD after receiving an allogenic stem cell transplant for acute acute myeloid leukemia. A diagnostic lymph node biopsy revealed monomorphic type, B cell phenotype, associated with Epstein-Barr virus, consistent with post-transplant lymphoproliferative disorder (PTLD). The morbidity and mortality of PTLD are high, and there is no standard protocol for treatment of PTLD. To prevent the occurrence of PTLD and early intervention are important for the prognosis of patients.

关键词： Post-Transplantation lymphoproliferative Disorder Allogeneic Hematopoietic Stem Cell Transplantation Epstein-Barr Virus

Dynamic monitoring of plasma Epstein-Barr Virus DNA load can predict the occurrence of lymphoproliferative disorders after haploidentical hematopoietic stem cell transplantation

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China Medical Abstracts(Internal Medicine) 2023年第3期40卷 187-187页

作者：陈静 Peking Univ People's Hosp Peking Univ Instit HematolNatl Clin Res CenterHematol DisBeijing Key LabHematopoietic Stem Cell TransplantBeijing 100044

Objective To determine the optimal cutoff value of Epstein-Barr virus(EBV)DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease(PTLD)after haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively *** cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD were determined through constructing the receiver operating characteristic(ROC)curve and calculating the Youden index.

关键词： hematopoietic diagnosis lymphoproliferative

Relative volume measured with magnetic resonance imaging is an articular collapse predictor in hematological pediatric patients with femoral head osteonecrosis

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World Journal of Radiology 2016年第8期8卷 750-756页

作者： Davide Ippolito Alessandro Masetto Cammillo Talei Franzesi Pietro A Bonaffini Alessandra Casiraghi Sandro Sironi Department of Diagnostic Radiology School of MedicineSan Gerardo HospitalUniversity of Milano-Bicocca

AIM To assess the potential value of femoral head(FH) volume measurements to predict joint collapse, as compared to articular surface involvement, in posttreatment osteonecrosis(ON) in pediatric patients affected by lymphoproliferative *** Considering 114 young patients with lymphoproliferative diseases undergone a lower-limbs magnetic resonance imaging(MRI) examination between November 2006 and August 2012 for a suspected post-treatment ON, we finally considered a total of 13 cases(7 males, mean age 15.2 ± 4.8 years), which developed a FH ON lesions(n = 23). The MRI protocol included coronal short tau inversion recovery and T1-weighted sequences, from the hips to the ankles. During the follow-up(elapsed time: 9.2 ± 2 mo), 13/23 FH articular surface(FHS)developed articular deformity. The first MRI studies with diagnosis of ON were retrospectively analyzed, measuring FH volume(FHV), FHS, ON volume(ONV) and the articular surface involved by ON(ONS). The relative involvement of FHS, in terms of volume [relative volume(RV): ONV/FHV] and articular surface [relative surface(RS): ONS/FHS], was then *** By using receiver operating characteristic curve analysis(threshold of 23% of volume involvement), RV predicted articular deformity in 13/13 FHS [sensitivity 100%, specificity 90%, accuracy 95%, positive predictive value(PPV) 93%, negative predictive value(NPV) 100%]. Considering a threshold of 50% of articular involvement, RS predicted articular deformity in 10/13 femoral heads(sensitivity 77%, specificity 100%, accuracy 87%, PPV 100%, NPV 77%).CONCLUSION RV might be a more reliable parameter than RS in predicting FH deformity and could represent a potential complementary diagnostic tool in the follow-up of femoral heads ON lesions.

关键词： Osteonecrosis Volume Articular surface lymphoproliferative diseases Femoral head Magnetic resonance imaging

The Role of Human Herpesvirus 8 Molecular Characterization in the Management of HIV Infected Patients Diagnosed with Malignancies Associated with Its Infection

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World Journal of AIDS 2013年第3期3卷 221-230页

作者： Martínez Pedro Ariel Kourí Vivian Blanco Orestes Capó Virginia Abad Yoandra Alemán Yoan Verdasquera Denis Jiménez Narciso Caballero Iraida Fleites Gilberto Ugarte Yaumara Calderón Odalys álvarez Alina Ulrich Hengge Institute of Tropical Medicine “Pedro Kourí” (IPK) Autopista Novia del Mediodía Habana Cuba

Despite the progress has been reached with Human herpesvirus 8 (HHV-8) research, there are gaps in the knowledge of viral induced oncogenesis. The aim of the present study was to identify possible associations between HHV-8 subtypes, HHV-8 loads and clinical manifestations of HIV infected patients diagnosed with different malignancies associated with HHV-8 infection. Forty six HIV-1 infected individuals diagnosed with different HHV-8 associated diseases were studied [37 epidemic Kaposi’s sarcoma (KS), 3 pleural effusion lymphoma (PEL);5 peripheral lymphadenopathies (PL);1 Hodgkin’s lymphoma (HL);1 non Hodgkin’s lymphoma (NHL)]. HHV-8 loads were determined by quantitative real time PCR (qRT-PCR) whilst HHV-8 subtypes were determined by open-reading frame (ORF)-K1 gen genotyping. HHV-8 subtypes B, A, C, A5 and E were exhibited by 31.8%, 23.4%, 19.1%, 17% and 8.5% of the studied patients, respectively. The median HHV-8 viral load did not differ between subtypes (p > 0.05) but HHV-8 viral loads were significantly higher in PEL than in epidemic KS lesion or lymph nodes (p = 0.04). Subtype B was detected in 60% of patients with B cell lymphoma (NHL, PEL and HL) whereas subtype E was only detected in patients with epidemic KS diagnosis. Our data suggest that HHV-8 DNA quantification instead of subtype identification could be used as a surrogate marker for monitoring its infection, not only in epidemic KS patients but also in HIV infected individuals with lymphoproliferative disorders.

关键词： Human Herpesvirus 8 or Kaposi’s Sarcoma-Associated Herpesvirus Real Time PCR Subtypes lymphoproliferative Disorders Cuban HIV/AIDS

Fatal septic shock caused by candida myocarditis associated with malignant lymphoma and Epstein-Barr virus mediated disorder

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Open Journal of Internal Medicine 2011年第2期1卷 24-28页

作者： Salah A. M. Said Bart J. F. Liebrand Nersing Bansraj Erik Eijken 不详

A 60-year-old man with known epilepsy was admitted to our hospital due to hypotension, fever and arrhythmia. He was treated medically and myocardial infarction was ruled out. Treatment of septic shock was established according to the guidelines of the early goal-guided therapy including vasopressors, inotropic agents, mechanical ventilation, and hemofiltration in combination with empirical treatment with antimicrobial drugs and hydrocortisone. The patient’s condition deteriorated rapidly into multiorgan failure resulting in a fatal outcome. Antemortem blood cultures were sterile. Autopsy findings were compatible with Epstein-Barr virus mediated lymphoproliferative disorder, malignant lymphoma, disseminated candidiasis and candida myocarditis. Post-mortem blood and tissue cultures were positive for growth of candida glabrata and candida albicans, respectively. The post-mortem examination documented Epstein-Barr virus mediated lymphoproliferative disorder and malignant small cell lymphoma associated with candida myocarditis. Prior to death, the patient did not receive antiviral or antifungal treatment. Fatal candida myocarditis associated with septic shock secondary to disseminated candidiasis in a 60-years old male patient with prior unknown immune compromised state caused by Epstein-Barr virus mediated lymphoproliferative disorder and malignant lymphoma is described.

关键词： Septic Shock Candida Myocarditis Epstein-Barr Virus Mediated lymphoproliferative Disorder Malignant Lymphoma Arrhythmia

Primary cutaneous anaplastic large cell lymphoma with subsequent leg involvement

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World Journal of Dermatology 2012年第3期1卷 38-40页

作者： Mitsuaki Ishida Norikazu Fujii Hidetoshi Okabe Division of Diagnostic Pathology Department of Clinical Laboratory Medicine Shiga University of Medical Science Shiga 520-2192 Japan Department of Dermatology Shiga University of Medical Science Shiga 520-2192 Japan

Primary cutaneous anaplastic large cell lymphoma(CALCL)is regarded as an indolent type of cutaneous T-cell ***,a few recent publications revealed that C-ALCL patients with initial leg involvement had significantly worse survival than those without initial leg ***,we report a case of C-ALCL with subsequent leg involvement,which led to death after chemoradiation therapy.A 75 years old Japanese man presented with multiple erythematous nodules in his left arm and the side of his left *** and immunohistochemical studies led to the diagnosis of primary *** the initial diagnosis,no leg lesion was *** year after the initial diagnosis,C-ALCL appeared in his right lower thigh and left *** therapy,low-dose etoposide and CHOP therapy were performed;however,the patient died of malignant lymphoma 4 years after the initial *** speculated that the occurrence of subsequent leg involvement may also be indicative of a worse prognosis,as in the case with initial leg involvement in ***,we propose that C-ALCL patients with initial or subsequentleg involvement should be classified as a distinct clinicopathological variant of C-ALCL("leg-type"involvement)and that they may require intense therapy.

关键词： Cutaneous lymphoma Cutaneous CD30-positive T-cell lymphoproliferative lesion Primary cutaneous anaplastic large cell lymphoma Leg involvement Prognosis Chemotherapy