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Sample records for posttransplant lymphoproliferative disease

  1. Posttransplant Lymphoproliferative Disease after Lung Transplantation

    PubMed Central

    Neuringer, Isabel P.

    2013-01-01

    Posttransplant lymphoproliferative disease (PTLD) after lung transplantation occurs due to immunosuppressant therapy which limits antiviral host immunity and permits Epstein-Barr viral (EBV) replication and transformation of B cells. Mechanistically, EBV survives due to latency, escape from cytotoxic T cell responses, and downregulation of host immunity to EBV. Clinical presentation of EBV may occur within the lung allograft early posttransplantation or later onset which is more likely to be disseminated. Improvements in monitoring through EBV viral load have provided a means of earlier detection; yet, sensitivity and specificity of EBV load monitoring after lung transplantation may require further optimization. Once PTLD develops, staging and tissue diagnosis are essential to appropriate histopathological classification, prognosis, and guidance for therapy. The overall paradigm to treat PTLD has evolved over the past several years and depends upon assessment of risk such as EBV-naïve status, clinical presentation, and stage and sites of disease. In general, clinical practice involves reduction in immunosuppression, anti-CD20 biologic therapy, and/or use of plasma cell inhibition, followed by chemotherapy for refractory PTLD. This paper focuses upon the immunobiology of EBV and PTLD, as well as the clinical presentation, diagnosis, prognosis, and emerging treatments for PTLD after lung transplantation. PMID:23533455

  2. Rituximab in association with rapamycin for post-transplant lymphoproliferative disease treatment.

    PubMed

    Garcia, Valter Duro; Bonamigo Filho, José Luz; Neumann, Jorge; Fogliatto, Laura; Geiger, Anna Maria; Garcia, Clotilde Druck; Barros, Vivianne; Keitel, Elizete; Bittar, Antonio Eduardo; Ferrera des Santos, Auri; Roithmann, Sergio

    2003-03-01

    Post-transplant lymphoproliferative disease (PTLD) is an uncommon but life-threatening complication of solid-organ and blood stem-cell transplants. It responds poorly to therapy, including reduction of immunosuppression, interferon, antivirals or chemotherapy. Small series of PTLD successfully treated with rituximab have been reported, and experimental studies suggest that rapamycin inhibits growth of human Epstein-Barr virus-transformed B lymphocytes. We report two cases of PTLD after renal transplantation that were successfully treated with rituximab in association with rapamycin. This report suggests that rituximab associated with rapamycin could be an effective and safe treatment for PTLD. PMID:12664217

  3. [Association of post-transplant lymphoproliferative disease and visceral leishmaniasis after kidney transplantation].

    PubMed

    Bacha, Mohamed Mongi; Abderrahim, Ezzeddine; Ounissi, Mondher; Chaouech, Dalel; Cherif, Mejda; Turki, Sami; Rajhi, Hatem; Znaidi, Nadia; Bahloul, Abdessalem; Trabelsi, Sonia; Khaled, Samira; Ben Abdallah, Taïeb; Ben Maïz, Hedi; Kheder, Adel

    2011-11-01

    Malignancies and opportunistic infections are frequently observed after solid-organ transplantation. Their occurrence strongly affects recipient survival. We report the case of a 29-year-old Tunisian kidney-recipient who was diagnosed simultaneously with post-transplant lymphoproliferative disease (PTLD) and visceral leishmaniasis (VL). Withdrawal of immunosuppressive therapy together with antiparasitic treatment using liposomal amphotericin B, and anti-CD20 antibodies medication resulted in cure of leishmaniasis and remission from PTLD. This case is of clinical interest because of the uncommon association of VL with PTLD after solid organ transplantation. It is also original by the favourable outcome of VL and PTLD, both known as life-threatening diseases. Also, it illustrates the predisposing role of immunosuppressive therapy in occurrence of opportunistic infections and malignancies after solid organ transplantation. PMID:21376690

  4. Post-transplant lymphoproliferative disorders.

    PubMed

    Dharnidharka, Vikas R; Webster, Angela C; Martinez, Olivia M; Preiksaitis, Jutta K; Leblond, Veronique; Choquet, Sylvain

    2016-01-01

    Post-transplant lymphoproliferative disorders (PTLDs) are a group of conditions that involve uncontrolled proliferation of lymphoid cells as a consequence of extrinsic immunosuppression after organ or haematopoietic stem cell transplant. PTLDs show some similarities to classic lymphomas in the non-immunosuppressed general population. The oncogenic Epstein-Barr virus (EBV) is a key pathogenic driver in many early-onset cases, through multiple mechanisms. The incidence of PTLD varies with the type of transplant; a clear distinction should therefore be made between the conditions after solid organ transplant and after haematopoietic stem cell transplant. Recipient EBV seronegativity and the intensity of immunosuppression are among key risk factors. Symptoms and signs depend on the localization of the lymphoid masses. Diagnosis requires histopathology, although imaging techniques can provide additional supportive evidence. Pre-emptive intervention based on monitoring EBV levels in blood has emerged as the preferred strategy for PTLD prevention. Treatment of established disease includes reduction of immunosuppression and/or administration of rituximab (a B cell-specific antibody against CD20), chemotherapy and EBV-specific cytotoxic T cells. Despite these strategies, the mortality and morbidity remains considerable. Patient outcome is influenced by the severity of presentation, treatment-related complications and risk of allograft loss. New innovative treatment options hold promise for changing the outlook in the future. PMID:27189056

  5. Post-Transplant Lymphoproliferative Disease (PTLD): Risk Factors, Diagnosis, and Current Treatment Strategies

    PubMed Central

    Al-Mansour, Zeina; Nelson, Beverly P.; Evens, Andrew M.

    2015-01-01

    Post-transplant lymphoproliferative diseases (PTLD) are heterogeneous lymphoid disorders ranging from indolent polyclonal proliferations to aggressive lymphomas that complicate solid organ or hematopoietic transplantation. Risk factors have been identified, including viral infections, degree of immunosuppression, recipient age and race, allograft type, and host genetic variations. Clinically, extra-nodal disease is common, with 10–15 % presenting with central nervous system (CNS) disease. Most PTLD cases are B cell (5–10 % T/NK cell or Hodgkin lymphoma), while approximately one-third are EBV-negative. World Health Organization (WHO) diagnostic categories are: early lesions, polymorphic, and monomorphic PTLD; although in practice, a clear separation is not always possible. Therapeutically, reduction in immunosuppression remains a mainstay, and recent data has documented the importance of rituximab +/− combination chemotherapy. Therapy for primary CNS PTLD should be managed according to immunocompetent CNS paradigms. Finally, novel treatment strategies for PTLD have emerged, including adoptive immunotherapy and rational targeted therapeutics (e.g., targeting downstream signaling pathways of virus-encoded latent membrane protein-2A). PMID:23737188

  6. Prevention of EBV lymphoma development by oncolytic myxoma virus in a murine xenograft model of post-transplant lymphoproliferative disease

    SciTech Connect

    Kim, Manbok; Rahman, Masmudur M.; Cogle, Christopher R.

    2015-07-10

    Epstein–Barr virus (EBV) has been associated with a variety of epithelial and hematologic malignancies, including B-, T- and NK cell-lymphomas, Hodgkin's disease (HD), post-transplant lymphoproliferative diseases (LPDs), nasopharyngeal and gastric carcinomas, smooth muscle tumors, and HIV-associated lymphomas. Currently, treatment options for EBV-associated malignancies are limited. We have previously shown that myxoma virus specifically targets various human solid tumors and leukemia cells in a variety of animal models, while sparing normal human or murine tissues. Since transplant recipients of bone marrow or solid organs often develop EBV-associated post-transplant LPDs and lymphoma, myxoma virus may be of utility to prevent EBV-associated malignancies in immunocompromised transplant patients where treatment options are frequently limited. In this report, we demonstrate the safety and efficacy of myxoma virus purging as a prophylactic strategy for preventing post-transplant EBV-transformed human lymphomas, using a highly immunosuppressed mouse xenotransplantation model. This provides support for developing myxoma virus as a potential oncolytic therapy for preventing EBV-associated LPDs following transplantation of bone marrow or solid organ allografts. - Highlights: • Myxoma virus effectively infects and purges EBV lymphoma cells in vivo. • Oncolytic myxoma virus effectively eradicates oncogenic EBV tumorigenesis. • Ex vivo pre-treatment of myxoma virus can be effective as a preventive treatment modality for post-transplant lymphoproliferative diseases.

  7. Retinochoroidal toxoplasmosis in a patient with cerebral post-transplant lymphoproliferative disease of Hodgkin's type: a diagnostic challenge.

    PubMed

    Mittal, Ruchi; Thumann, Gabrielle; Souteyrand, George; Kuerten, David; Coupland, Sarah E

    2015-12-01

    Toxoplasmosis is a relatively rare complication in renal transplant patients and can pose diagnostic challenges, especially when it manifests as an ocular inflammation. Authors hereby report an unusual case of a 57-year-old male who developed retinochoroidal toxoplasmosis after 15 years of renal transplant, the diagnoses of which were challenging as the patient was also a known case of cerebral post-transplant lymphoproliferative disease (PTLD) of Hodgkin's type, which misled the ophthalmologists towards a clinical diagnosis of ocular PTLD. Histopathology examination of the enucleated eye revealed numerous toxoplasmosis cysts within the retina and choroid. No ocular PTLD was observed. PMID:26239296

  8. Prevention of EBV lymphoma development by oncolytic myxoma virus in a murine xenograft model of post-transplant lymphoproliferative disease.

    PubMed

    Kim, Manbok; Rahman, Masmudur M; Cogle, Christopher R; McFadden, Grant

    2015-07-10

    Epstein-Barr virus (EBV) has been associated with a variety of epithelial and hematologic malignancies, including B-, T- and NK cell-lymphomas, Hodgkin's disease (HD), post-transplant lymphoproliferative diseases (LPDs), nasopharyngeal and gastric carcinomas, smooth muscle tumors, and HIV-associated lymphomas. Currently, treatment options for EBV-associated malignancies are limited. We have previously shown that myxoma virus specifically targets various human solid tumors and leukemia cells in a variety of animal models, while sparing normal human or murine tissues. Since transplant recipients of bone marrow or solid organs often develop EBV-associated post-transplant LPDs and lymphoma, myxoma virus may be of utility to prevent EBV-associated malignancies in immunocompromised transplant patients where treatment options are frequently limited. In this report, we demonstrate the safety and efficacy of myxoma virus purging as a prophylactic strategy for preventing post-transplant EBV-transformed human lymphomas, using a highly immunosuppressed mouse xenotransplantation model. This provides support for developing myxoma virus as a potential oncolytic therapy for preventing EBV-associated LPDs following transplantation of bone marrow or solid organ allografts. PMID:25843801

  9. Umbilical cord blood transplantation in adults with advanced hodgkin's disease: high incidence of post-transplant lymphoproliferative disease.

    PubMed

    Piñana, José Luis; Sanz, Jaime; Esquirol, Albert; Martino, Rodrigo; Picardi, Alessandra; Barba, Pere; Parody, Rocio; Gayoso, Jorge; Montesinos, Pau; Guidi, Stefano; Terol, Maria José; Moscardó, Federico; Solano, Carlos; Arcese, William; Sanz, Miguel A; Sierra, Jorge; Sanz, Guillermo

    2016-02-01

    We report the outcome of 30 consecutive patients with Hodgkin disease (HD) who underwent single-unit UCBT. Most (90%) patients had failed previous autologous hematopoietic stem cell transplantation. The conditioning regimens were based on combinations of thiotepa, busulfan, cyclophosphamide or fludarabine, and antithymocyte globulin. The cumulative incidence (CI) of myeloid engraftment was 90% [95% confidence interval (C.I.), 74-98%] with a median of 18 d (range, 10-48). CI of acute graft-versus-host disease (GvHD) grades II-IV was 30% (95% C.I., 17-44%), while the incidence of chronic GVHD was 42% (95% C.I., 23-77%). The non-relapse mortality (NRM) at 100 d and 4 yr was 30% (95% C.I., 13-46%) and 47% (95% C.I., 29-65%), respectively. EBV-related post-transplant lymphoproliferative disease (EBV-PTLD) accounted for more than one-third of transplant-related death, with an estimate incidence of 26% (95% C.I., 9-44). The incidence of relapse at 4 yr was 25% (95% C.I., 9-42%). Four-year event-free survival (EFS) and overall survival (OS) were 28% and 30%, respectively. Despite a high NRM and an unexpected high incidence of EBV-PTLD, UCBT in heavily pretreated HD patients is an option for patients lacking a suitable adult donor, provided the disease is not in refractory relapse. PMID:25845981

  10. Posttransplant lymphoproliferative disorders in transplant recipients.

    PubMed

    Timurağaoğlu, A; Uğur-Bilgin, A; Colak, D; Tuncer, M; Gölbaşi, I; Hazar, V; Kiliçarsłan, B; Undar, L; Demirbaş, A

    2006-03-01

    Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation, with a reported incidence between 0.8% and 32%. The incidence of PTLD mainly depends on the transplanted organ, the immunosuppressive drugs, the viral serology, and the age of the recipient. The aim of our study was to analyze our patients diagnosed with PTLD. Among 1040 transplantations, including 931 renal, 14 heart, 55 liver and 40 allogeneic peripheral blood stem cell (PBSC), 8 patients (7 male, 1 female) were diagnosed with PTLD. Five patients had undergone renal, one cardiac, one liver, and one PBSC transplantations. Four patients were diagnosed within the first year of transplantation. Six patients presented with abdominal disease, one with convulsions, and one with peripheral lymph node involvement. According to the World Health Organization classification system, six patients were diagnosed as diffuse large B-cell lymphoma, one patient Burkitt's lymphoma, and one polymorphic PTLD. At the time of diagnosis, 7 patients showed positive Epstein-Barr virus (EBV) and cytomegalovirus (CMV) Ig G and negative Ig M; one patient, positive EBV Ig M and negative CMV Ig G and M. EBV viral load was extremely high in the plasma of two patients by polymerase chain reaction. One of these patient's pathologic tissue revealed positive EBV DNA, which was not detected in six of the other eight patients. This patient was an 8-year-old boy diagnosed with Burkitt's lymphoma at 31 months after liver transplantation. Seven patients died of disease or complications of chemotherapy. Only one patient survived after the diagnosis of PTLD. In conclusion, even with treatment the mortality rate was high among our patients with PTLD. To decrease the incidence of PTLD and related mortality, risk factors must be evaluated in multicenter studies. PMID:16549195

  11. The accuracy of positron emission tomography in the detection of posttransplant lymphoproliferative disorder

    PubMed Central

    Dierickx, Daan; Tousseyn, Thomas; Requilé, Annelies; Verscuren, Raf; Sagaert, Xavier; Morscio, Julie; Wlodarska, Iwona; Herreman, An; Kuypers, Dirk; Van Cleemput, Johan; Nevens, Frederik; Dupont, Lieven; Uyttebroeck, Anne; Pirenne, Jacques; De Wolf-Peeters, Christiane; Verhoef, Gregor; Brepoels, Lieselot; Gheysens, Olivier

    2013-01-01

    We investigated sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-fluorodeoxyglucose-positron emission tomography in 170 cases with suspected or biopsy-proven posttransplant lymphoproliferative disorder. All solid organ and hematopoietic stem cell transplant recipients who underwent an 18F-fluorodeoxyglucose-positron emission tomography scan between 2003 and 2010 in our center for the indication posttransplant lymphoproliferative disorder, were retrospectively reviewed and results were compared with tissue biopsy whenever possible. One hundred and seventy positron emission tomography scans in 150 patients were eligible for evaluation. In 45 cases, the patient had a biopsy-confirmed posttransplant lymphoproliferative disorder before positron emission tomography scanning and positron emission tomography was performed for staging purposes. In the remaining 125 cases, positron emission tomography was performed to differentiate between posttransplant lymphoproliferative disorder and other diseases. 18F-fluorodeoxyglucose-uptake was quantitatively expressed by calculation of maximum and mean standardized uptake value in the most intense lesion or, in the absence of attenuation corrected positron emission tomography scans, by comparing uptake in target lesion to liver and mediastinal uptake. We found an overall sensitivity of 89%, specificity of 89%, positive predictive value of 91% and negative predictive value of 87% for posttransplant lymphoproliferative disorder detection by 18F-fluorodeoxyglucose-positron emission tomography. In a subanalysis of the 125 scans performed for differentiating posttransplant lymphoproliferative disorder from other diseases, sensitivity, specificity, positive predictive value and negative predictive value were 90%, 89%, 85% and 93%, respectively. 18F-fluorodeoxyglucose-uptake in posttransplant lymphoproliferative disorder was generally high with a median mean and maximum standardized uptake value of 9.0 (range 2.0–18.6) and 17.4 (range 2.6–26.4). Posttransplant lymphoproliferative disorder often had an atypical presentation on positron emission tomography with high incidence of extranodal involvement. In conclusion, from these data, we can conclude that 18F-fluorodeoxyglucose-positron emission tomography is highly sensitive for detecting posttransplant lymphoproliferative disorder and has an excellent ability to differentiate posttransplant lymphoproliferative disorder from non-malignant diseases. PMID:23065524

  12. Post-Transplant Lymphoproliferative Disorders: Role of Viral Infection, Genetic Lesions and Antigen Stimulation in the Pathogenesis of the Disease

    PubMed Central

    Capello, Daniela; Gaidano, Gianluca

    2009-01-01

    Post-transplant lymphoproliferative disorders (PTLD) are a life-threatening complication of solid organ transplantation or, more rarely, hematopoietic stem cell transplantation. The majority of PTLD is of B-cell origin and associated with EpsteinBarr virus (EBV) infection. PTLD generally display involvement of extranodal sites, aggressive histology and aggressive clinical behavior. The molecular pathogenesis of PTLD involves infection by oncogenic viruses, namely EBV, as well as genetic or epigenetic alterations of several cellular genes. At variance with lymphoma arising in immunocompetent hosts, whose genome is relatively stable, a fraction of PTLD are characterized by microsatellite instability as a consequence of defects in the DNA mismatch repair mechanism. Apart from microsatellite instability, molecular alterations of cellular genes recognized in PTLD include alterations of cMYC, BCL6, TP53, DNA hypermethylation, and aberrant somatic hypermutation of protooncogenes. The occurrence of IGV mutations in the overwhelming majority of PTLD documents that malignant transformation targets germinal centre (GC) B-cells and their descendants both in EBVpositive and EBVnegative cases. Analysis of phenotypic markers of B-cell histogenesis, namely BCL6, MUM1 and CD138, allows further distinction of PTLD histogenetic categories. PTLD expressing the BCL6+/MUM1+/-/CD138? profile reflect B-cells actively experiencing the GC reaction, and comprise diffuse large B-cell lymphoma (DLBCL) centroblastic and Burkitt lymphoma. PTLD expressing the BCL6?/MUM1+/CD138? phenotype putatively derive from B-cells that have concluded the GC reaction, and comprise the majority of polymorphic PTLD and a fraction of DLBCL immunoblastic. A third group of PTLD is reminiscent of post-GC and preterminally differentiated B-cells that show the BCL6?/MUM1+/CD138+ phenotype, and are morphologically represented by either polymorphic PTLD or DLBCL immunoblastic. PMID:21416004

  13. Epstein-Barr virus load in whole blood is associated with immunosuppression, but not with post-transplant lymphoproliferative disease in stable adult heart transplant patients.

    PubMed

    Doesch, Andreas O; Konstandin, Mathias; Celik, Sultan; Kristen, Arnt; Frankenstein, Lutz; Sack, Falk-Udo; Schnabel, Philipp; Schnitzler, Paul; Katus, Hugo A; Dengler, Thomas J

    2008-10-01

    Development of Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) is a serious complication following heart transplantation (HTX). This study investigates EBV DNA load in adult heart transplant recipients, its association with immunosuppression, and its potential as a marker for development of PTLD. EBV DNA load was measured prospectively by quantitative real-time polymerase chain reaction (PCR) in 172 stable HTX patients. Sixty-seven patients (39.0% of total) had a positive EBV PCR at initial examination [median 4.9 (range 1.1-16.9) years post-HTX]. In follow-up testing of 67 positive patients 6 months later, 36 patients continued to have a positive EBV PCR. Overall incidence of EBV DNA was significantly associated with calcineurin inihibitors, azathioprine medication, and with the absence of mycophenolate mofetil (MMF) treatment. In patients with positive EBV DNA levels at initial examination and negative levels at retesting, cyclosporine A levels were found to be significantly higher at initial examination (148.4 +/- 70.2 vs. 119.6 +/- 53.5 ng/ml, P < 0.05). Three patients (1.7%, 3/172) were diagnosed with PTLD during the course of the study (mean follow up 4.0 years). EBV DNA viral load determination does not appear to be useful for risk prediction or early diagnosis of PTLD in adults after HTX, but an association of EBV DNA load with qualitative and quantitative immunosuppression is demonstrated. PMID:18564989

  14. Isolated Upper Extremity Posttransplant Lymphoproliferative Disorder in a Child

    PubMed Central

    Halula, Sarah E.; Leino, Daniel G.; Patel, Manish N.; Racadio, John M.; Lungren, Matthew P.

    2015-01-01

    Posttransplant lymphoproliferative disorder (PTLD) is a well-described complication of solid organ and bone marrow transplants. The most common presentation is intra-abdominal lymphadenopathy or single or multiple intraparenchymal masses involving the liver, spleen, or kidneys. Here we describe the imaging and pathology findings of an unusual case of PTLD appearing as an intramuscular forearm lesion in a pediatric male. The manifestation of PTLD as an isolated upper extremity mass in a pediatric patient has to our knowledge not been described. PMID:26167324

  15. Post-Transplant Lymphoproliferative Disorder in Kidney Transplant Recipients: A Single-Center Experience in Japan.

    PubMed

    Ishihara, Hiroki; Shimizu, Tomokazu; Unagami, Kohei; Hirai, Toshihito; Toki, Daisuke; Omoto, Kazuya; Okumi, Masayoshi; Imai, Yoichi; Ishida, Hideki; Tanabe, Kazunari

    2016-04-01

    Post-transplant lymphoproliferative disorder is a serious complication of solid organ transplantation; however, few large studies have been performed in Asian institutions. We review our single-center experience with post-transplant lymphoproliferative disorder patients in Japan. We retrospectively evaluated patients with post-transplant lymphoproliferative disorder following kidney transplantation between January 1985 and December 2013. The patients were divided into early-onset post-transplant lymphoproliferative disorder (<1 year) and late-onset post-transplant lymphoproliferative disorder (≥1 year) groups. Thirteen patients had the disorder, an incidence rate of 0.75% (13/1730). Early-onset post-transplant lymphoproliferative disorder (N = 3) had not occurred for the last two decades. In the late-onset group (N = 10), the median time of onset was 108.7 months. The Kaplan-Meier 10-year overall survival rates were 76.9% and 95.4% in patients with and without the disorder, respectively (P = 0.0001). Post-transplant lymphoproliferative disorder significantly affected transplant recipients' mortality. Late-onset occurred even > 10 years after transplantation; therefore, long-term monitoring of patients is needed. PMID:26948427

  16. [Primary Central Nervous System Post-Transplant Lymphoproliferative Disorder in a Patient with Acute Lymphocytic Leukemia].

    PubMed

    Azuma, Yoshiko; Nakaya, Aya; Fujita, Shinya; Hotta, Masaaki; Fujita, Yukie; Yoshimura, Hideaki; Nakanishi, Takahisa; Satake, Atsushi; Ito, Tomoki; Ishii, Kazuyoshi; Nomura, Shosaku

    2015-08-01

    A 27-year-old woman with acute lymphocytic leukemia, who underwent allogeneic hematopoietic stem cell transplantation, complained of nausea and blurred vision 288 days after the transplantation. Intracranial tumors were identified on brain MRI. She received whole brain radiation after open biopsy, but she died. The tumors had characteristics of diffuse large B cell lymphoma, and she was finally diagnosed with primary central nervous system post-transplant lymphoproliferative disorder. This disease is rare and has a poor outcome. Therefore, accumulation of cases and establishment of treatments for this condition are urgently needed. PMID:26321719

  17. Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorder

    ClinicalTrials.gov

    2013-01-24

    Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Waldenström Macroglobulinemia

  18. Post-transplant lymphoproliferative disorder following cytomegalovirus reactivation in a lung recipient.

    PubMed

    Aoyama, Akihiro; Omasa, Mitsugu; Kondo, Nobuyuki; Chen, Fengshi; Date, Hiroshi; Bando, Toru

    2010-05-01

    Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication after lung transplantation, for which several risk factors including pretransplant seronegativity for Epstein-Barr virus are known. However, the impact of cytomegalovirus on PTLD remains to be determined. Here, we describe a case of Epstein-Barr virus-associated polymorphic PTLD that developed shortly after treatment for cytomegalovirus reactivation in a lung transplant recipient who was preoperatively seropositive for both cytomegalovirus and Epstein-Barr virus. PMID:20449718

  19. Current preventive strategies and management of Epstein-Barr virus-related post-transplant lymphoproliferative disease in solid organ transplantation in Europe. Results of the ESGICH Questionnaire-based Cross-sectional Survey.

    PubMed

    San-Juan, R; Manuel, O; Hirsch, H H; Fernández-Ruiz, M; López-Medrano, F; Comoli, P; Caillard, S; Grossi, P; Aguado, J M

    2015-06-01

    There is limited clinical evidence on the utility of the monitoring of Epstein-Barr virus (EBV) DNAemia in the pre-emptive management of post-transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients. We investigated current preventive measures against EBV-related PTLD through a web-based questionnaire sent to 669 SOT programmes in 35 European countries. This study was performed on behalf of the ESGICH study group from the European Society of Clinical Microbiology and Infectious Diseases. A total of 71 SOT programmes from 15 European countries participated in the study. EBV serostatus of the recipient is routinely obtained in 69/71 centres (97%) and 64 (90%) have access to EBV DNAemia assays. EBV monitoring is routinely used in 85.9% of the programmes and 77.4% reported performing pre-emptive treatment for patients with significant EBV DNAemia levels. Pre-emptive treatment for EBV DNAemia included reduction of immunosuppression in 50.9%, switch to mammalian target of rapamycin inhibitors in 30.9%, and use of rituximab in 14.5% of programmes. Imaging by whole-body 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) is used in 60.9% of centres to rule out PTLD and complemented computer tomography is used in 50%. In 10.9% of centres, FDG-PET is included in the first-line diagnostic workup in patients with high-risk EBV DNAemia. Despite the lack of definitive evidence, EBV load measurements are frequently used in Europe to guide diagnostic workup and pre-emptive reduction of immunosuppression. We need prospective and controlled studies to define the impact of EBV monitoring in reducing the risk of PTLD in SOT recipients. PMID:25686696

  20. Treatment of Recurrent Posttransplant Lymphoproliferative Disorder with Autologous Blood Stem Cell Transplant

    PubMed Central

    Malhotra, Bharat; Rahal, Ahmad K.; Farhoud, Hussam; Moore, Dennis F.; Kallail, K. James

    2015-01-01

    Background. Posttransplant lymphoproliferative disorders (PTLDs) occur after solid organ transplantation. Treatment guidelines include reduction in immunosuppression (RIS), radiation, rituximab, chemotherapy, and immunological agents. We present a rare case of recurrent diffuse large B-cell lymphoma presenting as a PTLD in a heart transplant patient treated with autologous blood stem cell transplant (ASCT) after failure of conventional therapy. Case Presentation. A 66-year-old male presented with a neck mass. He has a history of Hodgkin's disease status after staging laparotomy with splenectomy and heart transplantation due to dilated nonischemic cardiomyopathy 8 years prior to the development of PTLD. His examination was remarkable for right submandibular swelling. An excisional biopsy confirmed the diagnosis of diffuse large B-cell NHL. Patient received RIS, rituximab, chemotherapy, and radiation therapy with a complete remission. His lymphoma relapsed and he subsequently was treated with RICE salvage chemotherapy and consolidative high-dose chemotherapy with BEAC regimen followed by ASCT resulting in a complete remission. Conclusion. Patients with PTLD present a difficult therapeutic challenge. In this case, the patient's prior history of Hodgkin's disease, splenectomy, and a heart transplant appear to be unique features, the significance of which is unclear. ASCT might be a promising therapy for patients with relapsed or refractory PTLD. PMID:26688773

  1. Post-transplant lymphoproliferative disorder after kidney transplantation: time to adopt monitoring of Epstein-Barr virus?

    PubMed

    Biller, P; Michaux, L; Pauw, L De; Camboni, A; Mourad, M; Kanaan, N

    2015-06-01

    Although post-transplant lymphoproliferative disorder is a classical complication encountered after kidney transplantation, its diagnosis can still be challenging and its outcome life-threatening. Most cases are related to Epstein-Barr virus (EBV) infection and occur mainly in the first year post-transplant, favoured by the seronegative EBV status of the recipient transplanted with a kidney from a seropositive donor, and strong immunosuppression. We report the case of a young kidney-pancreas transplant recipient who developed post-transplant lymphoproliferative disorder (PTLD) early after transplantation, with a rapid fatal issue. We review the pathogenesis, clinical presentation, and management of PTLD with a focus on prevention. PMID:25541210

  2. Plasmacytoma-like Posttransplant Lymphoproliferative Disorder in a Pediatric Heart Transplant Recipient.

    PubMed

    Proctor Short, Sara Rhodes; Cook, Steven L; Kim, Andrew S; Lamour, Jacqueline M; Lowe, Eric J; Petersen, William C

    2016-03-01

    Posttransplant lymphoproliferative disorder (PTLD) is a diversely manifesting group of lymphoid or plasmacytic proliferations found in solid organ and bone marrow transplant recipients. PTLD occurs as a result of immunosuppression and is often driven by the Epstein Barr virus. Although most commonly of B-cell origin, similar to B-cell lymphomas, PTLD can rarely present as a plasmacytic process, resembling multiple myeloma. Although more common in adults, 8 cases of plasmacytoma-like PTLD have been reported in pediatric renal and combined small bowel-liver transplant recipients. Here, we present a rare report of a plasmacytoma-like PTLD case in a pediatric heart transplant recipient. PMID:26859193

  3. Outcomes of kidney retransplantation in recipients with prior post-transplant lymphoproliferative disorder.

    PubMed

    Rouphael, Bassem; Lankireddy, Srilakshmi; Lazaryan, Aleksandr; Kukla, Aleksandra; Ibrahim, Hassan N; Matas, Arthur J; Issa, Naim

    2016-01-01

    Post-transplant lymphoproliferative disease (PTLD) is an uncommon but serious complication of solid organ transplantation. Reduction in immunosuppression is the mainstay of PTLD treatment, but it may precipitate graft loss. Retransplantation remains controversial, as immunosuppression resumption may trigger PTLD relapse. Herein, we describe the experience of eight patients who underwent kidney retransplantation after successful PTLD treatment. Epstein-Barr virus (EBV) serology was not known before the first transplantation. PTLD was diagnosed 62.5 months (range 5-323 months) after transplantation and was confined to the renal allograft (n = 1), lymph nodes (n = 2), gastrointestinal tract (n = 4), or central nervous system (n = 1). Immunosuppression tapering (8/8), chemotherapy (6/8), oral cavity lymphoma excision (1/8), and allograft nephrectomy (1/8) led to hematological remission in all patients. Retransplantation was performed at a median of 55.5 months (range 29-95 months) after PTLD diagnosis. After a median follow-up of 62.5 months (range 2-125 months) allograft survival was 87.5% (seven functioning grafts, one failed graft from chronic rejection), with no recurrence of PTLD. In all, five patients remain alive; the other three died from causes other than PTLD. In conclusion, kidney retransplantation appears to be safe in patients with prior PTLD and without major risk of hematological recurrence provided that PTLD has remitted. PMID:26497471

  4. Hodgkin lymphoma post-transplant lymphoproliferative disorder: A comparative analysis of clinical characteristics, prognosis, and survival.

    PubMed

    Rosenberg, Aaron S; Klein, Andreas K; Ruthazer, Robin; Evens, Andrew M

    2016-06-01

    Hodgkin lymphoma post-transplant lymphoproliferative disorder (HL-PTLD) is an uncommon PTLD with unclear prognosis and differences between HL-PTLD and immunocompetent HL are not well defined. Patient characteristics were compared among 192 patients with HL-PTLD from the Scientific Registry of Transplant Recipients and 13,847 HL patients in SEER (HL-SEER). Overall survival (OS) and disease-specific survival (DSS) were compared after exact matching. Additionally, multivariable analyses were used to identify prognostic markers of survival and associations between treatment and survival. Median time from transplant to HL-PTLD diagnosis was 88 months. When compared with HL-SEER, patients with HL-PTLD were older (median age, 52 vs. 36 years, P = 0.001), more likely male (73% vs. 54%, P < 0.001), Caucasian (81% vs. 70%, P = 0.02), and had extranodal disease (42% vs. 3%, P < 0.001). Five-year OS for patients with HL-PTLD was 57% versus 80% for HL-SEER (P < 0.001); DSS was also inferior (P < 0.001). For patients with HL-PTLD, the use of any chemotherapy was associated with decreased hazard of death (HR = 0.36, P < 0.001). Furthermore, patients who received no chemotherapy or nontraditional HL regimens had increased hazard of death (aHR = 2.94, P = 0.001 and 2.01, P = 0.04) versus HL-specific chemotherapy regimens. In multivariable analysis, advanced age and elevated creatinine were associated with inferior OS (aHR = 1.26/decade P < 0.001 and 1.64/0.1 mg/dL increase P = 0.02). A prognostic score based on the number of these adverse factors (0, 1, 2) was associated with 10-year OS rates of 79%, 53%, and 11%, respectively (P < 0.001). Altogether, HL-PTLD patients have inferior survival when compared with HL-SEER. Furthermore, treatment with HL-specific chemotherapy was associated with improved OS, whereas age and creatinine identified patients with markedly divergent survival. Am. J. Hematol. 91:560-565, 2016. © 2016 Wiley Periodicals, Inc. PMID:26928381

  5. [Monomorphic post-transplant T-lymphoproliferative disorder after autologous stem cell transplantation for multiple myeloma].

    PubMed

    Ishikawa, Tetsuya; Shimizu, Hiroaki; Takei, Toshifumi; Koya, Hiroko; Iriuchishima, Hirono; Hosiho, Takumi; Hirato, Junko; Kojima, Masaru; Handa, Hiroshi; Nojima, Yoshihisa; Murakami, Hirokazu

    2016-01-01

    We report a rare case of T cell type monomorphic post-transplant lymphoproliferative disorders (PTLD) after autologous stem cell transplantation. A 53-year-old man with multiple myeloma received autologous stem cell transplantation and achieved a very good partial response. Nine months later, he developed a high fever and consciousness disturbance, and had multiple swollen lymph nodes and a high titer of Epstein-Barr (EB) virus DNA in his peripheral blood. Neither CT nor MRI of the brain revealed any abnormalities. Cerebrospinal fluid contained no malignant cells, but the EB virus DNA titer was high. Lymph node biopsy revealed T cell type monomorphic PTLD. Soon after high-dose treatment with methotrexate and cytosine arabinoside, the high fever and consciousness disturbance subsided, and the lymph node swelling and EB virus DNA disappeared. Given the efficacy of chemotherapy in this case, we concluded that the consciousness disturbance had been induced by central nervous system involvement of monomorphic PTLD. PMID:26861102

  6. Syk-induced phosphatidylinositol-3-kinase activation in Epstein-Barr virus posttransplant lymphoproliferative disorder.

    PubMed

    Hatton, O; Lambert, S L; Phillips, L K; Vaysberg, M; Natkunam, Y; Esquivel, C O; Krams, S M; Martinez, O M

    2013-04-01

    Posttransplant lymphoproliferative disorder (PTLD)-associated Epstein-Barr virus (EBV)+ B cell lymphomas are serious complications of solid organ and bone marrow transplantation. The EBV protein LMP2a, a B cell receptor (BCR) mimic, provides survival signals to virally infected cells through Syk tyrosine kinase. Therefore, we explored whether Syk inhibition is a viable therapeutic strategy for EBV-associated PTLD. We have shown that R406, the active metabolite of the Syk inhibitor fostamatinib, induces apoptosis and cell cycle arrest while decreasing downstream phosphatidylinositol-3'-kinase (PI3K)/Akt signaling in EBV+ B cell lymphoma PTLD lines in vitro. However, Syk inhibition did not inhibit or delay the in vivo growth of solid tumors established from EBV-infected B cell lines. Instead, we observed tumor growth in adjacent inguinal lymph nodes exclusively in fostamatinib-treated animals. In contrast, direct inhibition of PI3K/Akt significantly reduced tumor burden in a xenogeneic mouse model of PTLD without evidence of tumor growth in adjacent inguinal lymph nodes. Taken together, our data indicate that Syk activates PI3K/Akt signaling which is required for survival of EBV+ B cell lymphomas. PI3K/Akt signaling may be a promising therapeutic target for PTLD, and other EBV-associated malignancies. PMID:23398911

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

    PubMed

    Amorim Pellicioli, Ana Carolina; Luciano, Aline Alves; Rangel, Ana Lúcia Carrinho Ayroza; de Oliveira, Greison Rabelo; Santos Silva, Alan Roger; de Almeida, Oslei Paes; Vargas, Pablo Agustin

    2016-04-01

    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. PMID:26321430

  8. Epstein-Barr Virus-related Posttransplant Lymphoproliferative Disorder in Children: A Single-institution Experience.

    PubMed

    Jaing, Tang-Her; Wu, Chieh-Tsai; Chen, Shih-Hsiang; Wen, Yu-Chuan; Chang, Tsung-Yen; Chuang, Wen-Yu

    2016-04-01

    We report 4 pediatric cases of biopsy-proven posttransplant lymphoproliferative disorder (PTLD) in the context of allogeneic hematopoietic stem cell transplantation (HSCT). All cases showed diffuse staining with latent membrane protein-1 in immunohistochemistry. The median age at transplant of 4 patients with PTLD was 10.1 years (range, 2.2 to 13.2 y). The median interval between HSCT and the diagnosis of PTLD was 5.5 months (range, 4 to 8 mo). All patients were treated with rituximab at dosage of 375 mg/m at weekly intervals. Reduction of immunosuppression was warranted in all cases. All patients survived with median follow-up duration of 27 months. Although PTLD has been rare following allogeneic HSCT, reduction of immunosuppression combined with rituximab yielded significant response rates in patients with this infrequent but potentially lethal complication. The preliminary finding of this study demonstrated that severe aplastic anemia is closely associated with the development of PTLD in children. PMID:26886374

  9. Contrast-enhanced ultrasound findings of post-transplant lymphoproliferative disorder in a transplanted kidney: A case report and literature review

    PubMed Central

    Lampe, Alyssa; Duddalwar, Vinay A; Djaladat, Hooman; Aron, Manju; Gulati, Mittul

    2015-01-01

    Post-transplant lymphoproliferative disorder occurs in approximately one percent of kidney transplant recipients. We evaluated a seventy-seven year-old man with a solid mass in his transplant kidney. On contrast enhanced ultrasound, the mass enhanced but remained persistently hypovascular throughout exam. The enhancement pattern of the mass differed from that typical of clear cell renal cell carcinoma, the main differential diagnosis. Final pathology after partial nephrectomy confirmed post-transplant lymphoproliferative disorder. This is the first report of contrast enhanced ultrasound findings in a renal mass diagnosed as post-transplant lymphoproliferative disorder. Contrast enhanced ultrasound has a promising role in imaging of renal masses, particularly relevant in transplant patients due to the lack of nephrotoxicity. PMID:26629291

  10. Primary CNS lymphoproliferative disease, mycophenolate and calcineurin inhibitor usage

    PubMed Central

    Crane, Genevieve M.; Powell, Helen; Kostadinov, Rumen; Rocafort, Patrick Tim; Rifkin, Dena E.; Burger, Peter C.; Ambinder, Richard F.; Swinnen, Lode J.; Borowitz, Michael J.; Duffield, Amy S.

    2015-01-01

    Immunosuppression for solid organ transplantation increases lymphoproliferative disease risk. While central nervous system (CNS) involvement is more rare, we noticed an increase in primary CNS (PCNS) disease. To investigate a potential association with the immunosuppressive regimen we identified all post-transplant lymphoproliferative disease (PTLD) cases diagnosed over a 28-year period at our institution (174 total, 29 PCNS) and all similar cases recorded in a United Network for Organ Sharing-Organ Procurement and Transplant Network (UNOS-OPTN) data file. While no PCNS cases were diagnosed at our institution between 1986 and 1997, they comprised 37% of PTLD cases diagnosed from 2011–2014. PCNS disease was more often associated with renal vs. other organ transplant, Epstein-Barr virus, large B-cell morphology and mycophenolate mofetil (MMF) as compared to PTLD that did not involve the CNS. Calcineurin inhibitors were protective against PCNS disease when given alone or in combination with MMF. A multivariate analysis of a larger UNOS-OPTN dataset confirmed these findings, where both MMF and lack of calcineurin inhibitor usage were independently associated with risk for development of PCNS PTLD. These findings have significant implications for the transplant community, particularly given the introduction of new regimens lacking calcineurin inhibitors. Further investigation into these associations is warranted. PMID:26460822

  11. A unique case of rituximab-related posterior reversible encephalopathy syndrome in a heart transplant recipient with posttransplant lymphoproliferative disorder.

    PubMed

    Jaiswal, A; Sabnani, I; Baran, D A; Zucker, M J

    2015-03-01

    Rituximab is commonly used as a first line therapy to treat posttransplant lymphoproliferative disorders (PTLDs). It has also proved useful in the management of refractory antibody mediated graft rejection. We report an unusual case in which a heart transplant recipient being treated with rituximab for PTLD developed altered mental status, hallucinations and visual symptoms and magnetic resonance imaging (MRI) findings of symmetrical enhancement suggestive of posterior reversible leukoencephalopathy syndrome (PRES). Resolution of these clinical symptoms and radiological findings after discontinuation of therapy confirmed the diagnosis. This is the first case of PRES seen due to rituximab in a heart transplant recipient. Another unique feature of the case is the development of PRES after second cycle of rituximab as compared to prior reports in nonheart transplant patients in which the syndrome developed after first dose administration. The objective of this case report is to increase the awareness of this rare entity amongst immunocompromised transplant patients. PMID:25648447

  12. Syk-Induced Phosphatidylinositol-3-Kinase Activation in Epstein-Barr Virus Post-Transplant Lymphoproliferative Disorder

    PubMed Central

    Hatton, O.; Lambert, S. L.; Phillips, L. K.; Vaysberg, M.; Natkunam, Y.; Esquivel, C. O.; Krams, S. M.; Martinez, O. M.

    2012-01-01

    Post-transplant lymphoproliferative disorder (PTLD)-associated Epstein Barr virus (EBV)+ B-cell lymphomas are serious complications of solid organ and bone marrow transplantation. The EBV protein LMP2a, a B-cell receptor (BCR) mimic, provides survival signals to virally-infected cells through Syk tyrosine kinase. Therefore, we explored whether Syk inhibition is a viable therapeutic strategy for EBV-associated PTLD. We have shown that R406, the active metabolite of the Syk inhibitor fostamatinib, induces apoptosis and cell cycle arrest while decreasing downstream phosphatidylinositol-3′-kinase (PI3K)/Akt signaling in EBV+ B-cell lymphoma PTLD lines in vitro. However, Syk inhibition did not inhibit or delay the in vivo growth of solid tumors established from EBV-infected B-cell lines. Instead, we observed tumor growth in adjacent inguinal lymph nodes exclusively in fostamatinib-treated animals. In contrast, direct inhibition of PI3K/Akt significantly reduced tumor burden in a xenogeneic mouse model of PTLD without evidence of tumor growth in adjacent inguinal lymph nodes. Taken together, our data indicate that Syk activates PI3K/Akt signaling which is required for survival of EBV+ B-cell lymphomas. PI3K/Akt signaling may be a promising therapeutic target for PTLD, and other EBV-associated malignancies. PMID:23398911

  13. Histologic, molecular, and radiologic characterization of resolving cerebral posttransplant lymphoproliferative disorder.

    PubMed

    Dean, A F; Diss, T C; Wotherspoon, A C; Cox, T; Nevard, C

    1997-05-01

    Lymphoproliferative disorders (LPDs) are commoner in pediatric versus adult immunosuppressed transplant recipients, and frequently involve the central nervous system. In these circumstances, the justification for biopsy is heavily influenced by the likely diagnostic yield. The present study centers on a 12-y-old renal transplant patient who developed multifocal cerebral LPD and had serial magnetic resonance (MR) examinations during the course of her illness from which she has completely recovered upon reduction of immunosuppression. She underwent stereotaxic biopsy, which was analyzed by both immunocytochemistry and polymerase chain reaction to examine the general question of how to release the maximum amount of information contained within, as well as to obtain a tissue diagnosis in this particular case. We show that a combination of these methods permits identification of the immunophenotype, lineage, clonality, viral involvement, and origin of abnormal cellular infiltrates. The biopsy also showed a novel histologic pattern of LPD, comprising numerous benign T cells obscuring a tiny clone of B cells. The MR examinations documented, for the first time, the differences in signal that accompany clinical resolution at both biopsied and nonbiopsied sites, showing that the latter may be associated with reduction, but not elimination, of MR signal abnormality. We conclude: 1) a combination of conventional and polymerase chain reaction analysis offers the greatest diagnostic yield from stereotaxic biopsies, even when the available tissue is minimal; 2) a focal polyclonal T cell infiltrate should prompt further investigation to exclude an underlying B cell lesion. PMID:9128287

  14. Post-transplant lymphoproliferative disorders and Epstein-Barr virus DNAemia in a cohort of lung transplant recipients

    PubMed Central

    2011-01-01

    Background Post-transplant lymphoproliferative disorders (PTLD) are serious complications in lung transplant recipients. No consensus on EBV DNAemia levels predictive of PTLD has been reached. In addition, in many instances EBV DNAemia is determined in patients with suggestive symptoms only. Methods The characteristics of five patients with PTLD as well as the prevalence of EBV DNAmia in a cohort of 137 consecutive patients receiving lung transplantation are described. Results Twenty-six out of 137 patients (18.9%) were excluded from the analysis because lost at follow-up or dead from PTLD-independent reasons within three months of transplantation. EBV DNA in peripheral blood mononuclear cells (PBMC) was determined in 83/111 patients (74.8%) because of potential PTLD-related symptoms, while 28 patients (25.2%) showed no symptoms and were not examined. EBV DNAemia was positive in 53/83 patients (63.8%), and negative in 30/83 patients (36.2%). PTLD was diagnosed in five (4.5%) patients at a median time of 270 (range 120-870) days following transplantation. All five PTLD (three large B-cell lymphomas, one Hodgkin lymphoma and one possible pre-neoplastic lesion) were potentially associated with EBV infection. However, only 3/5 patients with PTLD had detectable EBV DNAemia: < 1,000 copies EBV DNA/1 × 105 PBMC in one patient and > 1,000 copies EBV DNA/1 × 105 PBMC in two patients. Conclusion A systematic multidisciplinary (clinical, radiologic, virologic and histologic) approach is mandatory for the diagnosis and management of PTLD in lung transplant recipients, while monitoring of symptomatic patients only may provide an incomplete or late picture of the clinical problem. In addition, staining for EBV antigens and quantification of EBV DNA in biopsy specimens should always be performed to understand the role of EBV infection in the pathogenesis of PTLD. PMID:21892950

  15. A Case Series of Primary Central Nervous System Post-Transplant Lymphoproliferative Disorder: Imaging and Clinical Characteristics

    PubMed Central

    Lake, Wendell; Chang, Julie E.; Kennedy, Tabassum; Morgan, Adam; Salamat, Shahriar; Başkaya, Mustafa

    2015-01-01

    Background Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a rare complication following solid organ transplantation (SOT). With increasing rates of SOT, PCNS-PTLD incidence is increasing. Objective Describe the characteristics of PCNS-PTLD patients requiring neurosurgical intervention. Methods From 2000-2011 ten patients with prior SOT underwent biopsy for evaluation of brain lesions and were diagnosed with PCNS-PTLD. Data collected included imaging characteristics, pathology, treatments administered, and survival outcomes. Results All patients had kidney transplantation, and 3 had concurrent pancreas transplantation. Median age at diagnosis was 49 years, with a median of 4.5 years from SOT to diagnosis (range 1.8-11.4 years). Presenting symptoms most often included focal neurologic deficits (n=6), although several patients had non-specific symptoms of headache and altered mental status. Brain lesions were generally multiple (n=7), supratentorial (n=8), and lobar or periventricular in distribution with ring-enhancement. Diagnosis was established by stereotactic (n=4) and open surgical biopsy (n=6). Treatments most frequently administered included reduction of immunosuppression (n=10), dexamethasone (n=10), rituximab (n=8), high-dose methotrexate (n=3), and whole-brain radiotherapy (n=6). Six patients remain alive without PCNS-PTLD relapse, including 4 patients who have sustained remissions beyond 2 years from diagnosis of PCNS-PTLD. Of 4 observed deaths, 1 was related to progressive PCNS-PTLD. Conclusion PCNS-PTLD must be considered in the differential diagnosis of any patient with prior SOT presenting with an intracranial lesion. Histologic diagnosis with brain biopsy is imperative given the risk for opportunistic infections that may have similar imaging findings and presentation. Prognosis is variable, although long-term survival has been reported. PMID:23685504

  16. Lymphoproliferative disease virus in wild turkeys in southeast United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously, retroviral neoplasms reported in wild upland game birds in the United States of America have typically been associated with reticuloendotheliosis virus (REV) infection. The information presented herein described the first reports of lymphoproliferative disease virus (LPDV) infection in ...

  17. Identification of lymphoproliferative disease virus in wild turkeys (Meleagris gallopavo) in the United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Viral-associated lymphoproliferative neoplasia in domestic poultry is caused by infection with a herpesvirus (Marek’s disease virus) or three species of retroviruses [Reticuloendotheliosis virus (REV), Avian leukosis/sarcoma virus, lymphoproliferative disease virus (LPDV)]. Previously, retroviral n...

  18. Small intestinal involvement by lymphoproliferative disorders post-renal transplantation: a report from the post-transplant lymphoproliferative disorder international survey.

    PubMed

    Khedmat, Hossein; Taheri, Saeed

    2013-05-01

    In this study, data on post-renal transplant lymphoproliferative disorders (PTLD) collected from the existing literature were pooled and analyzed to compare the characteristics, predictors and prognosis of small intestinal PTLDs. We performed a comprehensive search for the available data by Pubmed and Google scholar search engines for reports on this subject. Data from 18 previously published studies, comprising 120 renal allograft recipients, were included in the analysis. Renal transplant recipients with intestinal PTLD were significantly less likely to have Hogkin's and Hogkin's-like lesions (P = 0.044) and to be younger at the time of transplantation (P = 0.07). Except for Hodgkin's-like lesions, histopathological evaluations elsewhere were comparable between the group with PTLD in the small intestine and age- and sex-matched renal transplant recipients with PTLD in other sites. The overall mortality was relatively higher in the control group (P = 0.09). When death only due to PTLD was used as the outcome, a trend toward better outcome was seen for the intestinal PTLD group compared with the other localizations (P = 0.1). The 1- and 5-year survival rates for intestinal PTLD patients were 57% and 37%, respectively, compared with 54% and 21%, respectively, for the control group. According to our findings based on analysis of international data, renal transplant patients with small intestinal PTLD are more likely to be of younger age but less frequently represent Hodgkin's and Hodgkin's-like lesions. They also have better patient survival compared with transplant recipients with PTLD in other locations. Further multi-center prospective studies are needed to confirm our results. PMID:23640619

  19. Post-Transplant Lymphoproliferative Disorder (PTLD) Manifesting in the Oral Cavity of a 13-Year-Old Liver Transplant Recipient (LTx).

    PubMed

    Krasuska-Sławińska, Ewa; Minko-Chojnowska, Izabela; Pawłowska, Joanna; Dembowska-Bagińska, Bożenna; Pronicki, Maciej; Olczak-Kowalczyk, Dorota

    2015-01-01

    BACKGROUND Post-transplant lymphoproliferative disorder (PTLD) is a potential complication of solid organ or bone marrow transplants. The main PTLD risk factors are: the Epstein-Barr virus (EBV), transplant type, and use of immunosuppressants. It mainly consists of an uncontrolled growth of lymphocytes in transplant recipients under chronic immunosuppressive therapy. About 85% of PTLDs are EBV-containing B-cell proliferations; 14% are T-cell proliferations, of which only 40% contain EBV; and the remaining 1% is NK-cell or plasmocyte proliferations. PTLD may present various clinical manifestations, from non-specific mononucleosis-like syndrome to graft or other organ damage resulting from pathologic lymphocyte infiltration. PTLD may manifest in the oral cavity. CASE REPORT The objective of this study was to present the case of a 13-year-old female living-donor liver transplant recipient, resulting from biliary cirrhosis caused by congenital biliary atresia, with exophytic fibrous lesions on buccal mucosa and tongue. Exophytic and hyperplastic lesion of oral mucosa were removed and histopathological examination revealed polymorphic PTLD. The patient underwent 6 cycles of CHOP chemotherapy and all the oral lesions regressed completely. CONCLUSIONS All oral pathological lesions in organ transplant recipients need to be surgically removed and histopathologically examined because they present an increased risk of neoplastic transformations such as PTLD. PMID:26285106

  20. Outcome of treatment of Epstein-Barr virus-related post-transplant lymphoproliferative disorder in hematopoietic stem cell recipients: a comprehensive review of reported cases.

    PubMed

    Styczynski, J; Einsele, H; Gil, L; Ljungman, P

    2009-10-01

    Post-transplant lymphoproliferative disorder (PTLD) caused by Epstein-Barr virus (EBV) is an important complication in high-risk allogeneic hematopoietic stem cell transplant (HSCT) recipients. Before the current methods of anti-EBV therapy were introduced, the mortality from PTLD after HSCT was >80%. With current approaches the mortality from EBV-PTLD can be significantly reduced. The published literature and meeting abstracts were reviewed to assess the impact of different management strategies against EBV-PTLD. This analysis of reported outcomes indicates that preemptive use of rituximab and EBV-cytotoxic T lymphocytes (CTL) significantly reduced the risk of death due to EBV-PTLD in HSCT recipients with survival rates of 89.7% and 94.1%, respectively. Therapy of established PTLD also reduced the risk of fatal outcome. However, the overall success rates were lower than after preemptive therapy, reaching 63% and 88.2% of total EBV-DNA clearance with rituximab and CTL therapy, respectively. A reduction of immunosuppression and/or donor lymphocyte infusion might also reduce the risk of death due to EBV-PTLD. Although it is difficult to estimate these effects more precisely because of the frequent use of combination therapies, the responses to these modalities can be estimated to be 56.6% and 41.0%, respectively. Finally, chemotherapy seems not to contribute to improved survival of patients with PTLD after HSCT and antiviral agents are not active against PTLD. PMID:19558376

  1. Identification of lymphoproliferative disease virus in wild turkeys (Meleagris gallopavo) in the southeastern United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The eight cases described herein represent the first reports of lymphoproliferative disease virus (LPDV) infection in wild turkeys and the first identification of LPDV in North America. Systemic lymphoproliferative disease was presumably the cause of morbidity and mortality in five of the eight turk...

  2. Indolent T-cell lymphoproliferative disease of the gastrointestinal tract

    PubMed Central

    Perry, Anamarija M.; Warnke, Roger A.; Hu, Qinglong; Gaulard, Philippe; Copie-Bergman, Christiane; Alkan, Serhan; Wang, Huan-You; Cheng, Jason X.; Bacon, Chris M.; Delabie, Jan; Ranheim, Erik; Kucuk, Can; Hu, XiaoZhou; Weisenburger, Dennis D.

    2013-01-01

    Primary gastrointestinal (GI) T-cell lymphoma is an infrequent and aggressive disease. However, rare indolent clonal T-cell proliferations in the GI tract have been described. We report 10 cases of GI involvement by an indolent T-cell lymphoproliferative disease, including 6 men and 4 women with a median age of 48 years (range, 15-77 years). Presenting symptoms included abdominal pain, diarrhea, vomiting, food intolerance, and dyspepsia. The lesions involved oral cavity, esophagus, stomach, small intestine, and colon. The infiltrates were dense, but nondestructive, and composed of small, mature-appearing lymphoid cells. Eight cases were CD4−/CD8+, 1 was CD4+/CD8−, and another was CD4−/CD8−. T-cell receptor-γ chain gene rearrangement identified a clonal population in all 10 cases. There was no evidence of STAT3 SH2 domain mutation or activation. Six patients received chemotherapy because of an initial diagnosis of peripheral T-cell lymphoma, with little or no response, whereas the other 4 were followed without therapy. After a median follow-up of 38 months (range, 9-175 months), 9 patients were alive with persistent disease and 1 was free of disease. We propose the name “indolent T-LPD of the GI tract” for these lesions that can easily be mistaken for intestinal peripheral T-cell lymphoma, and lead to aggressive therapy. PMID:24009234

  3. EBV Lymphoproliferative Disease after Hematopoietic Stem Cell Transplant

    PubMed Central

    Rouce, Rayne H; Louis, Chrystal U; Heslop, Helen E

    2014-01-01

    PURPOSE OF REVIEW EBV reactivation can cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplant (SCT). Delays in reconstitution of EBV-specific T lymphocyte activity can lead to life-threatening EBV lymphoproliferative disease (EBV-PTLD). This review highlights recent advances in the understanding of pathophysiology, risk factors, diagnosis, and management of EBV viremia and PTLD. RECENT FINDINGS During the past decade, early detection strategies, such as serial measurement of EBV-DNA load, have helped to identify high-risk patients and to diagnose early lymphoproliferation. The most significant advances have come in the form of innovative treatment options, including manipulation of the balance between outgrowing EBV-infected B cells and the EBV cytotoxic T lymphocyte (EBV-CTL) response, and targeting infected B cells with monoclonal antibodies, chemotherapy, unmanipulated donor lymphocytes, and donor or more recently third party EBV-CTLs. Defining criteria for preemptive therapy and remains a challenge. SUMMARY EBV reactivation is a significant complication after SCT. Continued improvements in risk-stratification and treatment options are required to improve the morbidity and mortality caused by EBV associated diseases. Current approaches use Rituximab to deplete B cells or adoptive transfer of EBV-CTL to reconstitute immunity. The availability of rapid EBV specific T cell products offers the possibility of improved outcomes. PMID:25159713

  4. Upper airway obstruction and pulmonary abnormalities due to lymphoproliferative disease following bone marrow transplantation in children.

    PubMed

    Fletcher, B D; Heslop, H E; Kaste, S C; Bodner, S

    1998-07-01

    We report three patients who developed severe supraglottic airway obstruction due to Epstein-Barr virus lymphoproliferative disease following allogeneic bone marrow transplantation. In addition to enlarged pharyngeal lymphoid tissue seen in all three patients, two had supraglottic airway narrowing and two developed pulmonary lymphoproliferative disease. They were treated with unmanipulated T cells or EBV-specific cytotoxic T lymphocytes. Life-threatening upper airway obstruction is a radiologically detectable complication of allogeneic bone marrow transplantation in children. PMID:9662565

  5. Epstein-Barr virus latent and replicative gene expression in post-transplant lymphoproliferative disorders and AIDS-related non-Hodgkin's lymphomas. French Study Group of Pathology for HIV-associated Tumors.

    PubMed

    Rea, D; Delecluse, H J; Hamilton-Dutoit, S J; Marelle, L; Joab, I; Edelman, L; Finet, J F; Raphael, M

    1994-01-01

    In acquired immunodeficiency, B-cell proliferation is usually associated with Epstein-Barr virus (EBV), implying the impairment of the normal control of EBV and EBV-infected cells. It has been assumed that EBV infection is latent in lymphoproliferative disorders. In order to determine the type of latency and to investigate whether any lymphoproliferative disorders enter into the lytic cycle, we analyzed the expression of latent and replicative EBV genes in 9 post-transplant lymphoproliferative disorders (PTLD) and in 23 EBV-positive AIDS-related non-Hodgkin's lymphomas (AR-NHL). The PTLD cases were categorized into polyclonal or monoclonal polymorphic tumors and monoclonal monomorphic tumors. The AR-NHL cases included large-cell/immunoblastic (LC/IB) and Burkitt's lymphoma (BL) groups. We demonstrated that varying patterns of latent-viral-gene expression are exhibited showing the 3 forms of latency. Polymorphic PTLD and LC/IB AR-NHL frequently expressed type II or III latency, whereas monomorphic tumors and BL AR-NHL showed type I latency. It is noteworthy that 3 cases of BL AR-NHL expressed latency II form. Induction of lytic cycle highlighted by the expression of BZLF1 occurred in 55.5% of PTLD, 36% of LC/IB and 22% of BL AR-NHL. In contrast, late viral proteins indicating productive cycle were present in 22% of PTLD, 14% of LC/IB, and were absent in BL cases. These data suggest that the impairment of EBV control permits disruption of latency, but the initiation of the lytic cycle may not always lead to viral production. PMID:8172807

  6. Metabolic Bone Disease in the Post-transplant Population: Preventative and Therapeutic Measures.

    PubMed

    Nel, Johan Daniël; Epstein, Sol

    2016-05-01

    Post-transplant bone disease contributes significantly to patients' morbidity and mortality after transplantation and has an impact on their quality of life. This article discusses the major contributors to mechanisms causing bone loss, highlighting the role of preexisting disease in both kidney and liver failure and contributions from glucocorticoids and calcineurin inhibitors. Suggested monitoring and investigations are reviewed as well as treatment as far as the current literature supports, emphasizing the difference between kidney and liver recipients. PMID:27095646

  7. Avian oncogenesis induced by lymphoproliferative disease virus: a neglected or emerging retroviral pathogen?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lymphoproliferative disease virus (LPDV) is an exogenous oncogenic retrovirus that induces lymphoid tumors in some galliform species of birds. Historically, outbreaks of LPDV have been reported from Europe and Israel. Although the virus has previously never been detected in North America, herein we ...

  8. Deregulation of Fas ligand expression as a novel cause of autoimmune lymphoproliferative syndrome-like disease

    PubMed Central

    Nabhani, Schafiq; Ginzel, Sebastian; Miskin, Hagit; Revel-Vilk, Shoshana; Harlev, Dan; Fleckenstein, Bernhard; Hönscheid, Andrea; Oommen, Prasad T.; Kuhlen, Michaela; Thiele, Ralf; Laws, Hans-Jürgen; Borkhardt, Arndt; Stepensky, Polina; Fischer, Ute

    2015-01-01

    Autoimmune lymphoproliferative syndrome is frequently caused by mutations in genes involved in the Fas death receptor pathway, but for 20–30% of patients the genetic defect is unknown. We observed that treatment of healthy T cells with interleukin-12 induces upregulation of Fas ligand and Fas ligand-dependent apoptosis. Consistently, interleukin-12 could not induce apoptosis in Fas ligand-deficient T cells from patients with autoimmune lymphoproliferative syndrome. We hypothesized that defects in the interleukin-12 signaling pathway may cause a similar phenotype as that caused by mutations of the Fas ligand gene. To test this, we analyzed 20 patients with autoimmune lymphoproliferative syndrome of unknown cause by whole-exome sequencing. We identified a homozygous nonsense mutation (c.698G>A, p.R212*) in the interleukin-12/interleukin-23 receptor-component IL12RB1 in one of these patients. The mutation led to IL12RB1 protein truncation and loss of cell surface expression. Interleukin-12 and -23 signaling was completely abrogated as demonstrated by deficient STAT4 phosphorylation and interferon γ production. Interleukin-12-mediated expression of membrane-bound and soluble Fas ligand was lacking and basal expression was much lower than in healthy controls. The patient presented with the classical symptoms of autoimmune lymphoproliferative syndrome: chronic non-malignant, non-infectious lymphadenopathy, splenomegaly, hepatomegaly, elevated numbers of double-negative T cells, autoimmune cytopenias, and increased levels of vitamin B12 and interleukin-10. Sanger sequencing and whole-exome sequencing excluded the presence of germline or somatic mutations in genes known to be associated with the autoimmune lymphoproliferative syndrome. Our data suggest that deficient regulation of Fas ligand expression by regulators such as the interleukin-12 signaling pathway may be an alternative cause of autoimmune lymphoproliferative syndrome-like disease. PMID:26113417

  9. Application of polymerase chain reaction to detect rearrangement of immunoglobulin heavy chain genes in lymphoproliferative disease.

    PubMed

    Khalil, S H; Siegrist, K; Akhtar, M

    1997-07-01

    As part of our routine work-up in the diagnosis of lymphoproliferative disease, we used a rapid polymerase chain reaction (PCR) assay to amplify the DNA fragments of the framework 3 (FR3) region of the immunoglobulin heavy (IgH) chain genes. The assay does not involve hybridization, nested priming, or sequencing of the amplified PCR product. It was performed on 66 specimens of B-cell lymphoproliferative disease, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, multiple myeloma, hairy cell leukemia and follicular lymphoma. Twenty-six specimens of negative controls, including acute myeloid leukemia, chronic myeloid leukemia in myeloid transformation and idiopathic thrombocytopenic purpura, were also analyzed. The assay was performed with 77% sensitivity and 100% specificity. The standard IgH chain gene rearrangement by Southern blot analysis is reserved for the remaining negative cases if clinically indicated. PMID:17353588

  10. Epstein-Barr virus induced hemophagocytic lymphohistiocytosis in X-linked lymphoproliferative disease

    PubMed Central

    Sankararaman, Senthilkumar; Riel-Romero, Rosario Maria; Jeroudi, Majed; Gonzalez-Toledo, Eduardo

    2014-01-01

    X-linked lymphoproliferative disease (XLP) is a rare, often fatal genetic disorder characterized by extreme vulnerability to Epstein-Barr virus (EBV). EBV-induced hemophagocytic lymphohistiocytosis (HLH) is a known presentation in XLP. In EBV-induced HLH in XLP, the brain imaging findings in the acute phase include a non specific pattern. In this report, we highlight the magnetic resonance imaging and magnetic resonance spectroscopy findings in a child with EBV induced HLH in XLP. PMID:24966560

  11. Carcinoma of the tongue in a renal transplant recipient: a rare post-transplant malignancy.

    PubMed

    Prakash, Jai; Kumar, Mohan; Aralapuram, Kishan

    2015-01-01

    Current immunosuppression improved long-term outcome of transplant patients, but it also increased the incidence of de novo malignancy. Organ transplant recipients have a three to four-fold increased risk of developing carcinoma in comparison with the general population. Common malignancies encountered after transplantation include cancer of the skin, lips, post-transplant lymphoproliferative disease, ano-genital carcinoma and Kaposi sarcoma. Squamous cell carcinoma of the tongue is very rare. We report here a case of squamous cell carcinoma of the tongue in an adult male patient who developed it 11 years post-transplant. He underwent right hemiglossectomy and his graft function remained stable. PMID:25579725

  12. Systemic EBV T-cell lymphoproliferative disease of young adults.

    PubMed

    Kheyri, Zahedin; Mojtahedzadeh, Aydin; Zamani, Farhad; Zaremehrjerdi, Ali; Babaheidarian, Pegah

    2014-01-01

    T/NK cell proliferative EBV associated disease is a rare one which is more common in eastern Asian countries. EBV is originally associated with B cells, and EBV associated T cell lymphoma is so rare. Hence we decided to describe a patient treated with misleading diagnoses such as TB and sarcoidosis for almost two years. The liver was biopsied after admission in this center, and gastric and colonic biopsy was also performed due to gastrointestinal bleeding. Diffuse infiltration of chronic inflammatory cells was seen, especially lymphocytes some of which were atypical. T lymphocyte markers were seen in these cells by immunohistochemical staining. Further studies demonstrated T lymphocytes associated with EBV to be positive which is very rare event. Although going under chemotherapy, there were no response and the patient died. PMID:24901859

  13. Severe Puumala virus infection in a patient with a lymphoproliferative disease treated with icatibant.

    PubMed

    Laine, Outi; Leppänen, Ilona; Koskela, Sirpa; Antonen, Jaakko; Mäkelä, Satu; Sinisalo, Marjatta; Vaheri, Antti; Mustonen, Jukka

    2015-02-01

    Early identification of patients at risk of a severe course of hantaviral disease and lack of effective medication represent a global challenge in the treatment of this emerging infection. We describe a 67-year-old female patient with a history of chronic lymphoproliferative disease involving the spleen and an extremely severe acute Puumala hantavirus infection. She was treated with the bradykinin receptor antagonist icatibant and recovered. She is the second patient with a spleen abnormality and severe Puumala infection treated with icatibant in our hospital. We suggest that patients with spleen abnormalities may be more susceptible to severe hantavirus disease. The activation of the kinin-kallikrein system and the formation of bradykinin in hantavirus-infected endothelial cells indicate that the role of bradykinin receptor antagonist icatibant in the treatment of hantavirus disease is worth studying. PMID:25496418

  14. Treatment of EBV-related post-renal transplant lymphoproliferative disease with a tailored regimen including EBV-specific T cells.

    PubMed

    Comoli, Patrizia; Maccario, Rita; Locatelli, Franco; Valente, Umberto; Basso, Sabrina; Garaventa, Alberto; Tomà, Paolo; Botti, Gerardo; Melioli, Giovanni; Baldanti, Fausto; Nocera, Arcangelo; Perfumo, Francesco; Ginevri, Fabrizio

    2005-06-01

    The treatment of EBV-associated post-transplant lymphoproliferative disease (PTLD) poses a considerable challenge. Efforts have been made to define regimens based on combination of the available therapeutic agents, chosen and tailored on a patient-by-patient basis, with the aim of augmenting event-free patient and graft survival. Recently, autologous EBV-specific cytotoxic T-lymphocytes (CTL) have proved effective in enhancing EBV-specific immune responses and reducing viral load in organ transplant recipients with active infection. We investigated the use of a tailored combined approach including autologous EBV-specific CTL for the treatment of EBV-related PTLD developing after pediatric kidney transplantation. Five patients with disseminated monoclonal (n = 3) or localized polyclonal (n = 2) PTLD unresponsive to reduction of immunosuppression were enrolled. The patients with disseminated PTLD received 4-5 courses of reduced-dosage polychemotherapy, accompanied by rituximab on the first day of each course, while localized disease was removed surgically. At treatment completion, autologous EBV-specific CTL were infused. All patients showed a complete response to treatment, without therapy-related toxicity or rejection, and persist in remission with good renal function at a median follow-up of 31 months. These preliminary results suggest that a combined chemoimmunotherapy regimen including virus-specific T-cells is well tolerated and potentially effective as first-line treatment of EBV-related PTLD. PMID:15888049

  15. A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease.

    PubMed Central

    Sneller, M C; Straus, S E; Jaffe, E S; Jaffe, J S; Fleisher, T A; Stetler-Stevenson, M; Strober, W

    1992-01-01

    In mice, the two distinct autosomal recessive genes lpr and gld can induce a syndrome characterized by autoantibody formation and the progressive accumulation of an unusual CD4-CD8- T cell population in peripheral lymphoid tissue. This phenotype does not precisely mirror any human disease. In this report we describe two patients with a progressive lymphoproliferative disorder associated with autoimmunity. The peripheral blood and lymph nodes of these patients contained large numbers of an unusual CD4-CD8- T cell population. These CD4-CD8- T cells express surface markers characteristic of mature peripheral blood T cells (CD3, CD2, CD5), express the alpha/beta form of the T cell receptor, and do not express surface markers characteristic of immature thymocytes (CD1) or NK cells (CD16, CD56). Functionally, these cells exhibited deficient proliferation and lymphokine production upon stimulation with mitogenic antibodies to CD3 or CD2. Both proliferation and lymphokine production could be augmented by co-stimulation with an antibody directed at the CD28 determinant. The clinical and immunological features of this syndrome resemble the lymphoproliferative/autoimmune disease seen in lpr and gld mice. Images PMID:1386609

  16. Lymphoproliferative disorders in inflammatory bowel disease patients on immunosuppression: Lessons from other inflammatory disorders

    PubMed Central

    Lam, Grace Y; Halloran, Brendan P; Peters, Anthea C; Fedorak, Richard N

    2015-01-01

    Immunosuppressive agents, such as thiopurines, methotrexate, and biologics, have revolutionized the treatment of inflammatory bowel disease (IBD). However, a number of case reports, case control studies and retrospective studies over the last decade have identified a concerning link between immunosuppression and lymphoproliferative disorders (LPDs), the oncological phenomenon whereby lymphocytes divide uncontrollably. These LPDs have been associated with Epstein-Barr virus (EBV) infection in which the virus provides the impetus for malignant transformation while immunosuppression hampers the immune system’s ability to detect and clear these malignant cells. As such, the use of immunosuppressive agents may come at the cost of increased risk of developing LPD. While little is known about the LPD risk in IBD, more is known about immunosuppression in the post-transplantation setting and the development of EBV associated post-transplantation lymphoproliferative disorders (PTLD). In review of the PTLD literature, evidence is available to demonstrate that certain immune suppressants such as cyclosporine and T-lymphocyte modulators in particular are associated with an increased risk of PTLD development. As well, high doses of immunosuppressive agents and multiple immunosuppressive agent use are also linked to increased PTLD development. Here, we discuss these findings in context of IBD and what future studies can be taken to understand and reduce the risk of EBV-associated LPD development from immunosuppression use in IBD. PMID:26600976

  17. Immune-mediated neuropathy with Epstein-Barr virus-positive T-cell lymphoproliferative disease.

    PubMed

    Hattori, Takaaki; Arai, Ayako; Yokota, Takanori; Imadome, Ken-Ichi; Tomimitsu, Hiroyuki; Miura, Osamu; Mizusawa, Hidehiro

    2015-01-01

    A 47-year-old man with Epstein-Barr virus (EBV)-positive T/NK- cell lymphoproliferative disease (EBV-T/NK-LPD) developed acute-onset weakness. A nerve conduction study showed a conduction block in both the proximal and most distal segments. Although the patient's neuropathy transiently responded to intravenous immunoglobulin, it was progressive for at least 25 days until the start of prednisolone (PSL) administration, after which it remarkably improved. The neuropathy further improved after allogeneic bone marrow transplantation (BMT). The present patient's clinical course is not consistent with that of typical Guillain-Barré syndrome. This case suggests that EBV-T/NK-LPD can cause progressive immune-mediated neuropathy as a result of chronic EBV antigen presentation and can be treated with PSL and BMT. PMID:25742897

  18. Establishment and operation of a Good Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease.

    PubMed

    Vickers, Mark A; Wilkie, Gwen M; Robinson, Nicolas; Rivera, Nadja; Haque, Tanzina; Crawford, Dorothy H; Barry, Jacqueline; Fraser, Neil; Turner, David M; Robertson, Victoria; Dyer, Phil; Flanagan, Peter; Newlands, Helen R; Campbell, John; Turner, Marc L

    2014-11-01

    Epstein-Barr virus (EBV) is associated with several malignancies, including post-transplant lymphoproliferative disorder (PTLD). Conventional treatments for PTLD are often successful, but risk organ rejection and cause significant side effects. EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from peripheral blood lymphocytes provide an alternative treatment modality with few side effects, but autologous CTLs are difficult to use in clinical practice. Here we report the establishment and operation of a bank of EBV-specific CTLs derived from 25 blood donors with human leucocyte antigen (HLA) types found at high frequency in European populations. Since licensure, there have been enquiries about 37 patients, who shared a median of three class I and two class II HLA types with these donors. Cells have been infused into ten patients with lymphoproliferative disease, eight of whom achieved complete remission. Neither patient with refractory disease was matched for HLA class II. Both cases of EBV-associated non-haematopoietic sarcoma receiving cells failed to achieve complete remission. Thirteen patients died before any cells could be issued, emphasizing that the bank should be contacted before patients become pre-terminal. Thus, this third party donor-derived EBV-specific CTL cell bank can supply most patients with appropriately matched cells and most recipients have good outcomes. PMID:25066775

  19. Are T-LGL Leukemia and NK-Chronic Lymphoproliferative Disorder Really Two Distinct Diseases?

    PubMed Central

    Zambello, Renato; Teramo, Antonella; Gattazzo, Cristina; Semenzato, Gianpietro

    2014-01-01

    Mature Large Granular lymphocytes (LGL) disorders include a spectrum of conditions, ranging from polyclonal to clonal indolent and/or overt leukemic LGL proliferations. Most cases are represented by clonal expansions of TCRα/β+ LGL displaying a CD8+ phenotype with expression of cytotoxic T-cell antigens (CD57, CD16, TIA-1, perforin and granzyme B). Proliferations of CD3-CD16+ NK cells with a restricted patter of NK receptors are less common, usually comprising 15% of the cases. Main features are cytopenias, splenomegaly and autoimmune phenomena. Morphology, immunophenotyping and molecular analyses are crucial to establish a correct diagnosis of disease. According to the 2008 WHO classification, two separate entities account for the majority of cases, T-LGL leukemia and Chronic Lymphoproliferative Disease of NK cell (this latter still provisional). Although these disorders are characterized by the expansion of different cells types i.e. T and NK cells, with specific genetic features and abnormalities, compelling evidence supports the hypothesis that a common pathogenic mechanism would be involved in both disorders. As a matter of fact, a foreign antigen driven clonal selection is considered the initial step in the mechanism ultimately leading to generation of both conditions. In this chapter we will discuss recent advances on the pathogenesis of chronic T and NK disorders of granular lymphocytes, challenging the current WHO classification on the opportunity to separate T and NK disorders, which are likely to represent two sides of the same coin. PMID:24778993

  20. Molecular Surveillance for Lymphoproliferative Disease Virus in Wild Turkeys (Meleagris gallopavo) from the Eastern United States

    PubMed Central

    Thomas, Jesse M.; Allison, Andrew B.; Holmes, Edward C.; Phillips, Jamie E.; Bunting, Elizabeth M.; Yabsley, Michael J.; Brown, Justin D.

    2015-01-01

    Lymphoproliferative disease virus (LPDV) is a poorly understood, oncogenic avian retrovirus of domestic turkeys that has historically been restricted to Europe and Israel. However, a recent study reported LPDV in multiple wild turkey diagnostic cases from throughout the eastern United States of America (USA). To better understand the distribution of LPDV in the eastern USA, we surveyed 1,164 reportedly asymptomatic hunter-harvested wild turkeys from 17 states for the presence of LPDV proviral DNA by PCR. In total, 564/1,164 (47%) turkeys were positive for LPDV. Wild turkeys from each state had a relatively high prevalence of LPDV, although statewide prevalence varied from 26 to 83%. Phylogenetic analysis revealed two major clades of LPDV in the USA, although one was at a low frequency suggesting restricted transmission, as well as significant clustering by state of isolation. To determine the best tissue to target for diagnostic purposes, liver, spleen, and bone marrow were tested from a subset of 15 hunter-harvested wild turkeys and 20 wild turkey diagnostic cases. Overall, bone marrow provided the highest level of detection for both hunter-harvested turkeys and diagnostic cases. The sensitivity of LPDV detection between tissues was not significantly different for diagnostic cases, but was for hunter-harvested birds. These results indicate that LPDV infection is common and widespread in wild turkey populations throughout the eastern USA, even without overt signs of disease. PMID:25897755

  1. DIAGNOSING LYMPHOPROLIFERATIVE DISEASE VIRUS IN LIVE WILD TURKEYS (MELEAGRIS GALLOPAVO) USING WHOLE BLOOD.

    PubMed

    Alger, Katrina; Bunting, Elizabeth; Schuler, Krysten; Jagne, Jarra; Whipps, Christopher M

    2015-12-01

    Lymphoproliferative disease virus (LPDV) is a retrovirus that infects wild and domestic turkeys ( Meleagris gallopavo ). The first cases of LPDV in the United States were diagnosed in 2009, and subsequent surveillance has revealed the virus to be widespread in wild turkey populations throughout the eastern half of the country. More research is needed to determine whether LPDV is having a negative effect on turkey populations, but progress has been impeded by the lack of a simple method for diagnosing the virus in living birds. Infected animals may appear asymptomatic, and diagnostics currently rely on tissue or bone marrow, which can be difficult to obtain. This study investigated the reliability of polymerase chain reaction (PCR) to detect LPDV in whole blood, compared with previous methods using buffy coat (concentrated white blood cells) and bone marrow. Paired samples of whole blood and buffy coat were collected from 137 live turkeys and paired samples of whole blood and bone marrow were collected from 32 turkeys postmortem. Compared with buffy coat, whole blood had 97% sensitivity and 100% specificity. When compared with bone marrow, whole blood had 100% sensitivity and 89% specificity. Both comparisons had a high degree of agreement using Cohen's kappa statistic. Based on these results, PCR of whole blood provides detection of LPDV in living birds that is on par with both buffy coat and bone marrow. PMID:26667537

  2. Expression of HSV-1 receptors in EBV-associated lymphoproliferative disease determines susceptibility to oncolytic HSV.

    PubMed

    Wang, P-Y; Currier, M A; Hansford, L; Kaplan, D; Chiocca, E A; Uchida, H; Goins, W F; Cohen, J B; Glorioso, J C; van Kuppevelt, T H; Mo, X; Cripe, T P

    2013-07-01

    Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disease (LPD) after hematopoietic stem cell or solid organ transplantation remains a life-threatening complication. Expression of the virus-encoded gene product, EBER, has been shown to prevent apoptosis via blockade of PKR activation. As PKR is a major cellular defense against Herpes simplex virus (HSV), and oncolytic HSV-1 (oHSV) mutants have shown promising antitumor efficacy in preclinical models, we sought to determine whether EBV-LPD cells are susceptible to infection by oHSVs. We tested three primary EBV-infected lymphocyte cell cultures from neuroblastoma (NB) patients as models of naturally acquired EBV-LPD. NB12 was the most susceptible, NB122R was intermediate and NB88R2 was essentially resistant. Despite EBER expression, PKR was activated by oHSV infection. Susceptibility to oHSV correlated with the expression of the HSV receptor, nectin-1. The resistance of NB88R2 was reversed by exogenous nectin-1 expression, whereas downregulation of nectin-1 on NB12 decreased viral entry. Xenografts derived from the EBV-LPDs exhibited only mild (NB12) or no (NB88R2) response to oHSV injection, compared with a NB cell line that showed a significant response. We conclude that EBV-LPDs are relatively resistant to oHSV virotherapy, in some cases, due to low virus receptor expression but also due to intact antiviral PKR signaling. PMID:23254370

  3. Expression of HSV-1 Receptors in EBV-Associated Lymphoproliferative Disease Determines Susceptibility to Oncolytic HSV

    PubMed Central

    Wang, Pin-Yi; Currier, Mark A; Hansford, Loen; Kaplan, David; Chiocca, E. Antonio; Uchida, Hiroaki; Goins, William F.; Cohen, Justus B.; Glorioso, Joseph C.; van Kuppevelt, Toin H.; Mo, Xiaokui; Cripe, Timothy P

    2012-01-01

    Epstein-Barr virus (EBV)-associated B cell lymphoproliferative disease (LPD) after hematopoietic stem cell or solid organ transplantation remains a life-threatening complication. Expression of the virus-encoded gene product, EBER, has been shown to prevent apoptosis via blockade of PKR activation. Because PKR is a major cellular defense against Herpes simplex virus, and oncolytic HSV-1 (oHSV) mutants have shown promising anti-tumor efficacy in preclinical models, we sought to determine whether EBV-LPD cells are susceptible to infection by oHSVs. We tested three primary EBV-infected lymphocyte cell cultures from neuroblastoma (NB) patients as models of naturally acquired EBV-LPD. NB12 was most susceptible, NB122R was intermediate, and NB88R2 was essentially resistant. Despite EBER expression, PKR was activated by oHSV infection. Susceptibility to oHSV correlated with the expression of the HSV receptor, nectin-1. The resistance of NB88R2 was reversed by exogenous nectin-1 expression, whereas down-regulation of nectin-1 on NB12 decreased viral entry. Xenografts derived from the EBV-LPDs exhibited only mild (NB12) or no (NB88R2) response to oHSV injection, compared with a neuroblastoma cell line that showed a significant response. We conclude that EBV-LPDs are relatively resistant to oHSV virotherapy, in some cases due to low virus receptor expression but also due to intact anti-viral PKR signaling. PMID:23254370

  4. IFN-gamma gene polymorphisms associate with development of EBV+ lymphoproliferative disease in hu PBL-SCID mice.

    PubMed

    Dierksheide, Julie E; Baiocchi, Robert A; Ferketich, Amy K; Roychowdhury, Sameek; Pelletier, Ronald P; Eisenbeis, Charles F; Caligiuri, Michael A; VanBuskirk, Anne M

    2005-02-15

    Posttransplantation lymphoproliferative disorder (PTLD) is a devastating post-transplantation complication often associated with Epstein-Barr virus (EBV). Although the type and length of immunosuppression are risk factors, a patient's inherent immune capacity also likely contributes to this disorder. This report uses severe-combined immunodeficient mice given injections of human peripheral blood leukocytes (hu PBL-SCID [Severe Combined Immunodeficient] mice) to test the hypothesis that cytokine genotype associates with the development of EBV-associated lymphoproliferative disease (LPD). We observed that the A/A (adenosine/adenosine) genotype for base + 874 of the interferon gamma (IFN-gamma) gene was significantly more prevalent in PBLs producing rapid, high-penetrance LPD in hu PBL-SCID mice, compared to PBLs producing late, low-penetrance LPD or no LPD. In examining the relationship between genotype and cytolytic T-lymphocyte (CTL) function, transforming growth factor beta (TGF-beta) inhibited restimulation of CTLs in PBLs with adenosine at IFNG base + 874, but not in PBLs homozygous for thymidine. Importantly, neutralization of TGF-beta in hu PBL-SCID mice injected with A/A genotype PBLs resulted in reduced LPD development and expanded human CD8(+) cells. Thus, our data show that TGF-beta may promote tumor development by inhibiting CTL restimulation and expansion. Further, our data indicate that IFNG genotype may provide valuable information for both identifying transplant recipients at greater risk for PTLD and developing preventive and curative strategies. PMID:15498860

  5. Lymphoproliferative disease after lung and heart-lung transplantation: first description in Spain.

    PubMed

    Morales, P; Torres, J; Pérez-Enguix, D; Solé, A; Pastor, A; Segura, A; Zurbano, F

    2005-11-01

    Lymphoproliferative syndromes are the most common tumors in transplant recipients. More than 90% of posttransplantation lymphoproliferative syndromes (PTLS) are considered to be associated with Epstein-Barr virus, and 86% are of the B-cell line. Histopathology ranges from polymorphic-reactive to monomorphic forms. Clonality should be studied using molecular biology techniques. Clinically, a differentiation is usually made between early PTLS (occurring within 1 year after transplantation) and late PTLS, which occur as localized or disseminated nodal lymphomas. In localized forms, immunosuppression should be discontinued or decreased, and the involved area should be subsequently resected or irradiated. In disseminated cases, immunosuppression should be decreased and administration of acyclovir/ganciclovir should be considered. If this is not effective, treatment should be started with anti-CD20 monoclonal antibodies (rituximab). If no response occurs, use of chemotherapy, possibly with interferon, should be considered. Our aim was to report the incidence, clinical signs, and treatment in a series of patients undergoing lung transplantation (LTx). PMID:16386626

  6. Characterization of Clonality of Epstein-Barr Virus-Induced Human B Lymphoproliferative Disease in Mice with Severe Combined Immunodeficiency

    PubMed Central

    Nakamine, Hirokazu; Masih, Aneal S.; Okano, Motohiko; Taguchi, Yuichi; Pirruccello, Samuel J.; Davis, Jack R.; Mahloch, Mark L.; Beisel, Kirk W.; Kleveland, Kimberly; Sanger, Warren G.; Purtilo, David T.

    1993-01-01

    To improve the diagnostic accuracy and understanding of the pathogenesis of lymphoproliferative diseases (LPDs) occurring in immunosuppressed transplant recipients (post-transplantation LPD), clonality of Epstein-Barr virus-induced human LPDs in mice with severe combined immunodeficiency was examined by analyzing: 1) human immunoglobulin genes and their products, 2) the clonality of Epstein-Barr virus DNA, and 3) genetic alteration of c-myc or bcl-2 genes. A spectrum of clonality was found in the LPDs comparable with that reported for post-transplantation LPDs, although rearrangements of c-myc or bcl-2 genes were not detected. It is confirmed that this system is useful in terms of clonality for understanding the early phases in the pathogenesis of post-transplantation LPD or LPD in immune deficient patients. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5 PMID:8380952

  7. Oral Lesions and Lymphoproliferative Disorders

    PubMed Central

    Castellarin, P.; Pozzato, G.; Tirelli, G.; Di Lenarda, R.; Biasotto, M.

    2010-01-01

    Lymphoproliferative disorders are heterogeneous malignancy characterized by the expansion of a lymphoid clone more or less differentiated. At the level of the oral cavity, the lymphoproliferative disorder can occur in various ways, most commonly as lymphoid lesions with extranodal externalization, but sometimes, oral lesions may represent a localization of a disease spread. With regard to the primary localizations of lymphoproliferative disorders, a careful examination of the head and neck, oral, and oropharyngeal area is necessary in order to identify suspicious lesions, and their early detection results in a better prognosis for the patient. Numerous complications have been described and frequently found at oral level, due to pathology or different therapeutic strategies. These complications require precise diagnosis and measures to oral health care. In all this, oral pathologists, as well as dental practitioners, have a central role in the treatment and long-term monitoring of these patients. PMID:20871659

  8. Perceptions of post-transplant recidivism in liver transplantation for alcoholic liver disease

    PubMed Central

    Kawaguchi, Yoshikuni; Sugawara, Yasuhiko; Akamatsu, Nobuhisa; Kaneko, Junichi; Tanaka, Tomohiro; Tamura, Sumihito; Aoki, Taku; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Kokudo, Norihiro

    2014-01-01

    Although alcoholic liver disease (ALD) is regarded as a common indication for liver transplantation (LT), debatable issues exist on the requirement for preceding alcoholic abstinence, appropriate indication criteria, predictive factors for alcoholic recidivism, and outcomes following living-donor LT. In most institutions, an abstinence period of six months before LT has been adopted as a mandatory selection criterion. Data indicating that pre-transplant abstinence is an associated predictive factor for alcoholic recidivism supports the reasoning behind this. However, conclusive evidence about the benefit of adopting an abstinence period is yet to be established. On the other hand, a limited number of reports available on living-donor LT experiences for ALD patients suggest that organ donations from relatives have no suppressive effect on alcoholic recidivism. Prevention of alcoholic recidivism has proved to be the most important treatment after LT based on the resultant inferior long-term outcome of patients. Further evaluations are still needed to establish strategies before and after LT for ALD. PMID:25429319

  9. Perceptions of post-transplant recidivism in liver transplantation for alcoholic liver disease.

    PubMed

    Kawaguchi, Yoshikuni; Sugawara, Yasuhiko; Akamatsu, Nobuhisa; Kaneko, Junichi; Tanaka, Tomohiro; Tamura, Sumihito; Aoki, Taku; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Kokudo, Norihiro

    2014-11-27

    Although alcoholic liver disease (ALD) is regarded as a common indication for liver transplantation (LT), debatable issues exist on the requirement for preceding alcoholic abstinence, appropriate indication criteria, predictive factors for alcoholic recidivism, and outcomes following living-donor LT. In most institutions, an abstinence period of six months before LT has been adopted as a mandatory selection criterion. Data indicating that pre-transplant abstinence is an associated predictive factor for alcoholic recidivism supports the reasoning behind this. However, conclusive evidence about the benefit of adopting an abstinence period is yet to be established. On the other hand, a limited number of reports available on living-donor LT experiences for ALD patients suggest that organ donations from relatives have no suppressive effect on alcoholic recidivism. Prevention of alcoholic recidivism has proved to be the most important treatment after LT based on the resultant inferior long-term outcome of patients. Further evaluations are still needed to establish strategies before and after LT for ALD. PMID:25429319

  10. Epstein-Barr virus associated T-cell lymphoproliferative disease misdiagnosed as ulcerative colitis: a case report

    PubMed Central

    Zheng, Xiaodan; Xie, Jianlan; Zhou, Xiaoge

    2015-01-01

    Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disease (LPD) is not uncommon in China, but gastrointestinal involvement is very rare. We report on an immunocompetent patient with EBV-associated T-cell LPD of the colon. The 26-year-old man was initially misdiagnosed with ulcerative colitis (UC). A colon biopsy revealed the presence of small to medium-sized lymphoid cells infiltrating the intestinal wall. The neoplastic cells expressed CD3, CD5, and granzyme B, not CD56. EBV-encoded small ribonucleic acid was detected in the tumor cells of the colon as well as the lymph node, and the T-cell receptor gene rearrangement result displayed ? gene monoclonal rearrangement. The patient died 2 moths after the diagnosis. The clinical course of EBV-associated T-cell LPD is aggressive and the prognosis is poor, the wrong diagnosis may delay treatment. Therefore, we should be very careful to prevent misdiagnosis. When patients have multiple intestinal ulcers that are not typical of UC and the clinical course is unusual, although morphology looks like inflammatory change, pathologist should consider the possibility of EBV-associated LPD. The treatment strategy and prognosis of these two diseases are different. PMID:26339440

  11. Characterization of two distinct lymphoproliferative diseases caused by ectopic expression of the Notch ligand DLL4 on T cells.

    PubMed

    Xiong, Huizhong; Maraver, Antonio; Latkowski, Jo-Ann; Henderson, Tanya; Schlessinger, Karni; Ding, Yi; Shen, Jie; Tadokoro, Carlos E; Lafaille, Juan J

    2013-01-01

    Notch signaling is essential for the development of T cell progenitors through the interaction of NOTCH1 receptor on their surface with the ligand, Delta-like 4 (DLL4), which is expressed by the thymic epithelial cells. Notch signaling is quickly shut down once the cells pass β-selection, and CD4/CD8 double positive (DP) cells are unresponsive to Notch. Over the past two decades a number of papers reported that over-activation of Notch signaling causes T cell acute lymphoblastic leukemia (T-ALL), a cancer that prominently features circulating monoclonal CD4/CD8 double positive T cells in different mouse models. However, the possible outcomes of Notch over-activation at different stages of T cell development are unknown, and the fine timing of Notch signaling that results in T-ALL is poorly understood. Here we report, by using a murine model that ectopically expresses DLL4 on developing T cells, that the T-ALL onset is highly dependent on a sustained Notch activity throughout the DP stage, which induces additional mutations to further boost the signaling. In contrast, a shorter period of Notch activation that terminates at the DP stage causes a polyclonal, non-transmissible lymphoproliferative disorder that is also lethal. These observations resolved the discrepancy of previous papers on DLL4 driven hematological diseases in mice, and show the critical importance of the timing and duration of Notch activity. PMID:24386421

  12. Characterization of Two Distinct Lymphoproliferative Diseases Caused by Ectopic Expression of the Notch Ligand DLL4 on T Cells

    PubMed Central

    Latkowski, Jo-Ann; Henderson, Tanya; Schlessinger, Karni; Ding, Yi; Shen, Jie; Tadokoro, Carlos E.; Lafaille, Juan J.

    2013-01-01

    Notch signaling is essential for the development of T cell progenitors through the interaction of NOTCH1 receptor on their surface with the ligand, Delta-like 4 (DLL4), which is expressed by the thymic epithelial cells. Notch signaling is quickly shut down once the cells pass β-selection, and CD4/CD8 double positive (DP) cells are unresponsive to Notch. Over the past two decades a number of papers reported that over-activation of Notch signaling causes T cell acute lymphoblastic leukemia (T-ALL), a cancer that prominently features circulating monoclonal CD4/CD8 double positive T cells in different mouse models. However, the possible outcomes of Notch over-activation at different stages of T cell development are unknown, and the fine timing of Notch signaling that results in T-ALL is poorly understood. Here we report, by using a murine model that ectopically expresses DLL4 on developing T cells, that the T-ALL onset is highly dependent on a sustained Notch activity throughout the DP stage, which induces additional mutations to further boost the signaling. In contrast, a shorter period of Notch activation that terminates at the DP stage causes a polyclonal, non-transmissible lymphoproliferative disorder that is also lethal. These observations resolved the discrepancy of previous papers on DLL4 driven hematological diseases in mice, and show the critical importance of the timing and duration of Notch activity. PMID:24386421

  13. Epstein-Barr Virus-positive T-cell Lymphoproliferative Disease Following Umbilical Cord Blood Transplantation for Acute Myeloid Leukemia.

    PubMed

    Yui, Shunsuke; Yamaguchi, Hiroki; Imadome, Ken-Ichi; Arai, Ayako; Takahashi, Mikiko; Ohashi, Ryuji; Tamai, Hayato; Moriya, Keiichi; Nakayama, Kazutaka; Shimizu, Akira; Inokuchi, Koiti

    2016-01-01

    We report a case of the extremely rare condition Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease (LPD) which occurred after umbilical cord blood transplantation. A 25-year-old Japanese man underwent cord blood transplantation from a male human leukocyte antigen 4/6-matched donor due to acute myeloid leukemia with trisomy 8. Bone marrow examination on day 30 showed chimerism with at least 90% donor cells and complete hematological response. Chronic symptoms of graft-versus-host disease appeared only on the skin and were successfully treated with cyclosporine alone. Three years later, however, the patient experienced repeated cold-like symptoms and was hospitalized with liver dysfunction. A high fever developed and was followed by significant edema of the right side of the face. The EBV DNA copy number in whole peripheral blood was 2×10(4)/mL. Liver biopsy showed invasion of EBV-infected CD8-positive T cells. Southern blotting analysis of the whole peripheral blood showed that the T-cell receptor Cβ1 rearrangement was positive. On the basis of these results, EBV-positive T-cell LPD was diagnosed and treated with prednisolone, cyclosporine, and etoposide, followed by cyclophosphamide, doxorubicin, vincristine, and prednisone. However, the patient died of cardiac function failure, pneumonia, and pulmonary hemorrhage, all of unidentified cause. Most cases of EBV-related LPD after hematopoietic stem cell transplantation consist of EBV-positive B-cell LPD, and, to our knowledge, de novo EBV-positive T-cell LPD subsequent to transplantation has not been previously reported. PMID:26960588

  14. Study Provides Insights into Diagnosis, Treatment of Rare Immune Disease: Autoimmmune Lymphoproliferative Syndrome ...

    MedlinePlus

    ... Read more information on enabling JavaScript. Skip Content Marketing Share this: Main Content Area Study Provides Insights ... causes of death among ALPS patients, and suggests strategies to improve disease treatment and management. The Fas ...

  15. Disclosing the CXCR4 Expression in Lymphoproliferative Diseases by Targeted Molecular Imaging

    PubMed Central

    Wester, Hans Jrgen; Keller, Ulrich; Schottelius, Margret; Beer, Ambros; Philipp-Abbrederis, Kathrin; Hoffmann, Frauke; ime?ek, Jakub; Gerngross, Carlos; Lassmann, Michael; Herrmann, Ken; Pellegata, Natalia; Rudelius, Martina; Kessler, Horst; Schwaiger, Markus

    2015-01-01

    Chemokine ligand-receptor interactions play a pivotal role in cell attraction and cellular trafficking, both in normal tissue homeostasis and in disease. In cancer, chemokine receptor-4 (CXCR4) expression is an adverse prognostic factor. Early clinical studies suggest that targeting CXCR4 with suitable high-affinity antagonists might be a novel means for therapy. In addition to the preclinical evaluation of [68Ga]Pentixafor in mice bearing human lymphoma xenografts as an exemplary CXCR4-expressing tumor entity, we report on the first clinical applications of [68Ga]Pentixafor-Positron Emission Tomography as a powerful method for CXCR4 imaging in cancer patients. [68Ga]Pentixafor binds with high affinity and selectivity to human CXCR4 and exhibits a favorable dosimetry. [68Ga]Pentixafor-PET provides images with excellent specificity and contrast. This non-invasive imaging technology for quantitative assessment of CXCR4 expression allows to further elucidate the role of CXCR4/CXCL12 ligand interaction in the pathogenesis and treatment of cancer, cardiovascular diseases and autoimmune and inflammatory disorders. PMID:25825601

  16. Antigen-specific lymphoproliferative responses to tetanus toxoid: a means for the evaluation of Marek's disease virus-induced immunosuppression in chickens.

    PubMed

    Reddy, S K; Suresh, M; Karaca, K; Sharma, J M; McMillen, J; Schwartz, R D

    1996-12-01

    Antigen-specific lymphoproliferative responses were examined in chickens following immunization with tetanus toxoid (Ttx). The immune competence of chickens was assessed by mitogen assay utilizing phytohemagglutinin (PHA)-stimulation and Ttx-specific antigen proliferation assay (Ttx-APA). Immune spleen cells but not peripheral blood leucocytes demonstrated specific proliferation following stimulation in vitro in a Ttx-APA. In this study, we examined firstly the effects of Marek's disease (MD)-associated immunosuppression on specific immune responses. The humoral and cell-mediated immune responses were monitored by enzyme-linked immunosorbent assay (ELISA) and Ttx-APA, respectively. Secondly, we examined if vaccination against MD using a conventional herpesvirus of turkeys (HVT) vaccine and two recombinant HVT (rHVT) vaccines would affect the development of Ttx-specific immune responses. The rHVT vaccines used in this study included two constructs: one expressing both Newcastle disease virus (NDV) and MD virus (MDV) genes (HVT/NDV/MDV), and another expressing only MDV genes (HVT/MDV). The mitogenic responses of spleen cells of the vaccinated chickens were inconsistent allowing no definitive conclusions about vaccinal immunosuppression. The results of the Ttx-APA indicated that Ttx-specific lymphoproliferative responses provide a meaningful measure of immunosuppression. The MDV-induced immunosuppression resulted in the inhibition of Ttx-specific lymphoproliferation in vitro. Both HVT and rHVT vaccines were not immunosuppressive as indicated by the development of normal Ttx-specific lymphoproliferative responses in chickens. These results indicate that vaccination against MD results not only in the prevention of tumor formation but also protection from possible virus-induced immunosuppression. PMID:9032901

  17. Inherited CHST11/MIR3922 deletion is associated with a novel recessive syndrome presenting with skeletal malformation and malignant lymphoproliferative disease

    PubMed Central

    Chopra, Sameer S; Leshchiner, Ignaty; Duzkale, Hatice; McLaughlin, Heather; Giovanni, Monica; Zhang, Chengsheng; Stitziel, Nathan; Fingeroth, Joyce; Joyce, Robin M; Lebo, Matthew; Rehm, Heidi; Vuzman, Dana; Maas, Richard; Sunyaev, Shamil R; Murray, Michael; Cassa, Christopher A

    2015-01-01

    Glycosaminoglycans (GAGs) such as chondroitin are ubiquitous disaccharide carbohydrate chains that contribute to the formation and function of proteoglycans at the cell membrane and in the extracellular matrix. Although GAG-modifying enzymes are required for diverse cellular functions, the role of these proteins in human development and disease is less well understood. Here, we describe two sisters out of seven siblings affected by congenital limb malformation and malignant lymphoproliferative disease. Using Whole-Genome Sequencing (WGS), we identified in the proband deletion of a 55 kb region within chromosome 12q23 that encompasses part of CHST11 (encoding chondroitin-4-sulfotransferase 1) and an embedded microRNA (MIR3922). The deletion was homozygous in the proband but not in each of three unaffected siblings. Genotyping data from the 1000 Genomes Project suggest that deletions inclusive of both CHST11 and MIR3922 are rare events. Given that CHST11 deficiency causes severe chondrodysplasia in mice that is similar to human limb malformation, these results underscore the importance of chondroitin modification in normal skeletal development. Our findings also potentially reveal an unexpected role for CHST11 and/or MIR3922 as tumor suppressors whose disruption may contribute to malignant lymphoproliferative disease. PMID:26436107

  18. Restimulation-induced apoptosis of T cells is impaired in patients with X-linked lymphoproliferative disease caused by SAP deficiency

    PubMed Central

    Snow, Andrew L.; Marsh, Rebecca A.; Krummey, Scott M.; Roehrs, Philip; Young, Lisa R.; Zhang, Kejian; van Hoff, Jack; Dhar, Deepali; Nichols, Kim E.; Filipovich, Alexandra H.; Su, Helen C.; Bleesing, Jack J.; Lenardo, Michael J.

    2009-01-01

    X-linked lymphoproliferative disease (XLP) is a rare congenital immunodeficiency that leads to an extreme, usually fatal increase in the number of lymphocytes upon infection with EBV. It is most commonly defined molecularly by loss of expression of SLAM-associated protein (SAP). Despite this, there is little understanding of how SAP deficiency causes lymphocytosis following EBV infection. Here we show that T cells from individuals with XLP are specifically resistant to apoptosis mediated by TCR restimulation, a process that normally constrains T cell expansion during immune responses. Expression of SAP and the SLAM family receptor NK, T, and B cell antigen (NTB-A) were required for TCR-induced upregulation of key pro-apoptotic molecules and subsequent apoptosis. Further, SAP/NTB-A signaling augmented the strength of the proximal TCR signal to achieve the threshold required for restimulation-induced cell death (RICD). Strikingly, TCR ligation in activated T cells triggered increased recruitment of SAP to NTB-A, dissociation of the phosphatase SHP-1, and colocalization of NTB-A with CD3 aggregates. In contrast, NTB-A and SHP-1 contributed to RICD resistance in XLP T cells. Our results reveal what we believe to be novel roles for NTB-A and SAP in regulating T cell homeostasis through apoptosis and provide mechanistic insight into the pathogenesis of lymphoproliferative disease in XLP. PMID:19759517

  19. Conservative management of post-transplant central nervous system lymphoma.

    PubMed

    Valavoor, Shahul H; Ashraf, Zubair; Narwal, Rawan; Ratnam, Shobha

    2013-08-01

    Primary CNS lymphoma (PCNSL) is a rare B cell variant non-Hodgkins lymphoma that is confined to the brain, leptomeninges, spinal cord and eyes. Its incidence is increasing, primarily due to increase in the number of organ transplantations being undertaken. The majority of the PTLD (post-transplant lymphoproliferative disorder) is seen in kidney transplant recipients simply because they constitute a larger group of transplant recipients each year as compared to other solid organ transplantations. Primary infection of previously infected EBV seronegative patients and immunosuppression are found to be the main etiologic factors in the development of PTLD-PCNSL. There are no clear guidelines on treatment regimens, and it should be individualized according to patient comorbidities. We report a case of PCNS lymphoproliferative disorder in a kidney transplant recipient, which underwent complete remission with decreasing immunosuppression. The patient could not undergo chemotherapy/radiotherapy due to underlying comorbidities. We highlight the available treatment modalities for PTLD-PCNSL. PMID:22476860

  20. Mesenchymal stromal cells transiently alter the inflammatory milieu post-transplant to delay graft-versus-host disease

    PubMed Central

    Christensen, Melinda E.; Turner, Brie E.; Sinfield, Laura J.; Kollar, Katarina; Cullup, Hannah; Waterhouse, Nigel J.; Hart, Derek N.J.; Atkinson, Kerry; Rice, Alison M.

    2010-01-01

    Background Multipotent mesenchymal stromal cells suppress T-cell function in vitro, a property that has underpinned their use in treating clinical steroid-refractory graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. However the potential of mesenchymal stromal cells to resolve graft-versus-host disease is confounded by a paucity of pre-clinical data delineating their immunomodulatory effects in vivo. Design and Methods We examined the influence of timing and dose of donor-derived mesenchymal stromal cells on the kinetics of graft-versus-host disease in two murine models of graft-versus-host disease (major histocompatibility complex-mismatched: UBI-GFP/BL6 [H-2b]→BALB/c [H-2d] and the sibling transplant mimic, UBI-GFP/BL6 [H-2b]→BALB.B [H-2b]) using clinically relevant conditioning regimens. We also examined the effect of mesenchymal stromal cell infusion on bone marrow and spleen cellular composition and cytokine secretion in transplant recipients. Results Despite T-cell suppression in vitro, mesenchymal stromal cells delayed but did not prevent graft-versus-host disease in the major histocompatibility complex-mismatched model. In the sibling transplant model, however, 30% of mesenchymal stromal cell-treated mice did not develop graft-versus-host disease. The timing of administration and dose of the mesenchymal stromal cells influenced their effectiveness in attenuating graft-versus-host disease, such that a low dose of mesenchymal stromal cells administered early was more effective than a high dose of mesenchymal stromal cells given late. Compared to control-treated mice, mesenchymal stromal cell-treated mice had significant reductions in serum and splenic interferon-γ, an important mediator of graft-versus-host disease. Conclusions Mesenchymal stromal cells appear to delay death from graft-versus-host disease by transiently altering the inflammatory milieu and reducing levels of interferon-γ. Our data suggest that both the timing of infusion and the dose of mesenchymal stromal cells likely influence these cells’ effectiveness in attenuating graft-versus-host disease. PMID:20801899

  1. Post-transplant recurrent hepatitis B viral liver disease. Viral-burden, steatoviral, and fibroviral hepatitis B.

    PubMed Central

    Phillips, M. J.; Cameron, R.; Flowers, M. A.; Blendis, L. M.; Greig, P. D.; Wanless, I.; Sherman, M.; Superina, R.; Langer, B.; Levy, G. A.

    1992-01-01

    Recurrence of hepatitis is a well-documented complication of hepatitis B liver disease, post-transplantation. It is well established also that the earliest hepatocellular change is the appearance of hepatitis B viral (HBV) markers and that the disease is rapidly progressive. In this article on 17 liver transplants in 16 HBV positive patients with long-term follow-ups (100-1234 days), the distinctive pathologic features of this disease are emphasized: the extreme viral load, the steatosis, and/or fibrosis. An attempt to quantitate the magnitude of the viral burden was made and the result was a staggering figure. In one patient, an estimated 10(18) HBV core particles were present in the liver. One of two patterns of progression were noted. In four patients in addition to the massive nuclear hepatitis B core antigen (HBcAg) and cytoplasmic hepatitis B surface antigen (HBsAg) positivity, superimposed hepatitic changes led to diffuse hepatic fibrosis (fibroviral hepatitis B); and in another six patients, extraordinary hepatocellular viral marker positivity and steatosis were the hallmarks (steatoviral hepatitis B). Steatosis is not usually considered a feature of HBV liver pathology. These results suggest that more than one type of posttransfusion recurrent hepatitis B liver disease exists pathologically. Images Figure 1 Figure 2 Figure 3 PMID:1376555

  2. Post transplant lymphoproliferative disease in pediatric solid organ transplant patients: a possible role for [18F]-FDG-PET(/CT) in initial staging and therapy monitoring.

    PubMed

    von Falck, C; Maecker, B; Schirg, E; Boerner, A R; Knapp, W H; Klein, C; Galanski, M

    2007-09-01

    Post transplant lymphoproliferative disease (PTLD) is a severe complication after solid organ or bone marrow transplantation. In pediatric transplant recipients PTLD is the most common malignancy. The aim of this study was to evaluate a possible role for positron emission tomography with [18F]-2-fluoro-2-desoxy-glucose (FDG) in the initial staging and in therapy monitoring of pediatric patients suffering from biopsy-proven CD20-positive PTLD after solid organ transplantation. Seven pediatric patients were included. All available imaging studies - CT (n=15), MRI (n=16) and PET/PETCT (n=16) - were reviewed on a lesion by lesion base. The performance of FDG-PET in the initial staging and during therapy with a chimeric anti-CD20 antibody was compared to conventional cross sectional imaging and correlated with the clinical outcome. FDG-PET identified all sites of disease as shown by CT/MRI and helped to clarify the significance of equivocal findings. The initial stage of disease was correctly identified by FDG-PET alone when compared to CT/MRI. During therapy, FDG-PET was superior to conventional cross-sectional imaging in the early evaluation of response. PMID:17293073

  3. Treatment of Epstein-Barr virus lymphoproliferative disease after hematopoietic stem-cell transplantation with hydroxyurea and cytotoxic T-cell lymphocytes.

    PubMed

    Pakakasama, Samart; Eames, Gretchen M; Morriss, Michael C; Huls, M Helen; Rooney, Cliona M; Heslop, Helen E; Krance, Robert A

    2004-09-15

    Epstein-Barr virus (EBV) lymphoproliferative disease (LPD) is a potentially fatal complication that may follow allogeneic hematopoietic stem-cell transplantation (HSCT). In this article, the authors report a 2-year-old girl with Hurler's syndrome who developed multiple central nervous system (CNS) EBV LPD lesions 1 year after unrelated donor HSCT. Before this CNS occurrence, the patient had a complete response to rituximab treatment for EBV LPD of the spleen and lymph nodes; however, treatment of the CNS disease with rituximab proved ineffective. Because of reported favorable response of primary CNS EBV LPD in two human immunodeficiency virus-positive patients, the authors treated this patient with low-dose oral hydroxyurea. The patient improved clinically, with a decrease in size of multiple EBV LPD brain lesions. Subsequently, the patient received EBV-specific cytotoxic T-cell lymphocytes and remains well. The benefit and limited toxicity of hydroxyurea therapy merit its further consideration as treatment for EBV LPD. PMID:15371682

  4. De novo post-transplant thrombotic microangiopathy localized only to the graft in autosomal dominant polycystic kidney disease with thrombophilia

    PubMed Central

    Rolla, Davide; Fontana, Iris; Ravetti, Jean Louis; Marsano, Luigina; Bellino, Diego; Panaro, Laura; Ansaldo, Francesca; Mathiasen, Lisa; Storace, Giulia; Trezzi, Matteo

    2015-01-01

    Introduction: Thrombotic microangiopathy (TMA) is a serious complication of renal transplantation and is mostly related to the prothrombotic effect of calcineurin inhibitors (CNIs). A subset of TMA (29%-38%) is localized only to the graft. Case 1: A young woman suffering from autosomal dominant polycystic kidney disease (ADPKD) underwent kidney transplant. After 2 months, she showed slow renal deterioration (serum creatinine from 1.9 to 3.1 mg/dl), without hematological signs of hemolytic-uremic syndrome (HUS); only LDH enzyme transient increase was detected. Renal biopsy showed TMA: temporary withdraw of tacrolimus and plasmapheresis was performed. The renal function recovered (serum creatinine 1.9 mg/dl). From screening for thrombophilia, we found a mutation of the Leiden factor V gene. Case 2: A man affected by ADPKD underwent kidney transplantation, with delay graft function; first biopsy showed acute tubular necrosis, but a second biopsy revealed TMA, while no altered hematological parameters of HUS was detected. We observed only a slight increase of lactate dehydrogenase (LDH) levels. The tacrolimus was halved and plasmapheresis was performed: LDH levels normalized within 10 days and renal function improved (serum creatinine from 9 to 2.9 mg/dl). We found a mutation of the prothrombin gene. Only a renal biopsy clarifies the diagnosis of TMA, but it is necessary to pay attention to light increasing level of LDH. Conclusion: Prothrombotic effect of CNIs and mTOR inhibitor, mutation of genes encoding factor H or I, anticardiolipin antibodies, vascular rejection, cytomegalovirus infection are proposed to trigger TMA; we detected mutations of factor II and Leiden factor V, as facilitating conditions for TMA in patients affected by ADPKD. PMID:26693501

  5. A PLC-γ1-independent, RasGRP1-ERK dependent pathway drives lymphoproliferative disease in LAT-Y136F mutant mice

    PubMed Central

    Kortum, Robert L.; Rouquette-Jazdanian, Alexandre K.; Miyaji, Michihiko; Merrill, Robert K.; Markegard, Evan; Pinski, John M.; Wesselink, Amelia; Nath, Nandan N.; Alexander, Clayton P.; Li, Wenmei; Kedei, Noemi; Roose, Jeroen P.; Blumberg, Peter M.; Samelson, Lawrence E.; Sommers, Connie L.

    2012-01-01

    Mice expressing a germline mutation in the PLC-γ1 binding site of LAT (linker for activation of T cells) show progressive lymphoproliferation and ultimately die at 4–6 months of age. The hyper-activated T cells in these mice show defective TCR-induced calcium flux, but enhanced Ras/ERK activation that is critical for disease progression. Despite the loss of LAT-dependent PLC-γ1 binding and activation, genetic analysis revealed RasGRP1, and not Sos1 or Sos2, to be the major RasGEF responsible for ERK activation and the lymphoproliferative phenotype in these mice. Analysis of isolated CD4+ T cells from LAT-Y136F mice showed altered proximal TCR-dependent kinase signaling, which activated a Zap70- and LAT-independent pathway. Moreover, LAT-Y136F T cells showed ERK activation that was dependent on Lck and/or Fyn, PKCθ, and RasGRP1. These data demonstrate a novel route to Ras activation in vivo in a pathological setting. PMID:23209318

  6. Characterization of Epstein-Barr virus-infected B cells in patients with posttransplantation lymphoproliferative disease: disappearance after rituximab therapy does not predict clinical response.

    PubMed

    Yang, J; Tao, Q; Flinn, I W; Murray, P G; Post, L E; Ma, H; Piantadosi, S; Caligiuri, M A; Ambinder, R F

    2000-12-15

    Post-transplantation lymphoproliferative disease (PTLD) is associated with Epstein-Barr virus (EBV). Quantitative and qualitative differences in EBV in peripheral blood mononuclear cells (PBMCs) of PTLD patients and healthy controls were characterized. A quantitative competitive polymerase chain reaction (QC-PCR) technique confirmed previous reports that EBV load in PBMCs is increased in patients with PTLD in comparison with healthy seropositive controls (18 539 vs 335 per 10(6) PBMCs, P =.0002). The average frequency of EBV-infected cells was also increased (271 vs 9 per 10(6) PBMCs, P =.008). The distribution in numbers of viral genome copies per cell was assessed by means of QC-PCR at dilutions of PBMCs. There was no difference between PTLD patients and healthy controls. Similarly, no differences in the patterns of viral gene expression were detected between patients and controls. Finally, the impact of therapy on viral load was analyzed. Patients with a past history of PTLD who were disease-free (after chemotherapy or withdrawal of immunosuppression) at the time of testing showed viral loads that overlapped with those of healthy seropositive controls. Patients treated with rituximab showed an almost immediate and dramatic decline in viral loads. This decline occurred even in patients whose PTLD progressed during therapy. These results suggest that the increased EBV load in PBMCs of PTLD patients can be accounted for by an increase in the number of infected B cells in the blood. However, in terms of viral copy number per cell and pattern of viral gene expression, these B cells are similar to those found in healthy controls. Disappearance of viral load with rituximab therapy confirms the localization of viral genomes in PBMCs to B cells. However, the lack of relationship between the change in viral load and clinical response highlights the difference between EBV-infected PBMCs and neoplastic cells in PTLD. PMID:11110673

  7. Wildebeest-associated malignant catarrhal fever: perspectives for integrated control of a lymphoproliferative disease of cattle in sub-Saharan Africa.

    PubMed

    Wambua, Lillian; Wambua, Peninah Nduku; Ramogo, Allan Maurice; Mijele, Domnic; Otiende, Moses Yongo

    2016-01-01

    Wildebeest-associated malignant catarrhal fever (WA-MCF), an acute lymphoproliferative disease of cattle caused by alcelaphine herpesvirus 1 (AlHV-1), remains a significant constraint to cattle production in nomadic pastoralist systems in eastern and southern Africa. The transmission of WA-MCF is dependent on the presence of the wildlife reservoir, i.e. wildebeest, belonging to the species Connochaetes taurinus and Connochaetes gnou; hence, the distribution of WA-MCF is largely restricted to Kenya, Tanzania and the Republic of South Africa, where wildebeest are present. WA-MCF is analogous to sheep-associated MCF (SA-MCF) in many aspects, with the latter having sheep as its reservoir host and a more global distribution, mainly in developed countries with intensive livestock production systems. However, unlike SA-MCF, the geographic seclusion of WA-MCF may have contributed to an apparent neglect in research efforts aimed at increased biological understanding and control of the disease. This review aims to highlight the importance of WA-MCF and the need for intensified research towards measures for its integrated control. We discuss current knowledge on transmission and geographical distribution in eastern and southern Africa and the burden of WA-MCF in affected vulnerable pastoral communities in Africa. Recent findings towards vaccine development and pertinent knowledge gaps for future research efforts on WA-MCF are also considered. Finally, integrated control of WA-MCF based on a logical three-pronged framework is proposed, contextualizing vaccine development, next-generation diagnostics, and diversity studies targeted to the viral pathogen and cattle hosts. PMID:26446889

  8. Methotrexate-related lymphoproliferative disorder of the stomach in a patient with rheumatoid arthritis: a case of disease regression after methotrexate cessation.

    PubMed

    Ikeda, Kazuki; Nakamura, Takefumi; Kinoshita, Takahiro; Fujiwara, Mikio; Uose, Suguru; Someda, Hitoshi; Miyoshi, Takashi; Io, Katsuhiro; Nagai, Ken-Ichi

    2016-02-01

    We report the case of a 78-year-old woman with methotrexate-related gastric lymphoproliferative disorder (LPD). The patient had a history of rheumatoid arthritis (RA) and had been treated with methotrexate (MTX). Endoscopic examination revealed round elevated lesions in the stomach, and a biopsy specimen showed atypical lymphoid cell proliferation. Immunohistological study found these atypical cells to be positive for L-26 but not for CD3 or EBER. Therefore, we made a diagnosis of MTX-related LPD showing features of diffuse large B-cell lymphoma. Combined positron emission tomography-computed tomography (PET-CT) using 18F-fluorodeoxyglucose (FDG) showed increased avidity in the stomach in addition to slightly increased FDG-avidity in the mediastinum and left chest wall. We decided not to start chemotherapy but to discontinue administration of MTX, with follow-up using endoscopy and PET-CT. The endoscopic examinations after cessation of MTX demonstrated gradual regression of the elevated lesions. PET-CT 6 months after cessation showed no increased FDG avidity in the stomach. While disease regression was observed in the stomach, the other FDG-avid spots remained unchanged on PET-CT. Therefore, we performed chemotherapy as additional therapy. On PET-CT after chemotherapy, the FDG-avid spots remained unchanged for more than 1 year, and we eventually concluded that they were RA-related inflammatory lesions. In patients with MTX-related LPD, cessation of MTX may be a therapeutic option, but careful follow-up and chemotherapy in accordance with the clinical course are essential. PMID:26733461

  9. Correction of disease related anaemia of B-chronic lymphoproliferative disorders by recombinant human erythropoietin: maintenance is necessary to sustain response.

    PubMed

    Siakantaris, M P; Angelopoulou, M K; Vassilakopoulos, T P; Dimopoulou, M N; Kontopidou, F N; Pangalis, G A

    2000-12-01

    Thirty three B-chronic lymphoproliferative disorder (B-CLD) patients [22 with B-chronic lymphocytic leukemia (B-CLL), 5 with small lymphocytic lymphoma (SLL) and 6 with lymphoplasmacytic lymphoma (LPL)] with anaemia (Ht <32%) of no other cause but their disease, received recombinant human erythropoietin (r-HuEPO). The treatment protocol provided r-HuEPO in a dose of 150 U/kg s.c. thrice weekly for 3 mo. After 1.5 mo of r-HuEPO administration, if response was not satisfactory, r-HuEPO dose escalation was utilised by giving incremental doses of 50 U/kg more than the previous dose up to a maximum dose of 300 U/kg tiw. After maximal response, half of the responding patients discontinued therapy, while the other half received maintenance therapy at a dose of 150 U/kg s.c./w. Oral iron was given throughout the study. Pretreatment EPO levels were determined in all patients. A complete response (CR) was defined when Ht was >38% and a partial response (PR) when there was an increase of the Ht >6% from the initial value was achieved. Sixteen of the 22 B-CLL patients had Rai stage III disease and 6 stage IV, with a median duration of anaemia 27 months (6-38); twelve of them were receiving chlorambucil while the rest were on no treatment. Of the SLL and LPL group, 4 patients had Ann Arbor stage III disease and 7 stage IV with a median duration of anaemia 24 months (5-36); 8 patients were on chlorambucil. Complete response was achieved in 50% of the B-CLL group and 54% of the SLL and LPL group, with an overall response rate of 77% and 81% respectively. All patients on maintenance therapy had a continuous response, while all patients, in whom rHuEPO was discontinued, relapsed. No correlation was found between patients: with low or high pretreatment serum EPO levels; those receiving concomitant therapy or not; those with B-symptoms or not; those with a non-diffuse or diffuse bone marrow infiltration pattern; and with splenomegaly or not. Life quality was significantly improved and no major side effects were encountered. We conclude from our study that r-HuEPO is very effective in correcting disease-related anaemia in B-CLD, resulting in down-staging of Rai stage III patients and that maintenance therapy is necessary. Whether the correction of anaemia improves patients' overall survival, still remains to be seen. PMID:11426615

  10. Vaccine strategies to treat lymphoproliferative disorders.

    PubMed

    Radford, Kristen J; Vari, Frank; Hart, Derek N J

    2005-12-01

    Lymphoproliferative disorders, including follicular lymphoma (FL), multiple myeloma (MM) and chronic lymphatic leukaemia (CLL), are slowly progressive malignancies which remain incurable despite advances in therapy. Harnessing the immune system to recognise and destroy tumours is a promising new approach to treating these diseases. Dendritic cells (DC) are unique antigen-presenting cells that play a central role in the initiation and direction of immune responses. DC loaded ex vivo with tumour-associated antigens and administered as a vaccine have already shown promise in early clinical trials for a number of lymphoproliferative disorders, but the need for improvement is widely agreed. Recent advances in the understanding of basic DC biology and lessons from early clinical trials have provided exciting new insights into the generation of anti-tumour immune responses and the design of vaccine strategies. In this review we provide an overview of our current understanding of DC biology and their function in patients with lymphoproliferative disorders. We discuss the current status of clinical trials and new approaches to exploit the antigen presenting capacity of DC to design vaccines of the future. PMID:16373232

  11. Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases.

    PubMed

    Nash, Richard A; Dansey, Roger; Storek, Jan; Georges, George E; Bowen, James D; Holmberg, Leona A; Kraft, George H; Mayes, Maureen D; McDonagh, Kevin T; Chen, Chien-Shing; Dipersio, John; Lemaistre, C Fred; Pavletic, Steven; Sullivan, Keith M; Sunderhaus, Julie; Furst, Daniel E; McSweeney, Peter A

    2003-09-01

    High-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated for the control of severe autoimmune diseases. The addition of antithymocyte globulin (ATG) to high-dose chemoradiotherapy in the high-dose immunosuppressive therapy regimen and CD34 selection of the autologous graft may induce a higher degree of immunosuppression compared with conventional autologous HSCT for malignant diseases. Patients may be at higher risk of transplant-related complications secondary to the immunosuppressed state, including Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorder (PTLD), but this is an unusual complication after autologous HSCT. Fifty-six patients (median age, 42 years; range, 23-61 years) with either multiple sclerosis (n = 26) or systemic sclerosis (n = 30) have been treated. The median follow-up has been 24 months (range, 2-60 months). Two patients (multiple sclerosis, n = 1; systemic sclerosis, n = 1) had significant reactivations of herpesvirus infections early after HSCT and then developed aggressive EBV-PTLD and died on days +53 and +64. Multiorgan clonal B-cell infiltrates that were EBV positive by molecular studies or immunohistology were identified at both autopsies. Both patients had positive screening skin tests for equine ATG (Atgam) and had been converted to rabbit ATG (Thymoglobulin) from the first dose. Of the other 54 patients, 2 of whom had partial courses of rabbit ATG because of a reaction to the intravenous infusion of equine ATG, only 1 patient had a significant clinical reactivation of a herpesvirus infection (herpes simplex virus 2) early after HSCT, and none developed EBV-PTLD. The T-cell count in the peripheral blood on day 28 was 0/microL in all 4 patients who received rabbit ATG; this was significantly less than in patients who received equine ATG (median, 174/microL; P =.001; Mann-Whitney ranked sum test). Although the numbers are limited, the time course and similarity of the 2 cases of EBV-PTLD and the effect on day 28 T-cell counts support a relationship between the development of EBV-PTLD and the administration of rabbit ATG. The differences between equine and rabbit ATG are not yet clearly defined, and they should not be considered interchangeable in this regimen without further study. PMID:14506660

  12. Outcome of Rapamycin Therapy for Post-Transplant-Lymphoproliferative Disorder after Kidney Transplantation: Case Series

    PubMed Central

    Ashrafi, Farzaneh; Shahidi, Shahrzad; Mortazavi, Mojgan

    2015-01-01

    ABSTRACT Background Post-transplant lymphoproliferative disorders (PTLD) are a complication of chronic immunosuppressive therapy in solid organ transplantation with a high mortality rate. Alternative treatments such as rapamycin have been explored. Methods: A detailed retrospective analysis was performed according to data collected from 13 patients with PTLD. At the time of PTLD diagnosis, immunosuppressive therapy was decreased and rapamycin administered. Overall survival, disease-free survival of patients and graft survival were determined. Results: Among 590 kidney transplant recipients, 13 adult patients with PTLD were included in this study. The mean age of the patients was 42.15 (range: 25–58) years at the time of PTLD diagnosis, and 9 patients were male. Histology was distributed in 9 diffuse large B cell, 1 Malt lymphoma, 1 Burkitt lymphoma, 2 Hodgkin-like PTLD. The response rate to rapamycin alone was 30.8%. The mean overall survival period was 23.38 months and 11 patients are still alive. In total, 10 patients (76.9%) achieved a complete remission with functioning graft in 11 (84.6%) patients. Conclusion: Despite the retrospective focus and limited number of patients, this study provides promising results regarding the effectiveness of stopping calcineurin inhibitors and switching to rapamycin for patients with PTLD. PMID:25802698

  13. EpsteinBarr virus-positive T/NK-cell lymphoproliferative disorders

    PubMed Central

    Cai, Qingqing; Chen, Kailin; Young, Ken H

    2015-01-01

    EpsteinBarr virus, a ubiquitous human herpesvirus, can induce both lytic and latent infections that result in a variety of human diseases, including lymphoproliferative disorders. The oncogenic potential of EpsteinBarr virus is related to its ability to infect and transform B lymphocytes into continuously proliferating lymphoblastoid cells. However, EpsteinBarr virus has also been implicated in the development of T/natural killer cell lymphoproliferative diseases. EpsteinBarr virus encodes a series of products that mimic several growth, transcription and anti-apoptotic factors, thus usurping control of pathways that regulate diverse homeostatic cellular functions and the microenvironment. However, the exact mechanism by which EpsteinBarr virus promotes oncogenesis and inflammatory lesion development remains unclear. EpsteinBarr virus-associated T/natural killer cell lymphoproliferative diseases often have overlapping clinical symptoms as well as histologic and immunophenotypic features because both lymphoid cell types derive from a common precursor. Accurate classification of EpsteinBarr virus-associated T/natural killer cell lymphoproliferative diseases is a prerequisite for appropriate clinical management. Currently, the treatment of most T/natural killer cell lymphoproliferative diseases is less than satisfactory. Novel and targeted therapies are strongly required to satisfy clinical demands. This review describes our current knowledge of the genetics, oncogenesis, biology, diagnosis and treatment of EpsteinBarr virus-associated T/natural killer cell lymphoproliferative diseases. PMID:25613730

  14. Comparison of two real-time quantitative polymerase chain reaction strategies for minimal residual disease evaluation in lymphoproliferative disorders: correlation between immunoglobulin gene mutation load and real-time quantitative polymerase chain reaction performance.

    PubMed

    Della Starza, Irene; Cavalli, Marzia; Del Giudice, Ilaria; Barbero, Daniela; Mantoan, Barbara; Genuardi, Elisa; Urbano, Marina; Mannu, Claudia; Gazzola, Anna; Ciabatti, Elena; Guarini, Anna; Foà, Robin; Galimberti, Sara; Piccaluga, Pierpaolo; Gaidano, Gianluca; Ladetto, Marco; Monitillo, Luigia

    2014-09-01

    We compared two strategies for minimal residual disease evaluation of B-cell lymphoproliferative disorders characterized by a variable immunoglobulin heavy chain (IGH) genes mutation load. Twenty-five samples from chronic lymphocytic leukaemia (n = 18) or mantle cell lymphoma (n = 7) patients were analyzed. Based on IGH variable region genes, 22/25 samples carried > 2% mutations, 20/25 > 5%. In the IGH joining region genes, 23/25 samples carried > 2% mutations, 18/25 > 5%. Real-time quantitative polymerase chain reaction was performed on IGH genes using two strategies: method A utilizes two patient-specific primers, whereas method B employs one patient-specific and one germline primer, with different positions on the variable, diversity and joining regions. Twenty-three samples (92%) resulted evaluable using method A, only six (24%) by method B. Method B poor performance was specifically evident among mutated IGH variable/joining region cases, although no specific mutation load above, which the real-time quantitative polymerase chain reaction failed was found. The molecular strategies for minimal residual disease evaluation should be adapted to the B-cell receptor features of the disease investigated. PMID:24254547

  15. Lymphoproliferative lesions of the skin

    PubMed Central

    Cerroni, L

    2006-01-01

    Diagnosis and differential diagnosis of cutaneous lymphoproliferative disorders is one of the most difficult areas in dermatopathology, and biopsies are often taken to rule out a cutaneous lymphoma in patients with “unclear” or “therapy‐resistant” skin lesions. Histopathological features alone often enable a given case to be classified to a diagnostic group (eg, epidermotropic lymphomas), but seldom allow a definitive diagnosis to be made. Performing several biopsies from morphologically different lesions is suggested, especially in patients with suspicion of mycosis fungoides. Immunohistochemistry is often crucial for proper classification of the cases, but in some instances is not helpful (eg, early lesions of mycosis fungoides). Although molecular techniques provide new, powerful tools for diagnosing cutaneous lymphoproliferative disorders, results of molecular methods should always be interpreted with the clinicopathological features, keeping in mind the possibility of false positivity and false negativity. In many cases, a definitive diagnosis can be made only on careful correlation of the clinical with the histopathological, immunophenotypical and molecular features. PMID:16873563

  16. A Scheduled Program of Molecular Screening for Epstein-Barr Virus Decreases the Incidence of Post-transplantation Lymphoproliferative Disease in Pediatric Liver Transplantation.

    PubMed

    Soriano-López, D P; Alcántar-Fierros, J M; Hernández-Plata, J A; González-Jorge, A L; Velázquez-Ramos, S; Flores-Hernández, M A; Fuentes, V; Castañeda, P; Nieto, J; Sánchez, J L; López, B; Valencia-Mayoral, P; Varela-Fascinetto, G

    2016-03-01

    This is a cohort, retrospective, comparative study of all liver transplant recipients from a single center, from May 1998 to July 2015. Patients were divided into two groups according to the type of Epstein-Barr viral load monitoring. For group I (1998-2007), polymerase chain reaction (PCR) was not available or it was only qualitative with limited access. For group II (2008-2015), we used periodically scheduled quantitative PCR in plasma and leukocytes, with aggressive tapering of immunosuppression as soon as viral replication was detected. Ninety-eight recipients were included, 41 (41.8%) were Epstein-Barr virus (EBV) - seronegative before liver transplantation (LT). EBV replication was confirmed in 74 patients (75.5%), being more frequent in seronegative (87.8%) than seropositive patients (66.6%). Eight recipients (8.1%) developed post-transplantation lymphoproliferative disorder (PTLD) on average at 14.3 months post-LT, seven of eight were <3 years at LT, four of eight were D+/R- for EBV, and all had post-LT EBV replication confirmed by PCR. PTLD was classified as lymphoma (n = 4), polymorphic polyclonal (n = 3), and lymphoid hyperplasia (n = 1). Five patients died, and three cleared PTLD after immunosuppression tapering or interruption. There were no significant differences in the etiology, age at LT (5.6 vs. 7.3 years, P = .069), patients <4 years (53.2% vs. 35.3%, P = .103), or EBV seronegative recipients (44.7% vs. 37.3%, P = .54); however, the incidence of PTLD decreased from 14.9% to 1.9% (P = .026), and graft rejection from 51.1% to 29.4% (P = .039). One- and 5-year patient survival rates were 94.7% and 85%, respectively, with no differences between groups. This strategy dramatically decreased the incidence of PTLD (14.9% vs. 1.9%), without increasing the incidence of rejection; therefore, we recommend that it should be used in the follow-up of all pediatric LT recipients. PMID:27110023

  17. Human T cell leukemia virus-I-associated T-suppressor cell inhibition of erythropoiesis in a patient with pure red cell aplasia and chronic T gamma-lymphoproliferative disease.

    PubMed Central

    Levitt, L J; Reyes, G R; Moonka, D K; Bensch, K; Miller, R A; Engleman, E G

    1988-01-01

    Human retroviruses have recently been linked with T cell lymphoproliferative disorders and with the acquired immune deficiency syndrome. We investigated the mechanisms for acquired pure red cell aplasia and cutaneous anergy in a patient with the chronic T gamma-lymphoproliferative disease (T gamma-LPD) syndrome. Patient marrow erythroid progenitors (BFU-E) were 17 +/- 9% of control and were selectively increased to 88-102% of control after marrow T cell depletion. Patient Leu 2+ suppressor T cells spontaneously produced high titers of human gamma-interferon and resulted in a concentration-dependent selective inhibition (74-91%) of BFU-E when co-cultured with autologous or allogeneic marrow. Conditioned media (CM) derived from patient Leu 2+ T cells similarly inhibited growth of autologous or allogeneic marrow BFU-E. The inhibitory factor derived from patient CM was acid-labile (pH 2) and sensitive to trypsin; prior treatment of patient T cells with anti-HLA-DR monoclonal antibody plus complement abrogated the suppressive effect of T cell-derived CM. Patient peripheral blood mononuclear cells (PBMC) were unable to support growth of cultured interleukin 2 (IL 2)-dependent T cells, but responded to exogenous IL 2 in vitro with a 16-21-fold augmentation, relative to control, in mitogen-induced proliferation. Antibodies to HTLV-I core proteins p19 and p24 but not to HTLV-III proteins were detected in patient serum by Western blotting; patient cultured PBMC stained (7-11%) with antibodies to p19 and p24. Patient cultured PBMC demonstrated integrated HTLV-I genomic sequences by the Southern technique and expressed both specific HTLV-I genomic sequences by RNA dot blot plus reverse transcriptase activity. Utilizing a cloned DNA probe for the beta chain of the T cell receptor gene, patient PMBC demonstrated gene rearrangements providing presumptive evidence for clonality. The presence in serum of HTLV-I p19 and p24 antibodies, the expression of p19 and p24 core antigens on patient mononuclear cells, the evidence of HTLV-I proviral integration sequences and the expression of HTLV-I genomic sequences in patient cells, indicates infection with HTLV-I and raises the possibility of an etiologic link between human retrovirus infection and some instances of large granular lymphocytic leukemia (T gamma-LPD). Images PMID:2892860

  18. Autoimmune and Lymphoproliferative Complications of Common Variable Immunodeficiency.

    PubMed

    Maglione, Paul J

    2016-03-01

    Common variable immunodeficiency (CVID) is frequently complicated by the development of autoimmune and lymphoproliferative diseases. With widespread use of immunoglobulin replacement therapy, autoimmune and lymphoproliferative complications have replaced infection as the major cause of morbidity and mortality in CVID patients. Certain CVID complications, such as bronchiectasis, are likely to be the result of immunodeficiency and are associated with infection susceptibility. However, other complications may result from immune dysregulation rather than immunocompromise. CVID patients develop autoimmunity, lymphoproliferation, and granulomas in association with distinct immunological abnormalities. Mutations in transmembrane activator and CAML interactor, reduction of isotype-switched memory B cells, expansion of CD21 low B cells, heightened interferon signature expression, and retained B cell function are all associated with both autoimmunity and lymphoproliferation in CVID. Further research aimed to better understand that the pathological mechanisms of these shared forms of immune dysregulation may inspire therapies beneficial for multiple CVID complications. PMID:26857017

  19. Increased Risk of Post-Transplant Malignancy and Mortality in Transplant Tourists

    PubMed Central

    Chung, Mu-Chi; Wu, Ming-Ju; Chang, Chao-Hsiang; Muo, Chih-Hsin; Yu, Tung-Min; Ho, Hao-Chung; Shu, Kuo-Hsiung; Chung, Chi-Jung

    2014-01-01

    Abstract Information on post-transplant malignancy and mortality risk in kidney transplant tourists remains controversial and is an important concern. The present study aimed to evaluate the incidence of post-transplant malignancy and mortality risk between tourists and domestic transplant recipients using the claims data from Taiwan's universal health insurance. A retrospective study was performed on 2394 tourists and 1956 domestic recipients. Post-transplant malignancy and mortality were defined from the catastrophic illness patient registry by using the International Classification of Diseases, 9th Revision. Cox proportional hazard regression and Kaplan–Meier curves were used for the analyses. The incidence for post-transplant de novo malignancy in the tourist group was 1.8-fold higher than that of the domestic group (21.8 vs 12.1 per 1000 person-years). The overall cancer recurrence rate was approximately 11%. The top 3 post-transplant malignancies, in decreasing order, were urinary tract, kidney, and liver cancers, regardless of the recipient type. Compared with domestic recipients, there was significant higher mortality risk in transplant tourists (adjusted hazard ratio = 1.2, 95% confidence interval: 1.0–1.5). In addition, those with either pre-transplant or post-transplant malignancies were associated with increased mortality risk. We suggest that a sufficient waiting period for patients with pre-transplant malignancies should be better emphasized to eliminate recurrence, and transplant tourists should be discouraged because of the possibility of higher post-transplant de novo malignancy occurrence and mortality. PMID:25546686

  20. Hepatitis C virus-related lymphoproliferative disorders: An overview

    PubMed Central

    Zignego, Anna Linda; Giannini, Carlo; Ferri, Clodoveo

    2007-01-01

    Hepatitis C virus (HCV) is a global health problem affecting 3% of the world's population (about 180 million) and a cause of both hepatic and extrahepatic diseases. B-cell lymphoproliferative disorders, whose prototype is mixed cryoglobulinemia, represent the most closely related as well as the most investigated HCV-related extrahepatic disorder. The association between extrahepatic (lymphoma) as well as hepatic malignancies (hepatocellular carcinoma) has justified the inclusion of HCV among human cancer viruses. HCV-associated manifestations also include porphyria cutanea tarda, lichen planus, nephropathies, thyreopathies, sicca syndrome, idiopathic pulmonary fibrosis, diabetes, chronic polyarthritis, sexual dysfunctions, cardiopathy/atherosclerosis, and psychopathological disorders. A pathogenetic link between HCV virus and some lymphoproliferative disorders was confirmed by their responsiveness to antiviral therapy, which is now considered the first choice treatment. The aim of the present paper is to provide an overview of extrahepatic manifestations of HCV infection with particular attention to B-cell lymphoproliferative disorders. Available pathogenetic hypotheses and suggestions about the most appropriate, currently available, therapeutic approaches will also be discussed. PMID:17552031

  1. Lymphoproliferative disorders in individuals with chronic hepatitis B and C in the Turkish population.

    PubMed

    Idilman, Ramazan; Bozkus, Yusuf; Seval, Guldane; Mizrak, Dilsa; Cinar, Kubilay; Ustun, Yusuf; Bektas, Mehmet; Arat, Mutlu; Akbulut, Hakan; Doganay, Beyza; Ozden, Ali

    2011-06-01

    The aims of this cohort study were to evaluate the association of malignant lymphoproliferative disorders in patients with chronic viral hepatitis and to compare the results with those in individuals with non-alcoholic fatty liver disease. A total of 3,873 patients with chronic liver disease who were seen consecutively in the Liver Disease Outpatient Clinic between January 2001 and July 2007 were assessed retrospectively. The frequency of malignant lymphoproliferative disorders including non-Hodgkin's lymphoma, Hodgkin's lymphoma, and chronic lymphocytic leukemia in these patients was investigated. Of the total, 1,999 patients had chronic hepatitis B infection (male/female: 1,226/773, mean age: 45.1 ± 13.2 years), 978 had chronic hepatitis C infection (male/female: 437/541, mean age: 53.8 ± 13.7 years), and the remaining 896 had non-alcoholic fatty liver disease (male/female: 450/446, mean age: 50.8 ± 11.2 years). A malignant lymphoproliferative disorder was identified in 13 patients (male/female: 9/4, mean age: 52.8 ± 16.8 years) with chronic viral hepatitis, while no case of malignant lymphoproliferative disorder was identified in individuals with non-alcoholic fatty liver disease (P = 0.048). Among the patients with malignant lymphoproliferative disorders, seven had chronic hepatitis B infection and six had chronic hepatitis C infection; 11 had non-Hodgkin's lymphoma and two had chronic lymphocytic leukemia. All non-Hodgkin's lymphoma cases were B-cell lymphoma. Based on the data obtained in this investigation, the association with malignant lymphoproliferative disorders in chronic viral hepatitis seems to be high as compared to that occurring in individuals with non-alcoholic fatty liver disease. PMID:21503909

  2. Rabbit model for human EBV-associated hemophagocytic syndrome (HPS): sequential autopsy analysis and characterization of IL-2-dependent cell lines established from herpesvirus papio-induced fatal rabbit lymphoproliferative diseases with HPS.

    PubMed

    Hayashi, Kazuhiko; Jin, Zaishun; Onoda, Sachiyo; Joko, Hiromasa; Teramoto, Norihiro; Ohara, Nobuya; Oda, Wakako; Tanaka, Takehiro; Liu, Yi-Xuan; Koirala, Tirtha Raj; Oka, Takashi; Kondo, Eisaku; Yoshino, Tadashi; Takahashi, Kiyoshi; Akagi, Tadaatsu

    2003-05-01

    Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD). To elucidate the true nature of fatal LPD observed in Herpesvirus papio (HVP)-induced rabbit hemophagocytosis, reactive or neoplastic, we analyzed sequential development of HVP-induced rabbit LPD and their cell lines. All of the seven Japanese White rabbits inoculated intravenously with HVP died of fatal LPD 18 to 27 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in five of these seven rabbits. Sequential autopsy revealed splenomegaly and swollen lymph nodes, often accompanied by bleeding, which developed in the last week. Atypical lymphoid cells infiltrated many organs with a "starry sky" pattern, frequently involving the spleen, lymph nodes, and liver. HVP-small RNA-1 expression in these lymphoid cells was clearly demonstrated by a newly developed in situ hybridization (ISH) system. HVP-ISH of immunomagnetically purified lymphoid cells from spleen or lymph nodes revealed HVP-EBER1+ cells in each CD4+, CD8+, or CD79a+ fraction. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by PCR or Southern blot analysis. Clonality analysis of HVP-induced LPD by Southern blotting with TCR gene probe revealed polyclonal bands, suggesting polyclonal proliferation. Six IL-2-dependent rabbit T-cell lines were established from transplanted scid mouse tumors from LPD. These showed latency type I/II HVP infection and had normal karyotypes except for one line, and three of them showed tumorigenicity in nude mice. These data suggest that HVP-induced fatal LPD in rabbits is reactive polyclonally in nature. PMID:12707056

  3. Therapeutic trials for a rabbit model of EBV-associated Hemophagocytic Syndrome (HPS): effects of vidarabine or CHOP, and development of Herpesvirus papio (HVP)-negative lymphomas surrounded by HVP-infected lymphoproliferative disease.

    PubMed

    Hayashi, K; Joko, H; Koirala, T R; Onoda, S; Jin, Z-S; Munemasa, M; Ohara, N; Oda, W; Tanaka, T; Oka, T; Kondo, E; Yoshino, T; Takahashi, K; Yamada, M; Akagi, T

    2003-10-01

    Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS), which is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD), is a distinct disease characterized by high mortality. Treatment of patients with EBV-AHS has proved challenging. To develop some therapeutic interventions for EBV-AHS, we examined the effectiveness of an antiviral agent (vidarabine) or chemotherapy (CHOP), using a rabbit model for EBV-AHS. Fourteen untreated rabbits were inoculated intravenously with cell-free virions of the EBV-like virus Herpesvirus papio (HVP). All of the rabbits died of HVP-associated (LPD) and hemophagocytic syndrome (HPS) between 21 and 31 days after inoculation. Furthermore, three HVP-infected rabbits treated with vidarabine died between days 23 and 28 after inoculation, and their clinicopathological features were no different from those of untreated rabbits, indicating that this drug is not effective at all to treat HVP-induced rabbit LPD and HPS. Three of the infected rabbits that were treated with one course, with an incomplete set of three courses, or with three full courses of CHOP treatment died of HVP-induced LPD and HPS with a bleeding tendency and/or with opportunistic infections. They died on the 26th, 62nd and 105th day after virus inoculation, respectively. CHOP treatment transiently suppressed the HVP-induced LPD and contributed to the prolonged survival time of two infected rabbits. However, it did not remove all of the HVP-infected cells from the infected rabbits, and residual HVP-infected lymphocytes caused recurrences of rabbit LPD and HPS. The most interesting finding of this experiment was observed in the infected rabbit with the longest survival time of 105 days: HVP-negative lymphomas surrounded by HVP-induced LPD developed in the larynx and ileum of this rabbit, causing an obstruction of the lumen. We concluded that these were not secondary lymphomas caused by CHOP treatment, because no suspicious lesions were detected in three uninfected rabbits that were treated with three courses of CHOP for 120 days. It is therefore necessary to clarify the mechanism by which HVP-negative lymphomas associated with HVP-induced LPD can develop. Our data from therapeutic trials using EBV-AHS animal models indicate that vidarabine is not effective as an agent to treat HVP-infected rabbits, and even the cytotoxic chemotherapy of CHOP is not sufficient to cure the HVP-infected rabbits or to prolong the survival time of infected rabbits. Further studies will therefore be required to develop better therapies to treat EBV-AHS. PMID:12973684

  4. Pretransplant echocardiographic parameters as markers of posttransplant outcomes in liver transplant recipients.

    PubMed

    Bushyhead, Daniel; Kirkpatrick, James N; Goldberg, David

    2016-03-01

    Despite advances in liver transplantation and preoperative risk stratification, there remains significant posttransplant morbidity and mortality from cardiovascular and renal disease. There are limited and conflicting data on the role of pretransplant echocardiography to predict these outcomes. The purpose of our study was to determine if pretransplant echocardiographic parameters were associated with posttransplant survival and the development of incident cardiovascular events and chronic kidney disease (CKD). We conducted a retrospective cohort study of 397 adult liver transplant recipients at the University of Pennsylvania from January 1, 2005 to September 30, 2014. Patients with acute liver failure, those without a diagnosis of cirrhosis (eg, polycystic liver disease without portal hypertension), retransplants, and multiorgan transplants were excluded. In multivariable Cox regression models, tricuspid regurgitation graded greater than mild was associated with significantly increased posttransplant mortality (hazard ratio, 1.68; 95% confidence interval [CI], 1.03-2.75; P = 0.04). In multivariable competing risk models, increasing pulmonary artery systolic pressure (PASP) was associated with significantly increased risk of hospitalization for myocardial infarction or heart failure (subhazard ratio per 5 mm Hg increase in PASP, 1.79; 95% CI, 1.48-2.17; P < 0.001). In multivariable competing risk models, increased left ventricular ejection fraction (LVEF) was associated with a numerical but nonsignificant increased risk of stage 4 or 5 CKD (subhazard ratio, 1.11 per 5% increase in LVEF; 95% CI, 0.99-1.24; P = 0.07). In a post hoc analysis, LVEF ≥ 65% was the best cutoff for increased risk of CKD (subhazard ratio, 1.75; 95% CI, 1.06-2.89; P = 0.03). In conclusion, several pretransplant echocardiographic parameters were associated with posttransplant morbidity and mortality, suggesting that pretransplant echocardiography may be used as a tool to risk-stratify patients for posttransplant outcomes. Liver Transpl 22:316-323, 2016. © 2015 AASLD. PMID:26609681

  5. HLA Haplotype Mismatch Transplants and Posttransplant Cyclophosphamide

    PubMed Central

    Bacigalupo, Andrea; Sica, Simona

    2016-01-01

    The use of high dose posttransplant cyclophosphamide (PT-CY) introduced by the Baltimore group approximately 10 years ago has been rapidly adopted worldwide and is becoming a standard for patients undergoing unmanipulated haploidentical (HAPLO) transplants. PT-CY has been used following nonmyeloablative as well as myeloablative conditioning regimens, for bone marrow or peripheral blood grafts, for patients with malignant and nonmalignant disorders. Retrospective comparisons of HAPLO grafts with conventional sibling and unrelated donor grafts have been published and suggest comparable outcome. The current questions to be answered include the use of PT-CY for sibling and unrelated donors transplant, possibly in the context of prospective randomized trial. PMID:27143973

  6. Voriconazole-induced periostitis: beyond post-transplant patients.

    PubMed

    Reber, Joshua D; McKenzie, Gavin A; Broski, Stephen M

    2016-06-01

    Voriconazole-induced periostitis (VIP) is a rare but increasingly encountered entity since Food and Drug Administration (FDA) approval of the second generation antifungal medication in 2002. Literature reports most commonly include transplant recipients on immunosuppressive therapy simultaneously requiring antifungal therapy. Nontransplant patients receiving long-term voriconazole have an equal risk of developing the disease, but may experience a delay in diagnosis due to a lack of familiarity with the process outside of the post-transplant and/or immunosuppressed population. We present a case of VIP in a nontransplant, immunocompetent patient on suppressive antifungal therapy for prior abdominal aortic stent graft fungal infection. Radiologist review of current medications and recognition of periostitis on multiple imaging modalities may hasten the diagnosis and lead to earlier treatment and resolution of symptoms. PMID:26980228

  7. Image findings of monomorphic non-hogdkin lymphoproliferative disorder in a post renal transplant patient diagnosed with fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography.

    PubMed

    Kamaleshwaran, Koramadai Karuppusamy; Rajasekar, Thirugnanam; Shibu, Deepu; Radhakrishnan, Edathurthy Kalarikal; Shinto, Ajit Sugunan

    2014-07-01

    Post-transplant lymphoproliferative disorder (PTLD) is a heterogeneous group of lymphoid proliferations caused by immunosuppression after solid organ or bone marrow transplantation. PTLD is categorized by early lesion, polymorphic PTLD and monomorphic PTLD. Fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (F-18 FDG-PET/CT) scans have clinical significance in the evaluation of PTLD following renal transplantation. We report imaging findings of a monomorphic non-Hodgkin lymphoma, post renal transplant seen on FDG PET/CT in a 32-year-old lactating woman. Whole body FDG- ET/CT demonstrated uptake in right external iliac and inguinal lymph nodes. PMID:25210292

  8. Image findings of monomorphic non-hogdkin lymphoproliferative disorder in a post renal transplant patient diagnosed with fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography

    PubMed Central

    Kamaleshwaran, Koramadai Karuppusamy; Rajasekar, Thirugnanam; Shibu, Deepu; Radhakrishnan, Edathurthy Kalarikal; Shinto, Ajit Sugunan

    2014-01-01

    Post-transplant lymphoproliferative disorder (PTLD) is a heterogeneous group of lymphoid proliferations caused by immunosuppression after solid organ or bone marrow transplantation. PTLD is categorized by early lesion, polymorphic PTLD and monomorphic PTLD. Fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (F-18 FDG-PET/CT) scans have clinical significance in the evaluation of PTLD following renal transplantation. We report imaging findings of a monomorphic non-Hodgkin lymphoma, post renal transplant seen on FDG PET/CT in a 32-year-old lactating woman. Whole body FDG- ET/CT demonstrated uptake in right external iliac and inguinal lymph nodes. PMID:25210292

  9. X-Linked Lymphoproliferative Disease (XLP)

    MedlinePlus

    ... as development of severe mononucleosis in response to EBV infection. A blood test showing low antibody, or immunoglobulin, levels also ... this will not necessarily protect a child against EBV infection. Bone marrow or umbilical cord blood transplantation, which re-set and replenish the immune ...

  10. [Autoimmune lymphoproliferative syndrome: a case report and literature review].

    PubMed

    Sun, Jia-peng; Lu, Xin-tian; Zhao, Wei-hong; Hua, Ying

    2015-12-18

    We described 1 case of autoimmune lymphoproliferative syndrome (ALPS), first diagnosed in our hospital, and reviewed the recent literature. The 11-month old male patient presented with a history of splenomegaly and hepatomegaly since 1 month after birth. He suffered recurrent infectious diseases including cytomegalovirus infection, parvovirus B19 infection and chronic diarrhea disease. Besides, his symptoms included hemolytic anemia and thrombocytopenia. The laboratory abnormality indicated an expanded population of alpha/beta double-negative T cells (DNTs) (27.18% of lymphocytes, 35.16% of CD3+ T lymphocytes) in peripheral blood, and autoantibodies including antinuclear antibody, double-stranded DNA and rheumatic factor were positive. Hyper gamma globulinemia and positive direct Coombs tests were seen in the patient. His parents were both healthy and denied autoimmune diseases. We identified a heterozygous point mutation in exon 3 of the FAS gene carrying c.309 A>C, resulting in a single base pair substitution in exon 3 of FAS gene which changed the codon of Arg103 to Ser103. Unfortunately, we were unable to obtain the gene results of the child's parents. The patient was treated with glucocorticoids in our hospital and with mycophenolatemofetil in other hospital. And we were informed that his anemia condition relieved through the telephone follow-up, but he still suffered recurrent infections, hepatomegaly and splenomegaly still existed. As we all know ALPS is characterized by defective lymphocyte apoptosis, and thus cause lymphoproliferative disease and autoimmune disease, and increase the risk of lymphoma. It is more likely to be misdiagnosed as other diseases. ALPS should be suspected in the case of chronic lymphadenopathy, splenomegaly and autoimmune features. Flow cytometry approach is helpful for the diagnosis. Immunosuppressive drugs are the necessary treatment. PMID:26679669

  11. Risk of lymphoproliferative malignancy in celiac patients with a family history of lymphoproliferative malignancy

    PubMed Central

    Ludvigsson, Jonas F; Lebwohl, Benjamin; Rubio-Tapia, Alberto; Murray, Joseph A.; Green, Peter HR; Ekbom, Anders

    2013-01-01

    Background and aims Individuals with celiac disease (CD) are at increased risk of lymphoproliferative malignancy (LPM). We examined if a family history of LPM or any cancer influenced the risk of LPM in individuals with CD. Methods We identified 28,996 individuals with biopsy-verified CD (equal to villous atrophy, Marsh histopathology stage 3), of whom 616 had family history of LPM. Cox regression then estimated hazard ratios (HRs) for LPM in these 616 compared with two control groups. We also examined the risk of LPM in CD individuals with a family history of any cancer (n=8,439). Results During follow-up, 2/616 CD individuals with a family history of LPM, and 235/28,380 CD individuals without a family history of LPM developed LPM themselves. CD individuals with a family history of LPM were not at increased risk of LPM compared to general population controls (HR=1.18; 95%CI=0.27–5.10), or compared to CD individuals without a family history of LPM (adjusted HR=0.31; 95%CI=0.08–1.23). We found no increased risk of LPM in CD individuals with a family history of any cancer. Conclusion This study found no evidence that a family history of LPM or any cancer increases the risk of future LPM in individuals with CD. Despite the large number of study participants, this study is however limited by few positive events due to a low absolute risk of LPM even in individuals with CD. PMID:23440554

  12. KHSV(-) EBV(-) post-transplant effusion lymphoma with plasmablastic features: variant of primary effusion lymphoma?

    PubMed

    Lambe, Jennifer S; Oble, Darryl A; Nandula, Subhadra V; Sevilla, Deborah W; Colovai, Adriana I; Mansukhani, Mahesh; Chari, Ajai; Murty, Vundavalli V; Alobeid, Bachir; Bhagat, Govind

    2009-12-01

    Primary effusion lymphoma (PEL) is a rare type of B-cell non-Hodgkin lymphoma (NHL), which predominantly occurs in HIV-infected individuals, and is pathogenetically linked with Kaposi sarcoma (KS)-associated herpes virus/human herpes virus-8 (KSHV/HHV-8) infection with or without evidence of Epstein-Barr virus (EBV) co-infection. Although uncommon, PELs have been reported in immunocompetent patients and recipients of solid organ allografts. Rare cases of KSHV(-) EBV(+) post-transplant effusion lymphomas resembling PEL have also been described, as have KSHV(-) EBV(-) effusion lymphomas, the latter including those arising in individuals with chronic liver disease. We report a unique KSHV(-) EBV(-) post-transplant effusion lymphoma associated with serum paraproteins, occurring in an HIV(-) individual, which had cytologic features and phenotype similar to PEL, and displayed a complex karyotype including isochromosome 12p and translocation t(8;22), resulting in rearrangement of c-MYC. PMID:19337983

  13. Prevalence of pre-transplant electrocardiographic abnormalities and post-transplant cardiac events in patients with liver cirrhosis

    PubMed Central

    2014-01-01

    Background Although cardiovascular disease is thouht to be common in cirrhosis, there are no systematic investigations on the prevalence of electrocardiographic (ECG) abnormalities in these patients and data on the occurrence of post-transplant cardiac events in comparison with the general population are lacking. We aimed to study the prevalence and predictors of ECG abnormalities in patients with cirrhosis undergoing liver transplantation and to define the risk of cardiac events post-transplant compared to the general population. Methods Cirrhotic patients undergoing first-time liver transplantation between 1999–2007 were retrospectively enrolled. ECGs at pre-transplant evaluation were reviewed using the Minnesota classification and compared to healthy controls. Standardized incidence ratios for post-transplant cardiac events were calculated. Results 234 patients with cirrhosis were included, 186 with an available ECG (36% with alcoholic and 24% with viral cirrhosis; mean follow-up 4 years). Cirrhotics had a prolonged QTc interval, a Q wave, abnormal QRS axis deviation, ST segment depression and a pathologic T wave more frequently compared to controls (p < 0.05 for all). Arterial hypertension, older age, cirrhosis severity and etiology were related to ECG abnormalities. Compared to the general Swedish population, patients were 14 times more likely to suffer a cardiac event post-transplant (p < 0.001). A prolonged QTc interval and Q wave were related to post-transplant cardiac events (p < 0.05 for all). Conclusions Pre-transplant ECG abnormalities are common in cirrhosis and are associated with cardiovascular risk factors and cirrhosis severity and etiology. Post-transplant cardiac events are more common than in the general population. PMID:24708568

  14. Predictive roles of intraoperative blood glucose for post-transplant outcomes in liver transplantation

    PubMed Central

    Park, Chul Soo

    2015-01-01

    Diabetogenic traits in patients undergoing liver transplantation (LT) are exacerbated intraoperatively by exogenous causes, such as surgical stress, steroids, blood transfusions, and catecholamines, which lead to intraoperative hyperglycemia. In contrast to the strict glucose control performed in the intensive care unit, no systematic protocol has been developed for glucose management during LT. Intraoperative blood glucose concentrations typically exceed 200 mg/dL in LT, and extreme hyperglycemia (> 300 mg/dL) is common during the neohepatic phase. Only a few retrospective studies have examined the relationship between intraoperative hyperglycemia and post-transplant complications, with reports of infectious complications or mortality. However, no prospective studies have been conducted regarding the influence of intraoperative hyperglycemia in LT on post-transplant outcome. In addition to absolute blood glucose values, the temporal patterns in blood glucose levels during LT may serve as prognostic features. Persistent neohepatic hyperglycemia (without a decline) throughout LT is a useful indicator of early graft dysfunction. Moreover, intraoperative variability in glucose levels may predict the need for reoperation for hemorrhage after LT. Thus, there is an urgent need for guidelines for glucose control in these patients, as well as prospective studies on the impact of glucose control on various post-transplant complications. This report highlights some of the recent studies related to perioperative blood glucose management focused on LT and liver disease. PMID:26078559

  15. Post-transplant Adjustment – The Later Years

    PubMed Central

    Fredericks, Emily M.; Zelikovsky, Nataliya; Aujoulat, Isabelle; Hames, Anna; Wray, Jo

    2014-01-01

    As survival rates for pediatric solid organ transplantation have continued to improve, researchers and health care providers have increasingly focused on understanding and enhancing the health related quality of life (HRQOL) and psychosocial functioning of their patients. This manuscript reviews the psychosocial functioning of pediatric transplant recipients during the “later years”, defined as more than 3 years post-transplant, and focuses on the day-to-day impact of living with a transplant after the immediate period of adjustment and early years after surgery. Key topics reviewed include health-related quality of life, cognitive functioning, impact on the family, regimen adherence, and transition of responsibility for self-management tasks. Overall, pediatric transplant recipients evidence impairment in HRQOL, neuropsychological outcomes, and family functioning as compared to non-transplant recipients. However, the degree of impairment is influenced by a variety of factors including, disease severity, age, solid organ type, and study methodologies. Studies are limited by small samples, cross-sectional design, and the lack of universal assessment battery to allow for comparisons across solid organ populations. Areas for future research are discussed. PMID:25220845

  16. Association of severe myoclonic epilepsy of infancy (SMEI) with probable autoimmune lymphoproliferative syndrome-variant.

    PubMed

    Berio, A; Mangiante, G; Piazzi, A

    2014-01-01

    The paper reported on a case of severe myoclonic epilepsy of infancy (SMEI) associated with a probable autoimmune lymphoproliferative syndrome variant (Dianzani autoimmune lymphoproliferative disease) (DALD). A male patient with typical features of SMEI and a SCN1A gene variant presented in the first year of life with multiple lymph nodes, palpable liver at 2 cm from the costal margin, neutropenia, dysgammaglobulinemia, relative and sometimes absolute lymphocytosis. Subsequently the patient presented with constantly raised IgA in serum and positive antinuclear and thyroid antimicrosomal antibodies. The diagnosis of probable autoimmune lymphoproliferative syndrome was made; arthritis, skin and throat blisters, which appeared subsequently led to the diagnosis of linear IgA disease. On the basis of these unique associations, the Authors hypothesized that autoimmunity may be partly responsible of the severe epileptic symptomatology, perhaps mediated by autoantibodies against sodium channels or by accompanying cytotoxic T-lymphocytes. Corticosteroid treatment ameliorated the epilepsy and laboratory tests. Future studies will be necessary to evaluate the relevance of autoimmunity in SMEI. PMID:25669891

  17. β-HHVs and HHV-8 in Lymphoproliferative Disorders

    PubMed Central

    Quadrelli, C.; Barozzi, P.; Riva, G.; Vallerini, D.; Zanetti, E.; Potenza, L.; Forghieri, F.; Luppi, M.

    2011-01-01

    Similarly to Epstein-Barr virus (EBV), the human herpesvirus-8 (HHV-8) is a γ-herpesvirus, recently recognized to be associated with the occurrence of rare B cell lymphomas and atypical lymphoproliferations, especially in the human immunodeficiency virus (HIV) infected subjects. Moreover, the human herpesvirus-6 (HHV-6), a β-herpesvirus, has been shown to be implicated in some non-malignant lymph node proliferations, such as the Rosai Dorfman disease, and in a proportion of Hodgkin’s lymphoma cases. HHV-6 has a wide cellular tropism and it might play a role in the pathogenesis of a wide variety of human diseases, but given its ubiquity, disease associations are difficult to prove and its role in hematological malignancies is still controversial. The involvement of another β-herpesvirus, the human cytomegalovirus (HCMV), has not yet been proven in human cancer, even though recent findings have suggested its potential role in the development of CD4+ large granular lymphocyte (LGL) lymphocytosis. Here, we review the current knowledge on the pathogenetic role of HHV-8 and human β-herpesviruses in human lymphoproliferative disorders. PMID:22110893

  18. Comparison of Non-myeloablative Conditioning Regimens for Lymphoproliferative Disorders

    PubMed Central

    Hong, Sanghee; Le-Rademacher, Jennifer; Artz, Andrew; McCarthy, Philip L.; Logan, Brent R.; Pasquini, Marcelo C.

    2014-01-01

    Hematopoietic cell transplantation (HCT) with non-myeloablative conditioning (NMA) for lymphoproliferative diseases (LD) includes fludarabine with and without low-dose total body irradiation (TBI). Transplant outcomes were compared among patients ≥40 years with LD who received a HCT with TBI (N=382) and no-TBI (N=515) NMA from 2001 to 2011. The groups were comparable except for donor, graft, prophylaxis for graft-versus-host disease (GVHD), disease status and year of HCT. Cumulative incidences of grades II–IV GVHD at 100 days, were 29% and 20% (p=0.001), and chronic GVHD at 1 year were 54% and 44% (p=0.004) for TBI and no-TBI, respectively. Multivariate analysis of progression/relapse, treatment failure and mortality showed no outcome differences by conditioning. Full donor chimerism at day 100 was observed in 82% vs. 64% in the TBI and no-TBI groups, respectively (p=0.006). Subset of four most common conditioning/ GVHD prophylaxis combinations demonstrated higher rates of grades II–IV acute (p<0.001) and chronic GVHD (p<0.001) among recipients of TBI-mycophenolate mofetil (MMF) compared to other combinations. TBI-based NMA conditioning induces faster full donor chimerism but overall survival outcomes are comparable to no-TBI regimens. Combination of TBI and MMF are associated with higher rates of GVHD without impact on survival outcomes in patients with LD. PMID:25437248

  19. The impact of viral hepatitis-related hepatocellular carcinoma to post-transplant outcomes.

    PubMed

    Younossi, Z M; Stepanova, M; Saab, S; Ahmed, A; Lam, B; Srishord, M; Venkatesan, C; Wai, H; Henry, L

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common complication of HCV infection leading to liver transplantation. We evaluated the impact of aetiology of liver disease on patient and graft survival following liver transplantation for HCC. From the Scientific Registry of Transplant Recipients (2002-2011), all adults who underwent liver transplantation for HCC were retrospectively included. Aetiology of liver disease was grouped into HCV, HBV, HCV-HBV co-infection and nonviral liver disease. Of 8,733 liver transplant recipients with HCC, 5507 had HCV, 631 had HBV, 163 were co-infected, and 2432 had nonviral causes of liver disease. In follow-up (48 ± 32 months), 8.2% had graft failure and 29.5% died. The mean rates of graft failure were 9.5%, 4.7%, 6.1% and 6.4% in HCV, HBV, HCV-HBV co-infection and nonviral liver disease, respectively (P < 0.0001). Post-transplant mortality rate in patients with HBV was 20.2%, HCV 31.0%, HCV-HBV 28.5% and nonviral 28.5% (P < 0.0001). This difference was significant starting one year post-transplant and became even more prominent later in follow-up. Five-year post-transplant survival was 64.7% in HCV, 77.7% in HBV, 71.0% in HCV-HBV and 69.1% in nonviral HCC (P < 0.0001). A diagnosis of HCV in patients with HCC was also independently associated with an increased risk of both graft failure (adjusted hazard ratio = 1.84 (1.46-2.33), P < 0.0001) and mortality (1.35 (1.21-1.50), P < 0.0001) in multivariate analysis. Patients with HCV-related HCC are at higher risk of adverse post-transplant outcomes. These patients should be considered for preemptive interferon-free antiviral therapy prior to or immediately following liver transplantation. PMID:26289820

  20. Comparison of non-myeloablative conditioning regimens for lymphoproliferative disorders.

    PubMed

    Hong, S; Le-Rademacher, J; Artz, A; McCarthy, P L; Logan, B R; Pasquini, M C

    2015-03-01

    Hematopoietic cell transplantation (HCT) with non-myeloablative (NMA) conditioning for lymphoproliferative diseases (LD) includes fludarabine with and without low-dose TBI. Transplant outcomes were compared among patients aged ⩾40 years with LD who received a HCT with TBI (N=382) or no-TBI (N=515) NMA from 2001 to 2011. The groups were comparable except for donor, graft, prophylaxis for GVHD, disease status and year of HCT. Cumulative incidences of grades II-IV GVHD at 100 days were 29% and 20% (P=0.001) and of chronic GVHD at 1 year were 54% and 44% (P=0.004) for TBI and no-TBI, respectively. Multivariate analysis of progression/relapse, treatment failure and mortality showed no outcome differences by conditioning. Full donor chimerism at day 100 was observed in 82% vs 64% in the TBI and no-TBI groups, respectively (P=0.006). Subsets of the four most common conditioning/GVHD prophylaxis combinations demonstrated higher rates of grades II-IV acute (P<0.001) and chronic GVHD (P<0.001) among recipients of TBI-mycophenolate mofetil (MMF) compared with other combinations. TBI-based NMA conditioning induces faster full donor chimerism, but overall survival outcomes are comparable to no-TBI regimens. Combinations of TBI and MMF are associated with higher rates of GVHD without impact on survival outcomes in patients with LD. PMID:25437248

  1. Increased risk of post-transplant malignancy and mortality in transplant tourists: a nationwide population-based cohort study in Taiwan.

    PubMed

    Chung, Mu-Chi; Wu, Ming-Ju; Chang, Chao-Hsiang; Muo, Chih-Hsin; Yu, Tung-Min; Ho, Hao-Chung; Shu, Kuo-Hsiung; Chung, Chi-Jung

    2014-12-01

    Information on post-transplant malignancy and mortality risk in kidney transplant tourists remains controversial and is an important concern. The present study aimed to evaluate the incidence of post-transplant malignancy and mortality risk between tourists and domestic transplant recipients using the claims data from Taiwan's universal health insurance. A retrospective study was performed on 2394 tourists and 1956 domestic recipients. Post-transplant malignancy and mortality were defined from the catastrophic illness patient registry by using the International Classification of Diseases, 9th Revision. Cox proportional hazard regression and Kaplan-Meier curves were used for the analyses. The incidence for post-transplant de novo malignancy in the tourist group was 1.8-fold higher than that of the domestic group (21.8 vs 12.1 per 1000 person-years). The overall cancer recurrence rate was approximately 11%. The top 3 post-transplant malignancies, in decreasing order, were urinary tract, kidney, and liver cancers, regardless of the recipient type. Compared with domestic recipients, there was significant higher mortality risk in transplant tourists (adjusted hazard ratio = 1.2, 95% confidence interval: 1.0-1.5). In addition, those with either pre-transplant or post-transplant malignancies were associated with increased mortality risk. We suggest that a sufficient waiting period for patients with pre-transplant malignancies should be better emphasized to eliminate recurrence, and transplant tourists should be discouraged because of the possibility of higher post-transplant de novo malignancy occurrence and mortality. PMID:25546686

  2. Posttransplant sarcopenia: an underrecognized early consequence of liver transplantation.

    PubMed

    Dasarathy, Srinivasan

    2013-11-01

    Liver transplantation is believed to reverse the clinical and metabolic abnormalities of cirrhosis. Reduced skeletal muscle mass or sarcopenia contributes to increased mortality and adverse consequences of cirrhosis. Failure of reversal of sarcopenia of cirrhosis after liver transplantation is not well recognized. Six temporally, geographically, and methodologically distinct follow-up studies in 304 cirrhotics reported conflicting data on changes in indirect measures of skeletal muscle mass after transplantation. Distinct measures of body composition but not skeletal muscle mass were used and did not focus on the clinical consequences of sarcopenia after transplantation. A number of studies reported an initial rapid postoperative loss of lean mass followed by incomplete recovery with a maximum follow-up of 2 years. Posttransplant sarcopenia may be responsible for metabolic syndrome and impaired quality of life after liver transplantation. Potential reasons for failure to reverse sarcopenia after liver transplantation include use of immunosuppressive agents [mammalian target of rapamycin (mTOR) and calcineurin inhibitors] that impair skeletal muscle growth and protein accretion. Repeated hospitalizations, posttransplant infections, and renal failure also contribute to posttransplant sarcopenia. Finally, recovery from muscle deconditioning is limited by lack of systematic nutritional and physical-activity-based interventions to improve muscle mass. Despite the compelling data on sarcopenia before liver transplantation, the impact of posttransplant sarcopenia on clinical outcomes is not known. There is a compelling need for studies to examine the mechanisms and consequences of sarcopenia post liver transplantation to permit development of therapies to prevent and reverse this disorder. PMID:23912247

  3. Cytogenetic analysis of B-cell posttransplant lymphoproliferations validates the World Health Organization classification and suggests inclusion of florid follicular hyperplasia as a precursor lesion.

    PubMed

    Vakiani, Efsevia; Nandula, Subhadra V; Subramaniyam, Shivakumar; Keller, Christian E; Alobeid, Bachir; Murty, Vundavalli V; Bhagat, Govind

    2007-02-01

    Cytogenetic abnormalities in B-cell posttransplant lymphoproliferative disorders (PTLD) have not been well characterized. We thus performed cytogenetic analysis of 28 cases of B-cell PTLD, 1 infectious mononucleosis (IM)-like lesion, 9 polymorphic PTLD, 17 monomorphic PTLD, and 1 classical Hodgkin lymphoma (HL), and correlated the karyotypic findings with the phenotype, Epstein-Barr virus infection status, and clinical outcome. Karyotypes of 19 cases of posttransplant florid follicular hyperplasia (FFH) were also analyzed. Informative karyotypes were obtained in 20 (71.4%) of 28 PTLDs and 18 (94.7%) of 19 FFHs. Clonal karyotypic abnormalities were detected in 13 (65%) of 20 PTLDs, including 9 (75%) of 12 monomorphic PTLDs, 2 (33.3%) of 6 polymorphic PTLDs, 1 IM-like lesion, and 1 HL, and 2 (11.1%) of 18 FFHs. Recurrent chromosome breaks at 1q11-21 (n = 6, including 1 FFH), 14q32 (n = 3, including 1 FFH), 16p13 (n = 3), 11q23-24 (n = 2), and 8q24 (c-MYC) (n = 2); gains of chromosome 7 (n = 4), X (n = 3), 2 (n = 3), 12 (n = 2); and loss of chromosome 22 (n = 2, including 1 IM-like lesion) were identified. The presence of cytogenetic abnormalities did not correlate with PTLD phenotype, Epstein-Barr virus infection, or clinical outcome. We describe novel karyotypic aberrations in PTLD and report clonal cytogenetic abnormalities in posttransplant FFH and an IM-like lesion for the first time. Our findings provide validation of the current World Health Organization classification of PTLD and also suggest incorporation of FFH as the earliest recognizable precursor of PTLD. PMID:17134734

  4. Advances in Understanding the Pathogenesis of Epstein-Barr Virus-Associated Lymphoproliferative Disorders.

    PubMed

    Yang, Xi; Nishida, Naonori; Zhao, Xiaodong; Kanegane, Hirokazu

    2015-10-01

    Epstein-Barr virus (EBV) was discovered 50 years ago  from an african Burkitt lymphoma cell line. EBV-associated lymphoproliferative disorders (LPDs) are life- threatening diseases, especially in children. In this article, we review EBV-associated LPDs, especially in the area of primary immunodeficiency disease (PID). We searched PubMed for publications with key words including EBV infection, lymphoma, LPDs and PID, and selected the manuscripts written in English that we judged to be relevant to the topic of this review.On the basis of the data in the literature, we grouped the EBV-associated LPDs into four categories: nonmalignant disease, malignant disease, acquired immunodeficiency disease and PID. Each category has its own risk factor for LPD development. EBV-associated LPD is a complex disease, creating new challenges for diagnosis and treatment. PMID:26742434

  5. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    2016-04-22

    Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis

  6. Expression of Ki-67 nuclear antigen in B and T cell lymphoproliferative disorders.

    PubMed Central

    de Melo, N.; Matutes, E.; Cordone, I.; Morilla, R.; Catovksy, D.

    1992-01-01

    AIMS: To determine whether the proliferation rates of tumour cells may relate to prognosis and reflect disease activity. METHODS: Blood mononuclear cells from 155 patients with B cell (n = 120) or T cell (n = 35) chronic lymphoproliferative disorders were tested with the monoclonal antibody Ki-67 by indirect immunoperoxidase or immunoalkaline phosphatase techniques. B cell diseases included chronic lymphocytic leukaemia (CLL), CLL in prolymphocytic transformation (CLL/PL), prolymphocytic leukaemia (B-PLL) and non-Hodgkin's lymphoma (B-NHL) in leukaemic phase. The T cell diseases comprised large granular lymphocyte (LGL) leukaemia, T-PLL, and T-NHL. RESULTS: These showed significantly higher proportions of Ki-67 positive cells in T cell (11.2%) than in B cell (2.9%) disorders (p < 0.001). The highest values were found in NHL of both B and T cell types, particularly when low grade disease transformed to high grade. The lowest percentages of Ki-67 positive cells were found in CLL (1.4%) and LGL leukaemia (1.7%); intermediate values were seen in B PLL (3.3%) and T PLL (5.8%). CONCLUSIONS: There is a positive correlation between prognosis and proliferation rates in chronic B and T cell lymphoproliferative disorders. Estimation of Ki-67 in circulating leukaemic cells could be used to determine prognosis in low grade malignancies. Images PMID:1401173

  7. The expanding spectrum of the Autoimmune Lymphoproliferative Syndromes

    PubMed Central

    Oliveira, João Bosco

    2015-01-01

    1. Purpose of review Several autoimmune lymphoproliferative syndromes have been described lately. We review here the main clinical and laboratory findings of these new disorders. 2. Recent findings The prototypical autoimmune lymphoproliferative syndrome (ALPS) has had its diagnostic criteria modified; somatic mutations in RAS genes were found to cause an ALPS-like syndrome in humans; and mutations in a gene encoding a protein kinase C (PRKCD) were discovered to cause a syndrome of lymphoproliferation, autoimmunity and NK cell defect. 3. Summary The recent discoveries shed light into the molecular pathways governing lymphocyte death, proliferation and immune tolerance in humans. PMID:24240292

  8. Post-transplant dyslipidemia: Mechanisms, diagnosis and management.

    PubMed

    Agarwal, Arnav; Prasad, G V Ramesh

    2016-03-24

    Post-transplant dyslipidemia is highly prevalent and presents unique management challenges to the clinician. The two major outcomes to consider with post-transplant therapies for dyslipidemia are preserving or improving allograft function, and reducing cardiovascular risk. Although there are other cardiovascular risk factors such as graft dysfunction, hypertension, and diabetes, attention to dyslipidemia is warranted because interventions for dyslipidemia have an impact on reducing cardiac events in clinical trials specific to the transplant population. Dyslipidemia is not synonymous with hyperlipidemia. Numerous mechanisms exist for the occurrence of post-transplant dyslipidemia, including those mediated by immunosuppressive drug therapy. Statin therapy has received the most attention in all solid organ transplant recipient populations, although the effect of proper dietary advice and adjuvant pharmacological and non-pharmacological agents should not be dismissed. At all stages of treatment appropriate monitoring strategies for side effects should be implemented so that the benefits from these therapies can be achieved. Clinicians have a choice when there is a conflict between various transplant society and lipid society guidelines for therapy and targets. PMID:27011910

  9. Post-transplant dyslipidemia: Mechanisms, diagnosis and management

    PubMed Central

    Agarwal, Arnav; Prasad, G V Ramesh

    2016-01-01

    Post-transplant dyslipidemia is highly prevalent and presents unique management challenges to the clinician. The two major outcomes to consider with post-transplant therapies for dyslipidemia are preserving or improving allograft function, and reducing cardiovascular risk. Although there are other cardiovascular risk factors such as graft dysfunction, hypertension, and diabetes, attention to dyslipidemia is warranted because interventions for dyslipidemia have an impact on reducing cardiac events in clinical trials specific to the transplant population. Dyslipidemia is not synonymous with hyperlipidemia. Numerous mechanisms exist for the occurrence of post-transplant dyslipidemia, including those mediated by immunosuppressive drug therapy. Statin therapy has received the most attention in all solid organ transplant recipient populations, although the effect of proper dietary advice and adjuvant pharmacological and non-pharmacological agents should not be dismissed. At all stages of treatment appropriate monitoring strategies for side effects should be implemented so that the benefits from these therapies can be achieved. Clinicians have a choice when there is a conflict between various transplant society and lipid society guidelines for therapy and targets. PMID:27011910

  10. Management and prevention of post-transplant malignancies in kidney transplant recipients

    PubMed Central

    Stallone, Giovanni; Infante, Barbara; Grandaliano, Giuseppe

    2015-01-01

    The central issue in organ transplantation remains suppression of allograft rejection. Thus, the development of immunosuppressive drugs has been the key to successful allograft function. The increased immunosuppressive efficiency obtained in the last two decades in kidney transplantation dramatically reduced the incidence of acute rejection. However, the inevitable trade-off was an increased rate of post-transplant infections and malignancies. Since the incidence of cancer in immunosuppressed transplant recipients becomes greater over time, and the introduction of new immunosuppressive strategies are expected to extend significantly allograft survival, the problem might grow exponentially in the near future. Thus, cancer is becoming a major cause of morbidity and mortality in patients otherwise successfully treated by organ transplantation. There are at least four distinct areas requiring consideration, which have a potentially serious impact on recipient outcome after transplantation: (i) the risk of transmitting a malignancy to the recipient within the donor organ; (ii) the problems of previously diagnosed and treated malignancy in the recipient; (iii) the prevention of de novo post-transplant malignant diseases and (iv) the management of these complex and often life-threatening clinical problems. In this scenario, the direct and indirect oncogenic potential of immunosuppressive therapy should be always carefully considered. PMID:26413294

  11. Management and prevention of post-transplant malignancies in kidney transplant recipients.

    PubMed

    Stallone, Giovanni; Infante, Barbara; Grandaliano, Giuseppe

    2015-10-01

    The central issue in organ transplantation remains suppression of allograft rejection. Thus, the development of immunosuppressive drugs has been the key to successful allograft function. The increased immunosuppressive efficiency obtained in the last two decades in kidney transplantation dramatically reduced the incidence of acute rejection. However, the inevitable trade-off was an increased rate of post-transplant infections and malignancies. Since the incidence of cancer in immunosuppressed transplant recipients becomes greater over time, and the introduction of new immunosuppressive strategies are expected to extend significantly allograft survival, the problem might grow exponentially in the near future. Thus, cancer is becoming a major cause of morbidity and mortality in patients otherwise successfully treated by organ transplantation. There are at least four distinct areas requiring consideration, which have a potentially serious impact on recipient outcome after transplantation: (i) the risk of transmitting a malignancy to the recipient within the donor organ; (ii) the problems of previously diagnosed and treated malignancy in the recipient; (iii) the prevention of de novo post-transplant malignant diseases and (iv) the management of these complex and often life-threatening clinical problems. In this scenario, the direct and indirect oncogenic potential of immunosuppressive therapy should be always carefully considered. PMID:26413294

  12. Role of IgG4 serology in identifying common orbital lymphoproliferative disorders

    PubMed Central

    Li, Jing; Ma, Jian-Min; Ge, Xin

    2016-01-01

    AIM To explore the role of IgG4 serology in identifying common orbital lymphoproliferative disorders. METHODS Eighty-one patients with orbital lymphoproliferative diseases were treated in the Department of Ocular Oncology, Beijing Tongren Hospital, Capital Medical University between September 2010 and December 2012. Serum IgG4 levels were measured in 46 cases of idiopathic orbital inflammatory pseudotumor (IOIP), 17 benign lymphoepithelial lesion (BLEL), 12 cases of orbital mucosa-associated lymphoid tissue (MALT), and 6 cases of diffuse large B-cell lymphoma (DLBL) using immuno-scatter turbidmetry (ISTM). RESULTS The frequency of elevated IgG4 levels in patients with IOIP, BLEL, MALT, and DLBL was 30.43% (14/46), 76.47% (13/17), 8.33% (1/12), and 0.00 (0/6), respectively. Among the patients with elevated serum IgG4 levels, all IgG-IOIP patients were male, and 92.31% of the IgG4-BLEL patients were female (12/13). The mean serum IgG4 level of IgG4-IOIP patients was lower than that of individuals with IgG4-BLEL, but the variation in serum IgG4 levels was larger in IgG4-IOIP than IgG4-BLEL patients. Only one case of IgG4-MALT with elevated serum IgG4 levels had a medical history >10y, which was significantly longer than the MALT patients with normal serum IgG4 levels. There was no significant elevation of serum IgG4 levels in patients with DLBL. CONCLUSION Detecting serum IgG4 levels plays an important role in the differential diagnosis of orbital lymphoproliferative diseases. PMID:26949650

  13. Risk factors for lymphoproliferative disorders after allogeneic hematopoietic cell transplantation

    PubMed Central

    Gilbert, Ethel S.; Rizzo, J. Douglas; Socié, Gérard; Banks, Peter M.; Sobocinski, Kathleen A.; Horowitz, Mary M.; Jaffe, Elaine S.; Kingma, Douglas W.; Travis, Lois B.; Flowers, Mary E.; Martin, Paul J.; Deeg, H. Joachim; Curtis, Rochelle E.

    2009-01-01

    We evaluated 26 901 patients who underwent allogeneic hematopoietic cell transplantation (HCT) at 271 centers worldwide to define patterns of posttransplantation lymphoproliferative disorders (PTLDs). PTLDs developed in 127 recipients, with 105 (83%) cases occurring within 1 year after transplantation. In multivariate analyses, we confirmed that PTLD risks were strongly associated (P < .001) with T-cell depletion of the donor marrow, antithymocyte globulin (ATG) use, and unrelated or HLA-mismatched grafts (URD/HLA mismatch). Significant associations were also confirmed for acute and chronic graft-versus-host disease. The increased risk associated with URD/HLA-mismatched donors (RR = 3.8) was limited to patients with T-cell depletion or ATG use (P = .004). New findings were elevated risks for age 50 years or older at transplantation (RR = 5.1; P < .001) and second transplantation (RR = 3.5; P < .001). Lower risks were found for T-cell depletion methods that remove both T and B cells (alemtuzumab and elutriation, RR = 3.1; P = .025) compared with other methods (RR = 9.4; P = .005 for difference). The cumulative incidence of PTLDs was low (0.2%) among 21 686 patients with no major risk factors, but increased to 1.1%, 3.6%, and 8.1% with 1, 2, and more than 3 major risk factors, respectively. Our findings identify subgroups of patients who underwent allogeneic HCT at elevated risk of PTLDs for whom prospective monitoring of Epstein-Barr virus activation and early treatment intervention may be particularly beneficial. PMID:19264919

  14. Lymphoproliferative responses to human papillomaviruses in patients with cutaneous warts.

    PubMed

    Charleson, F C; Norval, M; Benton, E C; Hunter, J A

    1992-12-01

    In vitro lymphoproliferative responses of peripheral blood mononuclear cells (PBMC) from patients with cutaneous warts, caused by infection with human papillomavirus type 1 (HPV-1) or type 2 (HPV-2), were assayed during the course of treatment. Purified HPV-1 and HPV-2 were used as antigens, as well as herpes simplex virus (HSV) and concanavalin A (Con A). All patients had normal percentages of subsets within the PBMC population and normal lymphoproliferative responses to Con A, and those with a clinical history of HSV infections had positive lymphoproliferative responses to HSV. Responses to both HPV antigens were poor. Only 10 of 100 assays of PBMC from 26 patients showed a stimulation index greater than 2. Addition of interleukin 2 made little difference in most cases. No correlation of clinical status of warts, i.e. improving, unchanged or resolved, with lymphoproliferation was found. When the PBMC were depleted of plastic-adherent cells and enriched for T cells, some samples which had not shown a lymphoproliferative response to HPV-1 or HPV-2 became positive; this response was abolished when the adherent cells were re-added. Thus it is possible that the adherent cell population from a proportion of patients contains cells which suppress lymphoproliferation, or that an immunoregulatory network is present so that lymphoproliferation does not take place in vitro without prior activation and cloning of T cells. PMID:1335750

  15. Autoimmune lymphoproliferative syndrome-like syndrome presented as lupus-like syndrome with mycobacterial joint infection evolved into the lymphoma.

    PubMed

    Hong, Young Hoon; Lee, Choong Ki

    2009-03-01

    The autoimmune lymphoproliferative syndrome (ALPS) and ALPS-like syndrome are variable clinical conditions characterized by lymphoproliferative disease, autoimmune cytopenias and susceptibility to malignancy. A 59-year-old woman was admitted to the hospital for intractable generalized pain and stiffness with multiple swollen joints for 2 weeks. A low-grade fever, intermittent hypotension and confusion were associated with the pain. The evaluation revealed multiple joint bony erosions with effusion and a ruptured Baker's cyst and positive AFB testing on the joint biopsy of the right wrist. In addition, there were a macular skin rash with telangiectasia and perivascular lymphocyte infiltration, a cytopenia without abnormal cells, a hepatosplenomegaly, a pericardial thickness with effusion and pleural effusion. The patient was treated with anti-mycobacterial drugs, NSAIDs and glucocorticoids for 10 months. But with the symptoms worsening, the patient developed cervical lymph node enlargements and was diagnosed as a diffuse large B cell lymphoma with hemophagocytosis on biopsy. PMID:18820932

  16. Metabolic Serum Profiles for Patients Receiving Allogeneic Stem Cell Transplantation: The Pretransplant Profile Differs for Patients with and without Posttransplant Capillary Leak Syndrome

    PubMed Central

    Reikvam, Håkon; Grønningsæter, Ida-Sofie; Ahmed, Aymen Bushra; Hatfield, Kimberley; Bruserud, Øystein

    2015-01-01

    Allogeneic stem cell transplantation is commonly used in the treatment of younger patients with severe hematological diseases, and endothelial cells seem to be important for the development of several posttransplant complications. Capillary leak syndrome is a common early posttransplant complication where endothelial cell dysfunction probably contributes to the pathogenesis. In the present study we investigated whether the pretreatment serum metabolic profile reflects a risk of posttransplant capillary leak syndrome. We investigated the pretransplant serum levels of 766 metabolites for 80 consecutive allotransplant recipients. Patients with later capillary leak syndrome showed increased pretherapy levels of metabolites associated with endothelial dysfunction (homocitrulline, adenosine) altered renal regulation of fluid and/or electrolyte balance (betaine, methoxytyramine, and taurine) and altered vascular function (cytidine, adenosine, and methoxytyramine). Additional bioinformatical analyses showed that capillary leak syndrome was also associated with altered purine/pyrimidine metabolism (i.e., metabolites involved in vascular regulation and endothelial functions), aminoglycosylation (possibly important for endothelial cell functions), and eicosanoid metabolism (also involved in vascular regulation). Our observations are consistent with the hypothesis that the pretransplant metabolic status can be a marker for posttransplant abnormal fluid and/or electrolyte balance. PMID:26609191

  17. Critical role of NKT Cells in Posttransplant Alloantibody Production

    PubMed Central

    Zimmerer, J.M.; Swamy, P.; Sanghavi, P.B.; Wright, C.L.; Abdel-Rasoul, M.; Elzein, S.M.; Brutkiewicz, R.R.; Bumgardner, G.L.

    2014-01-01

    We previously reported that posttransplant alloantibody production in CD8-deficient hosts is IL-4+CD4+ T cell-dependent and IgG1 isotype-dominant. The current studies investigated the hypothesis that IL-4-producing NKT cells contribute to maximal alloantibody production. To investigate this, alloantibody levels were examined in CD8-deficient wild-type, CD1d KO and J?18 KO transplant recipients. We found that the magnitude of IgG1 alloantibody production was critically dependent on the presence of type I NKT cells, which are activated by day 1 posttransplant. Unexpectedly, type I NKT cell contribution to enhanced IgG1 alloantibody levels was IFN-?-dependent and IL-4-independent. Cognate interactions between Type I NKT and B cells alone do not stimulate alloantibody production. Instead, NKT cells appear to enhance maturation of IL-4+CD4+ T cells. To our knowledge, this is the first report to substantiate a critical role for type I NKT cells in enhancing in vivo antibody production in response to endogenous antigenic stimuli. PMID:25220596

  18. HTLV Tax gene expression in patients with lymphoproliferative disorders.

    PubMed Central

    Cardoso, E A; Miranda, N; Gameiro, P; Frade, M J; Figueiredo, M; Parreira, A

    1996-01-01

    AIMS: To study the expression of the human T lymphotropic virus (HTLV) Tax gene in peripheral blood mononuclear cells. METHODS: Blood was collected from 72 patients with lymphoproliferative disorders. Serum from all patients was assayed for antibodies directed against HTLV-I structural proteins by ELISA and western blotting. RNA was purified from fresh blood cells and amplified by reverse transcription polymerase chain reaction (RT-PCR). After Southern blotting, the PCR products were hybridised with a 32P end-labelled probe specific for the Tax gene. RESULTS: All samples were seronegative. A specific band for the Tax gene was found in five samples. Each of the patients positive for Tax gene expression had a different type of lymphoproliferative disorder. CONCLUSIONS: Infection by HTLV-I cannot be assessed solely by immunological assays, particularly when only disrupted virions are used. Sensitive molecular biology assays are essential for detecting viral gene expression in fresh blood cells. Images PMID:8944616

  19. Alemtuzumab in T-cell lymphoproliferative disorders.

    PubMed

    Dearden, Claire E; Matutes, Estella

    2006-01-01

    The humanized monoclonal antibody alemtuzumab binds to the CD52 antigen, a glycoprotein which is widely expressed on normal and malignant B and T lymphocytes. Recently it has been demonstrated in a number of clinical trials that alemtuzumab has clinical activity in mature T-cell diseases such as T-prolymphocytic leukaemia and cutaneous T-cell lymphoma, inducing responses in up to two thirds of heavily pre-treated relapsed/refractory patients. Response was associated with improved survival. The toxicity profile for the antibody is manageable. The major complications are infusional reactions associated with initial injections, and prolonged lymphopenia associated with reactivation of viruses. Future studies will be directed towards alternative (subcutaneous) routes and schedules of administration, use as first-line therapy, combination strategies, and role of alemtuzumab to purge minimal residual bone-marrow disease prior to stem-cell transplantation. PMID:16997184

  20. Genetics Home Reference: X-linked lymphoproliferative disease

    MedlinePlus

    ... condition is generally inherited in an X-linked recessive pattern . The genes associated with this condition are located on the ... will have two altered copies of an associated gene, males are affected by X-linked recessive disorders much more frequently than females. However, in ...

  1. Molecular etiology of an indolent lymphoproliferative disorder determined by whole-genome sequencing

    PubMed Central

    Parker, Jeremy D.K.; Shen, Yaoqing; Pleasance, Erin; Li, Yvonne; Schein, Jacqueline E.; Zhao, Yongjun; Moore, Richard; Wegrzyn-Woltosz, Joanna; Savage, Kerry J.; Weng, Andrew P.; Gascoyne, Randy D.; Jones, Steven; Marra, Marco; Laskin, Janessa; Karsan, Aly

    2016-01-01

    In an attempt to assess potential treatment options, whole-genome and transcriptome sequencing were performed on a patient with an unclassifiable small lymphoproliferative disorder. Variants from genome sequencing were prioritized using a combination of comparative variant distributions in a spectrum of lymphomas, and meta-analyses of gene expression profiling. In this patient, the molecular variants that we believe to be most relevant to the disease presentation most strongly resemble a diffuse large B-cell lymphoma (DLBCL), whereas the gene expression data are most consistent with a low-grade chronic lymphocytic leukemia (CLL). The variant of greatest interest was a predicted NOTCH2-truncating mutation, which has been recently reported in various lymphomas. PMID:27148583

  2. Antibodies against "DANGER" in the dynamic of post-transplant circulation.

    PubMed

    Taniguchi, Michiko

    2013-01-01

    Evidence that has accumulated about the impact of non-human leukocyte antigen (HLA) antibodies against tissue-restricted antigens supports the concept that humoral targets can be constantly altered by transplant-associated stresses such as ischemia-reperfusion (IR) injury, organ preservation, immunosuppressive drugs, and pre-existing diseases. This accounts for the growing interest in "danger" signals--in the form of damage-induced molecules--expanding our understanding of the humoral cause of allograft rejection and failure from thinking it is caused only by genetically determined HLA mismatches to seeing the role played by antibody recognition of antigens modified posttransplant. The heterogeneous repertoire of antibodies was evidenced by the recent protein microarray analysis that revealed increased posttransplant levels of heterogeneous antibodies against the targets localized in specific kidney compartments. Antibodies can also be developed against molecules dynamically generated in the circulation as damage-associated molecular patterns (DAMPs) that are the endogenous version of exogenous pathogen-associated molecular patterns (PAMPs). Antibodies against some DAMP molecules have been identified in many autoimmune diseases, but mostly have been elusive in transplant immunology. Those humoral DAMP targets include the well-studied high-mobility group box 1, IR injury-induced proteins, and oxidation-specific epitopes exposed on oxidized low-density lipoprotein. Moreover, understanding the intersection of endogenous DAMPs and exogenous PAMPs in transplant immunology may reveal a new aspect of humoral reactions. Recently reported cross-recognition by polyreactive antibodies of apoptotic cells may be one of many unidentified recognition patterns that indicate existence of an immune system strategy for defending against a number of stress-induced targets as a set of "danger." Given all these findings, the recent approach of identifying disease-specific panels of up-regulated proteins may help link them with pathogenic antibodies from the pool of heterogeneous antibodies whose pathological roles have remained unidentified, helping us understand the effect of those antibodies-and vice versa, helping us understand the impact of disease-specific antigens, not just up-regulated antigens, as a cause of humoral reactions. PMID:25095526

  3. Detection of antigen receptor gene rearrangements in lymphoproliferative malignancies by fluorescent polymerase chain reaction.

    PubMed

    Kerlan-Candon, S; Soua, Z; Lefranc, M P; Clot, J; Eliaou, J F

    1998-01-01

    Monoclonal rearrangements of antigen receptor genes in lymphoproliferative diseases are characterized by the specific sequence and the length of their junctional region, which can be used as markers of the proliferating clone. PCR techniques have greatly simplified routine detection of monoclonal rearrangements. But on the one hand, identification of the sequences requires sequencing methods and on the other hand, sizing of rearrangements by conventional analysis of PCR products on agarose or nondenaturing polyacrylamide gels may be uncertain. We have developed an approach based on amplification of rearranged IGH, TCRG and TCRD locus by fluorescent PCR associated to a computerized analysis of generated PCR products allowing their objective sizing. We tested this method on DNA samples from patients with acute lymphoblastic leukemia and chronic lymphocytic leukemia, whose pattern of IGH and TCRG rearrangements had been previously identified by Southern blot techniques. TCRG-PCR assay allowed detection of 100% of rearranged samples. No false-negative results were found but a high rate (60%) of Southern-negative and PCR-positive samples were identified. TCRD PCR-assay detected VD1-JD1 or VD2-D2/3 rearrangements in both acute lymphoblastic leukemia and chronic lymphocytic leukemia samples. IGH PCR assay permitted detection of all known rearranged samples. The sensitivity of these three different PCR assays (1% leukemic cells) was equivalent to that of other published PCR protocols. These results show the validity and reliability of the fluorescent PCR method for routine detection of IGH, TCRG and TCRD rearrangements. Sizing of PCR products by computerized analysis was also validated. It provides additional information on rearrangement patterns in lymphoproliferative diseases, as clonal rearrangements can be recognized by their size. This can be of great interest in various circumstances, particularly for detection and follow-up of oligoclonality. PMID:9459500

  4. Pre-transplant angiotensin receptor II type 1 antibodies and risk of post-transplant focal segmental glomerulosclerosis recurrence.

    PubMed

    Mujtaba, Muhammad A; Sharfuddin, Asif A; Book, Benita L; Goggins, William C; Khalil, Ali A; Mishler, Dennis P; Fridell, Johnathan A; Yaqub, Muhammad S; Taber, Tim E

    2015-07-01

    Post-kidney transplant recurrence of focal segmental glomerulosclerosis (FSGS) is a major problem. AT1R is expressed on podocyte; its expression is elevated in the proteinuric state. Using an ELISA, we tested pre-transplant sera of 28 patients with history of idiopathic FSGS for anti-AT1R levels and serum soluble urokinase-type plasminogen activator receptor (suPAR) as a biomarker for risk of recurrence of FSGS. Sera from 11 patients with polycystic kidney disease (PKD) were used as controls. Twelve patients had biopsy proven post-transplant FSGS recurrence at 1.5 months. No difference was found in the pre-transplant suPAR levels of FSGS patients (5993 ± 2292 pg/mL) vs. PKD (7334 ± 4538 pg/mL) (p = 0.23). Serum suPAR levels in patients with FSGS recurrence (5786 ± 1899 pg/mL) vs. no FSGS recurrence (6149 ± 2598 pg/mL) (p = 0.69) were not different. Anti-AT1R levels in patients with FSGS were 12.66 ± 11.85 U/mL vs. 8.69 ± 6.52 U/mL in PKD (p = 0.32); however, a difference was found in patients with and without FSGS recurrence 20.41 ± 14.36 U/mL 6.84 ± 4.181 U/mL, respectively (p < 0.01). Area under curve for suPAR and anti-AT1R to predict post-transplant FSGS recurrence was 0.51 and 0.84, respectively. Pre-transplant anti-AT1R levels appear to be a helpful biomarker in identifying patients at high risk of post-transplant FSGS recurrence. PMID:25973696

  5. X-linked lymphoproliferative syndrome. Natural history of the immunodeficiency.

    PubMed Central

    Sullivan, J L; Byron, K S; Brewster, F E; Baker, S M; Ochs, H D

    1983-01-01

    The X-linked lymphoproliferative syndrome is characterized by immunodeficiency to Epstein-Barr virus (EBV) manifested by severe or fatal infectious mononucleosis and acquired immunodeficiency. We studied immune responses in six males of a well-characterized kindred with the X-linked lymphoproliferative syndrome. Two males were studied before and during acute fatal EBV infection. Both individuals demonstrated normal cellular and humoral immunity before EBV infection. During acute EBV infection, both individuals developed vigorous cytotoxic cellular responses against EBV-infected and -uninfected target cells. Anomalous killer and natural killer T cell activity was demonstrated against a variety of lymphoid cell lines, autologous fibroblasts and autologous hepatocytes. Effector cells responsible for anomalous killing reacted with a pan-T cell monoclonal antibody, and belonged to the OKT.8 T cell subset. Death in each case was caused by liver failure, but one patient developed extensive liver necrosis, whereas the other developed a massive infiltration of the liver with EBV-infected immunoblasts after aggressive immunosuppressive therapy. Immunological studies were performed on four males who had survived EBV infection years previously. They demonstrated global cellular immune defects with deficiencies of lymphocyte proliferative responses to mitogens and antigens, humoral immune deficiencies, abnormalities of regulatory T cell subsets and deficient natural killer cell activity. We propose that an aberrant immune response triggered by acute EBV infection results in unregulated anomalous killer and natural killer cell activity against EBV infected and uninfected cells. These studies suggest that global immune defects appearing in males with X-linked lymphoproliferative syndrome who survive EBV infection are epiphenomenon. Images PMID:6306053

  6. Myeloablative Conditioning with PBSC Grafts for T Cell-Replete Haploidentical Donor Transplantation Using Posttransplant Cyclophosphamide

    PubMed Central

    Solomon, Scott R.; Solh, Melhem; Morris, Lawrence E.; Holland, H. Kent; Bashey, Asad

    2016-01-01

    Relapse is the main cause of treatment failure after nonmyeloablative haploidentical transplant (haplo-HSCT). In an attempt to reduce relapse, we have developed a myeloablative (MA) haplo-HSCT approach utilizing posttransplant cyclophosphamide (PT/Cy) and peripheral blood stem cells as the stem cell source. We summarize the results of two consecutive clinical trials, using a busulfan-based (n = 20) and a TBI-based MA preparative regimen (n = 30), and analyze a larger cohort of 64 patients receiving MA haplo-HSCT. All patients have engrafted with full donor chimerism and no late graft failures. Grade III-IV acute GVHD and moderate-severe chronic GVHD occurred in 23% and 30%, respectively. One-year NRM was 10%. Predicted three-year overall survival, disease-free survival, and relapse were 53%, 53%, and 26%, respectively, in all patients and 79%, 74%, and 9%, respectively, in patients with a low/intermediate disease risk index (DRI). In multivariate analysis, DRI was the most significant predictor of survival and relapse. Use of TBI (versus busulfan) had no significant impact on survival but was associated with significantly less BK virus-associated hemorrhagic cystitis. We contrast our results with other published reports of MA haplo-HSCT PT/Cy in the literature and attempt to define the comparative utility of MA haplo-HSCT to other methods of transplantation. PMID:26904123

  7. Myeloablative Conditioning with PBSC Grafts for T Cell-Replete Haploidentical Donor Transplantation Using Posttransplant Cyclophosphamide.

    PubMed

    Solomon, Scott R; Solh, Melhem; Morris, Lawrence E; Holland, H Kent; Bashey, Asad

    2016-01-01

    Relapse is the main cause of treatment failure after nonmyeloablative haploidentical transplant (haplo-HSCT). In an attempt to reduce relapse, we have developed a myeloablative (MA) haplo-HSCT approach utilizing posttransplant cyclophosphamide (PT/Cy) and peripheral blood stem cells as the stem cell source. We summarize the results of two consecutive clinical trials, using a busulfan-based (n = 20) and a TBI-based MA preparative regimen (n = 30), and analyze a larger cohort of 64 patients receiving MA haplo-HSCT. All patients have engrafted with full donor chimerism and no late graft failures. Grade III-IV acute GVHD and moderate-severe chronic GVHD occurred in 23% and 30%, respectively. One-year NRM was 10%. Predicted three-year overall survival, disease-free survival, and relapse were 53%, 53%, and 26%, respectively, in all patients and 79%, 74%, and 9%, respectively, in patients with a low/intermediate disease risk index (DRI). In multivariate analysis, DRI was the most significant predictor of survival and relapse. Use of TBI (versus busulfan) had no significant impact on survival but was associated with significantly less BK virus-associated hemorrhagic cystitis. We contrast our results with other published reports of MA haplo-HSCT PT/Cy in the literature and attempt to define the comparative utility of MA haplo-HSCT to other methods of transplantation. PMID:26904123

  8. Hematopoietic Neoplasias in Horses: Myeloproliferative and Lymphoproliferative Disorders

    PubMed Central

    MUÑOZ, Ana; RIBER, Cristina; TRIGO, Pablo; CASTEJÓN, Francisco

    2010-01-01

    Leukemia, i.e., the neoplasia of one or more cell lines of the bone marrow, although less common than in other species, it is also reported in horses. Leukemia can be classified according to the affected cells (myeloproliferative or lymphoproliferative disorders), evolution of clinical signs (acute or chronic) and the presence or lack of abnormal cells in peripheral blood (leukemic, subleukemic and aleukemic leukemia). The main myeloproliferative disorders in horses are malignant histiocytosis and myeloid leukemia, the latter being classified as monocytic and myelomonocytic, granulocytic, primary erythrocytosis or polycythemia vera and megakaryocytic leukemia. The most common lymphoproliferative disorders in horses are lymphoid leukemia, plasma cell or multiple myeloma and lymphoma. Lymphoma is the most common hematopoietic neoplasia in horses and usually involves lymphoid organs, without leukemia, although bone marrow may be affected after metastasis. Lymphoma could be classified according to the organs involved and four main clinical categories have been established: generalized-multicentric, alimentary-gastrointestinal, mediastinal-thymic-thoracic and cutaneous. The clinical signs, hematological and clinical pathological findings, results of bone marrow aspirates, involvement of other organs, prognosis and treatment, if applicable, are presented for each type of neoplasia. This paper aims to provide a guide for equine practitioners when approaching to clinical cases with suspicion of hematopoietic neoplasia. PMID:24833969

  9. Antibody levels and in vitro lymphoproliferative responses to Streptococcus pyogenes erythrogenic toxin A and mitogen of patients with rheumatic fever.

    PubMed Central

    Bahr, G M; Yousof, A M; Behbehani, K; Majeed, H A; Sakkalah, S; Souan, K; Jarrad, I; Geoffroy, C; Alouf, J E

    1991-01-01

    We investigated the in vitro lymphoproliferative responses to a streptococcal mitogen and erythrogenic toxin A of children with acute rheumatic fever (ARF) and patients with chronic rheumatic heart disease (CRHD). Antibody levels to the streptococcal products were also analyzed in the sera of those with ARF or chronic rheumatic heart disease as well as in the sera of children with streptococcal pharyngitis or poststreptococcal glomerulonephritis. Our results demonstrated that the individuals had depressed lymphoproliferative responses during the active stage of rheumatic fever. The depressed responses were not found either to be induced by time-sensitive mitogen-specific suppressor cells or to be related to a dose-response phenomenon. On the other hand, antibody levels to the extracellular mitogens were significantly elevated in the sera of children with ARF compared with the levels in the rest of the groups. The hyperresponsiveness noted among children with ARF was found to be at a quantitative level and was not due to recognition of more epitopes, as determined by Western blotting (immunoblotting). The profile of immune responsiveness in children with ARF to the streptococcal extracellular mitogens is discussed in relation to the pathogenesis of disease. Images PMID:1774298

  10. Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a consequence of genetic defect accumulation

    PubMed Central

    Magerus-Chatinet, Aude; Neven, Bénédicte; Stolzenberg, Marie-Claude; Daussy, Cécile; Arkwright, Peter D.; Lanzarotti, Nina; Schaffner, Catherine; Cluet-Dennetiere, Sophie; Haerynck, Filomeen; Michel, Gérard; Bole-Feysot, Christine; Zarhrate, Mohammed; Radford-Weiss, Isabelle; Romana, Serge P.; Picard, Capucine; Fischer, Alain; Rieux-Laucat, Frédéric

    2010-01-01

    Autoimmune diseases develop in approximately 5% of humans. They can arise when self-tolerance checkpoints of the immune system are bypassed as a consequence of inherited mutations of key genes involved in lymphocyte activation, survival, or death. For example, autoimmune lymphoproliferative syndrome (ALPS) results from defects in self-tolerance checkpoints as a consequence of mutations in the death receptor–encoding gene TNF receptor superfamily, member 6 (TNFRSF6; also known as FAS). However, some mutation carriers remain asymptomatic throughout life. We have now demonstrated in 7 ALPS patients that the disease develops as a consequence of an inherited TNFRSF6 heterozygous mutation combined with a somatic genetic event in the second TNFRSF6 allele. Analysis of the patients’ CD4–CD8– (double negative) T cells — accumulation of which is a hallmark of ALPS — revealed that in these cells, 3 patients had somatic mutations in their second TNFRSF6 allele, while 4 patients had loss of heterozygosity by telomeric uniparental disomy of chromosome 10. This observation provides the molecular bases of a nonmalignant autoimmune disease development in humans and may shed light on the mechanism underlying the occurrence of other autoimmune diseases. PMID:21183795

  11. Hemophagocytic syndrome following haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide.

    PubMed

    Jaiswal, Sarita Rani; Chakrabarti, Aditi; Chatterjee, Sumita; Bhargava, Sneh; Ray, Kunal; Chakrabarti, Suparno

    2016-02-01

    Hemophagocytic syndrome (HPS) is a rare but serious complication after allogeneic transplantation which has been reported to be particularly high after unrelated cord blood transplantation. We report on the incidence, risk factors and outcome of HPS in 51 patients (age 2-64 years) after haploidentical peripheral blood stem cell (PBSC) transplantation with post-transplantation cyclophosphamide (PTCY). The incidence of HPS was 12.2 %, occurring at a median of 18 days. The non-relapse mortality in patients with HPS was 83.3 % compared to 11.6 % in patients without HPS. Complete donor chimerism was documented in all patients with HPS. Definite infective etiology was identified in two patients only. The others were refractory to multiple lines of treatment and 3 patients underwent a second transplant. Even though the symptoms and biochemical markers of HPS showed prompt response in 2/3 patients undergoing a second allograft, they succumbed to infections before haematological recovery. The others succumbed to multi-organ failure or infections. Age < 10 years, transplantation for non-malignant disease and high CD34 content of the graft were identified as risk factors for HPS. Considering the fact that post-transplant HPS is usually a refractory and fatal condition, we discuss further attempts at deciphering the pathogenesis, developing modalities to prevent this complication and improve the outcome. PMID:26619832

  12. Is there an association between SV40 contaminated polio vaccine and lymphoproliferative disorders? An age-period-cohort analysis on Norwegian data from 1953 to 1997.

    PubMed

    Thu, Guri Olsen; Hem, Ling Yuan; Hansen, Svein; Møller, Bjørn; Norstein, Jarle; Nøkleby, Hanne; Grotmol, Tom

    2006-04-15

    Between 1955 and 1963, an estimated number of 150 million people in various parts of the world, including Norway, received poliomyelitis vaccine possibly contaminated with infectious simian virus 40 (SV40). Human studies have investigated the hypothesised association between SV40 and various cancers, but the results have so far been contradicting. The aim of the present study was to examine Norwegian cancer incidence data to assess a possible association between birth cohorts assumed to have been subjected to the vaccine and the incidence rate of lymphoproliferative disorders (excluding Hodgkin's lymphoma), further subdivided into non-Hodgkin's lymphoma (NHL), lymphocytic leukemia and plasma cell neoplasms. Between 1953 and 1997, the incidence rate of lymphoproliferative diseases combined increased about 3-fold in both males and females. Subgroup analysis showed that this increase was largely attributable to NHL. Age-period-cohort modelling of the subgroups, as well as of all groups combined, showed that the cohort effect was more prominent than the period effect. However, the variations in incidence patterns across the birth cohorts did not fit with the trends that would be expected if a SV40 contaminated vaccine did play a causative role. Thus, our data do not support the hypothesis of an association between the vaccine and any subgroup of lymphoproliferative diseases. PMID:16287082

  13. Familial Lymphoproliferative Malignancies and Tandem Duplication of NF1 Gene

    PubMed Central

    Fernandes, Gustavo; Souto, Mirela; Costa, Frederico; Oliveira, Edite; Garicochea, Bernardo

    2014-01-01

    Background. Neurofibromatosis type 1 is a genetic disorder caused by loss-of-function mutations in a tumor suppressor gene (NF1) which codifies the protein neurofibromin. The frequent genetic alterations that modify neurofibromin function are deletions and insertions. Duplications are rare and phenotype in patients bearing duplication of NF1 gene is thought to be restricted to developmental abnormalities, with no reference to cancer susceptibility in these patients. We evaluated a patient who presented with few clinical signs of neurofibromatosis type 1 and a conspicuous personal and familiar history of different types of cancer, especially lymphoproliferative malignancies. The coding region of the NF-1 gene was analyzed by real-time polymerase chain reaction and direct sequencing. Multiplex ligation-dependent probe amplification was performed to detect the number of mutant copies. The NF1 gene analysis showed the following alterations: mosaic duplication of NF1, TRAF4, and MYO1D. Fluorescence in situ hybridization using probes (RP5-1002G3 and RP5-92689) flanking NF1 gene in 17q11.2 and CEP17 for 17q11.11.1 was performed. There were three signals (RP5-1002G3conRP5-92689) in the interphases analyzed and two signals (RP5-1002G3conRP5-92689) in 93% of cells. These findings show a tandem duplication of 17q11.2. Conclusion. The case suggests the possibility that NF1 gene duplication may be associated with a phenotype characterized by lymphoproliferative disorders. PMID:25580325

  14. Sirolimus, Tacrolimus, Thymoglobulin and Rituximab as Graft-versus-Host-Disease Prophylaxis in Patients Undergoing Haploidentical and HLA Partially Matched Donor Hematopoietic Cell Transplantation

    ClinicalTrials.gov

    2015-12-09

    Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

  15. Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells

    ClinicalTrials.gov

    2015-07-29

    Stem Cell Transplantation; Bone Marrow Transplantation; Peripheral Blood Stem Cell Transplantation; Allogeneic Transplantation,; Genetic Diseases; Thalassemia; Pediatrics; Diamond-Blackfan Anemia; Combined Immune Deficiency; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; X-linked Lymphoproliferative Disease; Metabolic Diseases

  16. Disturbed B-lymphocyte selection in autoimmune lymphoproliferative syndrome.

    PubMed

    Janda, Ales; Schwarz, Klaus; van der Burg, Mirjam; Vach, Werner; Ijspeert, Hanna; Lorenz, Myriam Ricarda; Elgizouli, Magdeldin; Pieper, Kathrin; Fisch, Paul; Hagel, Joachim; Lorenzetti, Raquel; Seidl, Maximilian; Roesler, Joachim; Hauck, Fabian; Traggiai, Elisabetta; Speckmann, Carsten; Rensing-Ehl, Anne; Ehl, Stephan; Eibel, Hermann; Rizzi, Marta

    2016-05-01

    Fas is a transmembrane receptor involved in the maintenance of tolerance and immune homeostasis. In murine models, it has been shown to be essential for deletion of autoreactive B cells in the germinal center. The role of Fas in human B-cell selection and in development of autoimmunity in patients carrying FAS mutations is unclear. We analyzed patients with either a somatic FAS mutation or a germline FAS mutation and somatic loss-of-heterozygosity, which allows comparing the fate of B cells with impaired vs normal Fas signaling within the same individual. Class-switched memory B cells showed: accumulation of FAS-mutated B cells; failure to enrich single V, D, J genes and single V-D, D-J gene combinations of the B-cell receptor variable region; increased frequency of variable regions with higher content of positively charged amino acids; and longer CDR3 and maintenance of polyreactive specificities. Importantly, Fas-deficient switched memory B cells showed increased rates of somatic hypermutation. Our data uncover a defect in B-cell selection in patients with FAS mutations, which has implications for the understanding of the pathogenesis of autoimmunity and lymphomagenesis of autoimmune lymphoproliferative syndrome. PMID:26907631

  17. Impact of pre-transplant dialysis modality on post-transplant diabetes mellitus after kidney transplantation.

    PubMed

    Courivaud, Cécile; Ladrière, Marc; Toupance, Olivier; Caillard, Sophie; Hurault de Ligny, Bruno; Ryckelynck, Jean-Philippe; Moulin, Bruno; Rieu, Philippe; Frimat, Luc; Chalopin, Jean-Marc; Chauvé, Sylvie; Kazory, Amir; Ducloux, Didier

    2011-01-01

    Post-transplant diabetes mellitus (PTDM) is a well-known complication in renal transplant recipients (RTRs). While a number of risk factors for PTDM have been identified, the potential impact of pre-transplant dialysis modality on subsequent development of PTDM has not yet been explored. We performed a multicenter retrospective study on 2010 consecutive RTRs who did not have a history of diabetes prior to renal transplantation. PTDM was defined as a need for anti-diabetic therapy in an RTR without a history of diabetes prior to transplantation. Analysis of the risk factors for development of PTDM was performed with respect to pre-transplant dialysis modality. A total of 137 (6.8%) patients developed PTDM; 7% in the hemodialysis group and 6.5% in the peritoneal dialysis (PD) group (p = 0.85). In the multivariate analysis, age (p < 0.001), body mass index (BMI) (p < 0.001), use of tacrolimus (p = 0.002), and rejection episodes (p < 0.001) were identified as independent risk factors for development of PTDM. Patients in the PD group were younger (p = 0.004), had lower BMI (p = 0.07), and were less likely to have a history of hepatitis C (p = 0.007) and autosomal dominant polycystic kidney disease (p = 0.07). Adjustment for these variables did not modify the results. The results of this study suggest that pre-transplant dialysis modality does not have an impact on the subsequent development of PTDM in RTRs. PMID:21158919

  18. Approaches to Managing Autoimmune Cytopenias in Novel Immunological Disorders with Genetic Underpinnings Like Autoimmune Lymphoproliferative Syndrome

    PubMed Central

    Rao, V. Koneti

    2015-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of apoptosis. It is frequently caused by mutations in FAS (TNFRSF6) gene. Unlike most of the self-limiting autoimmune cytopenias sporadically seen in childhood, multi lineage cytopenias due to ALPS are often refractory, as their inherited genetic defect is not going to go away. Historically, more ALPS patients have died due to overwhelming sepsis following splenectomy to manage their chronic cytopenias than due to any other cause, including malignancies. Hence, current recommendations underscore the importance of avoiding splenectomy in ALPS, by long-term use of corticosteroid-sparing immunosuppressive agents like mycophenolate mofetil and sirolimus. Paradigms learnt from managing ALPS patients in recent years is highlighted here and can be extrapolated to manage refractory cytopenias in patients with as yet undetermined genetic bases for their ailments. It is also desirable to develop international registries for children with rare and complex immune problems associated with chronic multilineage cytopenias in order to elucidate their natural history and long-term comorbidities due to the disease and its treatments. PMID:26258116

  19. Epstein-Barr Virus-associated lymphoproliferative disorders: experimental and clinical developments

    PubMed Central

    Geng, Lingyun; Wang, Xin

    2015-01-01

    Epstein-Barr Virus (EBV), the first human virus related to oncogenesis, was initially identified in a Burkitt lymphoma cell line in 1964. EBV infects over 90% of the world’s population. Most infected people maintain an asymptomatic but persistent EBV infection lifelong. However, in some individuals, EBV infection has been involved in the development of cancer and autoimmune disease. Nowadays, oncogenic potential of EBV has been intensively studied in a wide range of human neoplasms, including Hodgkin’s lymphoma (HL), non-Hodgkin’s lymphoma (NHL), nasopharyngeal carcinoma (NPC), gastric carcinoma (GC), etc. EBV encodes a series of viral protein and miRNAs, promoting its persistent infection and the transformation of EBV-infected cells. Although the exact role of EBV in the oncogenesis remains to be clarified, novel diagnostic and targeted therapeutic approaches are encouraging for the management of EBV-related malignancies. This review mainly focuses on the experimental and clinical advances of EBV-associated lymphoproliferative disorders. PMID:26628948

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

    PubMed

    Luskin, M R; Heil, D S; Tan, K S; Choi, S; Stadtmauer, E A; Schuster, S J; Porter, D L; Vonderheide, R H; Bagg, A; Heitjan, D F; Tsai, D E; Reshef, R

    2015-10-01

    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. PMID:25988622

  1. Unusual gingival presentation of post-transplantation lymphoproliferative disorder: a case report and review of the literature.

    PubMed

    Raut, A; Huryn, J; Pollack, A; Zlotolow, I

    2000-10-01

    Post-transplantation lymphoproliferative disorder is a well-documented complication of solid organ or bone marrow transplantation. Histologically, it is characterized by an abnormal proliferation of lymphocytes, which can range from benign B-cell hyperplasia to malignant lymphoma. Non-Hodgkin's lymphoma (NHL) is associated with several risk factors, such as congenital or acquired immunodeficiency states, autoimmune disorders, and infectious agents (eg, Epstein-Barr virus). Primary sites of presentation in the head and neck are Waldeyer's ring, paranasal sinuses, salivary glands, the oral cavity, and the larynx. Clinical appearance of gingival NHL varies but is usually found to be an asymptomatic gingival enlargement or mass resembling a pyogenic granuloma. We present a patient with a gingival ulceration that was subsequently diagnosed as Epstein-Barr virus malignant lymphoma resulting from the immunosuppression needed to prevent graft-versus-host disease after bone marrow transplantation. PMID:11027379

  2. Intrafollicular Epstein-Barr virus-positive large B cell lymphoma. A variant of "germinotropic" lymphoproliferative disorder.

    PubMed

    Lorenzi, Luisa; Lonardi, Silvia; Essatari, Murad H M; Pellegrini, Vilma; Fisogni, Simona; Gazzola, Anna; Agostinelli, Claudio; Vermi, William; Rossi, Giuseppe; Massarelli, Giovannino; Pileri, Stefano A; Facchetti, Fabio

    2016-04-01

    Germinotropic lymphoproliferative disorders were previously described as localized disorders associated with coinfection by human herpes virus 8 and Epstein-Barr virus and characterized by good clinical outcome. We report the clinical, morphological, phenotypical, and molecular features of three cases of a hitherto unreported variant of Epstein-Barr virus (EBV)-positive, human herpes virus 8 (HHV8)-negative large B cell lymphoma with exclusive intrafollicular localization. All cases occurred in elderly individuals (63, 77, and 65 years old; one male, two females) without obvious immunedeficiency, who presented with high stage disease. Lymph nodes showed an effaced nodular architecture with abnormal B follicles colonized by EBV+ large, pleomorphic atypical cells, including Reed-Sternberg-like cells, showing an activated B cell phenotype (CD10-FOXP1-Bcl6-IRF4+ or CD10-FOXP1+Bcl6+IRF4+) and intense expression of CD30. No monoclonal light-chain restriction was detected by immunohistochemistry or in situ hybridization, and IGH rearrangement was polyclonal; notably, EBV clonality was detectable in one case. Lymphoma cells in all cases showed diffuse expression of the c-Myc protein, while Bcl2 was dim or negative; moreover, the strong expression of phosphorylated-STAT3 in tumor cell nuclei suggested activation of the JAK-STAT pathway. FISH analysis was performed in two cases and showed no translocations of BCL2, BCL6, MYC, and PAX5 genes. Response to treatment was poor in 2/3 patients: one died after 18 months, one is alive with disease after 12 months. The intrafollicular EBV-positive large B cell lymphoma expands the spectrum of EBV-associated lymphoproliferative disorders in immunocompetent individuals. PMID:26762526

  3. Ibrutinib: another weapon in our arsenal against lympho-proliferative disorders.

    PubMed

    Cabras, Maria Giuseppina; Angelucci, Emanuele

    2015-12-01

    In Volume 16, issue 12 of Expert Opinion on Pharmacotherapy, an important article on the new drug ibrutinib was published. This new drug promises to further improve outcome in the treatment of several lympho-proliferative disorders. In this editorial, the most important findings of the article looking particularly to the integration of ibrutinib in current clinical practice will be summarized. Finally this editorial will focus on the next challenges for scientists and physicians in the treatment of lympho-proliferative disorders. PMID:26549294

  4. Molecular and cytogenetic characterization of expanded B-cell clones from multiclonal versus monoclonal B-cell chronic lymphoproliferative disorders

    PubMed Central

    Henriques, Ana; Rodríguez-Caballero, Arancha; Criado, Ignacio; Langerak, Anton W.; Nieto, Wendy G.; Lécrevisse, Quentin; González, Marcos; Cortesão, Emília; Paiva, Artur; Almeida, Julia; Orfao, Alberto

    2014-01-01

    Chronic antigen-stimulation has been recurrently involved in the earlier stages of monoclonal B-cell lymphocytosis, chronic lymphocytic leukemia and other B-cell chronic lymphoproliferative disorders. The expansion of two or more B-cell clones has frequently been reported in individuals with these conditions; potentially, such coexisting clones have a greater probability of interaction with common immunological determinants. Here, we analyzed the B-cell receptor repertoire and molecular profile, as well as the phenotypic, cytogenetic and hematologic features, of 228 chronic lymphocytic leukemia-like and non-chronic lymphocytic leukemia-like clones comparing multiclonal (n=85 clones from 41 cases) versus monoclonal (n=143 clones) monoclonal B-cell lymphocytosis, chronic lymphocytic leukemia and other B-cell chronic lymphoproliferative disorders. The B-cell receptor of B-cell clones from multiclonal cases showed a slightly higher degree of HCDR3 homology than B-cell clones from mono clonal cases, in association with unique hematologic (e.g. lower B-lymphocyte counts) and cytogenetic (e.g. lower frequency of cytogenetically altered clones) features usually related to earlier stages of the disease. Moreover, a subgroup of coexisting B-cell clones from individual multiclonal cases which were found to be phylogenetically related showed unique molecular and cytogenetic features: they more frequently shared IGHV3 gene usage, shorter HCDR3 sequences with a greater proportion of IGHV mutations and del(13q14.3), than other unrelated B-cell clones. These results would support the antigen-driven nature of such multiclonal B-cell expansions, with potential involvement of multiple antigens/epitopes. PMID:24488564

  5. EBV-driven B-cell lymphoproliferative disorders: from biology, classification and differential diagnosis to clinical management

    PubMed Central

    Ok, Chi Young; Li, Ling; Young, Ken H

    2015-01-01

    Epstein–Barr virus (EBV) is a ubiquitous herpesvirus, affecting >90% of the adult population. EBV targets B-lymphocytes and achieves latent infection in a circular episomal form. Different latency patterns are recognized based on latent gene expression pattern. Latent membrane protein-1 (LMP-1) mimics CD40 and, when self-aggregated, provides a proliferation signal via activating the nuclear factor-kappa B, Janus kinase/signal transducer and activator of transcription, phosphoinositide 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein kinase pathways to promote cellular proliferation. LMP-1 also induces BCL-2 to escape from apoptosis and gives a signal for cell cycle progression by enhancing cyclin-dependent kinase 2 and phosphorylation of retinoblastoma (Rb) protein and by inhibiting p16 and p27. LMP-2A blocks the surface immunoglobulin-mediated lytic cycle reactivation. It also activates the Ras/PI3K/Akt pathway and induces Bcl-xL expression to promote B-cell survival. Recent studies have shown that ebv-microRNAs can provide extra signals for cellular proliferation, cell cycle progression and anti-apoptosis. EBV is well known for association with various types of B-lymphocyte, T-lymphocyte, epithelial cell and mesenchymal cell neoplasms. B-cell lymphoproliferative disorders encompass a broad spectrum of diseases, from benign to malignant. Here we review our current understanding of EBV-induced lymphomagenesis and focus on biology, diagnosis and management of EBV-associated B-cell lymphoproliferative disorders. PMID:25613729

  6. Posttransplant oral iron-chelating therapy in patients with beta-thalassemia major.

    PubMed

    Yesilipek, M Akif; Karasu, Gulsun; Kazik, Mediha; Uygun, Vedat; Ozturk, Zeynep

    2010-08-01

    Allogeneic hematopoetic stem cell transplantation (HSCT) is the only radical cure of beta-thalassemia. However, iron overload remains a cause of morbidity and mortality in posttransplant period. The authors present 7 patients as a preliminary report who underwent bone marrow transplant (BMT) and received oral chelating therapy (deferasirox) because of poor compliance to phlebotomy and desferrioxamine. The patients investigated mainly for possible side effects of deferasirox. No negative effect was seen in aspartate aminotransferase (AST), alanine aminotransferase (ALT), hemoglobin (Hb), and donor chimerism of the patients while serum ferritin levels significantly reduced (P = .018). Although serum creatinin significantly increased (P = .034), it was in normal limits in all patients. The authors believe that this report shows promising findings to plan further studies to clarify clinical safety and efficacy of deferasirox in posttransplant period. PMID:20604682

  7. Late post-transplant erythrocytosis in a hepatitis C-positive allograft recipient on sirolimus

    PubMed Central

    Ali, A. A. M.; Khanna, P.; Mehrotra, A.; Abraham, G.

    2011-01-01

    Hematological complications in renal transplant recipients include anemia, leukopenia, and post-transplant erythrocytosis (PTE). There are numerous causes for these which include immunosuppressive drugs, viral infections, etc. We report here a hepatitis C (HCV)-positive case who developed PTE while receiving rapamycin. As both HCV infection and rapamycin through different mechanisms can produce anemia, this case report highlights the rarity of erythrocytosis. PMID:21769178

  8. Structure of Post-Transplant Care in a Single Transplant Center.

    PubMed

    Szymańska, Agnieszka; Pączek, Leszek; Mucha, Krzysztof; Krajewska, Monika; Florczak, Michał; Ciszek, Michał; Sańko-Resmer, Joanna; Chmura, Andrzej; Nazarewski, Sławomir; Górski, Andrzej; Durlik, Magdalena; Krawczyk, Marek; Foroncewicz, Bartosz

    2016-01-01

    BACKGROUND The number of transplant surgeries across the globe has markedly increased in recent decades and is associated with improvement in outcomes. Factors that could improve the organization of post-transplant care are sought. The aim of our study was to evaluate the changes in post-transplant care in the largest Polish transplant center from 2010 to 2014. MATERIAL AND METHODS Analysis was performed in all transplant recipients followed up at our center. The following factors were evaluated: changes in patient inflow and outflow, changes in the number of ambulatory visits, causes of loss to follow-up of the patients, and changes in National Health Fund financing. All factors were measured in 5-year period from 2010 to 2014. RESULTS Stable year-to-year patient inflow increased by 31% in the total number of patients under follow-up within 5 years. In the same time, the total NHF spending increased by 32%, but spending per patient increased by only 11%. As a consequence, after the initial growth in the years 2010-2012, the number of ambulatory visits per patient per year tended to decline. CONCLUSIONS Our study revealed that the real challenge in long-term post-transplant care is the increasing number of patients and the increasing length of their follow-up. Potential risks related to financial expenditure discrepancy between short-term and long-term transplantation procedures were also found. PMID:27045270

  9. CCL2 gene polymorphism is associated with post-transplant diabetes mellitus.

    PubMed

    Dabrowska-Zamojcin, Ewa; Romanowski, Maciej; Dziedziejko, Violetta; Maciejewska-Karlowska, Agnieszka; Sawczuk, Marek; Safranow, Krzysztof; Domanski, Leszek; Pawlik, Andrzej

    2016-03-01

    Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation, especially in recipients treated with calcineurin inhibitors. Previous studies suggest that chronic inflammation and chemokines play an important role in the pathogenesis of diabetes. Single-nucleotide polymorphisms (SNPs) can increase or decrease transcriptional activity and can change the production of chemokines. The aim of this study was to examine the association between CCL2 and CCL5 gene polymorphisms and the development of post-transplant diabetes mellitus. The study included 315 patients who received kidney transplants and were treated with calcineurin inhibitors. Patients were divided into two subgroups: with PTDM (n=43) and without PTDM (n=272). An additive model of univariate Cox regression analysis showed that the hazard of PTDM development was significantly positively associated with the number of CCL2 rs1024611 G alleles (HR 1.65; 95%CI 1.08-2.53; p=0.021). Multivariate Cox regression analysis, taking into the account the recipient's sex, age and BMI, as well as the number of G alleles of the CCL2 rs1024611 polymorphism, revealed that this polymorphism is an independent risk factor for post-transplant diabetes. The results of our study suggest an association between the CCL2 gene rs1024611 G allele and PTDM in patients treated with tacrolimus or cyclosporine. PMID:26802601

  10. Posttransplant Complex Inferior Venacava Balloon Dilatation After Hepatic Vein Stenting

    SciTech Connect

    Kohli, Vikas; Wadhawan, Manav; Gupta, Subhash; Roy, Vipul

    2010-02-15

    Orthotopic and living related liver transplantation is an established mode of treatment of end-stage liver disease. One of the major causes of postoperative complications is vascular anastomotic stenosis. One such set of such complications relates to hepatic vein, inferior vena cava (IVC), or portal vein stenosis, with a reported incidence of 1-3%. The incidence of vascular complications is reported to be higher in living donor versus cadaveric liver transplants. We encountered a patient with hepatic venous outflow tract obstruction, where the hepatic vein had been previously stented, but the patient continued to have symptoms due to additional IVC obstruction. The patient required double-balloon dilatation of the IVC simultaneously from the internal jugular vein and IVC.

  11. Programmed death 1 and B and T lymphocyte attenuator immunoreceptors and their association with malignant T-lymphoproliferative disorders: brief review.

    PubMed

    Karakatsanis, Stamatis; Bertsias, George; Roussou, Paraskevi; Boumpas, Dimitrios

    2014-09-01

    Malignant T-cell lymphoproliferative diseases are relatively rare. T cells are activated through the T-cell receptor with the aid of costimulating molecules that can be either excitatory or inhibitory. Such pathways have been also implicated in mechanisms of malignant T-cell lymphoproliferative diseases' persistence and relapse by circumventing immune responses. To date, three major immunoinhibitory molecules have been recognized, namely programmed cell death-1 (PD-1), B and T lymphocyte attenuator (BTLA) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Although CTLA-4 is considered the 'gatekeeper' of immune tolerance, PD-1 negatively regulates immune responses broadly, whereas BTLA activation has been shown to inhibit CD8+ cancer-specific T cells. Both PD-1 and BTLA downregulate proximal T-cell receptor signalling cascade and are involved in immune evasion of leukaemias and lymphomas, even after allogeneic stem cell transplantation. These immunoregulatory molecules can have seemingly a synergistic effect on weakening the immune response of patients with haematological malignancies, and their manipulation represents a very active field of preclinical as well as clinical interest. PMID:24038528

  12. Epstein-Barr virus latent membrane protein-1 oncogene deletion in post-transplantation lymphoproliferative disorders.

    PubMed Central

    Scheinfeld, A. G.; Nador, R. G.; Cesarman, E.; Chadburn, A.; Knowles, D. M.

    1997-01-01

    Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is a multifunctional oncoprotein. A 30-bp deletion of the 3' end of the LMP1 gene (del-LMP1) has been identified in some EBV isolates. This deleted LMP1 gene encodes a protein, altered on the carboxy terminus, which is thought to have greater oncogenic potential than the wild type. Recently, it was suggested that del-LMP1 plays a role in the development of malignant lymphomas occurring in immunocompromised patients. To further elucidate the role of del-LMP1 in post-transplantation lymphoproliferative disorders (PT-LPDs) we analyzed 58 PT-LPD lesions from 36 heart and kidney organ transplant recipients. Overall, del-LMP1 was detected in 44% of the cases. Four plasmacytic hyperplasias (36%), eight polymorphic B-cell hyperplasias/polymorphic B-cell lymphomas (38%), and five malignant lymphomas/multiple myelomas (71%) exhibited del-LMP1. Two of the three patients displaying disease progression showed wild-type LMP1 gene (w-LMP1) and one showed del-LMP1. LMP1 status remained the same in all three patients during disease progression. In patients undergoing biopsy of multiple separate PT-LPD lesions representing different clonal lymphoid proliferations, LMP1 status was the same in all of the lesions in each patient. Furthermore, although the polyclonal lesions harbor multiple EBV infectious events, they either showed w- or del-LMP1 but not both. Analysis of the tissues without an apparent PT-LPD (peripheral blood, bone marrow, or colon) revealed EBV and LMP1 type identical to that found in the lesions. In conclusion, the presence or absence of del-LMP1 in PT-LPDs does not correlate with the histopathological category or the malignant nature of the lymphoid proliferation. LMP1 status does not change during disease progression and is the same within multiple lesions occurring in the same patient regardless of their clonal relationship. These findings suggest that 1) EBV infection in patients with PT-LPDs occurs with a w- or del-LMP1-type EBV isolate and does not change once a patient acquires the virus and 2) the infection is an early event in the development of PT-LPDs and transformation is induced regardless of the type of LMP1. Images Figure 1 Figure 2 Figure 3 PMID:9284829

  13. Chronic Disease and Childhood Development: Kidney Disease and Transplantation.

    ERIC Educational Resources Information Center

    Klein, Susan D.; Simmons, Roberta G.

    As part of a larger study of transplantation and chronic disease and the family, 124 children (10-18 years old) who were chronically ill with kidney disease (n=72) or were a year or more post-transplant (n=52) were included in a study focusing on the effects of chronic kidney disease and transplantation on children's psychosocial development. Ss…

  14. Idiopathic Pneumonia Syndrome and Thrombotic Microangiopathy Following Nonmyeloablative Haploidentical Peripheral Blood Stem Cell Transplantation and Posttransplant Cyclophosphamide

    PubMed Central

    Liu, Wei-Hsin; Chen, Wei-Ting; Fang, Li-Hua; Chen, Rong-Long

    2015-01-01

    Abstract Posttransplant high-dose cyclophosphamide (pT-HDCy) following T-cell-replete haploidentical bone marrow (BM) transplantation has been successfully utilized to control alloreactivity, mainly in ameliorating graft-versus-host disease (GVHD) and graft rejection. Recently, peripheral blood stem cells (PBSCs) have also been suggested to be a feasible and effective graft alternative to BM in the same setting. We report a case with refractory Hodgkin lymphoma treated with haploidentical PBSC transplantation with nonmyeloablative conditioning and pT-HDCy. Although engraftment with complete donor chimerism was achieved without classical GVHD, the patient suffered from idiopathic pneumonia syndrome followed by thrombotic microangiopathy. Although idiopathic pneumonia syndrome and thrombotic microangiopathy improved after treatment, the patient's lymphoma rapidly progressed nonetheless. This outcome may suggest that the alloreactivity against the classical GVHD targets is successfully eradicated by pT-HDCy, but alloreactivity against the lungs and endothelial cells is differentially preserved when utilizing granulocyte colony-stimulating factor-mobilized PBSCs as the graft source. The graft-versus-Hodgkin lymphoma effect was not observed in our patient. PMID:26200635

  15. MELD score as a predictor of pretransplant and posttransplant survival in OPTN/UNOS status 1 patients.

    PubMed

    Kremers, Walter K; van IJperen, Marrije; Kim, W Ray; Freeman, Richard B; Harper, Ann M; Kamath, Patrick S; Wiesner, Russell H

    2004-03-01

    The Model for End-Stage Liver Disease (MELD) score is predictive of survival and is used to prioritize patients with chronic liver disease patients for orthotopic liver transplantation (OLT). The aims of this study are (1) to assess the ability of MELD score at listing to predict pretransplant and posttransplant survival for nonchronic liver disease patients listed with the Organ Procurement and Transplantation Network/ United Network for Organ Sharing (OPTN/UNOS) as Status 1; and (2) to compare survival associated with 4 diagnostic groups within the Status 1 designation. The study population consisted of adult patients listed for OLT at Status 1 in the UNOS national database between November 1, 1999 and March 14, 2002 (N = 720). Events within 30 days of listing were analyzed using Kaplan-Meier and Cox regression methodology. Patients meeting criteria for fulminant hepatic failure without acetaminophen toxicity (FHF-NA, n = 312) had the poorest survival probability while awaiting OLT; this was negatively correlated with MELD score (P =.0001). These patients experienced the greatest survival benefit associated with OLT, with an estimated improvement of survival from about 58% to 91% (P <.0001). Patients listed for primary nonfunction within 7 days of OLT (n = 268) did not show mortality to be related to MELD score (P =.41) and did not show a significant association between survival and OLT (P =.68). In conclusion, liver allocation within the Status 1 designation may need to be further stratified by diagnosis, and MELD score may be useful for prioritizing FHF-NA candidates. PMID:14999695

  16. Loss-of-function of the protein kinase C δ (PKCδ) causes a B-cell lymphoproliferative syndrome in humans

    PubMed Central

    Kuehn, Hye Sun; Niemela, Julie E.; Rangel-Santos, Andreia; Zhang, Mingchang; Pittaluga, Stefania; Stoddard, Jennifer L.; Hussey, Ashleigh A.; Evbuomwan, Moses O.; Priel, Debra A. Long; Kuhns, Douglas B.; Park, C. Lucy; Fleisher, Thomas A.; Uzel, Gulbu

    2013-01-01

    Defective lymphocyte apoptosis results in chronic lymphadenopathy and/or splenomegaly associated with autoimmune phenomena. The prototype for human apoptosis disorders is the autoimmune lymphoproliferative syndrome (ALPS), which is caused by mutations in the FAS apoptotic pathway. Recently, patients with an ALPS-like disease called RAS-associated autoimmune leukoproliferative disorder, in which somatic mutations in NRAS or KRAS are found, also were described. Despite this progress, many patients with ALPS-like disease remain undefined genetically. We identified a homozygous, loss-of-function mutation in PRKCD (PKCδ) in a patient who presented with chronic lymphadenopathy, splenomegaly, autoantibodies, elevated immunoglobulins and natural killer dysfunction associated with chronic, low-grade Epstein-Barr virus infection. This mutation markedly decreased protein expression and resulted in ex vivo B-cell hyperproliferation, a phenotype similar to that of the PKCδ knockout mouse. Lymph nodes showed intense follicular hyperplasia, also mirroring the mouse model. Immunophenotyping of circulating lymphocytes demonstrated expansion of CD5+CD20+ B cells. Knockdown of PKCδ in normal mononuclear cells recapitulated the B-cell hyperproliferative phenotype in vitro. Reconstitution of PKCδ in patient-derived EBV-transformed B-cell lines partially restored phorbol-12-myristate-13-acetate–induced cell death. In summary, homozygous PRKCD mutation results in B-cell hyperproliferation and defective apoptosis with consequent lymphocyte accumulation and autoantibody production in humans, and disrupts natural killer cell function. PMID:23430113

  17. Human american cutaneous leishmaniasis (Leishmania b. braziliensis) in Brazil: lymphoproliferative responses and influence of therapy.

    PubMed Central

    Mendonça, S C; Coutinho, S G; Amendoeira, R R; Marzochi, M C; Pirmez, C

    1986-01-01

    The host defence to Leishmania parasites is believed to depend on cell-mediated immune responses. Three groups of inhabitants from an endemic area in Rio de Janeiro were studied: Group I consisted of 28 patients with cutaneous lesions, Group II of 28 healthy persons (without ulcers) but with positive Montenegro skin tests (MST) and Group III of 29 healthy persons with negative MST. The peripheral blood lymphocyte proliferative responses induced by leishmanial-antigens (Leishmania b. braziliensis lymphoproliferative response) as well as by Concanavalin A (Con A-lymphoproliferative response), both measured by 3H-thymidine incorporation were tested in each group. The results showed that: The Leishmania b. braziliensis lymphoproliferative response (L.b.b.-LPR) in healthy persons with positive MST (Group II) was higher than in patients prior to therapy (Group I); A significantly higher L.b.b.-LPR was found in patients and healthy persons with positive MST as compared to Group III (negative MST); The L.b.b.-LPR of Group I (patients) increased during antimonial therapy--this might possibly be related to the destruction of parasites; The levels of L.b.b.-LPR after therapy became similar to the ones before therapy; All individuals from the three groups had a positive Con A-lymphoproliferative response (Con A-LPR); All patients who had a histopathological picture of granulomatous reaction also had a positive L.b.b.-LPR; A poor response to antimonial therapy observed in six patients was associated with a low L.b.b.-LPR. PMID:3742876

  18. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update.

    PubMed

    Bacigalupo, A; Dominietto, A; Ghiso, A; Di Grazia, C; Lamparelli, T; Gualandi, F; Bregante, S; Van Lint, M T; Geroldi, S; Luchetti, S; Grasso, R; Pozzi, S; Colombo, N; Tedone, E; Varaldo, R; Raiola, A M

    2015-06-01

    This is a report of 148 patients with hematologic malignancies who received an unmanipulated haploidentical bone marrow transplant (BMT), followed by post-transplant high-dose cyclophosphamide (PT-CY). All patients received a myeloablative conditioning consisting of thiotepa, busulfan, fludarabine (n=92) or TBI, fludarabine (n=56). The median age was 47 years (17-74); 47 patients were in first remission (CR1), 37 in second remission (CR2) and 64 had an active disease; all patients were first grafts. The diagnosis was acute leukemia (n=75), myelodisplastic syndrome (n=24), myelofibrosis (n=16), high-grade lymphoma (n=15) and others (n=18). GVHD prophylaxis consisted in PT-CY on days +3 and +5, cyclosporine (from day 0), and mycophenolate (from day +1). The median day for neutrophil engraftment was day +18 (13-32). The cumulative incidence of grades II-IV acute GVHD was 24%, and of grades III-IV GVHD 10%. The incidence of moderate-severe chronic GVHD was 12%. With a median follow-up for the surviving patients of 313 days (100-1162), the cumulative incidence of transplant-related mortality (TRM) is 13%, and the relapse-related death is 23%. The actuarial 22 months overall survival is 77% for CR1 patients, 49% for CR2 patients and 38% for patients grafted in relapse (P<0.001). Major causes of death were relapse (22%), GVHD (2%) and infections (6%). We confirm our initial results, suggesting that a myeloablative conditioning regimen followed by unmanipulated haploidentical BMT with PT-CY, results in a low risk of acute and chronic GVHD and encouraging rates of TRM and overall survival, also for patients with active disease at the time of transplant. PMID:26039205

  19. Primary Cutaneous Anaplastic Large-Cell Lymphoma With 6p25.3 Rearrangement in a Cardiac Transplant Recipient: A Case Report and Review of the Literature.

    PubMed

    Olson, Luke C; Cheng, Esther; Mathew, Susan; Torres-Quinones, Marta; Magro, Cynthia

    2016-06-01

    Posttransplant lymphoproliferative disorders define an important form of lymphoproliferative disease causally linked with a state of iatrogenic immune dysregulation inherent to the posttransplant setting. Most posttransplant lymphoproliferative disorders are in the context of Epstein-Barr virus-associated B-cell lymphoproliferative disease, most notably diffuse large-cell B-cell lymphoma. A less common variant falls under the rubric of posttransplant T-cell lymphoproliferative disease, which is largely unrelated to Epstein-Barr virus infection. Anaplastic large-cell lymphoma (ALCL) is the most recognized form of posttransplant T-cell lymphoproliferative disease. Although the 6p25.3 translocation is seen in a variety of B-cell lymphoproliferative disorders, this particular translocation in the spectrum of T-cell lymphoproliferative disease is a fairly specific finding pointing toward a diagnosis of primary cutaneous ALCL and a rare subset of lymphomatoid papulosis. This translocation in the peripheral T-cell lymphoma setting serves as a favorable prognostic predictor. We report a case of an 81-year-old heart transplant recipient who developed an expansile neck mass 17 years after his heart transplant. A diagnosis of cutaneous ALCL was subsequently made with cytogenetic analysis yielding the 6p25.3 translocation. The characteristic biphasic morphology of a small-cell epidermotropic neoplastic cell populace in concert with a dermal based large-cell infiltrate characteristic for those cases of ALCL harboring this translocation was seen. After excision of the nodule, his azathioprine was withheld. He is currently alive and well without evidence of disease. PMID:26863058

  20. Effects of oncological treatments on semen quality in patients with testicular neoplasia or lymphoproliferative disorders

    PubMed Central

    Di Bisceglie, Cataldo; Bertagna, Angela; Composto, Emanuela R; Lanfranco, Fabio; Baldi, Matteo; Motta, Giovanna; Barberis, Anna M; Napolitano, Emanuela; Castellano, Elena; Manieri, Chiara

    2013-01-01

    Pretherapy sperm cryopreservation in young men is currently included in good clinical practice guidelines for cancer patients. The aim of this paper is to outline the effects of different oncological treatments on semen quality in patients with testicular neoplasia or lymphoproliferative disorders, based on an 8-year experience of the Cryopreservation Centre of a large public hospital. Two hundred and sixty-one patients with testicular neoplasia and 219 patients with lymphoproliferative disorders who underwent chemotherapy and/or radiotherapy and pretherapy semen cryopreservation were evaluated. Sperm and hormonal parameters (follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, inhibin B levels) were assessed prior to and 6, 12, 18, 24 and 36 months after the end of cancer treatment. At the time of sperm collection, baseline FSH level and sperm concentration were impaired to a greater extent in patients with malignant testicular neoplasias than in patients with lymphoproliferative disorders. Toxic effects on spermatogenesis were still evident at 6 and 12 months after the end of cancer therapies, while an improvement of seminal parameters was observed after 18 months. In conclusion, an overall increase in sperm concentration was recorded about 18 months after the end of cancer treatments in the majority of patients, even if it was not possible to predict the evolution of each single case ‘a priori'. For this reason, pretherapy semen cryopreservation should be considered in all young cancer patients. PMID:23542137

  1. Effects of oncological treatments on semen quality in patients with testicular neoplasia or lymphoproliferative disorders.

    PubMed

    Di Bisceglie, Cataldo; Bertagna, Angela; Composto, Emanuela R; Lanfranco, Fabio; Baldi, Matteo; Motta, Giovanna; Barberis, Anna M; Napolitano, Emanuela; Castellano, Elena; Manieri, Chiara

    2013-05-01

    Pretherapy sperm cryopreservation in young men is currently included in good clinical practice guidelines for cancer patients. The aim of this paper is to outline the effects of different oncological treatments on semen quality in patients with testicular neoplasia or lymphoproliferative disorders, based on an 8-year experience of the Cryopreservation Centre of a large public hospital. Two hundred and sixty-one patients with testicular neoplasia and 219 patients with lymphoproliferative disorders who underwent chemotherapy and/or radiotherapy and pretherapy semen cryopreservation were evaluated. Sperm and hormonal parameters (follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, inhibin B levels) were assessed prior to and 6, 12, 18, 24 and 36 months after the end of cancer treatment. At the time of sperm collection, baseline FSH level and sperm concentration were impaired to a greater extent in patients with malignant testicular neoplasias than in patients with lymphoproliferative disorders. Toxic effects on spermatogenesis were still evident at 6 and 12 months after the end of cancer therapies, while an improvement of seminal parameters was observed after 18 months. In conclusion, an overall increase in sperm concentration was recorded about 18 months after the end of cancer treatments in the majority of patients, even if it was not possible to predict the evolution of each single case 'a priori'. For this reason, pretherapy semen cryopreservation should be considered in all young cancer patients. PMID:23542137

  2. Early post-transplant complications following ABO-incompatible kidney transplantation

    PubMed Central

    Naciri Bennani, Hamza; Abdulrahman, Zhyiar; Allal, Asma; Sallusto, Federico; Delarche, Antoine; Game, Xavier; Esposito, Laure; Doumerc, Nicolas; Debiol, Bénédicte; Kamar, Nassim; Rostaing, Lionel

    2016-01-01

    Background: Living-kidney transplantation is increasing because of the scarcity of kidneys from deceased donors and the increasing numbers of patients on waiting lists for a kidney transplant. Living-kidney transplantation is now associated with increased long-term patient- and allograft-survival rates. Objectives: The purpose of this retrospective study was to identify, in a cohort of 44 ABO-incompatible (ABOi) live-kidney transplant patients, the main complications that occurred within 6 months post-transplantation, and to compare these findings with those from 44 matched ABO-compatible (ABOc) live-kidney transplant patients who were also from our center. Patients and Methods: This single-center retrospective study assessed post-transplantation complications in 44 ABO-i versus 44 matched ABO-c patients. All patients were comparable at baseline except that ABO-i patients had greater immunological risks. Results: During the 6-month post-transplant period, more ABO-i patients presented with postoperative bleeds, thus requiring significantly more blood transfusions. Bleeds were associated with significantly lower values of fibrinogen, platelets, prothrombin time, and hemoglobin levels. Surgical complications, patient- and graft-survival rates, and kidney-function statuses were similar between both groups at 6 months post-transplantation. Conclusions: We conclude that impairment of hemostatic factors at pre-transplant explained the increased risk of a post-transplant bleed in ABO-i patients. PMID:27047806

  3. Spontaneous Post-Transplant Disorders in NOD.Cg- Prkdcscid Il2rgtm1Sug/JicTac (NOG) Mice Engrafted with Patient-Derived Metastatic Melanomas

    PubMed Central

    Omodho, Lorna; Francis, Annick; Vander Borght, Sara; Marine, Jean-Christophe; van den Oord, Joost; Amant, Frédéric

    2015-01-01

    Patient-derived tumor xenograft (PDTX) approach is nowadays considered a reliable preclinical model to study in vivo cancer biology and therapeutic response. NOD scid and Il2rg-deficient mice represent the “gold standard” host for the generation of PDTXs. Compared to other immunocompromised murine lines, these mice offers several advantages including higher engraftment rate, longer lifespan and improved morphological and molecular preservation of patient-derived neoplasms. Here we describe a spectrum of previously uncharacterized post-transplant disorders affecting 14/116 (12%) NOD.Cg- Prkdcscid Il2rgtm1Sug/JicTac (NOG) mice subcutaneously engrafted with patient-derived metastatic melanomas. Affected mice exhibited extensive scaling/crusting dermatitis (13/14) associated with emaciation (13/14) and poor/unsuccessful tumor engraftment (14/14). In this context, the following pathological conditions have been recognized and characterized in details: (i) immunoinflammatory disorders with features of graft versus host disease (14/14); (ii) reactive lymphoid infiltrates effacing xenografted tumors (8/14); (iii) post-transplant B cell lymphomas associated with Epstein-Barr virus reactivation (2/14). We demonstrate that all these entities are driven by co-transplanted human immune cells populating patient-derived tumor samples. Since the exploding interest in the utilization of NOD scid and Il2rg-deficient mice for the establishment of PDTX platforms, it is of uppermost importance to raise the awareness of the limitations associated with this model. The disorders here described adversely impact tumor engraftment rate and animal lifespan, potentially representing a major confounding factor in the context of efficacy and personalized therapy studies. The occurrence of these conditions in the NOG model reflects the ability of this mouse line to promote efficient engraftment of human immune cells. Co-transplanted human lymphoid cells have indeed the potential to colonize the recipient mouse initiating the post-transplant conditions here reported. On the other hand, the evidence of an immune response of human origin against the xenotransplanted melanoma opens intriguing perspectives for the establishment of suitable preclinical models of anti-melanoma immunotherapy. PMID:25996609

  4. Research update: Avian Disease and Oncology Laboratory avian tumor viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomics and Immunogenetics Use of genomics to identify QTL, genes, and proteins associated with resistance to Marek’s disease. Marek’s disease (MD), a lymphoproliferative disease caused by the highly oncogenic herpesvirus Marek's disease virus (MDV), continues to be a major disease concern to the p...

  5. Nonalcoholic Fatty Liver Disease and Liver Transplantation.

    PubMed

    Pham, Tuan; Dick, Travis B; Charlton, Michael R

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is prevalent in the general population and a growing indication for liver transplant. Longer wait times and challenges with pretransplant survivorship are expected, underscoring the need for improved management of attendant comorbidities. Recognition with potential modification of obesity, sarcopenia, chronic kidney disease, and cardiovascular disease in patients with NAFLD may have important implications in the pretransplant and posttransplant periods. Although patients with NAFLD have generally favorable postoperative outcomes, they are at risk for developing recurrent disease in their allograft, driving the need for pharmacotherapies and dietary innovations appropriate for use in the posttransplant period. PMID:27063277

  6. GM-CSF and IL-2 induce specific cellular immunity and provide protection against Epstein-Barr virus lymphoproliferative disorder.

    PubMed

    Baiocchi, R A; Ward, J S; Carrodeguas, L; Eisenbeis, C F; Peng, R; Roychowdhury, S; Vourganti, S; Sekula, T; O'Brien, M; Moeschberger, M; Caligiuri, M A

    2001-09-01

    Epstein-Barr virus-associated lymphoproliferative disease (EBV-LPD) is a potentially life-threatening complication in immune-deficient patients. We have used the severe combined immune deficient (SCID) mouse engrafted with human leukocytes (hu-PBL-SCID) to evaluate the use of human cytokines in the prevention of EBV-LPD in vivo. Daily low-dose IL-2 therapy can prevent EBV-LPD in the hu-PBL-SCID mouse, but protection is lost if murine natural killer (NK) cells are depleted. Here we demonstrate that combined therapy with human GM-CSF and low-dose IL-2 is capable of preventing EBV-LPD in the hu-PBL-SCID mouse in the absence of murine NK cells. Lymphocyte depletion experiments showed that human NK cells, CD8(+) T cells, and monocytes were each required for the protective effects of GM-CSF and IL-2 combination therapy. This treatment resulted in a marked expansion of human CD3(+)CD8(+) lymphocytes in vivo. Using HLA tetramers complexed with EBV immunodominant peptides, a subset of these lymphocytes was found to be EBV-specific. These data establish that combined GM-CSF and low-dose IL-2 therapy can prevent the immune deficiencies that lead to fatal EBV-LPD in the hu-PBL-SCID mouse depleted of murine NK cells, and they point to a critical role for several human cellular subsets in mediating this protective effect. PMID:11560958

  7. GM-CSF and IL-2 induce specific cellular immunity and provide protection against Epstein-Barr virus lymphoproliferative disorder

    PubMed Central

    Baiocchi, Robert A.; Ward, Jacqueline S.; Carrodeguas, Lester; Eisenbeis, Charles F.; Peng, Ruoqi; Roychowdhury, Sameek; Vourganti, Srinivas; Sekula, Taryn; O’Brien, Maggie; Moeschberger, Melvin; Caligiuri, Michael A.

    2001-01-01

    Epstein-Barr virus–associated lymphoproliferative disease (EBV-LPD) is a potentially life-threatening complication in immune-deficient patients. We have used the severe combined immune deficient (SCID) mouse engrafted with human leukocytes (hu-PBL-SCID) to evaluate the use of human cytokines in the prevention of EBV-LPD in vivo. Daily low-dose IL-2 therapy can prevent EBV-LPD in the hu-PBL-SCID mouse, but protection is lost if murine natural killer (NK) cells are depleted. Here we demonstrate that combined therapy with human GM-CSF and low-dose IL-2 is capable of preventing EBV-LPD in the hu-PBL-SCID mouse in the absence of murine NK cells. Lymphocyte depletion experiments showed that human NK cells, CD8+ T cells, and monocytes were each required for the protective effects of GM-CSF and IL-2 combination therapy. This treatment resulted in a marked expansion of human CD3+CD8+ lymphocytes in vivo. Using HLA tetramers complexed with EBV immunodominant peptides, a subset of these lymphocytes was found to be EBV-specific. These data establish that combined GM-CSF and low-dose IL-2 therapy can prevent the immune deficiencies that lead to fatal EBV-LPD in the hu-PBL-SCID mouse depleted of murine NK cells, and they point to a critical role for several human cellular subsets in mediating this protective effect. PMID:11560958

  8. Transplant Problems That May Show Up Later

    MedlinePlus

    ... soon after transplant Next Topic Other transplant issues Transplant problems that may show up later The type ... called Second Cancers Caused by Cancer Treatment . Post-transplant lymphoproliferative disorder Post-transplant lymphoproliferative ( lim -fo-pruh- ...

  9. Epstein–Barr Virus-Positive T/NK-Cell Lymphoproliferative Disorders Manifested as Gastrointestinal Perforations and Skin Lesions

    PubMed Central

    Xiao, Hai-Juan; Li, Ji; Song, Hong-Mei; Li, Zheng-Hong; Dong, Mei; Zhou, Xiao-Ge

    2016-01-01

    Abstract Systemic Epstein–Barr virus (EBV)-positive T-cell lymphoproliferative disorders (LPDs) of childhood is a highly aggressive EBV-positive T/natural killer (NK)-cell LPD, which emerges in the background of chronic active EBV infection (CAEBV) or shortly after primary acute EBV infection. The clinical presentations of CAEBV are varied; patients with atypical manifestations are easily misdiagnosed. We described a 14-year-old boy suffering from digestive disorders and intermittent fever for 1 year and 9 months, whose conditions worsened and skin lesions occurred 2 months before hospitalization. He was diagnosed as inflammatory bowel diseases (IBD) and treated accordingly. His other clinical features, hepatosplenomegaly, lymphadenopathy, anemia, hypoalbuminemia, and elevated inflammatory marks, were found in hospitalization. The boy suffered from repeatedly spontaneous intestinal perforations shortly after hospitalization and died of intestinal hemorrhea. The pathological results of intestine and skin both showed EBV-positive T/NK-cell LPD (lymphoma stage). There are rare studies reporting gastrointestinal perforations in EBV-positive T/NK-cell LPD, let alone repeatedly spontaneous perforations. Based on the clinical features and pathological results of this patient, the disease progressed from CAEBV (T-cell type) to systemic EBV-positive T-cell LPD of childhood (lymphoma). Not all the patients with CAEBV could have unusual patterns of anti-EBV antibodies. However, the presence of high EBV loads (EBV-encoded early small ribonucleic acid (RNA) (EBER) in affected tissues and/or EBV deoxyribonucleic acid (DNA) in peripheral blood) is essential for diagnosing CAEBV. Maybe because of his less common clinical features for CAEBV and negative anti-EBV antibodies, the boy was not diagnosed correctly. We should have emphasized the test for EBER or EBV-DNA. Meanwhile, for the IBD patients whose manifestations were not typical, and whose conditions were not improved by suitable therapies against IBD, infectious and malignant diseases should be considered. PMID:26844502

  10. Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts.

    PubMed

    Loupy, Alexandre; Vernerey, Dewi; Tinel, Claire; Aubert, Olivier; Duong van Huyen, Jean-Paul; Rabant, Marion; Verine, Jrme; Nochy, Dominique; Empana, Jean-Philippe; Martinez, Frank; Glotz, Denis; Jouven, Xavier; Legendre, Christophe; Lefaucheur, Carmen

    2015-07-01

    Kidney allograft rejection can occur in clinically stable patients, but long-term significance is unknown. We determined whether early recognition of subclinical rejection has long-term consequences for kidney allograft survival in an observational prospective cohort study of 1307 consecutive nonselected patients who underwent ABO-compatible, complement-dependent cytotoxicity-negative crossmatch kidney transplantation in Paris (2000-2010). Participants underwent prospective screening biopsies at 1 year post-transplant, with concurrent evaluations of graft complement deposition and circulating anti-HLA antibodies. The main analysis included 1001 patients. Three distinct groups of patients were identified at the 1-year screening: 727 (73%) patients without rejection, 132 (13%) patients with subclinical T cell-mediated rejection (TCMR), and 142 (14%) patients with subclinical antibody-mediated rejection (ABMR). Patients with subclinical ABMR had the poorest graft survival at 8 years post-transplant (56%) compared with subclinical TCMR (88%) and nonrejection (90%) groups (P<0.001). In a multivariate Cox model, subclinical ABMR at 1 year was independently associated with a 3.5-fold increase in graft loss (95% confidence interval, 2.1 to 5.7) along with eGFR and proteinuria (P<0.001). Subclinical ABMR was associated with more rapid progression to transplant glomerulopathy. Of patients with subclinical TCMR at 1 year, only those who further developed de novo donor-specific antibodies and transplant glomerulopathy showed higher risk of graft loss compared with patients without rejection. Our findings suggest that subclinical TCMR and subclinical ABMR have distinct effects on long-term graft loss. Subclinical ABMR detected at the 1-year screening biopsy carries a prognostic value independent of initial donor-specific antibody status, previous immunologic events, current eGFR, and proteinuria. PMID:25556173

  11. Cryopreserved amniotic membrane as transplant allograft: viability and post-transplant outcome.

    PubMed

    Perepelkin, Natasha M J; Hayward, Kirsten; Mokoena, Tumelo; Bentley, Michael J; Ross-Rodriguez, Lisa U; Marquez-Curtis, Leah; McGann, Locksley E; Holovati, Jelena L; Elliott, Janet A W

    2016-03-01

    Amniotic membrane (AM) transplantation is increasingly used in ophthalmological and dermatological surgeries to promote re-epithelialization and wound healing. Biologically active cells in the epithelial and stromal layers deliver growth factors and cytokines with anti-inflammatory, anti-bacterial, anti-immunogenic and anti-fibrotic properties. In this work, confocal microscopy was used to show that our cryopreservation protocol for AM yielded viable cells in both the stromal and epithelial layers with favorable post-transplant outcome. AM was obtained from Caesarean-section placenta, processed into allograft pieces of different sizes (3 cm × 3 cm, 5 cm × 5 cm, and 10 cm × 10 cm) and cryopreserved in 10 % dimethyl sulfoxide using non-linear controlled rate freezing. Post-thaw cell viability in the entire piece of AM and in the stromal and epithelial cell layers was assessed using a dual fluorescent nuclear dye and compared to hypothermically stored AM, while surveys from surgical end-users provided information on post-transplant patient outcomes. There was no significant statistical difference in the cell viability in the entire piece, epithelial and stromal layers regardless of the size of allograft piece (p = 0.092, 0.188 and 0.581, respectively), and in the entire piece and stromal layer of hypothermically stored versus cryopreserved AM (p = 0.054 and 0.646, respectively). Surgical end-user feedback (n = 49) indicated that 16.3 % of AM allografts were excellent and 61.2 % were satisfactory. These results support the expanded clinical use of different sizes of cryopreserved AM allografts and address the issue of orientation of the AM during transplant for the treatment of dermatological defects and ocular surface disorders. PMID:26361949

  12. Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes.

    PubMed

    Shivaswamy, Vijay; Boerner, Brian; Larsen, Jennifer

    2016-02-01

    Post-transplant diabetes mellitus (PTDM) is a frequent consequence of solid organ transplantation. PTDM has been associated with greater mortality and increased infections in different transplant groups using different diagnostic criteria. An international consensus panel recommended a consistent set of guidelines in 2003 based on American Diabetes Association glucose criteria but did not exclude the immediate post-transplant hospitalization when many patients receive large doses of corticosteroids. Greater glucose monitoring during all hospitalizations has revealed significant glucose intolerance in the majority of recipients immediately after transplant. As a result, the international consensus panel reviewed its earlier guidelines and recommended delaying screening and diagnosis of PTDM until the recipient is on stable doses of immunosuppression after discharge from initial transplant hospitalization. The group cautioned that whereas hemoglobin A1C has been adopted as a diagnostic criterion by many, it is not reliable as the sole diabetes screening method during the first year after transplant. Risk factors for PTDM include many of the immunosuppressant medications themselves as well as those for type 2 diabetes. The provider managing diabetes and associated dyslipidemia and hypertension after transplant must be careful of the greater risk for drug-drug interactions and infections with immunosuppressant medications. Treatment goals and therapies must consider the greater risk for fluctuating and reduced kidney function, which can cause hypoglycemia. Research is actively focused on strategies to prevent PTDM, but until strategies are found, it is imperative that immunosuppression regimens are chosen based on their evidence to prolong graft survival, not to avoid PTDM. PMID:26650437

  13. Effects of nitrendipine on blood pressure and blood ciclosporin A level in patients with posttransplant hypertension.

    PubMed

    Copur, M S; Tasdemir, I; Turgan, C; Yasavul, U; Caglar, S

    1989-01-01

    In order to evaluate the antihypertensive effectiveness and interaction with ciclosporin A (CS-A) nitrendipine, a dihydropyridine derivative calcium entry blocking agent, was used in 16 (13 men, 3 women) hypertensive renal posttransplant patients followed by the Nephrology Department of Hacettepe University Hospital. The patients did not receive any antihypertensive drug for a 7-day period. They were then given 20 mg/day nitrendipine for 3 weeks. At the end of this period, mean (+/- SE) supine blood pressure fell from 163/108 +/- 3.6/1.87 to 141/87 +/- 3.8/2.2 mm Hg (p less than 0.01), while the heart rate was unchanged. 14 of 16 patients achieved full control of blood pressure levels with 20 mg/day nitrendipine, and only 2 patients needed a higher dosage of 30 mg/day (20 + 10 mg). After 3 weeks of treatment no significant variations in blood chemistry or renal functional parameters were noticed. There was also no difference between blood CS-A levels before and after treatment with nitrendipine (218.06 +/- 33 vs. 222.68 +/- 26 ng/ml, p greater than 0.05). We conclude that short-term therapy with nitrendipine in renal post-transplant patients does not appear to be harmful and longer term studies are needed to fully evaluate safety and efficacy of this drug. Because it influences neither blood chemistry nor renal functional parameters and blood CS-A level, it may be preferable to other calcium channel blocking agents in this group of patients. PMID:2662047

  14. Research update: Avian Disease and Oncology Laboratory avian tumor viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomics and Immunogenetics Marek’s disease (MD), a lymphoproliferative disease caused by the highly oncogenic herpesvirus Marek's disease virus (MDV), continues to be a major disease concern to the poultry industry. The fear of MD is further enhanced by unpredictable vaccine breaks that result in ...

  15. Marek's disease virus induced transient paralysis--a closer look

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s Disease (MD) is a lymphoproliferative disease of domestic chickens caused by a highly cell-associated alpha herpesvirus, Marek’s disease virus (MDV). Clinical signs of MD include depression, crippling, weight loss, and transient paralysis (TP). TP is a disease of the central nervous system...

  16. Unusual Indolent Course of a Chronic Active Epstein-Barr Virus-Associated Natural Killer Cell Lymphoproliferative Disorder

    PubMed Central

    Al-Riyami, Arwa Z.; Al-Farsi, Khalil; Al-Khabori, Murtadha; Al-Huneini, Mohammed; Al-Hadabbi, Ibrahim

    2016-01-01

    Natural killer (NK) cell lymphoproliferative disorders are uncommon and the Epstein-Barr virus (EBV) plays an important aetiological role in their pathogenesis. We report a 20-year-old male with a chronic active EBV infection associated with a NK cell lymphoproliferative disorder which had an unusual indolent course. He presented to the Sultan Qaboos University Hospital in Muscat, Oman, in December 2011 with a history of intermittent fever and coughing. Examinations revealed generalised lymphadenopathy, hepatosplenomegaly, leukocytosis, transaminitis, diffuse bilateral lung infiltrates and bone marrow lymphocyte involvement. A polymerase chain reaction (PCR) test revealed a high EBV viral load in the peripheral blood cells. The patient received a course of piperacillin-tazobactam for Klebsiella pneumoniae, but no active treatment for the lymphoproliferative disorder. However, his lymphocyte count, serum lactate dehydrogenase and liver enzymes dropped spontaneously. In addition, EBV PCR copies fluctuated and then decreased significantly. He remained clinically asymptomatic over the following four years. PMID:27226916

  17. Co-existence of acute myeloid leukemia with multilineage dysplasia and Epstein-Barr virus-associated T-cell lymphoproliferative disorder in a patient with rheumatoid arthritis: a case report

    PubMed Central

    Tokuhira, Michihide; Hanzawa, Kyoko; Watanabe, Reiko; Sekiguchi, Yasunobu; Nemoto, Tomoe; Toyozumi, Yasuo; Tamaru, Jun-ichi; Itoyama, Shinji; Suzuki, Katsuya; Kameda, Hideto; Mori, Shigehisa; Kizaki, Masahiro

    2009-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease mediated by inflammatory processes mainly at the joints. Recently, awareness of Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder (T-LPD) has been heightened for its association with methotraxate usage in RA patients. In the contrary, acute myeloid leukemia with multilineage dysplasia (AML-MLD) has never been documented to be present concomitantly with the above two conditions. In this report we present a case of an autopsy-proven co-existence of AML-MLD and EBV-associated T-LPD in a patient with RA. PMID:19566938

  18. OCTET-CY: a phase II study to investigate the efficacy of post-transplant cyclophosphamide as sole graft-versus-host prophylaxis after allogeneic peripheral blood stem cell transplantation

    PubMed Central

    Holtick, Udo; Chemnitz, Jens-Markus; Shimabukuro-Vornhagen, Alexander; Theurich, Sebastian; Chakupurakal, Geothy; Krause, Anke; Fiedler, Anne; Luznik, Leo; Hellmich, Martin; Wolf, Dominik; Hallek, Michael; von Bergwelt-Baildon, Michael; Scheid, Christof

    2016-01-01

    Objective Post-transplant cyclophosphamide is increasingly used as graft-versus-host disease (GvHD) prophylaxis in the setting of bone marrow transplantation. No data have been published on the use of single-agent GvHD prophylaxis with post-transplant cyclophosphamide in the setting of peripheral blood stem cell transplantation (PBSCT). Methods In a phase II trial, 11 patients with myeloma or lymphoma underwent conditioning with fludarabine and busulfan followed by T-replete PBSCT and application of 50 mg/kg/d of cyclophosphamide on day+3 and +4 without other concurrent immunosuppression (IS). Results Median time to leukocyte, neutrophil, and platelet engraftment was 18, 21, and 18 d. The incidence of grade II–IV and grade III–IV GvHD was 45% and 27%, with a non-relapse mortality (NRM) of 36% at one and 2 yr. After median follow-up of 927 d, overall and relapse-free survival was 64% and 34%. Three patients did not require any further systemic IS until day+100 and thereafter. Analysis of immune reconstitution demonstrated rapid T- and NK-cell recovery. B- and CD3+/CD161+NK/T-cell recovery was superior in patients not receiving additional IS. Conclusion Post-transplant cyclophosphamide as sole IS in PBSCT is feasible and allows rapid immune recovery. Increased rates of severe acute GvHD explain the observed NRM and may advise a temporary combination partner such as mTor-inhibitors in the PBSCT setting. PMID:25703164

  19. Genetic bases for Marek's disease resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek's disease (MD) is a highly contagious lymphoproliferative disease of chickens caused by MD virus (MDV). Therefore, the control of MD is of particular concern to the poultry industry. The poultry industry has been heavily relying on biosecurity and vaccination to control the spread and occurren...

  20. Pulmonary and retroperitoneal lesions induced by methotrexate-associated lymphoproliferative disorder in a patient with rheumatoid arthritis.

    PubMed

    Yamakawa, Hideaki; Yoshida, Masahiro; Katagi, Hiroaki; Hirooka, Shinichi; Okuda, Keitaro; Ishikawa, Takeo; Takagi, Masamichi; Kuwano, Kazuyoshi

    2016-05-01

    A 78-year-old man had fatigue and appetite loss for 5 months. He had been receiving low-dose methotrexate for rheumatoid arthritis. Computed tomography revealed multiple pulmonary infiltrations and muddiness of the fatty tissue surrounding the right kidney, ureter wall thickening, and hydroureter/nephrosis, which were suspected retroperitoneal fibrosis. Lung biopsy revealed polymorphic/lymphoplasmacytic lymphoproliferative disorder. Methotrexate withdrawal resulted in spontaneous regression. Therefore, retroperitoneal lesion may account for the diagnosis as having retroperitoneal lymphoproliferative disorder, not retroperitoneal fibrosis. PMID:24684409

  1. Chicks and SNPs--an entree into identifying genes conferring disease resistance in chicken

    Technology Transfer Automated Retrieval System (TEKTRAN)

    With high-density chicken rearing, control of infectious diseases are critical for economic viability and maintaining public confidence in poultry products. Among poultry diseases, Marek’s disease (MD), a lymphoproliferative disease caused by the highly oncogenic herpesvirus Marek's disease virus (M...

  2. Correlation between Mareks disease virus pathotype and replication

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mareks disease virus (MDV) is an alphaherpesvirus that causes Mareks disease (MD), a lymphoproliferative disease in chickens. Pathotyping has become an increasingly important assay for monitoring shifts in virulence of field strains, however, it is time-consuming and expensive and alternatives are...

  3. HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide after Busulfan-Containing Reduced-Intensity Conditioning.

    PubMed

    Sugita, Junichi; Kawashima, Naomi; Fujisaki, Tomoaki; Kakihana, Kazuhiko; Ota, Shuichi; Matsuo, Keitaro; Miyamoto, Toshihiro; Akashi, Koichi; Taniguchi, Shuichi; Harada, Mine; Teshima, Takanori

    2015-09-01

    Allogeneic hematopoietic stem cell transplantation (allo-SCT) using post-transplant cyclophosphamide (PTCy) is increasingly performed. We conducted a multicenter phase II study to evaluate the safety and efficacy of PTCy-based HLA-haploidentical peripheral blood stem cell transplantation (PTCy-haploPBSCT) after busulfan-containing reduced-intensity conditioning. Thirty-one patients were enrolled; 61% patients were not in remission and 42% patients had a history of prior allo-SCT. Neutrophil engraftment was achieved in 87% patients with a median of 19 days. The cumulative incidence of grades II to IV and III to IV acute graft-versus-host disease (GVHD) and chronic GVHD at 1 year were 23%, 3%, and 15%, respectively. No patients developed severe chronic GVHD. Day 100 nonrelapse mortality (NRM) rate was 19.4%. Overall survival, relapse, and disease-free survival rates were 45%, 45%, and 34%, respectively, at 1 year. Subgroup analysis showed that patients who had a history of prior allo-SCT had lower engraftment, higher NRM, and lower overall survival than those not receiving a prior allo-SCT. Our results suggest that PTCy-haploPBSCT after busulfan-containing reduced-intensity conditioning achieved low incidences of acute and chronic GVHD and NRM and stable donor engraftment and low NRM, particularly in patients without a history of prior allo-SCT. PMID:26093044

  4. Allosensitization does not alter post-transplant outcomes in pediatric patients bridged to transplant with a ventricular assist device.

    PubMed

    Castleberry, Chesney; Zafar, Farhan; Thomas, Tamara; Khan, Muhammad S; Bryant, Roosevelt; Chin, Clifford; Morales, David L S; Lorts, Angela

    2016-06-01

    Patients supported with a VAD are at increased risk for sensitization. We aimed to determine risk factors for sensitization as well as the impact of sensitization on post-transplant outcomes. The UNOS database (January 2004-June 2014) was used to identify patients (≤18 yrs) supported with a durable VAD. Rates and degree of sensitization in the VAD cohort were calculated. Post-transplant survival was determined comparing outcomes of sensitized vs. non-sensitized patients. There were 3097 patients included in the study; 19% (n = 579) were bridged with a VAD. Of these, 41.8% were sensitized vs. 29.9% of the patients who were not bridged with a VAD (p < 0.001). VAD was an independent predictor of sensitization (OR 2.05 [1.63-2.57]; p < 0.001). There was no difference in sensitization based on device type (continuous vs. pulsatile flow, p = 0.990). Post-transplant survival rates between the sensitized and non-sensitized VAD patients were not different, including patients with a PRA >50% and VAD patients with a positive DSC (p = 0.280 and 0.160, respectively). In conclusion, pediatric VAD patients are more likely to be sensitized, but there was no difference in sensitization based on device type. In addition, sensitization does not appear to impact outcomes. PMID:27102953

  5. 'A post-transplant person': Narratives of heart or lung transplantation and intensive care unit delirium.

    PubMed

    Flynn, Katy; Daiches, Anna; Malpus, Zoey; Yonan, Nizar; Sanchez, Melissa

    2014-07-01

    Exploring patients' narratives can lead to new understandings about perceived illness states. Intensive Care Unit delirium is when people experience transitory hallucinations, delusions or paranoia in the Intensive Care Unit and little is known about how this experience affects individuals who have had a heart or lung transplant. A total of 11 participants were recruited from two heart and lung transplant services and were invited to tell their story of transplant and Intensive Care Unit delirium. A narrative analysis was conducted and the findings were presented as a shared story. This shared story begins with death becoming prominent before the transplant: 'you live all the time with Mr Death on your shoulder'. Following the operation, death permeates all aspects of dream worlds, as dreams in intensive care 'tunes into the subconscious of your fears'. The next part of the shared story offers hope of restitution; however, this does not last as reality creeps in: 'I thought it was going to be like a miracle cure'. Finally, the restitution narrative is found to be insufficient and individuals differ in the extent to which they can achieve resolution. The societal discourse of a transplant being a 'gift', which gives life, leads to internalised responsibility for the 'success' or 'failure' of the transplant. Participants describe how their experiences impact their sense of self: 'a post-transplant person'. The clinical implications of these findings are discussed. PMID:24026357

  6. Prognostic and diagnostic value of procalcitonin in the post-transplant setting after liver transplantation

    PubMed Central

    Stirkat, Falk; Croner, Roland S.; Vassos, Nikolaos; Raptis, Dimitrios; Yedibela, Süleyman; Hohenberger, Werner; Müller, Volker

    2016-01-01

    Introduction The aim of the study was to assess the diagnostic accuracy of procalcitonin (PCT) as a marker for complications and as a prognostic factor for mortality after liver transplantation. Material and methods Liver transplant patients between January 2007 and April 2011 were prospectively included in the study. Procalcitonin serum concentration was recorded before, 6 h after reperfusion and then daily. Postoperative clinical course was prospectively analyzed from admission to discharge. Main surgical data such as operating procedure, type of reperfusion, operating and ischemic times, high urgency (HU) status and MELD score at the time of transplantation were also recorded. Results Sixteen patients with initial PCT > 5 ng/ml suffered ≥ 1 complication (p = 0.03). However, there was no association between the level of the 1st peak PCT and the further postoperative course or the occurrence of complications. Patients in whom a 2nd PCT peak occurred had a significantly higher risk for a complicated course, for a complicated sepsis course and for mortality (p < 0.0001). Warm ischemic time over 58 min, operating time over 389 min and HU status were significant independent factors for a complicated postoperative course (p < 0.001, p < 0.001 and p = 0.03 respectively). Conclusions Based on our results, we believe that PCT course and the occurrence of a 2nd peak seem to possess important diagnostic and prognostic power in the post-transplant setting after liver transplantation. PMID:27186183

  7. Post-transplant development of C1q-positive HLA antibodies and kidney graft survival.

    PubMed

    Piazza, Antonina; Poggi, Elvira; Ozzella, Giuseppina; Adorno, Domenico

    2013-01-01

    The development of de novo human leukocyte antigen (HLA) donor specific antibodies (DSA), detected by both cytotoxic or solid phase assays, was considered the major risk factor for allograft failure in kidney transplantation. However, it was shown that not all patients with persistent production of DSA suffered loss of their grafts. Modified Luminex-Single Antigen assays, able to identify C1q-fixing antibodies, represent a new strategy in assessing the clinical relevance of detected DSA. This study demonstrated that C1q-fixing capability of de novo DSA is a clinically relevant marker of worse outcome and inferior graft survival in kidney transplantation. In fact, our findings evidenced a very low graft survival only in the patients who developed DSA able to fix C1q during post-transplant course, while patients producing C1q-negative DSA had good graft survival, which was comparable to that found in our previous study for DSA-negative patients. Moreover, anti-HLA class II antibodies had a higher incidence than anti-HLA class I, and the ability to fix C1q was significantly more frequent among anti-DQ DSA than anti-DR DSA. Monitoring of de novo C1q-DSA production represents a useful, non-invasive tool for risk stratification and prediction of graft outcome in kidney transplantation. PMID:25095531

  8. Good outcome after liver transplantation for ALD without a 6 months abstinence rule prior to transplantation including post-transplant CDT monitoring for alcohol relapse assessment - a retrospective study.

    PubMed

    Kollmann, Dagmar; Rasoul-Rockenschaub, Susanne; Steiner, Irene; Freundorfer, Edith; Györi, Georg Philipp; Silberhumer, Gerd; Soliman, Thomas; Berlakovich, Gabriela Andrea

    2016-05-01

    Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT). The utility of fixed intervals of abstinence prior to listing is still a matter of discussion. Furthermore, post-LT long-term observation is challenging, and biomarkers as carbohydrate-deficient transferrin (CDT) may help to identify alcohol relapse. We retrospectively analyzed data from patients receiving LT for ALD from 1996 to 2012. A defined period of alcohol abstinence prior to listing was not a precondition, and abstinence was evaluated using structured psychological interviews. A total of 382 patients received LT for ALD as main (n = 290) or secondary (n = 92) indication; median follow-up was 73 months (0-213). One- and five-year patient survival and graft survival rates were 82% and 69%, and 80% and 67%, respectively. A total of 62 patients (16%) experienced alcohol relapse. Alcohol relapse did not have a statistically significant effect on patient survival (P = 0.10). Post-transplant CDT measurements showed a sensitivity and specificity of 84% and 85%, respectively. In conclusion, this large single-center analysis showed good post-transplant long-term results in patients with ALD when applying structured psychological interviews before listing. Relapse rates were lower than those reported in the literature despite using a strict definition of alcohol relapse. Furthermore, post-LT CDT measurement proved to be a useful supplementary tool for detecting alcohol relapse. PMID:26865285

  9. Lymphoproliferative response and T lymphocyte subsets in a medium-term multi-organ bioassay for carcinogenesis in Wistar rats.

    PubMed

    Spinardi-Barbisan, A L; Kaneno, R; Marchesan Rodrigues, M A; Fávero Salvadori, D M; Trindade Moreira, E L; Barbisan, L F; Viana de Camargo, J L

    2000-06-30

    The lymphoproliferative response and T lymphocyte subsets were evaluated at different stages of carcinogenesis in male Wistar rats sequentially initiated with N-diethylnitrosamine (DEN), N-butyl-N-4(hydroxybutyl)nitrosamine (BBN), N-methyl-N-nitrosourea (MNU), dihydroxy-di-N-propylnitrosamine (DHPN) and N, N'-dimethylhydrazine (DMH) (DMBDD initiation). One group was evaluated at the 4th week and other initiated group at the 30th week. Two initiated groups were also exposed through diet to 2-acetylaminofluorene (2-AAF) or phenobarbital (PB), from the 6th until the 30th week. Two groups received only 2-AAF or PB until the 30th week. Five groups were studied to evaluate the effects of each initiator. The lymphoproliferative response was induced in vitro by concanavalin A and the percentage of T lymphocyte subsets was determined by flow cytometry. All groups submitted to initiation only, initiation plus promotion, or promotion only, developed significantly more preneoplastic lesions than the untreated control group. The main target organs for tumor development were the liver, colon, urinary bladder, kidneys and Zymbal glands, mainly in the group treated with DMBDD+2-AAF. There were no alterations of the lymphoproliferative response and of the T lymphocyte subsets percentage in the DMBDD-treated group at the 4th and 30th weeks. At the 30th week, the T lymphocyte subsets percentage was also not affected in the initiated groups after treatments with 2-AAF or PB. The lymphoproliferative response, however, was decreased in the DMBDD+2-AAF group and in the groups treated only with 2-AAF or PB. The present results indicate that the initiating chemicals used in the DMBDD initiation protocol do not exert any influence on the immune system. The alteration of lymphoproliferative response induced at the advanced stage of carcinogenesis without alteration of T lymphocyte subsets may indicate that the influence of 2-AAF and PB on the immune system is functional and not toxic. PMID:10806299

  10. [Monoclonal antibodies of the IPO series in studying and diagnosing malignant lymphoproliferative diseases].

    PubMed

    Sidorenko, S P; Vetrova, E P; Iurchenko, O V; Shlapatskaia, L N; Berdova, A G; Elenskaia, A M; Bal'shin, M D; Gluzman, D F

    1990-04-01

    The authors have developed a panel of monoclonal antibodies (MCA) of IPO series (Institute of Problems of Oncology, Kiev). RPMI-1788 cell line, Daudi, as well as splenocytes of a patient with hairy-cell leukemia were used for immunization of mice. It has been shown that IPO-3, IPO-10 and IPO-24 MCA are directed against differentiation antigens of human B-lymphocytes. IPO-4 MCA reveal the antigen of activated T- and B-cells. IPO-5 and IPO-20 MCA recognize HLA-ABC, while IPO-37 a common leucocytic antigen. IPO-38 MCA are directed against the nuclear antigen. The possibilities of using IPO MCA in hematology have been discussed. PMID:2373343

  11. Surgical Management of Perforated Gastrointestinal Posttransplantation Lymphoproliferative Disorder After Heart Transplantation

    PubMed Central

    Osawa, Hideki; Uemura, Mamoru; Nishimura, Junichi; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Yamamoto, Hirofumi; Doki, Yuichiro; Mori, Masaki

    2015-01-01

    Posttransplantation lymphoproliferative disorder (PTLD) is a relatively rare and life-threatening complication after organ transplantation. From 1999 to 2012, 45 adult patients underwent heart transplantation at our hospital. Two of the patients developed PTLD after transplantation and required emergency surgery due to intestinal perforation. These cases were informative regarding the adequate surgical management of such cases. Both cases revealed Epstein-Barr virus-related PTLD. The optimal treatment of PTLD remains controversial, and PTLD with gastrointestinal perforation could be critical because the patients are already debilitated and immunocompromised after transplantation. Therefore, the nonspecific abdominal symptoms can be diagnostic for PTLD, and proper surgical intervention should be performed immediately. We present these two suggestive and rare cases in regard to the management of perforation with PTLD and a review of literature. PMID:25692442

  12. Temporal transcriptome changes induced by MDV in Marek's disease-resistant and -susceptible inbred chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mareks disease (MD) is a lymphoproliferative disease in chickens caused by Marek's disease virus (MDV) and characterized by T cell lymphoma and infiltration of lymphoid cells into various organs such as liver, spleen, peripheral nerves and muscle. Resistance to MD and disease risk have long been tho...

  13. Genome-wide identification of host genes directly regulated by Marek's disease virus (MDV) oncoprotein Meq

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek's disease (MD) is a contagious lymphoproliferative and neurotropic disease of poultry caused by the Marek's disease virus (MDV), an oncogenic alphaherpesvirus. Despite the use of vaccines, field strains of MDV continue to evolve resulting in unpredictable disease outbreaks. Therefore, understa...

  14. Posttransplant prophylactic intravenous immunoglobulin in kidney transplant patients at high immunological risk: a pilot study.

    PubMed

    Anglicheau, D; Loupy, A; Suberbielle, C; Zuber, J; Patey, N; Nol, L-H; Cavalcanti, R; Le Quintrec, M; Audat, F; Mjean, A; Martinez, F; Mamzer-Bruneel, M-F; Thervet, E; Legendre, C

    2007-05-01

    The effects of posttransplant prophylactic intravenous immunoglobulin (IVIg) were investigated in renal transplant recipients at high immunological risk. Thirty-eight deceased-donor kidney transplant recipients with previous positive complement-dependent cytotoxicity crossmatch (n=30), and/or donor-specific anti-HLA antibodies (n=14) were recruited. IVIg (2 g/kg) was administrated on days 0, 21, 42 and 63 with quadruple immunosuppression. Biopsy-proven acute cellular and humoral rejection rates at month 12 were 18% and 10%, respectively. Glomerulitis was observed in 31% and 60% of patients at months 3 and 12, respectively, while allograft glomerulopathy rose from 3% at month 3 to 28% at 12 months. Interstitial fibrosis/tubular atrophy increased from 18% at day 0 to 51% and 72% at months 3 and 12 (p<0.0001). GFR was 50 +/- 17 mL/min/1.73 m(2) and 48 +/- 17 mL/min/1.73 m(2) at 3 and 12 months. PRA decreased significantly after IVIg (class I: from 18 +/- 27% to 5 +/- 12%, p<0.01; class II: from 25 +/- 30% to 7 +/- 16%, p<0.001). Patient and graft survival were 97% and 95%, respectively and no graft was lost due to rejection (mean follow-up 25 months). In conclusion, prophylactic IVIg in high-immunological risk patients is associated with good one-year outcomes, with adequate GFR and a profound decrease in PRA level, but a significant increase in allograft nephropathy. PMID:17359509

  15. Association of Extrarenal Adverse Effects of Posttransplant Immunosuppression With Sex and ABCB1 Haplotypes

    PubMed Central

    Venuto, Rocco C.; Meaney, Calvin J.; Chang, Shirley; Leca, Nicolae; Consiglio, Joseph D.; Wilding, Gregory E.; Brazeau, Daniel; Gundroo, Aijaz; Nainani, Neha; Morse, Sarah E.; Cooper, Louise M.; Tornatore, Kathleen M.

    2015-01-01

    Abstract Extrarenal adverse effects (AEs) associated with calcineurin inhibitor (CNI) and mycophenolic acid (MPA) occur frequently but are unpredictable posttransplant complications. AEs may result from intracellular CNI accumulation and low activity of P-glycoprotein, encoded by the ABCB1 gene. Since ABCB1 single nucleotide polymorphisms (SNPs) and sex influence P-glycoprotein, we investigated haplotypes and extrarenal AEs. A prospective, cross-sectional study evaluated 149 patients receiving tacrolimus and enteric coated mycophenolate sodium or cyclosporine and mycophenolate mofetil. Immunosuppressive AE assessment determined individual and composite gastrointestinal, neurologic, aesthetic, and cumulative AEs. Lipids were quantitated after 12-hour fast. ABCB1 SNPs: c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642) were determined with haplotype associations computed using the THESIAS program, and evaluated by immunosuppression, sex and race using multivariate general linear models. Tacrolimus patients exhibited more frequent and higher gastrointestinal AE scores compared with cyclosporine with association to CTT (P = 0.018) and sex (P = 0.01). Aesthetic AE score was 3 times greater for cyclosporine with TTC haplotype (P = 0.005). Females had higher gastrointestinal (P = 0.022), aesthetic (P < 0.001), neurologic (P = 0.022), and cumulative AE ratios (P < 0.001). Total cholesterol (TCHOL), low-density lipoproteins (LDL), and triglycerides were higher with cyclosporine. The TTC haplotype had higher TCHOL (P < 0.001) and LDL (P = 0.005). Higher triglyceride (P = 0.034) and lower high-density lipoproteins (P = 0.057) were associated with TTT with sex-adjusted analysis. ABCB1 haplotypes and sex were associated with extrarenal AEs. Using haplotypes, certain female patients manifested more AEs regardless of CNI. Haplotype testing may identify patients with greater susceptibility to AEs and facilitate CNI individualization. PMID:26376376

  16. Association of Extrarenal Adverse Effects of Posttransplant Immunosuppression With Sex and ABCB1 Haplotypes.

    PubMed

    Venuto, Rocco C; Meaney, Calvin J; Chang, Shirley; Leca, Nicolae; Consiglio, Joseph D; Wilding, Gregory E; Brazeau, Daniel; Gundroo, Aijaz; Nainani, Neha; Morse, Sarah E; Cooper, Louise M; Tornatore, Kathleen M

    2015-09-01

    Extrarenal adverse effects (AEs) associated with calcineurin inhibitor (CNI) and mycophenolic acid (MPA) occur frequently but are unpredictable posttransplant complications. AEs may result from intracellular CNI accumulation and low activity of P-glycoprotein, encoded by the ABCB1 gene. Since ABCB1 single nucleotide polymorphisms (SNPs) and sex influence P-glycoprotein, we investigated haplotypes and extrarenal AEs. A prospective, cross-sectional study evaluated 149 patients receiving tacrolimus and enteric coated mycophenolate sodium or cyclosporine and mycophenolate mofetil. Immunosuppressive AE assessment determined individual and composite gastrointestinal, neurologic, aesthetic, and cumulative AEs. Lipids were quantitated after 12-hour fast. ABCB1 SNPs: c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642) were determined with haplotype associations computed using the THESIAS program, and evaluated by immunosuppression, sex and race using multivariate general linear models. Tacrolimus patients exhibited more frequent and higher gastrointestinal AE scores compared with cyclosporine with association to CTT (P = 0.018) and sex (P = 0.01). Aesthetic AE score was 3 times greater for cyclosporine with TTC haplotype (P = 0.005). Females had higher gastrointestinal (P = 0.022), aesthetic (P < 0.001), neurologic (P = 0.022), and cumulative AE ratios (P < 0.001). Total cholesterol (TCHOL), low-density lipoproteins (LDL), and triglycerides were higher with cyclosporine. The TTC haplotype had higher TCHOL (P < 0.001) and LDL (P = 0.005). Higher triglyceride (P = 0.034) and lower high-density lipoproteins (P = 0.057) were associated with TTT with sex-adjusted analysis. ABCB1 haplotypes and sex were associated with extrarenal AEs. Using haplotypes, certain female patients manifested more AEs regardless of CNI. Haplotype testing may identify patients with greater susceptibility to AEs and facilitate CNI individualization. PMID:26376376

  17. Lipoprotein metabolism differs between Marek's disease susceptible and resistant chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of chickens caused by MD virus and has an important impact on the poultry industry worldwide.There have been reports showing different physiological characteristics between MD susceptible and resistant chickens. However, little is known about whe...

  18. Influence of Marek’s disease virus on the core-gut microbiome of chickens resistant or susceptible to Marek’s disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease virus (MDV) is an a-herpesvirus and the causative agent for the lymphoproliferative disease of chickens known as Marek’s disease (MD). Worldwide poultry industry losses due to MD amount to $1-2 billion per year. Presently, there is limited knowledge on the potential influence of MDV ...

  19. Genome-wide identification of host genes directly regulated by Marek’s disease virus (MDV) oncoprotein Meq

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek's disease (MD) is a contagious lymphoproliferative and neurotropic disease of poultry caused by Marek's disease virus (MDV), an oncogenic alphaherpesvirus. Despite the use of vaccines, the field strains of MDV continue to evolve, resulting in unpredictable disease outbreaks. Therefore, underst...

  20. Mortality of one-week-old chickens during naturally occurring Marek's disease virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a serious economic disease of chickens which occurs worldwide. MD can present as one of several forms, with the most commonly occurring forms being the lymphoproliferative diseases. Under experimental conditions, an early mortality syndrome has been recognized following infec...

  1. Identification of Marek's disease virus genes mutated during serial passage-induced attenuation.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of chickens caused by gallid herpesvirus type 2 (GaHV-2). The disease is controlled through mass vaccination with live-attenuated strains. Attenuation of oncogenic GaHV-2 involves the serial passage of a virulent field isolate in avian embryo fib...

  2. Transcriptional profiling of chicken gene expression during cytolytic infection of Marek's disease virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD), a lymphoproliferative disease of chicken is caused by a highly cell-associated alpha-herpesvirus, Marek’s disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latent infection within CD4+ T cells. The expression analysis of limited viral and host transc...

  3. Marek's Disease Virus-Induced Immunosuppression: Array Analysis of Chicken Immune Response Gene Expression Profiling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of chickens induced by a highly cell-associated oncogenic alpha-herpesvirus, Marek’s disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latency infection within CD4+ T cells. Host-virus interaction, immune responses to...

  4. Non-MHC genomic variation affecting Marek’s disease resistance and vaccine protective efficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of the domestic chicken caused by a highly infectious, oncogenic herpesvirus commonly referred to as Marek’s disease virus (MDV). MD has been controlled by vaccination with non-oncogenic turkey herpesvirus (HVT), non-oncogenic chicken herpesvirus...

  5. Dynamic equilibrium of Marek’s disease genomes during in vitro serial passage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of chickens caused by gallid herpesvirus type 2 (GaHV-2). The disease is controlled through mass vaccination with live-attenuated strains. Attenuation of oncogenic GaHV-2 involves the serial passage of a virulent field isolate in avian embryo fib...

  6. Aggressive EBV-associated lymphoproliferative disorder: a prodrome to diffuse large B-cell lymphoma?

    PubMed

    Batra, Rashmi; Medeiros, Bruno C; Zehnder, James L; Warnke, Roger A; Natkunam, Yasodha

    2012-05-01

    A 19-year-old male patient presented with intermittent high fever and left cervical lymphadenopathy. The lymph node biopsy findings were interpreted as "Epstein-Barr virus (EBV)-associated lymphoproliferative disorder consistent with infectious mononucleosis." No molecular studies were performed at that time. The patient was followed without treatment. Five months later, the patient again presented with fever, lymphadenopathy, and splenomegaly. The lymph node biopsy showed features of a diffuse large B-cell lymphoma. Molecular studies on this lymph node biopsy showed a clonal EBV population, although polymerase chain reaction studies failed to reveal a clonal B-cell or T-cell population. A concurrent bone marrow biopsy showed features consistent with hemophagocytic syndrome. He had elevated ferritin, soluble interleukin-2 receptors and persistent EBV viremia. The patient responded to Rituxan for a short period with undetectable EBV levels. Subsequent right cervical lymph node, liver, and jejunal biopsies showed involvement by diffuse large B-cell lymphoma and the patient expired soon thereafter. PMID:22505014

  7. Post-transplantation lymphoproliferative disorders arising in solid organ transplant recipients are usually of recipient origin.

    PubMed Central

    Chadburn, A.; Suciu-Foca, N.; Cesarman, E.; Reed, E.; Michler, R. E.; Knowles, D. M.

    1995-01-01

    Recent clinical, pathological, and molecular studies have increased our understanding of posttransplantation lymphoproliferative disorders (PT-LPDs). Studies have shown that the majority of PT-LPDs arising in bone marrow transplant recipients are of donor origin; however, the source (host or donor) of the lymphoid cells that make up PT-LPDs arising in solid organ transplant recipients has not been systemically investigated. In this study, 18 PT-LPDs occurring in 16 organ transplant recipients (13 heart, 2 kidney, 1 lung), 9 donor tissues (for 10 recipients), and 14 uninvolved recipient tissues (from 12 patients) were examined employing restriction fragment length polymorphism analysis to determine their host or donor origin. The PstI-digested DNAs were analyzed by Southern blot hybridization using two highly informative polymorphic probes that map to chromosome 21 (CRI-PAT-pL427-4) and chromosome 7 (CRI-PAT-pS194). All solid organ PT-LPDs with corresponding uninvolved recipient DNA showed identical hybridization patterns; none of the PT-LPDs exhibited a hybridization pattern that matched donor DNA. These findings suggest that the vast majority of PT-LPDs arising in solid organ transplant recipients, in contrast to those arising in bone marrow transplant recipients, are of recipient origin. Images Figure 1 PMID:7495309

  8. FAS Haploinsufficiency Caused by Extracellular Missense Mutations Underlying Autoimmune Lymphoproliferative Syndrome.

    PubMed

    de Bielke, Mara Gabriela Simesen; Perez, Laura; Yancoski, Judith; Oliveira, Joo Bosco; Danielian, Silvia

    2015-11-01

    Mutations in the FAS gene are the most common cause of Autoimmune Lymphoproliferative Syndrome (ALPS), and the majority of them affect the intracellular domain of FAS protein, particularly the region termed death domain. However, approximately one third of these mutations affect the extracellular region of FAS and most are stop codons, with very few missense changes having been described to date. We previously described 7 patients with a FAS missense extracellular mutation, C107Y, two in homozygozity and 5 in heterozygosity. We investigated here the mechanistic effects of this mutation and observed that the homozygous patients did not show any FAS surface expression, while the heterozygous patients had diminished receptor expression. Aiming to understand why a missense mutation was abolishing receptor expression, we analyzed intracellular FAS protein trafficking using fluorescent fusion proteins of wild type FAS, two missense extracellular mutants (FAS-C107Y and FAS-C104Y) and one missense change localized in the intracellular region, FAS-D260E. The FAS-C107Y and FAS-C104Y mutants failed to reach the cell surface, being retained at the endoplasmic reticulum, unlike the WT or the FAS-D260E which were clearly expressed at the plasma membrane. These results support haploinsufficiency as the underlying mechanism involved in the pathogenesis of ALPS caused by extracellular FAS missense mutations. PMID:26563159

  9. Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations

    PubMed Central

    Price, Susan; Shaw, Pamela A.; Seitz, Amy; Joshi, Gyan; Davis, Joie; Niemela, Julie E.; Perkins, Katie; Hornung, Ronald L.; Folio, Les; Rosenberg, Philip S.; Puck, Jennifer M.; Hsu, Amy P.; Lo, Bernice; Pittaluga, Stefania; Jaffe, Elaine S.; Fleisher, Thomas A.; Lenardo, Michael J.

    2014-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) presents in childhood with nonmalignant lymphadenopathy and splenomegaly associated with a characteristic expansion of mature CD4 and CD8 negative or double negative T-cell receptor αβ+ T lymphocytes. Patients often present with chronic multilineage cytopenias due to autoimmune peripheral destruction and/or splenic sequestration of blood cells and have an increased risk of B-cell lymphoma. Deleterious heterozygous mutations in the FAS gene are the most common cause of this condition, which is termed ALPS-FAS. We report the natural history and pathophysiology of 150 ALPS-FAS patients and 63 healthy mutation-positive relatives evaluated in our institution over the last 2 decades. Our principal findings are that FAS mutations have a clinical penetrance of <60%, elevated serum vitamin B12 is a reliable and accurate biomarker of ALPS-FAS, and the major causes of morbidity and mortality in these patients are the overwhelming postsplenectomy sepsis and development of lymphoma. With longer follow-up, we observed a significantly greater relative risk of lymphoma than previously reported. Avoiding splenectomy while controlling hypersplenism by using corticosteroid-sparing treatments improves the outcome in ALPS-FAS patients. This trial was registered at www.clinicaltrials.gov as #NCT00001350. PMID:24398331

  10. SIGLEC-G deficiency increases susceptibility to develop B-cell lymphoproliferative disorders

    PubMed Central

    Simonetti, Giorgia; Bertilaccio, Maria Teresa Sabrina; Rodriguez, Tania Veliz; Apollonio, Benedetta; Dagklis, Antonis; Rocchi, Martina; Innocenzi, Anna; Casola, Stefano; Winkler, Thomas H.; Nitschke, Lars; Ponzoni, Maurilio; Caligaris-Cappio, Federico; Ghia, Paolo

    2014-01-01

    The sialic-acid-binding immunoglobulin-like lectin SIGLEC-G is a negative regulator of B-cell receptor-mediated calcium signaling. Its deficiency leads to reduced turnover and increased proliferation and survival of murine B-1a cells. Siglecg−/− mice show a premature expansion of polyclonal CD5+ B cells in the spleen and the peritoneal cavity. Here we studied the fate of B lymphocytes in Siglecg−/− mice over time. We demonstrate that in aging animals SIGLEC-G deficiency promotes progressive accumulation of monoclonal B lymphocytes and increases the susceptibility to develop B-cell lymphoproliferative disorders. Lymphoid tumors arising in aged Siglecg−/− mice are monoclonal and histologically heterogeneous as they include diffuse large B-cell lymphoma, follicular lymphoma, and medium-to-large B-cell monomorphic lymphoma but surprisingly not chronic lymphocytic leukemia. The tumors express high levels of BCL-2 and are transplantable. In keeping with these findings we have also observed a remarkable down-regulation of the human ortholog SIGLEC10 in human B-cell lymphoma and leukemia cell lines. Taken together, these observations indicate that the down-regulation of negative B-cell receptor regulators such as SIGLEC-G/SIGLEC10 may represent another mechanism relevant to the pathogenesis of B-cell lymphomas. PMID:24859880

  11. Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations.

    PubMed

    Price, Susan; Shaw, Pamela A; Seitz, Amy; Joshi, Gyan; Davis, Joie; Niemela, Julie E; Perkins, Katie; Hornung, Ronald L; Folio, Les; Rosenberg, Philip S; Puck, Jennifer M; Hsu, Amy P; Lo, Bernice; Pittaluga, Stefania; Jaffe, Elaine S; Fleisher, Thomas A; Rao, V Koneti; Lenardo, Michael J

    2014-03-27

    Autoimmune lymphoproliferative syndrome (ALPS) presents in childhood with nonmalignant lymphadenopathy and splenomegaly associated with a characteristic expansion of mature CD4 and CD8 negative or double negative T-cell receptor αβ(+) T lymphocytes. Patients often present with chronic multilineage cytopenias due to autoimmune peripheral destruction and/or splenic sequestration of blood cells and have an increased risk of B-cell lymphoma. Deleterious heterozygous mutations in the FAS gene are the most common cause of this condition, which is termed ALPS-FAS. We report the natural history and pathophysiology of 150 ALPS-FAS patients and 63 healthy mutation-positive relatives evaluated in our institution over the last 2 decades. Our principal findings are that FAS mutations have a clinical penetrance of <60%, elevated serum vitamin B12 is a reliable and accurate biomarker of ALPS-FAS, and the major causes of morbidity and mortality in these patients are the overwhelming postsplenectomy sepsis and development of lymphoma. With longer follow-up, we observed a significantly greater relative risk of lymphoma than previously reported. Avoiding splenectomy while controlling hypersplenism by using corticosteroid-sparing treatments improves the outcome in ALPS-FAS patients. This trial was registered at www.clinicaltrials.gov as #NCT00001350. PMID:24398331

  12. Endocrine and lymphoproliferative response changes produced by social stress in mice.

    PubMed

    Cacho, R; Fano, E; Areso, P; Garmendia, L; Vegas, O; Brain, P F; Azpíroz, A

    2003-03-01

    Daily dyadic resident-intruder encounters and uninterrupted cohabitation in pairs were used to assess the impact of different durations (5 and 15 days) of dominance and subordination experiences on splenic lymphoproliferative responses in male OF1 strain mice. HPA axis activity was assessed by measuring serum corticosterone levels, whereas splenic norepinephrine (NE) content provided a sympathetic activity index. Corticosterone levels in subordinate subjects were generally higher than in their control or dominant counterparts in both treatment paradigms. Corticosterone levels in dominant subjects were lower than in their control counterparts in both. Increasing the duration of treatments generally decreased such titers, especially so in subordinate subjects. No differences were detected in splenic NE content. Animals subjected to social interaction generally showed greater proliferation than their control counterparts. This effect was more pronounced in subordinates than dominants and after longer- rather than short-duration treatments. There was no inverse relation between proliferative responses and the subject's corticosterone levels. While corticosterone may have a general immunomodulating effect, other mediators apparently account for the effects produced by these social stress paradigms on splenic proliferative response. PMID:12676288

  13. KU HAPLOINSUFFIENCY CAUSES A LYMPHOPROLIFERATIVE DISORDER OF IMMATURE T-CELL PRECURSORS DUE TO IKAROS MALFUNCTION

    PubMed Central

    Ozer, Zahide; Qazi, Sanjive; Ishkhanian, Rita; Hasty, Paul; Ma, Hong; Uckun, Fatih M.

    2013-01-01

    Ikaros (IK) malfunction has been implicated in the pathogenesis of acute lymphoblastic leukemia (ALL), the most common form of childhood cancer. Therefore, a stringent regulation of IK activity is very important. Here we provide unique genetic and biochemical evidence that the Ku protein components Ku70 and Ku80 act as positive regulators of IK function via formation of IK-Ku70 and IK-Ku80 heterodimers with augmented sequence-specific DNA binding activity. siRNA-mediated depletion of Ku70 or Ku80 reduced the sequence-specific DNA binding activity of IK in EMSA as well as the RT-PCR measured IK target gene expression levels in human cells. The interaction of Ku components with IK likely contributes to the anti-leukemic effects of IK as a tumor suppressor, because Ku70 as well as Ku80 haploinsuffiency in mice caused development of a lymphoproliferative disorder (LPD) involving CD2+CD4+CD8+CD1+IL7R+ thymic T-cell precursors with functional IK deficiency. PMID:24478815

  14. Anemia treatment of lymphoproliferative malignancies with erypoiesis: an overview of state of the art.

    PubMed

    Cacic, Daniel Limi; Hervig, Tor; Seghatchian, Jerard

    2013-04-01

    Anemia is a common comorbidity of lymphoproliferative malignancies, especially in multiple myeloma. Blood transfusions and ESAs (erythropoiesis stimulating agents) are both possible treatment options, but the latter is often preferred because of the potential risks of unwanted side effects related to blood transfusions. Evidence is accumulating that the use of ESAs in above clinical conditions is safe and effective and not associated with an increase in mortality or serious adverse events. 69.1% of patients achieved a hemoglobin response defined as an increase in hemoglobin of>2g/dl while receiving ESAs and concomitant chemotherapy. If supplemented with iron the hemoglobin response rate can be increased and hence the total dosage and financial cost reduced. A hemoglobin response is often accompanied by an increase in quality of life. HYPO% (hypochromic erythrocytes<5%) is believed to be both a significant positive predictor for the Hb response and also an indicator for iron supplementation if?5%. Conventional biochemical markers like serum ferritin concentration and transferrin saturation are not reliable for this use. The effect of EPO stimulating agents as the predictor of the Hb response, quality of life, mortality and the potential adverse events are discussed. PMID:23465378

  15. Castleman's Disease Presenting as Localized Abdominal Mass and Paraneoplastic Pemphigus

    PubMed Central

    Kumar, Santosh; Bishnoi, Kshitij; Murugavaithianathan, Pragatheeswarane; Panwar, Vikas Kumar

    2016-01-01

    Castleman's disease is a rare, benign lymphoproliferative disorder of unknown origin. Paraneoplastic pemphigus is a common association which presents as oral mucosal ulcerations. Abdominal and retroperitoneal Castleman's disease present either as a localized disease or as a systemic disease. We hereby present a 15-year-old male patient with oral mucosal lesions with localized vague right lower abdominal mass who was diagnosed to have Castleman's disease with paraneoplastic pemphigus which was surgically excised. PMID:27014502

  16. Epstein-Barr Virus-Positive T/NK-Cell Lymphoproliferative Disorders Manifested as Gastrointestinal Perforations and Skin Lesions: A Case Report.

    PubMed

    Xiao, Hai-Juan; Li, Ji; Song, Hong-Mei; Li, Zheng-Hong; Dong, Mei; Zhou, Xiao-Ge

    2016-02-01

    Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorders (LPDs) of childhood is a highly aggressive EBV-positive T/natural killer (NK)-cell LPD, which emerges in the background of chronic active EBV infection (CAEBV) or shortly after primary acute EBV infection. The clinical presentations of CAEBV are varied; patients with atypical manifestations are easily misdiagnosed. We described a 14-year-old boy suffering from digestive disorders and intermittent fever for 1 year and 9 months, whose conditions worsened and skin lesions occurred 2 months before hospitalization. He was diagnosed as inflammatory bowel diseases (IBD) and treated accordingly. His other clinical features, hepatosplenomegaly, lymphadenopathy, anemia, hypoalbuminemia, and elevated inflammatory marks, were found in hospitalization. The boy suffered from repeatedly spontaneous intestinal perforations shortly after hospitalization and died of intestinal hemorrhea. The pathological results of intestine and skin both showed EBV-positive T/NK-cell LPD (lymphoma stage).There are rare studies reporting gastrointestinal perforations in EBV-positive T/NK-cell LPD, let alone repeatedly spontaneous perforations. Based on the clinical features and pathological results of this patient, the disease progressed from CAEBV (T-cell type) to systemic EBV-positive T-cell LPD of childhood (lymphoma). Not all the patients with CAEBV could have unusual patterns of anti-EBV antibodies. However, the presence of high EBV loads (EBV-encoded early small ribonucleic acid (RNA) (EBER) in affected tissues and/or EBV deoxyribonucleic acid (DNA) in peripheral blood) is essential for diagnosing CAEBV. Maybe because of his less common clinical features for CAEBV and negative anti-EBV antibodies, the boy was not diagnosed correctly. We should have emphasized the test for EBER or EBV-DNA. Meanwhile, for the IBD patients whose manifestations were not typical, and whose conditions were not improved by suitable therapies against IBD, infectious and malignant diseases should be considered. PMID:26844502

  17. Genome-wide Copy Number Variation and Temporal Genes Expression Analysis in Marek's Disease-Resistant or -Susceptible Inbred Lines of Chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Viruses that cause cancers are a great threat to human and animal health. Marek’s disease (MD) in chickens is a lymphoproliferative disease caused by Marek’s disease virus (MDV). The over-expression of Hodgkin’s disease antigen in MD makes it an ideal model to study the progression mechanism of Hodg...

  18. Usefullness of IGH/TCR PCR studies in lymphoproliferative disorders with inconclusive clonality by flow cytometry.

    PubMed

    Ribera, Jordi; Zamora, Lurdes; Juncà, Jordi; Rodríguez, Inés; Marcé, Silvia; Cabezón, Marta; Millá, Fuensanta

    2013-07-25

    In up to 5-15% of studies of lymphoproliferative disorders (LPD) flow cytometry (FCM) or immunomorphologic methods cannot discriminate malignant from reactive processes. The aim of this work was to determine the usefulness of PCR for solving these diagnostic uncertainties. We analyzed IGH and TCRγ genes by PCR in 106 samples with inconclusive FCM results. A clonal result was registered in 36/106 studies, with a LPD being confirmed in 27 (75%) of these cases. Specifically, 9/9 IGH clonal and 16/25 TCRγ clonal results were finally diagnosed with LPD. Additionally, 2 clonal TCRγ samples with suspicion of undefined LPD were finally diagnosed with T LPD. Although polyclonal results were obtained in 47 of the cases studied (38 IGH and 9 TCRγ), hematologic neoplasms were diagnosed in 4/38 IGH polyclonal and in 1/9 TCRγ polyclonal studies. There were also 14 PCR polyclonal results (4 IGH, 10 TCRγ), albeit non-conclusive. Of these, 2/4 were eventually diagnosed with B-cell lymphoma and 3/10 with T-cell LPD. In 8 IGH samples the results of PCR techniques were non-informative but in 3/8 cases a B lymphoma was finally confirmed. We concluded that PCR is a useful technique to identify LPD when FCM is inconclusive. A PCR clonal B result is indicative of malignancy but IGH polyclonal and non-conclusive results do not exclude lymphoid neoplasms. Interpretation of T-cell clonality should be based on all the available clinical and analytical data. © 2013 Clinical Cytometry Society. PMID:23894019

  19. Usefulness of IGH/TCR PCR studies in lymphoproliferative disorders with inconclusive clonality by flow cytometry.

    PubMed

    Ribera, Jordi; Zamora, Lurdes; Juncà, Jordi; Rodríguez, Inés; Marcé, Silvia; Cabezón, Marta; Millá, Fuensanta

    2014-01-01

    In up to 5-15% of studies of lymphoproliferative disorders (LPD), flow cytometry (FCM) or immunomorphologic methods cannot discriminate malignant from reactive processes. The aim of this work was to determine the usefulness of PCR for solving these diagnostic uncertainties. We analyzed IGH and TCRγ genes by PCR in 106 samples with inconclusive FCM results. A clonal result was registered in 36/106 studies, with a LPD being confirmed in 27 (75%) of these cases. Specifically, 9/9 IGH clonal and 16/25 TCRγ clonal results were finally diagnosed with LPD. Additionally, two clonal TCRγ samples with suspicion of undefined LPD were finally diagnosed with T LPD. Although polyclonal results were obtained in 47 of the cases studied (38 IGH and nine TCRγ), hematologic neoplasms were diagnosed in 4/38 IGH polyclonal and in 1/9 TCRγ polyclonal studies. There were also 14 PCR polyclonal results (four IGH, 10 TCRγ), albeit nonconclusive. Of these, 2/4 were eventually diagnosed with B-cell lymphoma and 3/10 with T-cell LPD. In eight IGH samples, the results of PCR techniques were noninformative but in 3/8 cases a B lymphoma was finally confirmed. We concluded that PCR is a useful technique to identify LPD when FCM is inconclusive. A PCR clonal B result is indicative of malignancy but IGH polyclonal and nonconclusive results do not exclude lymphoid neoplasms. Interpretation of T-cell clonality should be based on all the available clinical and analytical data. PMID:23943305

  20. Detection of cyclin D1 in B cell lymphoproliferative disorders by flow cytometry

    PubMed Central

    Jain, P; Giustolisi, G M; Atkinson, S; Elnenaei, M O; Morilla, R; Owusu-Ankomah, K; Rafiq-Mohammed, F; Matutes, E; Wotherspoon, A; Catovsky, D

    2002-01-01

    Aims: To describe and revise a flow cytometric assay for evaluating cyclin D1 overexpression in B cell lymphoproliferative disorders (B-LPDs). Methods: Cyclin D1 expression was evaluated in 11 healthy controls and 51 patients with B-LPD by flow cytometry using the 5D4 monoclonal antibody. In 25 cases, experiments were repeated up to four times with mononuclear cells (MNC) fixed in ethanol for 1–120 days to evaluate the consistency of cyclin D1 expression. Flow cytometry results were compared with fluorescence in situ hybridisation (FISH) for the t(11;14) translocation in 19 patients and with immunohistochemistry (IHC) using the DCS-6 monoclonal antibody in nine patients. Results: A mean fluorescence intensity ratio (MFIR) of 4.8 was defined as the cut off point for positivity based on cyclin D1 expression in healthy controls (mean + 3 SD). Ten patients overexpressed cyclin D1 by flow cytometry. These included five of eight patients with mantle cell lymphoma, four of 19 with chronic lymphocytic leukaemia, and one with follicular lymphoma. MFIR in the repeat experiments differed less than 25% in 20 of 25 patients and in no cases did it cross the cut off point. There was a good correlation between cyclin D1 expression by flow cytometry and FISH for t(11;14) in 15 of 19 patients and six of nine had concordant results with flow cytometry, FISH, and IHC. Conclusion: Cyclin D1 expression remains fairly stable once MNC are fixed in ethanol and the flow cytometric assay can be used for the routine screening of B-LPD. Further comparisons between flow cytometry, IHC, and FISH may be needed to ascertain the diagnostic value of the flow cytometric assay. PMID:12461064

  1. The genomes of Marek’s disease virus exist as quasispecies at defined intervals during serial passage-induced attenuation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of chickens caused by gallid herpesvirus type 2 (GaHV-2). The disease is controlled through mass vaccination with live-attenuated strains. Attenuation of oncogenic GaHV-2 involves the serial passage of a virulent field isolate in avian embryo fib...

  2. Characterizing the molecular basis of attenuation of Marek’s disease virus via in vitro serial passage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of chickens caused by the oncogenic Gallid herpesvirus 2, commonly known as Marek’s disease virus (MDV). MD vaccines, the primary control method, are often generated by repeated in vitro serial passage of this highly cell-associated virus to atte...

  3. High Serum Level of β2-Microglobulin in Late Posttransplant Period Predicts Subsequent Decline in Kidney Allograft Function: A Preliminary Study

    PubMed Central

    Trailin, Andriy V.; Pleten, Marina V.; Ostapenko, Tatiana I.; Iefimenko, Nadiia F.; Nikonenko, Olexander S.

    2015-01-01

    Background. Identification of patients at risk for kidney allograft (KAG) failure beyond the first posttransplant year is an unmet need. We aimed to determine whether serum beta-2-microglobulin (β2MG) in the late posttransplant period could predict a decline in KAG function. Methods. We assessed a value of single measurement of serum β2MG at one to seventeen years after transplantation in predicting the estimated glomerular filtration rate (eGFR) and the decline in eGFR over a period of two years in 79 recipients of KAG. Results. At baseline serum β2MG concentration was higher (P = 0.011) in patients with allograft dysfunction: 8.67 ± 2.48 µg/mL versus those with satisfactory graft function: 6.67 ± 2.13 µg/mL. Higher β2MG independently predicted the lower eGFR, the drop in eGFR by ≥25% after one and two years, and the value of negative eGFR slope. When combined with proteinuria and acute rejection, serum β2MG had excellent power in predicting certain drop in eGFR after one year (AUC = 0.910). In conjunction with posttransplant time serum β2MG had good accuracy in predicting certain eGFR drop after two years (AUC = 0.821). Conclusions. Elevated serum β2MG in the late posttransplant period is useful in identifying patients at risk for rapid loss of graft function. PMID:26633915

  4. Subcutaneous immunoglobulin in lymphoproliferative disorders and rituximab-related secondary hypogammaglobulinemia: a single-center experience in 61 patients

    PubMed Central

    Compagno, Nicolò; Cinetto, Francesco; Semenzato, Gianpietro; Agostini, Carlo

    2014-01-01

    Intravenous immunoglobulin replacement therapy represents the standard treatment for hypogammaglobulinemia secondary to B-cell lymphoproliferative disorders. Subcutaneous immunoglobulin infusion is an effective, safe and well-tolerated treatment approach in primary immunodeficiencies but no extensive data are available on their use in secondary hypogammaglobulinemia, a frequent phenomenon occurring after treatment with anti-CD20 monoclonal antibodies in lymphoproliferative disorders. In this retrospective study we evaluated efficacy (serum IgG trough levels, incidence of infections per year, need for antibiotics) and safety (number of adverse events) of intravenous (300 mg/kg/4 weeks) versus subcutaneous (75 mg/kg/week) immunoglobulin replacement therapy in 61 patients. In addition, the impact of the infusion methods on quality of life was compared. All patients were treated with subcutaneous immunoglobulin, and 33 out of them had been previously treated with intravenous immunoglobulin. Both treatments appeared to be effective in replacing Ig production deficiency and in reducing the incidence of infectious events and the need for antibiotics. Subcutaneous immunoglobulin obtained a superior benefit when compared to intravenous immunoglobulin achieving higher IgG trough levels, lower incidence of overall infection and need for antibiotics. The incidence of serious bacterial infections was similar with both infusion ways. As expected, a lower number of adverse events was registered with subcutaneous immunoglobulin, compared to intravenous immunoglobulin, with no serious adverse events. Finally, we observed an improvement in health-related quality of life parameters after the switch to subcutaneous immunoglobulin. Our results suggest that subcutaneous immunoglobulin is safe and effective in patients with hypogammaglobulinemia associated to lymphoproliferative disorders. PMID:24682509

  5. Role of diffusion weighted imaging in diagnosis of post transplant lymphoproliferative disorders: Case reports and review of literature

    PubMed Central

    Singh, A.; Das, C. J.; Gupta, A. K.; Bagchi, S.

    2016-01-01

    Post transplant lymphoproliferative disorder include a spectrum of conditions occurring in immunosuppressed post transplant recipients, lymphoma being the most ominous. 18F-fludeoxyglucose positron emission tomography with computed tomography CT) is the current imaging gold standard for lymphoma imaging as it allows both morphological and functional assessment. CT and/or conventional magnetic resonance imaging (MRI) are used for morphological evaluation in transplant recipients. Integrating diffusion weighted imaging with apparent diffusion coefficient analysis in MRI protocol enhances its sensitivity and may prove invaluable in response assessment in transplant recipients. PMID:27194838

  6. PCR Analysis of IgH and TCR-γ Gene Rearrangements as a Confirmatory Diagnostic Tool for Lymphoproliferative Disorders.

    PubMed

    Poopak, Behzad; Valeshabad, Ali Kord; Elahi, Fazel; Rezvani, Hamid; Khosravipour, Gelareh; Jahangirpour, Mohammad Ali; Bolouri, Shirin; Golkar, Tolou; Salari, Fatemeh; Shahjahani, Mohammad; Saki, Najmaldin

    2015-03-01

    This study investigates PCR analysis of immunoglobulin heavy chain (IgH) and T cell receptor (TCR) gene rearrangements on paraffin-embedded tissue sections and bone marrow aspirates of patients suspected to have lymphoproliferative disorders but with inconclusive diagnosis in histopathological examination. 130 samples of patients with inconclusive immunohistochemistry results were evaluated for clonal rearrangement of IgH and TCR genes. Based on histopathology examination, the patients were divided into three groups: the first group without any definite diagnosis of lymphoproliferative disorders (60 cases, 46.2 %), the second group suspected to have a lymphoproliferative disorder but in favor of benign disorders (19 cases, 14.6 %) and the third group suspect to lymphoproliferative disorders but relatively in favor of malignant disorders (51 cases, 39.2 %). After DNA extraction and quality control, semi-nested PCR was performed using consensus primers for amplification of TCR-γ and CDR-3 regions of IgH genes. PCR products were analyzed after heteroduplex analysis using polyacrylamide gel electrophoresis, and were subject to silver staining. Totally, in over half of the cases (55.4 %), a monoclonal pattern was found in IgH or TCR-γ genes rearrangements. Monoclonal IgH gene rearrangement was detected in 48.1 % of patients, whereas monoclonal TCR-γ gene rearrangement was found in 33.6 % of them, which was not statistically significant (P = 0.008). Only in 32 patients (24.6 %) were the results of TCR-γ and IgH gene rearrangements consistent with respect to the presence (2.3 %) or absence (22.3 %) of monoclonality. Finally, PCR analysis of TCR-γ and IgH gene rearrangements led to definite diagnosis in 105 patients (80.8 %), and only 25 cases (19.2 %) remained inconclusive. Our results emphasize the usefulness of gene rearrangement study in cases without a definite diagnosis in immunohistochemistry studies. Multiple PCR analysis results when combined with patient's clinical course and immunohistochemistry can lead to early diagnosis and subsequent therapy. PMID:25548443

  7. Screening for cardiovascular disease before kidney transplantation

    PubMed Central

    Palepu, Sneha; Prasad, G V Ramesh

    2015-01-01

    Pre-kidney transplant cardiac screening has garnered particular attention from guideline committees as an approach to improving post-transplant success. Screening serves two major purposes: To more accurately inform transplant candidates of their risk for a cardiac event before and after the transplant, thereby informing decisions about proceeding with transplantation, and to guide pre-transplant management so that post-transplant success can be maximized. Transplant candidates on dialysis are more likely to be screened for coronary artery disease than those not being considered for transplantation. Thorough history and physical examination taking, resting electrocardiography and echocardiography, exercise stress testing, myocardial perfusion scintigraphy, dobutamine stress echocardiography, cardiac computed tomography, cardiac biomarker measurement, and cardiac magnetic resonance imaging all play contributory roles towards screening for cardiovascular disease before kidney transplantation. In this review, the importance of each of these screening procedures for both coronary artery disease and other forms of cardiac disease are discussed. PMID:26722655

  8. Screening for cardiovascular disease before kidney transplantation.

    PubMed

    Palepu, Sneha; Prasad, G V Ramesh

    2015-12-24

    Pre-kidney transplant cardiac screening has garnered particular attention from guideline committees as an approach to improving post-transplant success. Screening serves two major purposes: To more accurately inform transplant candidates of their risk for a cardiac event before and after the transplant, thereby informing decisions about proceeding with transplantation, and to guide pre-transplant management so that post-transplant success can be maximized. Transplant candidates on dialysis are more likely to be screened for coronary artery disease than those not being considered for transplantation. Thorough history and physical examination taking, resting electrocardiography and echocardiography, exercise stress testing, myocardial perfusion scintigraphy, dobutamine stress echocardiography, cardiac computed tomography, cardiac biomarker measurement, and cardiac magnetic resonance imaging all play contributory roles towards screening for cardiovascular disease before kidney transplantation. In this review, the importance of each of these screening procedures for both coronary artery disease and other forms of cardiac disease are discussed. PMID:26722655

  9. The MYC/miR-17-92 axis in lymphoproliferative disorders: A common pathway with therapeutic potential

    PubMed Central

    Hernndez, Luis; Gattei, Valter

    2015-01-01

    MicroRNAs (miRNAs) represent a class of small non-coding single-stranded RNA molecules acting as master regulators of gene expression post transcriptionally by inhibiting the translation or inducing the degradation of target messenger RNAs (mRNAs). In particular, the miR-17-92 cluster is widely expressed in many different cell types and is essential for many developmental and pathogenic processes. As a strong oncogene, miR-17-92 can regulate multiple cellular processes that favor malignant transformation, promoting cell survival, rapid cell proliferation, and increased angiogenesis. The miR-17-92 cluster has been reported to be involved in hematopoietic malignancies including diffuse large B-cell lymphoma, mantle cell lymphoma, Burkitt's lymphoma, and chronic lymphocytic leukemia. Given the multiple and potent effects on cellular proliferation and apoptosis exerted by the miR-17-92 cluster, miRNAs belonging to the cluster surely represent attractive targets for cancer therapy also in the context of lymphoproliferative disorders. In the present review, we focus on the role of the miR-17-92 cluster in lymphoproliferative disorders, including diagnostic/prognostic implications, and on the potential applications of anti-miRNAs based therapies targeting miRNAs belonging to the cluster. PMID:26305986

  10. Detection of monoclonal T populations in patients with KIR-restricted chronic lymphoproliferative disorder of NK cells

    PubMed Central

    Gattazzo, Cristina; Teramo, Antonella; Passeri, Francesca; De March, Elena; Carraro, Samuela; Trimarco, Valentina; Frezzato, Federica; Berno, Tamara; Barilà, Gregorio; Martini, Veronica; Piazza, Francesco; Trentin, Livio; Facco, Monica; Semenzato, Gianpietro; Zambello, Renato

    2014-01-01

    The etiology of chronic large granular lymphocyte proliferations is largely unknown. Although these disorders are characterized by the expansion of different cell types (T and natural killer) with specific genetic features and abnormalities, several lines of evidence suggest a common pathogenetic mechanism. According to this interpretation, we speculated that in patients with natural killer-type chronic lymphoproliferative disorder, together with natural killer cells, also T lymphocytes undergo a persistent antigenic pressure, possibly resulting in an ultimate clonal T-cell selection. To strengthen this hypothesis, we evaluated whether clonal T-cell populations were detectable in 48 patients with killer immunoglobulin-like receptor-restricted natural killer-type chronic lymphoproliferative disorder. At diagnosis, in half of the patients studied, we found a clearly defined clonal T-cell population, despite the fact that all cases presented with a well-characterized natural killer disorder. Follow-up analysis confirmed that the TCR gamma rearrangements were stable over the time period evaluated; furthermore, in 7 patients we demonstrated the appearance of a clonal T subset that progressively matures, leading to a switch between killer immunoglobulin-like receptor-restricted natural killer-type disorder to a monoclonal T-cell large granular lymphocytic leukemia. Our results support the hypothesis that a common mechanism is involved in the pathogenesis of these disorders. PMID:25193965

  11. Vaccine by chicken line interaction alters the protective efficacy against challenge with a very virulent plus strain of Marek's disease virus in white leghorn chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens caused by Marek’s disease virus (MDV), an oncogenic and highly contagious a-herpesvirus. MD has been controlled by vaccination but sporadic outbreaks of MD still occur in some parts of the world. Efforts to improve vaccine ef...

  12. Quantitation of Marek’s disease virus in vaccinated population of resistant and susceptible chicken samples using real-time PCR

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of chicken caused by cell-associated alpha-herpesvirus, known as Marek’s disease virus (MDV). MD virus load in challenged chickens has been well studied, but the difference between the virus load in vaccinated MD resistant and susceptible chicken...

  13. Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation

    PubMed Central

    Rivinius, Rasmus; Helmschrott, Matthias; Ruhparwar, Arjang; Schmack, Bastian; Erbel, Christian; Gleissner, Christian A; Akhavanpoor, Mohammadreza; Frankenstein, Lutz; Darche, Fabrice F; Schweizer, Patrick A; Thomas, Dierk; Ehlermann, Philipp; Bruckner, Tom; Katus, Hugo A; Doesch, Andreas O

    2016-01-01

    Background Amiodarone is a frequently used antiarrhythmic drug in patients with end-stage heart failure. Given its long half-life, pre-transplant use of amiodarone has been controversially discussed, with divergent results regarding morbidity and mortality after heart transplantation (HTX). Aim The aim of this study was to investigate the effects of long-term use of amiodarone before HTX on early post-transplant atrial fibrillation (AF) and mortality after HTX. Methods Five hundred and thirty patients (age ≥18 years) receiving HTX between June 1989 and December 2012 were included in this retrospective single-center study. Patients with long-term use of amiodarone before HTX (≥1 year) were compared to those without long-term use (none or <1 year of amiodarone). Primary outcomes were early post-transplant AF and mortality after HTX. The Kaplan–Meier estimator using log-rank tests was applied for freedom from early post-transplant AF and survival. Results Of the 530 patients, 74 (14.0%) received long-term amiodarone therapy, with a mean duration of 32.3±26.3 months. Mean daily dose was 223.0±75.0 mg. Indications included AF, Wolff–Parkinson–White syndrome, ventricular tachycardia, and ventricular fibrillation. Patients with long-term use of amiodarone before HTX had significantly lower rates of early post-transplant AF (P=0.0105). Further, Kaplan–Meier analysis of freedom from early post-transplant AF showed significantly lower rates of AF in this group (P=0.0123). There was no statistically significant difference between patients with and without long-term use of amiodarone prior to HTX in 1-year (P=0.8596), 2-year (P=0.8620), 5-year (P=0.2737), or overall follow-up mortality after HTX (P=0.1049). Moreover, Kaplan–Meier survival analysis showed no statistically significant difference in overall survival (P=0.1786). Conclusion Long-term use of amiodarone in patients before HTX significantly reduces early post-transplant AF and is not associated with increased mortality after HTX. PMID:26937171

  14. Construction of a YAC contig and STS map spanning 2.5 Mbp in Xq25, the critical region for the X-linked lymphoproliferative (XLP) gene

    SciTech Connect

    Lanyi, A.; Li, B.F.; Li, S.

    1994-09-01

    X-linked lymphoproliferative disease (XLP) is characterized by a marked vulnerability in Epstein-Barr virus (EBV) infection. Infection of XLP patients with EBV invariably results in fatal mononucleosis, agammaglobulinemia or B-cell lymphoma. The XLP gene lies within a 10 cM region in Xq25 between DXS42 and DXS10. Initial chromosome studies revealed an interstitial, cytogenetically visible deletion in Xq25 in one XLP family (43-004). We estimated the size of the Xq25 deletion by dual laser flow karyotyping to involve 2% of the X chromosome, or approximately 3 Mbp of DNA sequences. To further delineate the deletion we performed a series of pulsed field gel electrophoresis (PFGE) analyses which showed that DXS6 and DXS100, two Xq25-specific markers, are missing from 45-004 DNA. Five yeast artificial chromosomes (YACs) from a chromosome X specific YAC library containing sequences deleted in patient`s 43-004 DNA were isolated. These five YACs did not overlap, and their end fragments were used to screen the CEPH MegaYAC library. Seven YACs were isolated from the CEPH MegaYAC library. They could be arranged into a contig which spans between DXS6 and DXS100. The contig contains a minimum of 2.5 Mbp of human DNA. A total of 12 YAC end clone, lambda subclones and STS probes have been used to order clones within the contig. These reagents were also used in Southern blot and patients showed interstitial deletions in Xq25. The size of these deletions range between 0.5 and 2.5 Mbp. The shortest deletion probably represents the critical region for the XLP gene.

  15. Serum Uric Acid and Renal Transplantation Outcomes: At Least 3-Year Post-transplant Retrospective Multivariate Analysis

    PubMed Central

    Zhang, Kun; Gao, Baoshan; Wang, Yuantao; Wang, Gang; Wang, Weigang; Zhu, Yaxiang; Yao, Liyu; Gu, Yiming; Chen, Mo; Zhou, Honglan; Fu, Yaowen

    2015-01-01

    Since the association of serum uric acid and kidney transplant graft outcome remains disputable, we sought to evaluate the predictive value of uric acid level for graft survival/function and the factors could affect uric acid as time varies. A consecutive cohort of five hundred and seventy three recipients transplanted during January 2008 to December 2011 were recruited. Data and laboratory values of our interest were collected at 1, 3, 6, 12, 24 and 36 months post-transplant for analysis. Cox proportional hazard model, and multiple regression equation were built to adjust for the possible confounding variables and meet our goals as appropriate. The current cohort study lasts for 41.86 ± 15.49 months. Uric acid level is proven to be negatively associated with eGFR at different time point after adjustment for age, body mass index and male gender (standardized β ranges from -0.15 to -0.30 with all P<0.001).Males with low eGFR but high level of TG were on CSA, diuretics and RAS inhibitors and experienced at least one episode of acute rejection and diabetic issue were associated with a higher mean uric acid level. Hyperuricemia was significantly an independent predictor of pure graft failure (hazard ratio=4.01, 95% CI: 1.25-12.91, P=0.02) after adjustment. But it was no longer an independent risk factor for graft loss after adjustment. Interestingly, higher triglyceride level can make incidence of graft loss (hazard ratio=1.442, for each unit increase millimoles per liter 95% CI: 1.008-2.061, P=0.045) and death (hazard ratio=1.717, 95% CI: 1.105-2.665, P=0.016) more likely. The results of our study suggest that post-transplant elevated serum uric acid level is an independent predictor of long-term graft survival and graft function. Together with the high TG level impact on poor outcomes, further investigations for therapeutic effect are needed. PMID:26208103

  16. Post-Transplant Membranous Nephropathy Associated with Chronic Active Antibody-Mediated Rejection and Hepatitis C Infection after Deceased Donor Renal Transplantation.

    PubMed

    Doke, Tomohito; Sato, Waichi; Takahashi, Kazuo; Hayashi, Hiroki; Koide, Sigehisa; Sasaki, Hitomi; Kusaka, Mamoru; Shiroki, Ryoichi; Hoshinaga, Kiyotaka; Takeda, Asami; Yuzawa, Yukio; Hasegawa, Midori

    2016-01-01

    A 53-year-old woman who had undergone deceased donor kidney transplantation twice, at 35 and 43 years of age, presented with renal impairment. She was infected with hepatitis C virus (HCV). The histology of the graft kidney revealed post-transplant membranous nephropathy (MN) with podocytic infolding and antibody-mediated rejection (AMR). IgG subclass staining showed fine granular deposits of IgG1 and IgG3, but not IgG4, in the glomerular capillary walls. Panel reactive antibody scores for human leukocyte antigen class I and class II were 92.67% and 66.68%, respectively. Thus, this case of post-transplanted MN was considered to be associated with AMR and HCV infection. PMID:26875963

  17. Presence of Epstein-Barr virus latency type III at the single cell level in post-transplantation lymphoproliferative disorders and AIDS related lymphomas.

    PubMed Central

    Brink, A A; Dukers, D F; van den Brule, A J; Oudejans, J J; Middeldorp, J M; Meijer, C J; Jiwa, M

    1997-01-01

    AIMS: To investigate the expression pattern of Epstein-Barr virus (EBV) latent genes at the single cell level in post-transplantation lymphoproliferative disorders and acquired immunodefiency syndrome (AIDS) related lymphomas, in relation to cellular morphology. METHODS: Nine post-transplantation lymphoproliferative disorders and three AIDS related lymphomas were subjected to immunohistochemistry using monoclonal antibodies specific for EBV nuclear antigen 1 (EBNA1) (2H4), EBNA2 (PE2 and the new rat anti-EBNA2 monoclonal antibodies 1E6, R3, and 3E9), and LMP1 (CS1-4 and S12). Double staining was performed combining R3 or 3E9 with S12. RESULTS: R3 and 3E9 anti-EBNA2 monoclonal antibodies were more sensitive than PE2, enabling the detection of more EBNA2 positive lymphoma cells. Both in post-transplantation lymphoproliferative disorders and AIDS related lymphomas, different expression patterns were detected at the single cell level. Smaller neoplastic cells were positive for EBNA2 but negative for LMP1. Larger and more blastic neoplastic cells, sometimes resembling Reed-Sternberg cells, were LMP1 positive but EBNA2 negative (EBV latency type II). Morphologically intermediate neoplastic cells coexpressing EBNA2 and LMP1 (EBV latency type III), were detected using R3 and 3E9, and formed a considerable part of the neoplastic population in four of nine post-transplantation lymphoproliferative disorders and two of three AIDS related lymphomas. All samples contained a subpopulation of small tumour cells positive exclusively for Epstein-Barr early RNA and EBNA1. The relation between cellular morphology and EBV expression patterns in this study was less pronounced in AIDS related lymphomas than in post-transplantation lymphoproliferative disorders, because the AIDS related lymphomas were less polymorphic than the post-transplantation lymphoproliferative disorders. CONCLUSIONS: In post-transplantation lymphoproliferative disorders and AIDS related lymphomas, EBV latency type III can be detected by immunohistochemistry in a subpopulation of tumour cells using sensitive monoclonal antibodies R3 and 3E9. Our data suggest that EBV infected tumour cells in these lymphomas undergo gradual changes in the expression of EBV latent genes, and that these changes are associated with changes in cellular morphology. Images PMID:9462239

  18. Focal Fat Masquerading as Malignancy in the Liver Graft of a Post-Transplant Patient

    PubMed Central

    Patrick, Caitlyn M.; Hayashi, Paul H.; Kozlowski, Tomasz; Greene, Kevin G.; Semelka, Richard C.

    2012-01-01

    Background and Aims Liver failure from non-alcoholic fatty liver disease (NAFLD) is an increasing indication for liver transplant and recurrence of fatty liver in transplanted grafts has been documented. Herein is described an atypical recurrence of steatosis as a de novo focal fatty lesion that mimicked a more ominous cancerous lesion. This presentation of recurrent NAFLD has not previously been described in the literature. Methods Chart review. Results Biopsy of an atypical lesion was found to be focal fat with surrounding steatohepatitis. Conclusions Non-alcoholic fatty liver disease may recur after liver transplant and manifest as a focal fatty lesion. It is important to catalogue the atypical presentations of the increasingly common NAFLD developing in transplanted livers. PMID:21559737

  19. The influence of mTOR inhibitors on immunity and the relationship to post-transplant malignancy

    PubMed Central

    2013-01-01

    The known role of mammalian target of rapamycin (mTOR) in the immune response has been rapidly evolving, from what was once thought to be a simple immunosuppressive antiproliferative effect on T cells to a very complex central role that serves to integrate multiple signals given to T cells, B cells and antigen-presenting cells. The complexity of this topic is demonstrated by recent data suggesting that mTOR inhibition can either inhibit or promote certain aspects of immune responses, depending on the nature of the antigenic stimulus, and the environmental conditions cueing the cellular immunological players. There is even evidence that, under mTOR inhibition, an immune response to one foreign entity (for example, an organ transplant) may be simultaneously completely different to that of another (for example, tumour or microorganism). To understand how this might be possible, it is necessary to investigate the central role that mTOR seems to have in shaping the immune response. This review is aimed at examining how mTOR controls the development and function of key immune cells, and puts this information primarily in the context of organ transplant rejection and post-transplant malignancy. PMID:24565200

  20. Importance of glucokinase -258G/A polymorphism in Asian Indians with post-transplant and type 2 diabetes mellitus.

    PubMed

    Khan, Imran Ali; Vattam, Kiran Kumar; Jahan, Parveen; Hasan, Qurratulain; Rao, Pragna

    2016-02-01

    Type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) are non-synonymous forms of diabetes. Glucokinase (GCK) plays a key role in glucose metabolism. The relationship between the GCK promoter and specific types of diabetes, such as PTDM and T2DM, in the Asian Indian population is unknown. We examined the occurrence of a specific GCK promoter variant (-258G/A) in patients with T2DM and PTDM. The case-control study enrolled 640 Asian Indian subjects, including controls (n = 250) and T2DM (n = 250), PTDM (n = 42), and non-post-transplant diabetes mellitus (non-PTDM) (n = 98) patients. Purified Deoxyribonucleic acid (DNA) was genotyped with the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. The digested PCR products were analyzed on 12% polyacrylamide gels. The anthropometric, biochemical, and clinical details of each group were documented. GCK -258G/A alleles and genotypes were not associated with T2DM. However, among PTDM subjects, we detected a higher frequency of heterozygotes (52.4%) and a positive association with alleles/genotypes. The results suggest that the promoter region (-258G/A) of GCK plays an important role in PTDM in Asian Indians. PMID:26989645

  1. Genetic Interactions Between TRPC6 and NPHS1 Variants Affect Posttransplant Risk of Recurrent Focal Segmental Glomerulosclerosis.

    PubMed

    Sun, Z J; Ng, K H; Liao, P; Zhang, Y; Ng, J L; Liu, I D; Tan, P H; Chong, S S C; Chan, Y H; Liu, J; Davila, S; Heng, C K; Jordan, S C; Soong, T W; Yap, H K

    2015-12-01

    Individuals with TRPC6 mutations have variable phenotypes, ranging from healthy carrier to focal segmental glomerulosclerosis (FSGS) leading to renal failure. Here, we describe a family where six members had a novel TRPC6 p.R68W (c.202C>T) mutation, two of whom had renal failure from FSGS, and one had proteinuria. One healthy carrier donated a kidney to her sister. Both donor and recipient had no proteinuria at 20 years posttransplant. Two synonymous NPHS1 polymorphisms, rs2285450 (c.294C>T) and rs437168 (c.2289C>T) segregated with renal failure in this family. These variants had higher allele frequencies in 97 unrelated patients with nephrotic syndrome or FSGS compared to 224 controls. Using patch-clamp experiments in HEK293 and podocytes, we showed that the p.R68W mutation increased TRPC6 current amplitudes, which may be explained by enhanced TRPC6 surface expression. Additionally, while wild-type nephrin suppressed TRPC6 currents, this ability was lost in the presence of NPHS1 c.294C>T polymorphism. When cells were transfected according to combined TRPC6 and NPHS1 genotypes in the family, those representing the donor had lower TRPC6 currents than cells representing the recipient, suggesting that interactions between TRPC6 and NPHS1 variants could possibly account for the variable penetrance of TRPC6 mutations and the absence of recurrence in the graft. PMID:26147534

  2. T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy.

    PubMed

    Heijink, D M; Kater, A P; Hazenberg, M D; Hagenbeek, A; Kersten, M J

    2016-05-01

    CAR T-cells are autologous T-cells transduced with a chimeric antigen receptor (CAR). The CAR contains an antigen recognition part (originating from an antibody), a T-cell receptor transmembrane and cytoplasmic signalling part, and one or more co-stimulatory domains. While CAR T-cells can be directed against any tumour target, most experience thus far has been obtained with targeting of the B-cell antigen CD19 that is expressed by B-cell acute lymphocytic leukaemia, chronic lymphocytic leukaemia and other B-cell lymphomas. The first clinical results are promising, although there are profound differences in response between patients with different haematological malignancies. Treatment-related side effects have been observed that require specific management. This review will explain the mechanism of action, summarise the experience to date and point out future directions for this hopeful new addition to the therapeutic armamentarium in the treatment of lymphoproliferative B-cell malignancies. PMID:27185772

  3. Lymphoproliferative and gamma interferon responses to stress-regulated Mycobacterium avium subsp. paratuberculosis recombinant proteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease in ruminants is a chronic infection of the intestines caused by Mycobacterium avium subsp. paratuberculosis. Economic losses associated with Johne’s disease arise due to premature culling, reduced production of milk and wool and mortalities. The disease is characterised by a long inc...

  4. A comparative evaluation of the protective efficacy of rMd5-delta-Meq and CV1988/Rispens against a vv+ strain of Marek's disease virus infection in a series of recombinant congenic strains of white leghorn chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens caused by a highly infectious, oncogenic alpha-herpesvirus known as Marek’s disease virus (MDV). MD is presently controlled by vaccination. Current MD vaccines include attenuated serotype 1 strains (e.g. CVI988/Rispens), avir...

  5. Insertion of reticuloendotheliosis virus long terminal repeat into the genome of CVI988 strain of Marek’s disease virus results in enhanced growth and protection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of chicken caused by serotype 1 MD virus (MDV). Vaccination of commercial poultry has drastically reduced losses from MD and the poultry industry cannot be sustained without the use of vaccines. Retrovirus insertion into herpesviruses genome is a...

  6. Choice of Unmanipulated T Cell Replete Graft for Haploidentical Stem Cell Transplant and Posttransplant Cyclophosphamide in Hematologic Malignancies in Adults: Peripheral Blood or Bone Marrow—Review of Published Literature

    PubMed Central

    Farhan, Shatha; Peres, Edward; Janakiraman, Nalini

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (SCT) is often the only curative option for many patients with malignant and benign hematological stem cell disorders. However, some issues are still of concern regarding finding a donor like shrinking family sizes in many societies, underrepresentation of the ethnic minorities in the registries, genetic variability for some races, and significant delays in obtaining stem cells after starting the search. So there is a considerable need to develop alternate donor stem cell sources. The rapid and near universal availability of the haploidentical donor is an advantage of the haploidentical SCT and an opportunity that is being explored currently in many centers especially using T cell replete graft and posttransplant cyclophosphamide. This is probably because it does not require expertise in graft manipulation and because of the lower costs. However, there are still lots of unanswered questions, like the effect of use of bone marrow versus peripheral blood as the source of stem cells on graft-versus-host disease, graft versus tumor, overall survival, immune reconstitution, and quality of life. Here we review the available publications on bone marrow and peripheral blood experience in the haploidentical SCT setting. PMID:27118973

  7. CD8+ Immunosenescence Predicts Post-Transplant Cutaneous Squamous Cell Carcinoma in High-Risk Patients.

    PubMed

    Bottomley, Matthew J; Harden, Paul N; Wood, Kathryn J

    2016-05-01

    Most morbidity associated with malignancy in long-term renal transplant recipients is due to cutaneous squamous cell carcinoma (SCC). Previously identified measures to stratify SCC risk have limited use, however. We hypothesized that an increased proportion of senescent, terminally differentiated CD8(+) T cells would identify renal transplant recipients at elevated SCC risk. Peripheral blood lymphocytes were isolated from 117 stable transplant recipients at high risk of SCC and analyzed phenotypically by flow cytometry. Participants were followed up prospectively for SCC development. The predictive value of variables was assessed using Cox regression. Age at transplant and enrollment, dialysis duration, and previous disease were predictive of SCC development during follow-up. Previously published clinical phenotype-based risk scores lost predictive value with the removal of age as a covariate. The percentage of CD57-expressing CD8(+) T cells was the strongest immunologic predictor of future SCC and correlated with increasing CD8(+) T cell differentiation. We dichotomized participants into those with a majority (CD57hi) and a minority (CD57lo) of CD8(+) T cells expressing CD57; CD57hi participants were more likely to develop SCC during follow-up (hazard ratio, 2.9; 95% confidence interval, 1.0 to 8.0), independent of potential confounders, and tended to develop earlier recurrence. The CD57hi phenotype was stable with time and associated with increasing age and cytomegalovirus seropositivity. Our results show that the CD57hi phenotype is a strong predictor of SCC development and recurrence in this cohort of long-term, high-risk renal transplant recipients. This information may allow identification of recipients who may benefit from intensive dermatologic screening and immunosuppression reduction. PMID:26563386

  8. Existence of circulating anti-endothelial cell antibodies after heart transplantation is associated with post-transplant acute allograft rejection.

    PubMed

    Lehle, Karla; Kroher, Johannes; Kolat, Philipp; von Süßkind-Schwendi, Marietta; Schmid, Christof; Haneya, Assad; Rupprecht, Leopold; Hirt, Stephan

    2016-05-01

    Anti-endothelial cell antibodies (AECA) may be involved in the development of heart allograft rejection. Its detection might be a cheap and noninvasive method to identify high-risk patients. An indirect immunofluorescence method on human umbilical vein endothelial cells was used to investigate the presence of AECAs in 260 pre- and post-transplant serum samples sequentially collected from 34 patients within the first year after heart transplantation (HTX). The presence of AECAs before (23.5 %) and early after HTX (14.7 %) was associated with a significantly increased risk of early acute rejection (75 and 60 %, respectively) compared to 33 % in AECA-negative patients (p = 0.049). Moreover, rejections from AECA-positive patients were more severe (p = 0.057) with a significantly increased incidence of multiple (p = 0.025). The mean number of the sum of rejection episodes was significantly higher in AECA-positive patients (p ≤ 0.05). Patients free of AECAs mainly received mycophenolate mofetil as primary immunosuppression (p = 0.067). Nevertheless, the presence of AECAs did not affect long-term outcome and mortality of HTX patients. Despite a low number of patient samples, the detection of AECAs before and early after HTX could be used as a biomarker for an increased risk of early acute rejection in high-risk patients. This easy method might be a valuable tool to support screening procedures to improve individualized immunosuppressive therapy. PMID:25820657

  9. EBV-Positive and EBV-Negative Posttransplant Diffuse Large B Cell Lymphomas Have Distinct Genomic and Transcriptomic Features.

    PubMed

    Finalet Ferreiro, J; Morscio, J; Dierickx, D; Vandenberghe, P; Gheysens, O; Verhoef, G; Zamani, M; Tousseyn, T; Wlodarska, I

    2016-02-01

    The molecular pathogenesis of posttransplant diffuse large B cell lymphoma (PT-DLBCL) is largely unknown. We have recently shown that Epstein-Barr virus-positive (EBV(+) ) and -negative (EBV(-) ) PT-DLBCL have distinct gene expression profiles, and the transcriptomic profile of EBV(-) PT-DLBCL is similar to that of DLBCL in immunocompetent individuals (IC-DLBCL). To validate these observations at the genomic level, we performed array-comparative genome hybridization (aCGH) analysis of 21 EBV(+) PT-DLBCL, 6 EBV(-) PT-DLBCL, and 11 control IC-DLBCL, and subsequently combined genomic and transcriptomic data. The analysis showed that EBV(+) and EBV(-) PT-DLBCL have distinct aCGH profiles and shared only one recurrent imbalance. EBV(-) PT-DLBCL, however, displayed at least 10 aberrations recurrent in IC-DLBCL, among which characteristic gain of 3/3q and 18q, and loss of 6q23/TNFAIP3 as well as 9p21/CDKN2A. The most prevalent aberration in EBV(+) PT-DLBCL was gain/amplification of 9p24.1 targeting PDCD1LG2/PDL2. Our data indicate that the FOXP1 oncogene and the tumor suppressor CDKNA2 implicated in EBV(-) DLBCL, do not play a critical role in the pathogenesis of EBV(+) PT-DLBCL. Altogether, genomic profiling of PT-/IC-DLBCL confirms that EBV(-) and EBV(+) PT-DLBCL are distinct entities, while EBV(-) PT-DLBCL has features in common with IC-DLBCL. These findings support the hypothesis that EBV(-) PT-DLBCL are de novo lymphomas in transplant recipients. PMID:26780579

  10. The Epstein-Barr virus and its association with human cancers.

    PubMed Central

    Baumforth, K R; Young, L S; Flavell, K J; Constandinou, C; Murray, P G

    1999-01-01

    The Epstein-Barr virus (EBV) has been linked to the development of a variety of human malignancies, including Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma, some T cell lymphomas, post-transplant lymphoproliferative disease, and more recently, certain cancers of the stomach and smooth muscle. This review summarizes these associations and in particular the role of the viral latent genes in the transformation process. PMID:10748864

  11. Feasibility and Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant High-Dose Cyclophosphamide for Children and Adolescents with Hematologic Malignancies: An AIEOP-GITMO Retrospective Multicenter Study.

    PubMed

    Berger, Massimo; Lanino, Edoardo; Cesaro, Simone; Zecca, Marco; Vassallo, Elena; Faraci, Maura; De Bortoli, Massimiliano; Barat, Veronica; Prete, Arcangelo; Fagioli, Franca

    2016-05-01

    Post-transplant high-dose cyclophosphamide (PTCy) is a novel approach to prevent graft-versus-host disease (GVHD) and rejection in patients given haploidentical hematopoietic stem cell transplantation (HSCT). Thirty-three patients with high-risk hematologic malignancies and lacking a match-related or -unrelated donor were treated with PTCy haploidentical HSCT in 5 Italian AIEOP centers. Nineteen patients had a nonmyeloablative preparative regimen (57%), and 14 patients received a full myeloablative conditioning regimen (43%). No patients received serotherapy; GVHD prophylaxis was based on PTCy (50 mg/kg on days +3 and +4) combined with mycophenolate plus tacrolimus or cyclosporine A. Neutrophil and platelet engraftment was achieved on days +17 (range, 14 to 37) and +27 (range, 16 to 71). One patient had autologous reconstitution for anti-HLA antibodies. Acute GVHD grades II to IV and III to IV and chronic GVHD developed in 22% (95% CI, 11 to 42), 3% (95% CI, 0 to 21), and 4% (95% CI, 0 to 27) of cases, respectively. The 1-year overall survival rate was 72% (95% CI, 56 to 88), progression-free survival rate was 61% (95% CI, 43 to 80), cumulative incidence of relapse was 24% (95% CI, 13 to 44), and transplant-related mortality was 9% (95% CI, 3 to 26). The univariate analysis for risk of relapse incidence showed how 3 significant variables, mother as donor (P = .02), donor gender as female (P = .04), and patient gender as female (P = .02), were significantly associated with a lower risk of relapse. Disease progression was the main cause of death. PTCy is a safe procedure also for children and adolescents who have already received several lines of chemotherapy. Among the different diseases, a trend for better 1-year rates of overall survival was obtained for nonacute leukemia patients. PMID:26860636

  12. CD3-CD4+ lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder.

    PubMed

    Lefèvre, Guillaume; Copin, Marie-Christine; Roumier, Christophe; Aubert, Hélène; Avenel-Audran, Martine; Grardel, Nathalie; Poulain, Stéphanie; Staumont-Sallé, Delphine; Seneschal, Julien; Salles, Gilles; Ghomari, Kamel; Terriou, Louis; Leclech, Christian; Morati-Hafsaoui, Chafika; Morschhauser, Franck; Lambotte, Olivier; Ackerman, Félix; Trauet, Jacques; Geffroy, Sandrine; Dumezy, Florent; Capron, Monique; Roche-Lestienne, Catherine; Taieb, Alain; Hatron, Pierre-Yves; Dubucquoi, Sylvain; Hachulla, Eric; Prin, Lionel; Labalette, Myriam; Launay, David; Preudhomme, Claude; Kahn, Jean-Emmanuel

    2015-08-01

    The CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome is characterized by hypereosinophilia and clonal circulating CD3(-)CD4(+) T cells. Peripheral T-cell lymphoma has been described during this disease course, and we observed in our cohort of 23 patients 2 cases of angio-immunoblastic T-cell lymphoma. We focus here on histopathological (n=12 patients) and immunophenotypic (n=15) characteristics of CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome. Atypical CD4(+) T cells lymphoid infiltrates were found in 10 of 12 CD3(-)CD4(+) L-HES patients, in lymph nodes (n=4 of 4 patients), in skin (n=9 of 9) and other extra-nodal tissues (gut, lacrymal gland, synovium). Lymph nodes displayed infiltrates limited to the interfollicular areas or even an effacement of nodal architecture, associated with proliferation of arborizing high endothelial venules and increased follicular dendritic cell meshwork. Analysis of 2 fresh skin samples confirmed the presence of CD3(-)CD4(+) T cells. Clonal T cells were detected in at least one tissue in 8 patients, including lymph nodes (n=4 of 4): the same clonal T cells were detected in blood and in at least one biopsy, with a maximum delay of 23 years between samples. In the majority of cases, circulating CD3(-)CD4(+) T cells were CD2(hi) (n=9 of 14), CD5(hi) (n=12 of 14), and CD7(-)(n=4 of 14) or CD7(low) (n=10 of 14). Angio-immunoblastic T-cell lymphoma can also present with CD3(-)CD4(+) T cells; despite other common histopathological and immunophenotypic features, CD10 expression and follicular helper T-cell markers were not detected in lymphoid variant of hypereosinophilic syndrome patients, except in both patients who developed angio-immunoblastic T-cell lymphoma, and only at T-cell lymphoma diagnosis. Taken together, persistence of tissular clonal T cells and histopathological features define CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome as a peripheral indolent clonal T-cell lymphoproliferative disorder, which should not be confused with angio-immunoblastic T-cell lymphoma. PMID:25682606

  13. Methotrexate-associated lymphoproliferative disorder presenting as extranodal NK/T-cell lymphoma arising in the lungs.

    PubMed

    Tajima, Shogo; Takanashi, Yusuke; Koda, Kenji; Fukayama, Masashi

    2015-12-01

    Patients having rheumatoid arthritis (RA) treated with methotrexate (MTX) are at an increased risk of developing lymphoproliferative disorder (LPD). Epstein-Barr virus (EBV) sometimes contributes to the development of MTX-associated LPD. Herein, we report the case of a 64-year-old Japanese woman with RA who showed complications of EBV-positive MTX-associated LPD. This case is exceedingly rare in that the LPD was confined to the lungs and its subclassification was extranodal NK/T-cell lymphoma. Only four cases of extranodal NK/T-cell lymphoma in the setting of MTX-associated LPD have ever been reported in the English language literature, only one of which was an extranasal NK/T-cell lymphoma, similar to our case. Extranasal NK/T-cell lymphomas show more aggressive behavior than nasal NK/T-cell lymphomas, possibly reflected by the considerable re-exacerbation of the lesions in only two months after the cessation of MTX in our case. However, the SMILE regimen (steroid, methotrexate, ifosfamide, l-asparaginase, and etoposide) was able to suppress tumor growth in this case. PMID:26459854

  14. Characterization of EBV-related Lymphoproliferative Lesions Arising in Donor Lymphocytes of Transplanted Human Tumor Tissues in the NOG Mouse

    PubMed Central

    Fujii, Etsuko; Kato, Atsuhiko; Chen, Yu Jau; Matsubara, Koichi; Ohnishi, Yasuyuki; Suzuki, Masami

    2014-01-01

    Human tumor tissue line models established in the severely immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Sug/Jic (NOD/Shi-scid, IL-2R?null or NOG) mouse are important tools for oncology research. During the establishment process, a lymphoproliferative lesion (LPL) that replaces the original tumor cells in the site of transplantation occurs. In the present study, we studied the impact of the LPL on the establishment process and the characteristics of the lesion, investigated the systemic distribution of the lesion in the mouse, and evaluated the potential of a simple identification method. The incidence of the lesion varied among tumor types, and the lesion was found to be the leading cause of unsuccessful establishment with gastric and colorectal cancer. The lesion consisted of a varying population of proliferating lymphoid cells that expressed CD20. The cells were positive for Epstein-Barr virus (EBV)-related antigens, and EBV DNA was detected. There was systemic distribution of the lesion within the NOG mouse, and the most consistent gross finding was splenomegaly. Additionally, identification of LPL-affected cases was possible by detecting splenomegaly in the 1st and 2nd generation mice at necropsy. From our findings the lesion was judged to arise from EBV-infected B cells originating from the donor, and monitoring splenomegaly at necropsy was thought effective as a simple method for identifying the lesion at an early stage of the establishment process. PMID:25077758

  15. Deficiency of Rap1-binding protein RAPL causes lymphoproliferative disorders through mislocalization of p27kip1.

    PubMed

    Katagiri, Koko; Ueda, Yoshihiro; Tomiyama, Takashi; Yasuda, Kaneki; Toda, Yoshinobu; Ikehara, Susumu; Nakayama, Keiichi I; Kinashi, Tatsuo

    2011-01-28

    RAPL (an alternative spliced form of Rassf5) is a critical Ras-related protein1 (Rap1) effector that regulates lymphocyte adhesion. Here, we have shown that in addition to this previously described function, RAPL also negatively controls lymphocyte proliferation and prevents autoimmunity and lymphoma. RAPL-deficient mice experienced age-related lupus-like glomerulonephritis and developed B cell lymphomas. RAPL-deficient lymphocytes showed hyperproliferation by enhanced S phase entry after antigen receptor ligation. Compared to wild-type cells, RAPL-deficient naive lymphocytes had a 2- to 3-fold increase in Cdk2 kinase activity with a cytoplasmic mislocalization of the cyclin-dependent kinase inhibitor p27(kip1). RAPL was found to suppress the phosphorylation of p27(kip1) on serine 10 (S10) and promoted p27(kip1) nuclear translocation. An S10A mutation in p27(kip1) corrected its cytoplasmic accumulation, reduced hyperproliferation in RAPL-deficient lymphocytes, and suppressed glomerulonephritis and development of B cell lymphoma. Thus, RAPL serves as a checkpoint for S phase entry to prevent lymphoproliferative disorders through the spatial regulation of p27(kip1). PMID:21194982

  16. Utility and diagnostic pitfalls of SOX11 monoclonal antibodies in mantle cell lymphoma and other lymphoproliferative disorders.

    PubMed

    Nakashima, Megan O; Durkin, Lisa; Bodo, Juraj; Lin, Jeffrey; Quintanilla-Martinez, Leticia; Fu, Kai; Hsi, Eric D

    2014-01-01

    Mantle cell lymphoma (MCL) is classically characterized by t(11;14) leading to cyclin D1 overexpression. Recently the transcription factor SOX11 has been discovered to be expressed in most MCL, including cyclin D1-negative cases. In this study we assess the performance of 2 commercially available monoclonal antibodies, Atlas Antibodies (Stockholm, Sweden) clone CLO142 and Cell Marque (Rocklin, CA) clone MRQ-58, for SOX11 immunohistochemistry in MCL, both cyclin D1 positive and cyclin D1 negative, as well as in cases of other small B-cell lymphoproliferative disorders, diffuse large B-cell lymphomas (DLBCLs), Burkitt lymphomas, and lymphoblastic leukemia/lymphomas. We also performed Western blots to further characterize the antibody specificity. Both antibodies show reliable, clear nuclear staining in MCL with variable specificity. However, the MRQ-58 antibody was more specific for MCL than CLO142, which showed considerably more nonspecific staining, especially in DLBCLs (59% positive vs. 4% positive with MRQ-58). In addition we reconfirmed the utility of SOX11 IHC for identifying cases of cyclin D1-negative blastoid MCL. However, we also identified cases of SOX11-positive DLBCL and splenic marginal zone lymphoma. Although SOX11 IHC is a powerful, and relatively accessible, tool to identify MCLs with variant immunophenotypes and/or morphology, these latter 2 cases highlight the need for strict criteria for interpreting SOX11 staining. PMID:25229384

  17. Croup as Unusual Presentation of Post-transplantation Lymphoproliferative Disorder after Liver Transplantation in an 18-month-old Child

    PubMed Central

    Keshtkari, A.; Dehghani, S. M.; Haghighat, M.; Imanieh, M. H.; Nasimfard, A.; Yousefi, G.; Javaherizadeh, H.

    2016-01-01

    Post-transplantation lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation that occurs due to immunosuppression and other risk factors. PTLD may present with involvement of other organs and with unusual presentation. The presentation is often extranodal (e.g., in the gastrointestinal tract, lung, or the central nervous system). Herein, we report on a 1.5-year-old girl who underwent liver transplantation almost 5 months prior to admission. She was on medications such as tacrolimus and prednisolone. Her presentation was started with symptoms of the upper respiratory infection followed by croupy cough and respiratory distress with no response to usual treatments. She had respiratory arrest during broncoscopy. Therefore, emergency tracheostomy was done. Biopsy from the paratracheal mass revealed large B cell non-Hodgkin lymphoma (PTLD, monomorphic and high grade). This case presentation shows that persistent upper airway symptoms, particularly stridor and croupy cough, in children who underwent liver transplant should be further evaluated; the physician needs to have a high degree of clinical suspicion for the diagnosis of PTLD in this situation. PMID:26889375

  18. Croup as Unusual Presentation of Post-transplantation Lymphoproliferative Disorder after Liver Transplantation in an 18-month-old Child.

    PubMed

    Keshtkari, A; Dehghani, S M; Haghighat, M; Imanieh, M H; Nasimfard, A; Yousefi, G; Javaherizadeh, H

    2016-01-01

    Post-transplantation lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation that occurs due to immunosuppression and other risk factors. PTLD may present with involvement of other organs and with unusual presentation. The presentation is often extranodal (e.g., in the gastrointestinal tract, lung, or the central nervous system). Herein, we report on a 1.5-year-old girl who underwent liver transplantation almost 5 months prior to admission. She was on medications such as tacrolimus and prednisolone. Her presentation was started with symptoms of the upper respiratory infection followed by croupy cough and respiratory distress with no response to usual treatments. She had respiratory arrest during broncoscopy. Therefore, emergency tracheostomy was done. Biopsy from the paratracheal mass revealed large B cell non-Hodgkin lymphoma (PTLD, monomorphic and high grade). This case presentation shows that persistent upper airway symptoms, particularly stridor and croupy cough, in children who underwent liver transplant should be further evaluated; the physician needs to have a high degree of clinical suspicion for the diagnosis of PTLD in this situation. PMID:26889375

  19. Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality

    PubMed Central

    Bárcena, Paloma; Jara-Acevedo, María; Tabernero, María Dolores; López, Antonio; Sánchez, María Luz; García-Montero, Andrés C.; Muñoz-García, Noemí; Vidriales, María Belén; Paiva, Artur; Lecrevisse, Quentin; Lima, Margarida; Langerak, Anton W.; Böttcher, Sebastian; van Dongen, Jacques J.M.

    2015-01-01

    Currently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for clonality, in the diagnostic work-up of chronic lymphoproliferative disorders of NK cells (CLPD-NK). For this purpose, a large panel of markers was evaluated by multiparametric flow cytometry on peripheral blood (PB) CD56low NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56low NK-cell expansions, and 37 with CLPD-NK of undetermined clonality; also, PB samples from 10 healthy adults were included. Clonality was established using the human androgen receptor (HUMARA) assay. Clonal NK cells were found to show decreased expression of CD7, CD11b and CD38, and higher CD2, CD94 and HLADR levels vs. normal NK cells, together with a restricted repertoire of expression of the CD158a, CD158b and CD161 killer-associated receptors. In turn, NK cells from both clonal and polyclonal CLPD-NK showed similar/overlapping phenotypic profiles, except for high and more homogeneous expression of CD94 and HLADR, which was restricted to clonal CLPD-NK. We conclude that the CD94hi/HLADR+ phenotypic profile proved to be a useful surrogate marker for NK-cell clonality. PMID:26556869

  20. Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorder in children and young adults has similar molecular signature to extranodal nasal natural killer/T-cell lymphoma but shows distinctive stem cell-like phenotype.

    PubMed

    Ng, Siok-Bian; Ohshima, Koichi; Selvarajan, Viknesvaran; Huang, Gaofeng; Choo, Shoa-Nian; Miyoshi, Hiroaki; Shimizu, Norio; Reghunathan, Renji; Chua, Hsin-Chieh; Yeoh, Allen Eng-Juh; Quah, Thuan-Chong; Koh, Liang-Piu; Tan, Poh-Lin; Chng, Wee-Joo

    2015-01-01

    We performed gene expression profiling in Epstein-Barr virus (EBV)-associated T/natural killer (NK)-cell lymphoproliferative disorder in children and young adults (TNKLPDC) in order to understand the molecular pathways deregulated in this disease and compared it with nasal-type NK/T-cell lymphoma (NKTL). The molecular and phenotypic signature of TNKLPDC is similar to NKTL, with overexpression of p53, survivin and EZH2. Down-regulation of EZH2 in TNKLPDC cell lines led to an increase in apoptosis and decrease in tumor viability, suggesting that EZH2 may be important for the survival of TNKLPDC cells and hence potentially a useful therapeutic target. Notably, our gene expression profiling revealed a distinctive enrichment of stem cell related genes in TNKLPDC compared to NKTL. This was validated by a significantly higher expression of aldehyde dehydrogenase 1 (ALDH1) in TNKLPDC cell lines compared to NKTL cell lines. The novel discovery of cancer stem cell properties in TNKLPDC has potential therapeutic implications in this group of disorders. PMID:25382618

  1. Eosinophilic density in graft biopsies positive for rejection and blood eosinophil count can predict development of post-transplant digestive tract eosinophilia.

    PubMed

    Bush, Jonathan W; Mohammad, Saeed; Melin-Aldana, Hector; Kagalwalla, Amir F; Arva, Nicoleta C

    2016-06-01

    EGID is a known post-transplant complication. Its etiology has been related to antirejection medication, but other factors may also play a role as only few transplant recipients develop EGID despite standardized treatment. This study aimed to determine whether EGID is associated with rejection events and with a specific phenotype of the rejection-positive graft biopsies in children with solid organ transplant. All patients with liver, heart, and kidney transplant followed at our institution were included in the study. Digestive tract eosinophilia was more common in heart and liver recipients and was a rare event after renal transplantation. Subjects with EGID had higher incidence of rejection and elevated peripheral blood AEC. The first rejection event and high AEC values preceded EGID diagnosis in the majority of patients. Histologically, the initial rejection-positive graft biopsy revealed accentuated eosinophilia in EGID patients compared with non-EGID cohort, which correlated with higher blood eosinophil counts at the time of first rejection episode. Prominent graft tissue and peripheral blood eosinophilia prior to EGID diagnosis suggests a predisposition for eosinophil activation in patients with post-transplant digestive eosinophilic disorder. These parameters can be used as markers for subsequent development of EGID. PMID:26917244

  2. Interactions between virus-related factors and post-transplant ascites in patients with hepatitis C and no cirrhosis: role of cryoglobulinemia.

    PubMed

    Tripon, Simona; Francoz, Claire; Albuquerque, Anna; Paradis, Valérie; Boudjema, Hamza; Voitot, Hélène; Belghiti, Jacques; Valla, Dominique; Durand, François

    2015-02-01

    Refractory ascites may appear in liver transplant recipients with recurrence of hepatitis C virus infection, even in the absence of advanced fibrosis. The mechanisms are unclear. The aim was to determine whether post-transplant cryoglobulinemia could be a predisposing factor for ascites in this population. Retrospective data of 82 liver transplant recipients with HCV recurrence surviving more than 1 year were collected. Cryoglobulinemia was systematically tested after transplantation. All patients had 1-year protocol biopsy with assessment of sinusoidal distension, perisinusoidal fibrosis, and centrolobular necrosis. Additional biopsies were performed when needed. Fourteen of 82 patients (17%) developed refractory ascites. When ascites appeared, fibrosis was stage F0-F1 in 36% and F2-F3 in 57%. Factors independently associated with post-transplant ascites were pretransplant refractory ascites (P = 0.001), fibrosis ≥stage 2 at 1 year (P = 0.002), perisinusoidal fibrosis at 1 year (P = 0.02), and positive cryoglobulinemia (P = 0.02). Patients with ascites had a significantly worse prognosis compared to those without ascites. Refractory ascites may occur in liver transplant recipients with HCV recurrence in the absence of advanced fibrosis. The finding that both positive cryoglobulinemia and perisinusoidal fibrosis at 1 year were significantly associated with ascites suggests that liver microangiopathy is involved in the mechanisms of HCV-related ascites. PMID:25267442

  3. Post-transplant donor-specific antibody production and graft outcome in kidney transplantation: results of sixteen-year monitoring by flow cytometry.

    PubMed

    Piazza, Antonina; Poggi, Elvira; Ozzella, Giuseppina; Borrelli, Laura; Scornajenghi, Alessandra; Iaria, Giuseppe; Tisone, Giuseppe; Adorno, Domenico

    2006-01-01

    Our data show that monitoring by sensitive flow cytometric techniques of the de novo production of anti-HLA antibodies in patients receiving kidney transplantation is a useful and noninvasive tool to identify the onset of an immune response towards the graft before any clinical manifestation of antibody-mediated graft injury. Consequently prospective posttransplant monitoring of anti-HLA donor-directed antibodies may offer the chance to realize an effective clinical intervention in order to prevent graft dysfunction and to prolong graft survival. The long follow-up period of the study allowed us to demonstrate a very low graft survival rate in patients who developed donor-specific HLA antibodies in comparison with patients who did not have antibodies, thus confirming the "humoral theory of transplantation". The posttransplant production of anti-HLA antibodies can predict not only graft failure but also chronic dysfunction of the graft. Moreover, our findings suggest that graft survival is influenced by the epitope- and locus-specificity of anti-HLA donor-directed antibodies. The interval between antibody appearance and loss of graft function was short in some patients but reached several years in others. Moreover, some patients showed consistent production of antibodies for many years and an uneventful clinical status. These findings suggest a mechanism of graft "accommodation" or the production of "harmless" antibodies. Immunosuppressive drug combinations able to inhibit T and B cell activation are useful tools to prevent the humoral immune response against graft and consequently to prolong graft survival. PMID:18365387

  4. Pre-stem cell transplantation enzyme replacement therapy in Hurler syndrome does not lead to significant antibody formation or delayed recovery of the endogenous enzyme post-transplant: a case report.

    PubMed

    Soni, Sandeep; Hente, Monica; Breslin, Nancy; Hersh, Joseph; Whitley, Chester; Cheerva, Alexandra; Bertolone, Salvatore

    2007-08-01

    Combined enzyme replacement therapy (ERT) and stem cell transplant (SCT) were done for a two year old boy with severe Hurler syndrome(HS) with the aim to decrease transplant related complications. He tolerated both the procedures well without any major complications. Urine glycosaminoglycans (GAGs) decreased post-transplant and child has improved clinically and neurologically. Insignificant titers of the anti-iduronidase antibodies which developed post-transplant did not affect the transplant outcome or the endogenous recovery of the alpha-L-iduronidase enzyme. PMID:17631030

  5. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant

    PubMed Central

    Gitto, Stefano; Villa, Erica

    2016-01-01

    Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent significant causes of morbidity and mortality. This is especially true for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic manifestations of metabolic syndrome and after liver transplant both recurrent and de novo steatosis can be found. Usually, post-transplant steatosis shows an indolent outcome with few cases of fibrosis progression. However, in the post-transplant setting, both metabolic syndrome and steatosis might play a key role in the stratification of morbidity and mortality risk, being commonly associated with cardiovascular disease. The single components of metabolic syndrome can be treated with targeted drugs while lifestyle intervention is the only reasonable therapeutic approach for transplant patients with non-alcoholic steatosis or steatohepatitis. PMID:27049380

  6. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant.

    PubMed

    Gitto, Stefano; Villa, Erica

    2016-01-01

    Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent significant causes of morbidity and mortality. This is especially true for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic manifestations of metabolic syndrome and after liver transplant both recurrent and de novo steatosis can be found. Usually, post-transplant steatosis shows an indolent outcome with few cases of fibrosis progression. However, in the post-transplant setting, both metabolic syndrome and steatosis might play a key role in the stratification of morbidity and mortality risk, being commonly associated with cardiovascular disease. The single components of metabolic syndrome can be treated with targeted drugs while lifestyle intervention is the only reasonable therapeutic approach for transplant patients with non-alcoholic steatosis or steatohepatitis. PMID:27049380

  7. Population pharmacokinetic–pharmacodynamic modelling of mycophenolic acid in paediatric renal transplant recipients in the early post-transplant period

    PubMed Central

    Dong, Min; Fukuda, Tsuyoshi; Cox, Shareen; de Vries, Marij T; Hooper, David K; Goebel, Jens; Vinks, Alexander A

    2014-01-01

    Aim The purpose of this study was to develop a population pharmacokinetic and pharmacodynamic (PK−PD) model for mycophenolic acid (MPA) in paediatric renal transplant recipients in the early post-transplant period. Methods A total of 214 MPA plasma concentrations−time data points from 24 patients were available for PK model development. In 17 out of a total of 24 patients, inosine monophosphate dehydrogenase (IMPDH) enzyme activity measurements (n = 97) in peripheral blood mononuclear cells were available for PK−PD modelling. The PK−PD model was developed using non-linear mixed effects modelling sequentially by 1) developing a population PK model and 2) incorporating IMPDH activity into a PK−PD model using post hoc Bayesian PK parameter estimates. Covariate analysis included patient demographics, co-medication and clinical laboratory data. Non-parametric bootstrapping and prediction-corrected visual predictive checks were performed to evaluate the final models. Results A two compartment model with a transit compartment absorption best described MPA PK. A non-linear relationship between dose and MPA exposure was observed and was described by a power function in the model. The final population PK parameter estimates (and their 95% confidence intervals) were CL/F, 22 (14.8, 25.2) l h−1 70 kg−1; Vc/F, 45.4 (29.6, 55.6) l; Vp/F, 411 (152.6, 1472.6)l; Q/F, 22.4 (16.0, 32.5) l h−1; Ka, 2.5 (1.45, 4.93) h−1. Covariate analysis in the PK study identified body weight to be significantly correlated with CL/F. A simplified inhibitory Emax model adequately described the relationship between MPA concentration and IMPDH activity. The final population PK−PD parameter estimates (and their 95% confidence intervals) were: E0, 3.45 (2.61, 4.56) nmol h−1 mg−1 protein and EC50, 1.73 (1.16, 3.01) mg l−1. Emax was fixed to 0. There were two African-American patients in our study cohorts and both had low IMPDH baseline activities (E0) compared with Caucasian patients (mean value 2.13 mg l−1 vs. 3.86 mg l−1). Conclusion An integrated population PK−PD model of MPA has been developed in paediatric renal transplant recipients. The current model provides information that will facilitate future studies and may be implemented in a Bayesian algorithm to allow a PK−PD guided therapeutic drug monitoring strategy. PMID:24837828

  8. Lymphoproliferative and Gamma Interferon Responses to Stress-Regulated Mycobacterium avium subsp. paratuberculosis Recombinant Proteins

    PubMed Central

    Gurung, Ratna B.; Begg, Douglas J.; Purdie, Auriol C.; de Silva, Kumudika; Bannantine, John P.

    2014-01-01

    Johne's disease in ruminants is a chronic infection of the intestines caused by Mycobacterium avium subsp. paratuberculosis. An important strategy to control disease is early detection, and a potentially efficient method for early detection is measurement of cell-mediated immune responses developed by the host in response to exposure or infection. One method is to measure lymphoproliferation and cytokine release from the host cells when exposed to the organism or parts of the organism. In this study, 10 recombinant M. avium subsp. paratuberculosis proteins known to be upregulated under in vitro stress conditions were evaluated by examining their ability to evoke memory as a result of exposure by vaccination or oral challenge with live Mycobacterium avium subsp. paratuberculosis. Out of 10 proteins, MAP2698c was found to induce higher cell-mediated immune responses in vaccinated and challenged sheep in comparison to healthy controls. The findings suggest that not all stress-regulated proteins have the diagnostic potential to detect cell-mediated immune responses in ovine paratuberculosis. PMID:24695774

  9. Successful treatment of posttransplantation lymphoproliferative disorder (PTLD) following renal allografting is associated with sustained CD8(+) T-cell restoration.

    PubMed

    Porcu, Pierluigi; Eisenbeis, Charles F; Pelletier, Ronald P; Davies, Elizabeth A; Baiocchi, Robert A; Roychowdhury, Sameek; Vourganti, Srinivas; Nuovo, Gerard J; Marsh, William L; Ferketich, Amy K; Henry, Mitchell L; Ferguson, Ronald M; Caligiuri, Michael A

    2002-10-01

    Posttransplantation lymphoproliferative disorder (PTLD) is a life-threatening Epstein-Barr virus (EBV)-associated B-cell malignancy occurring in 1% to 2% of renal transplantation patients. Host- and PTLD-related factors determining the likelihood of tumor response following reduction of immune suppression (IS) and antiviral therapy remain largely unknown. Standard therapy for PTLD is not well established. Eleven consecutive renal transplantation patients who developed EBV-positive PTLD 8 to 94 months after allografting were uniformly treated with acyclovir and IS reduction. All PTLDs were EBV-positive diffuse large B-cell lymphomas. Ten patients (91%) obtained a durable complete response (CR), and 9 (82%) have remained in continuous CR with a median follow-up of 29 months. Five patients (45%) lost their allograft. Of these, 4 patients had PTLD affecting the transplanted kidney. Peripheral blood CD8(+) T cells increased significantly (P =.0078) from baseline in 8 responders available for analysis. One of 2 patients whose absolute CD8(+) T-cell count subsequently dropped to baseline after IS reduction relapsed. The expanded CD8(+) T cells from 2 responders specifically recognized an immunodominant peptide from the EBV lytic gene BZLF-1. Another lytic EBV gene, thymidine kinase, was expressed in all 8 PTLDs tested. IS reduction and antiviral therapy for PTLD after renal transplantation is a highly successful therapeutic combination, but the risk of graft rejection is significant, particularly in patients with PTLD involving the renal allograft. A sustained expansion of CD8(+) T cells and a cellular immune response to EBV lytic antigens may be important for PTLD clearance in renal transplantation patients. PMID:12239141

  10. Fine-needle aspiration evaluation of lymphoproliferative lesions in human immunodeficiency virus-positive patients. A multiparameter approach.

    PubMed

    Shabb, N; Katz, R; Ordonez, N; Goodacre, A; Hirsch-Ginsberg, C; el-Naggar, A

    1991-02-15

    Forty-six fine-needle aspirates of lymphoproliferative lesions from 31 human immunodeficiency virus (HIV)-positive patients were reviewed using cytomorphologic, immunocytochemical, flow cytometric (FCM), cytogenetic, and molecular studies. There were 29 lymphomas (15 small non-cleaved cell [SNCL], 11 large cell [LCL], one small lymphocytic, and two Hodgkin's), 14 reactive hyperplasias, and three "atypical lymphoid proliferations." The reactive hyperplasias were characteristically polymorphic and polyclonal lymphoid populations; six of seven were diploid on FCM, the seventh was hypodiploid. Higher proliferative indices (mean, 11.6%) and higher RNA indices (mean, 1.2) characterized this subgroup compared with published reactive lymphoid hyperplasias from patients without HIV positivity. Aspirates of SNCL showed monotonous populations of intermediate-sized cells except in one patient where a giant cell syncytial variant occurred. Nine of 13 SNCL aspirates showed light chain restriction. JH rearrangement revealed B-cell lineage in one aspirate in which immunocytochemical study was negative for Kappa, lambda, B1, and Leu-4. Nine of 12 SNCL were diploid; the mean proliferative index was 25.6% and the mean RNA index 2.3. Chromosomal translocations involving the c-myc locus were demonstrated in five of seven SNCL aspirates karyotyped. Five of eight LCL showed light chain restriction the remaining three showed null cell phenotype. Large cell lymphomas were diploid on tetraploid with the mean proliferative index of 22.0% and mean RNA index of 2.2. One of two LCL aspirates karyotyped demonstrated c-myc translocation. Despite the multiparameter approach, a definitive diagnosis could not be reached in three aspirates. PMID:1991248

  11. Castleman's disease in childhood: report of three cases and review of the literature

    PubMed Central

    2011-01-01

    Castleman's disease (CD) is a rare, localized or generalized, lymphoproliferative disorder with a frequent mediastinal location, but possible in any lymph node or extra nodal site. It usually appears in young adults whilst it rarely occurs in childhood. There are only about 100 pediatric cases published, five of them in Italy. We report 3 cases of localized Castleman's disease, investigated in our Department in a 3 years period and reviewed the literature. PMID:22014148

  12. Systemic Epstein-Barr virus-positive T/natural killer-cell lymphoproliferative disorder: a case report and review of literature

    PubMed Central

    Tan, Xia; Liu, Xianling; Hu, Chunhong; Liu, Fuyou; Wu, Fang

    2014-01-01

    Systemic Epstein-Barr virus-positive T/natural killer-cell lymphoproliferative disorder (EBV + LPD) has predominantly been observed among pediatric patients as a life-threatening condition. The present study presents a rare case of EBV + LPD in an adult with good outcome. This patient’s history is more than 2 years and her condition was stable. She received 6 cycles of chemotherapy cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP). The evaluation was complete remission. The low levels of EBV-DNA in the peripheral blood may have potential benefit factor for the sensitivity to the chemotherapy and good outcome. PMID:25400787

  13. Epstein-Barr virus (EBV)-positive sporadic burkitt lymphoma: an age-related lymphoproliferative disorder?

    PubMed

    Satou, Akira; Asano, Naoko; Nakazawa, Atsuko; Osumi, Tomoo; Tsurusawa, Masahito; Ishiguro, Atsushi; Elsayed, Ahmed Ali; Nakamura, Naoya; Ohshima, Koichi; Kinoshita, Tomohiro; Nakamura, Shigeo

    2015-02-01

    Epstein-Barr virus (EBV) is detected in 20% to 30% of sporadic Burkitt lymphoma (sBL). However, only a few studies of EBV-positive (EBV) sBL have been reported, and its characteristics still remain controversial. To highlight the features of EBV sBL, we compared the clinicopathologic characteristics of 33 cases of EBV and 117 cases of EBV-negative (EBV) sBL in Japan. EBV sBL showed significantly higher age distribution (median, 42 vs. 13 y; P<0.0001) and higher frequency of patients older than 50 years (48% vs. 16%, P<0.0001). We also revealed the difference of the involved sites. The EBV group showed significantly higher incidence of involvement of tonsil (P=0.027), adrenal gland (P=0.011), and cervical lymph node (P=0.040). In addition, the EBV group tended to have higher incidence of nodal involvement (P=0.078) and involvement of para-aorta lymph node (P=0.084) and heart (P=0.050). In contrast, the gastrointestinal tract was less frequently affected in EBV sBL (P=0.024). In addition, the less positivity for MUM1 (P=0.020) of EBV sBL was highlighted. These results indicate that biological behavior and pathogenesis of EBV sBL might be different from those of EBV sBL. Our results demonstrate that EBV sBL has an aspect of age-related disease and is a distinct clinicopathologic subtype, which should be distinguished from EBV sBL. PMID:25321330

  14. [Transfer of skills: implementing post-transplant follow-up care status for transplant nurses: a report by the SFGM-TC].

    PubMed

    Cornillon, J; Peffault de Latour, R; Apaza, S; Bourg, M-A; Courbon, C; Evard, S; Guiraud, M; Le Bars, L; Petit, S; Magro, L; Schmitt, S; Tardieu, L; Samsonova, O; Tipton, R; Yakoub-Agha, I

    2014-08-01

    The number of Hematopoietic Stem Cell Transplantations has globally taken off in the past decade. However, this increase in transplantation activity has put in the spotlight the need to create a special transplantation-skilled population of nurses. This type of specialisation allocated solely to this activity has not existed within the French nursing community until now. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) sets up its forth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille. Here we report our results and recommendations regarding the implementation of a transplant nurse status for post-transplant follow-up care. PMID:24972456

  15. Targeting Pathogenic Post-Ischemic Self-Recognition by Natural IgM to Protect Against Post-Transplant Cardiac Reperfusion Injury

    PubMed Central

    Atkinson, Carl; Qiao, Fei; Yang, Xiaofeng; Zhu, Peng; Reaves, Nicholas; Kulik, Liudmila; Goddard, Martin; Holers, V. Michael; Tomlinson, Stephen

    2015-01-01

    Background Natural IgM antibodies represent a class of innate pattern recognition receptors that recognize danger associated molecular patterns expressed on stressed or dying cells. They play important roles in tissue homeostasis by disposing of pre-necrotic cells and suppressing inflammation. However, ischemic insult leads to a pathogenic level of IgM binding and complement activation, resulting in inflammation and injury. We investigate the role of self-reactive IgM in the unique setting of transplantation, where the donor organ undergoes both cold and warm ischemia, and global ischemic insult. Methods and Results By transplanting hearts from wild-type donor mice into antibody-deficient mice reconstituted with specific self-reactive IgM mAbs, we identified neoepitopes expressed post-transplant, and demonstrated a key role for IgM recognition of these epitopes in graft injury. With this information, we developed and characterized a therapeutic strategy that exploited the post-ischemia recognition system of natural antibodies. Based on neoepitope identification, we constructed an anti-annexin-IV single chain antibody (scFv) and an scFv linked to Crry, an inhibitor of C3 activation (scFv-Crry). In an allograft transplant model, in which recipients contain a full natural antibody repertoire, both constructs blocked graft IgM binding and complement activation, and significantly reduced graft inflammation and injury. Furthermore, scFv-Crry specifically targeted to the transplanted heart and, unlike complement deficiency, did not affect immunity to infection, an important consideration for immunosuppressed transplant recipients. Conclusions We identified pathophysiologically important epitopes expressed within the heart post-transplant, and describe a novel translatable strategy for targeted complement inhibition that has several advantages over currently available approaches. PMID:25825397

  16. PTEN and PI-3 kinase inhibitors control LPS signaling and the lymphoproliferative response in the CD19+ B cell compartment

    SciTech Connect

    Singh, Alok R.; Peirce, Susan K.; Joshi, Shweta; Durden, Donald L.

    2014-09-10

    Pattern recognition receptors (PRRs), e.g. toll receptors (TLRs) that bind ligands within the microbiome have been implicated in the pathogenesis of cancer. LPS is a ligand for two TLR family members, TLR4 and RP105 which mediate LPS signaling in B cell proliferation and migration. Although LPS/TLR/RP105 signaling is well-studied; our understanding of the underlying molecular mechanisms controlling these PRR signaling pathways remains incomplete. Previous studies have demonstrated a role for PTEN/PI-3K signaling in B cell selection and survival, however a role for PTEN/PI-3K in TLR4/RP105/LPS signaling in the B cell compartment has not been reported. Herein, we crossed a CD19cre and PTEN{sup fl/fl} mouse to generate a conditional PTEN knockout mouse in the CD19+ B cell compartment. These mice were further crossed with an IL-14α transgenic mouse to study the combined effect of PTEN deletion, PI-3K inhibition and expression of IL-14α (a cytokine originally identified as a B cell growth factor) in CD19+ B cell lymphoproliferation and response to LPS stimulation. Targeted deletion of PTEN and directed expression of IL-14α in the CD19+ B cell compartment (IL-14+PTEN-/-) lead to marked splenomegaly and altered spleen morphology at baseline due to expansion of marginal zone B cells, a phenotype that was exaggerated by treatment with the B cell mitogen and TLR4/RP105 ligand, LPS. Moreover, LPS stimulation of CD19+ cells isolated from these mice display increased proliferation, augmented AKT and NFκB activation as well as increased expression of c-myc and cyclinD1. Interestingly, treatment of LPS treated IL-14+PTEN-/- mice with a pan PI-3K inhibitor, SF1126, reduced splenomegaly, cell proliferation, c-myc and cyclin D1 expression in the CD19+ B cell compartment and normalized the splenic histopathologic architecture. These findings provide the direct evidence that PTEN and PI-3K inhibitors control TLR4/RP105/LPS signaling in the CD19+ B cell compartment and that pan PI-3 kinase inhibitors reverse the lymphoproliferative phenotype in vivo. - Highlights: • First genetic evidence that PTEN controls LPS/TLR4 signaling in B lymphocytes. • Evidence that PTEN regulates LPS induced lymphoproliferation in vivo. • PI-3 kinase inhibitors block LPS induced lymphoproliferation in vivo.

  17. In vitro lymphoproliferative assays with HgCl2 cannot identify patients with systemic symptoms attributed to dental amalgam.

    PubMed

    Cederbrant, K; Gunnarsson, L G; Hultman, P; Norda, R; Tibbling-Grahn, L

    1999-08-01

    Dental amalgam is suspected, by some exposed individuals, to cause various systemic psychological, sensory, and neurological symptoms. Since not all amalgam-bearers experience such reactions, an individual characteristic--for example, a susceptible immune system--might explain these conditions. In vitro lymphocyte proliferation is a valuable tool in the diagnosis of allergy. With HgCl2 as the antigen, however, the test is hampered, because Hg2+ can cause unspecific lymphocyte proliferation, optimal at 1.4 to 9.5 micrograms HgCl2/mL. Recently, the use of suboptimal HgCl2 concentrations (< or = 0.5 microgram/mL) has been suggested to circumvent these problems. The main aim of this study was to investigate whether patients with systemic symptoms alleged to result from the presence of dental amalgam differ from healthy controls, with reference to in vitro lymphoproliferative responses to HgCl2 < or = 0.5 microgram/mL. Three different test protocols--lymphocyte transformation test (LTT) in micro- and macro-cultures, and the memory lymphocyte immunostimulation assay (MELISA)--were used. Other immune parameters--such as a standard patch test for dental materials, the number of T- and B-lymphocytes, monocytes, granulocytes, and NK cells in peripheral blood, allergic symptoms, and predisposition--were also investigated. Twenty-three amalgam patients, 30 healthy blood donors with amalgam, ten healthy subjects without amalgam, and nine patients with oral lichen planus (OLP) adjacent to dental amalgam and a positive patch test to Hg0 were tested. None of the investigated immune parameters revealed any significant differences between amalgam patients and controls. The sensitivity of in vitro lymphocyte proliferation ranged from 33 to 67%, with the OLP patients as a positive control group, and the specificity from 0 to 70% for healthy controls with a negative patch test to Hg0. Thus, despite the use of HgCl2 < or = 0.5 microgram/mL, a high frequency of positive results was obtained among healthy subjects with or without dental amalgam. Consequently, in vitro lymphocyte proliferation with HgCl2 cannot be used as an objective marker for mercury allergy in dental amalgam-bearers. PMID:10439033

  18. A Primary Cutaneous CD30-Positive T-Cell Lymphoproliferative Disorder Arising in a Patient With Multiple Myeloma and Cutaneous Amyloidosis.

    PubMed

    Romano, Ryan C; Cohen, Daniel N; Howard, Matthew T; Wieland, Carilyn N

    2016-05-01

    CD30-positive cutaneous lymphoproliferative disorders, a group of T-cell neoplasms, including lymphomatoid papulosis (LyP) and cutaneous anaplastic large cell lymphoma, require careful clinicopathologic correlation for diagnosis. An association between LyP and the development of a second hematolymphoid malignancy has been established in the literature. LyP has also been reported with systemic amyloidosis, but no such reports have documented coexisting cutaneous amyloid deposition with LyP to our knowledge. A 66-year-old woman with cutaneous amyloidosis, secondary to multiple myeloma, in remission, presented with erythematous and dark-brown papules involving the right arm, scalp, and torso. Punch biopsy of the arm showed a dermal infiltrate of intermediate-sized lymphocytes, some of which displayed a plasmacytoid morphology and prominent nodular subepidermal amyloid deposition. Punch biopsy of the scalp similarly showed a nonepidermotropic dense dermal infiltrate of intermediate-sized plasmacytoid lymphocytes and multifocal amyloid deposition. Both infiltrates were immunophenotypically CD30-positive, anaplastic lymphoma kinase-negative T-cell lymphoproliferative processes. Subsequent studies showed no systemic involvement, and clinical correlation suggested a final diagnosis of LyP. We present this case of LyP, which histologically mimics a B-cell proliferation with a plasmacytoid morphology arising in association with cutaneous amyloidosis to highlight the importance of clinicopathologic correlation, a thorough battery of immunohistochemical studies, and consideration for a second hematologic malignancy arising in the setting of LyP. PMID:26981738

  19. Liver transplantation for nonalcoholic fatty liver disease: New challenges and new opportunities

    PubMed Central

    Shaker, Mina; Tabbaa, Adam; Albeldawi, Mazen; Alkhouri, Naim

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is becoming rapidly one of the most common indications for orthotopic liver transplantation in the world. Development of graft steatosis is a significant problem during the post-transplant course, which may happen as a recurrence of pre-existing disease or de novo NAFLD. There are different risk factors that might play a role in development of graft steatosis including post-transplant metabolic syndrome, immune-suppressive medications, genetics and others. There are few studies that assessed the effects of NAFLD on graft and patient survival; most of them were limited by the duration of follow up or by the number of patients. With this review article we will try to shed light on post-liver transplantation NAFLD, significance of the disease, how it develops, risk factors, clinical course and treatment options. PMID:24833862

  20. Marek's disease and new approaches to its control.

    PubMed

    Zelnk, V

    1995-02-01

    Marek's disease (MD) is a lymphoproliferative disorder induced by a herpesvirus. Several factors, including those virus-encoded and host-dependent, affect the course of the disease. Existing vaccination program is based on the use of attenuated strains of MD virus (MDV) serotype 1 and on strains of non-oncogenic serotype 2 (MDV2) and serotype 3 (herpesvirus of turkey-HVT) viruses. Failures resulting in disease progress have been reported and indicate need for production of new, more effective vaccines. It is likely that future development of MD vaccines will rely on recombinant molecules technology. PMID:7572471

  1. Current diagnosis and treatment of Castleman's disease.

    PubMed

    González García, A; Moreno Cobo, M Á; Patier de la Peña, J L

    2016-04-01

    Castleman's disease is not just a single disease but rather an uncommon, heterogeneous group of nonclonal lymphoproliferative disorders, which have a broad spectrum of clinical expression. Three histological types have been reported, along with several clinical forms according to clinical presentation, histological substrate and associated diseases. Interleukin-6, its receptor polymorphisms, the human immunodeficiency virus and the human herpes virus 8 are involved in the etiopathogenesis of Castleman's disease. The study of this disease has shed light on a syndrome whose incidence is unknown. Despite recent significant advances in our understanding of this disease and the increasing therapeutic experience with rituximab, tocilizumab and siltuximab, there are still difficult questions concerning its aetiology, prognosis and optimal treatment. PMID:26749192

  2. Genetic Diversity of the KIR/HLA System and Susceptibility to Hepatitis C Virus-Related Diseases

    PubMed Central

    De Re, Valli; Caggiari, Laura; De Zorzi, Mariangela; Repetto, Ombretta; Zignego, Anna Linda; Izzo, Francesco; Tornesello, Maria Lina; Buonaguro, Franco Maria; Mangia, Alessandra; Sansonno, Domenico; Racanelli, Vito; De Vita, Salvatore; Pioltelli, Pietro; Vaccher, Emanuela; Beretta, Massimiliano; Mazzaro, Cesare; Libra, Massimo; Gini, Andrea; Zucchetto, Antonella; Cannizzaro, Renato; De Paoli, Paolo

    2015-01-01

    Background The variability in the association of host innate immune response to Hepatitis C virus (HCV) infection requires ruling out the possible role of host KIR and HLA genotypes in HCV-related disorders: therefore, we therefore explored the relationships between KIR/HLA genotypes and chronic HCV infection (CHC) as they relate to the risk of HCV-related hepatocarcinoma (HCC) or lymphoproliferative disease progression. Methods and Findings We analyzed data from 396 HCV-positive patients with CHC (n = 125), HCC (118), and lymphoproliferative diseases (153), and 501 HCV-negative patients. All were HIV and HBV negative. KIR-SSO was used to determine the KIR typing. KIR2DL5 and KIR2DS4 variants were performed using PCR and GeneScan analysis. HLA/class-I genotyping was performed using PCR-sequence-based typing. The interaction between the KIR gene and ligand HLA molecules was investigated. Differences in frequencies were estimated using Fisher’s exact test, and Cochran-Armitage trend test. The non-random association of KIR alleles was estimated using the linkage disequilibrium test. We found an association of KIR2DS2/KIR2DL2 genes, with the HCV-related lymphoproliferative disorders. Furthermore, individuals with a HLA-Bw6 KIR3DL1+ combination of genes showed higher risk of developing lymphoma than cryoglobulinemia. KIR2DS3 gene was found to be the principal gene associated with chronic HCV infection, while a reduction of HLA-Bw4 + KIR3DS1+ was associated with an increased risk of developing HCC. Conclusions Our data highlight a role of the innate-system in developing HCV-related disorders and specifically KIR2DS3 and KIR2D genes demonstrated an ability to direct HCV disease progression, and mainly towards lymphoproliferative disorders. Moreover the determination of KIR3D/HLA combination of genes direct the HCV progression towards a lymphoma rather than an hepatic disease. In this contest IFN-α therapy, a standard therapy for HCV-infection and lymphoproliferative diseases, known to be able to transiently enhance the cytotoxicity of NK-cells support the role of NK cells to counterstain HCV-related and lymphoproliferative diseases. PMID:25700262

  3. Autoimmune Lymphoproliferative Syndrome (ALPS)

    MedlinePlus

    ... About NIAID News & Events Volunteer NIAID > Health & Research Topics > Autoimmune Lymphproliferative Syndrome (ALPS) Skip Website Tools Website Tools Print this page Order publications ​​​​​ Contact Info​ View a list of ...

  4. Autoimmune-Like Hepatitis: A "Hepatitic" Manifestation of Chronic Graft Versus Host Disease in Post-Stem Cell Transplant.

    PubMed

    Baniak, Nick M; Kanthan, Rani

    2016-04-01

    A 59-year-old female received a matched related donor stem cell transplant for chronic myelogenous leukemia. After being successfully treated with prednisone for chronic graft versus host disease that initially started 50 days posttransplant, she developed hepatic dysfunction during the steroid taper on day 531, as evidenced by jaundice, elevated liver enzymes, and increased bilirubin. Liver biopsy showed histology suggestive of autoimmune-like hepatitis, which is a rare manifestation of chronic "hepatitic" graft versus host disease. PMID:26464160

  5. Blood disorders typically associated with renal transplantation

    PubMed Central

    Yang, Yu; Yu, Bo; Chen, Yun

    2015-01-01

    Renal transplantation has become one of the most common surgical procedures performed to replace a diseased kidney with a healthy kidney from a donor. It can help patients with kidney failure live decades longer. However, renal transplantation also faces a risk of developing various blood disorders. The blood disorders typically associated with renal transplantation can be divided into two main categories: (1) Common disorders including post-transplant anemia (PTA), post-transplant lymphoproliferative disorder (PTLD), post-transplant erythrocytosis (PTE), and post-transplant cytopenias (PTC, leukopenia/neutropenia, thrombocytopenia, and pancytopenia); and (2) Uncommon but serious disorders including hemophagocytic syndrome (HPS), thrombotic microangiopathy (TMA), therapy-related myelodysplasia (t-MDS), and therapy-related acute myeloid leukemia (t-AML). Although many etiological factors involve the development of post-transplant blood disorders, immunosuppressive agents, and viral infections could be the two major contributors to most blood disorders and cause hematological abnormalities and immunodeficiency by suppressing hematopoietic function of bone marrow. Hematological abnormalities and immunodeficiency will result in severe clinical outcomes in renal transplant recipients. Understanding how blood disorders develop will help cure these life-threatening complications. A potential therapeutic strategy against post-transplant blood disorders should focus on tapering immunosuppression or replacing myelotoxic immunosuppressive drugs with lower toxic alternatives, recognizing and treating promptly the etiological virus, bacteria, or protozoan, restoring both hematopoietic function of bone marrow and normal blood counts, and improving kidney graft survival. PMID:25853131

  6. Blood disorders typically associated with renal transplantation.

    PubMed

    Yang, Yu; Yu, Bo; Chen, Yun

    2015-01-01

    Renal transplantation has become one of the most common surgical procedures performed to replace a diseased kidney with a healthy kidney from a donor. It can help patients with kidney failure live decades longer. However, renal transplantation also faces a risk of developing various blood disorders. The blood disorders typically associated with renal transplantation can be divided into two main categories: (1) Common disorders including post-transplant anemia (PTA), post-transplant lymphoproliferative disorder (PTLD), post-transplant erythrocytosis (PTE), and post-transplant cytopenias (PTC, leukopenia/neutropenia, thrombocytopenia, and pancytopenia); and (2) Uncommon but serious disorders including hemophagocytic syndrome (HPS), thrombotic microangiopathy (TMA), therapy-related myelodysplasia (t-MDS), and therapy-related acute myeloid leukemia (t-AML). Although many etiological factors involve the development of post-transplant blood disorders, immunosuppressive agents, and viral infections could be the two major contributors to most blood disorders and cause hematological abnormalities and immunodeficiency by suppressing hematopoietic function of bone marrow. Hematological abnormalities and immunodeficiency will result in severe clinical outcomes in renal transplant recipients. Understanding how blood disorders develop will help cure these life-threatening complications. A potential therapeutic strategy against post-transplant blood disorders should focus on tapering immunosuppression or replacing myelotoxic immunosuppressive drugs with lower toxic alternatives, recognizing and treating promptly the etiological virus, bacteria, or protozoan, restoring both hematopoietic function of bone marrow and normal blood counts, and improving kidney graft survival. PMID:25853131

  7. Kikuchi-Fujimoto Disease: Unusual Presentation of Rare Disease

    PubMed Central

    Vu, Duy; Reddy, Srini; Day, Lynn; Aydin, Nail; Misra, Subhasis

    2015-01-01

    Kikuchi-Fujimoto disease (KFD) is a rare, benign disorder that typically follows a self-limiting natural course and was initially described in young females of Asian descent. Its clinical presentation may mimic lymphoproliferative disorders, connective tissue disorders, and chronic infections. This often leads to misdiagnosis and inappropriate treatment. The exact cause of this condition remains unknown although autoimmune processes and certain infectious agents have been associated with the disease. The diagnosis of KFD is made histopathologically. Treatment is supportive and long-term follow-up is recommended due to increased risk of future development of systemic lupus erythematosus. Here we are presenting a case of a patient with an unusual presentation of KFD.

  8. Cutaneous necrotizing vasculitis. Relation to systemic disease.

    PubMed

    Lotti, T M; Comacchi, C; Ghersetich, I

    1999-01-01

    Cutaneous necrotizing vasculitis (CNV) is a complex multisystem disease generally involving the skin and mucous membranes, often accompanied by renal, gastrointestinal, pericardial, neurological, and articular signs and symptoms. CNV may be idiopatical or occur in association with a drug, infection, or underlying disease. CNV has been shown in patients with chronic infections (viral, bacterial, protozoa, helminthic), serum sickness, a variety of collagen vascular diseases (systemic lupus erythematous, Sjögren's syndrome, rheumatoid arthritis, Behçet's disease) hyperglobulinemic states, cryoglobulinemia, bowel bypass syndrome, ulcerative colitis, cystic fibrosis, primary biliary cirrhosis and HIV infection. Association with malignancies is not frequent. Lymphoproliferative disorders (Hodgkin's disease, mycosis fungoides, lymphosarcoma, adult T-cell leukemia, multiple mieloma) and solid tumors (lung cancer, colon carcinoma, renal, prostate, head and neck cancer and breast cancer) may be associated with CNV. Whenever possible, treatment is directed at the elimination of the cause. In other cases after adequate laboratory screening local and systemic therapy are recommended. PMID:10599332

  9. Diffuse Cystic Lung Disease. Part I.

    PubMed

    Gupta, Nishant; Vassallo, Robert; Wikenheiser-Brokamp, Kathryn A; McCormack, Francis X

    2015-06-15

    The diffuse cystic lung diseases (DCLDs) are a group of pathophysiologically heterogenous processes that are characterized by the presence of multiple spherical or irregularly shaped, thin-walled, air-filled spaces within the pulmonary parenchyma. Although the mechanisms of cyst formation remain incompletely defined for all DCLDs, in most cases lung remodeling associated with inflammatory or infiltrative processes results in displacement, destruction, or replacement of alveolar septa, distal airways, and small vessels within the secondary lobules of the lung. The DCLDs can be broadly classified according to underlying etiology as those caused by low-grade or high-grade metastasizing neoplasms, polyclonal or monoclonal lymphoproliferative disorders, infections, interstitial lung diseases, smoking, and congenital or developmental defects. In the first of a two-part series, we present an overview of the cystic lung diseases caused by neoplasms, infections, smoking-related diseases, and interstitial lung diseases, with a focus on lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis. PMID:25906089

  10. CD8-positive T-cell lymphoproliferative disorder associated with Epstein-Barr virus-infected B-cells in a rheumatoid arthritis patient under methotrexate treatment.

    PubMed

    Koji, Hitoshi; Yazawa, Takuya; Nakabayashi, Kimimasa; Fujioka, Yasunori; Kamma, Hiroshi; Yamada, Akira

    2016-03-01

    We report a 48-year-old female who developed lymphoproliferative disorder (LPD) during treatment of rheumatoid arthritis (RA) with methotrexate (MTX). She presented with multiple tumors in the cervical lymph nodes (LNs), multiple lung shadows and round shadows in both kidneys with pancytopenia and a high CRP level. The LN showed CD8-positive T-cell LPD associated with Epstein-Barr (EB) virus-infected B-cells. Clonality assays for immunoglobulin (Ig) heavy chain and T-cell receptor gamma (TCRγ) were negative. The cessation of MTX without chemotherapy resulted in the complete disappearance of the tumors and abnormal clinical features. We compared this case with previously published ones and discuss the pathological findings, presuming that the proliferation of CD8 T-cells was a reactive manifestation to reactivated EB virus-infected B-cells. PMID:24386983

  11. Localized Castleman's Disease in the Breast in a Young Woman

    PubMed Central

    Guio, José Ismael; López-Correa, Patricia

    2016-01-01

    Castleman's disease (CD) is a rare lymphoproliferative disorder of unknown etiology. It typically occurs in adulthood but it may also develop in childhood. Clinically, this disease may be classified as localized (unicentric) or systemic (multicentric). Six cases of breast CD have been described in the literature, and all have been reported in adults. Herein we describe the case of a 15-year-old female who presented with a slow-growing tumor in the right breast. The tumor was excised and histopathological examination demonstrated hyaline vascular variant CD. After two years of follow-up, the patient was asymptomatic without evidence of cervical or axillary lymphadenopathy. PMID:27073709

  12. Inferior graft survival of hepatitis B core positive grafts is not influenced by post-transplant hepatitis B infection in liver recipients-A 35-year single-center experience.

    PubMed

    Brandl, Andreas; Stolzlechner, Philipp; Eschertzhuber, Stephan; Aigner, Felix; Weiss, Sascha; Vogel, Wolfgang; Krannich, Alexander; Neururer, Sabrina; Pratschke, Johann; Graziadei, Ivo; Öllinger, Robert

    2016-04-01

    Nonoptimal liver grafts, and among them organs from anti-HBc+ donors, are increasingly used for liver transplantation. In this retrospective study including 1065 adult liver transplantations performed between 1977 and 2012, we analyzed long-term patient and graft survival and occurrence of HBV infection. A total of 52 (5.1%) patients received an anti-HBc+ graft. The 10-year graft and patient survival of these recipients were 50.9% and 59.0% compared to 72.0% and 76.5% (P = 0.001; P = 0.004) of patients receiving anti-HBc- grafts, respectively. Cox regression model showed that high urgency allocation (P = 0.003), recipient age (P = 0.027), anti-HCV+ recipients (P = 0.005), and anti-HBc+ organs (P = 0.048) are associated with decreased graft survival. Thirteen of 52 (25.0%) patients receiving anti-HBc+ grafts developed post-transplant HBV infection within a mean of 2.8 years. In this study, antiviral prophylaxis did not have significant impact on HBV infection, but long-term survival (P = 0.008). Development of post-transplant HBV infection did not affect adjusted 10-year graft survival (100% vs. 100%; P = 1). Anti-HBc+ liver grafts can be transplanted with reasonable but inferior long-term patient and graft survival. The inferior graft survival is not, however, related with post-transplant HBV infection as long as early diagnosis and treatment take place. PMID:26716608

  13. Haploidentical hematopoietic stem cell transplantation with post-transplant high-dose cyclophosphamide in high-risk children: A single-center study.

    PubMed

    Yesilipek, M Akif; Uygun, Vedat; Karasu, Gulsun; Daloglu, Hayriye; Dincer, Zeynep

    2016-05-01

    Recently, haploidentical transplantations have been performed with unmanipulated BM or PBSC. This approach is becoming more widely adopted with the use of PTCY. However, there is limited evidence about this approach in children. We present 15 children who received 16 haploidentical HSCT with unmanipulated BM or PBSC using PTCY for GVHD prophylaxis. Post-transplant CY(50 mg/kg IV) was given on the third and fifth day, and CsA or tacrolimus with MMF or MP was also used for GVHD prophylaxis. All patients engrafted at a median of 16 and 18 days for neutrophil and thrombocyte recovery, respectively. Grades II-III acute GVHD developed in seven patients, and mild chronic GVHD was found in two patients. Two patients died within the first 100 days due to sepsis (TRM 12.5%). Eleven patients are currently alive, with a median follow-up of 12 months (range 6-22 months). The 12-month OS and DFS were 75 ± 10.8% and 68.8 ± 11.6%, respectively. Our results with these high-risk patients are encouraging for haploidentical HSCT in pediatric patients. Future studies should continue to assess haploidentical HSCT, including comparison of other modalities, in a primary pediatric population. PMID:26707539

  14. Importance of glucokinase −258G/A polymorphism in Asian Indians with post-transplant and type 2 diabetes mellitus

    PubMed Central

    Khan, Imran Ali; Vattam, Kiran Kumar; Jahan, Parveen; Hasan, Qurratulain; Rao, Pragna

    2016-01-01

    Summary Type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) are non-synonymous forms of diabetes. Glucokinase (GCK) plays a key role in glucose metabolism. The relationship between the GCK promoter and specific types of diabetes, such as PTDM and T2DM, in the Asian Indian population is unknown. We examined the occurrence of a specific GCK promoter variant (−258G/A) in patients with T2DM and PTDM. The case-control study enrolled 640 Asian Indian subjects, including controls (n = 250) and T2DM (n = 250), PTDM (n = 42), and non-post-transplant diabetes mellitus (non-PTDM) (n = 98) patients. Purified Deoxyribonucleic acid (DNA) was genotyped with the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. The digested PCR products were analyzed on 12% polyacrylamide gels. The anthropometric, biochemical, and clinical details of each group were documented. GCK −258G/A alleles and genotypes were not associated with T2DM. However, among PTDM subjects, we detected a higher frequency of heterozygotes (52.4%) and a positive association with alleles/genotypes. The results suggest that the promoter region (−258G/A) of GCK plays an important role in PTDM in Asian Indians. PMID:26989645

  15. A Case of Retroperitoneal Castleman's Disease and an Update on the Latest Evidence

    PubMed Central

    Spartalis, Eleftherios; Charalampoudis, Petros; Kandilis, Apostolos; Athanasiou, Antonios; Tsaparas, Petros; Voutsarakis, Athanasios; Kostakis, Ioannis D.; Dimitroulis, Dimitrios; Svolou, Evanthia; Korkolopoulou, Penelope; Nikiteas, Nikolaos; Kouraklis, Gregory

    2014-01-01

    Castleman's disease is a benign lymphoproliferative condition with three distinct histological subtypes. Clinically it presents in either a unicentric or multicentric manner and can affect various anatomic regions, the mediastinum being the most frequent location. We herein present a rare case of unifocal retroperitoneal mass proved to be hyaline vascular Castleman's disease. We perform a review of the current literature pertaining to such lesions, focusing on the management of the various clinical and histological variants of the disease. Surgical excision is the treatment of choice for unifocal Castleman's disease. PMID:25431731

  16. Posttransplant outcome of atypical haemolytic uraemic syndrome in a patient with thrombomodulin mutation: a case without recurrence.

    PubMed

    Caroti, Leonardo; Di Maria, Lorenzo; Carta, Paolo; Moscarelli, Luciano; Cirami, Calogero; Minetti, Enrico Eugenio

    2015-06-01

    Atypical haemolytic uraemic syndrome (aHUS) is a rare disease characterized by thrombocytopenia, microangiopathic haemolytic anaemia and renal impairment. Mutations in genes encoding inhibitors of the alternative pathway of the complement system are involved in ∼50% of the cases. Thrombomodulin (THBD) gene mutations occur in ∼3-5% of the cases. The risk of aHUS recurrence after kidney transplantation depends on the complement abnormality involved. In all three cases of THBD mutation reported to date, aHUS recurred after kidney transplantation (KT) with early graft loss. No data exist about therapeutic approaches before kidney transplantation to reduce the risk of recurrence in patients carrying this mutation. Favourable data on the use of eculizumab have been reported, in terms of plasmatherapy withdrawal and renal function recovery in aHUS recurrence after KT. To our knowledge, this case report presents the first case of successful kidney transplantation in a patient with aHUS due to THBD mutation who was treated with a single plasma-exchange immediately before surgery without recurrence of the disease 12 months after transplantation. PMID:26034596

  17. Salvia Hispanica Seed in Reducing Risk of Disease Recurrence in Patients With Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-01-28

    Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Adult T-Cell Leukemia/Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; B Lymphoblastic Leukemia/Lymphoma; Blastic Plasmacytoid Dendritic Cell Neoplasm; Burkitt Leukemia; Central Nervous System Lymphoma; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Diffuse Large B-Cell Lymphoma; Enteropathy-Associated T-Cell Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3 Follicular Lymphoma; Hepatosplenic T-Cell Lymphoma; Hodgkin Lymphoma; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Mycosis Fungoides; Nasal Type Extranodal NK/T-Cell Lymphoma; Nodal Marginal Zone Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Post-Transplant Lymphoproliferative Disorder; Primary Cutaneous Anaplastic Large Cell Lymphoma; Primary Effusion Lymphoma; Sezary Syndrome; Splenic Marginal Zone Lymphoma; Subcutaneous Panniculitis-Like T-Cell Lymphoma; Systemic Anaplastic Large Cell Lymphoma; T Lymphoblastic Leukemia/Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  18. Challenges in transplantation for alcoholic liver disease

    PubMed Central

    Berlakovich, Gabriela A

    2014-01-01

    Transplantation for the treatment of alcoholic cirrhosis is more controversially discussed than it is for any other indication. The crucial aspect in this setting is abstinence before and after liver transplantation. We established pre-transplant selection criteria for potential transplant candidates. Provided that the underlying disease can be treated, there is no reason to withhold liver transplantation in a patient suffering from alcoholic cirrhosis. Evaluation of the patient by a multidisciplinary team, including an addiction specialist, is considered to be the gold standard. However, several centers demand a specified period of abstinence - usually 6 mo- irrespective of the specialist’s assessment. The 6-mo rule is viewed critically because liver transplantation was found to clearly benefit selected patients with acute alcoholic hepatitis; the benefit was similar to that achieved for other acute indications. However, the discussion may well be an academic one because the waiting time for liver transplantation exceeds six months at the majority of centers. The actual challenge in liver transplantation for alcoholic cirrhosis may well be the need for lifelong post-transplant follow-up rather than the patient’s pre-transplant evaluation. A small number of recipients experience a relapse of alcoholism; these patients are at risk for organ damage and graft-related death. Post-transplant surveillance protocols should demonstrate alcohol relapse at an early stage, thus permitting the initiation of adequate treatment. Patients with alcoholic cirrhosis are at high risk of developing head and neck, esophageal, or lung cancer. The higher risk of malignancies should be considered in the routine assessment of patients suffering from alcoholic cirrhosis. Tumor surveillance protocols for liver transplant recipients, currently being developed, should become a part of standard care; these will improve survival by permitting diagnosis at an early stage. In conclusion, the key factor determining the outcome of transplantation for alcoholic cirrhosis is intensive lifelong medical and psychological care. Post-transplant surveillance might be much more important than pre-transplant selection. PMID:25009374

  19. Long-term graft outcomes and patient survival are lower posttransplant in patients with a primary renal diagnosis of glomerulonephritis.

    PubMed

    Pruthi, Rishi; McClure, Mark; Casula, Anna; Roderick, Paul J; Fogarty, Damian; Harber, Mark; Ravanan, Rommel

    2016-04-01

    Glomerulonephritis (GN) is the primary diagnosis in 20% to 40% of patients receiving a renal transplant. Here we studied patient survival and graft outcomes in patients with GN transplanted in the UK. UK Renal Registry data were used to analyze patient survival and graft failure in incident transplant patients between 1997 to 2009 who had a diagnosis of primary GN, in comparison to patients transplanted with adult polycystic kidney disease (APKD) or diabetes. Multivariable regression analysis adjusted for age, sex, donor type, ethnicity, donor age, time on dialysis, human leukocyte antigen mismatch, cold ischemic time, and graft failure (for patient survival). Patients were followed up through December 2012. Of 4750 patients analyzed, 2975 had GN and 1775 APKD. Graft failure was significantly higher in membranoproliferative glomerulonephritis (MPGN) type II (hazard ratio: 3.5, confidence interval: 1.9-6.6), focal segmental glomerulosclerosis (2.4, 1.8-3.2), MPGN type I (2.3, 1.6-3.3), membranous nephropathy (2.0, 1.4-2.9), and IgA nephropathy (1.6, 1.3-2.0) compared to APKD. Survival was significantly reduced in patients with MPGN type II (4.7, 2.0-10.8), and those with lupus nephritis (1.8, 1.1-2.9). Overall graft failure for patients with GN was similar to those with diabetes. Thus, in comparison to outcomes in APKD, graft survival is significantly lower in most GNs, with variation in outcomes between different GNs. This information should assist in pretransplant counseling of patients. Further study is required to understand the reduced survival seen in lupus nephritis and MPGN type II, and to improve overall graft outcomes. PMID:26924061

  20. Use of biologics and chemotherapy in patients with inflammatory bowel diseases and cancer.

    PubMed

    Jauregui-Amezaga, Aranzazu; Vermeire, Séverine; Prenen, Hans

    2016-01-01

    Patients with inflammatory bowel disease have an additional risk of developing cancer compared with the general population. This is due to local chronic inflammation that leads to the development of gastrointestinal cancers and the use of thiopurines, associated with a higher risk of lymphoproliferative disorders, skin cancers, or uterine cervical cancers. Similar to the general population, a previous history of cancer in inflammatory bowel disease patients increases the risk of developing a secondary cancer. Large studies have not shown an increased risk of cancer in patients treated with biologics. In this review we discuss the prevention and treatment of cancer in patients with inflammatory bowel disease. PMID:27065724

  1. Use of biologics and chemotherapy in patients with inflammatory bowel diseases and cancer

    PubMed Central

    Jauregui-Amezaga, Aranzazu; Vermeire, Séverine; Prenen, Hans

    2016-01-01

    Patients with inflammatory bowel disease have an additional risk of developing cancer compared with the general population. This is due to local chronic inflammation that leads to the development of gastrointestinal cancers and the use of thiopurines, associated with a higher risk of lymphoproliferative disorders, skin cancers, or uterine cervical cancers. Similar to the general population, a previous history of cancer in inflammatory bowel disease patients increases the risk of developing a secondary cancer. Large studies have not shown an increased risk of cancer in patients treated with biologics. In this review we discuss the prevention and treatment of cancer in patients with inflammatory bowel disease. PMID:27065724

  2. 18F-FDG PET/CT in multicentric Castleman disease: a case report

    PubMed Central

    Zhang, Jiexin; Yang, Lu

    2016-01-01

    Castleman disease (CD) is a chronic lymphoproliferative disorder characterized by unexplained enlarged lymph nodes. According to lymph nodes distribution it contains two types of single-centric and multicentric (more than one site) disease. Multicentric Castleman disease (MCD) is rare, and shows unspecific manifestation with high misdiagnosis rate. Here we reported a case of MCD in a 43-year-old male. 18F-FDG PET/CT imaging demonstrated higher FDG uptake in multiple lymph nodes and slightly FDG uptake in spleen and bone marrow. Right inguinal Lymph node biopsy was taken and the results confirmed CD. PMID:26904580

  3. Deletion of receptor for advanced glycation end products exacerbates lymphoproliferative syndrome and lupus nephritis in B6-MRL Fas lpr/j mice.

    PubMed

    Goury, Antoine; Meghraoui-Kheddar, Aïda; Belmokhtar, Karim; Vuiblet, Vincent; Ortillon, Jeremy; Jaisson, Stéphane; Devy, Jerôme; Le Naour, Richard; Tabary, Thierry; Cohen, Jacques H M; Schmidt, Ann-Marie; Rieu, Philippe; Touré, Fatouma

    2015-04-15

    The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that interacts with advanced glycation end products, but also with C3a, CpG DNA oligonucleotides, and alarmin molecules such as HMGB1 to initiate a proinflammatory reaction. Systemic lupus erythematosus is an autoimmune disorder associated with the accumulation of RAGE ligands. We generated mice invalidated for RAGE in the lupus-prone B6-MRL Fas lpr/j background to determine the role of RAGE in the pathogenesis of systemic lupus erythematosus. We compared the phenotype of these mice with that of their wild-type and B6-MRL Fas lpr/j littermates. Lymphoproliferative syndrome, production of anti-dsDNA Abs, lupus nephritis, and accumulation of CD3(+)B220(+)CD4(-)CD8(-) autoreactive T cells (in the peripheral blood and the spleen) were significantly increased in B6-MRL Fas lpr/j RAGE(-/-) mice compared with B6-MRL Fas lpr/j mice (respectively p < 0.005, p < 0.05, p < 0.001, and p < 0.001). A large proportion of autoreactive T cells from B6-MRL Fas lpr/j mice expressed RAGE at their surface. Time course studies of annexin V expression revealed that autoreactive T cells in the spleen of B6-MRL Fas lpr/j-RAGE(-/-) mice exhibited a delay in apoptosis and expressed significantly less activated caspase 3 (39.5 ± 4.3%) than T cells in B6-MRL Fas lpr/j mice (65.5 ± 5.2%) or wild-type mice (75.3 ± 2.64%) (p = 0.02). We conclude that the deletion of RAGE in B6-MRL Fas lpr/j mice promotes the accumulation of autoreactive CD3(+)B220(+)CD4(-)CD8(-) T cells, therefore exacerbating lymphoproliferative syndrome, autoimmunity, and organ injury. This suggests that RAGE rescues the apoptosis of T lymphocytes when the death receptor Fas/CD95 is dysfunctional. PMID:25762779

  4. Lymphomatoid granulomatosis associated with azathioprine therapy in Crohn disease

    PubMed Central

    2014-01-01

    Background Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus-associated lymphoproliferative disorder. It most often occurs in patients with immunodeficiency and the clinical course ranges from indolent behavior to that of an aggressive malignancy. Pulmonary, central nervous system and dermatological manifestations are most common. To our knowledge this is the first reported case of LYG related to azathioprine therapy in Crohn disease. Case presentation A twenty-six year old Caucasian woman with colonic Crohn disease on maintenance azathioprine therapy presented with right upper quadrant pain and fever. Diagnostic imaging revealed extensive liver, pulmonary and cerebral lesions. A diagnosis of LYG was made based on the pattern of organ involvement and the immunohistochemical features on liver and lung biopsy. Conclusions Thiopurine therapy for inflammatory bowel disease is associated with an increased incidence of lymphoproliferative disorders. This report highlights the diagnostic challenges associated with LYG. As long-term thiopurine therapy remains central to the management of inflammatory bowel diseases it is essential that both patients and clinicians are aware of this potential adverse outcome. PMID:25022612

  5. Castleman's disease of a submandibular mass diagnosed on Fine Needle Cytology: Report of a case with histopathological, immunocytochemical and imaging correlations

    PubMed Central

    Malzone, Maria Gabriella; Campanile, Anna Cipolletta; Sanna, Veronica; Ionna, Franco; Longo, Francesco; De Chiara, Annarosaria; Setola, Sergio Venanzio; Botti, Gerardo; Fulciniti, Franco

    2016-01-01

    Summary Castleman's disease (CD) is an unusual inflammatory lymphoproliferative disorder of uncertain aetiology, mainly involving lymphatic tissue in the mediastinum, but also occurring in the neck, lung, abdomen, pelvis, skeletal muscle and retroperitoneum. Fine Needle Cytology (FNC) is a quick, cost-effective and safe diagnostic modality to investigate on organs involved by CD, also providing a guide to treatment and management of patients with lymphoadenopathy. We report a case of a 44-year-old man who underwent FNC of a submandibular mass with subsequent surgical excision. Cytology revealed an atypical lymphoproliferative process, which arose the suspicion of CD. Histopathological study of the excised masses combined with immunhistochemistry and imaging of the submandibular and neck areas, confirmed the suspicion. A final diagnosis of Unicentric Castleman's disease, hyaline-vascular type, was made. PMID:26989647

  6. Noncanonical MicroRNA (miRNA) Biogenesis Gives Rise to Retroviral Mimics of Lymphoproliferative and Immunosuppressive Host miRNAs

    PubMed Central

    Kincaid, Rodney P.; Chen, Yating; Cox, Jennifer E.; Rethwilm, Axel; Sullivan, Christopher S.

    2014-01-01

    ABSTRACT MicroRNAs (miRNAs) play regulatory roles in diverse processes in both eukaryotic hosts and their viruses, yet fundamental questions remain about which viruses code for miRNAs and the functions that they serve. Simian foamy viruses (SFVs) of Old World monkeys and apes can zoonotically infect humans and, by ill-defined mechanisms, take up lifelong infections in their hosts. Here, we report that SFVs encode multiple miRNAs via a noncanonical mode of biogenesis. The primary SFV miRNA transcripts (pri-miRNAs) are transcribed by RNA polymerase III (RNAP III) and take multiple forms, including some that are cleaved by Drosha. However, these miRNAs are generated in a context-dependent fashion, as longer RNAP II transcripts spanning this region are resistant to Drosha cleavage. This suggests that the virus may avoid any fitness penalty that could be associated with viral genome/transcript cleavage. Two SFV miRNAs share sequence similarity and functionality with notable host miRNAs, the lymphoproliferative miRNA miR-155 and the innate immunity suppressor miR-132. These results have important implications regarding foamy virus biology, viral miRNAs, and the development of retroviral-based vectors. PMID:24713319

  7. Forced miR-146a expression causes autoimmune lymphoproliferative syndrome in mice via downregulation of Fas in germinal center B cells.

    PubMed

    Guo, Qiuye; Zhang, Jinjun; Li, Jingyi; Zou, Liyun; Zhang, Jinyu; Xie, Zunyi; Fu, Xiaolan; Jiang, Shan; Chen, Gang; Jia, Qingzhu; Li, Fei; Wan, Ying; Wu, Yuzhang

    2013-06-13

    By inhibiting target gene expression, microRNAs (miRNAs) play major roles in various physiological and pathological processes. miR-146a, a miRNA induced upon lipopolysaccharide (LPS) stimulation and virus infection, is also highly expressed in patients with immune disorders such as rheumatoid arthritis, Sjögren's syndrome, and psoriasis. Whether the high level of miR-146a contributes to any of these pathogenesis-related processes remains unknown. To elucidate the function of miR-146a in vivo, we generated a transgenic (TG) mouse line overexpressing miR-146a. Starting at an early age, these TG mice developed spontaneous immune disorders that mimicked human autoimmune lymphoproliferative syndrome (ALPS) with distinct manifestations, including enlarged spleens and lymph nodes, inflammatory infiltration in the livers and lungs, increased levels of double-negative T cells in peripheral blood, and increased serum immunoglobulin G levels. Moreover, with the adoptive transfer approach, we found that the B-cell population was the major etiological factor and that the expression of Fas, a direct target of miR-146a, was significantly dampened in TG germinal center B cells. These results indicate that miR-146a may be involved in the pathogenesis of ALPS by targeting Fas and may therefore serve as a novel therapeutic target. PMID:23645835

  8. Improvement of the lymphoproliferative immune response and apoptosis inhibition upon in vitro treatment with zinc of peripheral blood mononuclear cells (PBMC) from HIV+ individuals.

    PubMed

    Neves, I; Bertho, A L; Veloso, V G; Nascimento, D V; Campos-Mello, D L; Morgado, M G

    1998-02-01

    Clinical improvement has been described in AIDS patients submitted to zinc therapy, but the mechanisms involved are not well understood. In order to evaluate the effect of the zinc ions in the enhancement of the immune response, we tested its role in the lymphoproliferative response to a mitogen, as well as in the prevention of apoptosis. The mitogenic effect of zinc (10(-4)M ZnCl2) on the lymphocyte proliferative response was observed in healthy controls as well as in HIV-1+ asymptomatic individuals. Very low stimulation index could be observed in AIDS patients (CD4+<200/mm3). However, zinc treatment of phytohaemagglutinin (PHA; 5 microg/ml)-stimulated PBMC cultures significantly enhanced 3H-thymidine incorporation in both asymptomatic and symptomatic groups. A decreased percentage of apoptotic cells could be identified in cell cultures from HIV-1+ individuals submitted to zinc treatment compared with cells treated only with PHA, as detected by both flow cytometry and agarose gel electrophoresis. Further studies with zinc supplementation associated to anti-retroviral therapy would be of great interest to evaluate the in vivo role of this oligoelement in the improvement of the immunological functions of HIV-1-infected individuals and AIDS patients. PMID:9486391

  9. Improvement of the lymphoproliferative immune response and apoptosis inhibition upon in vitro treatment with zinc of peripheral blood mononuclear cells (PBMC) from HIV+ individuals

    PubMed Central

    Neves, I; Bertho, A L; Veloso, V G; Nascimento, D V; Campos-Mello, D L A; Morgado, M G

    1998-01-01

    Clinical improvement has been described in AIDS patients submitted to zinc therapy, but the mechanisms involved are not well understood. In order to evaluate the effect of the zinc ions in the enhancement of the immune response, we tested its role in the lymphoproliferative response to a mitogen, as well as in the prevention of apoptosis. The mitogenic effect of zinc (10−4 m ZnCl2) on the lymphocyte proliferative response was observed in healthy controls as well as in HIV-1+ asymptomatic individuals. Very low stimulation index could be observed in AIDS patients (CD4+ < 200/mm3). However, zinc treatment of phytohaemagglutinin (PHA; 5 μg/ml)-stimulated PBMC cultures significantly enhanced 3H-thymidine incorporation in both asymptomatic and symptomatic groups. A decreased percentage of apoptotic cells could be identified in cell cultures from HIV-1+ individuals submitted to zinc treatment compared with cells treated only with PHA, as detected by both flow cytometry and agarose gel electrophoresis. Further studies with zinc supplementation associated to anti-retroviral therapy would be of great interest to evaluate the in vivo role of this oligoelement in the improvement of the immunological functions of HIV-1-infected individuals and AIDS patients. PMID:9486391

  10. Mucosal CD30-Positive T-Cell Lymphoproliferative Disorder Arising in the Oral Cavity Following Dental Implants: Report of the First Case.

    PubMed

    Yoon, Hye-Jung; Choe, Ji-Young; Jeon, Yoon Kyung

    2015-12-01

    Mucosal CD30-positive T-cell lymphoproliferative disorder (CD30+ T-cell LPD) is a novel entity with unique clinicopathological features and an indolent behavior. Here we report the first case of mucosal CD30+ T-cell LPD arising in the oral cavity following dental implant. A 70-year-old woman presented with swelling and redness of the oral mucosa of right maxilla and left mandible surrounding dental implants that had been placed 8 years previously. Radiological examination revealed enhancing oral lesions and multiple cervical lymph nodes. Microscopic examination showed diffuse infiltration of large anaplastic cells with characteristic morphology of hallmark cells described in anaplastic large cell lymphoma. These cells were diffusely positive for CD30, CD3, CD4, CD2, CD5, CD7, TIA-1, and TCR?F1, but negative for CD20, CD8, CD45, EMA, ALK, and Epstein-Barr virus. T-cell monoclonality was detected in a TCR? gene rearrangement study. This a unique case of mucosal CD30+ T-cell LPD with unusual presentation following dental implant. PMID:26261101

  11. The survival benefit of kidney transplantation in the setting of combined peripheral arterial disease and end-stage renal failure.

    PubMed

    Cassuto, James; Babu, Sateesh; Laskowski, Igor

    2016-05-01

    Given the deleterious effects of concomitant peripheral arterial disease (PAD) and severe renal disease, a role for aggressive screening and management of PAD in renal failure patients has been suggested. However, limited data exist detailing the impact of PAD on kidney waitlist survival and the potential benefit of transplantation in PAD. Multivariable COX regression and Kaplan-Meier survival models were fit using UNOS data to assess kidney waitlist and post-transplant five-yr survival. Compared to PAD-Dial- (no PAD or dialysis) waitlist survival, PAD+Dial- was associated with a 36%, PAD-Dial+ a 95%, and PAD+Dial+ a 190% increased risk of death. A significant survival benefit of kidney transplantation was identified in the PAD population (p < 0.001, HR = 0.440 comparing post-transplant to waitlist survival). Time to survival benefit (equal mortality between waitlist and post-transplant population) of kidney transplantation in PAD+ was realized 2.5 times sooner in pre-emptive transplantation than transplant after dialysis (154 d vs. 381 d), per unadjusted Kaplan-Meier analysis. To our knowledge, this is the first study to demonstrate a survival benefit of kidney transplantation in the setting of PAD. Pre-emptive transplantation with emphasis on living donation prior to dialysis should be advocated to improve outcomes in this high risk patient population. PMID:26914805

  12. Perivesical unicentric Castleman disease initially suspected to be metastatic prostate cancer

    PubMed Central

    Guthrie, Patrick J.; Thomas, John V.; Peker, Deniz; Turkbey, Baris; Rais-Bahrami, Soroush

    2016-01-01

    Unicentric Castleman disease (UCD) is a relatively rare lymphoproliferative disease, which commonly presents as a mediastinal mass and less frequently involves abdomen, pelvis, and retroperitoneum. We report a case of a 64-year-old man with newly diagnosed low-volume, Gleason 3 + 3 = 6 prostate adenocarcinoma, who in considering active surveillance versus treatment was found to have a left perivesical and iliac chain lymphadenopathy concerning for potential metastatic involvement. He underwent magnetic resonance imaging with ferumoxytol to assist in the diagnostic evaluation to better characterize his lymphadenopathy. Subsequently, he underwent robotic-assisted laparoscopic bilateral pelvic lymph node dissection and resection of left perivesical mass exhibiting hyaline vascular variant of UCD.

  13. Acute Kidney Disease After Liver and Heart Transplantation.

    PubMed

    Rossi, Ana P; Vella, John P

    2016-03-01

    After transplantation of nonrenal solid organs, an acute decline in kidney function develops in the majority of patients. In addition, a significant number of nonrenal solid organ transplant recipients develop chronic kidney disease, and some develop end-stage renal disease, requiring renal replacement therapy. The incidence varies depending on the transplanted organ. Acute kidney injury after nonrenal solid organ transplantation is associated with prolonged length of stay, cost, increased risk of death, de novo chronic kidney disease, and end-stage renal disease. This overview focuses on the risk factors for posttransplant acute kidney injury after liver and heart transplantation, integrating discussion of proteinuria and chronic kidney disease with emphasis on pathogenesis, histopathology, and management including the use of mechanistic target of rapamycin inhibition and costimulatory blockade. PMID:26502368

  14. High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

    ClinicalTrials.gov

    2016-03-14

    Post-Transplant Lymphoproliferative Disorder; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

  15. Radiolabeled Monoclonal Antibody With or Without Peripheral Stem Cell Transplantation in Treating Children With Recurrent or Refractory Lymphoma

    ClinicalTrials.gov

    2013-01-16

    AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma

  16. Molecular cytogenetic delineation of a novel critical genomic region in chromosome bands 11q22.3-923.1 in lymphoproliferative disorders.

    PubMed Central

    Stilgenbauer, S; Liebisch, P; James, M R; Schröder, M; Schlegelberger, B; Fischer, K; Bentz, M; Lichter, P; Döhner, H

    1996-01-01

    Aberrations of the long arm of chromosome 11 are among the most common chromosome abnormalities in lymphoproliferative disorders (LPD). Translocations involving BCL1 at 11q13 are strongly associated with mantle cell lymphoma. other nonrandom aberrations, especially deletions and, less frequently, translocations, involving bands 11q21-923 have been identified by chromosome banding analysis. To date, the critical genomic segment and candidate genes involved in these deletions have not been identified. In the present study, we have analyzed tumors from 43 patients with LPD (B-cell chronic lymphocytic leukemia, n = 40; mantle cell lymphoma, n = 3) showing aberrations of bands 11q21-923 by fluorescence in situ hybridization. As probes we used Alu-PCR products from 17 yeast artificial chromosome clones spanning chromosome bands 11q14.3-923.3, including a panel of yeast artificial chromosome clones recognizing a contiguous genomic DNA fragment of approximately 9-10 Mb in bands 11q22.3-923.3. In the 41 tumors exhibiting deletions, we identified a commonly deleted segment in band 11q22.3-923.1; this region is approximately 2-3 Mb in size and contains the genes coding for ATM (ataxia telangiectasia mutated), RDX (radixin), and FDX1 (ferredoxin 1). Furthermore, two translocation break-points were localized to a 1.8-Mb genomic fragment contained within the commonly deleted segment. Thus, we have identified a single critical region of 2-3 Mb in size in which 11q14-923 aberrations in LPD cluster. This provides the basis for the identification of the gene(s) at 11q22.3-923.1 that are involved in the pathogenesis of LPD. Images Fig. 1 PMID:8876224

  17. [Multicentric Castleman disease not associated with HHV-8 and HIV viruses].

    PubMed

    Forteski, Denise de Fatima; Netto, Fernanda Calil Machado; Lomonte, Andrea Barranjard Vannucci; dos Anjos, Bruno César Cavalcanti; Zerbini, Maria Claudia Nogueira; Zerbini, Cristiano Augusto de Freitas

    2014-01-01

    Castleman's disease (CD) is a polyclonal lymphoproliferative disorder also known as giant nodular hyperplasia or angiofollicular lymph node hyperplasia. It is a rare disease often associated to human immunodeficiency virus (HIV) and human herpes virus 8 (HHV-8). Histopathological findings in Castleman's disease suggest an exaggerated response to antigenic stimuli seen in other diseases associated with immune activation, such as rheumatoid arthritis. An important aspect of its pathogenesis is the autonomous production of interleukin-6 (IL-6). In this disease, the clinical manifestations are associated to IL-6 serum levels, and surgical removal of the compromised lymph nodes or use of anti-IL-6 antibodies can slow down the symptoms. We describe a multicentric Castleman's disease in a young woman not associated to HHV-8 virus infection or immunosuppression. A short review of the literature follows the description of this clinical case. PMID:25627230

  18. Candidates for liver transplantation with alcoholic liver disease: Psychosocial aspects.

    PubMed

    Telles-Correia, Diogo; Mega, Inês

    2015-10-21

    In Europe, 30% to 50% of liver transplantations are currently due to alcoholic liver disease (ALD). In the United States, this percentage is 17.2%. Post-transplant survival and other predictors of clinical course do not differ significantly from those in other types of transplanted patients, as long as there is no relapse of drinking. However, 20%-25% of these patients lapse or relapse to heavy drinking post-operatively, which has been associated with an increased risk of liver damage and mortality. It is therefore crucial to design specific selection and follow-up strategies aimed at this particular type of patient. Several good and poor prognosis factors that could help to predict a relapse have been suggested, among them the duration of abstinence, social support, a family history of alcoholism, abuse diagnosis versus alcohol dependence, non-acceptance of diagnosis related to alcohol use, presence of severe mental illness, non-adherence in a broad sense, number of years of alcoholism, and daily quantity of alcohol consumption. In this article, we discuss these and other, more controversial factors in selecting ALD patients for liver transplantation. Abstinence should be the main goal after transplantation in an ALD patient. In this article, we review the several definitions of post-transplant relapse, its monitoring and the psychopharmacological and psychotherapeutic treatment. PMID:26494959

  19. Candidates for liver transplantation with alcoholic liver disease: Psychosocial aspects

    PubMed Central

    Telles-Correia, Diogo; Mega, Inês

    2015-01-01

    In Europe, 30% to 50% of liver transplantations are currently due to alcoholic liver disease (ALD). In the United States, this percentage is 17.2%. Post-transplant survival and other predictors of clinical course do not differ significantly from those in other types of transplanted patients, as long as there is no relapse of drinking. However, 20%-25% of these patients lapse or relapse to heavy drinking post-operatively, which has been associated with an increased risk of liver damage and mortality. It is therefore crucial to design specific selection and follow-up strategies aimed at this particular type of patient. Several good and poor prognosis factors that could help to predict a relapse have been suggested, among them the duration of abstinence, social support, a family history of alcoholism, abuse diagnosis versus alcohol dependence, non-acceptance of diagnosis related to alcohol use, presence of severe mental illness, non-adherence in a broad sense, number of years of alcoholism, and daily quantity of alcohol consumption. In this article, we discuss these and other, more controversial factors in selecting ALD patients for liver transplantation. Abstinence should be the main goal after transplantation in an ALD patient. In this article, we review the several definitions of post-transplant relapse, its monitoring and the psychopharmacological and psychotherapeutic treatment. PMID:26494959

  20. Subclinical pulmonary function defects following autologous and allogeneic bone marrow transplantation: relationship to total body irradiation and graft-versus-host disease

    SciTech Connect

    Tait, R.C.; Burnett, A.K.; Robertson, A.G.; McNee, S.; Riyami, B.M.; Carter, R.; Stevenson, R.D. )

    1991-06-01

    Pulmonary function results pre- and post-transplant, to a maximum of 4 years, were analyzed in 98 patients with haematological disorders undergoing allogeneic (N = 53) or autologous bone marrow transplantation (N = 45) between 1982 and 1988. All received similar total body irradiation based regimens ranging from 9.5 Gy as a single fraction to 14.4 Gy fractionated. FEV1/FVC as a measure of airway obstruction showed little deterioration except in patients experiencing graft-versus-host disease in whom statistically significant obstructive ventilatory defects were evident by 6 months post-transplant (p less than 0.01). These defects appeared to be permanent. Restrictive ventilatory defects, as measured by reduction in TLC, and defects in diffusing capacity (DLCO and KCO) were also maximal at 6 months post-transplant (p less than 0.01). Both were related, at least in part, to the presence of GVHD (p less than 0.01) or use of single fraction TBI with absorbed lung dose of 8.0 Gy (p less than 0.05). Fractionated TBI resulted in less marked restricted ventilation and impaired gas exchange, which reverted to normal by 2 years, even when the lung dose was increased from 11.0 Gy to between 12.0 and 13.5 Gy. After exclusion of patients with GVHD (30% allografts) there was no significant difference in pulmonary function abnormalities between autograft and allograft recipients.

  1. Autoimmune Hemolytic Anemia and Hodgkin's Disease: An Unusual Pediatric Association.

    PubMed

    Gomes, Maria Miguel; Oliva, Tereza; Pinto, Armando

    2016-01-01

    Autoimmune hemolytic anemia (AIHA) is a recognized complication of lymphoproliferative disorders. AIHA associated with Hodgkin's disease (HD) is uncommon especially in the pediatric population. The diagnosis of AIHA is usually associated with HD at the time of initial presentation or during the course of disease, but it could precede it by years to months. In adults the association of AIHA and HD is more frequent in advanced stages and in the nodular sclerosis and mixed cellularity type HD. Warm immune hemolytic anemia is mainly controlled with steroids and chemotherapy. We report a case of a pediatric patient with direct antiglobulin positive test at the diagnosis of a late relapse of stage III B mixed cellularity type HD. PMID:26904342

  2. [Hibernoma and cervical rib: two rare diseases, the same manifestation].

    PubMed

    Antunes, J; Santos, S; Andrade, N; Simões, F; Salgado, C

    2013-07-01

    The hibernoma is a rare benign tumor of soft tissue, derived from remnants of fetal brown adipose tissue. A cervical rib is a supernumerary or accessory rib derived from the 7th cervical vertebra. CLINCAL CASE: 2-year-old girl, previously healthy, referenced to Pediatrics consultation, for left supraclavicular mass. No history of infectious diseases or systemic symptoms. At exam presented mass in supraclavicular left region, 1.5 to 2 cm in diameter, hard, mobile, non-adherent to the deep planes. Laboratory tests exclude an infectious or lymphoproliferative disease. In cervical radiograph we observed bilateral cervical ribs. Cervical ultrasound revealed calcified nodule 0.8 cm, compatible with calcified adenopathy. Biopsy was performed and histology revealed a hibernoma, which was completely removed surgically. This case illustrates the association of two diagnoses, uncommon in children. These were made during the investigation of lymphadenopathies, a frequent reason for pediatrics consultation. PMID:24482907

  3. Autoimmune Hemolytic Anemia and Hodgkin's Disease: An Unusual Pediatric Association

    PubMed Central

    Gomes, Maria Miguel; Oliva, Tereza; Pinto, Armando

    2016-01-01

    Autoimmune hemolytic anemia (AIHA) is a recognized complication of lymphoproliferative disorders. AIHA associated with Hodgkin's disease (HD) is uncommon especially in the pediatric population. The diagnosis of AIHA is usually associated with HD at the time of initial presentation or during the course of disease, but it could precede it by years to months. In adults the association of AIHA and HD is more frequent in advanced stages and in the nodular sclerosis and mixed cellularity type HD. Warm immune hemolytic anemia is mainly controlled with steroids and chemotherapy. We report a case of a pediatric patient with direct antiglobulin positive test at the diagnosis of a late relapse of stage III B mixed cellularity type HD. PMID:26904342

  4. Autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma: what 18F-fluorodeoxyglucose positron emission tomography/computed tomography can do in the management of these patients? Suggestions from a case report.

    PubMed

    Cistaro, A; Pazè, F; Durando, S; Cogoni, M; Faletti, R; Vesco, S; Vallero, S; Quartuccio, N; Treglia, G; Ramenghi, U

    2014-01-01

    A young patient with undefined autoimmune lymphoproliferative syndrome (ALPS-U) and low back pain underwent a CT and MRI study that showed enhancing vertebral lesions, some pulmonary nodules and diffuse latero-cervical lymphadenopathy. A (18)F-FDG-PET/CT scan showed many areas of intense (18)F-FDG uptake in multiple vertebrae, in some ribs, in the sacrum, in the liver, in both lungs, in multiple lymph nodes spread in the cervical, thoracic and abdominal chains. A bone marrow biopsy showed a "lymphomatoid granulomatosis", a rare variant of B-cell non-Hodgkin lymphoma (NHL). After the treatment, the (18)F-FDG-PET/CT scan showed a complete metabolic response. PMID:23845452

  5. A multigene array for measurable residual disease detection in AML patients undergoing SCT.

    PubMed

    Goswami, M; McGowan, K S; Lu, K; Jain, N; Candia, J; Hensel, N F; Tang, J; Calvo, K R; Battiwalla, M; Barrett, A J; Hourigan, C S

    2015-05-01

    AML is a diagnosis encompassing a diverse group of myeloid malignancies. Heterogeneous genetic etiology, together with the potential for oligoclonality within the individual patient, have made the identification of a single high-sensitivity marker of disease burden challenging. We developed a multiple gene measurable residual disease (MG-MRD) RQ-PCR array for the high-sensitivity detection of AML, retrospectively tested on 74 patients who underwent allo-SCT at the NHLBI in the period 1994-2012. MG-MRD testing on peripheral blood samples prior to transplantation demonstrated excellent concordance with traditional BM-based evaluation and improved risk stratification for post-transplant relapse and OS outcomes. Pre-SCT assessment by MG-MRD predicted all clinical relapses occurring in the first 100 days after allo-SCT compared with 57% sensitivity using WT1 RQ-PCR alone. Nine patients who were negative for WT1 prior to transplantation were correctly reclassified into a high-risk MG-MRD-positive group, associated with 100% post-transplant mortality. This study provides proof of principle that a multiple gene approach may be superior to the use of WT1 expression alone for AML residual disease detection. PMID:25665046

  6. Pre-and-post transplant considerations in patients with nonalcoholic fatty liver disease

    PubMed Central

    Khullar, Vikas; Dolganiuc, Angela; Firpi, Roberto J

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is currently the third most common indication for liver transplantation in the United States. With the growing incidence of obesity, NAFLD is expected to become the most common indication for liver transplantation over the next few decades. As the number of patients who have undergone transplantation for NAFLD increases, unique challenges have emerged in the management and long-term outcomes in patients. Risk factors such as obesity, hypertension, diabetes, and hyperlipidemia continue to play an important role in the pathogenesis of the disease and its recurrence. Patients who undergo liver transplantation for NAFLD have similar long-term survival as patients who undergo liver transplantation for other indications. Research shows that post-transplantation recurrence of NAFLD is commonplace with some patients progressing to recurrent non-alcoholic steatohepatitis and cirrhosis. While treatment of comorbidities is important, there is no consensus on the management of modifiable risk factors or the role of pharmacotherapy and immunosuppression in patients who develop recurrent or de novo NAFLD post-transplant. This review provides an outline of NAFLD as indication for liver transplantation with a focus on the epidemiology, pathophysiology and risk factors associated with this disease. It also provides a brief review on the pre-transplant considerations and post-transplant factors including patient characteristics, role of obesity and metabolic syndrome, recurrence and de novo NAFLD, outcomes post-liver transplantation, choice of medications, and options for immunosuppression. PMID:25032097

  7. Recurrence of diabetic kidney disease in a type 1 diabetic patient after kidney transplantation.

    PubMed

    Nyumura, Izumi; Honda, Kazuho; Babazono, Tetsuya; Horita, Shigeru; Murakami, Toru; Fuchinoue, Shohei; Uchigata, Yasuko

    2015-07-01

    Post-transplant hyperglycaemia of diabetic patients may cause recurrent diabetic kidney disease (DKD) in kidney allografts. We report a patient with slowly progressive DKD with calcineurin inhibitor toxicity (CNI) toxicity after the kidney transplantation. A 28-year-old female with type 1 diabetes mellitus underwent successful kidney transplantation from her mother in April 2003, and the kidney graft survived for more than 10 years. She was treated with combined immunosuppressive therapy consisting of cyclosporine and mycophenolate mofetil. After transplantation, she continued to take insulin injection four times per day, but her glycosylated haemoglobin (HbA1c) was above 10%. Protocol allograft kidney biopsies performed 5 and 10 years after transplantation revealed the recurrence of slowly progressive diabetic kidney disease. In addition, arteriolar hyalinosis partly associated with calcineurin inhibitor toxicity (CNI) was detected with progression. Post-transplant hyperglycaemia causes recurrent diabetic kidney disease (DKD) in kidney allografts, but its progression is usually slow. For long-term management, it is important to prevent the progression of the calcineurin inhibitor arteriolopathy, as well as maintain favourable glycaemic control. PMID:26031596

  8. Respiratory Syncytial Virus in Hematopoietic Cell Transplant Recipients: Factors Determining Progression to Lower Respiratory Tract Disease

    PubMed Central

    Kim, Yae-Jean; Guthrie, Katherine A.; Waghmare, Alpana; Walsh, Edward E.; Falsey, Ann R.; Kuypers, Jane; Cent, Anne; Englund, Janet A.; Boeckh, Michael

    2014-01-01

    Background. Respiratory syncytial virus (RSV) lower respiratory tract disease (LRD) is a life-threatening complication in hematopoietic cell transplant (HCT) recipients. Lymphopenia has been associated with an increased risk of progression from upper respiratory tract infection (URI) to LRD. Methods. This study retrospectively analyzed the significance of lymphocyte engraftment dynamics, lung function, smoking history, corticosteroids, antiviral treatment, viral subtypes, and RSV-specific neutralizing antibodies for the progression to LRD in 181 HCT recipients with RSV URI. Results. In multivariable models, smoking history, conditioning with high-dose total body irradiation, and an absolute lymphocyte count (ALC) ≤100/mm3 at the time of URI onset were significantly associated with disease progression. No progression occurred in patients with ALCs of >1000/mm3 at URI onset. Lymphocyte engraftment dynamics were similar in progressors and nonprogressors. Pre- and posttransplant donor and posttransplant recipient RSV subtype-specific neutralizing antibody levels, RSV viral subtypes, and corticosteroids also were not significantly associated with LRD progression. Conclusions. Host and transplant related factors appear to determine the risk of progression to LRD more than viral factors. Dysfunctional cell-mediated immunity appears to be important in the pathogenesis of progressive RSV disease after HCT. A characterization of RSV-specific T-cell immunity is warranted. PMID:24368837

  9. Liver Transplantation for Alcoholic Liver Disease.

    PubMed

    Addolorato, Giovanni; Bataller, Ramón; Burra, Patrizia; DiMartini, Andrea; Graziadei, Ivo; Lucey, Michael R; Mathurin, Philippe; OʼGrady, John; Pageaux, Georges; Berenguer, Marina

    2016-05-01

    Alcohol-related liver disease is the second most frequent indication for liver transplantation (LT), yet as many as 90% to 95% of patients with alcohol-related end-stage liver disease are never formally evaluated for LT. Furthermore, despite its significance as a cause of chronic liver disease and indication for LT, it has received little attention in recent years for several reasons, including the good posttransplant short-term results, and the lack of specific "drugs" used for this disease. A writing group, endorsed by the International Liver Transplant Society, was convened to write guidelines on Liver Transplantation for Alcoholic Liver Disease to summarize current knowledge and provide answers to controversial and delicate ethical as well as clinical problems. We report here a short version of the guidelines (long version available at www.ilts.org) with the final recommendations graded for level of evidence. The writing group membership is expected to remain active for 5 years, reviewing the guideline annually, and updating the online version when appropriate. PMID:26985744

  10. HIV-associated Multicentric Castleman Disease

    PubMed Central

    Reddy, Deepa; Mitsuyasu, Ronald

    2015-01-01

    Purpose of review HIV-associated multicentric Castleman disease (HIV MCD) is a rare lymphoproliferative disorder, the incidence of which appears to be increasing in the highly active antiretroviral therapy (HAART) era. Current knowledge of the disease is limited and this review will discuss what is known about the pathophysiology, diagnosis, management, and prognosis of HIV MCD. Recent findings HIV MCD has been shown to be associated with infection with human herpervirus-8 (HHV8). Vascular endothelial growth factor and the cytokine interleukin-6 (IL-6) are also thought to play a role in the pathogenesis of MCD. Currently, rituximab is often used alone or in combination with chemotherapy for treatment of MCD. Novel monoclonal antibodies targeting IL-6 and the IL-6 receptor are also being studied for the management of this disease. Summary Because HIV MCD is an uncommon diagnosis, comprehensive clinical studies have not been done, and understanding of the disease is incomplete. Further studies are needed to make definitive conclusions regarding optimal treatment of HIV MCD. PMID:21760504

  11. Pathophysiologic and treatment strategies for cardiovascular disease in end-stage renal disease and kidney transplantations.

    PubMed

    Ghanta, Mythili; Kozicky, Mark; Jim, Belinda

    2015-01-01

    The inextricable link between the heart and the kidneys predestines that significant cardiovascular disease ensues in the face of end-stage renal disease (ESRD). As a point of fact, the leading cause of mortality of patients on dialysis is still from cardiovascular etiologies, albeit differing in particular types of disease from the general population. For example, sudden cardiac death outnumbers coronary artery disease in patients with ESRD, which is the reverse for the general population. In this review, we will focus on the pathophysiology and treatment options of important traditional and nontraditional risk factors for cardiovascular disease in ESRD patients such as hypertension, anemia, vascular calcification, hyperparathyroidism, uremia, and oxidative stress. The evidence of erythropoietin-stimulating agents, phosphate binders, calcimimetics, and dialysis modalities will be presented. We will then discuss how these risk factors may be changed and perhaps exacerbated after renal transplantation. This is largely due to the immunosuppressive agents that are both crucial yet potentially detrimental in the posttransplant state. Calcineurin inhibitors, corticosteroids, and mammalian target of rapamycin inhibitors, the mainstay of transplant immunosuppression, are all known to increase the risks of developing new onset diabetes as well as the metabolic syndrome. Thus, we need to carefully negotiate between patients' cardiovascular profile and their risks of rejection. Finally, we end by considering strategies by which we may minimize cardiovascular disease in the transplant population, as this modality still confers the highest chance of survival in patients with ESRD. PMID:25420053

  12. Belatacept for prevention of acute rejection in adult patients who have had a kidney transplant: an update

    PubMed Central

    Wojciechowski, David; Vincenti, Flavio

    2012-01-01

    In June 2011, the US Food and Drug Administration approved belatacept for the prophylaxis of organ rejection in adult kidney transplant recipients. This review discusses the use of belatacept for the prevention of acute rejection as part of a maintenance immunosuppression regimen. Belatacept is a selective costimulation blocker designed to provide effective immunosuppression while avoiding the toxicities associated with calcineurin inhibitors. Phase III trial data have demonstrated that belatacept is noninferior to cyclosporine in 1-year patient and allograft survival. Three-year data demonstrate an ongoing improvement in mean measured glomerular filtration rate in belatacept-treated versus cyclosporine-treated patients. However, the rate of acute rejection was higher in belatacept-treated patients compared with cyclosporine. Specifically, there was a higher incidence of Banff type II rejections in patients treated with belatacept. Despite the higher Banff grade, rejections on belatacept were not associated with other factors associated with poor outcomes, such as the development of donor-specific antibodies or reduced estimated glomerular filtration rate. One safety issue that must be considered when using belatacept is the potential for increased risk of post-transplant lymphoproliferative disease. There were more cases of post-transplant lymphoproliferative disease in belatacept-treated patients, especially in recipients seronegative for Epstein–Barr virus or patients treated with lymphocyte-depleting agents. Therefore, belatacept can be recommended for use in Epstein–Barr virus antibody-positive recipients. PMID:23152668

  13. Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation

    PubMed Central

    2013-01-01

    Viral infections are important causes of morbidity and mortality after allogeneic stem cell hematopoietic transplantation (allo-HSCT). Although most viral infections present with asymptomatic or subclinical manifestations, viruses may result in fatal complications in severe immunocompromised recipients. Reactivation of latent viruses, such as herpesviruses, is frequent during the immunosuppression that occurs with allo-HSCT. Viruses acquired from community, such as the respiratory and gastrointestinal viruses, are also important pathogens of post-transplant viral diseases. Currently, molecular diagnostic methods have replaced or supplemented traditional methods, such as viral culture and antigen detection, in diagnosis of viral infections. The utilization of polymerase chain reaction facilitates the early diagnosis. In view of lacking efficacious agents for treatment of viral diseases, prevention of viral infections is extremely valuable. Application of prophylactic strategies including preemptive therapy reduces viral infections and diseases. Adoptive cellular therapy for restoring virus-specific immunity is a promising method in the treatment of viral diseases. PMID:24341630

  14. Clonal rearrangement for immunoglobulin and T-cell receptor genes in systemic Castleman's disease. Association with Epstein-Barr virus.

    PubMed Central

    Hanson, C. A.; Frizzera, G.; Patton, D. F.; Peterson, B. A.; McClain, K. L.; Gajl-Peczalska, K. J.; Kersey, J. H.

    1988-01-01

    Castleman's disease is a morphologically and clinically heterogeneous lymphoproliferative disorder. Both a localized benign variant and an aggressive form with systemic manifestations have been described. To investigate the differences between these variants of Castleman's disease, the authors analyzed lymph node DNA from 4 patients with the localized type and 4 with the systemic type of Castleman's disease for immunoglobulin and T-cell receptor gene rearrangements. The role of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) was also studied by viral genomic DNA probes. They detected clonal rearrangements in 3 of the 4 patients with the systemic variant of Castleman's; no patients with localized disease had rearrangements. Copies of EBV genome were also detected in 2 of the 3 patients with clonal rearrangements. These results suggest that systemic Castleman's disease is a disorder distinct from the classical localized variant in that it may evolve into a clonal lymphoproliferation. Images Figure 1 PMID:2833104

  15. Rosai-Dorfman Disease of the Central Nervous System

    PubMed Central

    Sandoval-Sus, Jose D.; Sandoval-Leon, Ana C.; Chapman, Jennifer R.; Velazquez-Vega, Jose; Borja, Maria J.; Rosenberg, Shai; Lossos, Alexander; Lossos, Izidore S.

    2014-01-01

    Abstract Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy (SHML), is an uncommon benign idiopathic lymphoproliferative disorder. The histologic hallmark of RDD is the finding of emperipolesis displayed by lesional histiocytes. While RDD most commonly affects lymph nodes, extranodal involvement of multiple organs has been reported, including the central nervous system (CNS). However, CNS involvement in RDD is rare and is not well characterized. As a result, therapeutic approaches to CNS involvement in RDD are not well established. Herein we report 6 cases of RDD with isolated CNS involvement and review the literature on RDD with CNS involvement. One of the presented cases exhibited intramedullary involvement of the spinal cord—a very rare form of RDD with CNS involvement. PMID:24797172

  16. Comparison of Three Distinct Prophylactic Agents Against Invasive Fungal Infections in Patients Undergoing Haplo-identical Hematopoietic Stem Cell Transplantation and Post-transplant Cyclophosphamide

    PubMed Central

    El-Cheikh, Jean; Crocchiolo, Roberto; Vai, Andrea; Furst, Sabine; Bramanti, Stefania; Sarina, Barbara; Granata, Angela; Faucher, Catherine; Mohty, Bilal; Harbi, Samia; Bouabdallah, Reda; Vey, Norbert; Santoro, Armando; Chabannon, Christian; Castagna, Luca; Blaise, Didier

    2015-01-01

    Over the past decade, invasive fungal infections (IFIs) have remained an important problem in patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-HSCT). The optimal approach for prophylactic antifungal therapy has yet to bedetermined. We conducted a retrospective analysis, comparing the safety and efficacy of micafungin 50mg/day vs. fluconazole 400mg/day vs. itraconazole 200mg/day as prophylaxis for adult patients with various haematological diseases receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) followed by high-dose cyclophosphamide (PT-Cy). Overall, 99 patients were identified: 30 patients received micafungin, 50 and 19 patients received itraconazole and fluconazole, respectively. After a median follow-up of 12 months (range: 1–51), proven or probable IFIs were reported in 3 patients (10%) in the micafungin, 5 patients in the itraconazole (10%) and 2 patients (11%) in the fluconazole group (p=0.998). Fewer patients in the micafungin group had invasive aspergillosis (1 [3%] vs. 3 [6%] in the itraconazole vs. 2 [11%] in the fluconazole group, p=0.589). Four patients (13%) in the micafungin group vs 13 (26%) patients in the itraconazole group and 10 (53%) patients in the fluconazole received empirical antifungal therapy (P = 0.19). No serious adverse events related to treatment were reported by patients, and there was no treatment discontinuation because of drug-related adverse events in both groups. The present analysis shows that micafungin did better than fluconazole in preventing invasive aspergillosis after transplant in these high-risk hematological diseases, as expected. In addition, micafungin was more effective than itraconazole in preventing all IFI episodes when also considering possible fungal infections. Future prospective studies would shed light on this issue, concerning this increasingly used transplant platform. PMID:26401237

  17. Emerging treatments in Castleman disease – a critical appraisal of siltuximab

    PubMed Central

    Koff, Jean L; Lonial, Sagar

    2016-01-01

    Castleman disease (CD) is a rare, heterogeneous lymphoproliferative disorder for which no standard of care currently exists. Evidence that the pathophysiology of CD is fueled by excessive interleukin-6 (IL-6) has led to considerable interest in therapeutic targeting of this cytokine. Siltuximab, a chimeric monoclonal antibody to IL-6, has thus emerged as a promising treatment option in a disease lacking efficacious therapy. Here, we review the findings of recent studies evaluating single-agent siltuximab treatment in CD, including the first-ever randomized clinical trial in this disease. Although much more work is needed to establish a standardized treatment approach, siltuximab appears to be a safe and effective treatment for patients with newly diagnosed and previously treated CD. PMID:26869762

  18. General anesthesia in a patient with multicentric Castleman's disease: a case report

    PubMed Central

    Huh, In Young; Lee, Sang Hyun; Kim, An Suk; Park, Se Hun; Kim, Dae-Young

    2015-01-01

    Castleman's disease (CD) is a rare lymphoproliferative disorder of undetermined etiology. Unicentric Castleman's disease is confined to a single lymph node; it is usually asymptomatic though sometimes has local manifestations related to mass effects. In contrast, multicentric Castleman's disease (MCD) typically presents with lymphoid hyperplasia at multiple sites; it is associated with systemic symptoms and abnormal laboratory findings, with a less favorable prognosis. In case of anesthesia in CD, an exhaustive preanesthetic evaluation is essential to identify associated clinical manifestations which may influence the management of the anesthesia. Perioperative careful monitoring and proper anesthetic management are both important. We report a case of general anesthesia with anesthetic management in a patient with MCD that has not been documented in the literature. PMID:26045937

  19. Pulmonary disease in patients with hematologic malignancies.

    PubMed

    Poletti, Venerino; Trisolini, Rocco; Tura, Sante

    2002-03-01

    Patients with hematologic neoplasms frequently experience pulmonary disease. The possibility of a malignant involvement of the lung parenchyma is a well recognized and not unusual event, secondary spread due to lymphoproliferative disorders being the most common situation. Furthermore, the development and the advances in treatment options such as hematopoietic stem cell transplantation, radiation therapy and/or combined drug regimen use have significantly widened the spectrum of non-neoplastic pulmonary complications that can crop up in these patients. Infections, drug/radiation-induced toxicity, and graft-versus-host disease (GVHD)-related complications account by now for most pulmonary problems in hematologic patients and represent a difficult challenge both in diagnostic and in therapeutic terms for the clinician. The aim of this review is to highlight the clinicopathologic spectrum of lung diseases which can occur in the setting of hematologic malignancies. A particular emphasis is devoted to the diagnostic approach, high-resolution computed tomography (HRCT) assuming a key role since different patterns of CT abnormalities are associated with a different yield of the available diagnostic tools and may help in narrowing the differential diagnosis. PMID:12002382

  20. Predictive value of bronchiolitis obliterans syndrome stage 0p in chronic graft-versus-host disease of the lung.

    PubMed

    Abedin, Sameem; Yanik, Gregory A; Braun, Thomas; Pawarode, Attaphol; Magenau, John; Goldstein, Steven C; Levine, John E; Kitko, Carrie L; Couriel, Daniel R

    2015-06-01

    Bronchiolitis obliterans syndrome (BOS) is a significant post-transplant complication with low survival. BOS stage 0p (BOS 0p) is a parameter detected on pulmonary function tests (PFTs) after lung transplantation to identify patients at risk to develop BOS. We performed a retrospective study on 442 patients who underwent allogeneic stem cell transplant from 2007 to 2011 to evaluate whether development of BOS 0p is a risk factor in this population for BOS. Patients who met criteria for BOS 0p were significantly more likely to develop BOS (hazard ratio [HR], 3.22; P < .001). BOS 0p was significantly associated with a history of lung disease pretransplant (HR, 2.48; P = .001) and chronic graft-versus-host disease (GVHD) outside the lung post-transplant (HR, 23; P < .001). Finally, BOS 0p criteria were adequately sensitive in predicting BOS (85%), with a high negative predictive value (98%). Our findings suggest a routine PFT screening strategy with the intent of detecting BOS 0p, especially among patients with prior lung disease and who developed chronic GVHD, could suitably identify an at-risk population for the development of BOS. PMID:25687798

  1. Left ventricular function, tricuspid incompetence, and incidence of coronary artery disease late after orthotopic heart transplantation.

    PubMed

    Herrmann, G; Simon, R; Haverich, A; Cremer, J; Dammenhayn, L; Schfers, H J; Wahlers, T; Borst, H G

    1989-01-01

    Functional results and data concerning the incidence and severity of graft atherosclerosis (GASC) and tricuspid incompetence (TI) in the intermediate term after orthotopic heart transplantation (HTX) are still striking. We examined 92 patients 1, 2, and 3 years after HTX by right and left heart catheterization in order to evaluate pump function, the status of the coronary arteries and the extend of TI, using a double indicator thermodilation technique. Mean left ventricular volumes and ejection fraction were normal 1 and 2 years post-transplant. The incidence of GASC was 8/87 (9.2%) at 1, and 11/92 (12%) at 2 years. It was more frequent (16%) in patients with preexisting coronary artery disease (IHD) than in patients with underlying dilative cardiomyopathy (DCM) (11%). At the end of the 1st postoperative year, 62% of patients were free of TI, whereas only 38% had normal valve function 2 years posttransplant. In 9/14 (64%) of patients, consecutively assessed at 1 and 2 years, TI had increased between both investigations. Preoperative haemodynamics, the number of endomyocardial biopsies and rejection episodes as well as preoperative cardiac size did not correlate with TI. Left ventricular volumes and ejection fraction are normal in the intermediate term after HTX. The incidence of GASC was less than 10% at 1 year and did not significantly increase thereafter. TI is a frequent and yet unexplained finding after HTX showing a considerable tendency to increase with time, but with little or not haemodynamic consequence. PMID:2627460

  2. The management of perioperative nutrition in patients with end stage liver disease undergoing liver transplantation.

    PubMed

    Zhang, Qi-Kun; Wang, Meng-Long

    2015-10-01

    Malnutrition is found in almost 100% of patients with end stage liver disease (ESLD) awaiting transplantation and malnutrition before transplantation leads to higher rates of post-transplant complications and worse graft survival outcomes. Reasons for protein energy malnutrition include several metabolic alterations such as inadequate intake, malabsorption, and overloaded expenditure. And also, stress from surgery, gastrointestinal reperfusion injury, immunosuppressive therapy and corticosteriods use lead to delayed bowl function recovery and disorder of nutrients absorption. In the pretransplant phase, nutritional goals include optimization of nutritional status and treatment of nutrition-related symptoms induced by hepatic decompensation. During the acute post-transplant phase, adequate nutrition is required to help support metabolic demands, replenish lost stores, prevent infection, arrive at a new immunologic balance, and promote overall recovery. In a word, it is extremely important to identify and correct nutritional deficiencies in this population and provide an adequate nutritional support during all phases of liver transplantation (LT). This study review focuses on prevalence, nutrition support, evaluation, and management of perioperative nutrition disorder in patients with ESLD undergoing LT. PMID:26605281

  3. The management of perioperative nutrition in patients with end stage liver disease undergoing liver transplantation

    PubMed Central

    Zhang, Qi-Kun

    2015-01-01

    Malnutrition is found in almost 100% of patients with end stage liver disease (ESLD) awaiting transplantation and malnutrition before transplantation leads to higher rates of post-transplant complications and worse graft survival outcomes. Reasons for protein energy malnutrition include several metabolic alterations such as inadequate intake, malabsorption, and overloaded expenditure. And also, stress from surgery, gastrointestinal reperfusion injury, immunosuppressive therapy and corticosteriods use lead to delayed bowl function recovery and disorder of nutrients absorption. In the pretransplant phase, nutritional goals include optimization of nutritional status and treatment of nutrition-related symptoms induced by hepatic decompensation. During the acute post-transplant phase, adequate nutrition is required to help support metabolic demands, replenish lost stores, prevent infection, arrive at a new immunologic balance, and promote overall recovery. In a word, it is extremely important to identify and correct nutritional deficiencies in this population and provide an adequate nutritional support during all phases of liver transplantation (LT). This study review focuses on prevalence, nutrition support, evaluation, and management of perioperative nutrition disorder in patients with ESLD undergoing LT. PMID:26605281

  4. Automated pattern-guided principal component analysis vs expert-based immunophenotypic classification of B-cell chronic lymphoproliferative disorders: a step forward in the standardization of clinical immunophenotyping

    PubMed Central

    Costa, E S; Pedreira, C E; Barrena, S; Lecrevisse, Q; Flores, J; Quijano, S; Almeida, J; del Carmen García- Macias, M; Bottcher, S; Van Dongen, J J M; Orfao, A

    2010-01-01

    Immunophenotypic characterization of B-cell chronic lymphoproliferative disorders (B-CLPD) is becoming increasingly complex due to usage of progressively larger panels of reagents and a high number of World Health Organization (WHO) entities. Typically, data analysis is performed separately for each stained aliquot of a sample; subsequently, an expert interprets the overall immunophenotypic profile (IP) of neoplastic B-cells and assigns it to specific diagnostic categories. We constructed a principal component analysis (PCA)-based tool to guide immunophenotypic classification of B-CLPD. Three reference groups of immunophenotypic data files—B-cell chronic lymphocytic leukemias (B-CLL; n=10), mantle cell (MCL; n=10) and follicular lymphomas (FL; n=10)—were built. Subsequently, each of the 175 cases studied was evaluated and assigned to either one of the three reference groups or to none of them (other B-CLPD). Most cases (89%) were correctly assigned to their corresponding WHO diagnostic group with overall positive and negative predictive values of 89 and 96%, respectively. The efficiency of the PCA-based approach was particularly high among typical B-CLL, MCL and FL vs other B-CLPD cases. In summary, PCA-guided immunophenotypic classification of B-CLPD is a promising tool for standardized interpretation of tumor IP, their classification into well-defined entities and comprehensive evaluation of antibody panels. PMID:20844562

  5. Inhibitors of apoptosis (IAPs) regulate intestinal immunity and inflammatory bowel disease (IBD) inflammation.

    PubMed

    Pedersen, Jannie; LaCasse, Eric C; Seidelin, Jakob B; Coskun, Mehmet; Nielsen, Ole H

    2014-11-01

    The inhibitor of apoptosis (IAP) family members, notably cIAP1, cIAP2, and XIAP, are critical and universal regulators of tumor necrosis factor (TNF) mediated survival, inflammatory, and death signaling pathways. Furthermore, IAPs mediate the signaling of nucleotide-binding oligomerization domain (NOD)1/NOD2 and other intracellular NOD-like receptors in response to bacterial pathogens. These pathways are important to the pathogenesis and treatment of inflammatory bowel disease (IBD). Inactivating mutations in the X-chromosome-linked IAP (XIAP) gene causes an immunodeficiency syndrome, X-linked lymphoproliferative disease type 2 (XLP2), in which 20% of patients develop severe intestinal inflammation. In addition, 4% of males with early-onset IBD also have inactivating mutations in XIAP. Therefore, the IAPs play a greater role in gut homeostasis, immunity and IBD development than previously suspected, and may have therapeutic potential. PMID:25282548

  6. Chronic kidney disease after liver transplantation in human immunodeficiency virus/hepatitis C virus-coinfected recipients versus human immunodeficiency virus-infected recipients without hepatitis C virus: results from the National Institutes of Health multi-site study.

    PubMed

    Bahirwani, Ranjeeta; Barin, Burc; Olthoff, Kim; Stock, Peter; Murphy, Barbara; Rajender Reddy, K

    2013-06-01

    Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are both associated with chronic kidney disease (CKD), a major complication after orthotopic liver transplantation (OLT). The aim of this study was to assess predictors of post-OLT CKD in HIV/HCV-coinfected recipients versus HIV-infected recipients without HCV (HIV/non-HCV recipients). Data from a National Institutes of Health study of 116 OLT recipients (35 HIV/non-HCV recipients and 81 HIV/HCV-coinfected recipients) from 2003 to 2010 (Solid Organ Transplantation in HIV: Multi-Site Study) were analyzed for the pretransplant CKD prevalence [estimated glomerular filtration rate (eGFR) < 60 mL/minute for ≥3 months] and the incidence of CKD up to 3 years posttransplant. Proportional hazards models were performed to assess predictors of posttransplant CKD. A contemporaneous cohort of HCV-monoinfected transplant recipients from the Scientific Registry of Transplant Recipients database was also analyzed. The median age at transplant was 48 years, the median serum creatinine level was 1.1 mg/dL, and the median eGFR was 77 mL/minute. Thirty-four patients were suspected to have pretransplant CKD; 20 of these patients (59%) had posttransplant CKD. Among the 82 patients without pretransplant CKD (26 HIV/non-HCV patients and 56 HIV/HCV-coinfected patients), the incidence of stage 3 CKD 3 years after OLT was 62% (55% of HIV/non-HCV patients and 65% of HIV/HCV-coinfected patients), and the incidence of stage 4/5 CKD was 8% (0% of HIV/non-HCV patients and 12% of HIV/HCV-coinfected patients). In a multivariate analysis, older age [[hazard ratio (HR) = 1.05 per year, P = 0.03] and the CD4 count (HR = 0.90 per 50 cells/μL, P = 0.01) were significant predictors of CKD. HCV coinfection was significantly associated with stage 4/5 CKD (HR = 10.8, P = 0.03) after adjustments for age. The cumulative incidence of stage 4/5 CKD was significantly higher for HIV/HCV-coinfected patients versus HIV/non-HCV transplant recipients and HCV-monoinfected transplant recipients (P = 0.001). In conclusion, CKD occurs frequently in HIV-infected transplant recipients. Predictors of posttransplant CKD include older age and a lower posttransplant CD4 count. HCV coinfection is associated with a higher incidence of stage 4/5 CKD. PMID:23512786

  7. Cholestasis and end-stage liver disease.

    PubMed

    Protheroe, S M; Kelly, D A

    1998-12-01

    Protein-energy malnutrition is an inevitable consequence of chronic liver disease, particularly in the developing infant. Severe malnutrition with loss of fat stores and muscle wasting affects between 60% and 80% of infants with liver disease (Beath, 1993a; Holt et al, 1997). Reduced energy intake secondary to anorexia, vomiting and fat malabsorption, in association with a disordered metabolism of carbohydrate and protein, increased energy requirements and vitamin and mineral deficiencies, contributes towards growth failure. Reversal of malnutrition is one of the key aims of liver transplantation and is achieved in the majority of long-term survivors. The aetiology of persistent growth failure post-transplantation is multifactorial and is related to pre-operative malnutrition, glucocorticoid administration, feeding problems and post-operative complications. Strategies to prevent pre- and post-transplant growth failure include early referral for liver transplantation and a multidisciplinary approach to nutritional support, which may increase survival and improve the quality of life and outcome of liver transplantation. PMID:10079909

  8. Castleman disease of the mesentery as the great mimic: Incidental finding of one case and the literature review.

    PubMed

    Lv, Ang; Hao, Chunyi; Qian, Honggang; Leng, Jiahua; Liu, Wendy

    2015-06-01

    Castleman disease is an uncommon benign lymphoproliferative disorder characterized by hyperplasia of lymphoid follicles. More commonly described in the mediastinum, its occurrence in the mesentery is exceedingly rare, which is easily to be ignored in differential diagnosis when an abdominal mass is found. We report the case of an asymptomatic 71-year-old woman with a homogenous and hypervascular mass at the inner side of duodenojejunal junction. Based on the clinical suspicion of a gastrointestinal stromal tumor, a surgical resection was performed. Final diagnosis of the mass was hyaline vascular variant of Castleman disease. Here, we summarize the clinicopathological and radiological features of this disease by literature review, which may be helpful to bring awareness of this entity and improve the clinical decision making when similar scenarios are encountered. PMID:26166374

  9. Intensive therapy and autotransplantation in Hodgkin's disease.

    PubMed

    Reece, D E; Phillips, G L

    1994-09-01

    Intensive therapy and autologous marrow or peripheral blood stem cell transplantation is often utilized in Hodgkin's disease patients whose disease has progressed after primary conventional chemotherapy. A number of studies have described long-term disease-free survival in up to 50% of transplanted patients. High-dose chemotherapy conditioning regimens such as "CBV" or "BEAM" have been used more often than regimens containing total body irradiation. Usually unpurged autologous bone marrow has been utilized as the source of hematopoietic stem cell reconstitution, although recently the use of "primed" peripheral blood stem cells has increased markedly. The challenges of transplant-related toxicity and recurrence of disease post-transplant are discussed, as well as possible strategies to reduce these problems. The use of autologous transplantation is discussed in three clinical settings: patients who have failed to enter a complete remission (CR) after primary chemotherapy, those who have relapsed within 12 months of attaining a CR and those who have relapsed after a longer (i.e., > or = 12 months) first CR. When compared with conventional salvage chemotherapy, transplantation appears to produce a higher long-term disease-free survival rate in all of these patient groups. However, assessment of an advantage for autotransplantation, particularly in patients with long first remissions, is difficult without a Phase III trial. On the other hand, recently updated results from our center indicate that 72% of patients relapsing after long initial remissions benefit from autotransplantation at this point in their disease course, and that transplant-related mortality is low in this setting. Other issues addressed include the potential role of autologous transplantation as consolidation therapy in selected high-risk patients in an initial CR, as well as the utility of conventional chemotherapy and involved-field radiotherapy in conjunction with autotransplantation. PMID:7804123

  10. Renal Function and Transplantation in Liver Disease.

    PubMed

    Parajuli, Sandesh; Foley, David; Djamali, Arjang; Mandelbrot, Didier

    2015-09-01

    Kidney injury is associated with increased morbidity and mortality in liver transplant recipients. Since the introduction of the model for end-stage liver disease for the allocation of organs for liver transplantation in 2002, the heavy weighting of serum creatinine in the model for end-stage liver disease score has significantly increased the incidence of renal dysfunction seen among patients undergoing liver transplantation. As a result, the frequency of simultaneous liver-kidney (SLK) transplantation compared to liver transplantation alone (LTA) has also increased. The decision to perform SLK rather than LTA is an important one because the benefits to the liver transplant recipient receiving a kidney transplant must be balanced with the benefits of using that organ for a patient with end-stage renal disease. However, predicting whether or not a patient with liver failure has reversible kidney disease, and therefore does not also need a kidney transplant, is difficult. The severity and duration of pretransplant renal dysfunction, hepatitis c, diabetes, and other risk factors for kidney disease are associated with an increased risk of posttransplant end-stage renal disease. However, there are currently no clinical findings that accurately predict renal recovery post liver transplant. As a result, the rate of SLK versus LTA differs significantly between transplant centers. To increase consistency across centers, multiple guidelines have been proposed to guide the decision between SLK and LTA, but their poor predictive value has limited their uniform adoption. Nevertheless, adoption of uniform rules for the allocation of kidneys would reduce the variability between centers in rates of SLK transplant. PMID:26308413

  11. Unicentric Castleman's Disease Arising from an Intrapulmonary Lymph Node

    PubMed Central

    Ota, Hideki; Kawai, Hideki; Matsuo, Tsubasa

    2013-01-01

    Castleman's disease is an uncommon lymphoproliferative disorder of unknown etiology, most often involving the mediastinum. It has 2 distinct clinical forms: unicentric and multicentric. Unicentric Castleman's disease arising from an intrapulmonary lymph node is rare, and establishing a preoperative diagnosis of this disease is very difficult mainly due to a lack of specific imaging features. We report a case of intrapulmonary unicentric Castleman's disease in an asymptomatic 19-year-old male patient who was accurately diagnosed by preoperative computed tomography (CT). The mass was incidentally found on a routine chest X-ray. A subsequent dynamic CT showed a well-defined, hypervascular, soft-tissue mass with small calcifications located in the perihilar area of the right lower lung. Three-dimensional CT (3D-CT) angiography indicated that the mass was receiving its blood supply through a vascular network at its surface that originated from 2 right bronchial arteries. The clinical history and CT findings were consistent with a diagnosis of unicentric Castleman's disease, and we safely and successfully removed the tumor via video-assisted thoracoscopic surgical lobectomy. This case shows that the imaging characteristics of these rare tumors on contrast-enhanced CT combined with 3D-CT angiography can be helpful in reliably establishing a correct preoperative diagnosis. PMID:23841009

  12. Surgical management of isolated retroperitoneal Castleman's disease: A case report

    PubMed Central

    XU, JUN; ZHOU, BO; CAO, HUA-LI; WANG, BO; YAN, SHENG; ZHENG, SHU-SEN

    2016-01-01

    Castleman's disease (CD) is an uncommon, poorly understood lymphoproliferative disease. Retroperitoneal forms may present as either a unicentric or multicentric disease. The present study reports the case of a 36-year-old man who was referred to the First Affiliated Hospital, School of Medicine, Zhejiang University (Hangzhou, China), for a detailed examination of an abdominal mass. The abdominal ultrasound and computed tomography scans revealed a solid mass localized in the region between segment 1 of the liver and the pancreas. An endosonography-guided fine-needle aspiration biopsy revealed chronic inflammation and lymphadenosis. The present study reports a rare case, in which the patient was treated with an exploratory laparotomy and resection. The retroperitoneal mass was pathologically diagnosed as CD of the hyaline vascular type. The patient was closely followed-up for 11 months and is presently free of disease. In conclusion, the possibility of unicentric CD should be considered when facing a solid hypervascular retroperitoneal mass. A complete surgical resection may successfully treat the disease without an unnecessarily extensive resection for the unicentric type. PMID:26998133

  13. Multicentric Castleman Disease With Tubulointerstitial Nephritis Mimicking IgG4-related Disease: Two Case Reports.

    PubMed

    Zoshima, Takeshi; Yamada, Kazunori; Hara, Satoshi; Mizushima, Ichiro; Yamagishi, Masakazu; Harada, Kenichi; Sato, Yasuharu; Kawano, Mitsuhiro

    2016-04-01

    Multicentric Castleman disease is a benign lymphoproliferative disorder with heterogenous clinical symptoms and involves systemic organs in addition to lymph nodes. Elevated serum IgG4 levels and IgG4-positive plasma cell (IgG4+PC) infiltrates have been reported in lymph nodes, lung and skin in some multicentric Castleman disease cases, resembling IgG4-related disease (IgG4-RD) histologically. However, no report has been available regarding IgG4+PC infiltration in the kidneys of multicentric Castleman disease. Here, we report 2 cases of multicentric Castleman disease complicated by IgG4-related disease (IgG4-RD) histologically. However, there has been no report published on PC-rich tubulointerstitial nephritis, lymphadenopathy, with numerous IgG4+PC infiltration, and elevated serum IgG4 levels, mimicking IgG4-RD. The blood examinations revealed systemic inflammation and elevated C-reactive protein and interleukin-6 levels. Corticosteroid therapy was partially effective in both cases, and combination therapy of corticosteroid and tocilizumab was needed in both cases. Moreover, after triple therapy with corticosteroid, rituximab and cyclophosphamide were used in 1 case to tame the severe inflammation. The present cases suggest that if continuously elevated serum C-reactive protein levels and partial corticosteroid responsiveness are encountered, multicentric Castleman disease should be considered rather than IgG4-RD as a differential diagnosis even if serum IgG4 is elevated and IgG4+PCs infiltrate systemic organs. PMID:26598921

  14. Subacute radiation dermatitis: a histologic imitator of acute cutaneous graft-versus-host disease

    SciTech Connect

    LeBoit, P.E.

    1989-02-01

    The histopathologic changes of radiation dermatitis have been classified either as early effects (necrotic keratinocytes, fibrin thrombi, and hemorrhage) or as late effects (vacuolar changes at the dermal-epidermal junction, atypical radiation fibroblasts, and fibrosis). Two patients, one exposed to radiation therapeutically and one accidentally, are described. Skin biopsy specimens showed an interface dermatitis characterized by numerous dyskeratotic epidermal cells with lymphocytes in close apposition (satellite cell necrosis); that is, the epidermal changes were similar to those in acute graft-versus-host disease. Because recipients of bone marrow transplants frequently receive total body irradiation as part of their preparatory regimen, the ability of radiation to cause persistent epidermal changes similar to those in acute graft-versus-host disease could complicate the interpretation of posttransplant skin biopsy specimens.

  15. Late graft loss or death in pediatric liver transplantation: an analysis of the SPLIT database.

    PubMed

    Soltys, K A; Mazariegos, G V; Squires, R H; Sindhi, R K; Anand, R

    2007-09-01

    Late graft loss (LGL) and late mortality (LM) following liver transplantation (LT) in children were analyzed from the studies of pediatric liver transplantation (SPLIT) database. Univariate and multivariate associations between pre- and postoperative factors and LGL and LM in 872 patients alive with their primary allografts 1 year after LT were reviewed. Thirty-four patients subsequently died (LM) and 35 patients underwent re-LT (LGL). Patients who survive the first posttransplant year had 5-year patient and graft survival rates of 94.2% and 89.2%, respectively. Graft loss after the first year was caused by rejection in 49% of the cases with sequelae of technical complications accounting for an additional 20% of LGL. LT for tumor, steroid resistant rejection, reoperation in the first 30 days and >5 admissions during the first posttransplant year were independently associated with LGL in multivariate analysis. Malignancy, infection, multiple system organ failure and posttransplant lymphoproliferative disease accounted for 61.8% of all late deaths after LT. LT performed for FHF and tumor were associated with LM. Patients who are at or below the mean for weight at the time of transplant were also at an increased risk of dying. Frequent readmission was also found to be associated with LM. PMID:17608834

  16. Post-transplant Merkel Cell Carcinoma.

    PubMed

    Koljonen, Virve; Sahi, Helka; Böhling, Tom; Mäkisalo, Heikki

    2016-04-12

    Malignant tumours are the foremost complications of immunosuppressive treatment. They are a major challenge for organ transplant recipients and their treating physicians. This paper reviews the aetiology and current treatment of an unusual neuroendocrine skin cancer, Merkel cell carcinoma (MCC), caused by a Merkel cell polyomavirus infection. MCC occurs more frequently than expected in immunosuppressed subjects, especially in organ transplant recipients. The current literature comprises reports of 79 organ transplant recipients with MCC. The risk of MCC in organ transplant recipients is increased up to 66-182-fold compared with the general population. In addition to the increased risk of developing MCC, immunosuppressed individuals have poorer MCC-specific survival. The aim of this review article is to familiarize organ transplant doctors with this unique and clinically challenging skin cancer, and to provide recent data on the diagnosis and current treatment recommendations for an immunosuppressed population. PMID:26554531

  17. Asymptomatic Isolated Retroperitoneal Castleman's Disease: A Case Report.

    PubMed

    Rajabiani, Afsaneh; Abdollahi, Alireza; Farahani, Zahra

    2015-09-01

    Castleman's disease, giant lymph node hyperplasia, is a kind of benign lymphoproliferative disease with gentle behavior. Its etiology and prevalence are unclear. This rare disease is usually found in mediastinal area asymptomatically and incidentally. It is also rare to see this tumor in the retroperitoneum. In this study, we have introduced a 34-year-old woman who referred just with occasional abdominal pain caused by compressive symptoms. Laboratory findings only reported microcytic anemia (MCH: 18.5, MCV: 63, Hemoglobin 10.2 g/dl). Chest and abdominal X-ray imaging showed no remarkable point. In abdominal ultrasonography, a solid and firm tumor with 12.2×5.3×6.6 cm was reported in patient's retroperitoneum. Patient's surgery was done and the tumor (covered by a fibrous thick capsule, with no bizarre appearance and bleeding) was completely removed. Pathologic examination indicated a Castleman's tumor, type of unicentric and hyaline-vascular. This item had been one of the rare reported items of Castleman's disease in the retroperitoneal space. PMID:26379356

  18. Late-onset graft-versus-host disease after pediatric living-related liver transplantation for Langerhans cell histiocytosis.

    PubMed

    Yuksekkaya, Hasan Ali; Arikan, Cigdem; Tumgor, Gokhan; Aksoylar, Serap; Kilic, Murat; Aydogdu, Sema

    2011-09-01

    GVHD is the most common and well-known cause of morbidity and mortality following allogeneic BM transplantation. The GVHD following OLT is an uncommon complication but has a high mortality and poses a major diagnostic and therapeutic challenge. We herein discussed a 12-month-old girl with multi-system LCH, who developed end-stage liver disease despite intensive chemotherapy. She underwent ABO-compatible liver transplantation at 28 months while in remission from LCH. The donor was her 26-yr-old father. Post-operative course was uneventful. The GVHD manifested with skin rash and BM suppression on post-transplant day 94 and confirmed by both microchimerism and skin biopsy. Prednisolone, basiliximab, and ATG were administered immediately but the bone marrow suppression was not improved and the patient died because of Candida sepsis at six-month post-transplant. GVHD after OLT should be keep in mind in patients with rash and BM suppression after liver transplantation. In LDLT, a patient who carries risk factors should investigated for optimal HLA matching. PMID:21884342

  19. Castleman disease variant of POEMS syndrome complicated with multiple cerebral infarction: a rare case report and review of literature

    PubMed Central

    Yu, Hang; Yao, Fang; Li, Yue; Li, Jian; Cui, Quan-Cai

    2015-01-01

    POEMS syndrome is a rare hematological disorder associated with plasma cell dyscrasia characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. Castleman disease is a lymphoproliferative disorder that can be present in POEMS patients, which can be defined as Castleman disease variant of POEMS syndrome. Herein, we described a 24-year-old male patient diagnosed with this syndrome and also suffered from multiple cerebral infarctions. This patient showed no evidence of monoclonal gammopathy and failed to have electromyography examined. The final diagnosis was established with the help of the axillary lymph node biopsy. As a rare case of POEMS syndrome without evidence fulfilling the major mandatory diagnostic criteria and with cerebrovascular involvement, its characteristics was discussed with a brief literature review in order to facilitate further understanding of the POEMS syndrome. PMID:26722578

  20. Gene mutations and alternate RNA splicing result in truncated Ig L chains in human gamma H chain disease.

    PubMed

    Cogn, M; Bakhshi, A; Korsmeyer, S J; Guglielmi, P

    1988-09-01

    The lack of covalently associated L chains features H chain disease proteins produced in some human B cell lymphoproliferative disorders. We cloned and characterized the single rearranged kappa L chain gene from the leukemic lymphocytes of a patient (RIV) affected with gamma 1 H chain disease, to determine the molecular basis for absent L chain. This kappa allele had undergone an effective V-J rearrangement. Extensive somatic mutation focused about the V-J region created a sequence that was only 75% homologous to its germ-line counterpart. Altered acceptor (V kappa) and donor (J kappa) splice sites resulted in an aberrant splice between the leader and C kappa exons and a truncated 850-bp kappa mRNA. RIV leukemic cells as well as myeloma cells transfected with the RIV kappa gene synthesized a truncated protein. Simultaneous defects in H and L chains genes may reflect a hypermutational mechanism for Ig genes in B cells. PMID:3137264

  1. The clinical significance of EBV DNA in the plasma and peripheral blood mononuclear cells of patients with or without EBV diseases.

    PubMed

    Kanakry, Jennifer A; Hegde, Aparna M; Durand, Christine M; Massie, Allan B; Greer, Amy E; Ambinder, Richard F; Valsamakis, Alexandra

    2016-04-21

    Epstein-Barr virus (EBV) is a ubiquitous virus that establishes a latent infection within the host and in some cases can lead to the development of EBV-associated lymphomas, lymphoproliferative disorders, hemophagocytic lymphohistiocytosis, solid tumors, and other diseases. We studied the clinical significance of detecting EBV DNA in the plasma and peripheral blood mononuclear cells (PBMCs) of 2146 patients who had blood specimens sent to the Johns Hopkins Hospital clinical laboratory for viral quantitative real-time polymerase chain reaction assay over a 5-year period. Within this largely immunocompromised and hospitalized cohort, 535 patients (25%) had EBV detected in plasma or PBMCs. When EBV was detected in the absence of an EBV(+)disease (n = 402), it was present only in PBMCs in 69% of cases. Immunocompromised patients were less likely to have EBV in plasma than in PBMCs in the absence of EBV(+)disease. In patients with active, systemic EBV(+)diseases (n = 105), EBV was detected in plasma in 99% of cases but detected in PBMCs in only 54%. Across a range of copy number cutoffs, EBV in plasma had higher specificity and sensitivity for EBV(+)disease as compared with EBV in PBMCs. EBV copy number in plasma distinguished untreated, EBV(+)lymphoma from EBV(+)lymphoma in remission and EBV(-)lymphoma, and also distinguished untreated, EBV(+)posttransplantation lymphoproliferative disorder (PTLD) from EBV(+)PTLD in remission and EBV(-)PTLD. EBV copy number quantification is a useful diagnostic marker across the spectrum of EBV(+)diseases, even among immunocompromised patients, with plasma specimens more indicative of EBV(+)disease than PBMCs. PMID:26744460

  2. Clinical implications and prognostic role of minimal residual disease detection in follicular lymphoma

    PubMed Central

    Lobetti-Bodoni, Chiara; Mantoan, Barbara; Monitillo, Luigia; Genuardi, Elisa; Drandi, Daniela; Barbero, Daniela; Bernocco, Elisa; Boccadoro, Mario

    2013-01-01

    The identification of patients at high risk of relapse is a critical goal of modern translational research in oncohematology. Minimal residual disease (MRD) detection by polymerase chain reaction-based methods is routinely employed in the management of patients with acute lymphoblastic leukemia. Current knowledge indicates that it is also a useful prognostic tool in several mature lymphoproliferative disorders and particularly in follicular lymphoma (FL). Based on this evidence clinical trials employing MRD-based risk stratification are currently ongoing in FL. In this review the ‘state of the art’ of MRD evaluation in FL is discussed. A short description of technical issues and recent methodological advances is provided. Then, the bulk of the review focuses on critical take-home messages for clinicians working in the field. Finally, we discuss future perspectives of MRD detection and more generally outcome prediction in FL. PMID:23730496

  3. Clinical implications and prognostic role of minimal residual disease detection in follicular lymphoma.

    PubMed

    Lobetti-Bodoni, Chiara; Mantoan, Barbara; Monitillo, Luigia; Genuardi, Elisa; Drandi, Daniela; Barbero, Daniela; Bernocco, Elisa; Boccadoro, Mario; Ladetto, Marco

    2013-06-01

    The identification of patients at high risk of relapse is a critical goal of modern translational research in oncohematology. Minimal residual disease (MRD) detection by polymerase chain reaction-based methods is routinely employed in the management of patients with acute lymphoblastic leukemia. Current knowledge indicates that it is also a useful prognostic tool in several mature lymphoproliferative disorders and particularly in follicular lymphoma (FL). Based on this evidence clinical trials employing MRD-based risk stratification are currently ongoing in FL. In this review the 'state of the art' of MRD evaluation in FL is discussed. A short description of technical issues and recent methodological advances is provided. Then, the bulk of the review focuses on critical take-home messages for clinicians working in the field. Finally, we discuss future perspectives of MRD detection and more generally outcome prediction in FL. PMID:23730496

  4. Isolated microcytic anemia disclosing a unicentric Castleman disease: The interleukin-6/hepcidin pathway?

    PubMed

    Vinzio, Stéphane; Ciarloni, Laetitia; Schlienger, Jean-Louis; Rohr, Serge; Méchine, Agnès; Goichot, Bernard

    2008-07-01

    Castleman disease (CD) is a rare lymphoproliferative disorder of uncertain origin. Anemia is commonly reported and is related to an inflammatory mechanism. Occasionally an autoimmune hemolytic anemia appears as the leading clinical feature. Three histological types have been differentiated, a hyaline-vascular type (HV), a plasma cell type (PC), and a mixed type. Clinically CD is separated into unicentric (localized) or multicentric (generalized) forms. The former is most frequently of HV type (80-90%), affecting a single lymph node. The PC type is encountered in 10-20% of the unicentric CD and in almost all of the multicentric cases. Numerous systemic manifestations have been described usually associated with PC type. An isolated and markedly microcytic anemia revealing a unicentric CD has never been reported in English literature. Recent data concerning iron metabolism, interleukin-6 and hepcidin provide interesting clues to understand the particular microcytic anemia of CD. PMID:18549942

  5. XMEN DISEASE: A COMBINED IMMUNE DEFICIENCY WITH MAGNESIUM DEFECT

    PubMed Central

    Ravell, Juan; Chaigne-Delalande, Benjamin; Lenardo, Michael

    2015-01-01

    Purpose of review To describe the role of the magnesium transporter 1 (MAGT1) in the pathogenesis of “X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia” (XMEN) disease and its clinical implications. Recent findings The magnesium transporter protein MAGT1 participates in intracellular Mg2+ homeostasis and facilitates a transient Mg2+ influx induced by activation of the T cell receptor (TCR). Loss-of-function mutations in MAGT1 cause an immunodeficiency named XMEN syndrome characterized by CD4 lymphopenia, chronic EBV infection, and EBV-related lymphoproliferative disorders. Patients with XMEN disease have impaired T cell activation and decreased cytolytic function of natural killer (NK) and CD8+ T cells due to decreased expression of the natural killer stimulatory receptor natural-killer group 2, member D (NKG2D). Patients may have defective specific antibody responses secondary to T cell dysfunction, but B cells have not been shown to be directly affected by mutations in MAGT1. Summary XMEN disease has revealed a novel role for free intracellular magnesium in the immune system. Further understanding of the MAGT1 signaling pathway may lead to new diagnostic and therapeutic approaches. PMID:25313976

  6. Small Bowel and Liver/Small Bowel Transplantation in Children

    PubMed Central

    Reyes, Jorge; Tzakis, Andreas G.; Todo, Satoru; Nour, Bakr; Starzl, Thomas E.

    2010-01-01

    A clinical trial of intestinal transplantation was initiated at the University of Pittsburgh in May 1990. Eleven children received either a combined liver/small bowel graft (n = 8) or an isolated small bowel graft (n = 3). Induction as well as maintenance immunosuppression was with FK-506 and steroids. Four patients were male, and seven were female; the age range was 6 months to 10.2 years. There were 3 deaths (all in recipients of the combined liver/small bowel graft), which were attributed to graft-versus-host disease (n = 1), posttransplant lymphoproliferative disease (n = 1), and biliary leak (n = 1). Transplantation of the intestine has evolved into a feasible operation, with an overall patient and graft survival rate of 73%. These survivors are free of total parenteral nutrition, and the majority are home. These encouraging results justify further clinical trials. PMID:8062049

  7. Two consecutive partial liver transplants in a patient with Classic Maple Syrup Urine Disease.

    PubMed

    Chin, H L; Aw, M M; Quak, S H; Huang, J; Hart, C E; Prabhakaran, K; Goh, D L

    2015-09-01

    Maple syrup urine disease is caused by a deficiency in the branched chain ketoacid dehydrogenase (BCKAD) complex. This results in the accumulation of branched chain amino acids (BCAA) and branched chain ketoacids in the body. Even when aggressively treated with dietary restriction of BCAA, patients experience long term cognitive, neurological and psychosocial problems. Liver transplantation from deceased donors has been shown to be an effective modality in introducing adequate BCKAD activity, attaining a metabolic cure for patients. Here, we report the clinical course of the first known patient with classic MSUD who received two consecutive partial liver grafts from two different living non-carrier donors and his five year outcome posttransplant. We also show that despite the failure of the first liver graft, and initial acute cellular rejection of the second liver graft in our patient, his metabolic control remained good without metabolic decompensation. PMID:26937410

  8. Risk factors for lung diseases after renal transplantation

    PubMed Central

    Pencheva, Ventsislava P.; Petrova, Daniela S.; Genov, Diyan K.; Georgiev, Ognian B.

    2015-01-01

    Background: Lung diseases are one of the major causes of morbidity and mortality after renal transplantation. The aim of the study is to define the risk factors for infectious and noninfectious pulmonary complications in kidney transplant patients. Materials and Methods: We prospectively studied 267 patients after renal transplantation. The kidney recipients were followed-up for the development of pulmonary complications for a period of 7 years. Different noninvasive and invasive diagnostic tests were used in cases suspected of lung disease. Results: The risk factors associated with the development of pulmonary complications were diabetes mellitus (odds ratio [OR] = 4.60; P = 0.001), arterial hypertension (OR = 1.95; P = 0.015), living related donor (OR = 2.69; P = 0.004), therapy for acute graft rejection (OR = 2.06; P = 0.038), immunosuppressive regimens that includes mycophenolate (OR = 2.40; P = 0.011), azathioprine (OR = 2.25; P = 0.023), and tacrolimus (OR = 1.83; P = 0.041). The only factor associated with the lower risk of complications was a positive serology test for Cytomegalovirus of the recipient before transplantation (OR = 0.1412; P = 0.001). Conclusion: The risk factors can be used to identify patients at increased risk for posttransplant lung diseases. Monitoring of higher-risk patients allow timely diagnosis and early adequate treatment and can reduce the morbidity and mortality after renal transplantation. PMID:26958045

  9. Memory B-cell reconstitution following allogeneic hematopoietic stem cell transplantation is an EBV-associated transformation event.

    PubMed

    Burns, David M; Tierney, Rose; Shannon-Lowe, Claire; Croudace, Jo; Inman, Charlotte; Abbotts, Ben; Nagra, Sandeep; Fox, Christopher P; Chaganti, Sridhar; Craddock, Charles F; Moss, Paul; Rickinson, Alan B; Rowe, Martin; Bell, Andrew I

    2015-12-17

    Allogeneic stem cell transplantation (allo-HSCT) provides a unique opportunity to track Epstein-Barr virus (EBV) infection in the context of the reconstituting B-cell system. Although many allo-HSCT recipients maintain low or undetectable levels of EBV DNA posttransplant, a significant proportion exhibit elevated and rapidly increasing EBV loads which, if left untreated, may lead to potentially fatal EBV-associated posttransplant lymphoproliferative disease. Intriguingly, this high-level EBV reactivation typically arises in the first 3 months posttransplant, at a time when the peripheral blood contains low numbers of CD27+ memory cells which are the site of EBV persistence in healthy immunocompetent donors. To investigate this apparent paradox, we prospectively monitored EBV levels and B-cell reconstitution in a cohort of allo-HSCT patients for up to 12 months posttransplant. In patients with low or undetectable levels of EBV, the circulating B-cell pool consisted predominantly of transitional and naive cells, with a marked deficiency of CD27+ memory cells which lasted >12 months. However, among patients with high EBV loads, there was a significant increase in both the proportion and number of CD27+ memory B cells. Analysis of sorted CD27+ memory B cells from these patients revealed that this population was preferentially infected with EBV, expressed EBV latent transcripts associated with B-cell growth transformation, had a plasmablastic phenotype, and frequently expressed the proliferation marker Ki-67. These findings suggest that high-level EBV reactivation following allo-HSCT may drive the expansion of latently infected CD27+ B lymphoblasts in the peripheral blood. PMID:26450987

  10. Memory B-cell reconstitution following allogeneic hematopoietic stem cell transplantation is an EBV-associated transformation event

    PubMed Central

    Burns, David M.; Tierney, Rose; Shannon-Lowe, Claire; Croudace, Jo; Inman, Charlotte; Abbotts, Ben; Nagra, Sandeep; Fox, Christopher P.; Chaganti, Sridhar; Craddock, Charles F.; Moss, Paul; Rickinson, Alan B.; Rowe, Martin

    2015-01-01

    Allogeneic stem cell transplantation (allo-HSCT) provides a unique opportunity to track Epstein-Barr virus (EBV) infection in the context of the reconstituting B-cell system. Although many allo-HSCT recipients maintain low or undetectable levels of EBV DNA posttransplant, a significant proportion exhibit elevated and rapidly increasing EBV loads which, if left untreated, may lead to potentially fatal EBV-associated posttransplant lymphoproliferative disease. Intriguingly, this high-level EBV reactivation typically arises in the first 3 months posttransplant, at a time when the peripheral blood contains low numbers of CD27+ memory cells which are the site of EBV persistence in healthy immunocompetent donors. To investigate this apparent paradox, we prospectively monitored EBV levels and B-cell reconstitution in a cohort of allo-HSCT patients for up to 12 months posttransplant. In patients with low or undetectable levels of EBV, the circulating B-cell pool consisted predominantly of transitional and naive cells, with a marked deficiency of CD27+ memory cells which lasted >12 months. However, among patients with high EBV loads, there was a significant increase in both the proportion and number of CD27+ memory B cells. Analysis of sorted CD27+ memory B cells from these patients revealed that this population was preferentially infected with EBV, expressed EBV latent transcripts associated with B-cell growth transformation, had a plasmablastic phenotype, and frequently expressed the proliferation marker Ki-67. These findings suggest that high-level EBV reactivation following allo-HSCT may drive the expansion of latently infected CD27+ B lymphoblasts in the peripheral blood. PMID:26450987

  11. Prion Diseases

    MedlinePlus

    ... cow" disease) in cattle; Creutzfeldt-Jakob disease in humans; scrapie in sheep; and chronic wasting disease in deer and elk. Much about TSE diseases remains unknown. The diseases are characterized by certain misshapen ...

  12. Rh Disease

    MedlinePlus

    ... Loss > Birth defects & other health conditions > Rh disease Rh disease E-mail to a friend Please fill ... treatment usually can prevent Rh disease. How does Rh disease affect a fetus or newborn? Rh disease ...

  13. Lyme Disease

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Lyme Disease Lyme disease, or borreliosis, is caused by ... designed to increase our understanding of this disease. Lyme Disease A History of Lyme Disease, Symptoms, Diagnosis, ...

  14. A Multidisciplinary Approach to Castleman Disease of the Neck.

    PubMed

    Shams, Alexandra A; Ahmed, Mostafa M; Scalzitti, Nicholas J; Howell, Della L; Hall, Jordan M; Ritter, John L; Maturo, Stephen C

    2016-02-01

    Castleman disease (CD) is a rare lymphoproliferative disorder that occurs in adults and rarely in the pediatric population. The disease is characterized by slowly enlarging masses that can form anywhere within the lymphatic system. It is an uncommon cause of a neck mass in both children and adults that presents insidiously and nonspecifically. A 21-year-old woman was referred to the otolaryngology service because of an asymptomatic neck mass found incidentally on computed tomographic imaging 15 months earlier. On repeat imaging, the lesion was characterized as a homogenously enhancing soft tissue mass and appeared stable in size compared with previous studies. Given the nondiagnostic radiologic features, tissue sampling was pursued, first using fine-needle aspiration and ultimately excisional biopsy. The excision revealed histopathology consistent with unicentric, hyaline-vascular CD. Excision is the gold standard for treatment of this variant of CD. The patient was referred to the hematology/oncology service but was subsequently lost to follow-up. This case illustrates a rare cause of a neck mass in a young adult and exemplifies the extremely broad differential in this setting. In addition, it highlights the importance of a systematic and thorough approach to diagnosing neck masses in children and adults. PMID:26840960

  15. Atypical Cutaneous Manifestations in Adult Onset Still's Disease.

    PubMed

    Nataraja, Champa; Griffiths, Hedley

    2016-01-01

    Adult Onset Still's Disease (AOSD), an adult variant of systemic onset juvenile idiopathic arthritis, is a rare systemic inflammatory disorder of unknown aetiology. The rarity of this disease is associated with low index of suspicion and delayed diagnosis in patients suffering from it and in the presence of atypical features the diagnosis can be further challenging. This is a case report on a 24-year-old woman, who was a diagnostic dilemma for 2 years due to the nonspecific symptoms of recurrent fever, generalized maculopapular persistent pruritic and tender rash, and polyarthralgia. She was initially diagnosed as leukocytoclastic vasculitis on a skin biopsy and was managed by a dermatologist with various medications including NSAIDs, hydroxychloroquine, dapsone, colchicine, cyclosporine, and high doses of oral steroids with minimal response. Subsequently, she has had multiple admissions with similar symptoms with raised inflammatory markers and negative septic workup. On one occasion, her iron study revealed hyperferritinaemia which led to the suspicion of AOSD. Once the rheumatic fever and infectious, malignant, autoimmune, and lymphoproliferative disorders were excluded, she was diagnosed as probable AOSD and managed successfully with IL-1 (interleukin-1) receptor antagonist, Anakinra, with remarkable and lasting response both clinically and biochemically. PMID:26981304

  16. Atypical Cutaneous Manifestations in Adult Onset Still's Disease

    PubMed Central

    Nataraja, Champa; Griffiths, Hedley

    2016-01-01

    Adult Onset Still's Disease (AOSD), an adult variant of systemic onset juvenile idiopathic arthritis, is a rare systemic inflammatory disorder of unknown aetiology. The rarity of this disease is associated with low index of suspicion and delayed diagnosis in patients suffering from it and in the presence of atypical features the diagnosis can be further challenging. This is a case report on a 24-year-old woman, who was a diagnostic dilemma for 2 years due to the nonspecific symptoms of recurrent fever, generalized maculopapular persistent pruritic and tender rash, and polyarthralgia. She was initially diagnosed as leukocytoclastic vasculitis on a skin biopsy and was managed by a dermatologist with various medications including NSAIDs, hydroxychloroquine, dapsone, colchicine, cyclosporine, and high doses of oral steroids with minimal response. Subsequently, she has had multiple admissions with similar symptoms with raised inflammatory markers and negative septic workup. On one occasion, her iron study revealed hyperferritinaemia which led to the suspicion of AOSD. Once the rheumatic fever and infectious, malignant, autoimmune, and lymphoproliferative disorders were excluded, she was diagnosed as probable AOSD and managed successfully with IL-1 (interleukin-1) receptor antagonist, Anakinra, with remarkable and lasting response both clinically and biochemically. PMID:26981304

  17. Comparison of Subcutaneous versus Intravenous Alemtuzumab for Graft-versus-Host Disease Prophylaxis with Fludarabine/Melphalan-Based Conditioning in Matched Unrelated Donor Allogeneic Stem Cell Transplantation.

    PubMed

    Patel, Khilna; Parmar, Sapna; Shah, Shreya; Shore, Tsiporah; Gergis, Usama; Mayer, Sebastian; van Besien, Koen

    2016-03-01

    The objective of this study was to compare infusion-related reactions and outcomes of using subcutaneous (subQ) alemtuzumab versus intravenous (i.v.) alemtuzumab as graft-versus-host disease (GVHD) prophylaxis for matched unrelated donor stem cell transplantations. Outcomes include incidence of cytomegalovirus (CMV)/Epstein-Barr (EBV) viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, time to engraftment, relapse rate, and survival. We conducted a retrospective study of all adult matched unrelated donor stem cell transplantations patients who received fludarabine/melphalan with subQ or i.v. alemtuzumab in combination with tacrolimus as part of their conditioning for unrelated donor transplantation at New York-Presbyterian/Weill Cornell Medical Center from January 1, 2012 to March 21, 2014. Alemtuzumab was administered at a total cumulative dose of 100 mg (divided over days -7 to -3). Forty-six patients received an unrelated donor stem cell transplantation with fludarabine/melphalan and either subQ (n = 26) or i.v. (n = 20) alemtuzumab in combination with tacrolimus. Within the evaluable population, 130 subQ and 100 i.v. alemtuzumab doses were administered. For the primary outcome, ≥grade 2 infusion-related reactions occurred in 11 (8%) versus 25 (25%) infusions in the subQ and i.v. cohorts, respectively (P = .001). Overall, 12 injections (9%) in the subQ arm versus 26 infusions (26%) in the i.v. arm experienced an infusion-related reaction of any grade (P = .001). There were no significant differences between the subQ and i.v. arms in rates of reactivation of CMV/EBV, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, relapse, or survival. Subcutaneous administration of alemtuzumab for GVHD prophylaxis was associated with fewer infusion-related reactions compared with i.v. administration in the SCT setting. Incidences of acute and chronic GVHD were similar between both arms. There was also no difference in reactivation of CMV/EBV viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, relapse, or survival. PMID:26524732

  18. Genetics Home Reference: autoimmune lymphoproliferative syndrome

    MedlinePlus

    ... immune system may attack red blood cells (autoimmune hemolytic anemia ), white blood cells (autoimmune neutropenia), or platelets (autoimmune ... years later, most frequently as a combination of hemolytic anemia and thrombocytopenia, also called Evans syndrome. People with ...

  19. The Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) equation best characterizes kidney function in patients being considered for lung transplantation

    PubMed Central

    Osho, Asishana A.; Castleberry, Anthony W.; Snyder, Laurie D.; Palmer, Scott M.; Stafford-Smith, Mark; Lin, Shu S.; Davis, R. Duane; Hartwig, Matthew G.

    2015-01-01

    BACKGROUND Methods for direct measurement of glomerular filtration rate (GFR) are expensive and inconsistently applied across transplant centers. The Modified Diet in Renal Disease (MDRD) equation is commonly used for GFR estimation, but is inaccurate for GFRs > 60 ml/min per 1.73 m2. The Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) and Wright equations have shown improved predictive capabilities in some patient populations. We compared these equations to determine which one correlates best with direct GFR measurement in lung transplant candidates. METHODS We conducted a retrospective cohort analysis of 274 lung transplant recipients. Pre-operative GFR was measured directly using a radionuclide GFR assay. Results from the MDRD, CKDEPI, Wright, and Cockroft–Gault equations were compared with direct measurement. Findings were validated using logistic regression models and receiver operating characteristic (ROC) analyses in looking at GFR as a predictor of mortality and renal function outcomes post-transplant. RESULTS Assessed against the radionuclide GFR measurement, CKDEPI provided the most consistent results, with low values for bias (0.78), relative standard error (0.03) and mean absolute percentage error (15.02). Greater deviation from radionuclide GFR was observed for all other equations. Pearson’s correlation between radionuclide and calculated GFR was significant for all equations. Regression and ROC analyses revealed equivalent utility of the radionuclide assay and GFR equations for predicting post-transplant acute kidney injury and chronic kidney disease (p < 0.05). CONCLUSIONS In patients being evaluated for lung transplantation, CKDEPI correlates closely with direct radionuclide GFR measurement and equivalently predicts post-operative renal outcomes. Transplant centers could consider replacing or supplementing direct GFR measurement with less expensive, more convenient estimation by using the CKDEPI equation. PMID:25107351

  20. Childhood, adolescent and young adult non-Hodgkin lymphoma: state of the science.

    PubMed

    Cairo, Mitchell S; Pinkerton, Ross

    2016-05-01

    The 5th International Symposium on Childhood, Adolescent and Young Adult (CAYA) Non-Hodgkin Lymphoma (NHL) was held in Varese, Italy, from 21-25 October 2015. This review represents a summary of the scientific sessions of this international symposium including childhood, adolescent and young adult (AYA) NHL in countries with limited socio-economic resources, AYA NHL, anaplastic large cell lymphoma, post-transplant lymphoproliferative disease, B-cell NHL, lymphoblastic lymphoma, T/natural killer cell NHL and immunological therapies in NHL. Most importantly, the new International Paediatric NHL Staging System (IPNHLSS) and International Paediatric NHL Response Criteria (IPNHLRC) were introduced during the symposium. The symposium brought together a multinational and multidisciplinary group of clinicians and basic scientists focused in this field of haematological malignancies. PMID:27133800

  1. Parkinson's Disease

    MedlinePlus

    ... Deep Brain Stimulation Consortium Meeting Summary Parkinson's Disease Cell Biology Meeting Summary Parkinson's Disease Cell Biology Meeting Summary Udall Centers Meeting—Expediting Parkinson’s Disease ...

  2. Gamma Heavy Chain Disease with T-cell Large Granular Lymphocytic Leukemia: A Case Report and Review of the Literature.

    PubMed

    Iijima, Masahide; Sekiguchi, Naohiro; Nagata, Akihisa; Wagatsuma, Miyuki; Midorikawa, Kiyoe; Kurimoto, Miwa; Noto, Satoshi; Yamada, Kazuaki; Takezako, Naoki

    2016-01-01

    Gamma heavy chain disease (gHCD) is a rare lymphoproliferative disorder characterized by the production of a truncated immunoglobulin heavy chain. Although some cases of gHCD are concurrent with other lymphoid neoplasms, few have been reported. We herein present the case of a 73-year-old woman with gHCD and T-cell large granular lymphocytic leukemia. A multiparameter flow cytometry analysis revealed neoplastic cells that were positive for CD28, a marker of T-cell activation, the anti-apoptotic antigen of neoplastic plasma cells, CD38 and CD45. The results of this multiparameter flow cytometry analysis may contribute to furthering the understanding of the clinicopathological features of gHCD. PMID:26875967

  3. Clinical utility of cytomegalovirus viral load testing for predicting CMV disease in D+/R- solid organ transplant recipients.

    PubMed

    Humar, Atul; Paya, Carlos; Pescovitz, Mark D; Dominguez, Ed; Washburn, Kenneth; Blumberg, Emily; Alexander, Barbara; Freeman, Richard; Heaton, Nigel; Mueller, Barbara

    2004-04-01

    Despite prophylaxis, cytomegalovirus (CMV) disease is common in donor seropositive (D+)/recipient seronegative (R-) transplant patients after cessation of prophylaxis. Early detection of CMV may allow for pre-emptive therapy to prevent active disease. The clinical utility of quantitative plasma viral load measurements for predicting CMV disease was determined in 364 D+/R- organ transplant patients receiving prophylaxis (100 d of valganciclovir or oral ganciclovir). Measurements were performed every 2 weeks until day 100 and at months 4, 4.5, 5, 6, 8 and 12 post-transplant. CMV disease occurred in 64 (17.6%) patients by 12 months. Using a positive cut-off value of >400 copies/mL, sensitivity was 38%, specificity 60%, positive predictive value 17%, and negative predictive value 82% for prediction of CMV disease. Therefore, routine monitoring would have predicted disease in only 24/64 (38%) patients. The test characteristics were not improved by changing the viral load cut-off point for defining a positive result. Similarly, single time point measures at the end of prophylaxis or month 4 had low sensitivity for disease prediction. Overall, regular CMV plasma viral load measurements were only of modest value in predicting CMV disease. PMID:15023158

  4. Meningococcal Disease

    MedlinePlus

    ... Disease Mumps Pertussis (Whooping Cough) Pneumococcal Disease Rubella (German Measles) Shingles (Herpes Zoster) Tetanus (Lockjaw) Professional Resources ... Disease Mumps Pertussis (Whooping Cough) Pneumococcal Disease Rubella (German Measles) Shingles (Herpes Zoster) Tetanus (Lockjaw) You May ...

  5. Lentil Diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Major lentil diseases around the world have been described and reviewed. The major diseases include Ascochyta blight, Fusarium wilt, Botrytis Gray Mold, Lentil rust, Stemphylium blight, Anthracnose, and virus diseases. The management practices for these diseases are also presented....

  6. Thirteen-And-A-Half Syndrome.

    PubMed

    Allbon, Daniel S; La Hood, Ben

    2016-06-01

    We describe a 50-year-old man who developed eight-and-a-half syndrome associated with an ipsilateral trigeminal nerve palsy because of a post-transplant lymphoproliferative disorder. This case widens the spectrum of eight-and-a-half syndrome to include a thirteen-and-a-half syndrome. PMID:26928599

  7. Peri-Implant Diseases

    MedlinePlus

    ... Disease and Heart Disease Gum Disease and Other Systemic Diseases Gum Disease and Women Gum Disease and Men ... Disease and Heart Disease Gum Disease and Other Systemic Diseases Gum Disease and Women Gum Disease and Men ...

  8. Gum Disease and Men

    MedlinePlus

    ... Disease and Heart Disease Gum Disease and Other Systemic Diseases Gum Disease and Women Gum Disease and Men ... Disease and Heart Disease Gum Disease and Other Systemic Diseases Gum Disease and Women Gum Disease and Men ...

  9. Gum Disease in Children

    MedlinePlus

    ... Disease and Heart Disease Gum Disease and Other Systemic Diseases Gum Disease and Women Gum Disease and Men ... Disease and Heart Disease Gum Disease and Other Systemic Diseases Gum Disease and Women Gum Disease and Men ...

  10. Gum Disease Symptoms

    MedlinePlus

    ... Disease and Heart Disease Gum Disease and Other Systemic Diseases Gum Disease and Women Gum Disease and Men ... Disease and Heart Disease Gum Disease and Other Systemic Diseases Gum Disease and Women Gum Disease and Men ...

  11. Gum Disease and Women

    MedlinePlus

    ... Disease and Heart Disease Gum Disease and Other Systemic Diseases Gum Disease and Women Gum Disease and Men ... Disease and Heart Disease Gum Disease and Other Systemic Diseases Gum Disease and Women Gum Disease and Men ...

  12. Discovery of Innovative Therapies for Rare Immune-Mediated Inflammatory Diseases via Off-Label Prescription of Biologics: The Case of IL-6 Receptor Blockade in Castlemans Disease

    PubMed Central

    Musters, Anne; Assaf, Amira; Gerlag, Danielle M.; Tak, Paul P.; Tas, Sander W.

    2015-01-01

    Biologics have revolutionized the field of clinical immunology and proven to be both effective and safe in common immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, inflammatory bowel diseases, and various hematological disorders. However, in patients with rare, severe IMIDs failing on standard therapies, it is virtually impossible to conduct randomized controlled trials. Therefore, biologics are usually prescribed off-label in these often severely ill patients. Unfortunately, off-label prescription is sometimes hampered in these diseases due to a lack of reimbursement that is often based on a presumed lack of evidence for effectiveness. In the present article, we will discuss that off-label prescription of biologics can be a good way to discover new treatments for rare diseases. This will be illustrated using a case of multicentric Castlemans disease, an immune-mediated lymphoproliferative disorder, in which off-label tocilizumab (humanized anti-IL-6 receptor blocking antibody) treatment resulted in remarkable clinical improvement. Furthermore, we will give recommendations for monitoring efficacy and safety of biologic treatment in rare IMIDs, including the use of registries. In conclusion, we put forward that innovative treatments for rare IMIDs can be discovered via off-label prescription of biologicals, provided that this is based on rational arguments including knowledge of the pathophysiology of the disease. PMID:26697019

  13. Marek's disease vaccines: a solution for today but a worry for tomorrow?

    PubMed

    Gimeno, Isabel M

    2008-07-18

    Marek's disease (MD) is a lymphoproliferative disease of chickens that, in the absence of control measures, is capable of causing devastating losses in commercial poultry flocks. MD has been successfully controlled by vaccination since 1968. However, vaccine efficacy has decreased concomitantly with the increase in virulence of Marek's disease virus (MDV). The constant evolution of MDV has forced the development of new vaccines or vaccine strategies that control the more virulent emergent strains. However, this race between the introduction of new vaccines and the evolution of MDV represents a major threat for the poultry industry. In addition to vaccination, other factors might have contributed to the evolution of MDV (intensive methods of chicken production, early exposure of the chickens to MDV and administration of vaccines at very low doses). From all the possible factors influencing MDV evolution, the effect of vaccination has received the greatest attention. MD vaccines protect with great efficacy against the development of the disease but they do not prevent infection or transmission. Sterilizing immunity could be a solution to stop the evolution of the virus but it has been proven to be extremely difficult, if at all possible, to obtain with MDV or with other herpesviruses. Other solutions to improve vaccine-induced protection are discussed in this paper. PMID:18773529

  14. Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies

    ClinicalTrials.gov

    2015-08-04

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Myeloid Leukemia in Remission; Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia

  15. BK virus disease after allogeneic stem cell transplantation: a cohort analysis.

    PubMed

    Rorije, Nienke M G; Shea, Margaret M; Satyanarayana, Gowri; Hammond, Sarah P; Ho, Vincent T; Baden, Lindsey R; Antin, Joseph H; Soiffer, Robert J; Marty, Francisco M

    2014-04-01

    The clinical epidemiology of BK virus (BKV) disease after allogeneic hematopoietic stem cell transplantation (HSCT) is not well defined. We evaluated 491 patients transplanted from January 2010 to December 2011 at a single transplant center to assess incidence, severity, and risk factors for BKV disease after HSCT. BKV disease was defined as BKV detection in urine by PCR testing in association with genitourinary symptoms without other concurrent genitourinary conditions. BKV disease occurred in 78 patients (15.9%), for an incidence rate of .47/1000 patient-days (95% confidence interval [CI], .37 to .59); BKV disease was considered severe in 27 patients (5.5%). In multivariate Cox modeling, time-dependent acute graft-versus-host disease (aGVHD) grades II to IV (adjusted hazard ratio [aHR] 4.25; 95% CI, 2.51 to 7.21), cord blood HSCT (aHR 2.28; 95% CI, 1.01 to 5.15), post-transplant mycophenolate use (aHR 3.31; 95% CI, 1.83 to 5.99), and high-dose cyclophosphamide conditioning (aHR 2.34, 95% CI 1.45 to 3.77) were significant predictors of BKV disease. Time-dependent aGVHD grades III to IV (aHR 10.5; 95% CI, 4.44 to 25.0) and cord blood HSCT (aHR 5.40; 95% CI, 1.94 to 15.0) were independent risk factors for severe BKV disease. BKV disease is common and is associated with significant and prolonged morbidity after HSCT. Prospective studies are needed to better define the morbidity of post-HSCT BKV disease and inform the design of prophylaxis and treatment trials. PMID:24462984

  16. Fatal Outcome of Multiple Clinical Presentations of Human Herpesvirus 8-related Disease After Solid Organ Transplantation.

    PubMed

    Vijgen, Sandrine; Wyss, Caroline; Meylan, Pascal; Bisig, Bettina; Letovanec, Igor; Manuel, Oriol; Pascual, Manuel; de Leval, Laurence

    2016-01-01

    Kaposi sarcoma is the most common human herpesvirus 8 (HHV-8)-related disease described after solid organ transplantation. Multicentric Castleman disease and hemophagocytic syndrome are other potential HHV-8-induced entities but are less frequently reported. We describe the case of a liver transplant recipient who presented with an acute febrile illness 1 year after transplantation with a rapidly fatal outcome. Autopsy revealed 3 distinct HHV-8-related entities: Kaposi sarcoma, HHV-8-associated multicentric Castleman disease with microlymphomas and a severe hemophagocytic syndrome. Retrospective serologic tests suggested that HHV-8 was likely transmitted by the seropositive donor at the time of transplantation. To our knowledge, this is the first case of copresentation of 3 clinical presentations of HHV-8-mediated human disease in the post-transplant setting. Considering the absence of systematic screening of organ donors/recipients for HHV-8 infection, HHV-8-related illness should be suspected in transplant recipients who present with acute febrile illness, systemic symptoms, lymphadenopathies, and/or multiorgan failure to rapidly document the diagnosis and provide timely an adequate treatment. PMID:26120765

  17. Basiliximab treatment for autoimmune bowel disease in a pediatric heart transplant patient.

    PubMed

    Puri, K; Kocoshis, S; Risma, K; Perez, L; Hart, C; Chin, C; Ryan, T D; Jefferies, J L; Schumacher, K R; Castleberry, C

    2015-11-01

    Autoimmune-mediated bowel disease has been reported after pediatric heart transplantation. Recognition and treatment of these patients has been difficult. We describe a patient who responded to steroids and basiliximab therapy after an inflammatory process secondary to abnormal T-cell activation. Our patient is a 28-month-old female who received a heart transplant at five wk of age. At 24 months post-transplant, she developed fever and bloody stools. Initial investigations were significant for an elevated ESR (>120) and CRP (15.2). Symptoms persisted despite bowel rest and mycophenolate discontinuation. Endoscopic evaluation revealed discontinuous ulcerative disease involving esophagus, terminal ileum, right and left colon, necessitating extensive bowel resection. She had additional airway inflammation leading to a TEF at the site of esophageal ulceration, requiring tracheostomy. Immune evaluation revealed autoimmune dysregulation that responded to parenteral methylprednisolone. Chronic basiliximab therapy allowed for successful weaning of steroids with sustained remission. She has been transitioned to sirolimus and tacrolimus maintenance immunosuppression with plans to discontinue basiliximab once off steroids. In conclusion, bowel disease in the setting of pediatric heart transplantation can be severe and refractory to traditional treatment methods. Tailoring immune therapy to activated T cells can result in remission. Basiliximab therapy was used in our patient to maintain steroid-induced remission, but long-term complications of this disease process are unknown. PMID:26374667

  18. Alzheimer Disease

    MedlinePlus

    ... Sledding, Skiing, Snowboarding, Skating Crushes What's a Booger? Alzheimer Disease KidsHealth > For Kids > Alzheimer Disease Print A ... slow it down. When Someone You Love Has Alzheimer Disease You might feel sad or angry — or ...

  19. Stargardt Disease

    MedlinePlus

    ... Congenital Amaurosis Macular Degeneration Retinitis Pigmentosa Stargardt Disease Usher Syndrome Other Retinal Diseases Glossary News & Research News & ... for retinal degenerative diseases like retinitis pigmentosa (RP), Usher syndrome and macular degeneration . Back to top What ...

  20. Crohn's Disease

    MedlinePlus

    Crohn's disease causes inflammation of the digestive system. It is one of a group of diseases called inflammatory ... small intestine called the ileum. The cause of Crohn's disease is unknown. It may be due to an ...

  1. Krabbe disease

    MedlinePlus

    ... for Krabbe disease. Some people have had a bone marrow transplant in the early stages of the disease, but ... counseling is recommended for people with a family history of Krabbe disease who are considering having children. ...

  2. Hookworm Disease

    MedlinePlus

    ... Parasitic Roundworm Diseases Laboratory of Parasitic Diseases National Library of Medicine, MedlinePlus World Health Organization ​​ Hookworm Disease Skip Content Marketing Share this: JavaScript is disabled in your browser. ...

  3. Lyme Disease

    MedlinePlus

    ... Lyme Disease Teen information A A A ... Lyme disease is the result of infection with the bacteria Borrelia burgdorferi. The disease is transmitted by infected ticks that also feed on mice and deer. The tick can be found attached ...

  4. Huntington's Disease

    MedlinePlus

    Huntington's disease (HD) is an inherited disease that causes certain nerve cells in the brain to waste away. ... express emotions. If one of your parents has Huntington's disease, you have a 50 percent chance of getting ...

  5. Kawasaki Disease

    MedlinePlus

    ... him/her feel better? Should I tell my child’s school/daycare provider that he/she has Kawasaki disease? Could I get Kawasaki disease from my child? Source Kawasaki Disease by KA Taubert, ST Shulman ( ...

  6. Fabry's Disease

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Fabry Disease Information Page Table of Contents (click to jump ... is being done? Clinical Trials Organizations What is Fabry Disease? Fabry disease is caused by the lack of ...

  7. Heart Disease

    MedlinePlus

    ... Sledding, Skiing, Snowboarding, Skating Crushes What's a Booger? Heart Disease KidsHealth > For Kids > Heart Disease Print A ... chest pain, heart attacks, and strokes . What Is Heart Disease? The heart is the center of the ...

  8. Alzheimer's Disease

    MedlinePlus

    Alzheimer's disease (AD) is the most common form of dementia among older people. Dementia is a brain disorder that ... higher if a family member has had the disease. No treatment can stop the disease. However, some ...

  9. Sandhoff Disease

    MedlinePlus

    ... Sandhoff diseases for use in humans. NIH Patient Recruitment for Sandhoff Disease Clinical Trials At NIH Clinical Center Throughout the U.S. and Worldwide NINDS Clinical Trials Organizations Column1 Column2 National Tay-Sachs and Allied Diseases ...

  10. Cardiac transplantation for end-stage heart disease.

    PubMed

    Argenziano, M; Goldstein, D J; Oz, M C; Rose, E A

    1999-01-01

    In the nearly 30 years since the first successful human heart transplant, a variety of developments have allowed this form of cardiac replacement therapy to flourish. These have included improvements in surgical and critical care technology, as well as breakthroughs in immunosuppressive pharmacology, the most notable of which was the introduction of cyclosporine in 1980. Subsequently, indications and exclusion criteria for heart transplantation have evolved, guided by the constraints of a limited donor supply and facilitated by an improved understanding of prognostic risk factors. Current 1- and 5-year survival estimates are encouraging, and despite the frequency of acute rejection, current management strategies have, for the most part, limited the fatal consequences of this complication. Graft atherosclerosis, however, has continued to complicate the posttransplant course of many patients, and despite therapeutic strategies aimed at a variety of potential pathogenic mechanisms, this entity remains the most common cause of late death after transplantation. In these patients and other victims of allograft failure, retransplantation remains a viable option. Finally, the recent trend of selecting increasingly critically ill transplant recipients, although not associated with inferior survival, has driven the costs of this form of cardiac replacement therapy to unprecedented levels. These issues, as well as current developments in the fields of mechanical cardiac assistance, xenotransplantation, and cardiac gene therapy, will certainly result in a continually evolving role for cardiac transplantation in the treatment of end-stage heart disease. PMID:11208247

  11. Liver transplantation in alcoholic liver disease current status and controversies

    PubMed Central

    Singal, Ashwani K; Chaha, Khushdeep S; Rasheed, Khalid; Anand, Bhupinderjit S

    2013-01-01

    Alcoholic cirrhosis remains the second most common indication for liver transplantation. A comprehensive medical and psychosocial evaluation is needed when making a decision to place such patients on the transplant list. Most transplant centers worldwide need a minimum of 6 mo of alcohol abstinence for listing these patients. Patients with alcohol dependence are at high risk for relapse to alcohol use after transplantation (recidivism). These patients need to be identified and require alcohol rehabilitation treatment before transplantation. Recidivism to the level of harmful drinking is reported in about 15%-20% cases. Although, recurrent cirrhosis and graft loss from recidivism is rare, occurring in less than 5% of all alcoholic cirrhosis-related transplants, harmful drinking in the post-transplant period does impact the long-term outcome. The development of metabolic syndrome with cardiovascular events and de novo malignancy are important contributors to non liver-related mortality amongst transplants for alcoholic liver disease. Surveillance protocols for earlier detection of de novo malignancy are needed to improve the long-term outcome. The need for a minimum of 6 mo of abstinence before listing makes transplant a nonviable option for patients with severe alcoholic hepatitis who do not respond to corticosteroids. Emerging data from retrospective and prospective studies has challenged the 6 mo rule, and beneficial effects of liver transplantation have been reported in select patients with a first episode of severe alcoholic hepatitis who are unresponsive to steroids. PMID:24106395

  12. Recognizing and managing chronic graft-versus-host disease.

    PubMed

    Lee, Stephanie J; Flowers, Mary E D

    2008-01-01

    Chronic graft-versus-host disease (GVHD) is an immune-mediated disorder that occurs frequently after allogeneic hematopoietic cell transplantation (HCT). Most cases are diagnosed within the first year at a median of 4 to 6 months after HCT, but 5-10% of cases are initially diagnosed beyond the first post-transplant year. Chronic GVHD most often involves the skin and mouth, but almost any other organ system can be involved. Correct diagnosis is critical so that appropriate therapy can be started promptly to minimize symptoms and prevent irreversible organ damage. Initial treatment should be with cortico-steroid-based therapy. Optimal secondary treatment as not been established, although a large number of agents may provide benefits. A 2004 NIH conference focused on development of consensus criteria for chronic GVHD. Six papers published in 2005 and 2006 propose consensus definitions for chronic GVHD diagnosis and scoring, pathology, biomarkers, response criteria, supportive care and design of clinical trials. This review will focus on common clinical presentations and principles for managing chronic GVHD. The most frequently used secondary therapies and ongoing trials are summarized. New concepts from the NIH consensus conference are discussed. PMID:19074071

  13. Bladder Diseases

    MedlinePlus

    ... frequent, urgent urination Bladder cancer Doctors diagnose bladder diseases using different tests. These include urine tests, x- ... National Institute of Diabetes and Digestive and Kidney Diseases

  14. Marek's disease: a model for protection against herpesvirus-induced tumours.

    PubMed

    Schat, K A

    1987-01-01

    Marek's disease (MD) is a lymphoproliferative disease of chickens caused by a herpesvirus (MDV). Several effective vaccines have been developed and MD is therefore often considered as a model for studying antitumour vaccines. Key factors for the understanding of vaccine-induced immunity are discussed. Three serotypes have been characterized: serotype 1 or oncogenic MDV, serotype 2 or non-oncogenic MDV and serotype 3 or herpesvirus of turkeys. The three serotypes have clearly different genomes and proteins. The pathogenesis of infection with serotype 1 MDV can be divided into an early cytolytic phase, a latent phase and a second cytolytic infection combined with the development of tumours and permanent immunosuppression. The activation of T cells during the early cytolytic phase is important for establishing infection in the target cells for latency and transformation. Immune responses by B cells, and especially by T cells, are directed against viral infection. Evidence is presented that Marek's disease tumour-associated surface antigen is not involved in the antitumour responses. Moreover, the importance of antitumour immune responses in MD is questioned. Vaccinal immunity is dependent more on T cells than B cells and is directed against virus antigens. It is proposed that the evidence claimed for an antitumour response induced by vaccination actually relates to an antiviral response. The relevance of new, highly oncogenic strains causing MD in vaccinated chickens is discussed. PMID:2825984

  15. Parvovirus B19 detected in Rosai–Dorfman disease in nodal and extranodal manifestations

    PubMed Central

    Mehraein, Y; Wagner, M; Remberger, K; Füzesi, L; Middel, P; Kaptur, S; Schmitt, K; Meese, E

    2006-01-01

    Sinus histiocytosis with massive lymphadenopathy (SHML), also designated as Rosai–Dorfman disease (RDD), is a rare benign reactive lymphoproliferative disorder. It is defined by a characteristic histopathology with sinus histiocytosis and haemophagocytosis known as emperipolesis. In histiocytes S100 is strongly expressed, whereas CD1a staining typically is negative. The disease mainly manifests at a single lymph node; however, multilocular and extranodal affection can occur. Causative infectious agents, and virus infections in particular, have repeatedly been suspected, although until now the origin of the disease has been unclear. Four cases of RDD (two nodal sites and two extranodal upper respiratory tract sites) were analysed for parvovirus B19 (B19) infection by immunohistochemistry to detect B19 capsid proteins VP1/VP2. In all the four cases, huge numbers of B19‐positive cells were partly detected. The positive cells were identified either as lymphocytes or, in one extranodal case, also as respiratory epithelial cells. This is the first report of B19 infection in RDD tissue, indicating that B19 may be associated with the pathogenesis of SHML. PMID:17142576

  16. Successful management of EBV-PTLD in allogeneic bone marrow transplant recipient by virological-immunological monitoring of EBV infection, prompt diagnosis and early treatment.

    PubMed

    Chiereghin, Angela; Bertuzzi, Clara; Piccirilli, Giulia; Gabrielli, Liliana; Squarzoni, Diego; Turello, Gabriele; Ferioli, Martina; Sessa, Mariarosaria; Bonifazi, Francesca; Zanoni, Lucia; Sabattini, Elena; Lazzarotto, Tiziana

    2016-02-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorder (EBV-PTLD) is an uncommon, but frequently fatal, complication after allogeneic hematopoietic stem cell transplant. Prospective post-transplant virological and immunological monitoring allowed to successfully manage a patient who developed both polymorphic and monomorphic, "diffuse large B-cell lymphoma like", as an EBV-PTLD, 65days after allogeneic bone marrow transplant. Early detection of significant increase in EBV DNA level in patient's peripheral blood (peak of viral load equal to 119,039copies/mL whole blood, +56day after transplant) led to administration of pre-emptive anti-CD20 monoclonal antibody (rituximab) and close clinical monitoring. After one week, physical exam revealed laterocervical adenopathy. Histopathologic features, immunohistochemical characterization and in situ hybridization study allowed to establish a diagnosis of EBV-related PTLD. Immunological monitoring showed no EBV-specific T-cell responses during EBV replication, thus potentially explaining the occurrence of high EBV load with subsequent PTLD development. A total of four doses of anti-CD20 monoclonal antibody were administered and at the end of the treatment, EBV infection was cleared and imaging technique showed complete disease remission. In conclusion, the early use of anti-CD20 monoclonal antibody proved to be a safe and effective treatment strategy for EBV-PTLD. Moreover, combined virological-immunological monitoring of EBV infection may more accurately assess patients at higher risk for EBV-PTLD. PMID:26687013

  17. [Prion diseases].

    PubMed

    Stoĭda, N I; Zavalishin, I A

    2012-01-01

    Prion diseases are a family of progressive neurodegenerative disorders caused by prions. There are four human prion diseases: Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, fatal insomnia and Kuru. They can arise in three different ways: acquired, familial or sporadic. We review clinical presentations, pathophysiology, morphological picture, diagnostic procedures and available treatment options of prion diseases. PMID:23235426

  18. Heart Diseases

    MedlinePlus

    ... you're like most people, you think that heart disease is a problem for others. But heart disease is the number one killer in the ... of disability. There are many different forms of heart disease. The most common cause of heart disease ...

  19. Newcastle disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Newcastle disease (ND), referred to as Exotic Newcastle disease (END) in the U. S., is an acute viral disease of domestic poultry and many other bird species and a recognized worldwide problem. Occurrence of END is due to an infection with virulent strains of Newcastle disease virus (NDV) and is a ...

  20. Outcomes after hematopoietic stem cell transplantation for children with I-cell disease.

    PubMed

    Lund, Troy C; Cathey, Sara S; Miller, Weston P; Eapen, Mary; Andreansky, Martin; Dvorak, Christopher C; Davis, Jeffrey H; Dalal, Jignesh D; Devine, Steven M; Eames, Gretchen M; Ferguson, William S; Giller, Roger H; He, Wensheng; Kurtzberg, Joanne; Krance, Robert; Katsanis, Emmanuel; Lewis, Victor A; Sahdev, Indira; Orchard, Paul J

    2014-11-01

    Mucolipidosis type II (MLII), or I-cell disease, is a rare but severe disorder affecting localization of enzymes to the lysosome, generally resulting in death before the 10th birthday. Although hematopoietic stem cell transplantation (HSCT) has been used to successfully treat some lysosomal storage diseases, only 2 cases have been reported on the use of HSCT to treat MLII. For the first time, we describe the combined international experience in the use of HSCT for MLII in 22 patients. Although 95% of the patients engrafted, overall survival was low, with only 6 patients (27%) alive at last follow-up. The most common cause of death post-transplant was cardiovascular complications, most likely due to disease progression. Survivors were globally delayed in development and often required complex medical support, such as gastrostomy tubes for nutrition and tracheostomy with mechanical ventilation. Although HSCT has demonstrated efficacy in treating some lysosomal storage disorders, the neurologic outcome and survival for patents with MLII were poor. Therefore, new medical and cellular therapies should be sought for these patients. PMID:25016194

  1. Outcomes after Hematopoietic Stem Cell Transplant for Children with I-Cell Disease

    PubMed Central

    Lund, Troy C.; Cathey, Sara S.; Miller, Weston P.; Eapen, Mary; Andreansky, Martin; Dvorak, Christopher C.; Davis, Jeffrey H.; Dalal, Jignesh D.; Devine, Steven M.; Eames, Gretchen M.; Ferguson, William S.; Giller, Roger H.; He, Wensheng; Kurtzberg, Joanne; Krance, Robert; Katsanis, Emmanuel; Lewis, Victor A.; Sahdev, Indira; Orchard, Paul J.

    2014-01-01

    Mucolipidosis type II (MLII), or I-Cell Disease, is a rare, but severe disorder affecting localization of enzymes to the lysosome, generally resulting in death before the 10th birthday. Although hematopoietic stem cell transplant (HSCT) has been used to successfully treat some lysosomal storage diseases, there have been only two case reports in the use of HSCT to treat MLII. For the first time, we describe the combined international experience in the use of HSCT for MLII in 22 patients. Although 95% of the patients engrafted, the overall survival was low with only 6 patients (27%) alive at last follow-up. The most common cause of death post-transplant was cardiovascular complications, most likely due to disease progression. Survivors were globally delayed in development, and often required complex medical support such as gastrostomy tubes for nutrition, and tracheostomy with mechanical ventilation. Although HSCT has demonstrated efficacy in treating some lysosomal storage disorders, the neurologic outcome and survival for patents with MLII were poor. Therefore new medical and cellular therapies should be sought for these patients. PMID:25016194

  2. Medical resource utilization and costs associated with autosomal dominant polycystic kidney disease in the USA: a retrospective matched cohort analysis of private insurer data

    PubMed Central

    Knight, Tyler; Schaefer, Caroline; Krasa, Holly; Oberdhan, Dorothee; Chapman, Arlene; Perrone, Ronald D

    2015-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) results in kidney cyst development and enlargement, resulting in chronic kidney disease (CKD) leading to renal failure. This study sought to determine if ADPKD patients in the early stages of CKD contribute to a sizable economic burden for the US health care system. Methods This was a retrospective, matched cohort study, reviewing medical resource utilization (MRU) and costs for adults in a US private-payer claims database with a diagnosis code of ADPKD (ICD-9-CM 753.13). ADPKD patients were matched by age grouping (0–17, 18–34, 35–44, 45–54, 55–64, and 65+ years) and sex to controls to understand the burden of ADPKD. Descriptive statistics on 6-month MRU and costs were assessed by CKD stages, dialysis use, or previous renal transplant. Results The analysis included ADPKD patients in CKD stages 1–5 (n=316 to n=860), dialysis (n=586), and post-transplant (n=615). Mean ages did not differ across CKD stages (range 43–56 years). Men were the majority in the later stages but the minority in the early stages. The proportion of patients with at least one hospitalization increased with CKD stage, (12% to >40% CKD stage 2 to stage 5, dialysis or post-transplant). The majority had at least one hospital outpatient visit and at least one pharmacy claim. Total 6-month per-patient costs were greater among ADPKD patients than in age-matched and sex-matched healthy non-ADPKD controls (P<0.001 for all comparisons). Conclusion ADPKD patients with normal kidney function are associated with a significant economic burden to the health care system relative to the general population. Any treatments that delay progression to later stages of CKD may provide potential health care cost offsets. PMID:25759590

  3. Kimura disease

    PubMed Central

    AlGhamdi, Fares E.; Al-Khatib, Talal A.; Marzouki, Hani Z.; AlGarni, Mohammed A

    2016-01-01

    Kimura disease is a chronic inflammatory disease that mainly manifests as a lump in the cervical region. Although the underlying pathophysiology is not clear yet, the diagnosis can be established based on specific histopathological characteristics. The first case of this disease was described in China, as well as the majority of subsequent cases that were also described in the Far East countries made Kimura disease traditionally a disease of adult patients of Asian descent. This report describes the occurrence of Kimura disease in pediatric non-Asian patient with a similar clinicopathologic presentation. PMID:26905356

  4. Research Areas: Liver Disease

    MedlinePlus

    ... weight control and nutrition, urologic diseases, endocrine and metabolic diseases, and blood diseases La Información de la Salud ... Program Digestive Disease and Nutrition Endocrine Disease and Metabolic Disease Hematologic Disease Kidney Disease Liver Disease Obesity Urologic ...

  5. Celiac Disease

    MedlinePlus

    ... problems in your small intestine when you eat gluten, a protein found in wheat, rye, and barley. Gluten is poison to people who have celiac disease. What does gluten do to people who have celiac disease? In ...

  6. Celiac Disease

    MedlinePlus

    ... immune disease in which people can't eat gluten because it will damage their small intestine. If you have celiac disease and eat foods with gluten, your immune system responds by damaging the small ...

  7. Tickborne Diseases

    MedlinePlus

    ... on a blade of grass. Credit: CDC. Rocky Mountain spotted fever, a bacterial disease transmitted by the ... Ehrlichiosis and Anaplasmosis Lyme Disease Relapsing Fever Rocky Mountain Spotted Fever Tularemia back to top ​​​​ Last Updated ...

  8. Menkes Disease

    MedlinePlus

    ... NICHD Research Information Clinical Trials Resources and Publications Menkes Disease: Overview Skip sharing on social media links Share this: Page Content Menkes disease is a genetic disorder that affects how copper ...

  9. Heart Disease

    MedlinePlus

    ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ...

  10. Gaucher Disease

    MedlinePlus

    ... one of the inherited metabolic disorders known as lipid storage diseases. Lipids are fatty materials that include oils, fatty acids, ... research to find ways to treat and prevent lipid storage disorders such as Gaucher disease. For example, ...

  11. Alexander Disease

    MedlinePlus

    ... no exact animal model for the disease; however, mice have been engineered to produce the same mutant ... GFAP found in individuals with Alexander disease. These mice form Rosenthal fibers and have a predisposition for ...

  12. Huntington disease

    MedlinePlus

    Huntington disease is a disorder in which nerve cells in certain parts of the brain waste away, or ... Huntington disease is caused by a genetic defect on chromosome 4. The defect causes a part of DNA ...

  13. Kawasaki Disease

    MedlinePlus

    ... including the arteries, veins, and capillaries. Sometimes Kawasaki disease affects the coronary arteries, which carry oxygen-rich blood ... can't pass it to another child. Kawasaki disease affects children of all races and ages and both ...

  14. Parkinson's Disease

    MedlinePlus

    ... You may have seen the actor Michael J. Fox on TV talking about Parkinson's disease. He has ... and help find a cure. Mostly adults (like Fox and boxer Muhammad Ali) get Parkinson's disease. It's ...

  15. Menkes Disease

    MedlinePlus

    ... defective gene named ATPTA 1 that regulates the metabolism of copper in the body. The disease primarily ... Menkes disease is also characterized by subnormal body temperature and strikingly peculiar hair, which is kinky, colorless ...

  16. Lyme disease

    MedlinePlus

    ... R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases . 8th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 243. Wright WF. Diagnosis and management of Lyme disease. Am Fam Physician . 2012;85: ...

  17. Hashimoto's Disease

    MedlinePlus

    ... disease often leads to reduced thyroid function, or hypothyroidism. Hypothyroidism is a disorder that occurs when the thyroid ... Hashimoto’s disease is the most common cause of hypothyroidism in the United States. 1 Read more in ...

  18. Graves' Disease

    MedlinePlus

    ... our online catalog. ​ Additional Links Hashimoto's Disease Hyperthyroidism Hypothyroidism Pregnancy & Thyroid Disease Thyroid Tests Find a Specialist ... everyone who receives radioactive iodine treatment eventually develops hypothyroidism, which occurs when the thyroid does not make ...

  19. Addison's Disease

    MedlinePlus

    ... example, a problem with your pituitary gland can cause secondary Addison’s disease. Or, you may develop Addison’s disease if you suddenly stop taking a corticosteroid medicine (such as prednisone). Corticosteroids ...

  20. Fifth disease

    MedlinePlus

    Parvovirus B19; Erythema infectiosum; Slapped cheek rash ... Fifth disease is caused by human parvovirus B19. It often affects preschoolers or school-age children during the spring. The disease spreads through the fluids in the nose and ...

  1. Fifth Disease

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Parvovirus B19 and Fifth Disease Note: Javascript is disabled ... message, please visit this page: About CDC.gov . Parvovirus Home About Parvovirus B19 Fifth Disease Pregnancy and ...

  2. Coeliac disease.

    PubMed

    Freeman, Hugh; Lemoyne, Michel; Pare, Pierre

    2002-02-01

    Increased awareness of non-classical presentations and more reliable screening tests have led to higher detection rates for coeliac disease in elderly adults. Clinical presentations are influenced largely by the long-standing course of the subclinical disease before diagnosis. In the majority of elderly patients, weight loss, diarrhoea and iron deficiency anaemia are present. With a delay in diagnosis, there are increased risks of associated autoimmune diseases, of neoplasms (mostly small bowel lymphoma) and of metabolic bone diseases. Thyroid disease is the most common autoimmune disease. Lymphoma may be the initial presentation or may complicate the clinical course of well established coeliac disease. Osteopenia is very common at presentation, can be clinically severe and require specific therapy in addition to the gluten-free diet. The high risk of complications in elderly patients with coeliac disease warrants a systematic approach in their investigation and management. PMID:11977927

  3. Kawasaki disease

    MedlinePlus

    ... pubmed/23283289 . Mason JC. Rheumatic diseases of the cardiovascular system. In: Mann DL, Zipes DP, Libby P, Bonow RO, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine . 10th ed. Philadelphia, PA: Elsevier Saunders; 2014: ...

  4. Chagas Disease

    MedlinePlus

    Chagas disease is caused by a parasite. It is common in Latin America but not in the United States. ... nose, the bite wound or a cut. The disease can also spread through contaminated food, a blood ...

  5. Bone Diseases

    MedlinePlus

    ... avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds ... break Osteogenesis imperfecta makes your bones brittle Paget's disease of bone makes them weak Bones can also ...

  6. Wilson Disease

    MedlinePlus

    Wilson disease is a rare inherited disorder that prevents your body from getting rid of extra copper. You need ... copper into bile, a digestive fluid. With Wilson disease, the copper builds up in your liver, and ...

  7. Eye Diseases

    MedlinePlus

    ... the back of the eye Macular degeneration - a disease that destroys sharp, central vision Diabetic eye problems ... defense is to have regular checkups, because eye diseases do not always have symptoms. Early detection and ...

  8. Fifth Disease

    MedlinePlus

    Fifth disease is a viral infection caused by parvovirus B19. The virus only infects humans; it's not the same parvovirus that dogs and cats can get. Fifth disease mostly affects children. Symptoms can include a low ...

  9. Addison Disease

    MedlinePlus

    ... blood pressure and water and salt balance. Addison disease happens if the adrenal glands don't make ... problem with your immune system usually causes Addison disease. The immune system mistakenly attacks your own tissues, ...

  10. Parkinson's Disease

    MedlinePlus

    Parkinson's disease (PD) is a type of movement disorder. It happens when nerve cells in the brain don't ... coordination As symptoms get worse, people with the disease may have trouble walking, talking, or doing simple ...

  11. Meniere's Disease

    MedlinePlus

    Meniere's disease is a disorder of the inner ear. It can cause severe dizziness, a roaring sound in your ... together over several days. Some people with Meniere's disease have "drop attacks" during which the dizziness is ...

  12. Liver Diseases

    MedlinePlus

    ... remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, ... the skin, can be one sign of liver disease. Cancer can affect the liver. You could also ...

  13. Endocrine Diseases

    MedlinePlus

    ... low, you may have a hormone disorder. Hormone diseases also occur if your body does not respond ... In the United States, the most common endocrine disease is diabetes. There are many others. They are ...

  14. Raynaud's Disease

    MedlinePlus

    Raynaud's disease is a rare disorder of the blood vessels, usually in the fingers and toes. It causes the ... secondary Raynaud's, which is caused by injuries, other diseases, or certain medicines. People in colder climates are ...

  15. Parasitic Diseases

    MedlinePlus

    ... a bug bite, or sexual contact. Some parasitic diseases are easily treated and some are not. Parasites ... be seen with the naked eye. Some parasitic diseases occur in the United States. Contaminated water supplies ...

  16. Legionnaires' Disease

    MedlinePlus

    Legionnaires' disease is a type of pneumonia caused by bacteria. You usually get it by breathing in mist from ... spread from person to person. Symptoms of Legionnaires' disease include high fever, chills, a cough, and sometimes ...

  17. Krabbe Disease

    MedlinePlus

    ... cell degeneration seen in Krabbe disease. NIH Patient Recruitment for Krabbe Disease Clinical Trials At NIH Clinical Center Throughout the U.S. and Worldwide NINDS Clinical Trials Organizations Column1 Column2 United Leukodystrophy Foundation 224 North 2nd ...

  18. Kennedy's Disease

    MedlinePlus

    ... to prevent, treat, and cure them. NIH Patient Recruitment for Kennedy's Disease Clinical Trials At NIH Clinical Center Throughout the U.S. and Worldwide NINDS Clinical Trials Organizations Column1 Column2 Kennedy's Disease Association P.O. Box ...

  19. Reportable diseases

    MedlinePlus

    ... Botulism Brucellosis Chancroid Chickenpox Chlamydia trachomatis Cholera Coccidioidomycosis Cryptosporidiosis Cyclosporiasis Diphtheria Giardiasis Gonorrhea Haemophilus influenza, invasive disease ...

  20. Current treatment of hepatitis C-associated rheumatic diseases

    PubMed Central

    2012-01-01

    The hepatitis C virus (HCV) is both hepatotropic and lymphotropic, responsible for a great number of hepatic and extrahepatic immune-system disorders that comprise the so-called HCV syndrome. HCV-associated rheumatic diseases are characterized by frequent clinico-serological overlap; therefore, correct classification of individual patients is necessary before therapeutic decisions are made. This is particularly difficult to do, however, because of the coexistence of viral infection and complex autoimmune alterations. In this context, mixed cryoglobulinemia syndrome (MCs) represents the prototype of virus-related autoimmune-lymphoproliferative diseases. MCs can be treated at different levels by means of etiological treatment with antivirals (peg-interferon-alpha plus ribavirin) aimed at HCV eradication and/or pathogenetic/symptomatic treatments directed to both immune-system alterations and the vasculitic process (rituximab, cyclophosphamide, steroids, plasmapheresis, and so on). In clinical practice, the therapeutic strategy should be modulated according to severity/activity of the MCs and possibly tailored to each individual patient's conditions. Cryoglobulinemic skin ulcers may represent a therapeutic challenge, which should be managed by means of both local and systemic treatments. HCV-associated arthritis should be differentiated from the simple comorbidity of HCV infection and classical rheumatoid arthritis. It may be treated with low doses of steroids and/or hydroxychloroquine; the use of biologics (rituximab) may be considered in more severe cases. Primary Sjögren's syndrome is rarely associated with HCV infection, while sicca syndrome and myalgia are frequently detectable in hepatitis C patients, with or without cryoglobulinemic vasculitis. Other autoimmune rheumatic disorders (poly/dermatomyositis, polyarteritis nodosa, osteosclerosis, fibromyalgia, and so on) have been reported as potentially associated with HCV infection in patient populations from different countries, suggesting the role of genetic and/or environmental co-factors. The therapeutic approach to these disorders should be decided according to each individual patient's evaluation, including hepatic, virological, and immunological findings. PMID:22731694

  1. Sever's Disease

    MedlinePlus

    ... any problems linked with Sever's disease? No long-term problems have been linked with Sever's disease. However, call your doctor if your child's heel pain does not get better with treatment, gets worse or if you notice changes in skin color or swelling. Prevention Can Sever's disease be prevented? ...

  2. Lyme Disease.

    ERIC Educational Resources Information Center

    Taylor, George C.

    1991-01-01

    This overview of the public health significance of Lyme disease includes the microbiological specifics of the infectious spirochete, the entomology and ecology of the ticks which are the primary disease carrier, the clinical aspects and treatment stages, the known epidemiological patterns, and strategies for disease control and for expanded public…

  3. Kawasaki disease

    PubMed Central

    Kawasaki, Tomisaku

    2006-01-01

    Short history of Kawasaki disease, clinical features (principal symptoms and other significant symptoms or findings), diagnosis, cardiovascular involvement, epidemiology. Pathological features (lesion of vessels and lesion of organs exclusive of vessels), comparison between infantile periarteritis nodosa (IPN)/Kawasaki disease and classic periarteritis nodosa (CPN), etiology, treatment and management of Kawasaki disease are described. PMID:25792773

  4. Meniere's Disease.

    ERIC Educational Resources Information Center

    Schessel, David A.

    1997-01-01

    Meniere's disease is characterized by unpredictable spells of severe vertigo and fluctuations in hearing and tinnitus. This article discusses the incidence of Meniere's disease, the present status of our understanding of this disease, controversies in its diagnosis, and the multiple therapeutic modalities recruited in its treatment. (Contains…

  5. Meniere's Disease.

    ERIC Educational Resources Information Center

    Schessel, David A.

    1997-01-01

    Meniere's disease is characterized by unpredictable spells of severe vertigo and fluctuations in hearing and tinnitus. This article discusses the incidence of Meniere's disease, the present status of our understanding of this disease, controversies in its diagnosis, and the multiple therapeutic modalities recruited in its treatment. (Contains

  6. Behcet's Disease

    MedlinePlus

    ... with Behçet’s disease keep their joints strong and flexible. What Is the Prognosis for a Person With Behçet’s Disease? Most people with Behçet’s disease can lead productive lives and control symptoms with proper medicine, rest, and exercise. Doctors ...

  7. NEWCASTLE DISEASE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Concise information about Newcastle disease (ND) is provided for a book that serves as a quick reference guide to the infectious, parasitic, metabolic, nutritional, and toxic diseases of domesticated animals and birds as well some exotic species that a veterinarian might encounter. Newcastle disease...

  8. Crinkle Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crinkle disease of hop was first described in Europe in 1930, and subsequent reports of the disease appear in literature published in the 1960s and 1970s. The disease appears to be of little importance in most regions of hop production. A fastidious rickettsia-like organism (RLO) is thought to cau...

  9. Liver transplantation for alcoholic liver disease: Lessons learned and unresolved issues

    PubMed Central

    Ursic-Bedoya, José; Faure, Stéphanie; Donnadieu-Rigole, Hélène; Pageaux, Georges-Philippe

    2015-01-01

    The use of liver transplantation (LT) as a treatment for alcoholic liver disease (ALD) has been highly controversial since the beginning. The ever increasing shortage of organs has accentuated the low priority given to patients suffering from ALD, which is considered a “self-inflicted” condition. However, by improving the long-term survival rates, making them similar to those from other indications, and recognizing that alcoholism is a primary disease, ALD has become one of the most common indications for LT in Europe and North America, a situation thought unfathomable thirty years ago. Unfortunately, there are still many issues with the use of this procedure for ALD. There are significant relapse rates, and the consequences of excessive drinking after LT range from asymptomatic biochemical and histological abnormalities to graft failure and death. A minimum three-month period of sobriety is required for an improvement in liver function, thus making LT unnecessary, and to demonstrate the patient’s commitment to the project, even though a longer abstinence period does not guarantee lower relapse rates after LT. Recent data have shown that LT is also effective for severe alcoholic hepatitis when the patient is unresponsive to corticosteroids therapy, with low relapse rates in highly selected patients, although these results must be confirmed before LT becomes a standard procedure in this setting. Finally, LT for ALD is accompanied by an increased risk of de novo solid organ cancer, skin cancer, and lymphoproliferative disorders, which has a large impact on the survival rates. PMID:26494956

  10. Liver transplantation for alcoholic liver disease: Lessons learned and unresolved issues.

    PubMed

    Ursic-Bedoya, José; Faure, Stéphanie; Donnadieu-Rigole, Hélène; Pageaux, Georges-Philippe

    2015-10-21

    The use of liver transplantation (LT) as a treatment for alcoholic liver disease (ALD) has been highly controversial since the beginning. The ever increasing shortage of organs has accentuated the low priority given to patients suffering from ALD, which is considered a "self-inflicted" condition. However, by improving the long-term survival rates, making them similar to those from other indications, and recognizing that alcoholism is a primary disease, ALD has become one of the most common indications for LT in Europe and North America, a situation thought unfathomable thirty years ago. Unfortunately, there are still many issues with the use of this procedure for ALD. There are significant relapse rates, and the consequences of excessive drinking after LT range from asymptomatic biochemical and histological abnormalities to graft failure and death. A minimum three-month period of sobriety is required for an improvement in liver function, thus making LT unnecessary, and to demonstrate the patient's commitment to the project, even though a longer abstinence period does not guarantee lower relapse rates after LT. Recent data have shown that LT is also effective for severe alcoholic hepatitis when the patient is unresponsive to corticosteroids therapy, with low relapse rates in highly selected patients, although these results must be confirmed before LT becomes a standard procedure in this setting. Finally, LT for ALD is accompanied by an increased risk of de novo solid organ cancer, skin cancer, and lymphoproliferative disorders, which has a large impact on the survival rates. PMID:26494956

  11. Myocosis fungoides--an update on a non-mycotic disease.

    PubMed

    Makdisi, Joy; Friedman, Adam

    2013-07-01

    Mycosis fungoides was first described in 1806 by the French physician Jean Louis Alibert in a patient whose skin lesions developed into mushroom-like tumors. Though it is not an infectious disease, it was termed mycosis fungoides (MF) due to its fungating appearance. In 1870, Bazin further described MF, proposing the three classical stages of the cutaneous disease: patch, plaque, and tumor. The term cutaneous T-cell lymphoma (CTCL) was first utilized in 1975 by Lutzner et al to describe a group of malignant infiltrative disorders of the skin including MF and Sézary syndrome. CTCLs comprise a spectrum of extranodal non-Hodgkin's lymphomas that are characterized by primary cutaneous involvement of a dominant clonal T-cell. As molecular biology and immunohistochemistry techniques have become more developed, CTCL has become understood to be a heterogeneous assembly of disorders that vary with regards to clinical course, histopathology, therapeutic considerations, and prognosis. MF, a low-grade lymphoproliferative disorder, is the most common type of CTCL, comprising 54% of CTCLs. It is a rare, extranodal, non-Hodgkin's lymphoma and is an epidermotropic neoplasm composed of CD4+ (helper) lymphocytes Sézary syndrome is a related leukemic subtype of CTCL that presents with diffuse skin involvement as well as circulating tumor cells in the peripheral blood. PMID:23884501

  12. [Cryoglobulins in systemic and rheumatological diseases. Report of 70 cases (author's transl)].

    PubMed

    García-Bragado, F; Vilardell, M; Fonollosa, V; Gallart, M T; Rodrigo, M J; Tornos, J

    1980-03-25

    Cryoglobulins are immunoglobulins characterized by precipitating when serum is cooled and redissolving when serum is heated. There is strong evidence to consider mixed cryoglobulins as circulating immunocomplexes. Cryoglobulins have been demonstrated in association to hematologic, hepatic, lymphoproliferative, autoimmune and infectious conditions. There is also an essential or idiopathic variant. The present report studies a series of 70 patients with several rheumatic and systemic diseases, and a group of ten patients with cutaneous vasculitis. Significant levels of cryoglobulins have been detected in nine cases (overall incidence 12.8 percent). The diagnoses corresponding to these patients were as follows: systemic lupus erythematosus in three cases, dermatopolymyositis in three cases, Sjögren's syndrome in two cases, and Wegener's granulomatosis in one case. Cryoglobulins could not be demonstrated in patients with rheumatoid artritis, sclerodermia, periarteritis nodosa, cutaneous vasculitis, Reiter's syndrome, ankylosing spondilitis and acute articular rheumatism. Among patients with systemic lupus erythematosus a good correlation has been observed between the presence of serum cryoglobulins, the activity and severity of the diseases and the decrease of serum complement levels. PMID:6966024

  13. Allogeneic hematopoietic cell transplantation for peripheral T-cell NHL results in long-term disease control

    PubMed Central

    Zain, Jasmine; Palmer, Joycelynne M.; Delioukina, Maria; Thomas, Sandra; Tsai, Ni-Chun; Nademanee, Auayporn; Popplewell, Leslie; Gaal, Karl; Senitzer, David; Kogut, Neil; O'Donnell, Margaret; Forman, Stephen J.

    2012-01-01

    The study analyzed outcomes of a consecutive case series of 37 patients with peripheral T-cell non-Hodgkin lymphoma, from related and unrelated donors, using allogeneic hematopoietic cell transplantation (allo-HCT), between the years 2000 and 2007. All patients were pretreated; the majority had either relapsed or progressive disease (n=25, 68%), 13 had cutaneous histologies (CTCL), and all were ineligible for autologous transplant. Fully ablative conditioning regimens were used in 13 patients while 24 patients underwent reduced intensity conditioning (RIC). At five years the overall survival (OS) and progression-free survival (PFS) probabilities were 52.2% and 46.5%, respectively. At the time of analysis, 9 (24.3%) patients had either relapsed (n=6) or progressed (n=3) post allo-HCT. The cumulative incidences of relapse/progression and non-relapse mortality at 5 years were 24.3% and 28.9%. No statistically significant variables for survival or relapse were discovered by univariate Cox-regression analysis of disease and patient characteristics; differences between CTCL and other histologies were not significant. The median follow-up of 64.0 months (range: 16.4–100.4) indicates a mature data-set with probable cure in the survivors. The relapse/progression curves reached and maintained plateaus after 1 year post-transplant, demonstrating that long-term disease control is possible after allo-HCT in PTCL patients with advanced disease. PMID:21699453

  14. Prion Diseases

    PubMed Central

    Geschwind, Michael D.

    2016-01-01

    Purpose of Review This article presents an update on the clinical aspects of human prion disease, including the wide spectrum of their presentations. Recent Findings Prion diseases, a group of disorders caused by abnormally shaped proteins called prions, occur in sporadic (Jakob-Creutzfeldt disease), genetic (genetic Jakob-Creutzfeldt disease, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia), and acquired (kuru, variant Jakob-Creutzfeldt disease, and iatrogenic Jakob-Creutzfeldt disease) forms. This article presents updated information on the clinical features and diagnostic methods for human prion diseases. New antemortem potential diagnostic tests based on amplifying prions in order to detect them are showing very high specificity. Understanding of the diversity of possible presentations of human prion diseases continues to evolve, with some genetic forms progressing slowly over decades, beginning with dysautonomia and neuropathy and progressing to a frontal-executive dementia with pathology of combined prionopathy and tauopathy. Unfortunately, to date, all human prion disease clinical trials have failed to show survival benefit. A very rare polymorphism in the prion protein gene recently has been identified that appears to protect against prion disease; this finding, in addition to providing greater understanding of the prionlike mechanisms of neurodegenerative disorders, might lead to potential treatments. Summary Sporadic Jakob-Creutzfeldt disease is the most common form of human prion disease. Genetic prion diseases, resulting from mutations in the prion-related protein gene (PRNP), are classified based on the mutation, clinical phenotype, and neuropathologic features and can be difficult to diagnose because of their varied presentations. Perhaps most relevant to this Continuum issue on neuroinfectious diseases, acquired prion diseases are caused by accidental transmission to humans, but fortunately, they are the least common form and are becoming rarer as awareness of transmission risk has led to implementation of measures to prevent such occurrences. PMID:26633779

  15. Prion diseases.

    PubMed

    McKintosh, Edward; Tabrizi, Sarah J; Collinge, John

    2003-04-01

    Prion diseases are incurable neurodegenerative conditions affecting both animals and humans. They may be sporadic, infectious, or inherited in origin. Human prion diseases include Creutzfeldt-Jakob desease (CJD), Gerstmann-Straussler-Scheinker disease, kuru, and fatal familial insomnia. The appearance of variant CJD, and the demonstration that is caused by strains indistinguishable from bovine spongiform encephalopathy (BSE) in cattle, has led to the threat of a major epidemic of human prion disease in the UK and other countries where widespread dietary exposure to bovine prions has occurred. This article reviews the history and epidemiology of these diseases, and then focuses on important areas of current research in human prion disorders. PMID:12707849

  16. [Pick's disease].

    PubMed

    Yamamoto, Kazuki; Ogihara, Tomomi

    2016-03-01

    Pick's disease is a type of frontotemporal lobar degeneration(FTLD) with circumscribed atrophy in the frontotemporal lobe. The terminology for Pick's disease has evolved over time. Pick's disease was a term formerly used to define a disorder with symptoms caused by frontal and temporal lobe dysfunction. Therefore, the diagnosis was previously based on clinical features and the distribution of brain atrophy. Pick's disease is currently defined by the presence of tau-positive Pick bodies, and thus can be diagnosed only pathologically. The clinical phenotypes of Pick's disease include behavioral variant FTD (bvFTD), progressive nonfluent aphasia (PNFA) and semantic dementia (SD). PMID:27025090

  17. Leprosy patients with lepromatous disease recognize cross-reactive T cell epitopes in the Mycobacterium leprae 10-kD antigen

    PubMed Central

    Hussain, R; Dockrell, H M; Shahid, F; Zafar, S; Chiang, T J

    1998-01-01

    T cell responses play a critical role in determining protective responses to leprosy. Patients with self-limiting tuberculoid leprosy show high T cell reactivity, while patients with disseminated lepromatous form of the disease show absent to low levels of T cell reactivity. Since the T cell reactivity of lepromatous patients to purified protein derivative (PPD), a highly cross-reactive antigen, is similar to that of tuberculoid patients, we queried if lepromatous patients could recognize cross-reactive epitopes in Mycobacterium leprae antigens as well. T cell responses were analysed to a recombinant antigen 10-kD (a heat shock cognate protein) which is available from both M. tuberculosis (MT) and M. leprae (ML) and displays 90% identity in its amino acid sequence. Lymphoproliferative responses were assessed to ML and MT 10 kD in newly diagnosed leprosy patients (lepromatous, n = 23; tuberculoid, n = 65). Lepromatous patients showed similar, but low, lymphoproliferative responses to ML and MT 10 kD, while tuberculoid patients showed much higher responses to ML 10 kD. This suggests that the tuberculoid patients may be recognizing both species-specific and cross-reactive epitopes in ML 10 kD, while lepromatous patients may be recognizing only cross-reactive epitopes. This was further supported by linear regression analysis. Lepromatous patients showed a high concordance in T cell responses between ML and MT 10 kD (r = 0.658; P < 0.0006) not observed in tuberculoid patients (r = 0.203; P > 0.1). Identification of cross-reactive T cell epitopes in M. leprae which could induce protective responses should prove valuable in designing second generation peptide-based vaccines. PMID:9822277

  18. Prion diseases.

    PubMed

    Takada, Leonel T; Geschwind, Michael D

    2013-09-01

    Prion diseases are a group of diseases caused by abnormally conformed infectious proteins, called prions. They can be sporadic (Jakob-Creutzfeldt disease [JCD]), genetic (genetic JCD, Gerstmann-Sträussler-Scheinker, and familial fatal insomnia), or acquired (kuru, variant JCD, and iatrogenic JCD). The clinical features associated with each form of prion disease, the neuroimaging findings, cerebrospinal fluid markers, and neuropathological findings are reviewed. Sporadic JCD is the most common form of human prion disease, and will be discussed in detail. Genetic prion diseases are caused by mutations in the prion-related protein gene (PRNP), and they are classified based on the mutation, clinical phenotype, and neuropathological features. Acquired prion diseases fortunately are becoming rarer, as awareness of transmission risk has led to implementation of measures to prevent such occurrences, but continued surveillance is necessary to prevent future cases. Treatment and management issues are also discussed. PMID:24234356

  19. Management of hepatitis C in patients with chronic kidney disease.

    PubMed

    Carvalho-Filho, Roberto J; Feldner, Ana Cristina C A; Silva, Antonio Eduardo B; Ferraz, Maria Lucia G

    2015-01-14

    Hepatitis C virus (HCV) infection is highly prevalent among chronic kidney disease (CKD) subjects under hemodialysis and in kidney transplantation (KT) recipients, being an important cause of morbidity and mortality in these patients. The vast majority of HCV chronic infections in the hemodialysis setting are currently attributable to nosocomial transmission. Acute and chronic hepatitis C exhibits distinct clinical and laboratorial features, which can impact on management and treatment decisions. In hemodialysis subjects, acute infections are usually asymptomatic and anicteric; since spontaneous viral clearance is very uncommon in this context, acute infections should be treated as soon as possible. In KT recipients, the occurrence of acute hepatitis C can have a more severe course, with a rapid progression of liver fibrosis. In these patients, it is recommended to use pegylated interferon (PEG-IFN) in combination with ribavirin, with doses adjusted according to estimated glomerular filtration rate. There is no evidence suggesting that chronic hepatitis C exhibits a more aggressive course in CKD subjects under conservative management. In these subjects, indication of treatment with PEG-IFN plus ribavirin relies on the CKD stage, rate of progression of renal dysfunction and the possibility of a preemptive transplant. HCV infection has been associated with both liver disease-related deaths and cardiovascular mortality in hemodialysis patients. Among those individuals, low HCV viral loads and the phenomenon of intermittent HCV viremia are often observed, and sequential HCV RNA monitoring is needed. Despite the poor tolerability and suboptimal efficacy of antiviral therapy in CKD patients, many patients can achieve sustained virological response, which improve patient and graft outcomes. Hepatitis C eradication before KT theoretically improves survival and reduces the occurrence of chronic graft nephropathy, de novo glomerulonephritis and post-transplant diabetes mellitus. PMID:25593456

  20. MELDEQ : An alternative Model for End-Stage Liver Disease score for patients with hepatocellular carcinoma.

    PubMed

    Marvin, Michael R; Ferguson, Nicole; Cannon, Robert M; Jones, Christopher M; Brock, Guy N

    2015-05-01

    Multiple studies have demonstrated an advantage for hepatocellular carcinoma (HCC) patients under the current liver allocation system, such that the United Network for Organ Sharing (UNOS) recently voted in support of a proposal to delay granting Model for End-Stage Liver Disease (MELD) exception points to all HCC patients for 6 months, independently of a candidate's native MELD score or alpha-fetoprotein (AFP) level. We obtained UNOS data on adult patients who were added to the wait list between January 22, 2005 and September 30, 2009, and we explored the relationship between HCC, MELD, AFP, and other factors that contribute to not only dropout on the wait list but posttransplant survival as well. The aim was to establish an equivalent Model for End-Stage Liver Disease (MELDEQ ) score for HCC patients that would reduce the disparity in access to transplantation between HCC and non-HCC patients. We determined risk groups for HCC patients with dropout hazards equivalent to those of non-HCC patients, and we evaluated projections for HCC wait-list dropout/transplantation probabilities on the basis of the MELDEQ prioritization scheme. Projections indicate that lower risk HCC patients (MELDEQ  ≤ 18) would have dropout probabilities similar to those of non-HCC patients in the same MELD score range, whereas dropout probabilities for higher risk HCC patients would actually be improved. The posttransplant survival of all HCC risk groups is lower than that of their non-HCC counterparts, with 1-year survival of 0.77 (95% CI, 0.70-0.85) for MELDEQ scores ≥ 31. These results suggest that HCC patients with a combination of a low biochemical MELD score and a low AFP level (MELDEQ  ≤ 15) would receive a marked advantage in comparison with patients with chemical MELD scores in a similar range and that a delay of 6 months for listing may be appropriate. In contrast, patients with MELDEQ scores > 15 would likely be adversely affected by a universal 6-month delay in listing. PMID:25694099