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1

Posttransplant lymphoproliferative disease after lung transplantation.  

PubMed

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

Neuringer, Isabel P

2013-01-01

2

Posttransplant Lymphoproliferative Disorders  

Microsoft Academic Search

In 1968, Starzl reported the clinical observation that transplant patients are prone to develop lymphomatous growths (1).\\u000a The term posttransplant lymphoproliferative disorder (PTLD) is applied to a group of lymphoproliferative disorders arising in a pharmacologically immunocompromised host after\\u000a solid-organ or allogeneic stem cell transplantation. Among iatrogenic immune deficiency states, PTLD is quite common (2).\\u000a PTLDs are the most serious complications

Thomas M. Habermann

3

Pediatric Central Nervous System Posttransplant Lymphoproliferative Disorder  

Microsoft Academic Search

Summary: Post-transplant lymphoproliferative disorder complicates approximately 1% of all renal transplants (1). The usual site of occurrence is within the abdomen, thorax, allograft, or head and neck. Central nervous system in- volvement is uncommon but, when present, occurs in iso- lation, sparing other organ systems. Few articles in the radiology literature have focused on the acute and fol- low-up central

Kimberly C. Brennan; Lisa H. Lowe; Gabrielle A. Yeaney

4

Differentiation of EBV-induced post-transplant Hodgkin lymphoma from Hodgkin-like post-transplant lymphoproliferative disease.  

PubMed

The development of lymphomas after SOT is a well-known complication of the immunosuppressive therapy necessary to prevent graft rejection. Epstein-Barr virus plays a central role in the pathogenesis of lymphomas because of its ability to transform infected cells. Differentiating PTLD from malignant lymphomas, especially HL can be challenging. We report on two patients, who developed EBV-associated lymphomas several years after SOT. A histological examination of lymph nodes led to a diagnosis of HL in both patients, who were started on chemotherapy according to current treatment protocols. A rapid and complete remission in one patient prompted us to analyze the expression pattern of EBV-latency genes. In this patient, the EBV expression profile revealed a latency type III suggesting the diagnosis of Hodgkin-like PTLD. The other patient required six courses of chemotherapy plus radiotherapy to reach a complete remission. In his tumor cells, a restricted EBV-latency type II pattern was found, suggesting a diagnosis of classical HL. These two cases demonstrate that in post-transplant lymphomas with histological features of HL, an analysis of the expression pattern of EBV proteins might aid in the differentiation between PTLD and HL. PMID:18466428

Rohr, Jan C; Wagner, Hans J; Lauten, Melchior; Wacker, Hans H; Jüttner, Eva; Hanke, Christof; Pohl, Martin; Niemeyer, Charlotte M

2008-06-01

5

Posttransplant Lymphoproliferative Disorders in Liver Transplantation  

PubMed Central

Objective To evaluate the incidence of posttransplant lymphoproliferative disease (PTLD) and the risk factors and the impact of this complication on survival outcomes in a large cohort of liver transplant recipients at a single institution. Summary Background Data Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, in large part due to the availability and reliance on the use of nonspecifically directed immunosuppression. However, as predicted and subsequently verified in 1968, an increased incidence of certain de novo malignancies has been observed, particularly with regards to lymphoid neoplasms. While many reports have confirmed and clarified the nature of PTLD, the literature is fraught with conflicting experience and outcomes with PTLD. Methods Four thousand consecutive patients who underwent liver transplants between February 1981 and April 1998 were included in this analysis and were followed to November 2001. The effect of recipient age at the time of transplant, recipient gender, diagnosis, baseline immunosuppression, grading of PTLD, and association with Epstein-Barr virus were compared. The causes of death were also examined. Treatment for PTLD varied over the 20-year period, but all included massive reduction or elimination of baseline immunosuppression. Results The 1-year patient survival for liver transplant patients with PTLD was 85%, while the overall patient survival for the entire cohort was 53%. The actuarial 20-year survival was estimated at 45%. The overall median time to PTLD presentation was 10 months, and children had an incidence of PTLD that was threefold higher than adults. Patient survival was better in children, in patients transplanted in the era of tacrolimus immunosuppression, in patients with polymorphic PTLD, and in those with limited disease. Interestingly, neither the presence or absence of Epstein-Barr virus nor the timing of PTLD presentation appeared to influence overall patient survival. Patients transplanted for alcohol-related liver disease had a similar incidence of PTLD but had a higher risk of mortality. Conclusions While PTLD continues to pose problems in patients receiving liver transplants, improvements in patient survival have been observed over time. While it is too early to assess the impact of new advances in prophylaxis, diagnosis, and treatment, such approaches are based on an increased knowledge of the pathophysiology of PTLD. PMID:12368671

Jain, Ashok; Nalesnik, Mike; Reyes, Jorge; Pokharna, Renu; Mazariegos, George; Green, Michael; Eghtesad, Bijan; Marsh, Wallis; Cacciarelli, Thomas; Fontes, Paulo; Abu-Elmagd, Kareem; Sindhi, Rakesh; Demetris, Jake; Fung, John

2002-01-01

6

Complete immunosuppressive withdrawal as a uniform approach to post-transplant lymphoproliferative disease in pediatric liver transplantation.  

PubMed

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) in pediatric liver transplant recipients is associated with a high mortality (up to 60%) and the younger age groups, who are predominantly EBV-naïve, are at highest risk for development of this disease. The aim of this study is to assess, in this high-risk group, patient outcome and graft loss to rejection when complete withdrawal of immunosuppressive agents (IMS) is instituted as the mainstay of treatment in addition to the use of standard therapy. A retrospective analysis of 335 pediatric patients whose liver transplants were performed by our team between September 1988 and September 2002, was carried out through review of computer records, database and patient charts. Fifty patients developed either EBV or PTLD; 80% were < or =2 yr of age. Of these 50 patients, 19 had a positive tissue diagnosis for PTLD and 31 were diagnosed with EBV infection, 14 of whom had positive tissue for EBV. Fifty-eight percent of patients who developed PTLD and 51.6% of patients with EBV received antibody for induction or treatment of rejection prior to onset of disease. Forty-six patients (92%) received post-transplant antiviral prophylaxis with ganciclovir or acyclovir. Antiviral treatment included ganciclovir in 76%, acyclovir in 20% and Cytogam (in addition to one of the former agents) in 44%. In those with PTLD, treatment included chemotherapy (n = 1), Rituximab (n = 2), and ocular radiation (n = 1). IMS was stopped in all patients with PTLD and in 19 with EBV infection and was held as long as there was no allograft rejection. Eight patients have remained off IMS for a mean of 1535.5 +/- 623 days. Of the 21 patients who were restarted on IMS for acute rejection, 18 responded to steroids and/or reinstitution of low-dose calcineurin inhibitors. The mean time to rejection while off IMS in this group was 107.43 +/- 140 days (range: 7-476). Two patients were re-transplanted for chronic rejection; one had chronic rejection that existed prior to discontinuing IMS. The mortality rate in our series was 31.6% in those with PTLD and 6% in those with EBV disease. The cause of death was related to PTLD or sepsis in all cases; no deaths were due to graft loss from acute or chronic rejection. PTLD is associated with high mortality in the pediatric population. Based on this report, we advocate aggressive management of PTLD that is composed of early cessation of IMS, the use of antiviral therapy, and chemotherapy when indicated. Episodes of rejection that occur after stopping IMS can be successfully treated with standard therapy without graft loss to acute rejection. PMID:15176965

Hurwitz, Melissa; Desai, Dev M; Cox, Kenneth L; Berquist, William E; Esquivel, Carlos O; Millan, Maria T

2004-06-01

7

Post-transplant lymphoproliferative disorder—the potential of proliferation signal inhibitors  

Microsoft Academic Search

Post-transplant lymphoproliferative disorder (PTLD) is a heterogeneous group of diseases characterized by abnormal lymphoid proliferation following transplan- tation. These lymphomas, in particular, have been shown to have a higher incidence in renal transplant recipients compared with the general age-matched population. The effect of different immunosuppressive regimens on the incidence of PTLD has been assessed in a number of studies. Although

Julio Pascual

8

Pediatric post-transplant lymphoproliferative disorder after cardiac transplantation  

Microsoft Academic Search

Post-transplant lymphoproliferative disorder (PTLD) is a well recognized and potentially fatal complication after pediatric\\u000a cardiac transplantation. PTLD encompasses a wide spectrum, ranging from benign hyperplasia to more aggressive lymphoma. Most\\u000a cases are Epstein-Barr virus (EBV)-related B-cell tumors resulting from impaired immunity due to immunosuppressive therapy.\\u000a Pediatric recipients, often seronegative for EBV at transplantation, have a greater risk for PTLD than

Hideaki Ohta; Norihide Fukushima; Keiichi Ozono

2009-01-01

9

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

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

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

10

Epstein-Barr virus infection and posttransplant lymphoproliferative disorder.  

PubMed

Epstein-Barr virus (EBV) is an important pathogen in recipients of solid organ transplants (SOT). Infection with EBV manifests as a spectrum of diseases/malignancies ranging from asymptomatic viremia through infectious mononucleosis to posttransplant lymphoproliferative disorder (PTLD). EBV disease and its associated PTLD is more frequently seen when primary EBV infection occurs after transplant, a common scenario in pediatric SOT recipients. Intensity of immunosuppressive therapies also influences the risk for PTLD. The use of EBV viral load monitoring facilitates the diagnosis and management of EBV/PTLD as well as being used to inform preemptive therapy with reduction of immunosuppression, the most effective intervention for prevention of and treatment for PTLD. Other therapies, including the rituximab (anti-CD20 monoclonal antibody) and traditional chemotherapy, are also useful in the treatment of established PTLD. The future development of standards for management based on EBV viral load and routine monitoring of EBV-specific CTL responses promise further improvement in outcomes with EBV and PTLD. PMID:23347213

Green, M; Michaels, M G

2013-02-01

11

Post-Transplant Lymphoproliferative Disorders after Heart or Kidney Transplantation at a Single Centre: Presentation and Response to Treatment  

Microsoft Academic Search

Post-transplant lymphoproliferative disorders (PTLD) is a serious complication after solid organ transplantation. Reduction of immunosuppression (RI) alone is not able to control the disease. We report a prospective analysis of 30 patients with PTLD after heart or kidney transplantation. Only 5 of 30 patients, treated solely with RI, obtained a complete response. Five patients were treated heterogeneously; in the remaining

S. M. L. Aversa; S. Stragliotto; D. Marino; F. Calabrese; P. Rigotti; F. Marchini; A. Gambino; G. Feltrin; C. Boso; F. Canova; C. Soldà; R. Mazzarotto; P. Burra

2008-01-01

12

Activation and Adoptive Transfer of Epstein-Barr Virus-Specific Cytotoxic T Cells in Solid Organ Transplant Patients with Posttransplant Lymphoproliferative Disease  

Microsoft Academic Search

The treatment of Epstein-Barr virus (EBV)-associated lymphoproliferative disease (PTLD) in EBV seronegative solid organ transplant recipients who acquire their EBV infection after engraftment poses a considerable challenge because of underlying immunosuppression that inhibits the virus-specific cytotoxic T cell (CTL) response in vivo. We have developed a protocol for activating autologous EBV-specific CTL lines from these patients and show their potential

Rajiv Khanna; Scott Bell; Martina Sherriti; Andrew Galbraith; Scott R. Burrows; Lee Rafter; Belinda Clarke; Richard Slaughter; Michael C. Falk; Jo Douglass; Trevor Williams; Suzanne L. Ellioti; Denis J. Moss

1999-01-01

13

Post-transplant lymphoproliferative disease of donor origin, following haematopoietic stem cell transplantation in a patient with blastic plasmacytoid dendritic cell neoplasm.  

PubMed

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare condition that originates from dendritic cells. We report on the first case of Epstein-Barr virus (EBV)-driven post-transplant lymphoproliferative disorder (PTLD) of donor origin in a BPDC patient post-allogeneic haematopoietic stem cell transplantation (HSCT). Flow cytometry study identified a cell population CD4+/CD56+/CD45RA+/CD123+/TCL1+ suggestive of BPDCN diagnosis, which was confirmed by a lymph node biopsy (cells positive for BCL11a, BDCA-2, CD2AP, CD123, TCL1 and S100). Cytogenetic analysis revealed a complex karyotype: (19 metaphase) 47,XX,t(1;6)(q21;q2?5),-13?+?2mar[11]/47, XX, +21 [3]/46,XX [5]. The patient was started on acute myeloid leukaemia (AML) induction schedule, and subsequently an allogeneic HSCT was performed. On day +36 post-HSCT, bone marrow biopsy/aspirate showed complete morphological remission, and chimerism study showed 100% donor chimera. However, on day +37, the patient was found to have enlarged cervical and supraclavicular lymphoadenopathy, splenomegaly and raised lactic dehydrogenase. EBV-DNA copies in blood were elevated, consistent with a lytic cycle. A lymph node biopsy showed EBV encoded RNA and large atypical B cells (CD45dim-, CD4+/CD56+, monoclonal for k-chain, CD19+/CD20+/CD21+/CD22+/CD38+/CD43+/CD79?-/CD5-/CD10-), consistent with PTLD monomorphic type. Chimerism study showed that PTLD was of donor origin. This case together with the recent literature findings on BPDCN and PTLD are discussed. PMID:22915052

Piccin, Andrea; Morello, Enrico; Svaldi, Mirija; Haferlach, Torsten; Facchetti, Fabio; Negri, Giovanni; Vecchiato, Cinzia; Fisogni, Simona; Pusceddu, Irene; Cortelazzo, Sergio

2012-12-01

14

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

ClinicalTrials.gov

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

2013-01-24

15

Posttransplant lymphoproliferative disorder presenting as a small bowel obstruction in a patient with pancreas transplantation alone  

PubMed Central

Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication associated with the transplant recipient. We chronicle a case of PTLD in a failed graft presenting as a small bowel obstruction in a pancreas-only transplant patient. While typical symptoms may be elusive in the complex immunosuppressed patient, graft pain along with persistent graft pancreatitis and a positive Epstein-Barr viremia should raise suspicion for an underlying PTLD. PMID:25484508

Kruel, Cleber R.; Shiller, S. Michelle; Anthony, Tiffany L.; Goldstein, Robert M.; Kim, Peter T. W.; Levy, Marlon F.; McKenna, Gregory J.; Onaca, Nicholas; Testa, Giuliano; Klintmalm, Goran B.

2014-01-01

16

EBV-positive mucocutaneous ulcer in organ transplant recipients: a localized indolent posttransplant lymphoproliferative disorder.  

PubMed

Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBV MCU) is a B-cell lymphoproliferative disorder occurring in elderly or iatrogenic immunocompromised patients. It has not been reported in solid organ transplant recipients. We observed 7 patients with EBV MCU in a cohort of 70 transplant recipients with EBV posttransplant lymphoproliferative disorder (PTLD). Transplants included: 5 renal, 1 heart, and 1 lung. Median patient age was 61; 5 were male. EBV MCU was observed in oral mucosa in 4 and gastrointestinal tract in 3. Duration of immunosuppressive therapy before EBV MCU was 0.6 to 13 years. Ulcers were undermined by inflammatory cells and polymorphic or monomorphic large cell lymphoproliferation. Reed-Sternberg-like cells were present in 5/7. Large B cells were CD20, CD30, and EBV-encoded RNA positive in all cases. Diagnosis in 3 recent patients was EBV MCU; 4 patients diagnosed before familiarity with EBV MCU were classified as monomorphic large cell (n=3) and polymorphic (n=1) PTLD. None of the patients had EBV DNA in their blood (<1000 copies/mL) at diagnosis or follow-up versus 35/44 transplant patients with systemic PTLD (P<0.001). All lesions resolved with reduced immunosuppression (7/7), change in immunosuppression (2/7), and rituximab (3/7). Five patients are living: 4 healthy, 1 awaiting second renal transplant. Two patients died 3 and 5 years after resolution of EBV MCU. No patient recurred with EBV MCU or other PTLDs. EBV MCU mimics more aggressive categories of PTLD but lacks EBV DNA in blood, which may be a useful distinguishing feature. Lesions are likely to resolve with conservative management. Awareness of EBV MCU in the posttransplant setting is necessary for appropriate diagnosis and treatment. PMID:25007145

Hart, Melissa; Thakral, Beenu; Yohe, Sophia; Balfour, Henry H; Singh, Charanjeet; Spears, Michael; McKenna, Robert W

2014-11-01

17

Post-transplant lymphoproliferative disorder resembling Wilms tumor. Diagnostic dilemma: renal biopsy or nephrectomy?  

PubMed

Post-transplant lymphoproliferative disorder is a life-threatening neoplasm that can occur after orthotopic liver transplant. We report a 14-month-old female status-post OLT with an atypical presentation of PTLD as a solitary renal mass. At eight-wk post-transplant, she presented with elevated transaminases, CMV counts (73,000 copies/mL), and EBV counts (35,000 copies/mL). CT scan revealed a solid heterogeneously enhancing right renal mass measuring 2.6 × 2.4 × 3.3 cm. The radiological diagnosis was Wilms tumor, although PTLD could not be excluded. Complete resection of a Wilms tumor is potentially curative. A needle biopsy would upstage the malignancy and result in radiochemotherapy that is deleterious to a liver graft. The mass was not amenable to partial nephrectomy. A total nephrectomy, given life-long nephrotoxic immunosuppressants, was an unfavorable option. Thus, needle biopsy was performed. Histology confirmed monoclonal, EBV-associated PTLD and diffuse large B-cell lymphoma. Her therapy included immunosuppression reduction, cyclophosphamide, steroids, and anti-CD20 monoclonal antibody. Concomitantly, she received Cytogam and gancyclovir. Complete remission was achieved three months after chemotherapy. This case illustrates that young age, CMV infection, and EBV infection are strong risk factors for PTLD. With such risk factors present, any mass or lesion in a solid organ transplant patient should be considered PTLD until proven otherwise. PMID:20670357

Cheng, Edaire; Fustino, Nicholas; Klesse, Laura; Chinnakotla, Srinath; Sanghavi, Rinarani

2011-12-01

18

Hodgkin lymphoma post-transplant lymphoproliferative disorder following pediatric renal transplant: serial imaging with F-18 FDG PET/CT.  

PubMed

Post-transplant lymphoproliferative disorder (PTLD) occurs in 1.2% of pediatric renal transplant patients, and is frequently Epstein-Barr Virus mediated. Hodgkin Lymphoma PTLD is the rarest of the 4 types of PTLDs recognized by the World Health Organization, with an incidence of <4% of all PTLD patients. It has a distinct clinical course and treatment from all other types of PTLD. This is a case of a 16-year-old girl who had a renal transplant in 2000 due to Moya Moya disease. Her first F-18 FDG PET/CT done in 2006 showed mildly FDG-avid mediastinal adenopathy (histologically nonspecific reactive nodes), however in 2009, after presenting with fevers, a repeat PET/CT showed extensive intensely FDG-avid disease. Biopsy of a supraclavicular node identified Hodgkin Lymphoma PTLD. The patient was treated with chemotherapy and reimaged, showing excellent response to therapy. In contrast, classic PTLD is treated by withdrawal of immunosuppression and administration of Rituximab. F-18 FDG PET/CT is known to be very useful in the staging and monitoring of response to therapy in the setting of classic PTLD. In this case, serial F-18 FDG PET/CT scans proved very useful in the evaluation and follow-up of the rare and distinct Hodgkin Lymphoma PTLD subtype. PMID:20706047

Makis, William; Lisbona, Robert; Derbekyan, Vilma

2010-09-01

19

Posttransplant lymphoproliferative disorder complicating hematopoietic stem cell transplantation in a patient with dyskeratosis congenita.  

PubMed

Dyskeratosis congenita (DC) is a rare inherited disorder characterized by bone marrow failure and cancer predisposition. We present a case of a 28-year-old woman with DC who was admitted for hematopoietic stem cell transplantation (HSCT) for aplastic anemia and who developed acute myeloid leukemia with complex genetic karyotype abnormalities including the MLL (11q23) gene, 1q25, and chromosome 8. After transplantation, a monomorphic Epstein-Barr virus (EBV) negative posttransplant-associated lymphoproliferative disorder (PTLD) diffuse large B-cell lymphoma was discovered involving the liver, omental tissue, and peritoneal fluid samples showing additional MLL (11q23) gene abnormalities by fluorescence in situ hybridization. Despite treatment, the patient died of complications associated with transplantation and invasive fungal infection. This case represents the first bona fide documented case of EBV-negative monomorphic PTLD host derived, with MLL gene abnormalities in a patient with DC, and shows another possible mechanism for the development of a therapy-related lymphoid neoplasm after transplantation. PMID:23222806

Bohn, Olga L; Whitten, Joseph; Spitzer, Barbara; Kobos, Rachel; Prockop, Susan; Boulad, Farid; Arcila, Maria; Wang, Lu; Teruya-Feldstein, Julie

2013-10-01

20

Severe post-transplant lymphoproliferative disorder after living donor liver transplantation.  

PubMed

Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication after transplantation. A living donor liver transplantation was performed on a 31-year-old man for fulminant hepatitis. He again developed liver dysfunction after 7?months. He was diagnosed as having acute cellular rejection and the steroid pulse therapy introduced resulted in little improvement. He gradually developed a high fever and right axillary lymphadenopathy appeared. Chest computed tomography (CT) was performed revealing small lung nodules and axillary lymphadenopathy. Because his serological status for Epstein-Barr virus was positive, PTLD was highly suspected and immunosuppression treatment was withdrawn with little improvement. One week later, he developed tachycardia. Chest CT was re-performed revealing an infiltration to the left cardiac chamber. For diagnosis, axillary lymph node biopsy was performed and during the procedure, he developed ventricular tachycardia (VT). Immunohistological staining revealed PTLD of T lymphocytes, and chemotherapy was introduced on the same day he developed VT. After two cycles of tetrahydropyranyl, adriamycin, cyclophosphamide, vincristine, prednisolone and etoposide treatment, he completely recovered. This is a first case report of severe PTLD with VT, and our case implies the feasibility of chemotherapy after the appearance of dissemination symptoms. PMID:24750572

Kuramitsu, Kaori; Fukumoto, Takumi; Fukushima, Kenji; Iwasaki, Takeshi; Tominaga, Masahiro; Matsui, Toshimitsu; Kawakami, Fumi; Itoh, Tomoo; Ku, Yonson

2015-03-01

21

Treatment of recurrent posttransplant lymphoproliferative disorder of the central nervous system with high-dose methotrexate.  

PubMed

Posttransplant lymphoproliferative disorder (PTLD) is a frequent complication of intestinal transplantation and is associated with a poor prognosis. There is currently no consensus on optimal therapy. Recurrent PTLD involving the central nervous system (CNS) represents a particularly difficult therapeutic challenge. We report the successful treatment of CNS PTLD in a pediatric patient after liver/small bowel transplantation. Initial immunosuppression (IS) was with thymoglobulin, solucortef, tacrolimus, and mycophenolate mofetil. EBV viremia developed 8 weeks posttransplantation, and despite treatment with cytogam and valganciclovir the patient developed a polymorphic, CD20+, EBV+ PTLD with peripheral lymphadenopathy. Following treatment with rituximab, the lymphadenopathy resolved, but a new monomorphic CD20-, EBV+, lambda-restricted, plasmacytoid PTLD mesenteric mass emerged. Complete response of this PTLD was achieved with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy; however, 4 months off therapy he developed CNS PTLD (monomorphic CD20-, EBV+, lambda-restricted, plasmacytoid PTLD) of the brain and spine. IS was discontinued and HD-MTX (2.5-5?gm/m(2)/dose) followed by intrathecal HD-MTX (2?mg/dose ×2-3 days Q 7-10 days per cycle) was administered Q 4-7 weeks. After 3 cycles of HD-MTX, the CSF was negative for malignant cells, MRI of head/spine showed near-complete response, and PET/CT was negative. The patient remains in complete remission now for 3.5 years after completion of systemic and intrathecal chemotherapy. Conclusion. HD-MTX is an effective therapy for CNS PTLD and recurrent PTLD that have failed rituximab and CHOP chemotherapy. PMID:23984169

Twist, Clare J; Castillo, Ricardo O

2013-01-01

22

Treatment of Recurrent Posttransplant Lymphoproliferative Disorder of the Central Nervous System with High-Dose Methotrexate  

PubMed Central

Posttransplant lymphoproliferative disorder (PTLD) is a frequent complication of intestinal transplantation and is associated with a poor prognosis. There is currently no consensus on optimal therapy. Recurrent PTLD involving the central nervous system (CNS) represents a particularly difficult therapeutic challenge. We report the successful treatment of CNS PTLD in a pediatric patient after liver/small bowel transplantation. Initial immunosuppression (IS) was with thymoglobulin, solucortef, tacrolimus, and mycophenolate mofetil. EBV viremia developed 8 weeks posttransplantation, and despite treatment with cytogam and valganciclovir the patient developed a polymorphic, CD20+, EBV+ PTLD with peripheral lymphadenopathy. Following treatment with rituximab, the lymphadenopathy resolved, but a new monomorphic CD20?, EBV+, lambda-restricted, plasmacytoid PTLD mesenteric mass emerged. Complete response of this PTLD was achieved with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy; however, 4 months off therapy he developed CNS PTLD (monomorphic CD20?, EBV+, lambda-restricted, plasmacytoid PTLD) of the brain and spine. IS was discontinued and HD-MTX (2.5–5?gm/m2/dose) followed by intrathecal HD-MTX (2?mg/dose ×2-3 days Q 7–10 days per cycle) was administered Q 4–7 weeks. After 3 cycles of HD-MTX, the CSF was negative for malignant cells, MRI of head/spine showed near-complete response, and PET/CT was negative. The patient remains in complete remission now for 3.5 years after completion of systemic and intrathecal chemotherapy. Conclusion. HD-MTX is an effective therapy for CNS PTLD and recurrent PTLD that have failed rituximab and CHOP chemotherapy. PMID:23984169

Twist, Clare J.; Castillo, Ricardo O.

2013-01-01

23

Rituximab is highly effective for pure red cell aplasia and post-transplant lymphoproliferative disorder after unrelated hematopoietic stem cell transplantation  

PubMed Central

Pure red cell aplasia (PRCA) and post-transplant lymphoproliferative disorder (PTLD) constitute rare complications after allogeneic hematopoietic stem cell transplantation (AlloHSCT). The incidence of EBV-PTLD is above 1%, but it may increase in patients with well-known risk factors such as EBV seronegativity at the time of transplantation, T-cell depletion of donor grafts, HLA mismatch and use of antithymocyte globulin (ATG) for prophylaxis of graft versus host disease. The risk factors for PRCA were defined and they include: 1) elevated post-transplant anti-donor isohemagglutinin titers, 2) reduced-intensity conditioning before transplant, 3) the presence of anti-A agglutinin and 4) ciclosporin for graft versus host disease (GVHD) prophylaxis and 5) transplant from sibling donor. The anti-CD20 monoclonal antibody rituximab remains the first line treatment for PTLD following AlloHSCT, but its efficacy in PRCA is limited. Reduction of immunosuppression is also strongly advised. This is the first report on an adult patient who simultaneously developed PRCA and PTLD after ABO-mismatched AlloHSCT. The early introduction of rituximab resulted in prompt resolution of clinical symptoms with subsequent full recovery. PMID:23788882

Kopi?ska, Anna; Frankiewicz, Andrzej; Grygoruk-Wi?niowska, Iwona; Kyrcz-Krzemie?, S?awomira

2012-01-01

24

Cell lineage in lymphoproliferative disease.  

PubMed

Surface marker techniques have made a major contribution to the understanding and classification of lymphoproliferative disorders by permitting the determination of B- and T-cell lineage. The frequent malignant proliferations of B lymphocytes are identified by the presence of surface immunoglobulin of a single light-chain type; Ia-like (HLA-DR) antigen is present as well. While most T-cell proliferations exhibit the classic receptor for sheep erythrocytes, commercially available monoclonal antisera permit the secure identification of T cells and their subclassification into inducer-helper and cytotoxic-suppressor subsets. Surface markers have also allowed the separation of a fraction of patients with acute lymphocytic leukemia whose cells have T-lymphocyte markers from the majority whose cells show subtle evidence of early B-cell differentiation. PMID:6340492

Aisenberg, A C

1983-04-01

25

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

PubMed

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

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

2015-03-01

26

Blood microvesicles during chronic lymphoproliferative diseases.  

PubMed

The levels of CD19 (+) and CD20(+) microvesicles were estimated in the blood of patients with B-cell chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma by flow cytometry method. It was found that the number of B cell microvesicles is several times higher in patients than in volunteers. The level of CD20 (+) microvesicles directly correlated with the number of CD20(+) lymphocytes in patients with chronic lymphoproliferative diseases. Extramedullary tumors cells can be a source of CD19 (+) microvesicles. PMID:24319739

Domnikova, N P; Dolgikh, T Yu; Sholenberg, E V; Vorontsova, E V; Goreva, O B; Mel'nikova, E V; Gorbachenko, E A; Grishanova, A Yu

2013-11-01

27

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

PubMed Central

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

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

2012-01-01

28

A lymphoproliferative disease in Manx cats with similarities to autoimmune lymphoproliferative syndrome (ALPS) in people  

Microsoft Academic Search

In 2009–2010, an unusual lymphoproliferative disease was identified in multiple siblings from successive litters of Manx cats, suggesting a genetic predisposition to development of this disease. Presentation of disease in the cats had multiple similarities with the human disease ALPS, a rare inherited disorder that causes persistent lymphoproliferation, together with variable manifestations of autoimmunity and increased susceptibility to neoplasia. The

D Aberdein; JS Munday; KG Thompson; RA Fairley

2011-01-01

29

Rare presentation of post-transplant lymphoproliferative disorder isolated to gastroesophageal junction  

PubMed Central

Post transplant lymphoproliferative disorder (PTLD) represents a life threatening disorder occurring after transplantation, ranging from a polyclonal mononucleosis like illness to a monomorphic high grade neoplasm with cytologic and histopathologic evidence indicative of transformation to lymphoma. PTLD of diffuse large B-cell lymphoma (DLBCL) subtype, isolated to the esophagus is a rare diagnosis. We describe the first case of an immunocompromised adult patient diagnosed with DLBCL-PTLD limited to his esophagus without an associated mass or locoregional lymphadenopathy on imaging since the institution of the revised Cheson criteria, which includes positron emission tomography-computed tomography as the standard staging modality. Even more unique to our case was the suggestion of underlying cytomegalovirus (CMV) gastritis leading to a hypothesis about a less well understood relationship between CMV and Epstein Barr virus (EBV). In the post transplant setting, immunocompromised state, or EBV positive state, upper gastrointestinal symptoms should prompt investigation with an upper endoscopy (EGD). Additionally, specific to our case, the fact that the patients’ presentation was suspicious for CMV gastritis raises the possibility that the CMV infection predated his PTLD increasing his risk of acquiring PTLD. This reemphasizes the importance and diagnostic utility of early screening with EGD in patients after transplantation. PMID:24363831

Haverkos, Brad M; Oza, Veeral M; Johnson, Andrea; Walker, Jon; Shana’ah, Arwa

2013-01-01

30

Rapamycin improves lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome (ALPS).  

PubMed

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by defective Fas-mediated apoptosis, leading to lymphadenopathy, hepatosplenomegaly, and an increased number of double-negative T cells (DNTs). Treatment options for patients with ALPS are limited. Rapamycin has been shown to induce apoptosis in normal and malignant lymphocytes. Since ALPS is caused by defective lymphocyte apoptosis, we hypothesized that rapamycin would be effective in treating ALPS. We tested this hypothesis using rapamycin in murine models of ALPS. We followed treatment response with serial assessment of DNTs by flow cytometry in blood and lymphoid tissue, by serial monitoring of lymph node and spleen size with ultrasonography, and by enzyme-linked immunosorbent assay (ELISA) for anti-double-stranded DNA (dsDNA) antibodies. Three-dimensional ultrasound measurements in the mice correlated to actual tissue measurements at death (r = .9648). We found a dramatic and statistically significant decrease in DNTs, lymphadenopathy, splenomegaly, and autoantibodies after only 4 weeks when comparing rapamycin-treated mice with controls. Rapamycin induced apoptosis through the intrinsic mitochondrial pathway. We compared rapamycin to mycophenolate mofetil, a second-line agent used to treat ALPS, and found rapamycin's control of lymphoproliferation was superior. We conclude that rapamycin is an effective treatment for murine ALPS and should be explored as treatment for affected humans. PMID:16757690

Teachey, David T; Obzut, Dana A; Axsom, Kelly; Choi, John K; Goldsmith, Kelly C; Hall, Junior; Hulitt, Jessica; Manno, Catherine S; Maris, John M; Rhodin, Nicholas; Sullivan, Kathleen E; Brown, Valerie I; Grupp, Stephan A

2006-09-15

31

Rapamycin improves lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome (ALPS)  

PubMed Central

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by defective Fas-mediated apoptosis, leading to lymphadenopathy, hepatosplenomegaly, and an increased number of double-negative T cells (DNTs). Treatment options for patients with ALPS are limited. Rapamycin has been shown to induce apoptosis in normal and malignant lymphocytes. Since ALPS is caused by defective lymphocyte apoptosis, we hypothesized that rapamycin would be effective in treating ALPS. We tested this hypothesis using rapamycin in murine models of ALPS. We followed treatment response with serial assessment of DNTs by flow cytometry in blood and lymphoid tissue, by serial monitoring of lymph node and spleen size with ultrasonography, and by enzyme-linked immunosorbent assay (ELISA) for anti–double-stranded DNA (dsDNA) antibodies. Three-dimensional ultrasound measurements in the mice correlated to actual tissue measurements at death (r = .9648). We found a dramatic and statistically significant decrease in DNTs, lymphadenopathy, splenomegaly, and autoantibodies after only 4 weeks when comparing rapamycin-treated mice with controls. Rapamycin induced apoptosis through the intrinsic mitochondrial pathway. We compared rapamycin to mycophenolate mofetil, a second-line agent used to treat ALPS, and found rapamycin's control of lymphoproliferation was superior. We conclude that rapamycin is an effective treatment for murine ALPS and should be explored as treatment for affected humans. PMID:16757690

Teachey, David T.; Obzut, Dana A.; Axsom, Kelly; Choi, John K.; Goldsmith, Kelly C.; Hall, Junior; Hulitt, Jessica; Manno, Catherine S.; Maris, John M.; Rhodin, Nicholas; Sullivan, Kathleen E.; Brown, Valerie I.; Grupp, Stephan A.

2006-01-01

32

Post-transplant lymphoproliferative disorder presenting as a tumor adjacent to the renal allograft: A case report and review of the literature  

PubMed Central

Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication of solid organ transplantation. The current report presents the case of a 42-year-old male who developed PTLD within the first year following renal transplantation. The disorder manifested as a tumor adjacent to the lower pole of the renal allograft and resulted in urinary obstruction. Durable complete remission was achieved as a result of surgical resection followed by a reduction in immunosuppression and low-dose rituximab-based chemotherapy, indicating that this therapeutic strategy may be safe and effective for the treatment of specific cases of localized and resectable PTLD. PMID:25364435

GAO, CHEN; PENG, LONGKAI; PENG, FENGHUA; TUO, TING; LI, DAIQIANG

2014-01-01

33

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 ...

34

Rituximab treatment for posttransplant lymphoproliferative disorder (PTLD) induces complete remission of recurrent nephrotic syndrome  

Microsoft Academic Search

A 12-year-old Japanese boy who underwent kidney transplantation with a kidney from his mother developed severe proteinuria immediately after the operation. Because his original disease was nephrotic syndrome (focal segmental glomerulosclerosis, or FSGS) and electron microscopic examination of the renal biopsy showed foot process fusion, we diagnosed this as a recurrence of nephrotic syndrome to the transplanted kidney. Four months

Kandai Nozu; Kazumoto Iijima; Masato Fujisawa; Atsuko Nakagawa; Norishige Yoshikawa; Masafumi Matsuo

2005-01-01

35

Clinicopathologic features of post-transplant lymphoproliferative disorders arising after pediatric small bowel transplant.  

PubMed

Few studies examined the clinicopathologic features of PTLD arising in pediatric SBT patients. Particularly, the association between ATG and PTLD in this population has not been described. Retrospective review of 81 pediatric patient charts with SBT--isolated or in combination with other organs--showed a PTLD incidence of 11%, occurring more frequently in females (median age of four yr) and with clinically advanced disease. Monomorphic PTLD was the most common histological subtype. There was a significant difference in the use of ATG between patients who developed PTLD and those who did not (p < 0.01); a similar difference was seen with the use of sirolimus (p < 0.001). These results suggested a link between the combination of ATG and sirolimus and development of more clinically and histologically advanced PTLD; however, the risk of ATG by itself was not clear. EBV viral loads were higher in patients with PTLD, and median time between detection of EBV to PTLD diagnosis was three months. However, viral loads at the time of PTLD diagnosis were most often lower than at EBV detection, thereby raising questions on the correlation between decreasing viral genomes and risk of PTLD. PMID:24118781

Nassif, S; Kaufman, S; Vahdat, S; Yazigi, N; Kallakury, B; Island, E; Ozdemirli, M

2013-12-01

36

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...

37

Hepatitis C infection and lymphoproliferative disease: accidental comorbidities?  

PubMed

Chronic hepatitis C virus (HCV) infection has been associated with liver cancer and cirrhosis, autoimmune disorders such as thyroiditis and mixed cryoglobulinema, and alterations in immune function and chronic inflammation, both implicated in B cell lymphoproliferative diseases that may progress to non-Hodgkin lymphoma (NHL). HCV bound to B cell surface receptors can induce lymphoproliferation, leading to DNA mutations and/or lower antigen response thresholds. These findings and epidemiological reports suggest an association between HCV infection and NHL. We performed a systematic review of the literature to clarify this potential relationship. We searched the English-language literature utilizing Medline, Embase, Paper First, Web of Science, Google Scholar, and the Cochrane Database of Systematic Reviews, with search terms broadly defined to capture discussions of HCV and its relationship with NHL and/or lymphoproliferative diseases. References were screened to further identify relevant studies and literature in the basic sciences. A total of 62 reports discussing the relationship between HCV, NHL, and lymphoproliferative diseases were identified. Epidemiological studies suggest that at least a portion of NHL may be etiologically attributable to HCV, particularly in areas with high HCV prevalence. Studies that showed a lack of association between HCV infection and lymphoma may have been influenced by small sample size, short follow-up periods, and database limitations. The association appears strongest with the B-cell lymphomas relative to other lymphoproliferative diseases. Mechanisms by which chronic HCV infection promotes lymphoproliferative disease remains unclear. Lymphomagenesis is a multifactorial process involving genetic, environmental, and infectious factors. HCV most probably have a role in the lymphomagenesis but further study to clarify the association and underlying mechanisms is warranted. PMID:25473174

Khoury, Tawfik; Chen, Shmuel; Adar, Tomer; Jacob, E Ollech; Mizrahi, Meir

2014-11-21

38

Hepatitis C infection and lymphoproliferative disease: Accidental comorbidities?  

PubMed Central

Chronic hepatitis C virus (HCV) infection has been associated with liver cancer and cirrhosis, autoimmune disorders such as thyroiditis and mixed cryoglobulinema, and alterations in immune function and chronic inflammation, both implicated in B cell lymphoproliferative diseases that may progress to non-Hodgkin lymphoma (NHL). HCV bound to B cell surface receptors can induce lymphoproliferation, leading to DNA mutations and/or lower antigen response thresholds. These findings and epidemiological reports suggest an association between HCV infection and NHL. We performed a systematic review of the literature to clarify this potential relationship. We searched the English-language literature utilizing Medline, Embase, Paper First, Web of Science, Google Scholar, and the Cochrane Database of Systematic Reviews, with search terms broadly defined to capture discussions of HCV and its relationship with NHL and/or lymphoproliferative diseases. References were screened to further identify relevant studies and literature in the basic sciences. A total of 62 reports discussing the relationship between HCV, NHL, and lymphoproliferative diseases were identified. Epidemiological studies suggest that at least a portion of NHL may be etiologically attributable to HCV, particularly in areas with high HCV prevalence. Studies that showed a lack of association between HCV infection and lymphoma may have been influenced by small sample size, short follow-up periods, and database limitations. The association appears strongest with the B-cell lymphomas relative to other lymphoproliferative diseases. Mechanisms by which chronic HCV infection promotes lymphoproliferative disease remains unclear. Lymphomagenesis is a multifactorial process involving genetic, environmental, and infectious factors. HCV most probably have a role in the lymphomagenesis but further study to clarify the association and underlying mechanisms is warranted. PMID:25473174

Khoury, Tawfik; Chen, Shmuel; Adar, Tomer; Jacob, E Ollech; Mizrahi, Meir

2014-01-01

39

Reversible methotrexate associated lymphoproliferative disease evolving into Hodgkin's disease.  

PubMed

We describe a case of nodular sclerosing Hodgkin's disease (NSHD) developing in a 61-year-old woman with seropositive rheumatoid arthritis treated with oral methotrexate (MTX) 5 to 15 mg/week for 5 years. Computed tomography (CT) of the abdomen revealed splenomegaly and marked abdominal and retroperitoneal lymphadenopathy. MTX was discontinued; several weeks later prednisone 10 mg/day was added to control worsening polyarthralgia. Repeat CT at 3 months showed almost complete regression of the splenomegaly and lymphadenopathy. However, CT studies at 10 months showed asymptomatic progression of lymphadenopathy, which on biopsy revealed NSHD. Patients with apparently reversible MTX associated lymphoproliferative disorder require periodic monitoring for asymptomatic development of malignant lymphoma. PMID:10743830

Moseley, A C; Lindsley, H B; Skikne, B S; Tawfik, O

2000-03-01

40

Normalized Quantification by Real-Time PCR of Epstein-Barr Virus Load in Patients at Risk for Posttransplant Lymphoproliferative Disorders  

PubMed Central

The load of Epstein-Barr virus (EBV) in peripheral blood mononuclear cells of transplant recipients represents a predictive parameter for posttransplant lymphoproliferative disorders (PTLD). The aim of our work was to develop a rapid and reliable PCR protocol for the quantification of cell-associated EBV DNA in transplant recipients. In contrast to previous studies, a protocol that facilitated quantification independent of photometric nucleic acid analysis was established. We took advantage of the real-time PCR technology which allows for single-tube coamplification of EBV and genomic C-reactive protein (CRP) DNA. EBV copy numbers were normalized by division by the amount of CRP DNA, with the quotient representing the actual amount of amplifiable genomic DNA per reaction. Coamplification of CRP DNA did not result in a diminished detection limit for EBV. By using the protocol without normalization, EBV copy numbers in 4 out of 10 PTLD patients were within the normal range determined with data for 114 transplant recipients that served as controls. After normalization, however, all of the PTLD patients had a higher viral load than the control population, indicating an increased sensitivity of the assay. Moreover, EBV copy numbers obtained for one patient by conventional quantification and suggestive of relapsing PTLD were within normal range after normalization. We conclude that normalization of PCR signals to coamplified genomic DNA allows a more accurate quantification of cell-bound EBV. PMID:11158107

Jabs, Wolfram J.; Hennig, Holger; Kittel, Michael; Pethig, Klaus; Smets, Françoise; Bucsky, Peter; Kirchner, Holger; Wagner, Hans J.

2001-01-01

41

Treatment of rare co-occurrence of Epstein-Barr virus-driven post-transplant lymphoproliferative disorder and hemophagocytic lymphohistiocytosis after allogeneic stem cell transplantation.  

PubMed

In both conditions, post-transplant lymphoproliferative disorder (PTLD) and hemophagocytic lymphohistiocytosis (HLH), infection with Epstein-Barr virus (EBV) is a key mechanism: almost all PTLD in allogeneic stem cell transplantation (alloSCT) is caused by EBV-related neoplastic lymphoproliferation, and secondary HLH is most frequently triggered by EBV infection. Therefore, concomitant EBV-driven PTLD and HLH early after alloSCT require an approach to eliminate EBV and balance immune activation simultaneously. We report on a patient who developed simultaneous PTLD and signs of HLH on day 64 after alloSCT. Treatment was comprised of stopping cyclosporine, short-course dexamethasone, and 3 courses of rituximab. The patient showed full recovery and complete remission of lymphadenopathy. This result indicates that immediate reduction in EBV-carrying B cells by rituximab, suppression of general inflammation, and parallel support of reconstitution of long-term T-cell function, might be an appropriate therapeutic approach in this rare situation. PMID:25179757

Weber, T; Wickenhauser, C; Monecke, A; Gläser, C; Stadler, M; Desole, M; Ligeti, K; Behrmann, C; Müller-Tidow, C; Müller, L P

2014-12-01

42

Epstein-Barr virus-related post-transplant lymphoproliferative disorder occurring after bone marrow transplantation for aplastic anemia in Down's syndrome.  

PubMed

It is well established that Down's syndrome exhibits a predisposition to development of leukemia, however, association between aplastic anemia and Down's syndrome is exceptional. Herein, we describe a case of aplastic anemia occurring in Down's syndrome following post-transplant lymphoproliferative disorder (PTLD) after bone marrow transplantation (BMT). A 27-year-old Japanese male with Down's syndrome presented with a headache. Laboratory tests revealed severe pancytopenia, and bone marrow biopsy demonstrated hypocellular bone marrow with decrease of trilineage cells, which led to a diagnosis of aplastic anemia. One year after diagnosis, he was incidentally found to have an anterior mediastinal tumor, which was histopathologically diagnosed as seminoma. Subsequently, he received BMT from a female donor, and engraftment was observed. Three months after transplantation, he experienced cough and high fever. Biopsy specimen from the lung revealed diffuse proliferation of large-sized lymphoid cells expressing CD20 and EBER. These lymphoid cells had XY chromosomes. Thus, a diagnosis of EBV-associated PTLD was made. This is the seventh documented case of aplastic anemia occurring in Down's syndrome. Association between aplastic anemia and Down's syndrome has not been established, therefore, additional clinicopathological studies are needed. Moreover, this is the first case to undergo BMT for aplastic anemia in Down's syndrome. Although engraftment was observed, he developed EBV-positive PTLD. The neoplastic cells of the present case were considered to be of recipient origin, although the majority of PTLD cases with BMT are of donor origin. PMID:24427369

Furuya, Aya; Ishida, Mitsuaki; Hodohara, Keiko; Yoshii, Miyuki; Okuno, Hiroko; Horinouchi, Akiko; Nakanishi, Ryota; Harada, Ayumi; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Yoshida, Takashi; Okabe, Hidetoshi

2014-01-01

43

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...

44

Checking whether there is an increased risk of post-transplant lymphoproliferative disorder and other cancers with specific modern immunosuppression regimens in renal transplantation: Protocol for a network meta-analysis of randomized and observational studies  

PubMed Central

Background Patients undergoing renal transplant procedures require multi-agent immunosuppressive regimens both short term (induction phase) and long term (maintenance phase) to minimize the risk of organ rejection. There are several drug classes and agents for immunosuppression. Use of these agents may increase the risk of different harms including not only infections, but also malignancies including post-transplant lymphoproliferative disorder. There is a need to identify which regimens minimize the risk of such outcomes. The objective of this systematic review and network meta-analysis of randomized and observational studies is to explore whether certain modern regimens of immunosuppression used to prevent organ rejection in renal transplant patients are associated with an increased risk of post-transplant lymphoproliferative disorder and other malignancies. Methods/design ‘Modern’ regimens were defined to be those evaluated in controlled studies beginning in 1990 or later. An electronic literature search of Medline, Embase and the Cochrane Central Register of Controlled Trials has been designed by an experienced information specialist and peer reviewed by a second information specialist. Study selection and data collection will be performed by two reviewers. The outcomes of interest will include post-transplant lymphoproliferative disorder and other incident forms of malignancy occurring in adult renal transplant patients. Network meta-analyses of data from randomized and observational studies will be performed where judged appropriate based on a review of the clinical and methodological features of included studies. A sequential approach to meta-analysis will be used to combine data from different designs. Discussion Our systematic review will include both single-agent and multi-agent modern pharmacotherapy regimens in patients undergoing renal transplantation. It will synthesize malignancy outcomes. Our work will also add to the development of methods for network meta-analysis across study designs to assess treatment safety. Trial registration PROSPERO Registration Number: CRD42013006951 PMID:24559430

2014-01-01

45

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

Microsoft Academic Search

We report three patients who developed severe supraglottic airway obstruction due to Epstein-Barr virus lymphoproliferative\\u000a disease following allogeneic bone marrow transplantation. In addition to enlarged pharyngeal lymphoid tissue seen in all three\\u000a patients, two had supraglottic airway narrowing and two developed pulmonary lymphoproliferative disease. They were treated\\u000a with unmanipulated T cells or EBV-specific cytotoxic T lymphocytes. Life-threatening upper airway obstruction

Barry D. Fletcher; Helen E. Heslop; Sue C. Kaste; Sara Bodner

1998-01-01

46

[Systemic EBV+ T-cell lymphoproliferative disease of childhood].  

PubMed

Systemic EBV+ T-cell lymphoproliferative disease of childhood is a recent entity described in the 2008 World Health Organisation tumours of haematopoietic system and lymphoid tissues as a clonal T-cell EBV+ systemic proliferation. It occurs after acute or chronic active EBV infection. We report the case of a caucasian, immunocompetent 12-year-old girl, with no particular history, who presented with hemophagocytic lymphohistiocytosis in the aftermath of an infectious mononucleosis. Main symptoms were multiple organ failure, hepatosplenomegaly and pancytopenia. Histopathology of peripheral lymph node and bone marrow revealed a T-cell, CD8+, EBV+ lymphoproliferation. An elevated viral load was detected in blood by PCR. The patient died within 3 weeks. Since most of the cases have been reported in Asia and South America, few cases still have been described in Europe. Unlike B-cell lymphoproliferation in immunocompromised individuals, T-cell EBV+ lymphoproliferation occurs in immunocompetent patients and seems to be the consequence of a proliferative disorder of EBV-infected T-cells, attributed to a cytotoxic T-cell response deficiency. These T-cell proliferations are more frequently immunoreactive for CD8 than CD4. A key feature of the diagnosis might be EBV viral load. PMID:25132446

Lemaire, Anne-Sophie; Daussay, Dorothée; Bouchindhomme, Brigitte; Grardel, Nathalie; Botte, Astrid; Copin, Marie-Christine

2014-08-01

47

Lymphoproliferative disease in mice infected with murine gammaherpesvirus 68.  

PubMed Central

Murine gammaherpesvirus is a natural pathogen of wild rodents. In the laboratory it establishes an infection of epithelial cells and persists in B lymphocytes in a latent form. Inbred mice chronically infected with the virus develop a lymphoproliferative disease (LPD) similar to that seen in patients infected with Epstein-Barr virus. The frequency of LPD over a period of 3 years was 9% of all infected animals, with 50% of these displaying high grade lymphomas. The incidence of LPD was greatly increased when infected mice were treated with cyclosporin A. The majority of mice used in the experiments were BALB/c, although lymphomas were detected in mice on other genetic backgrounds, ie, CBA and B10Br. Lymphomas were associated with both lymphoid and nonlymphoid tissues (liver, lung, and kidney). In all cases of lymphomas studied thus far, there was a mixed B cell (B220+ve) and T cell (CD3+ve) phenotype. The B cells were light chain restricted, indicative of a clonal origin. Variable numbers of virus genome-positive cells were detected by in situ hybridization in and around the lymphomas. In contrast, no lytic antigen-positive cells were detected, indicating that genome-positive cells were either latently infected or undergoing an abortive infection. These observations suggest that murine gammaherpesvirus-infected mice may be an important model to study the pathogenesis of LPD associated with other gammaherpesviruses, such as Epstein-Barr virus. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7943173

Sunil-Chandra, N. P.; Arno, J.; Fazakerley, J.; Nash, A. A.

1994-01-01

48

Post-Transplant Skin Cancer: The Influence of Organ and Pre-Transplant Disease  

Microsoft Academic Search

Post-transplant skin malignancies have been extensively studied [1–6], but the role of the transplanted organ in the occurrence\\u000a of tumours is still discussed. This chapter reviews the epidemiological, clinical, and therapeutic aspects of skin cancers\\u000a in populations of kidney (KTR), heart (HTR), and liver transplant recipients (LTR). Furthermore, some data on the impact of\\u000a the pre-existing disease leading to organ

Sylvie Euvrard; Alain Claudy

49

X-linked lymphoproliferative disease: Genetic lesions and clinical consequences  

Microsoft Academic Search

X-linked lymphoproliferative disorder (XLP) was first described almost 30 years ago; remarkably, the three major manifestations\\u000a of XLP, fulminant infectious mononucleosis (FIM), lymphoma, and dysgammaglobulinemia, are all described in the report of the\\u000a initial kindred. Subsequent establishment of an XLP registry has led to recognition of more unusual phenotypes in affected\\u000a males; concurrently, much progress has been made in caring

Andrew J. MacGinnitie; Raif Geha

2002-01-01

50

Molecular genetic haplotype segregation studies in three families with X-linked lymphoproliferative disease  

Microsoft Academic Search

Three families with X-linked lymphoproliferative disease were studied. Affected males clinically presented with severe or fatal infectious mononucleosis, acquired hypogammaglobulinaemia, hypergammaglobulinaemia M, and malignant lymphoma including Hodgkin disease. Haplotype analysis using various DNA markers from Xq25-q27 allowed the prediction of the carrier status in females and identification of the XLP status in asymptomatic males.

V. Schuster; S. Seidenspinner; T. Grimm; W. Kreß; S. Zielen; M. Bock; H. W. Kreth

1994-01-01

51

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 ...

52

Gene Rearrangement in B and T-Lymphoproliferative Disease Detected by the Polymerase Chain Reaction  

Microsoft Academic Search

Gene rearrangement and monoclonality have been detected in normal cells and in lymphoproliferative disease by using the polymerase chain reaction and primers for the V and J regions of the lg heavy chain gene or T-cell receptor ychain gene. Using the lg primers monoclonality was detected in 20 of 20 normal B-lymphocyte clones and in 39 of 52 cases of

K. J. Trainor; M. J. Brisco; J. H. Wan; S. Neoh; S. Grist; A. A. Morley

53

Inflammatory bowel disease and lymphoproliferative disorders: the dust is starting to settle  

Microsoft Academic Search

The risk of lymphoproliferative disorders (LDs) has become a major concern for clinicians managing patients with inflammatory bowel disease (IBD). Yet it is difficult to distinguish the possible responsibility of immunosuppressive therapy from the background risk due to the inflammatory disorder itself. LDs are clonal B or T cell proliferation showing considerable heterogeneity and the incidence has increased since the

H Sokol; L Beaugerie

2009-01-01

54

Molecular signature of Epstein Barr virus-positive Burkitt lymphoma and post-transplant lymphoproliferative disorder suggest different roles for Epstein Barr virus  

PubMed Central

Epstein Barr virus (EBV) infection is commonly associated with human cancer and, in particular, with lymphoid malignancies. Although the precise role of the virus in the pathogenesis of different lymphomas is largely unknown, it is well recognized that the expression of viral latent proteins and miRNA can contribute to its pathogenetic role. In this study, we compared the gene and miRNA expression profile of two EBV-associated aggressive B non-Hodgkin lymphomas known to be characterized by differential expression of the viral latent proteins aiming to dissect the possible different contribution of such proteins and EBV-encoded miRNAs. By applying extensive bioinformatic inferring and an experimental model, we found that EBV+ Burkitt lymphoma presented with significant over-expression of EBV-encoded miRNAs that were likely to contribute to its global molecular profile. On the other hand, EBV+ post-transplant diffuse large B-cell lymphomas presented a significant enrichment in genes regulated by the viral latent proteins. Based on these different viral and cellular gene expression patterns, a clear distinction between EBV+ Burkitt lymphoma and post-transplant diffuse large B-cell lymphomas was made. In this regard, the different viral and cellular expression patterns seemed to depend on each other, at least partially, and the latency type most probably played a significant role in their regulation. In conclusion, our data indicate that EBV influence over B-cell malignant clones may act through different mechanisms of transcriptional regulation and suggest that potentially different pathogenetic mechanisms may depend upon the conditions of the interaction between EBV and the host that finally determine the latency pattern. PMID:25566237

Navari, Mohsen; Fuligni, Fabio; Laginestra, Maria A.; Etebari, Maryam; Ambrosio, Maria R.; Sapienza, Maria R.; Rossi, Maura; De Falco, Giulia; Gibellini, Davide; Tripodo, Claudio; Pileri, Stefano A.; Leoncini, Lorenzo; Piccaluga, Pier P.

2014-01-01

55

Development of an Epstein-Barr virus-associated lymphoproliferative disorder in a patient treated with azacitidine for chronic myelomonocytic leukaemia.  

PubMed

Some chemotherapeutic agents can cause iatrogenic lymphoproliferative disorders. In analogy to what has been observed with other nucleoside analogues such as cladribine and fludarabine, we document the first case of an Epstein-Barr virus-positive, iatrogenic immunodeficiency-associated, lymphoproliferative disease, formally resembling polymorphic post-transplant lymphoproliferative disease in a patient treated with azacitidine (Vidaza) for chronic myelomonocytic leukaemia (CMML). A 78-year-old female patient was diagnosed with CMML in January 2012, and treatment with azacitidine was initiated, which lasted for five cycles from February until June 2012. The patient was hospitalized in June 2012 under the suspicion of pneumonia. Transformation of the CMML was suspected at that time too. During hospitalization, a generalized enlargement of the lymph nodes and the spleen was noticed. The patient rapidly deteriorated and finally died of respiratory insufficiency. At autopsy, an Epstein-Barr virus-associated lymphoproliferative disorder, resembling polymorphic post-transplant lymphoproliferative disease with involvement of the lymph nodes, the spleen and the lung and causing necrotizing pneumonia, was diagnosed. Diagnostic criteria for diffuse large B-cell lymphoma or infectious mononucleosis-like lymphoproliferative disease were not met. This is the first documented case of an azacitidine-associated lymphoproliferative disease, raising awareness for possible not yet known side effects of this drug, which should be kept in mind by oncologists and pathologists. PMID:23625339

Menter, T; Schlageter, M; Bastian, L; Haberthür, R; Rätz Bravo, A E; Tzankov, A

2014-03-01

56

A novel latent membrane 2 transcript expressed in Epstein-Barr virus–positive NK- and T-cell lymphoproliferative disease encodes a target for cellular immunotherapy  

PubMed Central

Therapeutic targeting of virus-encoded proteins using cellular immunotherapy has proved successful for Epstein-Barr virus (EBV)–associated posttransplant lymphoproliferative disease. However, the more limited repertoire and immunogenicity of EBV-encoded proteins in other malignancies such as Hodgkin lymphoma and extranodal natural killer (NK)/T lymphoma has been more challenging to target. The immunosubdominant latent membrane protein 2 (LMP2) is considered the optimal target in such Latency II tumors, although data relating to its expression in T/NK malignancies are limited. In addressing the validity of LMP2 as an immunotherapeutic target we found that LMP2-specific effector CD8+ T cells recognized and killed EBV-positive NK- and T-cell tumor lines, despite an apparent absence of LMP2A protein and barely detectable levels of LMP2 transcripts from the conventional LMP2A and LMP2B promoters. We resolved this paradox by identifying in these lines a novel LMP2 mRNA, initiated from within the EBV terminal repeats and containing downstream, epitope-encoding exons. This same mRNA was also highly expressed in primary (extra-nodal) NK/T lymphoma tissue, with virtually undetectable levels of conventional LMP2A/B transcripts. Expression of this novel transcript in T/NK-cell lymphoproliferative diseases validates LMP2 as an attractive target for cellular immunotherapy and implicates this truncated LMP2 protein in NK- and T-cell lymphomagenesis. This study is registered at clinicaltrials.gov as NCT00062868. PMID:20671118

Fox, Christopher P.; Haigh, Tracey A.; Taylor, Graham S.; Long, Heather M.; Lee, Steven P.; Shannon-Lowe, Claire; O'Connor, Simon; Bollard, Catherine M.; Iqbal, Javeed; Chan, Wing C.; Rickinson, Alan B.; Bell, Andrew I.

2010-01-01

57

A novel latent membrane 2 transcript expressed in Epstein-Barr virus-positive NK- and T-cell lymphoproliferative disease encodes a target for cellular immunotherapy.  

PubMed

Therapeutic targeting of virus-encoded proteins using cellular immunotherapy has proved successful for Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disease. However, the more limited repertoire and immunogenicity of EBV-encoded proteins in other malignancies such as Hodgkin lymphoma and extranodal natural killer (NK)/T lymphoma has been more challenging to target. The immunosubdominant latent membrane protein 2 (LMP2) is considered the optimal target in such Latency II tumors, although data relating to its expression in T/NK malignancies are limited. In addressing the validity of LMP2 as an immunotherapeutic target we found that LMP2-specific effector CD8(+) T cells recognized and killed EBV-positive NK- and T-cell tumor lines, despite an apparent absence of LMP2A protein and barely detectable levels of LMP2 transcripts from the conventional LMP2A and LMP2B promoters. We resolved this paradox by identifying in these lines a novel LMP2 mRNA, initiated from within the EBV terminal repeats and containing downstream, epitope-encoding exons. This same mRNA was also highly expressed in primary (extra-nodal) NK/T lymphoma tissue, with virtually undetectable levels of conventional LMP2A/B transcripts. Expression of this novel transcript in T/NK-cell lymphoproliferative diseases validates LMP2 as an attractive target for cellular immunotherapy and implicates this truncated LMP2 protein in NK- and T-cell lymphomagenesis. This study is registered at clinicaltrials.gov as NCT00062868. PMID:20671118

Fox, Christopher P; Haigh, Tracey A; Taylor, Graham S; Long, Heather M; Lee, Steven P; Shannon-Lowe, Claire; O'Connor, Simon; Bollard, Catherine M; Iqbal, Javeed; Chan, Wing C; Rickinson, Alan B; Bell, Andrew I; Rowe, Martin

2010-11-11

58

Characterization of three overlapping deletions causing X-linked lymphoproliferative disease  

SciTech Connect

Blot hybridization was used to find DNA sequences missing in a male who lacked two-thirds of Xq25. The probes were used to discover two additional males with deletions resulting in X-linked lymphoproliferative disease (XLP). All three deletions have a region in common, and DXS739 is within this candidate region. The new deletions were also detectable using chromosome banding, and the smallest removes only one-third of Xq25. XLP is the only consequence of the deletions. 11 refs., 2 figs.

Skare, J.; Bailin Wu; Wyandt, H.; Milunsky, A. (Boston Univ., MA (United States)); Madan, S.; Pulijaal, V.; Nitowsky, H. (Albert Einstein College of Medicine, Bronx, NY (United States)); Purtilo, D.; Grierson, H. (Univ. of Nebraska, Omaha (United States)); Haber, D.; Wissink, J.; Housman, D. (Massachusetts Inst. of Technology, Cambridge (United States)); Nelson, D. (Baylor College, Houston, TX (United States)); Sylla, B.; Lenoir, G. (International Agency for Research on Cancer, Lyon (France)); Glaser, J. (Bronx-Jacobi Hospital, NY (United States)); White, B. (McMaster Univ., Hamilton, Ontario (Canada)); Holden, J. (Queen's Univ., Kingston, Ontario (Canada))

1993-04-01

59

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

PubMed

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

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

2015-02-01

60

Epstein Barr virus-associated lymphoproliferative diseases: the virus as a therapeutic target  

PubMed Central

Epstein Barr virus (EBV)-associated lymphoproliferative diseases (LPDs) express all EBV latent antigens (type III latency) in immunodeficient patients and limited antigens (type I and II latencies) in immunocompetent patients. Post-transplantation lymphoproliferative disease (PTLD) is the prototype exhibiting type III EBV latency. Although EBV antigens are highly immunogenic, PTLD cell proliferation remains unchecked because of the underlying immunosuppression. The restoration of anti-EBV immunity by EBV-specific T cells of either autologous or allogeneic origin has been shown to be safe and effective in PTLDs. Cellular therapy can be improved by establishing a bank of human leukocyte antigen-characterized allogeneic EBV-specific T cells. In EBV+ LPDs exhibiting type I and II latencies, the use of EBV-specific T cells is more limited, although the safety and efficacy of this therapy have also been demonstrated. The therapeutic role of EBV-specific T cells in EBV+ LPDs needs to be critically reappraised with the advent of monoclonal antibodies and other targeted therapy. Another strategy involves the use of epigenetic approaches to induce EBV to undergo lytic proliferation when expression of the viral thymidine kinase renders host tumor cells susceptible to the cytotoxic effects of ganciclovir. Finally, the prophylactic use of antiviral drugs to prevent EBV reactivation may decrease the occurrence of EBV+ LPDs. PMID:25613733

Tse, Eric; Kwong, Yok-Lam

2015-01-01

61

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

PubMed Central

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 describe the widespread distribution, genetic diversity, pathogenesis, and evolution of LPDV in the United States. Characterization of the provirus genome of the index LPDV case from North America demonstrated an 88% nucleotide identity to the Israeli prototype strain. Although phylogenetic analysis indicated that the majority of viruses fell into a single North American lineage, a small subset of viruses from South Carolina were most closely related to the Israeli prototype. These results suggest that LPDV was transferred between continents to initiate outbreaks of disease. However, the direction (New World to Old World or vice versa), mechanism, and time frame of the transcontinental spread currently remain unknown. PMID:24503062

Allison, Andrew B.; Keel, M. Kevin; Philips, Jamie E.; Cartoceti, Andrew N.; Munk, Brandon A.; Nemeth, Nicole M.; Welsh, Trista I.; Thomas, Jesse M.; Crum, James M.; Lichtenwalner, Anne B.; Fadly, Aly M.; Zavala, Guillermo; Holmes, Edward C.; Brown, Justin D.

2014-01-01

62

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 Central

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

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

2014-01-01

63

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

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

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

64

Staged Hand-Assisted Bilateral Native Nephrectomy for Management of Posttransplant Polyuria in an Adult with Dent's Disease  

PubMed Central

Polyuria after kidney transplantation causes graft dysfunction and increased thrombotic risk. We present a case of a polyuric adult with Dent's disease who underwent staged bilateral native nephrectomies, the first operation before transplant and the second four months after transplant. This led to improved allograft function maintained during four years of follow-up. The retroperitoneal laparoscopic approach was well tolerated and allowed continuation of peritoneal dialysis before transplantation. A staged approach helps regulate fluid balance perioperatively and may be tailored to individual need according to posttransplant urine output. This novel approach should be considered for polyuric patients with tubular dysfunction including Dent's disease. PMID:25649339

Montero, Rosa M.; Olsburgh, Jonathon

2015-01-01

65

Lymphoma and other lymphoproliferative disorders in inflammatory bowel disease: a review.  

PubMed

The lymphoproliferative disorders (LDs) are a heterogeneous group of at least 70 conditions that result from the clonal proliferation of B, T, and NK cells. Inflammatory bowel disease (IBD)-associated lymphomas are typically B-cell LD, while T-cell or Hodgkin's lymphomas are rare. In IBD patients not on immunosuppression, the risk of LD seems to be similar or slightly higher than the background population risk. Thiopurine therapy is associated with an increased risk: the relative risk is increased four- to sixfold and the absolute risk varies between 1 in 4000-5000 for those aged 20-29 to 1 in 300-400 in those over 70. It is difficult to quantify the risk of anti- tumor necrosis factor (TNF) therapy alone; however, it appears to be less than for thiopurines alone. There is particular concern regarding the development of post-transplant-like LD in those with latent epstein-barr virus (EBV) infection exposed to immunosuppressives, the occurrence of hepatosplenic T cell lymphoma in patients treated with combination anti-TNF and thiopurine therapy, and the development of hemophagocytic lymphohistiocytosis in those who acquire a primary EBV or other infections while on immunosuppressive medication. There are currently no guidelines for monitoring EBV (or other virus) status in patients on immunosuppression, although it could be used to monitor those who have a prior history of lymphoma and are about to start a thiopurine or anti-TNF agent. In discussing the risks of lymphoproliferative disorders associated with agents used for the treatment of IBD, patients can often be reassured that the benefits of such therapy still outweigh the small, but real, risks. PMID:23094824

Subramaniam, Kavitha; D'Rozario, James; Pavli, Paul

2013-01-01

66

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

PubMed Central

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 TCR?/?+ 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

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

2014-01-01

67

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

MedlinePLUS

... Results of Study Researchers led by V. Koneti Rao, M.D., and Michael Lenardo, M.D., of ... A, Lo B, Pittaluga S, Jaffe ES, Fleisher TA, Rao VK, Lenardo MJ. Natural history of autoimmune lymphoproliferative ...

68

Using flow cytometry to screen patients for X-linked lymphoproliferative disease due to SAP deficiency and XIAP deficiency  

Microsoft Academic Search

X-linked lymphoproliferative disease is a rare congenital immunodeficiency that is most often caused by mutations in SH2D1A, the gene encoding signaling lymphocyte activation molecule (SLAM)-associated protein (SAP). XLP caused by SAP deficiency is most often characterized by fulminant mononucleosis\\/EBV- associated hemophagocytic lymphohistiocytosis (HLH), lymphoma, and dysgammaglobulinemia. XLP has also been found to be caused by mutations in BIRC4, the gene

Rebecca A. Marsh; Jack J. Bleesing; Alexandra H. Filipovich

2010-01-01

69

Inflammatory bowel disease and lymphoproliferative disorders: the dust is starting to settle.  

PubMed

The risk of lymphoproliferative disorders (LDs) has become a major concern for clinicians managing patients with inflammatory bowel disease (IBD). Yet it is difficult to distinguish the possible responsibility of immunosuppressive therapy from the background risk due to the inflammatory disorder itself. LDs are clonal B or T cell proliferation showing considerable heterogeneity and the incidence has increased since the 1970s. The strongest and best-established risk factors for LDs are primary and acquired immunodeficiency (HIV, immunosuppressant), notably via defective immune surveillance of Epstein-Barr virus. In many auto-immune diseases (eg, Sjögren's syndrome), inflammatory diseases (eg, rheumatoid arthritis) or chronic suppuration (chronic pyothorax), the risk of LD is increased. In IBD patients, in general, the risk of LD seems to be similar to or very slightly higher than in the general population. The role of immunosuppressants in lymphomagenesis is difficult to individualise because other factors potentially involved are inter-linked. Concordant data suggest that thiopurine therapy is associated with a moderately increased risk of LD. Data regarding methotrexate are scarce and come from diseases other than IBD but the risk seems low. Data regarding risk of LD in IBD patients receiving anti-tumour necrosis factor alpha (TNFalpha) agents are insufficient at this time, mainly because most of the patients are co-treated with thiopurines. The recently individualised risks of hepatosplenic T cell lymphoma and fatal post-mononucleosis LD, in young male patients with IBD who are co-treated with anti-TNFalpha and thiopurines, and EBV-seronegative IBD males, respectively, are probably low but remain to be better quantified. PMID:19749141

Sokol, H; Beaugerie, L

2009-10-01

70

Follow-up of post-transplant minimal residual disease and chimerism in childhood lymphoblastic leukaemia: 90 d to react.  

PubMed

Relapse after transplantation is a major cause of treatment failure in paediatric acute lymphoblastic leukaemia (ALL). Here, we report the findings of a prospective national study designed to investigate the feasibility of immune intervention in children in first or subsequent remission following myeloablative conditioning. This study included 133 children who received a transplant for ALL between 2005 and 2008. Minimal Residual Disease (MRD) based on T cell receptor/immunoglobulin gene rearrangements was measured on days -30, 30, 90 and 150 post-transplantation. Ciclosporin treatment was rapidly discontinued and donor lymphocyte infusions (DLI) were programmed for patients with a pre- or post-transplant MRD status ?10(-3) . Only nine patients received DLI. Pre- and post-transplant MRD status, and the duration of ciclosporin were independently associated with 5-year overall survival (OS), which was 62·07% for the whole cohort. OS was substantially higher in patients cleared of MRD than in those with persistent MRD (52·3% vs. 14·3%, respectively). Only pre-transplant MRD status (Hazard Ratio 2·57, P = 0·04) and duration of ciclosporin treatment (P < 0·001) were independently associated with relapse. The kinetics of chimerism were not useful for predicting relapse, whereas MRD monitoring up to 90 d post-transplantation was a valuable prognostic tool to guide therapeutic intervention. PMID:25522886

Pochon, Cécile; Oger, Emmanuel; Michel, Gérard; Dalle, Jean-Hugues; Salmon, Alexandra; Nelken, Brigitte; Bertrand, Yves; Cavé, Hélène; Cayuela, Jean-Michel; Grardel, Nathalie; Macintyre, Elizabeth; Margueritte, Geneviève; Méchinaud, Françoise; Rohrlich, Pierre; Paillard, Catherine; Demeocq, François; Schneider, Pascale; Plantaz, Dominique; Poirée, Marilyne; Eliaou, Jean-François; Semana, Gilbert; Drunat, Séverine; Jonveaux, Philippe; Bordigoni, Pierre; Gandemer, Virginie

2015-04-01

71

Systemic Epstein-Barr virus positive T-cell lymphoproliferative disease of childhood with hemophagocytic syndrome.  

PubMed

Epstein-Barr virus (EBV) associated lymphoproliferative disease (LPD) are commonly derived from B-cells, however, it is becoming more and more apparently that EBV can also infect T-lymphocytes. Systemic EBV positive T-cell LPD of childhood is rare and characterized by an extremely aggressive course and poor prognosis. Here, we report a 22-year-old female of systemic EBV positive TLPD with acute EBV infection and review the clinical features of this disorder. A 22-year-old previously healthy female without immunocompromised status presented with persisting coach and fever resistant to conventional therapies. Physical examination showed hemorrhage and hepatosplenomegaly. Laboratory examinations revealed severe pancytopenia, disseminated intra-vascular coagulopathy (DIC), and anti-EBV-IgM positivity. Peripheral blood smears and bone marrow investigation identified a number of atypical lymphocytes. Flow cytometry (FCM) did not show any significant evidence of leukemia or lymphoma. The lymph node biopsy showed apparent infiltration of lymphocytes, which expressed CD2+, CD3+, CD7+ and TIA1+. There was no CD20+ or CD56+ cells. EBV early RNA (EBER) was positive. Cytogenetic analysis showed a normal karyotype. T-cell receptor (TCR) gene rearrangement revealed a polyclonal pattern. The patient received prednisolone and IVIG therapy with a transient good condition, and then died of multiorgan failure one week after diagnosis. PMID:25400806

Chen, Guoshu; Chen, Li; Qin, Xiaohua; Huang, Zhuoya; Xie, Xiaoling; Li, Guowei; Xu, Bing

2014-01-01

72

Primary cold agglutinin-associated lymphoproliferative disease: a B-cell lymphoma of the bone marrow distinct from lymphoplasmacytic lymphoma  

PubMed Central

Primary chronic cold agglutinin disease is a rare hemolytic disease mediated by monoclonal IGHV4-34-encoded cold agglutinins with a predominant specificity for the blood group antigen I. Bone marrow from 54 patients was studied to type the underlying lymphoproliferative disorder better. Bone marrow biopsies showed circumscribed intra-parenchymatous nodules with small monotonous monoclonal B cells in 40/54 patients (median infiltration: 10% of marrow cells) with a CD20+, IgMs+, IgDs+, CD27+, CD5?/+, CD11c?, CD23?, CD38? immunophenotype. Neither plasmacytoid cytological features nor expression of plasma cell differentiation-associated transcription factors MUM1, XBP1 and BLIMP1 were noted in these B cells. However, a limited number of mature monoclonal IgM+, IgD? plasma cells were present outside the lymphoid nodules and were diffusely scattered throughout the marrow. Of interest, the MYD88 L265P mutation, typical of lymphoplasmacytic lymphoma, was not detected (17/17 cases). Somatically mutated monoclonal IGHV4-34 gene rearrangement was demonstrated in eight patients with frozen samples (mean sequence homology 95.4%). However, mutations of BCL6 intron 1 were not demonstrated, except in one patient, suggesting that the lymphoma cells had not matured in the germinal center. In conclusion, cold agglutinin-associated lymphoproliferative disease displays homogeneous histological and immunophenotypic features. The absence of plasmacytoid cells, the presence of plasma cells predominantly outside the nodular lymphoid infiltrates, IGHV4-34 restriction and absence of MYD88 L265P mutation strongly suggest that cold agglutinin-associated lymphoproliferative disease is a distinct entity that is different from lymphoplasmacytic lymphoma. PMID:24143001

Randen, Ulla; Trøen, Gunhild; Tierens, Anne; Steen, Chloé; Warsame, Abdirashid; Beiske, Klaus; Tjønnfjord, Geir E.; Berentsen, Sigbjørn; Delabie, Jan

2014-01-01

73

Autoimmune lymphoproliferative syndrome in pregnancy: A case of favorable mother-fetal outcome in a well-controlled disease.  

PubMed

The autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by the dysregulation of the Fas apoptotic pathway. The Fas gene is expressed at the maternal-fetal interface and is involved in the regulation of immune response and implantation. Altered Fas expression may result in altered apoptosis and, ultimately, affect both the immune response and implantation; it is in fact associated with recurrent pregnancy loss, preterm premature rupture of membranes and pre-eclampsia. Currently, there are over 500 cases of ALPS reported worldwide from various racial and ethnic backgrounds. Up to date, the published work contains no specific reports on pregnancy outcome in women affected by ALPS. We present a case of full-term uneventful pregnancy in a patient affected by ALPS. A specific clinical follow-up in a pregnant woman with primary immunologic disease is suggested. PMID:25302402

Patti, Simona; Perrone, Giuseppina; De Pratti, Valentina; Quinti, Isabella; Milito, Cinzia; Brunelli, Roberto

2015-03-01

74

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

PubMed Central

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

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

2014-01-01

75

SATB1 overexpression promotes malignant T-cell proliferation in cutaneous CD30+ lymphoproliferative disease by repressing p21.  

PubMed

Cutaneous CD30(+) lymphoproliferative disease (CD30(+)LPD), characterized by the presence of CD30(+) anaplastic large T cells, comprises the second most common group of cutaneous T-cell lymphoma (CTCL). However, little is known about the pathobiology of the CD30(+) lymphoma cells, as well as the mechanisms of disease progression. Here we report that Special AT-rich region binding protein 1 (SATB1), a thymocyte specific chromatin organizer, is over-expressed in CD30(+) lymphoma cells in most CD30(+)LPDs, and its expression is upregulated during disease progression. Our findings show that SATB1 silencing in CD30(+)LPD cells leads to G1 cell cycle arrest mediated by p21 activation. Using chromatin immunoprecipitation, luciferase assays, and mutational analysis, we demonstrate that SATB1 directly regulates the transcription of p21 in a p53-independent manner. Moreover, DNA demethylation on a specific CpG-rich region of the SATB1 promoter is associated with the upregulation of SATB1 during disease progression. These experiments define a novel SATB1-p21 pathway in malignant CD30(+) T lymphocytes, which provides novel molecular insights into the pathogenesis of CD30(+)LPDs and possibly leads to new therapies. PMID:24747435

Wang, Yang; Gu, Xiaoguang; Zhang, Gaolei; Wang, Lin; Wang, Tingting; Zhao, Yun; Zhang, Xiuyan; Zhou, Youwen; Kadin, Marshall; Tu, Ping

2014-05-29

76

Blood dendritic cell levels associated with impaired IL-12 production and T-cell deficiency in patients with kidney disease: implications for post-transplant viral infections  

PubMed Central

Summary Reduced pretransplant blood myeloid dendritic cell (mDC) levels are associated with post-transplant BK viremia and cytomegalovirus (CMV) disease after kidney transplantation. To elucidate potential mechanisms by which mDC levels might influence these outcomes, we studied the association of mDC levels with mDC IL- 12 production and T-cell level/function. Peripheral blood (PB) was studied in three groups: (i) end stage renal disease patients on hemodialysis (HD; n = 81); (ii) chronic kidney disease stage IV-V patients presenting for kidney transplant evaluation or the day of transplantation (Eval/Tx; n = 323); and (iii) healthy controls (HC; n = 22). Along with a statistically significant reduction in mDC levels, reduced CD8+ T-cell levels were also demonstrated in the kidney disease groups compared with HC. Reduced PB mDC and monocyte-derived DC (MoDC) IL-12 production was observed after in vitro LPS stimulation in the HD versus HC groups. Finally, ELISpot assays demonstrated less robust CD3+ INF-? responses by MoDCs pulsed with CMV pp65 peptide from HD patients compared with HC. PB mDC level deficiency in patients with kidney disease is associated with deficient IL-12 production and T-cell level/function, which may explain the known correlation of CD8+ T-cell lymphopenia with deficient post-transplant antiviral responses. PMID:24963818

Chen, Ping; Sun, Qianmei; Huang, Yanfei; Atta, Mohamed G.; Turban, Sharon; Segev, Dorry L.; Marr, Kieren A.; Naqvi, Fizza F.; Alachkar, Nada; Kraus, Edward S.; Womer, Karl L.

2015-01-01

77

Autoimmune Lymphoproliferative Syndrome (ALPS)  

MedlinePLUS

... JavaScript on. Read more information on enabling JavaScript. Autoimmune Lymphoproliferative Syndrome (ALPS) Top Banner Content Area Skip Content Marketing Share this: Main Content Area Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder ...

78

Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV lymphoproliferative disease following T-cell--depleted SCT  

Microsoft Academic Search

Reactivation of the Epstein-Barr virus (EBV) after allogeneic stem cell transplantation (allo-SCT) may evoke a protective cellular immune response or may be complicated by the development of EBV-lymphoproliferative disease (EBV-LPD). So far, very little is known about the incidence, recurrence, and sequelae of EBV reactivation following allo-SCT. EBV reactivation was retrospectively monitored in 85 EBV-seropositive recipients of a T-cell--depleted (TCD)

Joost W. J. van Esser; Bronno van der Holt; Ellen Meijer; Hubert G. M. Niesters; J. J. Cornelissen; R. Trenschel; S. F. Thijsen; Loon van A. M; L. F. Verdonck; F. Frassoni; A. Bacigalupo; B. Löwenberg; U. W. Schaefer; J. W. Gratama; A. D. M. E. Osterhaus

2001-01-01

79

Systematic Epstein-Barr virus-positive T-cell lymphoproliferative disease presenting as a persistent fever and cough: a case report  

PubMed Central

Introduction Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is an extremely rare disorder and classically arises following primary acute or chronic active Epstein-Barr virus infection. It is characterized by clonal proliferation of Epstein-Barr virus-infected T-cells with an activated cytotoxic phenotype. This disease has a rapid clinical course and is more frequent in Asia and South America, with relatively few cases being reported in Western countries. The clinical and pathological features of the disease overlap with other conditions including infectious mononucleosis, chronic active Epstein-Barr virus infection, hemophagocytic lymphohistiocytosis and natural killer cell malignancies. We describe the rare case of systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease in a 16-year-old Malay boy. Case presentation He presented with a six-month history of fever and cough, with pulmonary and mediastinal lymphadenopathy and severe pancytopenia. Medium- to large-sized, CD8+ and Epstein-Barr virus-encoded RNA-positive atypical lymphoid cells were present in the bone marrow aspirate. He subsequently developed fatal virus-associated hemophagocytic syndrome and died due to sepsis and multiorgan failure. Conclusions Although systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is a disorder which is rarely encountered in clinical practice, our case report underlines the importance of a comprehensive diagnostic approach in the management of this disease. A high level of awareness of the disease throughout the diagnosis process for young patients who present with systemic illness and hemophagocytic syndrome may be of great help for the clinical diagnosis of this disease. PMID:25163591

2014-01-01

80

Distinct B-cell and T-cell lymphoproliferative disease prevalence among dog breeds indicates heritable risk.  

PubMed

Immunophenotypes in lymphoproliferative diseases (LPD) are prognostically significant, yet causative factors for these conditions, and specifically those associated with heritable risk, remain elusive. The full spectrum of LPD seen in humans occurs in dogs, but the incidence and lifetime risk of naturally occurring LPD differs among dog breeds. Taking advantage of the limited genetic heterogeneity that exists within dog breeds, we tested the hypothesis that the prevalence of LPD immunophenotypes would differ among different breeds. The sample population included 1,263 dogs representing 87 breeds. Immunophenotype was determined by the presence of clonal rearrangements of immunoglobulin heavy chain or T-cell receptor gamma chain. The probability of observing the number of B-cell or T-cell tumors in a particular breed or breed group was compared with three reference populations. Significance was computed using chi2 test, and logistic regression was used to confirm binomial predictions. The data show that, among 87 breeds tested, 15 showed significant differences from the prevalence of LPD immunophenotypes seen across the dog population as a whole. More significantly, elevated risk for T-cell LPD seems to have arisen ancestrally and is retained in related breed groups, whereas increased risk for B-cell disease may stem from different risk factors, or combinations of risk factors, arising during the process of breed derivation and selection. The data show that domestic dogs provide a unique and valuable resource to define factors that mediate risk as well as genes involved in the initiation of B-cell and T-cell LPD. PMID:15994938

Modiano, Jaime F; Breen, Matthew; Burnett, Robert C; Parker, Heidi G; Inusah, Seidu; Thomas, Rachael; Avery, Paul R; Lindblad-Toh, Kerstin; Ostrander, Elaine A; Cutter, Gary C; Avery, Anne C

2005-07-01

81

An essential role for ?-herpesvirus latency-associated nuclear antigen homolog in an acute lymphoproliferative disease of cattle.  

PubMed

Wildebeests carry asymptomatically alcelaphine herpesvirus 1 (AlHV-1), a ?-herpesvirus inducing malignant catarrhal fever (MCF) to several ruminant species (including cattle). This acute and lethal lymphoproliferative disease occurs after a prolonged asymptomatic incubation period after transmission. Our recent findings with the rabbit model indicated that AlHV-1 infection is not productive during MCF. Here, we investigated whether latency establishment could explain this apparent absence of productive infection and sought to determine its role in MCF pathogenesis. First, whole-genome cellular and viral gene expression analyses were performed in lymph nodes of MCF-developing calves. Whereas a severe disruption in cellular genes was observed, only 10% of the entire AlHV-1 genome was expressed, contrasting with the 45% observed during productive infection in vitro. In vivo, the expressed viral genes included the latency-associated nuclear antigen homolog ORF73 but none of the regions known to be essential for productive infection. Next, genomic conformation analyses revealed that AlHV-1 was essentially episomal, further suggesting that MCF might be the consequence of a latent infection rather than abortive lytic infection. This hypothesis was further supported by the high frequencies of infected CD8(+) T cells during MCF using immunodetection of ORF73 protein and single-cell RT-PCR approaches. Finally, the role of latency-associated ORF73 was addressed. A lack of ORF73 did not impair initial virus replication in vivo, but it rendered AlHV-1 unable to induce MCF and persist in vivo and conferred protection against a lethal challenge with a WT virus. Together, these findings suggest that a latent infection is essential for MCF induction. PMID:23630278

Palmeira, Leonor; Sorel, Océane; Van Campe, Willem; Boudry, Christel; Roels, Stefan; Myster, Françoise; Reschner, Anca; Coulie, Pierre G; Kerkhofs, Pierre; Vanderplasschen, Alain; Dewals, Benjamin G

2013-05-21

82

Disclosing the CXCR4 Expression in Lymphoproliferative Diseases by Targeted Molecular Imaging  

PubMed Central

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.

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

2015-01-01

83

[The larynx in lymphoproliferative and myeloproliferative diseases. Part II: Laryngeal autopsy findings and discussion].  

PubMed

Lymphoreticular neoplasms of the larynx are rare and comprise a heterogeneous group of tumors. A systematic survey of the literature and autoptic evaluation of the larynx in a relatively small number of patients with systemic lymphoreticular malignancies yielded the following findings: Primary tumors of the larynx must be clearly distinguished from laryngeal involvement by systemic or leukemic infiltrations. By far the most common primary hemopoietic tumors of the larynx are extramedullary plasmacytoma (about 90 cases published) and non-Hodgkin's lymphoma (NHL; about 65 cases published). Primary Hodgkin's disease, granulocytic sarcoma and mast cell sarcoma are extremely rare at this site. Plasmacytoma and NHL both preferentially involve the supraglottis. The subglottis is infrequently affected. Laryngeal plasmacytoma and NHL usually present clinically as localized stage IE and IIE tumors that exhibit no significant tendency to recur or generalize. The therapy of choice is local irradiation while chemotherapy should be reserved for recurrent or progressive disease. Prognosis is favourable in most cases of primary laryngeal plasmacytoma and NHL. Secondary involvement of the larynx by systemic lesions or leukemic infiltrations is usually associated with a very poor prognosis. The prognosis of patients with laryngeal involvement in acute or chronic myeloid leukemia is always poor. Although the histopathological diagnoses given in many case reports are often difficult to compare because of differences in terminology, there seems to be a marked preponderance of B-cell tumors of high-grade malignancy (centroblastic or immunoblastic lymphoma in the Kiel classification of NHL) that probably represents lymphomas originating from mucosa-associated lymphoid tissue (MALT).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7928429

Horny, H P

1994-07-01

84

Retroviral induction of acute lymphoproliferative disease and profound immunosuppression in adult C57BL/6 mice  

PubMed Central

We have shown that a mixture of murine leukemia viruses (MuLV) causes the acute onset of lymphoproliferation and immunosuppression when injected into adult C57BL/6 mice. The ecotropic/MCF (mink cell focus- inducing) mixture of MuLV stimulates polyclonal B lymphocyte proliferation and differentiation to antibody-secreting cells. Serum Ig levels are elevated for all isotypes except IgA. The viral infection leads to a rapid decline in T lymphocyte responses to mitogens and alloantigens, as well as a decrease in helper cell activity. Specific antibody responses to both T-dependent and T-independent antigens are impaired, and the response of B lymphocytes to mitogens is abolished. The profound immunosuppression seems to be due to the MuLV-induced polyclonal activation of lymphocytes. No active suppression of normal lymphocyte responses by cells from virus-infected mice was observed. The disease induced by the LP-BM5 MuLV isolate thus seems a promising model for the study of lymphocyte activation and the mechanisms of retrovirus-induced immunosuppression. PMID:2984305

1985-01-01

85

Prognostic implication of morphology, cyclinE2 and proliferation in EBV-associated T/NK lymphoproliferative disease in non-immunocompromised hosts.  

PubMed

BackgroundEBV-associated T/NK-cell lymphoproliferative diseases (TNKLPD) is a rare spectrum of disease that occurs more commonly in Asia, and Central and South America. It commonly affects children and young adults and is an aggressive disease that is poorly understood with no known biologic markers that can predict prognosis. The systemic form of TNKLPD includes chronic active EBV infection of T/NK type, aggressive NK cell leukemia and systemic EBV¿+¿T-cell lymphoproliferative disease of childhood.MethodsIn this study, we analyse the clinicopathologic and genetic features of 22 cases of systemic TNKLPD in non-immunocompromised patients, including chronic active EBV infection of T/NK cell type and systemic EBV¿+¿T-cell lymphoproliferative disease of childhood. We also performed gene expression profiling in a subset of cases to identify markers that may be of prognostic relevance and validated our results using immunohistochemistry.ResultsThe median age is 14.9 years and two of our 22 cases occurring in patients older than 30 years. Fifteen of 17 cases (88%) with adequate data were of T-cell origin. Eleven of 22 cases revealed polymorphic cellular infiltrate (P-group) while the rest showed monomorphic lymphoid infiltrate (M-group). We found a significant difference in survival between P-group vs M-group patients with median survival not yet reached in P-group, and 1 month in M-group (p =0.0001), suggesting a role for morphology in predicting patient outcome. We also performed gene expression profiling in a subset of patients and compared the genes differentially expressed between P-group and M-group cases to identify markers of prognostic value. We identified cyclin E2 gene and protein to be differentially expressed between patients with good outcome (P-group, median expression 8%) and poor outcome (M-group, median expression 42%) (p =0.0005). In addition, the upregulation of cyclin E2 protein in M-group cases correlated with a higher Ki67 proliferation rate (Pearson correlation r =0.73, p =0.0006) detected by immunohistochemistry. High cyclin E2 expression was also significantly associated with shorter survival (p =0.0002).ConclusionOur data suggests the potential role of monomorphic morphology, high cyclin E2 and Ki67 expression as adverse prognostic factors for TNKLPD. PMID:25475054

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

2014-12-01

86

EXPRESSION OF EPSTEIN–BARR VIRUS–ENCODED SMALL RNA (BY THE EBER-1 GENE) IN LIVER SPECIMENS FROM TRANSPLANT RECIPIENTS WITH POST-TRANSPLANTATION LYMPHOPROLIFERATIVE DISEASE  

PubMed Central

Background Epstein–Barr virus (EBV)–associated post-transplantation lymphoproliferative disease (PTLD) develops in 1 to 10 percent of transplant recipients, in whom it can be treated by a reduction in the level of immunosuppression. We postulated that the tissue expression of the small RNA transcribed by the EBER-1 gene during latent EBV infection would identify patients at risk for PTLD. Methods We studied EBER-1 gene expression in liver specimens obtained from 24 patients 2 days to 22 months before the development of PTLD, using in situ hybridization with an oligonucleotide probe. Control specimens were obtained from 20 recipients of allografts with signs of injury due to organ retrieval, acute graft rejection, or viral hepatitis in whom PTLD had not developed 9 to 71 months after the biopsy. Results Of the 24 patients with PTLD, 17 (71 percent) had specimens in which 1 to 40 percent of mononuclear cells were positive for the EBER-1 gene. In addition, 10 of these 17 patients (59 percent) had specimens with histopathological changes suggestive of EBV hepatitis. In every case, EBER-1–positive cells were found within the lymphoproliferative lesions identified at autopsy. Only 2 of the 20 controls (10 percent) had specimens with EBER-1–positive cells (P< 0.001), and such cells were rare. Conclusions EBER-1 gene expression in liver tissue precedes the occurrence of clinical and histologic PTLD. The possibility of identifying patients at risk by the method we describe here and preventing the occurrence of PTLD by a timely reduction of immunosuppression needs to be addressed by future prospective studies. PMID:1331789

Randhawa, Parmjeet S.; Jaffe, Ronald; Demetris, Anthony J.; Nalesnik, Michael; Starzl, Thomas E.; Chen, Yuan Yuan; Weiss, Lawrence M.

2010-01-01

87

Early posttransplant nephrotic range proteinuria as a presenting feature of minimal change disease and acute T cell-mediated rejection.  

PubMed

Early-onset nephrotic range proteinuria is an extremely rare presentation of an acute rejection episode. Herein, we have reported a patient who developed nephrotic range proteinuria 7 days after receiving a renal allograft from his sister despite minor changes in serum creatinine levels. A kidney biopsy spcimen revealed a T cell-mediated acute rejection process concomitant with minimal change disease (MCD). Proteinuria and renal dysfunction improved dramatically in response to corticosteroids. The possibility of acute cellular rejection and coexisting MCD should be considered in patients with early posttransplantation nephrosis and normal serum creatinine levels. The coexistence of these entities provides support for the role of T cells in the pathogenesis of MCD. PMID:23267783

Nongnuch, A; Assanatham, M; Sumethkul, V; Chalermsanyakorn, P; Kitiyakara, C

2014-01-01

88

Employment post-transplant: a biopsychosocial analysis.  

PubMed

Employment following renal transplantation has been lower than predicted at the time of the original end-stage renal disease (ESRD) legislation more than 30 years ago. This paper uses the biopsychosocial model to identify predictors of employment for 411 individuals transplanted at a single, large Midwestern academic center. Less than 50% of respondents reported part-time or full-time employment post-transplant. Factors found to predict employment were age at the time of transplant, race, sex, and patient perception of physical functioning. Individuals who were younger when transplanted, Caucasian, and males were more likely to be employed full-time following transplantation as were those who perceived themselves to have a higher level of physical functioning. No biological factors, including serum creatinine, mean arterial pressure (MAP), and diabetic status, were significant predictors of employment. The biopsychosocial model is used to discuss the implications of these findings for post-transplant employment and social work intervention. PMID:17855228

Raiz, Lisa; Monroe, Jacquelyn

2007-01-01

89

XIAP deficiency: a unique primary immunodeficiency best classified as X-linked familial hemophagocytic lymphohistiocytosis and not as X-linked lymphoproliferative disease  

PubMed Central

X-linked inhibitor of apoptosis (XIAP) deficiency, caused by BIRC4 mutations, is described to cause X-linked lymphoproliferative disease (XLP) phenotypes. However, compared with XLP caused by SLAM-Associated Protein deficiency (SH2D1A mutation), XIAP deficiency was originally observed to be associated with a high incidence of hemophagocytic lymphohistiocytosis (HLH) and a lack of lymphoma, suggesting that classification of XIAP deficiency as a cause of XLP may not be entirely accurate. To further characterize XIAP deficiency, we reviewed our experience with 10 patients from 8 unrelated families with BIRC4 mutations. Nine of 10 patients developed HLH by 8 years of age. Most patients presented in infancy, and recurrent HLH was common. There were no cases of lymphoma. Lymphocyte defects thought to contribute to HLH development in SLAM-Associated Protein deficiency were not observed in XIAP deficiency. We conclude that XIAP deficiency is a unique primary immunodeficiency that is more appropriately classified as X-linked familial hemophagocytic lymphohistiocytosis. PMID:20489057

Madden, Lisa; Kitchen, Brenda J.; Mody, Rajen; McClimon, Brad; Jordan, Michael B.; Bleesing, Jack J.; Zhang, Kejian; Filipovich, Alexandra H.

2010-01-01

90

A PLC-?1-independent, RasGRP1-ERK dependent pathway drives lymphoproliferative disease in LAT-Y136F mutant mice  

PubMed Central

Mice expressing a germline mutation in the PLC-?1 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-?1 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, PKC?, and RasGRP1. These data demonstrate a novel route to Ras activation in vivo in a pathological setting. PMID:23209318

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

91

Systemic lymphoproliferative responses to rotavirus.  

PubMed

In comparison with healthy adults, elderly patients and patients who had received renal transplants had significantly lower lymphoproliferative responses to rotavirus (P = 0.04, P = 0.002, respectively) and phytohaemagglutinin (P = 0.001). However, following acute rotavirus infection, elderly persons mounted good lymphoproliferative and specific antibody responses to rotavirus. No lymphoproliferative response or specific antibody to rotavirus was detected in a child with cartilage hair hypoplasia. In cord blood samples, specific antibodies were detected in the absence of a lymphoproliferative response to rotavirus. Increases in lymphoproliferative responses as well as specific antibodies were not detected in immune adult recipients of a human rotavirus vaccine (RIT 4375), but a recipient of a bovine vaccine (RIT 4237) had an increase in lymphoproliferative response to rotavirus between 13 and 28 days postvaccination. Stimulation indices for both rotavirus and phytohaemagglutinin within the vaccine groups were comparable to the healthy laboratory personnel group. PMID:2842446

Totterdell, B M; Banatvala, J E; Chrystie, I L; Ball, G; Cubitt, W D

1988-05-01

92

Posttransplantation lymphoproliferative disease in miniature swine after allogeneic hematopoietic cell transplantation: similarity to human PTLD and association with a porcine gammaherpesvirus.  

PubMed

Posttransplantation lymphoproliferative disease (PTLD) is a major complication of current clinical transplantation regimens. The lack of a reproducible large-animal model of PTLD has limited progress in understanding the pathogenesis of and in developing therapy for this clinically important disease. This study found a high incidence of PTLD in miniature swine undergoing allogeneic hematopoietic stem cell transplantation and characterized this disease in swine. Two days before allogeneic peripheral blood stem cell transplantation, miniature swine were conditioned with thymic irradiation and in vivo T-cell depletion. Animals received cyclosporine daily beginning 1 day before transplantation and continuing for 30 to 60 days. Flow cytometry and histologic examination were performed to determine the cell type involved in lymphoproliferation. Polymerase chain reaction was developed to detect and determine the level of porcine gammaherpesvirus in involved lymph node tissue. PTLD in swine is morphologically and histologically similar to that observed in human allograft recipients. Nine of 21 animals developed a B-cell lymphoproliferation involving peripheral blood (9 of 9), tonsils, and lymph nodes (7 of 9) from 21 to 48 days after transplantation. Six of 9 animals died of PTLD and 3 of 9 recovered after reduction of immunosuppression. A novel porcine gammaherpesvirus was identified in involved tissues. Miniature swine provide a genetically defined large-animal model of PTLD with many characteristics similar to human PTLD. The availability of this reproducible large-animal model of PTLD may facilitate the development and testing of diagnostic and therapeutic approaches for prevention or treatment of PTLD in the clinical setting. PMID:11222395

Huang, C A; Fuchimoto, Y; Gleit, Z L; Ericsson, T; Griesemer, A; Scheier-Dolberg, R; Melendy, E; Kitamura, H; Fishman, J A; Ferry, J A; Harris, N L; Patience, C; Sachs, D H

2001-03-01

93

Mature T/NK-cell lymphoproliferative disease and Epstein-Barr virus infection are more frequent in patients with rheumatoid arthritis treated with methotrexate.  

PubMed

We retrospectively analyzed in 54 consecutively enrolled Japanese patients with rheumatoid arthritis (RA) and lymphoproliferative disease (LPD) relevant clinicopathological characteristics, in particular paying attention to treatment with methotrexate (MTX). Between the 28 patients treated with MTX (MTX-treated group) and the 26 who were not (non-MTX group), there was no difference in age, interval between onset of RA and LPD, and lymphoma stage. Immunohistochemical analysis showed that in the MTX-treated group, 15 (53 %) patients had mature B-cell LPD, eight (29 %) mature T/NK-cell LPD, and five (18 %) had Hodgkin lymphoma. In the non-MTX group, 22 (84 %) had mature B-cell LPD, 2 (8 %) had mature T/NK-cell LPD, and 2 (8 %) had Hodgkin lymphoma. The frequency of mature T/NK-cell LPD was significantly higher in the MTX-treated group (p?

Kondo, Seiji; Tanimoto, Kazuki; Yamada, Kozue; Yoshimoto, Goichi; Suematsu, Eiichi; Fujisaki, Tomoaki; Oshiro, Yumi; Tamura, Kazuo; Takeshita, Morishige; Okamura, Seiichi

2013-04-01

94

[The larynx in lymphoproliferative and myeloproliferative diseases. I: An overview with special reference to primary laryngeal malignant lymphomas and plasmacytomas].  

PubMed

Lymphoreticular neoplasms of the larynx are rare and comprise a heterogeneous group of tumors. A systematic survey of the literature and autoptic evaluation of the larynx in a relatively small number of patients with systemic lymphoreticular malignancies yielded the following findings: Primary tumors of the larynx must be clearly distinguished from laryngeal involvement by systemic or leukemic infiltrations. By far the most common primary hemopoietic tumors of the larynx are extramedullary plasmacytoma (about 90 cases published) and non-Hodgkin's lymphoma (NHL; about 65 cases published). Primary Hodgkin's disease, granulocytic sarcoma and mast cell sarcoma are extremely rare at this site. Plasmacytoma and NHL both preferentially involve the supraglottis. The subglottis is infrequently affected. Laryngeal plasmacytoma and NHL usually present clinically as localized stage IE and IIE tumors that exhibit no significant tendency to recur or generalize. The therapy of choice is local irradiation while chemotherapy should be reserved for recurrent or progressive disease. Prognosis is favorable in most cases of primary laryngeal plasmacytoma and NHL. Secondary involvement of the larynx by systemic lesions or leukemic infiltrations is usually associated with a very poor prognosis. The prognosis of patients with laryngeal involvement in acute or chronic myeloid leukemia is always poor. Although the histopathological diagnoses given in many case reports are often difficult to compare because of differences in terminology, there seems to be a marked preponderance of B-cell tumors of high-grade malignancy (centroblastic or immunoblastic lymphoma in the Kiel classification of NHL) that probably represents lymphomas originating from mucosa-associated lymphoid tissue (MALT).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8071093

Horny, H P

1994-06-01

95

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

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

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

96

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

PubMed Central

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

Ashrafi, Farzaneh; Shahidi, Shahrzad; Mortazavi, Mojgan

2015-01-01

97

Post-transplant nephrotic syndrome: A comprehensive clinicopathologic study  

Microsoft Academic Search

Post-transplant nephrotic syndrome: A comprehensive clinicopathologic study.BackgroundPost-transplant (Tx) nephrotic syndrome (NS) is not well defined.MethodsSeventy-four renal transplant recipients with NS were studied.ResultsBiopsies showed chronic allograft nephropathy (CAN) in 31 patients; recurrent glomerular disease (GN) in 15, de novo GN in 18, and undetermined GN in 9. NS developed 0.25 to 384 months post-Tx and was treated with angiotensin-converting enzyme inhibitors

ULKEM YAKUPOGLU; ELZBIETA BARANOWSKA-DACA; DANIEL ROSEN; ROBERTO BARRIOS; Wadi N. Suki; Luan D. Truong

2004-01-01

98

Epstein–Barr virus-positive T/NK-cell lymphoproliferative disorders  

PubMed Central

Epstein–Barr 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 Epstein–Barr virus is related to its ability to infect and transform B lymphocytes into continuously proliferating lymphoblastoid cells. However, Epstein–Barr virus has also been implicated in the development of T/natural killer cell lymphoproliferative diseases. Epstein–Barr 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 Epstein–Barr virus promotes oncogenesis and inflammatory lesion development remains unclear. Epstein–Barr 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 Epstein–Barr 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 Epstein–Barr virus-associated T/natural killer cell lymphoproliferative diseases. PMID:25613730

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

2015-01-01

99

Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorders.  

PubMed

Epstein-Barr 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 Epstein-Barr virus is related to its ability to infect and transform B lymphocytes into continuously proliferating lymphoblastoid cells. However, Epstein-Barr virus has also been implicated in the development of T/natural killer cell lymphoproliferative diseases. Epstein-Barr 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 Epstein-Barr virus promotes oncogenesis and inflammatory lesion development remains unclear. Epstein-Barr 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 Epstein-Barr 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 Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases. PMID:25613730

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

2015-01-01

100

Posttransplant Epstein-Barr virus related lymphoproliferative disorder with a primary cutaneous presentation  

E-print Network

et al. 14 cases of pseudo-B-cell lymphoma in which all, byB and T-cell lineages, ranging from plasma-cell overgrowth to aggressive lymphomas.B-cell lineages [ 10 ]. CD30 has classically been expressed in anaplastic large cell lymphoma

Snavely, Nicholas R; Sonabend, Michael; Rosen, Ted

2007-01-01

101

Posttransplant anemia in solid organ recipients.  

PubMed

Posttransplantation anemia (PTA) is a prevalent sequela of solid organ transplantation and a potential independent risk factor for cardiovascular morbidity and mortality in kidney transplant recipients. There are multiple causes of PTA, some of which are associated with early phase anemia (<6 months), whereas others more often induce anemia in the late posttransplant phase (>6 months). Although impaired kidney function contributes to PTA, it is only one of many factors that result in anemia in transplant recipients. Other causes include iron deficiency, medications, infections, acute rejection, inflammation, and erythropoietin deficiency. Unlike in the predialysis chronic kidney disease population, the impact of anemia after kidney transplantation outcomes is unknown. This is in large part due to the absence of controlled trials that address whether correction of anemia improves allograft function or patient morbidity and mortality. Current guidelines recommend evaluation for hemoglobin level of less than 12 g/dL and treatment when the value falls less than 11 g/dL and a target of 11 to 12 g/dL. Additional treatments may entail removing the cause of the anemia, nutritional supplementation, and/or an erythrocyte stimulating agent. PMID:20303457

Blosser, Christopher D; Bloom, Roy D

2010-04-01

102

Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with clonal lymphoproliferative disorders after orthotopic liver transplantation: a report of three cases  

Microsoft Academic Search

Background\\/Aims: Post-transplant lymphoproliferative disorders (PT-LPD) are a well-known complication of organ transplantation. Their incidence after liver transplantation in adults ranges from 1.8 to 4%. Reduction of immunosuppression led to remission in a few cases. Other treatments include chemotherapy, interferon alpha therapy and\\/or intravenous-immunoglobulins, or antiviral drugs. However, monoclonal antibodies directed against B-cell specific antigens have rarely been used in those

Simona Zompi; Micheline Tulliez; Filoména Conti; Véronique Leblond; Philippe Gaulard; Philippe Blanche; François Durand; Damaj Ghandi; François Dreyfus; Albert Louvel; Yvon Calmus; Didier Bouscary

2000-01-01

103

Maternal onset de novo SH2D1A mutation and lymphocytic choriomeningitis virus infection in a patient with X-linked lymphoproliferative disease type 1: A case report  

PubMed Central

X-linked lymphoproliferative disease type 1 (XLP1) is a rare genetic immunodeficiency disease, which occurs due to germline mutations in the SH2D1A gene. This gene has been reported to encode the adaptor molecule signaling lymphocytic activation molecule-associated protein XLP1 is generally triggered by the Epstein-Barr virus (EBV) infection. The present study reported the case of a 4-year-old male who presented with a high fever, hypogammaglobulinemia, diffuse lung disease and encephalitis. The patient was infected with the lymphocytic choriomeningitis virus (LCMV), not EBV or any other human herpes virus. The patient was found to carry a SH2D1A c.7G>T/p.A3S mutation, which was inherited from the mother and maternal grandfather, as well as a SH2D1A c.228T>A/p.Y76X mutation, which was identified to be a maternal-onset de novo mutation at the time of germline development of the patient’s mother. To the best of our knowledge, the present study is the first reported case of maternal-onset XLP1 with a de novo SH2D1A mutation and LCMV infection. PMID:25572984

LIU, JINRONG; TIAN, WENJUN; WANG, FANG; TENG, WEN; ZHANG, YANG; TONG, CHUNRONG; ZHANG, CHONGLIN; JU, YING; ZHANG, BINGCHANG; ZHAO, SHUNYING; LIU, HONGXING

2015-01-01

104

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

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

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

105

Maternal onset de novo SH2D1A mutation and lymphocytic choriomeningitis virus infection in a patient with X?linked lymphoproliferative disease type 1: A case report.  

PubMed

X?linked lymphoproliferative disease type 1 (XLP1) is a rare genetic immunodeficiency disease, which occurs due to germline mutations in the SH2D1A gene. This gene has been reported to encode the adaptor molecule signaling lymphocytic activation molecule?associated protein XLP1 is generally triggered by the Epstein?Barr virus (EBV) infection. The present study reported the case of a 4?year?old male who presented with a high fever, hypogammaglobulinemia, diffuse lung disease and encephalitis. The patient was infected with the lymphocytic choriomeningitis virus (LCMV), not EBV or any other human herpes virus. The patient was found to carry a SH2D1A c.7G>T/p.A3S mutation, which was inherited from the mother and maternal grandfather, as well as a SH2D1A c.228T>A/p.Y76X mutation, which was identified to be a maternal?onset de novo mutation at the time of germline development of the patient's mother. To the best of our knowledge, the present study is the first reported case of maternal?onset XLP1 with a de novo SH2D1A mutation and LCMV infection. PMID:25572984

Liu, Jinrong; Tian, Wenjun; Wang, Fang; Teng, Wen; Zhang, Yang; Tong, Chunrong; Zhang, Chonglin; Ju, Ying; Zhang, Bingchang; Zhao, Shunying; Liu, Hongxing

2015-05-01

106

Prevalence of hepatitis B and C viruses in patients with lymphoproliferative disorders  

Microsoft Academic Search

The etiology of most lymphoproliferative disorders remains unclear, though several hypotheses have been proposed. One of the\\u000a conjectured mechanisms is infection of a tumor clone by an oncologic virus. Recently, evidence has arisen implicating both\\u000a hepatitis B and, even more so, hepatitis C viruses in the pathogenesis of lymphoproliferative disease. Based on this information,\\u000a we surveyed the prevalence of hepatitis

Vahap Okan; Mehmet Yilmaz; Aysen Bayram; Cem Kis; Sami Cifci; Hakan Buyukhatipoglu; Mustafa Pehlivan

2008-01-01

107

?-HHVs and HHV-8 in Lymphoproliferative Disorders  

PubMed Central

Similarly to Epstein-Barr virus (EBV), the human herpesvirus-8 (HHV-8) is a ?-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 ?-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 ?-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 ?-herpesviruses in human lymphoproliferative disorders. PMID:22110893

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

2011-01-01

108

Cytomegalovirus and polyomavirus BK posttransplant  

Microsoft Academic Search

Virus replication and progression to disease in transplant patients is determined by patient-, graft- and virus-specific factors. This complex interaction is modulated by the net state of immunosuppression and its impact on virus-specific cellular immunity. Due to the increasing potency of immunosuppressive regi- mens, graft rejections have decreased, but susceptibility to infections has increased. Therefore, cytomegalovirus (CMV) remains the most

Adrian Egli; Simone Binggeli; Sohrab Bodaghi; Alexis Dumoulin; Georg A. Funk; Nina Khanna; David Leuenberger; Rainer Gosert; Hans H. Hirsch

2007-01-01

109

Fas\\/Apo1 mutations and autoimmune lymphoproliferative syndrome in a patient with type 2 autoimmune hepatitis  

Microsoft Academic Search

Inherited mutations of the Fas\\/Apo1\\/CD95 gene, a cell-surface receptor involved in cell death signaling and in the control of self-reactivity, characterize the recently identified autoimmune lymphoproliferative syndromes. A patient with type 2 autoimmune hepatitis with the immunologic and genetic features of autoimmune lymphoproliferative syndrome is described. The clinical picture was dominated by liver disease with hepatosplenomegaly and positivity for anti-liver-kidney

L Pensati; A Costanzo; A Ianni; D Accapezzato; R Iorio; G Natoli; R Nisini; C Almerighi; C Balsano; P Vajro; A Vegnente; M Levrero

1997-01-01

110

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

Microsoft Academic Search

The autoimmune lymphoproliferative syndrome (ALPS) and ALPS-like syndrome are variable clinical conditions characterized by\\u000a lymphoproliferative disease, autoimmune cytopenias and susceptibility to malignancy. A 59-year-old woman was admitted to the\\u000a hospital for intractable generalized pain and stiffness with multiple swollen joints for 2 weeks. A low-grade fever, intermittent\\u000a hypotension and confusion were associated with the pain. The evaluation revealed multiple joint bony

Young Hoon Hong; Choong Ki Lee

2009-01-01

111

T cell lymphoproliferative disorders associated with anti-tumor necrosis factor alpha antibody therapy for ulcerative colitis: literature summary.  

PubMed

The enhanced risk of development of lymphoproliferative disorders in patients with inflammatory bowel disease has been attributed to immunosuppressive/immunomodulatory therapies. Infliximab is a chimeric monoclonal immunoglobulin G1 antibody directed against tumor necrosis factor alpha (TNF-?) that was approved by the Food and Drug Administration (FDA) in 1998 as an effective therapeutic agent against inflammatory bowel disease. Malignant lymphomas of both B and T cell lineage have been described in patients undergoing therapy involving TNF-? blockade. To date, eight cases of Epstein-Barr virus (EBV)-negative hepatosplenic T cell lymphoma associated with infliximab have been reported to the FDA's Adverse Event Reporting System, as well as several other T cell lymphoproliferative disorders with aggressive clinical outcomes. We present the histologic, immunophenotypic, and molecular features of a T cell lymphoproliferative disorder involving the axillary lymph node of a 33-year-old male following infliximab treatment for ulcerative colitis. These EBV-negative lymphomas suggest that lymphoproliferative disorders following infliximab treatment for inflammatory bowel disease may involve EBV-independent immune dysregulation. The spectrum of lymphoproliferative disorders associated with infliximab and the potential mechanisms by which they occur are discussed. PMID:19669196

Schmidt, Lindsay A; Lim, Megan S

2009-07-01

112

Autoimmune Lymphoproliferative Syndrome Misdiagnosed as Hemophagocytic Lymphohistiocytosis  

PubMed Central

Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder of apoptosis, most commonly due to mutations in the FAS (TNFRSF6) gene. It presents with chronic lymphadenopathy, splenomegaly, and symptomatic multilineage cytopenias in an otherwise healthy child. Unfortunately, these clinical findings are also noted in other childhood lymphoproliferative conditions, such as leukemia, lymphoma, and hemophagocytic lymphohistiocytosis, which can confound the diagnosis. This report describes a 6-year-old girl with symptoms misdiagnosed as hemophagocytic lymphohistiocytosis and treated with chemotherapy before the recognition that her symptoms and laboratory values were consistent with a somatic FAS mutation leading to ALPS. This case should alert pediatricians to include ALPS in the differential diagnosis of a child with lymphadenopathy, splenomegaly, and cytopenias; obtain discriminating screening laboratory biomarkers, such as serum vitamin B-12 and ferritin levels; and, in the setting of a highly suspicious clinical scenario for ALPS, pursue testing for somatic FAS mutations when germ-line mutation testing is negative. PMID:24101757

Rudman Spergel, Amanda; Walkovich, Kelly; Price, Susan; Niemela, Julie E.; Wright, Dowain; Fleisher, Thomas A.

2013-01-01

113

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

PubMed Central

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?post-transplant (p?post-transplant cardiac events (p?Post-transplant cardiac events are more common than in the general population. PMID:24708568

2014-01-01

114

[KHSV/EBV associated germinotropic lymphoproliferative disorder: a rare entity, case report and review of the literature].  

PubMed

We report a case of KSHV/EBV associated germinotropic lymphoproliferative disorder (LPG) in a 49-year-old African patient, without immunosuppression. LPG is a rare entity arising in immunocompetent patients in opposition to other lymphoproliferative disorders associated to Kaposi sarcoma-associated herpes virus (KSHV). The disease presents itself as localized lymphadenopathy with an infiltration of germinal centers by plasmablastic cells coinfected by KSHV and EBV (Epstein-Barr Virus). After treatment, the outcome is favorable. Differential diagnosis in our case, due to the presence of clusters of Hodgkin-like cells in the mantle zone, included lymphocyte rich classic Hodgkin lymphoma (LHCRL) and nodular lymphocyte predominant Hodgkin lymphoma (LHNPL). Finally, we highlight the differential diagnostic criteria of KSHV lymphoproliferative diseases. PMID:25439990

Taris, Michaël; de Mascarel, Antoine; Riols, Mercédès; Delwail, Vincent; Milpied, Noël; Dubus, Pierre; Parrens, Marie

2014-10-01

115

[New Developments in CKD-MBD. The management of posttransplant CKD-MBD : When, Who, and How?].  

PubMed

Chronic kidney disease - mineral and bone disorder (CKD-MBD) in kidney transplant recipients has a complex pathophysiology, which is a combination of carryover of mineral and bone disorder during the dialysis period and dynamic change in bone and mineral metabolism after transplantation. The most important thing is to know that this pathophysiology is a continuum from the early stage of CKD through the dialysis period to the post-transplant period. However, the current treatment approaches among Japanese nephrologists are based on three different categories : nephrologists elaborately treating predialysis patients against end-stage renal disease ; dialysis doctors aggressively coping with their patients' deadly complications ; and transplant doctors concentrating on post-transplant follow-ups for better graft survival. In this article, I would like to explain the pathophysiology of post-transplant CKD-MBD and then to introduce a new role -- that not only transplant doctors, but also dialysis doctors, should play a crucial role in CKD-MBD in the post-transplant period. PMID:25423932

Fujii, Naohiko

2014-12-01

116

Urinary Calprotectin and Posttransplant Renal Allograft Injury  

PubMed Central

Objective Current methods do not predict the acute renal allograft injury immediately after kidney transplantation. We evaluated the diagnostic performance of urinary calprotectin for predicting immediate posttransplant allograft injury. Methods In a multicenter, prospective-cohort study of 144 incipient renal transplant recipients, we postoperatively measured urinary calprotectin using an enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR) after 4 weeks, 6 months, and 12 months. Results We observed a significant inverse association of urinary calprotectin concentrations and eGFR 4 weeks after transplantation (Spearman r?=??0.33; P<0.001). Compared to the lowest quartile, patients in the highest quartile of urinary calprotectin had an increased risk for an eGFR less than 30 mL/min/1.73 m2 four weeks after transplantation (relative risk, 4.3; P<0.001; sensitivity, 0.92; 95% CI, 0.77 to 0.98; specificity, 0.48; 95% CI, 0.31 to 0.66). Higher urinary calprotectin concentrations predicted impaired kidney function 4 weeks after transplantation, as well as 6 months and 12 months after transplantation. When data were analyzed using the urinary calprotectin/creatinine-ratio similar results were obtained. Urinary calprotectin was superior to current use of absolute change of plasma creatinine to predict allograft function 12 months after transplantation. Urinary calprotectin predicted an increased risk both in transplants from living and deceased donors. Multivariate linear regression showed that higher urinary calprotectin concentrations and older donor age predicted lower eGFR four weeks, 6 months, and 12 months after transplantation. Conclusions Urinary calprotectin is an early, noninvasive predictor of immediate renal allograft injury after kidney transplantation. PMID:25402277

Bistrup, Claus; Marcussen, Niels; Pagonas, Nikolaos; Seibert, Felix S.; Arndt, Robert; Zidek, Walter; Westhoff, Timm H.

2014-01-01

117

Familial Aggregation of Lymphoproliferative Disorders from the Scandinavian Family Cancer Database  

Cancer.gov

Familial aggregation of lymphoproliferative disorders from the Scandinavian family cancer database Print This Page Familial Aggregation of Lymphoproliferative Disorders from the Scandinavian Family Cancer Database Our Research

118

AL amyloidosis associated with B-cell lymphoproliferative disorders: frequency and treatment outcomes.  

PubMed

AL amyloidosis, a systemic disorder characterized by widespread deposition of amyloid fibrils derived from monoclonal Ig light chains in organs and soft tissues, is typically caused by an underlying plasma cell dyscrasia. However, this disease can also be associated rarely with a B-cell lymphoproliferative disorder. In this report, we describe the presentation and clinical course of 16 patients with this association. Although amyloid-related organ involvement in these patients was typical of AL amyloidosis, the patients in this series were on average older and more likely to be female than patients with disease associated with a plasma cell dyscrasia. They were also more likely to have multisystem involvement. Treatment decisions were based primarily on the dominent hematopathologic features of the associated lymphoproliferative disorder. However, high-dose melphalan and stem cell transplantation was the primary therapy in 5 patients, and each of these patients had prolonged survival, ranging from 36 to 102 months. PMID:16795060

Sanchorawala, V; Blanchard, E; Seldin, D C; O'Hara, Carl; Skinner, M; Wright, D G

2006-09-01

119

Predictors of left ventricular remodelling in kidney transplant recipents in the first posttransplant year.  

PubMed

Cardiovascular diseases (CVD) are a major cause of morbidity and leading cause of mortality in almost 50% of patients (pts) with chronic kidney disease (CKD), including kidney transplant recipients. Left ventricular hypertrophy (LVH) is the most common structural alteration and powerful risk factor for cardiovascular complications in the uremic patients. The aim of this study is to analyze predictors of the left ventricular remodelling in the first year after kidney transplantation based on comparison of echocardiographic findings, which had been done before and twelve months after transplantation. In five years retrospective study, we followed up 30 kidney transplant patients in the first post-transplant year. All patients data - blood pressure, BMI, ECG, blood haemoglobin, serum protein, calcium, phosphorus, product of calcium and phosphorus, the values of parathyroid hormone, serum creatinine and creatinine clearance were recorded just before kidney transplantation and in one month interval after transplantation in the first post-transplant year. Echocardiographic examination was done before transplantation and one year after kidney transplantation. Before transplantation, 33% of patients had normal echocardiographic finding and 67% of patients had echocardiographic signs of left ventricular hypertrophy. After first post-transplant year, 63% of patients showed normal echocardiographic finding of LV, while 37% of patients remained with LV hypertrophy. Diastolic dysfunction of LV until the end of study had been reduced in 40% of pts compared to 70% pts at the beginning of the study. The positive echocardiographic remodelling of LV significantly correlated with rising values of haemoglobin (p<0.05), creatinine clearance (p=0.039) and with the reduction of the serum creatinine values (p=0.047), as well as values of parathyroid hormone (p=0.022). These results confirmed positive relationship between echocardiographic remodelling of left ventricular hypertrophy and elimination uraemia-related risk factors after successful renal transplantation. PMID:20433432

Dzemidzi?, Jasminka; Rasi?, Senija; Saracevi?, Adnan; Rebi?, Damir; Uncanin, Snezana; Srna, Amira; Muslimovi?, Alma

2010-04-01

120

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

PubMed

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

Berio, A; Mangiante, G; Piazzi, A

2014-01-01

121

Causes and consequences of the autoimmune lymphoproliferative syndrome.  

PubMed

Autoimmune lymphoproliferative syndrome (ALPS) is the first autoimmune hematological disease whose genetic basis has been defined. It is a disorder of apoptosis in which the inability of lymphocytes to die leads to lymphadenopathy, hypersplenism, and autoimmune cytopenias of childhood onset. More than 200 ALPS patients have been studied over the last 15 years and followed by our colleagues and ourselves at the Clinical Center of the National Institutes of Health. Based upon this experience we have determined that patients with germline mutations of the intracellular domain of Fas protein, the most frequent single genetic cause of ALPS, have a significantly increased risk of developing Hodgkin and non-Hodgkin lymphoma (NHL), underscoring the critical role played by cell surface receptor-mediated apoptosis in eliminating redundant proliferating lymphocytes with autoreactive and oncogenic potential. The major determinants of morbidity and mortality in ALPS are the severity of the autoimmune disease, hypersplenism, asplenia-related sepsis, and the risk of lymphoma, which in itself requires long-term surveillance. Though most episodes of cytopenias respond to courses of conventional immunomodulatory agents, some ALPS patients, especially those with massive splenomegaly and hypersplenism, may require splenectomy and/or ongoing immunosuppressive treatment. Thus, ALPS highlights the importance of cell death pathways in health and disease. PMID:16522544

Rao, V Koneti; Straus, Stephen E

2006-02-01

122

Posttransplant Outcomes of Peritoneal Dialysis Versus Hemodialysis Patients  

Microsoft Academic Search

The impact of dialysis modality on posttransplant outcomes remains controversial. The authors have compared primary failure, delayed graft function (DGF), acute rejection episodes as well as patient and allograft survivals among patients undergoing renal transplantation between 2004 and 2009, according to the modality of hemodialysis (HD) versus peritoneal dialysis (PD). We studied 306 patients (268 HD and 38 PD) with

C. Freitas; M. Fructuoso; L. S. Martins; M. Almeida; S. Pedroso; L. Dias; A. C. Henriques; A. Cabrita

2011-01-01

123

Sirolimus for Autoimmune Disease of Blood Cells  

ClinicalTrials.gov

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

2014-10-17

124

DiGeorge syndrome who developed lymphoproliferative mediastinal mass  

PubMed Central

DiGeorge syndrome is an immunodeficient disease associated with abnormal development of 3rd and 4th pharyngeal pouches. As a hemizygous deletion of chromosome 22q11.2 occurs, various clinical phenotypes are shown with a broad spectrum. Conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcemia are the classic triad of DiGeorge syndrome. As this syndrome is characterized by hypoplastic or aplastic thymus, there are missing thymic shadow on their plain chest x-ray. Immunodeficient patients are traditionally known to be at an increased risk for malignancy, especially lymphoma. We experienced a 7-year-old DiGeorge syndrome patient with mediastinal mass shadow on her plain chest x-ray. She visited Severance Children's Hospital hospital with recurrent pneumonia, and throughout her repeated chest x-ray, there was a mass like shadow on anterior mediastinal area. We did full evaluation including chest computed tomography, chest ultrasonography, and chest magnetic resonance imaging. To rule out malignancy, video assisted thoracoscopic surgery was done. Final diagnosis of the mass which was thought to be malignancy, was lymphoproliferative lesion.

Kim, Kyu Yeun; Hur, Ji Ae; Kim, Ki Hwan; Cha, Yoon Jin; Lee, Mi Jung

2015-01-01

125

DiGeorge syndrome who developed lymphoproliferative mediastinal mass.  

PubMed

DiGeorge syndrome is an immunodeficient disease associated with abnormal development of 3rd and 4th pharyngeal pouches. As a hemizygous deletion of chromosome 22q11.2 occurs, various clinical phenotypes are shown with a broad spectrum. Conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcemia are the classic triad of DiGeorge syndrome. As this syndrome is characterized by hypoplastic or aplastic thymus, there are missing thymic shadow on their plain chest x-ray. Immunodeficient patients are traditionally known to be at an increased risk for malignancy, especially lymphoma. We experienced a 7-year-old DiGeorge syndrome patient with mediastinal mass shadow on her plain chest x-ray. She visited Severance Children's Hospital hospital with recurrent pneumonia, and throughout her repeated chest x-ray, there was a mass like shadow on anterior mediastinal area. We did full evaluation including chest computed tomography, chest ultrasonography, and chest magnetic resonance imaging. To rule out malignancy, video assisted thoracoscopic surgery was done. Final diagnosis of the mass which was thought to be malignancy, was lymphoproliferative lesion. PMID:25861334

Kim, Kyu Yeun; Hur, Ji Ae; Kim, Ki Hwan; Cha, Yoon Jin; Lee, Mi Jung; Kim, Dong Soo

2015-03-01

126

Deciphering leukemic B-cell chronic lymphoproliferative disorders.  

PubMed

Diagnosis of leukemic B-cell chronic lymphoproliferative disorders (B-CLPD) is a frequent challenge in hematology. In this multicentric study, we prospectively studied 165 new consecutive leukemic patients with B-CLPD selected on the basis of Royal Marsden Hospital scoring system < or =3. The primary aim of the study was to try to decipher the atypical cases and identify homogenous subgroups. Overall, morphological examination contributed to diagnosis in only 20% cases, all of them CD5 negative. Thirty additional cases were CD5 negative suggestive of leukemic marginal zone lymphoma in most cases. The significantly poorer survival of the 26 cyclin D1 positive cases justifies recommending its systematic determination among atypical B-CLPD. CD20 expression segregated clearly two subgroups among CD5 positive cyclin D1 negative B-CLPD. The 17 patients with the CD20 dim profile represent a homogeneous subgroup very close to typical B-cell chronic lymphocytic leukemia (B-CLL) on morphological, phenotypical and cytogenetical criteria. In contrast, the subgroup of 51 patients with a CD20 bright profile is heterogeneous. Their significantly lower p27 expression level suggest the presence of a proliferative component, underlying a more aggressive disease. Further genomic studies are warranted to establish their precise nature. These cases should not be included in the same therapeutic trials as B-CLL. PMID:17071481

Ugo, Valérie; Leporrier, Nathalie; Salaun, Véronique; Letestu, Rémi; Radford-Weiss, Isabelle; Ramond, Sylvie; Nataf, Joelle; Guesnu, Martine; Picard, Françoise; Brouzes, Chantal; Perrot, Jean-Yves; Valensi, Françoise; Levy, Vincent; Ajchenbaum-Cymbalista, Florence; Troussard, Xavier

2006-10-01

127

How I treat autoimmune lymphoproliferative syndrome  

PubMed Central

Autoimmune lymphoproliferative syndrome (ALPS) represents a failure of apoptotic mechanisms to maintain lymphocyte homeostasis, permitting accumulation of lymphoid mass and persistence of autoreactive cells that often manifest in childhood with chronic nonmalignant lymphadenopathy, hepatosplenomegaly, and recurring multilineage cytopenias. Cytopenias in these patients can be the result of splenic sequestration as well as autoimmune complications manifesting as autoimmune hemolytic anemia, immune-mediated thrombocytopenia, and autoimmune neutropenia. More than 300 families with hereditary ALPS have now been described; nearly 500 patients from these families have been studied and followed worldwide over the last 20 years by our colleagues and ourselves. Some of these patients with FAS mutations affecting the intracellular portion of the FAS protein also have an increased risk of B-cell lymphoma. The best approaches to diagnosis, follow-up, and management of ALPS, its associated cytopenias, and other complications resulting from infiltrative lymphoproliferation and autoimmunity are presented. This trial was registered at www.clinicaltrial.gov as #NCT00001350. PMID:21885601

Oliveira, João Bosco

2011-01-01

128

Progression of liver fibrosis in post-transplant hepatitis C: mechanisms, assessment and treatment.  

PubMed

Liver fibrosis results from an excessive wound healing response in most chronic liver diseases, such as hepatitis C. Despite great advances in antiviral therapy in recent years, progressive liver fibrosis remains a major problem for patients with recurrent hepatitis C after liver transplantation. Liver biopsy remains a central tool in the management of HCV-positive liver transplant recipients, but reliable non-invasive methods for the assessment of liver fibrosis, such as ultrasound elastography, are increasingly being incorporated in the management of post-transplant patients, helping predict prognosis, guide treatment decisions, and stratify patients for emerging antifibrotic therapies. In this manuscript, we will review the natural history as well as tools to monitor fibrosis progression in the HCV-positive liver transplant recipient, the mechanisms underlying rapid fibrosis progression in up to 30% of these patients, the effect of antiviral therapies and highlight promising antifibrotic approaches. PMID:23262248

Berenguer, Marina; Schuppan, Detlef

2013-05-01

129

Risk factors for lymphoproliferative disorders after allogeneic hematopoietic cell transplantation  

PubMed Central

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

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

130

Hepatitis C management in post-transplant patients.  

PubMed

Hepatitis C virus (HCV)-related cirrhosis is the leading cause for liver transplantation (LT) in developed countries. One of the most troubling complications following LT in patients with HCV is that of recurrence. Unfortunately, this occurs in nearly all patients with HCV. Patients suffering recurrence are known to have faster times to fibrosis and consequently higher rates of graft failure. In general, patients whom undergo transplantation for HCV cirrhosis have higher mortalities comparatively. It is for this reason that HCV in post-transplant patients must be strictly monitored for and treated. Until recently, treatment with standard therapy or pegylated interferon and ribavirin was only marginally effective and the use in this population was off-label. With the advent of direct acting antivirals (DAA), hopes for improved sustained virologic response (SVR) exists. This review will attempt to provide an update regarding recent data for HCV treatment in post-transplant patients, and by doing so, hopefully shed light on a previously dim and dreaded illness. PMID:25390286

Hilgenfeldt, E; Firpi, R J

2015-03-01

131

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

PubMed

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

Hong, Young Hoon; Lee, Choong Ki

2009-03-01

132

Chemoselection of allogeneic HSC after murine neonatal transplantation without myeloablation or post-transplant immunosuppression.  

PubMed

The feasibility of allogeneic transplantation, without myeloablation or post-transplant immunosuppression, was tested using in vivo chemoselection of allogeneic hematopoietic stem cells (HSCs) after transduction with a novel tricistronic lentiviral vector (MGMT(P140K)-2A-GFP-IRES-TK (MAGIT)). This vector contains P140K-O(6)-methylguanine-methyltransferase (MGMT(P140K)), HSV-thymidine kinase (TK(HSV)), and enhanced green fluorescent protein (eGFP) enabling (i) in vivo chemoselection of HSC by conferring resistance to benzylguanine (BG), an inhibitor of endogenous MGMT, and to chloroethylating agents such as 1,3-bis(2-chloroethyl)nitrosourea (BCNU) and, (ii) depletion of proliferating cells such as malignant clones or transduced donor T cells mediating graft versus host disease (GVHD), by expression of the suicide gene TK(HSV) and Ganciclovir (GCV) administration. Non-myeloablative transplantation of transduced, syngeneic, lineage-depleted (Lin(-)) BM in neonates resulted in 0.67% GFP(+) mononuclear cells in peripheral blood. BG/BCNU chemoselection, 4 and 8 weeks post-transplant, produced 50-fold donor cell enrichment. Transplantation and chemoselection of major histocompatibility complex (MHC)-mismatched MAGIT-transduced Lin(-) BM also produced similar expansion for >40 weeks. The efficacy of this allotransplant approach was validated in Hbb(th3) heterozygous mice by correction of ?-thalassemia intermedia, without toxicity or GVHD. Negative selection, by administration of GCV resulted in donor cell depletion without graft ablation, as re-expansion of donor cells was achieved with BG/BCNU treatment. These studies show promise for developing non-ablative allotransplant approaches using in vivo positive/negative selection. PMID:22871662

Falahati, Rustom; Zhang, Jianqing; Flebbe-Rehwaldt, Linda; Shi, Yimin; Gerson, Stanton L; Gaensler, Karin Ml

2012-11-01

133

Single nucleotide polymorphism-arrays provide new insights in the pathogenesis of post-transplant diffuse large B-cell lymphoma.  

PubMed

Post-transplant lymphoproliferative disorders (PTLD) are complications of solid organ transplantation associated with severe morbidity and mortality. Diffuse large B-cell lymphoma (DLBCL) represents the most common form of monomorphic PTLD. We studied 44 cases of post-transplant DLBCL (PT-DLBCL) with high-density genome wide single nucleotide polymorphism-based arrays, and compared them with 105 cases of immunocompetent DLBCL (IC-DLBCL) and 28 cases of Human Immunodeficiency Virus-associated DLBCL (HIV-DLBCL). PT-DLBCL showed a genomic profile with specific features, although their genomic complexity was overall similar to that observed in IC- and HIV-DLBCL. Among the loci more frequently deleted in PT-DLBCL there were small interstitial deletions targeting known fragile sites, such as FRA1B, FRA2E and FRA3B. Deletions at 2p16.1 (FRA2E) were the most common lesions in PT-DLBCL, occurring at a frequency that was significantly higher than in IC-DLBCL. Genetic lesions that characterized post-germinal center IC-DLBCL were under-represented in our series of PT-DLBCL. Two other differences between IC-DLBCL and PT-DLBCL were the lack of del(13q14.3) (MIR15/MIR16) and of copy neutral LOH affecting 6p [major histocompatibility complex (MHC) locus] in the latter group. In conclusion, PT-DLBCL presented unique features when compared with IC-DLBCL. Changes in PT-DLBCL were partially different to those in HIV-DLBCL, suggesting different pathogenetic mechanisms in the two conditions linked to immunodeficiency. PMID:20230398

Rinaldi, Andrea; Capello, Daniela; Scandurra, Marta; Greiner, Timothy C; Chan, Wing C; Bhagat, Govind; Rossi, Davide; Morra, Enrica; Paulli, Marco; Rambaldi, Alessandro; Rancoita, Paola M V; Inghirami, Giorgio; Ponzoni, Maurilio; Moreno, Santiago M; Piris, Miguel A; Mian, Michael; Chigrinova, Ekaterina; Zucca, Emanuele; Favera, Riccardo D; Gaidano, Gianluca; Kwee, Ivo; Bertoni, Francesco

2010-05-01

134

Acquired C1-inhibitor deficiency and lymphoproliferative disorders: a tight relationship.  

PubMed

Angioedema due to the acquired deficiency of C1-inhibitor is a rare disease known as acquired angioedema (AAE), which was first described in a patient with high-grade lymphoma and is frequently associated with lymphoproliferative diseases, including expansion of B cell clones producing anti-C1-INH autoantibodies, monoclonal gammopathy of uncertain significance (MGUS) and non-Hodgkin lymphoma (NHL). AAE is clinically similar to hereditary angioedema (HAE), and is characterized by recurrent episodes of sub-cutaneous and sub-mucosal edema. It may affect the face, tongue, extremities, trunk and genitals. The involvement of the gastrointestinal tract causes bowel sub-occlusion with severe pain, vomiting and diarrhea, whereas laryngeal edema can be life-threatening. Unlike those with HAE, AAE patients usually have late-onset symptoms, do not have a family history of angioedema and present variable response to treatment due to the hyper-catabolism of C1-inhibitor. Reduced C1-inhibitor function leads to activation of the classic complement pathway with its consumption and activation of the contact system leading to the generation of the vasoactive peptide bradykinin, which increases vascular permeability and induces angioedema. Lymphoprolipherative diseases and AAE are tightly linked with either angioedema or limphoprolyferation being the first symptom. Experimental data indicate that neoplastic tissue and/or anti-C1-inhibitor antibodies induce C1-inhibitor consumption, and this is further supported by the observation that cytotoxic treatment of the lymphoproliferative diseases associated with AAE variably reverses the complement impairment and leads to a clinical improvement in angioedema symptoms. PMID:23490322

Castelli, Roberto; Zanichelli, Andrea; Cicardi, Marco; Cugno, Massimo

2013-09-01

135

HTLV Tax gene expression in patients with lymphoproliferative disorders.  

PubMed Central

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

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

1996-01-01

136

Yersinia enterocolitica Infection Simulating Lymphoproliferative Disease, after Liver Transplant.  

PubMed

We describe a 14-year-old girl, who was 13?y after liver transplantation for biliary atresia with an unremarkable postoperative course. She presented with fever of up to 40°C, extreme fatigue, malaise, anorexia, and occasional vomiting. On physical examination the only finding was splenomegaly. Lab results showed hyperglobulinemia and an elevated sedimentation rate. Liver function tests were normal except for mild elevation of ?GTP. Abdominal U/S and CT demonstrated an enlarged spleen with retroperitoneal and mesenteric lymph nodes enlargement. An exhaustive evaluation for infectious causes, autoimmune conditions, and malignancy was negative. A full recovery after 5 months prompted testing for self-limited infectious etiologies. Yersinia enterocolitica infection was diagnosed. PMID:25126442

Jakobovich, E; Koplewitz, B; Marva, E; Granot, E

2014-01-01

137

Genetics Home Reference: X-linked lymphoproliferative disease  

MedlinePLUS

... without EBV infection, usually have an enlarged spleen (splenomegaly), and may also have inflammation of the large ... lymphoma ; molecule ; mutation ; proliferation ; protein ; recessive ; sex chromosomes ; splenomegaly ; susceptibility ; syndrome ; virus ; X-linked recessive You may ...

138

Peripheral blood cells chimerism after unrelated cord blood transplantation in children: kinetics, predictive factors and impact on post-transplant outcome.  

PubMed

This study aimed to describe kinetics of complete donor chimerism occurrence (cDC, >99·9% donor) after unrelated cord blood transplantation (UCBT), to identify its predictive factors and its impact on post-transplant outcome. Ninety-four children who received single UCBT after a myeloablative conditioning regimen had blood chimerism evaluation at predefined post-transplant dates, using a real-time polymerase chain reaction method with 0·1% sensitivity. Cumulative incidence of cDC at 1 year post-transplantation was 61·8%. Three predictive factors were identified in multivariate analysis: history of malignant disease (P = 0·03), older age (above 2·16 years, the first quartile of age, P = 0·0055) and higher level of cord/recipient human leucocyte antigen mismatch (4/6 vs. 5-6/6, P < 0·001) increased the probability of post-transplant cDC. Although graft cell dose had a strong impact on haematological recovery, it did not apparently influence cDC occurrence. Early cDC (i.e. more than 99·9% donor chimerism on days 15-30 post-transplant) appeared useful to predict engraftment (P = 0·003) as well as acute and chronic graft-versus-host disease (GvHD). Severe acute or chronic GvHD never occurred in patients with DC ?99·9%, suggesting than even minimal residual host haematopoiesis is associated with a very low risk of GvHD after UCBT. PMID:24779895

Elkaim, Elodie; Picard, Christophe; Galambrun, Claire; Barlogis, Vincent; Loundou, Anderson; Curtillet, Catherine; Oudin, Claire; Thuret, Isabelle; Chambost, Hervé; Michel, Gérard

2014-08-01

139

Donor Risk Index Predicts Graft Failure Reliably But Not Post-Transplant Infections  

PubMed Central

Abstract Background: The Donor Risk Index (DRI) is used to predict graft survival following liver transplantation, but has not been used to predict post-operative infections in graft recipients. We hypothesized that lower-quality grafts would result in more frequent infectious complications. Methods: Using a prospectively collected infection data set, we matched liver transplant recipients (and the respective allograft DRI scores) with their specific post-transplant infectious complications. All transplant recipients were organized by DRI score and divided into groups with low-DRI and high-DRI scores. Results: We identified 378 liver transplants, with 189 recipients each in the low-DRI and high-DRI groups. The mean DRI scores for the low- and high-DRI-score groups were 1.14±0.01 and 1.74±0.02, respectively (p<0.0001 for the difference). The mean Model for End-Stage Liver Disease (MELD) scores were 26.25±0.53 and 24.76±0.55, respectively (p=0.052), and the mean number of infectious complications per patient were 1.60±0.19 and 1.94±0.24, respectively (p=0.26). Logistic regression showed only length of hospital stay and a history of vascular disease as being associated independently with infection, with a trend toward significance for MELD score (p=0.13). Conclusion: We conclude that although DRI score predicts graft-liver survival, infectious complications depend more heavily on recipient factors. PMID:24283760

Gillen, Jacob R.; Hranjec, Tjasa; Stokes, Jayme B.; Brayman, Kenneth L.; Kumer, Sean C.; Schmitt, Timothy M.; Sawyer, Robert G.

2014-01-01

140

Visceral leishmaniasis in the early post-transplant period after kidney transplantation: clinical features and therapeutic management.  

PubMed

Visceral leishmaniasis (VL) is a rare complication of kidney transplantation, with <100 cases reported in the literature. It is a life-threatening condition and usually occurs as a late complication after transplantation, with a median delay of 18 months between transplantation and onset of disease. We report the clinical features and management of 5 kidney transplant recipients who presented with VL in the early post-transplant period. All patients were successfully treated with liposomal amphotericin B (L-AMB), but 2 patients experienced graft loss. VL should be considered in the differential diagnosis in kidney transplant recipients living in endemic areas, who present with unexplained fever and pancytopenia in the early post-transplant period. Leishmania serology should be included in the screening of all transplant recipients, in order to identify a group of patients who could benefit from preemptive anti-Leishmania therapy. Therapy with L-AMB is highly effective and well tolerated in kidney transplant recipients with VL. PMID:20534033

Veroux, M; Corona, D; Giuffrida, G; Cacopardo, B; Sinagra, N; Tallarita, T; Giaquinta, A; Zerbo, D; Veroux, P F

2010-10-01

141

Post-transplant renal function in the first year predicts long-term kidney transplant survival  

Microsoft Academic Search

Post-transplant renal function in the first year predicts long-term kidney transplant survival.BackgroundImprovements in long-term kidney graft survival have been recently noted. However, the reasons for this were unclear. This study examined post-transplant renal function within the first year as an independent variable influencing long-term survival.MethodsThe influence of demographic characteristics (age, sex, race); transplant variables (cadaver versus living donor, cold ischemia

Sundaram Hariharan; Maureen A Mcbride; Wida S Cherikh; Christine B Tolleris; Barbara A Bresnahan; Christopher P Johnson

2002-01-01

142

Case Report Fulminant EBV-driven CD8 T-cell Lymphoproliferative Disorder Following Primary Acute EBV Infection: A Unique Spectrum of T-Cell Malignancy  

Microsoft Academic Search

Fulminant Epstein-Barr virus (EBV)-driven clonal T-cell lymphoproliferative disorder (T-LPD) is rare and most patients are of Asian origin. The disease usually develops shortly after primary acute EBV infection and the mechanism remains poorly understood. Here we report such a rare case in a 28-year-old Caucasian female with systemic lupus erythematosus (SLE). Immunophenotypic and molecular studies revealed that the proliferating lymphoid

Ken H. Young; Dahua Zhang; Jeffery T. Malik; Eliot C. Williams

143

Orally active vitamin d for potential chemoprevention of posttransplant malignancy.  

PubMed

Posttransplant malignancy (PTM) is a limiting factor both for patient and allograft survival in kidney transplant recipients (KTRs). We hypothesized that active vitamin D compounds (AVD) could reduce PTM development in KTRs. Ambulatory KTRs in a Japanese prospective cohort were followed from August 2007 to November 2010. The outcome of interest was newly diagnosed PTM. A propensity score (PS) of having received AVDs was estimated using 26 clinically relevant factors. We used the Cox proportional hazards model with stratification by PS tertiles on the assumption that baseline hazard functions differ among tertiles. As sensitivity analyses, we used inverse probability weighting and PS matching. Among 218 participants, the median age was 50 (interquartile range [IQR], 40 to 59) years, 63.3% were male, median time since transplantation was 11.2 (IQR, 5.2 to 17.1) years, and mean estimated GFR was 41.3 (SD, 15.6) mL/min per 1.73 m(2). At baseline, 42.2% had been treated with AVDs mainly for glucocorticoid-induced osteoporosis. AVDs used were calcitriol (58.7%) and alfacalcidol (41.3%). During follow-up, PTM developed in 5.4% of 92 AVD users and 8.7% of 126 nonusers. Poor vitamin D status was common in the participants, but the serum 25-hydroxyvitamin D level was not significantly associated with PTM in Cox regression analysis. After stratifying patients by PS tertiles, we found that AVDs were significantly associated with a lower risk of PTM (HR 0.25 [0.07 to 0.82]). Sensitivity analyses yielded similar results. AVDs are potential chemopreventive agents against PTM in KTRs. PMID:22926340

Obi, Yoshitsugu; Ichimaru, Naotsugu; Hamano, Takayuki; Tomida, Kodo; Matsui, Isao; Fujii, Naohiko; Okumi, Masayoshi; Kaimori, Jun-Ya; Yazawa, Koji; Kokado, Yukito; Tsubakihara, Yoshiharu; Nonomura, Norio; Rakugi, Hiromi; Takahara, Shiro; Isaka, Yoshitaka

2012-10-01

144

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

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

2013-10-22

145

Hematopoietic Neoplasias in Horses: Myeloproliferative and Lymphoproliferative Disorders  

PubMed Central

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

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

2010-01-01

146

Cutaneous lymphoid hyperplasia: a lymphoproliferative continuum with lymphomatous potential.  

PubMed

Cutaneous lymphoid hyperplasia (CLH) has been proposed to be the benign end of a continuum of lymphoproliferative disorders with cutaneous lymphoma at its malignant extreme. An intermediate condition, known as "clonal CLH," was first recognized by us and shown to be a transitional state capable of eventuating in overt lymphoma. To better determine the prevalence of dominant clonality and risk of lymphoma among CLH cases, we studied the immunohistology and clonality of fresh-frozen samples from 44 CLH patients referred to a multidisciplinary cutaneous lymphoproliferative disorders program. Using a large panel of lymphoid markers, the cases were divided into 38 typical mixed B-cell/T-cell type CLH and 6 T-cell-rich type (T-CLH), the latter containing > 90% T cells. Of the 44 patients, 38 had solitary or localized lesions (4 cases of T-CLH), and 6 had regional/generalized lesions (2 cases of T-CLH). Forty cases were of idiopathic etiology. Suspected etiologies among 4 other cases included mercuric tattoo pigment, doxepin, clozapine, and bacterial infection. Immunoglobulin heavy chain (IgH) and T-cell receptor (TCR)-gamma gene rearrangements (GR) were studied using polymerase chain reaction assays, which are approximately 80% sensitive. Overall, 27 cases (61%) showed clonal CLH: 12 IgH+ (27%; 3 cases of T-CLH); 13 TCR+ (30%; 1 case of T-CLH); and 2 IgH+/TCR+ (4%; neither case was T-CLH). Two cases (4%; 1 case of T-CLH) progressed to cutaneous B-cell lymphoma. Both of these patients presented with regional lesions. Our findings indicate that clonal overgrowth is common in CLH, links CLH to lymphoma, and probably involves both B- and T-cell lineages (although TCR GR by B cells and vice versa could not be ruled out). The high prevalence of dominant clonality in our series may have resulted from the sensitivity of our PCR assays as well as patient selection. PMID:12827617

Nihal, Minakshi; Mikkola, Debra; Horvath, Nancy; Gilliam, Anita C; Stevens, Seth R; Spiro, Timothy P; Cooper, Kevin D; Wood, Gary S

2003-06-01

147

Familial Lymphoproliferative Malignancies and Tandem Duplication of NF1 Gene  

PubMed Central

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

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

2014-01-01

148

Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorders.  

PubMed

Primary infection with Epstein-Barr virus (EBV) is usually asymptomatic and, in a normal host, EBV remains latent in B cells after primary infection for the remainder of life. Uncommonly, EBV can infect T or natural killer (NK) cells in a person with a defect in innate immunity, and EBV infection can cause unique systemic lymphoproliferative diseases (LPD) of childhood. Primary infection in young children can be complicated by hemophagocytic lymphohistiocytosis or fulminant systemic T-cell LPD of childhood. Uncommonly, patients can develop chronic active EBV (CAEBV) disease-type T/NK LPD, which includes CAEBV infection of the systemic form, hydroa vacciniforme-like T-cell LPD, and mosquito-bite hypersensitivity. The clinical course of CAEBV disease-type T/NK LPD can be smoldering, persistent or progressive, depending on the balance between viral factors and host immunity. Aggressive NK-cell leukemia, hydroa vacciniforme-like T-cell lymphoma, or uncommonly extranodal NK/T-cell lymphoma can develop in children and young adults with CAEBV disease-type T/NK-cell LPD. Extranodal T/NK-cell lymphoma is a disease of adults, and its incidence begins to increase in the third decade and comprises the major subtype of T/NK LPD throughout life. Aggressive NK-cell leukemia and nodal T/NK-cell lymphoma of the elderly are fulminant diseases, and immune senescence may be an important pathogenetic factor. This review describes the current progress in identifying different types of EBV-associated T/NK-cell LPD and includes a brief presentation of data from Korea. PMID:24438142

Park, Sanghui; Ko, Young H

2014-01-01

149

Filgrastim, lenograstim and pegfilgrastim in the mobilization of peripheral blood progenitor cells in patients with lymphoproliferative malignancies.  

PubMed

Patients with lymphoproliferative disorders, candidate to autologous stem cell transplantation (ASCT), require mobilization with chemotherapy and granulocyte colony -stimulating factor (G-CSF). This study looked for differences in hematopoietic peripheral stem cells (HPSCs) mobilization in response to the three available G-CSFs, namely lenograstim, filgrastim, and pegfilgrastim. Between 2000 and 2012, 146 patients (66 M and 80 F) who underwent ASCT for multiple myeloma, non-Hodgkin's lymphoma or Hodgkin's lymphoma were studied. All patients received induction therapy and then a mobilization regimen with cyclophosphamide plus lenograstim, or filgrastim, or pegfilgrastim. From days 12 to 14, HPSCs were collected by two to three daily leukaphereses. Our results show that high-dose cyclophosphamide plus lenograstim achieved adequate mobilization and the collection target more quickly and with fewer leukaphereses as compared to filgrastim and pegfilgrastim. No differences between the three regimens were observed regarding toxicity and days to WBC and platelet recovery. Thus, lenograstim may represent the ideal G-CSF for PBSC mobilization in patients with lymphoproliferative diseases. Further studies are needed to confirm these results and better understand the biological bases of these differences. PMID:24722996

Ria, Roberto; Reale, Antonia; Melaccio, Assunta; Racanelli, Vito; Dammacco, Franco; Vacca, Angelo

2014-04-11

150

A de novo monoclonal immunoglobulin deposition disease in a kidney transplant recipient: a case report  

PubMed Central

Introduction Myeloma following kidney transplantation is a rare entity. It can be divided into two groups: relapse of a previous myeloma and de novo myeloma. Some of these myelomas can be complicated by a monoclonal immunoglobulin deposition disease, which is even less common. Less than ten cases of monoclonal immunoglobulin deposition disease after renal graft have been reported in the literature. The treatment of these patients is not well codified. Case presentation We report the case of a 43-year-old white European man who received a renal transplant for a nephropathy of unknown etiology and developed a nephrotic syndrome with kidney failure at 2-years follow-up. We diagnosed a de novo monoclonal immunoglobulin deposition disease associated with a kappa light chain multiple myeloma, which is a very uncommon presentation for this disease. Three risk factors were identified in this patient: Epstein–Barr virus reactivation with cytomegalovirus co-infection; intensified immunosuppressive therapy during two previous rejection episodes; and human leukocyte antigen-B mismatches. Chemotherapy treatment and decrease in the immunosuppressive therapy were followed by remission and slight improvement of renal function. A relapse occurred 8 months later and his renal function worsened rapidly requiring hemodialysis. He died from septic shock 4 years after the diagnosis of monoclonal immunoglobulin deposition disease. Conclusions This rare case of post-transplant lymphoproliferative disorder with an uncommon presentation illustrates the fact that treatment in such a situation is very difficult to manage because of a small number of patients reported and a lack of information on this disease. There are no guidelines, especially concerning the immunosuppressive therapy management. PMID:24942882

2014-01-01

151

Atypical hydroa vacciniforme-like epstein-barr virus associated T/NK-cell lymphoproliferative disorder.  

PubMed

Epstein-Barr virus (EBV)-associated T-cell/natural killer (NK)-cell lymphoproliferative disorders (EBV-T/NK-LPDs) accompany severe chronic active EBV infection (CAEBV) or comprise the CAEBV disease entity. The CAEBV disease entity has the common feature of lymphoproliferation of T or NK cells (primarily), and B cells (rarely), with chronic activation of EBV infection. The disease is rare and seems to be more prevalent in East Asian countries. The CAEBV disease entity encompasses heterogenous disorders, including hydroa vacciniforme (HV), hypersensitivity to mosquito bites, EBV-associated hemophagocytic syndrome, NK/T-cell lymphoma, and NK-cell leukemia. Atypical HV-like eruptions are present on sun-exposed and nonexposed areas with facial edema, fever, and hepatosplenomegaly, unlike classic HV. Recently, it has been suggested that classic HV and atypical HV-like eruptions are variants within the same disease spectrum of EBV-T/NK-LPD. We report a Korean boy with an atypical HV-like eruption and various systemic manifestations, including fever, sore throat, abdominal pain, headaches, seizures, and hematologic abnormalities for 2 years. After the initial mild eruption, which resembled a viral exanthem, ulceronecrotic skin lesions gradually developed and were associated with a high-grade fever and constitutional symptoms. He had a CAEBV infection, which showed a predominant proliferation of NK cells with high EBV DNA levels in the peripheral blood. However, in the skin lesions, there were nonneoplastic CD4 T-cell infiltrations predominantly showing a monoclonal T-cell receptor-? gene rearrangement and positive EBV in situ hybridization. PMID:23169419

Lee, Hye Young; Baek, Jin Ok; Lee, Jong Rok; Park, Sang Hui; Jeon, In Sang; Roh, Joo Young

2012-12-01

152

Extra-intestinal malignancies in inflammatory bowel disease: results of the 3rd ECCO Pathogenesis Scientific Workshop (III).  

PubMed

The incidence of lymphoproliferative disorders (LD) is increasing in developed countries. Patients with inflammatory bowel disease (IBD) exposed to thiopurines are at additional risk of three specific forms of LD: Epstein-Barr-Virus-related post-transplant like LD, hepato-splenic T-cell lymphoma and post-mononucleosis lymphoproliferation. The risk of the two latter forms of LD can be reduced when considering specific immunosuppressive strategies in young males. It is still unclear whether the risk of uterine cervix abnormalities is increased in IBD women, irrespective of the use of immunosuppressants. Given the excess risk demonstrated in various other contexts of immunosuppression, it is currently recommended that all women with IBD, particularly those receiving immunosuppressants, strictly adhere to a screening program of cervical surveillance and undergo vaccination against HPV, when appropriate. Patients with IBD receiving immunosuppressants are at increased risk of skin cancers. The risk of non-melanoma skin cancer is notably increased in patients receiving thiopurines. Recent data suggest that the risk of melanoma is mildly increased in patients exposed to anti-TNF therapy. All IBD patients should adhere to a program of sun protection and dermatological surveillance, whose details should take into account the other non-IBD-related risk factors. PMID:23721759

Magro, Fernando; Peyrin-Biroulet, Laurent; Sokol, Harry; Aldeger, Xavier; Costa, Antonia; Higgins, Peter D; Joyce, Joel C; Katsanos, Konstantinos H; Lopez, Anthony; de Xaxars, Teresa Mas; Toader, Elena; Beaugerie, Laurent

2014-01-01

153

Chronic Disease and Childhood Development: Kidney Disease and Transplantation.  

ERIC Educational Resources Information Center

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…

Klein, Susan D.; Simmons, Roberta G.

154

The ambiguous boundary between EBV-related hemophagocytic lymphohistiocytosis and systemic EBV-driven T cell lymphoproliferative disorder  

PubMed Central

Epstein Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (EBV-HLH) is a form of acquired, infection-related HLH which typically represents a fulminant presentation of an acute EBV infection of CD8+ T cells with 30-50% mortality rate. Systemic EBV-positive lymphoproliferative disease of childhood (SE-LPD) is a rare T cell lymphoproliferative disorder predominantly arising in the setting of acute EBV infection, often presenting with HLH. Since both entities have been associated with clonal T cell populations, the discrimination between these diseases is often ambiguous. We report a unique case of a 21 years old female who presented with clinical and laboratory findings of florid HLH in the setting of markedly elevated EBV titers (>1 million) and an aberrant T cell population shown to be clonal by flow cytometry, karyotype, and molecular studies. This case raises the differential of EBV-HLH versus SE-LPD. Review of the literature identified 74 cases of reported EBV-HLH and 21 cases of SE-LPD with associated HLH in 25 studies. Of those cases with available outcome data, 62 of 92 cases (67%) were fatal. Of 60 cases in which molecular clonality was demonstrated, 37 (62%) were fatal, while all 14 cases (100%) demonstrating karyotypic abnormalities were fatal. Given the karyotypic findings in this sentinel case, a diagnosis of SE-LPD was rendered. The overlapping clinical and pathologic findings suggest that EBV-HLH and SE-LPD are a biologic continuum, rather than discrete entities. The most clinically useful marker of mortality was an abnormal karyotype rather than other standards of clonality assessment. PMID:25337215

Smith, Megan C; Cohen, Daniel N; Greig, Bruce; Yenamandra, Ashwini; Vnencak-Jones, Cindy; Thompson, Mary Ann; Kim, Annette S

2014-01-01

155

Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis  

Microsoft Academic Search

.   There is limited information regarding the incidence and features of post-transplant diabetes mellitus (PTDM) in pediatric\\u000a renal transplant recipients. We noted a recent increased frequency of PTDM and reviewed charts of children who underwent renal\\u000a transplantation from 1 September 1986 to 31 August 1999 to characterize the risk factors and natural history of PTDM. Sixteen\\u000a children were identified with

Louise C. Greenspan; Stephen E. Gitelman; Mary Ann Leung; David V. Glidden; Robert S. Mathias

2002-01-01

156

Efficacy of early post-transplant herbicides in leeks ( Allium porrum L.)  

Microsoft Academic Search

Three field studies were conducted to determine the selectivity on leeks (Allium porrum L.) of early post-transplant herbicides and their efficacy on weed populations and crop yields. Herbicide treatments were cinmethylin, metolachlor, oxyfluorfen, prodiamine, and pendimethalin. Both a non-treated and a weed-free control were added. The most common species were the broadleaved weeds Eclipta alba (L.) Hassk., Rorippa teres (Michx.)

James P. Gilreath; Bielinski M. Santos; Phyllis R. Gilreath; Donald N. Maynard

2008-01-01

157

Short communication Efficacy of early post-transplant herbicides in leeks (Allium porrum L.)  

Microsoft Academic Search

Three field studies were conducted to determine the selectivity on leeks (Allium porrum L.) of early post-transplant herbicides and their efficacy on weed populations and crop yields. Herbicide treatments were cinmethylin, metolachlor, oxyfluorfen, prodiamine, and pendimethalin. Both a non-treated and a weed-free control were added. The most common species were the broadleaved weeds Eclipta alba (L.) Hassk., Rorippa teres (Michx.)

James P. Gilreath; Bielinski M. Santos; Phyllis R. Gilreath; Donald N. Maynard

158

Autoimmune lymphoproliferative syndrome with defective Fas: genotype influences penetrance.  

PubMed Central

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte homeostasis and immunological tolerance. Most patients have a heterozygous mutation in the APT1 gene, which encodes Fas (CD95, APO-1), mediator of an apoptotic pathway crucial to lymphocyte homeostasis. Of 17 unique APT1 mutations in unrelated ALPS probands, 12 (71%) occurred in exons 7-9, which encode the intracellular portion of Fas. In vitro, activated lymphocytes from all 17 patients showed apoptotic defects when exposed to an anti-Fas agonist monoclonal antibody. Similar defects were found in a Fas-negative cell line transfected with cDNAs bearing each of the mutations. In cotransfection experiments, Fas constructs with either intra- or extracellular mutations caused dominant inhibition of apoptosis mediated by wild-type Fas. Two missense Fas variants, not restricted to patients with ALPS, were identified. Variant A(-1)T at the Fas signal-sequence cleavage site, which mediates apoptosis less well than wild-type Fas and is partially inhibitory, was present in 13% of African American alleles. Among the ALPS-associated Fas mutants, dominant inhibition of apoptosis was much more pronounced in mutants affecting the intracellular, versus extracellular, portion of the Fas receptor. Mutations causing disruption of the intracellular Fas death domain also showed a higher penetrance of ALPS phenotype features in mutation-bearing relatives. Significant ALPS-related morbidity occurred in 44% of relatives with intracellular mutations, versus 0% of relatives with extracellular mutations. Thus, the location of mutations within APT1 strongly influences the development and the severity of ALPS. PMID:10090885

Jackson, C E; Fischer, R E; Hsu, A P; Anderson, S M; Choi, Y; Wang, J; Dale, J K; Fleisher, T A; Middelton, L A; Sneller, M C; Lenardo, M J; Straus, S E; Puck, J M

1999-01-01

159

Localized peripancreatic plasma cell Castleman disease.  

PubMed

Castleman disease (CD) is a rare, benign, and usually systemic lymphoproliferative disorder. Unicentric Castleman disease of the pancreas is extremely rare, with only less than 10 cases described in the literature. We describe a case of an isolated peripancreatic localization of a plasma cell-type Castleman disease, its clinical presentation, the diagnostic evaluation, and the cure of disease by surgical excision. PMID:20079482

Charalabopoulos, Alexandre; Misiakos, Evangelos P; Foukas, Perikles; Tsapralis, Dimitrios; Charalampopoulos, Anestis; Liakakos, Theodore; Macheras, Anastasios

2010-05-01

160

Risk for Lymphoma and the Results of Follow-up Gut Biopsies in Patients with Celiac Disease  

MedlinePLUS

... of Follow-up Gut Biopsies in Patients With Celiac Disease The full report is titled “Mucosal Healing and Risk for Lymphoproliferative Malignancy in Celiac Disease. A PopulationBased Cohort Study.” It is in the ...

161

[Post-transplant recurrence of glomerulonephritis: a complex clinical case].  

PubMed

Lupus nephritis (LN) seldom recurs in a grafted kidney. By contrast, primary membranoproliferative glomerulonephritis (MPGN), which has been included, along with hemolytic uremic syndrome and age-related maculopathy, among the complement dysregulation diseases, has a high recurrence rate and is considered a contraindication to living-donor kidney transplant because of the poor prognosis. We report the case of a young girl with LN-related chronic renal failure who underwent a living donor transplant from her mother. After four months she had a recurrence that did not match the criteria for LN. Graft biopsies and revision of the clinical course pointed to type II MPGN on the basis of a lack of ARA criteria, persistent isolated low C3 levels, and response to plasma therapy. If confirmed by genetic analysis, the patient might benefit from treatment with the monoclonal antibody against the C5-C9 complex, eculizumab. PMID:21132668

Bonucchi, Decenzio; Leonelli, Marco; Damiano, Francesca; Granito, Maria; Ghiandai, Giulia; De Amicis, Sara; Americo, Claudio; Ligabue, Giulia; Albertazzi, Vittorio; Cappelli, Gianni

2010-01-01

162

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

PubMed Central

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

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

163

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

PubMed Central

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

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

2015-01-01

164

Fibroblast Growth Factor-23 and Parathyroid Hormone Are Associated with Post-Transplant Bone Mineral Density Loss  

PubMed Central

Background and objectives: Among the multiple factors contributing to bone mineral density (BMD) loss after renal transplantation, hypophosphatemia is increasingly recognized to play an important role. Hypophosphatemia occurs in up to 90% of the renal transplant recipients in the early post-transplant period and is caused by renal phosphate wasting. We hypothesized that a high pretransplant level of the recently described phosphaturic hormone fibroblast growth factor 23 (FGF-23) is a risk factor for accelerated BMD loss occurring within the first post-transplant year. Design, setting, participants, & measurements: We performed a two-center observational retrospective cohort study in 127 incident renal transplant recipients. Serum full-length FGF-23, parathyroid hormone (PTH), and parameters of mineral metabolism were determined at the time of transplantation. BMD was assessed by osteodensitometry at the time of transplantation and 1 year later. Results: A moderate decrease of BMD was observed during the first post-transplant year. High FGF-23 levels were associated with BMD loss at the lumbar spine and total hip region, whereas low PTH levels were associated with BMD loss at all three regions. Cumulative doses of prednisone and post-transplant serum phosphate level were not correlated with BMD changes. Conclusion: Our data indicate that patients with a high serum FGF-23 level and/or a low PTH level at the time of transplantation are at risk for increased BMD loss during the first post-transplant year. PMID:20634326

Claes, Kathleen; Devogelaer, Jean-Pierre; Vanderschueren, Dirk; Depresseux, Genevieve; Goffin, Eric; Evenepoel, Pieter

2010-01-01

165

Immunophenotypic characterization of acute leukemias and chronic lymphoproliferative disorders: practical recommendations and classifications  

Microsoft Academic Search

Immunophenotypic characterization of leukemic cells has become essential for the diagnosis of acute leukemias (AL) and chronic lymphoproliferative disorders (CLPD). Immunophenotyping allows to classify AL according to (i) lineage assignement of the leukemic clone based on the degree of specificity (or “score”) of expressed markers, (ii) the différentiation level of the clone and (iii) the presence of irrelevant markers. In

R. Garand; N. Robillard

1997-01-01

166

Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS)  

Microsoft Academic Search

Autoimmune lymphoproliferative syn- drome (ALPS) is a rare disorder of dis- rupted lymphocyte homeostasis. Clinical manifestations of ALPS vary but typically include autoimmune cytopenias, organo- megaly, lymphadenopathy, and increased risk of malignancies. A similar spectrum of symptoms may be seen in some pa- tients with Evans syndrome (ES), a hema- tologic disorder defined by autoimmune destruction of at least 2

David T. Teachey; Catherine S. Manno; Kelly M. Axsom; Timothy Andrews; John K. Choi; Barbara H. Greenbaum; Joseph M. McMann; Kathleen E. Sullivan; Susan F. Travis; Stephan A. Grupp

2004-01-01

167

Post-transplantation Lymphoproliferative Disorder in Heart and Kidney Transplant Patients: A Single-Center Experience  

Microsoft Academic Search

Background: Post-transplantation lymphoproliferative disorder (PTLD) after heart transplantation is a fatal complication, and standard treatment is either ineffective or too toxic. We have studied the incidence, clinical course, prognostic factors, and different treatment regimens pertaining to PTLD in 110 heart and 80 kidney transplant recipients.Methods: Information was abstracted from chart review of 110 heart transplant recipients and 80 kidney transplant

Sanjeev Wasson; Mohammad N. Zafar; John Best; Hanumanth K. Reddy

2006-01-01

168

Post-transplantation Lymphoproliferative Disorder in Heart and Kidney Transplant Patients: A Single-Center Experience  

Microsoft Academic Search

Background: Post-transplantation lymphoproliferative disorder (PTLD) after heart trans- plantation is a fatal complication, and standard treatment is either ineffective or too toxic. We have studied the incidence, clinical course, prognostic factors, and different treatment regi- mens pertaining to PTLD in 110 heart and 80 kidney transplant recipients. Methods: Information was abstracted from chart review of 110 heart transplant recipients and

Sanjeev Wasson; Mohammad N. Zafar; John Best; Hanumanth K. Reddy

169

Post-transplant soluble CD30 levels are associated with early subclinical rejection in kidney transplantation.  

PubMed

Several studies have shown association of high pre- or post-transplant levels of soluble CD30 (sCD30) with acute rejection and poor late kidney transplant outcome. Our goal was to investigate whether sCD30 levels at month-3 post-transplant are associated with subclinical rejection, presence of CD30(+) cells within the graft, and expression of immune response genes in peripheral blood mononuclear cells. The study comprised 118 adult first kidney graft recipients, transplanted at a single center, receiving tacrolimus in low concentration. All were submitted to a protocol biopsy at month-3. Subclinical rejection was identified in 10 biopsies and sCD30 levels?61.88ng/mL (P=0.004), younger recipient age (P=0.030) and non-Caucasian ethnicity (P=0.011) were independently associated with this outcome. Rare CD30(+) cells were present in only two biopsies. There was a correlation between sCD30 levels and CD30 gene expression in peripheral blood mononuclear cells (r=0.385, P=0.043). These results show that high sCD30 levels are independent predictors of graft dysfunction and may contribute to patient selection protocols by indicating those who could benefit from a more thorough evaluation. PMID:25698648

Grenzi, Patricia C; Campos, Érika F; Silva, Hélio T; Felipe, Claudia R; Franco, Marcelo F; Soares, Maria F; Medina-Pestana, José O; Gerbase-DeLima, Maria

2015-03-01

170

Association of high post-transplant soluble CD30 serum levels with chronic allograft nephropathy.  

PubMed

The purpose of this study was to evaluate the association of post-transplant soluble CD30 (sCD30) levels, isolated or in combination with of anti-HLA class II antibodies and of serum creatinine levels, with kidney graft loss due to chronic allograft nephropathy (CAN), and type of lesions in graft biopsies for cause. The study comprised 511 first kidney graft recipients, transplanted at a single center, with a graft functioning for at least 2.8 years. A single blood sample was collected from each patient. sCD30 levels were determined by ELISA, and HLA antibodies by Luminex assay. The minimum follow-up after testing was 9.3 years. High sCD30 levels, set at sCD30 ? 34.15 ng/mL, the presence of HLA class II antibodies, and serum creatinine ? 1.9 mg/dL were independently associated with CAN-graft loss (P values <0.0001, 0.05, <0.0001, respectively), and the combined hazard ratio for CAN-graft loss was 20.2. Analyses of 166 biopsies for cause showed that high sCD30 levels and creatinine were independently associated with interstitial lesions. Post-transplant sCD30 serum levels, especially in conjunction with information regarding HLA class II antibodies and serum creatinine levels, provide valuable information regarding graft outcome and could be useful for the management of kidney transplant recipients. PMID:23928467

Grenzi, Patricia C; Campos, Érika F; Tedesco-Silva, Hélio; Felipe, Claudia R; Franco, Marcello F; Soares, Maria Fernanda; Medina-Pestana, José Osmar; Gerbase-Delima, Maria

2013-12-01

171

Waldenström's macroglobulinemia harbors a unique proteome where Ku70 is severely underexpressed as compared with other B-lymphoproliferative disorders  

PubMed Central

Waldenström's macroglobulinemia (WM) is a clonal B-cell lymphoproliferative disorder (LPD) of post-germinal center nature. Despite the fact that the precise molecular pathway(s) leading to WM remain(s) to be elucidated, a hallmark of the disease is the absence of the immunoglobulin heavy chain class switch recombination. Using two-dimensional gel electrophoresis, we compared proteomic profiles of WM cells with that of other LPDs. We were able to demonstrate that WM constitutes a unique proteomic entity as compared with chronic lymphocytic leukemia and marginal zone lymphoma. Statistical comparisons of protein expression levels revealed that a few proteins are distinctly expressed in WM in comparison with other LPDs. In particular we observed a major downregulation of the double strand repair protein Ku70 (XRCC6); confirmed at both the protein and RNA levels in an independent cohort of patients. Hence, we define a distinctive proteomic profile for WM where the downregulation of Ku70—a component of the non homologous end-joining pathway—might be relevant in disease pathophysiology. PMID:22961060

Perrot, A; Pionneau, C; Azar, N; Baillou, C; Lemoine, F M; Leblond, V; Merle-Béral, H; Béné, M-C; Herbrecht, R; Bahram, S; Vallat, L

2012-01-01

172

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...

173

Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab  

PubMed Central

We report on posttransplant relapsed pediatric patients with B-precursor acute lymphoblastic leukemia with no further standard of care therapy who were treated with the T-cell engaging CD19/CD3-bispecific single-chain antibody construct blinatumomab on a compassionate use basis. Blast load was assessed prior to, during and after blinatumomab cycle using flow cytometry to detect minimal residual disease, quantitative polymerase chain reaction for rearrangements of the immunoglobulin or T-cell receptor genes, and bcr/abl mutation detection in one patient with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blinatumomab was administered as a 4-week continuous intravenous infusion at a dosage of 5 or 15 ?g/m2/day. Nine patients received a total of 18 cycles. Four patients achieved complete remission after the first cycle of treatment; 2 patients showed a complete remission from the second cycle after previous reduction of blast load by chemotherapy. Three patients did not respond, of whom one patient proceeded to a second cycle without additional chemotherapy and again did not respond. Four patients were successfully retransplanted in molecular remission from haploidentical donors. After a median follow up of 398 days, the probability of hematologic event-free survival is 30%. Major toxicities were grade 3 seizures in one patient and grade 3 cytokine release syndrome in 2 patients. Blinatumomab can induce molecular remission in pediatric patients with posttransplant relapsed B-precursor acute lymphoblastic leukemia and facilitate subsequent allogeneic hematopoietic stem cell transplantation from haploidentical donor with subsequent long-term leukemia-free survival. PMID:24727818

Schlegel, Patrick; Lang, Peter; Zugmaier, Gerhard; Ebinger, Martin; Kreyenberg, Hermann; Witte, Kai-Erik; Feucht, Judith; Pfeiffer, Matthias; Teltschik, Heiko-Manuel; Kyzirakos, Christina; Feuchtinger, Tobias; Handgretinger, Rupert

2014-01-01

174

Phagocytic activity of monocytes, their subpopulations and granulocytes during post-transplant adverse events after hematopoietic stem cell transplantation.  

PubMed

Phagocytosis of granulocytes and monocytes presents a major mechanism that contributes to the clearance of pathogens and cell debris. We analyzed the phagocytic activity of the peripheral blood cell monocytes, three monocyte subpopulations and granulocytes before and up to one year after hematopoietic stem cell transplantation, as well as during transplant-related adverse events. 25 pediatric patients and young adults (median age of 11.0 years) with hemato-oncological malignancies and non malignancies were enrolled in the prospective study. Ingestion of fluorescence-labeled Escherichia coli bacteria was used to assess the phagocytic activity of monocytes and their subpopulations and granulocytes by means of flow cytometry in the patient group as well as in a control group (n=36). During sepsis, a significant increase of phagocytic activity of monocytes (P=0.0003) and a significant decrease of the phagocytic activity of granulocytes (P=0.0003) and the CD14+ CD16++ monocyte subpopulation (P=0.0020) occurred. At the onset of a veno-occlusive disease, a significant increase of phagocytic activity in the CD14++ CD16+ monocyte subpopulation (P=0.001) and a significant decrease in the phagocytic activity of the CD14++ CD16- monocyte subpopulation (P=0.0048) were observed. In conclusion, the phagocytic activity of monocytes, their subpopulations and granulocytes might be a useful and easy determinable parameter that enables identification of post-transplant complications after hematopoietic stem cell transplantation. The alterations of phagocytic activity contribute to the altered immune response that accompanies adverse events after hematopoietic stem cell transplantation. PMID:25541241

Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Erbacher, Annika; Haufe, Susanne; Schwarze, Carl Philipp; Handgretinger, Rupert; Hofbeck, Michael; Kerst, Gunter

2015-05-01

175

Cardiac transplantation: Pre-transplant infectious diseases evaluation and post-transplant prophylaxis  

Microsoft Academic Search

Screening of recipients and donors of cardiac allografts for infectious pathogens, and the use of appropriate immunization\\u000a and antimicrobial prophylaxis strategies, remain important for the control of infection following heart transplantation. However,\\u000a the risk of infectious complications in a particular patient must often be weighed against the risk of delaying or denying\\u000a allograft transplantation. In addition, the ongoing degree of

Susan Keay

2002-01-01

176

Micophenolat Mofetil versus Azathioprine: effects on renal graft function in early posttransplant period.  

PubMed

All conventional immunosuppressive tree drugs-protocols are based on Cyclosporine; consisting of low doses of Cyclosporine (CsA), Azathioprine (AZA) or Mycophenolate Mofetil (MMF) and Prednisolone. AZA has been used in clinical transplantation for more than 30 years and was the first immunosuppressive agent to achieve widespread use in organ transplantation. MMF was introduced in clinical practice in 1995 after several clinical trials proved that it was more efficient than AZA for prevention of acute rejection episodes. Our aim was to evaluate influence of AZA and MMF on renal graft function in early post-transplant stage. Study recruited 74 patients who underwent kidney transplantation in University Clinical Centre Tuzla. All patients received CsA and corticosteroid-based immunosuppression, as a part of triple immunosuppressive regiment, 40 patients received AZA and 34 MMF. In order to assess renal graft function, following parameters were evaluated: glomerular filtration rate GFR (ml/min) creatinine clearance (CrCl) (ml/min), 24 h urine output (ml/day), and from the serum potassium, sodium, urea and creatinine (mmol/dm3). Significantly higher average values of 24 hour urine output were recorded during first seven postoperative days in patients receiving MMF compared to those treated with AZA. Serum creatinine values showed statistically significant decrease, starting with the second postoperative day, in MMF vs. AZA group (168,7+/-70,5 vs. 119,9+/-42,6; p<0,0007). GFR was significantly higher in MMF compared to the AZA group of patients. On the first post-transplant day CrCl was higher in AZA group (24,3+/-10 vs. 17,5+/-7,3; p=0,01), next six days situation is reversed CrCl is significantly higher in the MMF group (43,7+/-15 vs. 53, 4+/-22, 8 p=0,006). MMF vs. AZA therapy was associated with protective effect against worsening of renal function in first seven post-transplant days. PMID:19485949

Ljuca, Farid; Imamovi?, Semir; Mesi?, Deso; Hasuki?, Sefik Hasuki?; Omerovi?, Safet; Bazardzanovi?, Mustafa; Iljazagi?-Halilovi?, Fatima

2009-05-01

177

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

PubMed Central

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

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

178

The association of early post-transplant glucose levels with long-term mortality  

Microsoft Academic Search

Aims\\/objective  We aimed to assess the long-term effects of post-transplant glycaemia on long-term survival after renal transplantation.\\u000a \\u000a \\u000a \\u000a Methods  Study participants were 1,410 consecutive transplant recipients without known diabetes who underwent an OGTT 10 weeks post-transplant\\u000a and were observed for a median of 6.7 years (range 0.3–13.8 years). The HRs adjusted for age, sex, traditional risk factors\\u000a and transplant-related risk factors were estimated.\\u000a \\u000a \\u000a \\u000a \\u000a Results  Each 1 mmol\\/l increase

T. G. Valderhaug; J. Hjelmesæth; A. Hartmann; J. Røislien; H. A. Bergrem; T. Leivestad; P. D. Line; T. Jenssen

2011-01-01

179

Complementary and alternative medicine: risks and special considerations in pretransplant and posttransplant patients.  

PubMed

Although herbs and botanicals have been available for thousands of years, detailed scientific research regarding the potential health benefits and risks of dietary supplements has been conducted only for the past 15-20 years. Millions of Americans use herbal supplements regularly, but many are not aware of the possible hidden dangers. Organ transplant recipients and patients with end-stage organ failure awaiting transplantation are at particularly high risk for potential complications due to herbal supplement use. This review provides background information regarding complementary and alternative medicine (CAM) use in the United States, regulatory history of dietary supplements in the United States, and concerns and special considerations regarding the risks associated with dietary/herbal supplement use in pretransplant and posttransplant patients. PMID:24710858

Corey, Rebecca L; Rakela, Jorge

2014-06-01

180

Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop.  

PubMed

Lymphadenopathy in children for which no infectious or malignant cause can be ascertained constitutes a challenging diagnostic dilemma. Autoimmune lymphoproliferative syndrome (ALPS) is a human genetic disorder of lymphocyte apoptosis resulting in an accumulation of lymphocytes and childhood onset chronic lymphadenopathy, splenomegaly, multilineage cytopenias, and an increased risk of B-cell lymphoma. In 1999, investigators at the National Institutes of Health (NIH) suggested criteria to establish the diagnosis of ALPS. Since then, with approximately 500 patients with ALPS studied worldwide, significant advances in our understanding of the disease have prompted the need for revisions to the existing diagnostic criteria and classification scheme. The rationale and recommendations outlined here stem from an international workshop held at NIH on September 21 and 22, 2009, attended by investigators from the United States, Europe, and Australia engaged in clinical and basic science research on ALPS and related disorders. It is hoped that harmonizing the diagnosis and classification of ALPS will foster collaborative research and better understanding of the pathogenesis of autoimmune cytopenias and B-cell lymphomas. PMID:20538792

Oliveira, Joao B; Bleesing, Jack J; Dianzani, Umberto; Fleisher, Thomas A; Jaffe, Elaine S; Lenardo, Michael J; Rieux-Laucat, Frederic; Siegel, Richard M; Su, Helen C; Teachey, David T; Rao, V Koneti

2010-10-01

181

Immunological Basis for Resistance and Susceptibility to Marek's Disease  

Technology Transfer Automated Retrieval System (TEKTRAN)

Marek’s disease (MD) is a contagious lymphoproliferative disease of domestic chickens 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. Mechanisms of viral pathogenesis, r...

182

B- and T-cell markers in lymphoproliferative disorders with blood and bone marrow involvement.  

PubMed

B- and T-cell surface markers were determined in 26 adult patients with lymphoproliferative malignancies who had bone marrow and blood involvement. The patients in whom more than 60% of the abnormal cells were immunoglobulin-bearing cells were considered to have B-cell lymphoproliferative malignancy. The diagnosis of a T-cell disorder was made in those patients in whom more than 70% of the cells formed E rosettes (T cells). Those patients in whom 30% and more of the abnormal cells did not show B- and T-cell surface markers were regarded as suffering from "null" cell disorder. The B-cell type of lymphoproliferative malignancy was the most commonly encountered (63%) with an equal male to female ratio. In addition, 4 male patients with "hairy-cell" leukaemia were shown to have a B-cell disorder. T-cell disorders were found in 3 male patients; 1 patient had acute lymphoblastic leukaemia and in the other 2 the histopathological diagnosis was well-differentiated lymphoma and Sternberg sarcoma. Four patients with "null" cell lymphoma were found, the histopathological diagnoses in all were poorly-differentiated lymphocytic lymphoma, and 3 of the 4 patients were males. Further haematological investigations of the B-cell and the non-B-cell disorders showed that although the bone marrow was equally extensively infiltrated in both groups, the non-B-cell disroders were more commonly associated with complications of anemia and thrombocytopenia. It is therefore postulated that the abnormal lymphoid cell involved in B-cell disorders is an end-stage cell and not the haemopoietic stem cell. PMID:358421

Katz, J; Lea, R; Livni, N; Lewis, D; Lynch, S R; Skikne, B; Bezwoda, W

1978-05-20

183

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

PubMed

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

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

2013-01-01

184

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

PubMed

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

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

2013-09-11

185

Bordetella bronchiseptica infection in stage IV Hodgkin's disease  

PubMed Central

It is well known that patients with lymphoproliferative disorders have an altered immune status and are susceptible to opportunistic and non-opportunistic infections. The authors report the first case of a patient with advanced Hodgkin's disease who developed pneumonia caused by the animal pathogen Bordetella bronchiseptica. The most likely source of this organism was the patient's dog. While B. bronchiseptica is often responsible for outbreaks of pneumonia and septicaemia in wild and domestic animals, its role and incidence in human infections is not known. It is felt that patients with underlying lymphoproliferative diseases and pneumonia should be questioned about any contact with animals. PMID:7339608

Stoll, David B.; Murphey, Shelia A.; Ballas, Samir K.

1981-01-01

186

Tumour angiogenesis in Epstein-Barr virus-associated post-transplant smooth muscle tumours.  

PubMed

Epstein-Barr virus (EBV)-associated post-transplant smooth muscle tumours (PTSMT), are rare complications following organ/stem cell transplantation. Despite the mainly benign behaviour of PTSMT, alternative therapies are needed for those patients with progressive tumours. In tumours not approachable by surgery or reduction of immunosuppression, the angiogenic microenvironment might be a potential target of therapy, an approach that is well utilised in other soft tissue neoplasms. In a previous study, we evaluated the expression of EBV-related genes and the microRNA profile in PTSMT, but so far the characteristics of angiogenesis in PTSMT are not known. Therefore, the aim of this study was to evaluate the expression pattern of angiogenesis-related genes in PTSMT, in order to identify potential target molecules for anti-angiogenic therapy.PTSMT (n?=?5 tumours) were compared with uterine leiomyomas (n?=?7). Analyses included real-time PCR of 45 angiogenesis-associated genes, immunohistochemistry (CD31, prostaglandin endoperoxide synthase 1/PTGS1) and assessment of tumour vascularisation by conventional histopathology.PTSMT showed similar or fewer vessels than leiomyomas. Of the genes under investigation, 23 were down-deregulated (pro-angiogenic and some anti-angiogenic factors) and five were up-regulated (e.g. PTGS1 which is expressed at very low levels in leiomyomas but moderately higher levels in PTSMT).In summary, no particular target molecule could be identified, because tumour angiogenesis in PTSMT is characterised by low levels of major pro-angiogenic factors and there is no prominent increase in tumour vascularisation. EBV can induce angiogenesis via its viral late membrane protein 1 (LMP1) but PTSMT frequently do not express LMP1, which could be an explanation why, despite EBV infection, PTSMT show no exaggerated tumour angiogenesis. PMID:24398114

Jonigk, Danny; Izykowski, Nicole; Maegel, Lavinia; Schormann, Eileen; Ludewig, Britta; Kreipe, Hans; Hussein, Kais

2014-01-01

187

Tumour angiogenesis in Epstein-Barr virus-associated post-transplant smooth muscle tumours  

PubMed Central

Epstein-Barr virus (EBV)-associated post-transplant smooth muscle tumours (PTSMT), are rare complications following organ/stem cell transplantation. Despite the mainly benign behaviour of PTSMT, alternative therapies are needed for those patients with progressive tumours. In tumours not approachable by surgery or reduction of immunosuppression, the angiogenic microenvironment might be a potential target of therapy, an approach that is well utilised in other soft tissue neoplasms. In a previous study, we evaluated the expression of EBV-related genes and the microRNA profile in PTSMT, but so far the characteristics of angiogenesis in PTSMT are not known. Therefore, the aim of this study was to evaluate the expression pattern of angiogenesis-related genes in PTSMT, in order to identify potential target molecules for anti-angiogenic therapy. PTSMT (n?=?5 tumours) were compared with uterine leiomyomas (n?=?7). Analyses included real-time PCR of 45 angiogenesis-associated genes, immunohistochemistry (CD31, prostaglandin endoperoxide synthase 1/PTGS1) and assessment of tumour vascularisation by conventional histopathology. PTSMT showed similar or fewer vessels than leiomyomas. Of the genes under investigation, 23 were down-deregulated (pro-angiogenic and some anti-angiogenic factors) and five were up-regulated (e.g. PTGS1 which is expressed at very low levels in leiomyomas but moderately higher levels in PTSMT). In summary, no particular target molecule could be identified, because tumour angiogenesis in PTSMT is characterised by low levels of major pro-angiogenic factors and there is no prominent increase in tumour vascularisation. EBV can induce angiogenesis via its viral late membrane protein 1 (LMP1) but PTSMT frequently do not express LMP1, which could be an explanation why, despite EBV infection, PTSMT show no exaggerated tumour angiogenesis. PMID:24398114

2014-01-01

188

Lymphoproliferative responses and protection in conventional piglets inoculated orally with virulent or attenuated porcine epidemic diarrhoea virus  

Microsoft Academic Search

Lymphocyte proliferative responses were evaluated in mucosal (mesenteric lymph nodes) and systemic (spleen and blood) lymphoid tissues of conventional piglets inoculated with the virulent or attenuated isolates of porcine epidemic diarrhoea virus (PEDV) strain CV-777 and challenged 21 days later with the virulent isolate of the same virus. A lymphoproliferative assay was developed in which mononuclear cells isolated from lymphoid

M. L de Arriba; A Carvajal; J Pozo; P Rubio

2002-01-01

189

Effective treatment of high-grade lymphoproliferative disorder after renal transplantation using autologous lymphocyte activated killer cell therapy  

Microsoft Academic Search

Posttransplantation lymphoproliferative disorders (PTLD) is not uncommon and can occur in 2% to 5% of solid organ recipients on immunosuppression. Epstein-Barr virus (EBV) infection or reactivation and intensive anti-T lymphocyte treatment are important pathogenetic factors for a large proportion of these disorders. Nonclonal lesions with polymorphous histology have a potential for regressing when the immunosuppressants are reduced or stopped. Clonal

PK Li; K Tsang; CC Szeto; TY Wong; CB Leung; SF Lui; S Yu; FM Lai

1998-01-01

190

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...

191

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...

192

Global gene expression profiling of Marek's disease virus during cytolytic and latency infection  

Technology Transfer Automated Retrieval System (TEKTRAN)

Marek’s disease (MD), a lymphoproliferative disease of domestic chickens, is caused by an avian alpha-herpesvirus, Marek’s disease virus (MDV). MDV causes an early cytolytic infection in B cells followed by a latency infection in CD4+ T cells. The transcriptional analysis of a limited number of MD...

193

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...

194

Transcriptional profiling of Marek's disease virus genes during cytolytic and latent infection  

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 transcripts ha...

195

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...

196

Epidemiology and Clinical Features of Post-Transplant Bloodstream Infection: An Analysis of 222 Consecutive Liver Transplant Recipients  

PubMed Central

Background Bloodstream infection (BSI) is a significant cause of morbidity and mortality in liver transplant (LT) recipients. This study aimed to investigate the epidemiology and clinical features of post-transplant BSI in LT recipients. Materials and Methods The microbiology, frequency, and outcome of post-transplant BSI in the first year after LT were retrospectively analyzed in 222 consecutive patients who had received liver transplants at a single center between 2005 and 2011. The risk factors for post-transplant BSI and death were evaluated. Results During a 1-year period after LT, 112 episodes of BSI occurred in 64 of the 222 patients (28.8%). A total of 135 microorganisms were isolated from 112 BSI episodes including 18 polymicrobial episodes. The median time to BSI onset ranged from 8 days for Klebsiella pneumoniae to 101 days for enterococci, and the overall median for all microorganisms was 28 days. The most frequent pathogens were Enterobacteriaceae members (32.5%), enterococci (17.8%), yeasts (14.0%), Staphylococcus aureus (10.3%), and Acinetobacter baumannii (10.3%); most of them showed resistance to major antibiotics. The major sources of BSI were biliary tract (36.2%), abdominal and/or wound (28.1%), and intravascular catheter (18.5%) infections. The independent risk factors for post-transplant BSI were biliary complications (odds ratio [OR]: 2.91, 95% confidence interval [CI]: 1.29 to 6.59, P = 0.010) and longer hospitalization in the intensive care unit (OR: 1.04, 95% CI: 1.00 to 1.08, P < 0.001) after LT. BSI was an independent risk factor for death (hazard ratio [HR]: 3.92, 95% CI: 2.22 to 6.91, P < 0.001), with a poorer survival rate observed in patients with BSI than in those without BSI (1-year survival rate: 60.0% versus 89.5%, respectively, P < 0.001) after LT. The strongest predictors for death in patients with BSI were hepatocellular carcinoma (HR: 3.82, 95% CI: 1.57 to 9.32, P = 0.003), candidemia (HR: 3.71, 95% CI: 1.58 to 8.71, P = 0.003), polymicrobial bacteremia (HR: 3.18, 95% CI: 1.39 to 7.28, P = 0.006), and post-transplant hemodialysis (HR: 2.44, 95% CI: 1.02 to 5.84, P = 0.044). Conclusions BSI was a frequent post-transplant complication, and most of the causative pathogens were multi-drug resistant. Biliary complications and BSIs resulting from biliary infection are major problems for LT recipients. The prevention of BSI and biliary complications is critical in improving prognosis in liver transplant recipients. PMID:24396633

Kim, Hyun Kyung; Park, Yong Keun; Wang, Hee-Jung; Kim, Bong Wan; Shin, So Youn; Lim, Seung-Kwan

2013-01-01

197

Pre-transplant and post-transplant soluble CD30 for prediction and diagnosis of acute kidney allograft rejection  

Microsoft Academic Search

Background  Serum levels of soluble CD30 (sCD30) have been considered as a predictor of acute kidney allograft rejection. We have evaluated\\u000a the pre-transplant and post-transplant levels of sCD30 with the aim of determining its value in predicting and diagnosing\\u000a kidney rejection.\\u000a \\u000a \\u000a \\u000a Methods  We measured sCD30 serum levels before kidney transplantation, 5 days post-operatively, and at creatinine elevation episodes.\\u000a The predictive value of

Mohsen Nafar; Farhat Farrokhi; Mohammad Vaezi; Amir-Ebrahim Entezari; Fatemeh Pour-Reza-Gholi; Ahmad Firoozan; Behzad Eniollahi

2009-01-01

198

Preceeding the rejection: in search for a comprehensive post-transplant immune monitoring platform.  

PubMed

The survival of a transplanted organ is dependent on maintenance of continuous immunosuppression. However, even the strictest adherence to the recommended drug levels does not prevent the occurrence of numerous complications associated with immunosuppression. The efficacy of immunosuppression therapy protocols would be enhanced greatly by the availability of biotechnologies capable of identifying and predicting immunological events prior to the manifestation of clinical parameters indicating graft failure. The aim of the study was to evaluate the potential contribution of some modern tools for post-transplantation monitoring, and to propose a method for combining them into a comprehensive mechanism for this purpose. The technologies utilized in this study are among a group of 'cutting edge' diagnostic methods at the initial steps of evaluation for their potential contribution for post-transplantation immune monitoring. This study was a pioneering opportunity to combine and utilize these tools jointly. The method of research was based on monitoring 13 adult kidney transplant recipients. The Immuknow assay determined cellular immunity status by quantitative measurement of intracellular ATP level in CD4(+) lymphocytes after PHA stimulation. Sera were analyzed for concentration of soluble CD30 reflecting primary allo-stimulation and for donor specific anti-HLA antibodies responsible for accelerated and refractory rejection. The results were correlated with clinical and pathological parameters and appraisal of predictive value was attempted. In Immuknow assay analysis ATP incremental changes indicative of rejection or infection were found in 75% and in 50% incidences, respectively. In stable patients, the ATP deviation from the preoperative baseline, indicative of stable engraftment, was much less pronounced than in other habitual clinical tests. CD30 concentrations were measured greatly above normal values prior to biopsy-proven rejection episodes, both before and after the transplant operation. Anti-HLA antibodies were elevated at a later stage, concurrently with clinical manifestation of graft failure and rejection. Anti-HLA antibody level remained negligible in patients going through a stable post-transplant clinical course. Overall, the utilization of the platform of combined biotechnologies could serve as a valuable tool for immune monitoring in organ transplantation, allowing for therapeutic intervention that can favorably affect the clinical outcome. PMID:17584596

Israeli, Moshe; Yussim, Alex; Mor, Eitan; Sredni, Benjamin; Klein, Tirza

2007-07-01

199

Hepatitis C and Kidney Disease  

PubMed Central

Multiple extrahepatic manifestations have been associated with chronic hepatitis C, the most important among them being cryoglobulinemia, glomerulonephritis, porphyria cutanea tarda, lichen planus, seronegative arthritis, and lymphoproliferative disorders as in the sudies of Bonkovsky and Mehta (2001) and El-Serag et al. (2002). We will discuss in this paper chronic hepatitis C- related kidney disease and course and management of patients with chronic hepatitis C in special circumstances like hemodialysis and kidney transplantation. PMID:21188196

Hayat, Ashik; Mitwalli, Ahmad

2010-01-01

200

External validation of the estimated posttransplant survival score for allocation of deceased donor kidneys in the United States.  

PubMed

The US kidney allocation system adopted in 2013 will allocate the best 20% of deceased donor kidneys (based on the kidney donor risk index [KDRI]) to the 20% of waitlisted patients with the highest estimated posttransplant survival (EPTS). The EPTS has not been externally validated, raising concerns as to its suitability to discriminate between kidney transplant candidates. We examined EPTS using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. We included 4983 adult kidney-only deceased donor transplants over 2000-2011. We constructed three Cox models for patient survival: (i) EPTS alone; (ii) EPTS plus donor age, hypertension and HLA-DR mismatch; and (iii) EPTS plus log(KDRI). All models demonstrated moderately good discrimination, with Harrell's C statistics of 0.67, 0.68 and 0.69, respectively. These results are virtually identical to the internal validation that demonstrated a c-statistic of 0.69. These results provide external validation of the EPTS as a moderately good tool for discriminating posttransplant survival of adult kidney-only transplant recipients. PMID:24903739

Clayton, P A; McDonald, S P; Snyder, J J; Salkowski, N; Chadban, S J

2014-08-01

201

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...

202

Notch-Deficient Skin Induces a Lethal Systemic B-Lymphoproliferative Disorder by Secreting TSLP, a Sentinel for Epidermal Integrity  

Microsoft Academic Search

Epidermal keratinocytes form a highly organized stratified epithelium and sustain a competent barrier function together with dermal and hematopoietic cells. The Notch signaling pathway is a critical regulator of epidermal integrity. Here, we show that keratinocyte-specific deletion of total Notch signaling triggered a severe systemic B-lymphoproliferative disorder, causing death. RBP-j is the DNA binding partner of Notch, but both RBP-j–dependent

Shadmehr Demehri; Zhenyi Liu; Jonghyeob Lee; Meei-Hua Lin; Seth D Crosby; Christopher J Roberts; Perry W Grigsby; Jeffrey H Miner; Andrew G Farr; Raphael Kopan

2008-01-01

203

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

Microsoft Academic Search

Posttransplantation lymphoproliferative disorder (PTLD) is a life-threatening Ep- stein-Barr virus (EBV)-associated B-cell malignancy occurring in 1% to 2% of renal transplantation patients. Host- and PTLD-related factors determining the like- lihood of tumor response following reduc- tion of immune suppression (IS) and anti- viral therapy remain largely unknown. Standard therapy for PTLD is not well established. Eleven consecutive renal transplantation patients

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

2002-01-01

204

Cold agglutinin disease in fibrolamellar hepatocellular carcinoma: a rare association with a rare cancer variant  

PubMed Central

Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia. Although it can occur secondary to lymphoproliferative disorders and autoimmune or infectious diseases, CAD is rarely reported as secondary to solid tumors. We report a case of a woman aged 18 years diagnosed with a well-differentiated hepatocellular carcinoma of the fibrolamellar subtype, who was shown to have CAD also. Her general condition, including CAD, improved after targeted therapy with sorafenib for the hepatocellular carcinoma and only conservative measures for the CAD that consisted of avoidance of cold. In summary, although it is an extremely rare association and less common than lymphoproliferative disorders, CAD can be associated with solid tumors. PMID:21293066

Al-Matham, Khalid; Alabed, Iehab; Zaidi, Syed Z. A.; Qushmaq, Khalid A.

2011-01-01

205

No effect of C-reactive protein (CRP) haplotypes on CRP levels and post-transplant morbidity and mortality in renal transplantation.  

PubMed

Increased serum C-reactive protein (CRP) levels have been associated with all-cause and cardiovascular mortality after kidney transplantation. As genetic variations within the CRP gene determine CRP serum levels, we analyzed the association of both serum CRP levels, and post-transplant morbidity/mortality with CRP-genotypes/haplotypes. We determined CRP levels pretransplant, at 3 and 6 months post-transplant in 402 first kidney recipients, genotyped the three functionally distinct polymorphisms, and subsequently reconstructed the different haplotypes. Four different CRP-haplotypes were observed with a frequency >1%: CGC (33.3%), CGT (30.2%), CAT (29.7%) and GGT (6.8%). CRP levels pretransplantation or 3 and 6 months post-transplant were not different in patients with different CRP-haplotypes. Furthermore, no association of CRP-haplotypes/diplotypes was found with acute rejection, delayed graft function, all-cause mortality or cardiovascular events. In our renal transplant population, we found no association of CRP-haplotypes/diplotypes with either CRP levels or with post-transplant morbidity/mortality. In this inflammation-prone population, rather small genetically determined differences in serum CRP observed in normal populations presumably are overridden by background inflammation. Life long genetically determined increased serum CRP levels appear not to have an impact in our study, implying that CRP is more likely only a marker of current inflammation than a causative agent of cardiovascular morbidity and mortality. PMID:18266777

Krüger, Bernd; Böger, Carsten A; Schröppel, Bernd; Farkas, Stefan; Schnitzbauer, Andreas A; Hoffmann, Ute; Obed, Aiman; Murphy, Barbara T; Banas, Bernhard; Krämer, Bernhard K

2008-05-01

206

Deconvoluting Post-Transplant Immunity: Cell Subset-Specific Mapping Reveals Pathways for Activation and Expansion of Memory T, Monocytes and B Cells  

Microsoft Academic Search

A major challenge for the field of transplantation is the lack of understanding of genomic and molecular drivers of early post-transplant immunity. The early immune response creates a complex milieu that determines the course of ensuing immune events and the ultimate outcome of the transplant. The objective of the current study was to mechanistically deconvolute the early immune response by

Yevgeniy A. Grigoryev; Sunil M. Kurian; Zafi Avnur; Dominic Borie; Jun Deng; Daniel Campbell; Joanna Sung; Tania Nikolcheva; Anthony Quinn; Howard Schulman; Stanford L. Peng; Randolph Schaffer; Jonathan Fisher; Tony Mondala; Steven Head; Stuart M. Flechner; Aaron B. Kantor; Christopher Marsh; Daniel R. Salomon

2010-01-01

207

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

PubMed Central

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

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

2013-01-01

208

Angiolymphoid hyperplasia with eosinophilia: evidence for a T-cell lymphoproliferative origin.  

PubMed

Angiolymphoid hyperplasia with eosinophilia (ALHE) is commonly regarded an angioproliferative process characterized by the presence of prominent, bizarrely shaped blood vessels. These vessels are accompanied by an inflammatory infiltrate that is thought to be a reactive component. Both the cell of origin and the pathogenesis of ALHE remain controversial. To define the histogenesis of this disorder, we analyzed the phenotypic and genotypic profile of the inflammatory infiltrate in ALHE by immunohistochemistry and T-cell receptor gene rearrangement by polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis, as well as automated high-resolution PCR fragment analysis. Five of 7 ALHE patients displayed a clonal T-cell population and proliferative T-cell activity in lesional tissue. Most of these cases followed a protracted and therapy-reluctant course with recurrences. These data suggest that ALHE or a subset of ALHE cases harboring a clonal T-cell population may represent a T-cell lymphoproliferative disorder of a benign or low-grade malignant nature. PMID:12395376

Kempf, Werner; Haeffner, Andreas C; Zepter, Karoline; Sander, Christian A; Flaig, Michael J; Mueller, Beatrix; Panizzon, Renato G; Hardmeier, Thomas; Adams, Volker; Burg, Günter

2002-10-01

209

Peripheral T-cell and NK cell lymphoproliferative disorders: cell of origin, clinical and pathological implications.  

PubMed

T-cell lymphoproliferative disorders are a heterogeneous group of neoplasms with distinct clinical-biological properties. The normal cellular counterpart of these processes has been postulated based on functional and immunophenotypic analyses. However, T lymphocytes have been proven to be remarkably capable of modulating their properties, adapting their function in relationship with multiple stimuli and to the microenvironment. This impressive plasticity is determined by the equilibrium among a pool of transcription factors and by DNA chromatin regulators. It is now proven that the acquisition of specific genomic defects leads to the enforcement/activation of distinct pathways, which ultimately alter the preferential activation of defined regulators, forcing the neoplastic cells to acquire features and phenotypes distant from their original fate. Thus, dissecting the landscape of the genetic defects and their functional consequences in T-cell neoplasms is critical not only to pinpoint the origin of these tumors but also to define innovative mechanisms to re-adjust an unbalanced state to which the tumor cells have become addicted and make them vulnerable to therapies and targetable by the immune system. In our review, we briefly describe the pathological and clinical aspects of the T-cell lymphoma subtypes as well as NK-cell lymphomas and then focus on the current understanding of their pathogenesis and the implications on diagnosis and treatment. PMID:25510275

Inghirami, Giorgio; Chan, Wing C; Pileri, Stefano

2015-01-01

210

A novel recurrent NPM1-TYK2 gene fusion in cutaneous CD30-positive lymphoproliferative disorders.  

PubMed

The spectrum of cutaneous CD30-positive lymphoproliferative disorders (LPDs) includes lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma. Chromosomal translocations targeting tyrosine kinases in CD30-positive LPDs have not been described. Using whole-transcriptome sequencing, we identified a chimeric fusion involving NPM1 (5q35) and TYK2 (19p13) that encodes an NPM1-TYK2 protein containing the oligomerization domain of NPM1 and an intact catalytic domain in TYK2. Fluorescence in situ hybridization revealed NPM1-TYK2 fusions in 2 of 47 (4%) primary cases of CD30-positive LPDs and was absent in other mature T-cell neoplasms (n = 151). Functionally, NPM1-TYK2 induced constitutive TYK2, signal transducer and activator of transcription 1 (STAT1), STAT3, and STAT5 activation. Conversely, a kinase-defective NPM1-TYK2 mutant abrogated STAT1/3/5 signaling. Finally, short hairpin RNA-mediated silencing of TYK2 abrogated lymphoma cell growth. This is the first report of recurrent translocations involving TYK2, and it highlights the novel therapeutic opportunities in the treatment of CD30-positive LPDs with TYK2 translocations. PMID:25349176

Velusamy, Thirunavukkarasu; Kiel, Mark J; Sahasrabuddhe, Anagh A; Rolland, Delphine; Dixon, Catherine A; Bailey, Nathanael G; Betz, Bryan L; Brown, Noah A; Hristov, Alexandra C; Wilcox, Ryan A; Miranda, Roberto N; Medeiros, L Jeffrey; Jeon, Yoon K; Inamdar, Kedar V; Lim, Megan S; Elenitoba-Johnson, Kojo S J

2014-12-11

211

Chronic Graft Loss and Death in Patients With Post-Transplant Malignancy in Living Kidney Transplantation: A Competing Risk Analysis  

PubMed Central

Background: Malignancy is a common complication after renal transplantation. Death with functioning graft and chronic graft loss are two competing outcomes in patients with post-transplant malignancies. Objectives: The purpose of our study was to evaluate the risk factors associated with cumulative incidence of these two outcomes. Patients and Methods: Fine-Gray model was used for 266 cases with post-transplant malignancy in Iran. These patients were followed-up from the diagnosis until the date of last visit, chronic graft loss, or death, subsequently. Results: At the end of the study, as competing events, chronic graft loss and death with functioning graft were seen in 27 (10.2%) and 53 cases (19.9%), respectively, while 186 cases (69.9%) were accounted as censored. The incidence rate of death was approximately two-time of the incidence rate of chronic graft loss (8.6 vs. 4.4 per 100 person-years). In multivariate analysis, significant risk factors associated with cumulative incidence of death included age (P < 0.007, subhazard ratio (SHR) = 1.03), type of cancer (P < 0.0001), and response to treatment (P < 0.0001, SHR = 0.027). The significant risk factors associated with cumulative incidence of chronic graft loss were gender (P = 0.05, SHR = 0.37), treatment modality (P < 0.0001), and response to treatment (P = 0.048, SHR = 0.47). Conclusions: Using these factors, nephrologists may predict the occurrence of graft loss or death. If the probability of graft loss was higher, physicians can decrease the immunosuppressive medications dosage to decrease the incidence of graft loss. PMID:25032129

Salesi, Mahmoud; Rostami, Zohreh; Rahimi Foroushani, Abbas; Mehrazmay, Ali Reza; Mohammadi, Jamile; Einollahi, Behzad; Asgharian, Saeed; Eshraghian, Mohammad Reza

2014-01-01

212

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...

213

Medical care of kidney transplant recipients after the first posttransplant year.  

PubMed

Kidney transplantation is the treatment of choice for patients with ESRD. Despite improvements in short-term patient and graft outcomes, there has been no major improvement in long-term outcomes. The use of kidney allografts from expanded-criteria donors, polyoma virus nephropathy, underimmunosuppression, and incomplete functional recovery after rejection episodes may play a role in the lack of improvement in long-term outcomes. Other factors, including cardiovascular disease, infections, and malignancies, also shorten patient survival and therefore reduce the functional life of an allograft. There is a need for interventions that improve long-term outcomes in kidney transplant recipients. These patients are a unique subset of patients with chronic kidney disease. Therefore, interventions need to address disease progression, comorbid conditions, and patient mortality through a multifaceted approach. The Kidney Disease Outcomes Quality Initiative from the National Kidney Foundation, the European Best Practice Guidelines, and the forthcoming Kidney Disease: Improving Global Outcomes clinical practice guidelines can serve as a cornerstone of this approach. The unique aspects of chronic kidney disease in the transplant recipient require the integration of specific transplant-oriented problems into this care schema and a concrete partnership among transplant centers, community nephrologists, and primary care physicians. This article reviews the contemporary aspects of care for these patients. PMID:17699268

Djamali, Arjang; Samaniego, Millie; Muth, Brenda; Muehrer, Rebecca; Hofmann, R Michael; Pirsch, John; Howard, Andrew; Mourad, Georges; Becker, Bryan N

2006-07-01

214

Fatal Epstein-Barr virus primo infection in a 25-year-old man treated with azathioprine for Crohn's disease.  

PubMed

We report a case of Epstein-Barr virus (EBV) primo infection with the development of successive infectious mononucleosis, hemophagocytic lymphohistiocytosis, and B-cell lymphoproliferative disorder in a patient treated with azathioprine for Crohn's disease. This case report suggests that specific EBV-related clinical and virological management should be considered when treating a patient with inflammatory bowel disease with azathioprine. PMID:19193838

N'guyen, Y; Andreoletti, L; Patey, M; Lecoq-Lafon, C; Cornillet, P; Léon, A; Jaussaud, R; Fieschi, C; Strady, C

2009-04-01

215

Renal involvement in myeloproliferative and lymphoproliferative disorders. A study of autopsy cases.  

PubMed

A considerable proportion of cases of myeloproliferative and lymphoproliferative disorders exhibit renal involvement. However, it is unclear whether the cytologic features, immunophenotype or grade of malignancy of the cells infiltrating the kidney differ from those of the primary tumor. This study was performed on 120 autopsy cases with the following diagnoses: acute myelogenous leukemia (AML, n = 22; subtypes M1 + M2, n = 12, subtype M4, n = 10), chronic myelogenous leukemia (CML, n = 7), agnogenic myeloid metaplasia/myelofibrosis (AMM/MF, n = 6), acute lymphocytic leukemia (ALL, n = 6), chronic lymphocytic leukemia (CLL, n = 9), other low-grade non-Hodgkin's lymphomas (low-grade NHL, n = 24), high-grade NHL (n = 21) and multiple myeloma (MM, n = 25). Renal involvement was investigated by light microscopy and immunohistochemistry. It was found in 34% of the cases, and was most common in ALL (83%) and low-grade NHL (50%) and least common in high-grade NHL (10%) and MM (12%). Dense infiltration of almost the entire kidney was most commonly seen in AML, low-grade NHL and ALL. Infiltration was bilateral and involved both the cortex and medulla in the majority of cases. When involvement of other organs was compared with that of the kidney, the lung was found to be involved in approximately the same number of cases, but liver involvement was more common and heart involvement less common. Reactive lymphocytic infiltration of the kidney was found in 18 of the 120 cases (15%), and was distinguished from scanty tumorous infiltration by immunohistochemical staining. No major phenotypical differences were found between the tumor cells infiltrating the kidney and those of the primary tumors in the bone marrow or lymph nodes. However, in one case of CML, the cells infiltrating the kidney were negative for KP1 and chloroacetate esterase, but could be identified by reactivity for CD34. The grade of malignancy in NHL was similar in both the nodal and renal manifestations. PMID:9065578

Xiao, J C; Walz-Mattmüller, R; Ruck, P; Horny, H P; Kaiserling, E

1997-02-01

216

Cyclin D1 overexpression allows identification of an aggressive subset of leukemic lymphoproliferative disorder.  

PubMed

The conjunction of clinical features, cell morphology and immunological characteristics allows an accurate diagnosis in most cases of B cell chronic lymphoproliferative disorders (CLD). However, the diagnosis remains uncertain in a small percentage of cases, often referred as to unclassified B cell proliferation or atypical chronic lymphocytic leukemia (CLL). We have studied retrospectively the 192 cases of leukemic CLD seen in our institution over a 3-year period, for which both clinical and routine biological data at presentation were available. Forty cases (20%) did not fit into any of the well-identified categories according to the FAB criteria and remained unclassified. We assessed cyclin D1 expression in all of these cases and found that 10 of them expressed a high level of cyclin D1 protein. We compared the characteristics of these 10 cases with those of the 30 cyclin D1 negative CLD. Despite non-distinctive cytological and phenotypic features, the 10 cyclin D1 positive patients exhibited a strikingly uniform clinical presentation with elevated leukocytosis, massive spleen enlargement and no superficial lymphadenopathy. Their outcome was very poor with a median survival of 10 months, contrasting with the prolonged survival of the cyclin D1 negative patients. The cytological features of tumor cells from these 10 patients with cyclin D1 positive unclassified leukemic CLD were similar to those of the circulating lymphoid cells from 15 patients with histologically proven mantle cell lymphoma (MCL) and primary or secondary blood involvement. Therefore, cyclin D1 expression allowed identification among the unclassified CLD, a subset of aggressive disorders which represent a leukemic counterpart of MCL (mantle cell leukemia). We suggest that determination of cyclin D1 expression by any technique available should be systematically included when investigating atypical CLL. PMID:10482984

Levy, V; Ugo, V; Delmer, A; Tang, R; Ramond, S; Perrot, J Y; Vrhovac, R; Marie, J P; Zittoun, R; Ajchenbaum-Cymbalista, F

1999-09-01

217

Castleman's disease presenting as a tracheal mass.  

PubMed

Castleman's disease (CD) is a rare lymphoproliferative disorder of uncertain cause. The most common site of involvement is the mediastinum. Endotracheal CD is extremely rare. We report a case of unicentric, hyaline-vascular type CD presenting as an obstructive tracheal mass. The tumor was successfully managed by rigid bronchoscopy with argon plasma coagulation. There was no recurrence at the 2-month follow-up visit. PMID:24792274

Yu, Jin Yeong; Oh, In Jae; Kim, Kyu Sik; Kim, Yu Il; Lim, Sung Chul; Kim, Young Chul; Choi, Yoo Duk; Kwon, Yong Soo

2014-05-01

218

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

PubMed

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-? 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-? genes rearrangements. Monoclonal IgH gene rearrangement was detected in 48.1 % of patients, whereas monoclonal TCR-? 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-? and IgH gene rearrangements consistent with respect to the presence (2.3 %) or absence (22.3 %) of monoclonality. Finally, PCR analysis of TCR-? 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

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

219

Epstein-Barr virus related lymphoma in inflammatory bowel disease.  

PubMed

Epstein-Barr virus (EBV) induced lymphoproliferative disease is a well-known, feared complication of EBV primo-infection in children treated with immunomodulators or immunosuppressive drugs, eg after transplantation. As the incidence of inflammatory bowel disease (IBD) in young children is rising, more young EBV naive patients are treated with immunomodulatory agents. It is not yet clear whether these patients carry the same risk as transplanted patients to develop lymphoproliferative disease and if so, whether their evolution is comparable. We present the history of a young patient with Crohn's disease who developed an EBV related lymphoma shortly after the primo-infection while being treated with azathioprine. This case argues for a rigorous follow up of young IBD patients treated with immune suppressive drugs, also regarding EBV status. PMID:18396748

Van Biervliet, S; Velde, S Vande; De Bruyne, R; De Looze, D; De Vos, M; Van Winckel, M

2008-01-01

220

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...

221

Posttransplant Metabolic Syndrome in the Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients (WISP-R) Pilot Trial.  

PubMed

Posttransplant metabolic syndrome (PTMS)-obesity, hypertension, elevated triglycerides, low HDL and glucose intolerance-is a major contributor to morbidity after adult liver transplant. This analysis of the Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients (WISP-R) pilot trial is the first prospective study of PTMS after pediatric liver transplant. Twenty children were enrolled in WISP-R, at median age 8.5 years (IQR 6.4-10.8), and weaned from calcineurin-inhibitor monotherapy. The 12 children who tolerated complete immunosuppression withdrawal were compared to matched historical controls. At baseline, 45% of WISP-R subjects and 58% of controls had at least one component of PTMS. Calcineurin-inhibitor withdrawal in the WISP-R subjects did not impact the prevalence of PTMS components compared to controls. At 5 years, despite weaning off of immunosuppression, 92% of the 12 tolerant WISP-R subjects had at least one PTMS component and 58% had at least two; 33% were overweight or obese, 50% had dyslipidemia, 33% glucose intolerance and 42% systolic hypertension. Overweight/obesity increased the risk of hypertension in all children. Compared to controls, WISP-R tolerant subjects had similar GFR at baseline but did have higher GFR at 2, 3 and 4 years. Further study of PTMS and immunosuppression withdrawal after pediatric liver transplant is warranted. PMID:25648649

Perito, E R; Mohammad, S; Rosenthal, P; Alonso, E M; Ekong, U D; Lobritto, S J; Feng, S

2015-03-01

222

Inflammation-based scores do not predict post-transplant recurrence of hepatocellular carcinoma in patients within Milan criteria.  

PubMed

Increased preoperative inflammation scores, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and inflammation-based index (IBI) have been related to post-transplant HCC recurrence. We evaluated the association between inflammation-based scores (NLR, PLR, IBI) and post-LT HCC recurrence as well as tumor necrosis after transarterial embolization. 150 consecutive patients who underwent transplantation for HCC within the Milan criteria between 1996 and 2010 were included; data regarding inflammatory markers, patient and tumor characteristics were analyzed. NLR, PLR, and IBI were not significantly associated with post-LT HCC recurrence or worse overall survival. Increased NLR and PLR were associated with complete tumor necrosis in the subset of patients who received preoperative transarterial embolization (P < 0.05). Cox regression analysis revealed that absence of neoadjuvant transarterial therapy (OR = 4.33, 95% CI = 1.28-14.64; P = 0.02) and no fulfillment of the Milan criteria in the explanted liver (OR = 3.34, 95% CI = 1.08-10.35; P = 0.04) were independently associated with post-LT HCC recurrence inflammation-based scores did not predict HCC recurrence post-LT in our group of patients. NLR and PLR were associated with better response to TAE, as this was recorded histologically in the explanted liver. Histological fulfillment of the Milan criteria and absence of neoadjuvant transarterial treatment were significantly associated with post-LT HCC recurrence. PMID:25088400

Parisi, Ioanna; Tsochatzis, Emmanuel; Wijewantha, Hasitha; Rodríguez-Perálvarez, Manuel; De Luca, Laura; Manousou, Pinelopi; Fatourou, Evangelia; Pieri, Giulia; Papastergiou, Vassilios; Davies, Neil; Yu, Dominic; Luong, TuVinh; Dhillon, Amar Paul; Thorburn, Douglas; Patch, David; O'Beirne, James; Meyer, Tim; Burroughs, Andrew K

2014-11-01

223

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

PubMed Central

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

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

224

A rare case of bilateral orbital Castleman disease.  

PubMed

Castleman disease is a non-neoplastic cause of lymphadenopathy, first described in 1956 by Dr. Benjamin Castleman. Orbital involvement in Castleman disease is extremely rare. We report a case of bilateral orbital Castleman disease in a 48-year-old Asian male who presented with bilateral inferior dystopia. MRI revealed bilateral extraconal superior orbital mass. Histopathology and immunohistochemistry of the mass revealed features of Castleman disease of hyaline vascular type. Castleman disease should be a differential in suspected idiopathic orbital inflammatory disease and lymphoproliferative disorders. PMID:24831817

Mukherjee, Bipasha; Alam, Mohammad Shahid; Krishnakumar, S

2014-08-01

225

Acute renal failure and severe hypertension from a page kidney post-transplant biopsy.  

PubMed

Page kidney refers to a clinical picture characterized by acute onset of hypertension due to external compression of the kidneys from hematoma, tumor, lymphocele, or urinoma. Hypertension is believed to result from renin-angiotensin-aldosterone activation triggered by renal hypoperfusion and microvascular ischemia. Renal failure, in addition to hypertension, may occur in the setting of a single functional kidney or a diseased contralateral kidney. We report a case of a patient who had a transplant kidney biopsy complicated by a subcapsular perinephric hematoma. The patient presented with an acute increase in blood pressure and a rapid rise in serum creatinine following a transplant kidney routine biopsy. He underwent emergent evacuation of the perinephric hematoma, with consequent decrease of his blood pressure and return of serum creatinine back to his baseline level. Early recognition and rapid intervention are needed in order to correct hypertension and reverse acute renal failure in Page kidney occurring in renal transplant recipients. PMID:20694451

Posadas, Maria Aurora; Yang, Vincent; Ho, Bing; Omer, Muhammad; Batlle, Daniel

2010-01-01

226

The urine microRNA profile may help monitor post-transplant renal graft function  

PubMed Central

Non-invasive, cost-effective biomarkers that allow accurate monitoring of graft function are needed in kidney transplantation. Since microRNAs (miRNAs) have emerged as promising disease biomarkers we sought to establish an miRNA signature in urinary cell pellets comparing kidney transplant patients diagnosed with chronic allograft dysfunction (CAD) with interstitial fibrosis and tubular atrophy and those recipients with normal graft function. Overall, we evaluated 191 samples from 125 deceased donor primary kidney transplant recipients in the discovery, initial validation and the longitudinal validation studies for non-invasive monitoring of graft function. Of 1,733 mature miRNAs studied using microarrays, 22 were found to be differentially expressed between groups. Ontology and pathway analyses showed inflammation as the principal biological function associated with these miRNAs. Twelve selected miRNAs were longitudinally evaluated in urine samples of an independent set of 66 patients, at two time-points post-kidney transplant. A subset of these miRNAs was found to be differentially expressed between groups early post-kidney transplant before histological allograft injury was evident. Thus, a panel of urine miRNAs was identified as potential biomarkers for monitoring graft function and anticipating progression to CAD in kidney transplant patients. PMID:24025639

Maluf, Daniel G; Dumur, Catherine I; Suh, Jihee L; Scian, Mariano J; King, Anne L; Cathro, Helen; Lee, Jae K; Gehrau, Ricardo C; Brayman, Kenneth L; Gallon, Lorenzo; Mas, Valeria R

2013-01-01

227

Immunotherapy for EBV-associated malignancies  

Microsoft Academic Search

Since 1995 to date, more than 250 patients with EBV-related diseases received virus-specific CTL. Cell therapy proved to be\\u000a safe and effective, and achieved some complete remissions also in patients who failed all previous standard treatments. The\\u000a first clinical results with EBV-specific CTL were obtained for both prophylaxis and treatment of post-transplant lymphoproliferative\\u000a disease arising in stem cell transplant or

Anna Merlo; Riccardo Turrini; Riccardo Dolcetti; Paola Zanovello; Antonio Rosato

2011-01-01

228

Posttransplant Nephrocalcinosis Is Associated with Poor Renal Allograft Function: A Single-Center Experience  

PubMed Central

Background Nephrocalcinosis, characterized by intratubular and/or parenchymal deposition of calcium phosphate and calcium oxalate crystals, is frequently seen in renal allograft biopsies; however, the clinical consequence of this histologic finding remains unknown. Kidney transplant recipients with good allograft function usually demonstrate improvement in biochemical parameters; however, persistent hyperparathyroidism remains prevalent in this population of patients. We identified renal allografts with nephrocalcinosis and evaluated the effects on renal allograft function and survival. Methods We conducted a single-center, retrospective review of kidney allograft biopsies performed at our center from December 1, 2006 to November 30, 2012. Biopsies with nephrocalcinosis as the primary diagnosis were included in the final analysis. Biochemical parameters at the time of biopsy included serum creatinine, phosphate, calcium, intact parathyroid hormone (iPTH), 25-hydroxy vitamin D, and albumin. Serum creatinine was measured at 1, 3, 6, and 12 months after nephrocalcinosis was diagnosed. The use of calcimimetics, vitamin D analogs, active vitamin D, and bisphosphonates was also reviewed. Results We identified 12 patients with nephrocalcinosis as the primary diagnosis on renal biopsy. The average age of these patients was 52.2 ± 11.9 years, and the average time since transplantation was 2.3 ± 2.7 years. The baseline serum creatinine was 1.37 ± 0.4 mg/dL before the onset of acute kidney injury (AKI). Mean iPTH and 25-hydroxy vitamin D at the time of AKI were 495.66 ± 358.9 pg/mL and 19.9 ± 13.3 ng/mL, respectively. Renal function deteriorated in all patients, and mean serum creatinine at 12-month follow up was 2.37 ± 1.3 mg/dL (P=0.028). One patient progressed to end-stage renal disease at the end of the study period. Conclusion The histologic finding of nephrocalcinosis is associated with poor renal allograft function. Metabolic abnormalities including hyperparathyroidism persist in renal allograft recipients despite normal allograft function and may be associated with the development of nephrocalcinosis in renal transplant recipients. PMID:25829877

Moiz, Abdul; Javed, Tariq; Garces, Jorge; Dornelles, Adriana; Staffeld-Coit, Catherine

2015-01-01

229

Necrotic lymphoma in a patient with post-transplantation lymphoproliferative disorder: ultrasonography and CT findings with pathologic correlation  

PubMed Central

Seventeen months after kidney transplantation for the treatment of nephrotic syndrome, a retroperitoneal mass was incidentally detected in a 30-year-old man during routine follow-up. Ultrasonography revealed a mass measuring 5.5 cm×4.3 cm located between the liver and the atrophic right kidney, which showed markedly heterogeneous internal echogenicity. Contrast-enhanced computed tomography displayed a mild degree of enhancement only at the periphery of the mass, while the center lacked perceivable intensification. The patient underwent surgical resection. The final pathological diagnosis was non-Hodgkin lymphoma (diffuse large B-cell lymphoma), and extensive necrosis was observed on microscopic examination. We found that the prominent heterogeneous echogenicity of the mass (an unusual finding of lymphoma) demonstrated on ultrasonography is a result of extensive necrosis, which may sometimes occur in patients with post-transplantation lymphoproliferative disorder. PMID:25541069

2015-01-01

230

Necrotic lymphoma in a patient with post-transplantation lymphoproliferative disorder: ultrasonography and CT findings with pathologic correlation.  

PubMed

Seventeen months after kidney transplantation for the treatment of nephrotic syndrome, a retroperitoneal mass was incidentally detected in a 30-year-old man during routine follow-up. Ultrasonography revealed a mass measuring 5.5 cm×4.3 cm located between the liver and the atrophic right kidney, which showed markedly heterogeneous internal echogenicity. Contrast-enhanced computed tomography displayed a mild degree of enhancement only at the periphery of the mass, while the center lacked perceivable intensification. The patient underwent surgical resection. The final pathological diagnosis was non-Hodgkin lymphoma (diffuse large B-cell lymphoma), and extensive necrosis was observed on microscopic examination. We found that the prominent heterogeneous echogenicity of the mass (an unusual finding of lymphoma) demonstrated on ultrasonography is a result of extensive necrosis, which may sometimes occur in patients with post-transplantation lymphoproliferative disorder. PMID:25541069

Lee, Minsu; Kim, Sang Kyum; Chung, Yong Eun; Choi, Jin-Young; Park, Mi-Suk; Lim, Joon Seok; Kim, Myeong-Jin; Kim, Honsoul

2015-04-01

231

Methotrexate-associated lymphoproliferative disorder arising in the retromolar triangle and lung of a patient with rheumatoid arthritis.  

PubMed

We report an extremely rare case of massive methotrexate-associated lymphoproliferative disorder (MTX-LPD) arising in the retromolar triangle and lung of a patient with rheumatoid arthritis. The patient was a 75-year-old woman who was referred to our department because of severe pain associated with a unilateral ulcer on the left retromolar triangle. The tumor had an extranodal location in the retromolar triangle and in the right lung. A clinicopathologic examination found a lymphocytic infiltrate with increasingly atypical histopathologic features. Atypical large cells were strongly positive in Epstein-Barr virus-encoded small RNA in situ hybridization and in staining with CD20 antibodies. MTX-LPD was diagnosed based on the medical history and histopathologic results. The lesion responded well to withdrawal of MTX followed by R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. There have been no signs of recurrence for 4 years since withdrawal of MTX. PMID:24811204

Kudoh, Masanori; Harada, Hiroyuki; Matsumoto, Koshi; Sato, Yuriko; Omura, Ken; Ishii, Yoshimasa

2014-10-01

232

Extracorporeal photopheresis in chronic graft-versus-host disease  

Microsoft Academic Search

Despite significant advances in stem cell manipulation and post-transplant immunosuppression, chronic graft-versus-host disease (cGVHD) remains a cause of major long-term morbidity in survivors of allogeneic stem cell transplantation. Extracorporeal photopheresis (ECP) is a novel therapeutic intervention which has demonstrated efficacy in patients with refractory acute and chronic GVHD. Clinical responses have been reported in skin and visceral GVHD. While the

FM Foss; G Gorgun; KB Miller

2002-01-01

233

Disseminated mucormycosis associated with invasive pulmonary aspergillosis in a patient treated for post-transplant high-grade non-Hodgkin's lymphoma.  

PubMed

The incidence of mucormycosis, defined as systemic infection caused by fungi of the class Phycomycetes has been increasing over the past 2 decades, especially in profoundly immunocompromised hosts. We report a new case in a patient presenting with post-transplant high-grade non-Hodgkin's lymphoma who received a prolonged treatment with voriconazole and caspofungin for an invasive pulmonary aspergillosis. Definite diagnosis of mucormycosis was made by liver biopsy of nodules mimicking progressive lymphoma. The patient died 1 week after the diagnosis of mucormycosis despite the administration of liposomal amphotericin B. The role of voriconazole and caspofungin in the emergence of mucormycosis is discussed. PMID:15370266

Blin, Nicolas; Morineau, Nadine; Gaillard, Fanny; Morin, Odile; Milpied, Noël; Harousseau, Jean-Luc; Moreau, Philippe

2004-10-01

234

Nodular Regenerative Hyperplasia and Portal Hypertension in a Patient with Coeliac Disease  

PubMed Central

Nodular regenerative hyperplasia (NRH) of the liver is often associated with rheumatologic or lymphoproliferative disorders and a cause of portal hypertension in some patients. We report the case of a 71-year-old patient with celiac disease and unexplained portal hypertension. Biopsy of the liver revealed NRH as the underlying cause. The patient did not suffer from an autoimmune, rheumatologic or lymphoproliferative disease. A thrombophilic disorder that might cause NRH was ruled out. Celiac disease is often associated with mild elevation of liver enzymes and steatosis of the liver, but the association with NRH was described in only a few patients. We discuss the possible relationship of celiac disease and NRH. PMID:22606433

Biecker, Erwin; Fischer, Hans-Peter; Schepke, Michael

2011-01-01

235

A Phase I Trial of Epstein-Barr Virus Gp350 Vaccine for Children With Chronic Kidney Disease Awaiting Transplantation  

Microsoft Academic Search

Background. Vaccination against Epstein-Barr virus (EBV), inducing an antibody response to the envelope glycoprotein gp350, might protect EBV-negative children with chronic kidney disease from lymphoproliferative disease after transplantation. Methods. A phase I trial recruited children with chronic kidney disease to two successive cohorts given three injections of 12.5 mu g (n=6) and 25 mu g (n=10) recombinant gp350\\/alhydrogel vaccine over

Lesley Rees; E Jane Tizard; Andrew J. Morgan; W David Cubitt; Susan Finerty; Titilade A. Oyewole-Eletu; Karen Owen; Collin Royed; Servi J. Stevens; Rukshana C. Shroff; Manjit K. Tanday; A Douglas Wilson; Jaap M. Middeldorp; Peter L. Amlot; Neil M. Steven

2009-01-01

236

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

PubMed

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

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

2015-02-01

237

Idiopathic multicentric Castleman's disease. A clinicopathologic and immunohistochemical study of five cases  

Microsoft Academic Search

Several lymphoproliferative disorders may be interpreted as multicentric Castleman's disease (MCD) clinicopathologically. These include HIV infection, autoimmune-disease-associated lymphadenopathy, idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia, “idiopathic MCD”, POEMS syndrome (polyneuropathy, anasarca, organomegaly, endocrinopathy, M-proteins, and skin lesions), and non-Hodgkin's lymphomas. Among these, idiopathic MCD appears to be relatively rare. We report on the clinicopathologic and immunohistologic findings of five cases of

Masaru Kojima; Shigeo Nakamura; Masafumi Nishikawa; Hideaki Itoh; Shuichi Miyawaki; Nobuhide Masawa

2005-01-01

238

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

PubMed

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

Farruggia, Piero; Trizzino, Antonino; Scibetta, Nunzia; Cecchetto, Giovanni; Guerrieri, Patrizia; D'Amore, Emanuele S G; D'Angelo, Paolo

2011-01-01

239

High Fatality Rate of Epstein-Barr Virus-Associated Lymphoproliferative Disorder Occurring after Bone Marrow Transplantation with Rabbit Antithymocyte Globulin Conditioning Regimens  

Microsoft Academic Search

Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (EBV-LPD) following bone marrow transplantation can be fatal. The major risk factors for the development of EBV-LPD are ex vivo T-cell depletion or in vivo T-cell depletion with either antithymocyte globulin (ATG) or monoclonal anti-T-cell antibodies. Between March 1999 and January 2001, a total of 23 transplants with ATG of equine source (20 transplants) and

E. Peres; S. Savasan; J. Klein; M. Abidi; R. Dansey; E. Abella

2005-01-01

240

Increased incidence of EBV-associated lymphoproliferative disorders after allogeneic stem cell transplantation from matched unrelated donors due to a change of T cell depletion technique  

Microsoft Academic Search

Here, the influence of T vs T and B cell depletion on the incidence of EBV-associated lymphoproliferative disorder (EBV-LPD) after bone marrow transplantation (BMT) from a matched unrelated donor (MUD) is analyzed. From 1982 to 1997 the soy bean agglutinin\\/sheep red blood cell (SBA\\/SRBC) method was used for T cell depletion. This technique is well established, but the use of

E Meijer; ICM Slaper-Cortenbach; SFT Thijsen; AW Dekker; LF Verdonck

2002-01-01

241

Potential pathways for regulation of NK and T cell responses: differential X-linked lymphoproliferative syndrome gene product SAP interactions with SLAM and 2B4  

Microsoft Academic Search

SAP, the gene that is altered or absent in the X-linked lymphoproliferative syndrome (XLP), encodes a small protein that comprises a single SH2 domain and binds to the cell-surface protein SLAM which is present on activated or memory T and B cells. Because defective NK cell activity also has been reported in XLP patients, we studied the SAP gene in

Joan Sayos; Khuong B. Nguyen; Chengbin Wu; Susan E. Stepp; Duncan Howie; John D. Schatzle; Vinay Kumar; Christine A. Biron; Cox Terhorst

2000-01-01

242

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

PubMed Central

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

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

2014-01-01

243

Prevalence and correlates of medication non-adherence among kidney transplant recipients more than 6 months post-transplant: a cross-sectional study  

PubMed Central

Background Among kidney transplant recipients, non-adherence with immunosuppressive medications frequently precedes allograft loss. We sought to determine the prevalence and correlates of medication non-adherence among kidney transplant recipients. Methods We performed a single-center, cross-sectional study of kidney transplant recipients who were at least 6 months post-transplant. We measured self-reported adherence using the Immunosuppressive Therapy Adherence Scale (ITAS, which is scored from 0 to 12, where higher scores indicate increased adherence) and barriers to adherence using the Immunosuppressive Therapy Barriers Scale (ITBS). We also used validated scales to measure perceived stress, health literacy, anxiety, depression, and interpersonal support. Results The 252 patients included in the study were 59.9% male, 27.0% Black, and at a median of 2.9 years post-transplant (interquartile range [IQR] 1.4-5.8). On the ITAS, 59.1% scored a perfect 12, 26.6% scored 10–11, and 14.3% scored 0–9. In univariate models, non-adherence (defined as ITAS score ?9) was significantly associated with increased scores on scales for perceived stress (OR 1.12, 95% CI 1.01-1.25) and depression (OR 1.14, 95% CI 1.02-1.28), and with more self-reported barriers to adherence on the ITBS (OR 1.15, 95% CI 1.08-1.22). After adjusting for sociodemographic factors, stress and depression were not associated with non-adherence. Higher scores on the ITBS (corresponding to more self-described barriers to adherence) were associated with lower scores on the ITAS (P?

2013-01-01

244

Molecular Pathogenesis of Post-Transplant Acute Kidney Injury: Assessment of Whole-Genome mRNA and MiRNA Profiles  

PubMed Central

Acute kidney injury (AKI) affects roughly 25% of all recipients of deceased donor organs. The prevention of post-transplant AKI is still an unmet clinical need. We prospectively collected zero-hour, indication as well as protocol kidney biopsies from 166 allografts between 2011 and 2013. In this cohort eight cases with AKI and ten matched allografts without pathology serving as control group were identified with a follow-up biopsy within the first twelve days after engraftment. For this set the zero-hour and follow-up biopsies were subjected to genome wide microRNA and mRNA profiling and analysis, followed by validation in independent expression profiles of 42 AKI and 21 protocol biopsies for strictly controlling the false discovery rate. Follow-up biopsies of AKI allografts compared to time-matched protocol biopsies, further baseline adjustment for zero-hour biopsy expression level and validation in independent datasets, revealed a molecular AKI signature holding 20 mRNAs and two miRNAs (miR-182-5p and miR-21-3p). Next to several established biomarkers such as lipocalin-2 also novel candidates of interest were identified in the signature. In further experimental evaluation the elevated transcript expression level of the secretory leukocyte peptidase inhibitor (SLPI) in AKI allografts was confirmed in plasma and urine on the protein level (p<0.001 and p?=?0.003, respectively). miR-182-5p was identified as a molecular regulator of post-transplant AKI, strongly correlated with global gene expression changes during AKI. In summary, we identified an AKI-specific molecular signature providing the ground for novel biomarkers and target candidates such as SLPI and miR-182-5p in addressing AKI. PMID:25093671

Wilflingseder, Julia; Sunzenauer, Judith; Toronyi, Eva; Heinzel, Andreas; Kainz, Alexander; Mayer, Bernd; Perco, Paul; Telkes, Gábor; Langer, Robert M.; Oberbauer, Rainer

2014-01-01

245

Podocyte effacement closely links to suPAR levels at time of post-transplant focal segmental glomerulosclerosis occurrence and improves with therapy  

PubMed Central

Background Focal segmental glomerulosclerosis (FSGS) recurs after kidney transplantation in more than 30 % of cases and can lead to allograft loss. Serum soluble urokinase -type plasminogen activator receptor (suPAR) is implicated in the pathogenesis of native and recurrent FSGS. Methods We conducted a retrospective study of 25 adults with post-transplant FSGS. We investigated the relationship between suPAR levels and podocyte changes and the impact of therapy on podocyte structure. We assessed response to therapy by improvement in proteinuria, allograft function and resolution of histologic changes. Results A median of 15 (interquartile range: 10–23) plasmapheresis sessions was administered; 13 of the subjects also received rituximab. Median pre-treatment suPAR levels were higher among those with severe (?75%) versus those with mild (?25%) podocyte foot process effacement (13,030 vs. 4,806 pg/mL; P=0.02). Overall, mean ± standard deviation of proteinuria improved from 5.1 ± 3.8 to 2.1 ± 2.8 mg/dL (P=0.003), mean podocyte effacement decreased from 57 ± 33% to 22 ± 22 % (P=0.0001), estimated glomerular filtration rates increased from median (interquartile range) of 32.9 (20.6 – 44.2) to 39.3 (28.8 – 63.4) (P<0.0001) and suPAR levels decreased from a median of 6,781 pg/ml to 4,129 pg/ml (P=0.02) with therapy. Conclusions Podocyte effacement is the first pathological manifestation of FSGS post-transplant. The degree of podocyte effacement correlates with suPAR levels at time of diagnosis. Response to therapy results in significant reduction of suPAR levels and complete or significant improvement of podocyte effacement. PMID:23842190

Alachkar, Nada; Wei, Changli; Arend, Lois J.; Jackson, Annette M.; Racusen, Lorraine C; Fornoni, Alessia; Burke, George; Rabb, Hamid; Kakkad, Kavita; Reiser, Jochen; Estrella, Michelle M.

2013-01-01

246

[A unique case of destructive polyarthritis associated with multicentric Castleman's disease].  

PubMed

This is an original report of a 75-year-old woman suffering from multicentric Castleman's disease associated with a destructive polyarthritis, which do not correspond to any known rhumatologic disease. Cattleman's disease (angiofollicular lymph node hyperplasia) is a lymphoproliferative disorder of unknown etiology. Two forms are described: a localized and a multicentric. In the literature, associations of Cattleman's disease and connective tissue disease such as rheumatoid arthritis have been described. Association with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M component, skin changes) and amylosis have also been described. PMID:11357052

Carpentier-Planchon, V; Bouillanne, O; Cabane, J; Droulers, A; Bodak, A

2001-03-01

247

Extranodal Castleman disease of the extremities: a case report and review of the literature.  

PubMed

Castleman disease is a rare lymphoproliferative disorder of unknown etiology that most commonly presents as a mediastinal nodal mass or, in the extranodal form of the disease, a mass located in the mediastinum or retroperitoneum. It is exceptionally uncommon for Castleman disease to present in the extremities. We report a rare case of extranodal Castleman disease presenting as a muscular forearm mass. We compare our case with the seven other reported cases in which Castleman disease presented as an isolated soft tissue mass in the extremities. PMID:24970669

Eward, William C; DeWitt, Suzanne B; Brigman, Brian E; Kontogeorgakos, Vasilios; Lagoo, Anand S

2014-11-01

248

Genetic Diversity of the KIR/HLA System and Susceptibility to Hepatitis C Virus-Related Diseases  

PubMed Central

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-? 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

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

249

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

PubMed

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

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

250

Blood disorders typically associated with renal transplantation  

PubMed Central

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

Yang, Yu; Yu, Bo; Chen, Yun

2015-01-01

251

Blood disorders typically associated with renal transplantation.  

PubMed

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

Yang, Yu; Yu, Bo; Chen, Yun

2015-01-01

252

A Case of Retroperitoneal Castleman's Disease and an Update on the Latest Evidence  

PubMed Central

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

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

253

Development of mucosal and systemic lymphoproliferative responses and protective immunity to human group A rotaviruses in a gnotobiotic pig model.  

PubMed Central

Gnotobiotic pigs were orally inoculated with virulent Wa strain (G1P1A[8]) human rotavirus (group 1), attenuated Wa rotavirus (group 2) or diluent (controls) and were challenged with virulent Wa rotavirus 21 days later. On various postinoculation or postchallenge days, virus-specific responses of systemic (blood and spleen) and intestinal (mesenteric lymph node and ileal lamina propria) mononuclear cells (MNC) were assessed by lymphoproliferative assays (LPA). After inoculation, 100% of group 1 pigs and 6% of group 2 pigs shed virus. Diarrhea occurred in 95, 12, and 13% of group 1, group 2, and control pigs, respectively. Only groups 1 and 2 developed virus-specific LPA responses prior to challenge. Group 1 developed significantly greater mean virus-specific LPA responses prior to challenge and showed no significant changes in tissue mean LPA responses postchallenge, and 100% were protected against virulent virus challenge. By comparison, both group 2 and controls had significantly lower LPA responses at challenge and both groups showed significant increases in mean LPA responses postchallenge. Eighty-one percent of group 2 and 100% of control pigs shed challenge virus, and both groups developed diarrhea that was similar in severity postchallenge. The virus-specific LPA responses of blood MNC mirrored those of intestinal MNC, albeit at a reduced level and only at early times postinoculation or postchallenge in all pigs. In a separate study evaluating antibody-secreting-cell responses of these pigs (L. Yuan, L.A. Ward, B.I. Rosen, T.L. To, and L.J. Saif, J. Virol. 70:3075-3083, 1996), we found that the magnitude of a tissue's LPA response positively correlated with the numbers of virus-specific antibody-secreting cells for that tissue, supporting the hypothesis that the LPA assesses T-helper-cell function. The magnitude of LPA responses in systemic and intestinal tissues also strongly correlated with the degree of protective immunity elicited by the inoculum (p = 0.81). We conclude that blood may provide a temporary "window" for monitoring intestinal T cells and that the LPA can be used to assess protective immunity to human rotaviruses. PMID:8705681

Ward, L A; Yuan, L; Rosen, B I; Tô, T L; Saif, L J

1996-01-01

254

A novel homozygous Fas ligand mutation leads to early protein truncation, abrogation of death receptor and reverse signaling and a severe form of the autoimmune lymphoproliferative syndrome.  

PubMed

We report a novel type of mutation in the death ligand FasL that was associated with a severe phenotype of the autoimmune lymphoproliferative syndrome in two patients. A frameshift mutation in the intracellular domain led to complete loss of FasL expression. Cell death signaling via its receptor and reverse signaling via its intracellular domain were completely abrogated. In vitro lymphocyte proliferation induced by weak T cell receptor stimulation could be blocked and cell death was induced by engagement of FasL in T cells derived from healthy individuals and a heterozygous carrier, but not in FasL-deficient patient derived cells. Expression of genes implicated in lymphocyte proliferation and activation (CCND1, NFATc1, NF-?B1) was increased in FasL-deficient T cells and could not be downregulated by FasL engagement as in healthy cells. Our data thus suggest, that deficiency in FasL reverse signaling may contribute to the clinical lymphoproliferative phenotype of ALPS. PMID:25451160

Nabhani, Schafiq; Hönscheid, Andrea; Oommen, Prasad T; Fleckenstein, Bernhard; Schaper, Jörg; Kuhlen, Michaela; Laws, Hans-Jürgen; Borkhardt, Arndt; Fischer, Ute

2014-12-01

255

Screening for CMV-specific T cell proliferation to identify patients at risk of developing late onset CMV disease  

Microsoft Academic Search

Thirty patients undergoing allogeneic BMT were screened post-transplant together with their marrow donors for CMV-specific T cell proliferation and the occurrence of CMV disease. Twenty-one of these patients received a marrow transplant from an HLA-matched sibling donor, and nine from an HLA-matched unrelated donor. All these patients were either CMV seropositive and\\/or had received a transplant from a CMV-seropositive donor.

H Krause; H Hebart; G Jahn; CA Müller; H Einsele

1997-01-01

256

Risk Factors for Chronic Graft-Versus-Host Disease After HLA-Identical Sibling Bone Marrow Transplantation  

Microsoft Academic Search

Chronic graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation. We analyzed risk factors for chronic GVHD in 2,534 recipients of HLA-identical sibling transplants surviving at least 90 days after transplantation. The actuarial probability of develop- ing chronic GVHD within three years posttransplant was 46% T 3% (95% confidence interval). The most important risk factor for chronic GVHD

Kerry Atkinson; Mary M. Horowitz; Robert Peter Gale; Dirk W. van Bekkum; Eliane Gluckman; Robert A. Good; Niels Jacobsen; Hans-Jochem Kolb; Alfred A. Rimm; Olle Ringden; Ciril Rozman; Kathleen A. Sobocinski

2010-01-01

257

Epstein-Barr virus infection in transplant recipients: Summary of a workshop on surveillance, prevention and treatment  

PubMed Central

Diseases caused by the Epstein-Barr virus are of great significance among organ transplant recipients. One of these diseases, post-transplant lymphoproliferative disease, is a major complication among organ transplant recipients. Management of this entity is problematic due to the difficulties with laboratory surveillance, diagnosis, prevention and treatment. A group of Canadian and American experts was assembled to discuss these aspects of Epstein-Barr virus diseases in Canadian organ transplant recipients. This report summarizes the relevant background literature and levels of evidence in relation to the outcomes of the deliberations and recommendations by the expert panel. PMID:18159378

Allen, Upton; Alfieri, Caroline; Preiksaitis, Jutta; Humar, Atul; Moore, Dorothy; Tapiero, Bruce; Tellier, Raymond; Green, Michael; Davies, Dele; Hébert, Diane; Weitzman, Sheila; Petric, Martin; Jacobson, Kevan

2002-01-01

258

Post-transplant malignant neoplasia associated with cyclosporine-based immunotherapy: prevalence, risk factors and survival in feline renal transplant recipients.  

PubMed

The study objective was to compare the prevalence of malignant neoplasia in feline renal transplant recipients (n?=?111) with a control population of cats that did not receive transplantation (n?=?142); and to determine whether the development of post-transplant malignant neoplasia (PTMN) affects long-term survival. Twenty-five (22.5%) renal transplant recipients were diagnosed with PTMN, and of those 14 (56%) were diagnosed with lymphoma. The overall survival time in cats that developed PTMN following renal transplantation (median 646 days, IQR 433-1620 days) was not significantly different from the survival time in cats that did not develop PTMN (median 728 days, IQR 201-1942 days), although median survival after diagnosis of PTMN was only 13 days. Six control cats (4.2%) were diagnosed with malignant neoplasia. Compared to the control population, transplant cats had a 6.6 times higher odds of developing malignant neoplasia and a 6.7 times higher odds of developing lymphoma. PMID:25303015

Wormser, C; Mariano, A; Holmes, E S; Aronson, L R; Volk, S W

2014-10-10

259

Post-transplant reactivation of hepatitis C virus: lymphocyte infiltration and the expression of adhesion molecules and their ligands in liver allografts.  

PubMed

Hepatitis C virus (HCV) recurrence after liver transplantation has been associated with chronic rejection. Biopsies from 10 patients with post-transplant HCV were examined for expression of adhesion molecules ICAM-1, VCAM-1, and ELAM-1, number of lymphocytes positive for their ligands LFA-1, VLA-4, and SLeX, and activation markers MHC class II antigens and IL2-R by immunohistochemistry. The phenotypes of the graft-infiltrating lymphocytes were determined. Results were compared to those for patients with normal graft function or rejection. Five recipients with HCV reactivation and one with de novo HCV had a biopsy available showing induction of ICAM-1 in sinusoidal endothelium (p<0.05) and hepatocytes (p<0.01), and Class II antigens in hepatocytes (p<0.01), compared to normal controls. Lymphocytes in the graft infiltrate expressed LFA-1, VLA-4, and Class II antigens, but IL2-R was not significantly expressed. CD3+, CD4+, and CD8+ cells were observed. In our study, HCV recurrence was not associated with acute or chronic rejection, and the inflammation was due to the viral infection. PMID:16689823

Lipson, Katri; Lappalainen, Maija; Höckerstedt, Krister; Lautenschlager, Irmeli

2006-04-01

260

Transferred WT1-reactive CD8+ T cells can mediate antileukemic activity and persist in post-transplant patients  

PubMed Central

Relapse remains a leading cause of death after allogeneic hematopoietic cell transplantation (HCT) for patients with high-risk leukemias. The potentially beneficial donor T-cell-mediated graft-versus-leukemia (GVL) effect is often mitigated by concurrent graft versus host disease (GVHD). Providing T-cells that can selectively target Wilms’ Tumor Antigen 1 (WT1), a transcription factor over-expressed in leukemias that contributes to the malignant phenotype, represents a potential opportunity to promote anti-leukemic activity without inducing GVHD. HLA A*0201-restricted WT1-specific donor-derived CD8+ cytotoxic T-cell (CTL) clones were administered post-HCT to 11 relapsed or high-risk leukemia patients without any evidence of on-target toxicity. The last four treated patients received CTL clones generated with exposure to IL-21 as a means to prolong in vivo CTL survival, as IL-21 can limit terminal differentiation of antigen-specific T-cells generated in vitro. Transferred cells exhibited direct evidence of anti-leukemic activity in 2 patients: a transient response in one patient with advanced progressive disease and the induction of a prolonged remission in a patient with minimal residual disease (MRD). Additionally, three treated patients at high risk for relapse post-HCT survive without leukemia relapse, GVHD or additional anti-leukemic treatment. CTL generated in the presence of IL-21, which were transferred in these latter three patients and the patient with MRD, all remained detectable long-term and maintained/acquired in vivo phenotypic and functional characteristics associated with long-lived memory CD8+ T-cells. This study supports expanding efforts to immunologically target WT1, and provides insights into the requirements necessary to establish potent persistent T-cell responses in patients. PMID:23447018

Chapuis, A.G.; Ragnarsson, G. B.; Nguyen, H. N.; Chaney, C. N.; Pufnock, J. S.; Schmitt, T. M.; Duerkopp, N.; Roberts, I. M.; Pogosov, G. L.; Ho, W. Y.; Ochsenreither, S.; Wölfl, M.; Bar, M.; Radich, J. P.; Yee, C; Greenberg, P. D.

2013-01-01

261

Radiotherapy of unicentric mediastinal Castleman's disease  

PubMed Central

Castleman's disease is a slowly progressive and rare lymphoproliferative disorder. Here, we report a 55-year-old woman with superior mediastinal Castleman's disease being misdiagnosed for a long term. We found a 4.3 cm mass localized in the superior mediastinum accompanied with severe clinical symptoms. The patient underwent an exploratory laparotomy, but the mass failed to be totally excised. Pathologic examination revealed a mediastinal mass of Castleman's disease. After radiotherapy of 30 Gy by 15 fractions, the patient no longer presented previous symptoms. At 3 months after radiotherapy of 60 Gy by 30 fractions, Computed tomography of the chest showed significantly smaller mass, indicating partial remission. Upon a 10-month follow-up, the patient was alive and free of symptoms. PMID:21527068

Li, Yue-Min; Liu, Peng-Hui; Zhang, Yu-Hai; Xia, Huo-Sheng; Li, Liang-Liang; Qu, Yi-Mei; Wu, Yong; Han, Shou-Yun; Liao, Guo-Qing; Pu, Yong-Dong

2011-01-01

262

Multicentric Castleman's Disease in a Child Revealed by Chronic Diarrhea  

PubMed Central

Multicentric Castleman's disease is a rare benign and unexplained lymphoproliferative disorder that is extremely uncommon in children. It presents with fever, systemic symptoms, generalized lymphadenopathy, and laboratory markers of inflammation. Its treatment is not standardized and its prognosis is poor. We report a novel case of multicentric Castleman's disease in a 13-year-old girl who had presented with chronic diarrhea as the only initial presenting symptom. The diagnosis of celiac or inflammatory bowel diseases was suspected, but two and a half years later, the diagnosis of multicentric Castleman's disease was brought following the appearance of abdominal mass whose biopsy revealed Castleman's disease in the plasma cell form. The outcome was favorable after treatment by corticosteroid, chemotherapy, and surgery. The occurrence of diarrhea as the initial symptom of multicentric Castleman's disease without lymph node involvement is very rare. This case report underlines the diagnostic difficulties and the long interval between onset and diagnosis when diarrhea occurs first. PMID:25737793

Benmiloud, Sarra; Chaouki, Sana; Atmani, Samir; Hida, Moustapha

2015-01-01

263

Simultaneous presentation of relapsing Hodgkin's disease and treatment-related non-Hodgkin's lymphoma  

SciTech Connect

A 55-year-old white man was diagnosed in 1975 with Hodgkin's disease stage IIA, mixed cellularity. He was treated with 4,500 rads to an inverted-Y field followed by six cycles of MOPP and remained in complete remission. In 1983 a right axillary lymph node biopsy showed recurrent Hodgkin's disease, mixed cellularity. While receiving his initial chemotherapy he developed persistent epigastric distress. Endoscopic gastric biopsy demonstrated a diffuse large-cell non-Hodgkin's lymphoma. Surface marker studies confirmed the separate identity of these two malignant lymphoproliferative processes. This represents the first reported simultaneous occurrence of relapsing Hodgkin's disease with treatment-related non-Hodgkin's lymphoma.

Perri, R.T.; Allen, J.I.; Oken, M.M.; Limas, C.; Kay, N.E.

1985-01-01

264

Lymphomatoid granulomatosis associated with azathioprine therapy in Crohn disease  

PubMed Central

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

2014-01-01

265

A Retrospective Study to Compare the use of Tacrolimus and Cyclosporine in Combination with Adriamycin in Post-Transplant Liver Cancer Patients.  

PubMed

The aim of this study was to compare the clinical effect of tacrolimus (TAC) versus cyclosporine (CycA) in post-transplant hepatic cancer patients undergoing adriamycin hydrochloride (ADM) chemotherapy. Patients with advanced hepatic cancer who underwent liver transplant and subsequent therapy between March 2007 and March 2009 in our hospital were selected for this study. All of these patients were treated with chemotherapeutic agent adriamycin, with respect to immunosuppressant, whereas they received either TAC or CycA, and hence represented two groups, TAC and controls, respectively. The short- and long-term outcomes of two therapies, ADM + TAC and ADM + CsA, were compared. The TAC group patients showed improved remission compared to the control group (40 cases with 46.0 % versus 32 cases with 31.1 % remission, respectively). The 5-year survival in TAC group was significantly prolonged (20.7 %) compared to that of the controls (8.7 %). The short-term outcomes, such as serum levels of calcium, biomarkers of cardiac toxicity/functioning, and regulatory T lymphocytes counts (markers of immune functioning), were found to be significantly more auspicious with TAC treatment than with CycA. Our study showed that use of TAC plus ADM resulted in improved patient survival, tolerance of the graft, and remission compared to CycA combined with ADM. The serum levels of various markers in the short follow-up analysis indicated a better cardiac and immune functioning with TAC than with CycA treatment. PMID:25287673

Gu, Liangfeng; Jin, Wei; Kan, Liandi; Wang, Xia; Shan, Chunlei; Fan, Hui

2015-03-01

266

Castleman's disease: from basic mechanisms to molecular therapeutics.  

PubMed

Castleman's disease is a rare lymphoproliferative disorder in which there has been recent progress in elucidating underlying mechanisms with potential therapeutic implications. Unicentric Castleman's disease is an indolent condition that is often treated with local approaches. In contrast, patients with multicentric Castleman's disease (MCD) have a less favorable prognosis and require systemic treatment. Cytotoxic chemotherapy, with its attendant risk for toxicity, has been widely used to treat MCD, with variable efficacy. The discovery of putative etiologic factors and targets in MCD, particularly human herpes virus 8, CD20, and interleukin (IL)-6, has been translated into the use of rituximab and anti-IL-6-based therapy, as well as antiviral agents. In this article, we review the current state of the art of our understanding of Castleman's disease and its treatment and we provide insight into future treatment strategies based on disease biology. PMID:21441298

El-Osta, Hazem E; Kurzrock, Razelle

2011-01-01

267

Castleman's Disease: From Basic Mechanisms to Molecular Therapeutics  

PubMed Central

Castleman's disease is a rare lymphoproliferative disorder in which there has been recent progress in elucidating underlying mechanisms with potential therapeutic implications. Unicentric Castleman's disease is an indolent condition that is often treated with local approaches. In contrast, patients with multicentric Castleman's disease (MCD) have a less favorable prognosis and require systemic treatment. Cytotoxic chemotherapy, with its attendant risk for toxicity, has been widely used to treat MCD, with variable efficacy. The discovery of putative etiologic factors and targets in MCD, particularly human herpes virus 8, CD20, and interleukin (IL)-6, has been translated into the use of rituximab and anti–IL-6-based therapy, as well as antiviral agents. In this article, we review the current state of the art of our understanding of Castleman's disease and its treatment and we provide insight into future treatment strategies based on disease biology. PMID:21441298

El-Osta, Hazem E.

2011-01-01

268

Siltuximab: a new option for the management of Castleman's disease.  

PubMed

Castleman's disease is a rare lymphoproliferative disorder the underlying mechanism of which remains unclear. However, interleukin-6 (IL-6) may play a role in the pathogenesis of the disease. Blockade of the IL-6 pathway has been explored in multiple preclinical and clinical studies with promising results for the treatment of different types of cancer and Castleman's disease. Siltuximab is a human/murine chimeric immunoglobulin G1kappa (IgG1kappa) monoclonal antibody against human IL-6. It binds to IL-6 neutralizing its biological activity. Recent phase II clinical studies in patients with multicentric Castleman's disease have shown the efficacy and safety of siltuximab in patients with this condition. Results from this study led to the recent approval of siltuximab for the treatment of Castleman's disease by the FDA and EMA. PMID:25685858

Barquero, N

2015-01-01

269

Peri-operative kidney injury and long-term chronic kidney disease following orthotopic heart transplantation in children.  

PubMed

Significant advances in cardiac intensive care including extracorporeal life support have enabled children with complex congenital heart disease and end-stage heart failure to be supported while awaiting transplantation. With an increasing number of survivors after heart transplantation in children, the complications from long-term immunosuppression, including renal insufficiency, are becoming more apparent. Severe renal dysfunction after heart transplant is defined by a serum creatinine level?>2.5 mg/dL (221 ?mol/L), and/or need for dialysis or renal transplant. The degree of renal dysfunction is variable and is progressive over time. About 3-10 % of heart transplant recipients will go on to develop severe renal dysfunction within the first 10 years post-transplantation. Multiple risk factors for chronic kidney disease post-transplant have been identified, which include pre-transplant worsening renal function, recipient demographics and morbidity, peri-transplant haemodynamics and long-term exposure to calcineurin inhibitors. Renal insufficiency increases the risk of post-transplant morbidity and mortality. Hence, screening for renal dysfunction pre-, peri- and post-transplantation is important. Early and timely detection of renal insufficiency may help minimize renal insults, and allow prompt implementation of renoprotective strategies. Close monitoring and pre-emptive management of renal dysfunction is an integral aspect of peri-transplant and subsequent post-transplant long-term care. PMID:25115875

Hoskote, Aparna; Burch, Michael

2015-06-01

270

Impact of graft-versus-host disease on survival.  

PubMed

Hematopoietic stem-cell transplantation is potentially curative treatment for malignant and non-malignant diseases. The development and severity of graft-versus-host disease (GVHD) is strongly related with post-transplant outcomes. GVHD may at the same time improve survival by decreasing the risk of disease relapse and increase non-relapse mortality by causing organ failure and predisposing the recipient to life-threatening infections. Currently available classifications attempt to separate GVHD into subgroups according to their risk of post-transplant death. The heterogeneity of both acute and chronic GVHD is a major barrier for a clear recognition of these subgroups. Multiple organ involvement and severity of organ dysfunction are the hallmarks of GVHD classifications. The development of GVHD is also predicted by a number of factors related to GVHD prophylaxis, donor type, degree of HLA matching, graft source, and conditioning regimen intensity. These factors not only affect the development of GVHD, they may independently be associated with survival. Modulation of GVHD risk factors can decrease the risk or severity of GVHD but does not universally result in an improvement in survival. Additional risk factors present after the onset of GVHD - including thrombocytopenia, hyperbilirubinemia, previous acute GVHD, extensive skin involvement, among others - further increase the risk for GVHD-related mortality. Recognition of such key factors assists in determining a population with high-risk GVHD that would benefit from up-front experimental therapies in the context of clinical trials. PMID:18503986

Pasquini, Marcelo C

2008-06-01

271

Methotrexate-induced Hodgkin disease in a patient with systemic lupus erythematosus.  

PubMed

Methotrexate sodium use in the management of various immunologic disorders has increased--as have the number of reported adverse effects associated with this therapy. While methotrexate has helped combat various autoimmune and cancerous disorders, the paradoxical risk of causing an often fatal malignancy may still occur as a result of the drug's effect on suppressing immune function. We present a case of methotrexate-induced Hodgkin disease in a 48-year-old man with a history of systemic lupus erythematosus (SLE). Discontinuation of methotrexate facilitated Hodgkin disease reversal. In addition, we review other lymphoproliferative hematologic malignancies caused by methotrexate. PMID:19556391

Sliesoraitis, Sarunas; Khan, Rizwan; Rothman, Jan

2009-06-01

272

Predicting end-stage renal disease after liver transplant.  

PubMed

Few equations have been developed to predict end-stage renal disease (ESRD) after deceased donor liver transplant. This retrospective observational cohort study analyzed all adult deceased donor liver transplant recipients in the Scientific Registry of Transplant Recipients (SRTR) database, 1995-2010. The prediction equation for ESRD was developed using candidate predictor variables available in SRTR after implementation of the allocation policy based on the model for end-stage liver disease. ESRD was defined as initiation of maintenance dialysis therapy, kidney transplant or registration on the kidney transplant waiting list. We used Cox proportional hazard models to develop separate equations for assessing risk of ESRD by 6 months posttransplant and between 6 months and 5 years posttransplant. Variables in the 6-month equation included recipient age, history of diabetes, history of dialysis before liver transplant, history of malignancy, body mass index, serum creatinine and liver donor risk index. Variables in the 6-month to 5-year equation included recipient race, history of diabetes, hepatitis C status, serum albumin, serum bilirubin and serum creatinine. The prediction equations have good calibration and discrimination (C statistics 0.74-0.78). We have produced risk prediction equations that can be used to aid in understanding the risk of ESRD after liver transplant. PMID:23668976

Israni, A K; Xiong, H; Liu, J; Salkowski, N; Trotter, J F; Snyder, J J; Kasiske, B L

2013-07-01

273

Hematopoietic stem cell transplantation in patients with chronic kidney disease.  

PubMed

Patients with significant medical comorbidities such as chronic kidney disease (CKD) traditionally have been excluded from hematopoietic stem cell transplantation (HSCT) because of unacceptably high transplant-related morbidity and mortality, an exclusion that can have enormous consequences for patients with CKD from myeloma in particular. Much of the excess HSCT-related morbidity among CKD patients relates to the toxic effects of conditioning regimens, which have a narrow therapeutic index even in patients with normal renal function. Common posttransplant complications are more challenging to prevent and manage in patients with CKD. In selected centers, autologous HSCT is performed with some frequency in patients with advanced CKD and even dialysis-dependent end-stage renal disease (ESRD), with acceptable outcomes, but cure from malignancy rarely is obtained. Allogeneic transplants using reduced-intensity conditioning regimens are being used with increasing frequency in patients with CKD, for both nonmalignant and malignant conditions, relying in the latter case on a graft-versus-malignancy effect to eliminate residual malignancy. In patients with ESRD from myeloma who have suitable donors, simultaneous allogeneic HSCT and kidney transplantation from a human leukocyte antigen-identical sibling provides the opportunity to treat both the malignant condition and the ESRD, avoiding the risks of posttransplant care in a dialysis-dependent patient and freeing the patient of the subsequent burdens of both ongoing dialysis and immunosuppression. PMID:21146125

Heher, Eliot C; Spitzer, Thomas R

2010-11-01

274

Deletion of Receptor for Advanced Glycation End Products Exacerbates Lymphoproliferative Syndrome and Lupus Nephritis in B6-MRL Fas lpr/j Mice.  

PubMed

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

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

275

Radiolabeled Monoclonal Antibody With or Without Peripheral Stem Cell Transplantation in Treating Children With Recurrent or Refractory Lymphoma  

ClinicalTrials.gov

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

2013-01-16

276

Epstein-Barr virus (EBV)-associated lymphoproliferative disease in the SCID mouse model: implications for the pathogenesis of EBV-positive lymphomas in man  

PubMed Central

When human peripheral blood lymphocytes (PBLs) from Epstein-Barr virus (EBV)-seropositive donors are injected intraperitoneally into SCID mice, EBV+ B cell tumors develop within weeks. A preliminary report (Mosier, D. E., R. J. Gulizia, S. M. Baird, D. D. Richman, D. B. Wilson, R. I. Fox, and T. J. Kipps, 1989. Blood. 74(Suppl. 1):52a) has suggested that such tumors resemble the EBV-positive malignancy, Burkitt's lymphoma. The present work shows that generally the human (hu) PBL-SCID tumors are distinct from Burkitt's lymphoma and instead resemble lymphoblastoid cell lines (LCLs) generated by EBV-infection of normal B cells in vitro in terms of: (a) their cell surface phenotype, with expression of B cell activation antigens and adhesion molecules, (b) normal karyotype, and (c) viral phenotype, with expression of all the transformation-associated EBV latent proteins and, in a minority of cells, productive cycle antigens. Indeed, in vitro-transformed LCLs also grow when inoculated into SCID mice, the frequency of tumor outgrowth correlating with the in vitro growth phenotype of the LCL which is itself determined by the identity of the transforming virus (i.e., type 1 or type 2 EBV). Histologically the PBL-derived hu-SCID tumors resemble the EBV+ large cell lymphomas that develop in immuno- suppressed patients and, like the human tumors, often present at multiple sites as individual monoclonal or oligoclonal foci. The remarkable efficiency of tumor development in the hu-SCID model suggests that lymphomagenesis involves direct outgrowth of EBV- transformed B cells without requirement for secondary genetic changes, and that selection on the basis of cell growth rate alone is sufficient to explain the monoclonal/oligoclonal nature of tumor foci. EBV+ large cell lymphoma of the immunosuppressed may arise in a similar way. PMID:1845872

1991-01-01

277

Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases  

PubMed Central

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including rheumatoid arthritis (RA). EBV in nature infects only humans, but in an experimental setting, a limited species of new-world monkeys can be infected with the virus. Small animal models, suitable for evaluation of novel therapeutics and vaccines, have not been available. Humanized mice, defined here as mice harboring functioning human immune system components, are easily infected with EBV that targets cells of the hematoimmune system. Furthermore, humanized mice can mount both cellular and humoral immune responses to EBV. Thus, many aspects of human EBV infection, including associated diseases (e.g., lymphoproliferative disease, hemophagocytic lymphohistiocytosis and erosive arthritis resembling RA), latent infection, and T-cell-mediated and humoral immune responses have been successfully reproduced in humanized mice. Here we summarize recent achievements in the field of humanized mouse models of EBV infection and show how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus. PMID:25436886

Fujiwara, Shigeyoshi; Matsuda, Go; Imadome, Ken-Ichi

2013-01-01

278

Noncanonical MicroRNA (miRNA) Biogenesis Gives Rise to Retroviral Mimics of Lymphoproliferative and Immunosuppressive Host miRNAs  

PubMed Central

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

Kincaid, Rodney P.; Chen, Yating; Cox, Jennifer E.; Rethwilm, Axel; Sullivan, Christopher S.

2014-01-01

279

Occurrence of Epstein-Barr virus-associated plasmacytic lymphoproliferative disorder after antithymocyte globulin therapy for aplastic anemia: a case report with review of the literature  

PubMed Central

It is well established that patients with immunosuppression have a higher risk of development of lymphoproliferative disorders (LPDs), and Epstein-Barr virus (EBV) is associated with development of LPDs. Aplastic anemia (AA) is an immune-mediated hematological disorder, and immunosuppression therapy (IST), such as antithymocyte globulin (ATG), is widely used for treatment of AA. However, occurrence of LPD without bone marrow transplantation has been extremely rarely documented in patients with IST for AA. Herein, we report the 6th documented case of EBV-associated LPD after IST for AA and review the clinicopathological features of this extremely rare complication. A 46-year-old Japanese female was admitted for evaluation of progressive pancytopenia. Bone marrow biopsy revealed fatty marrow with marked decrease of trilineage cells, and bone marrow aspiration demonstrated no dysplastic changes. IST with rabbit ATG was administered, after which, she developed high fever. Bone marrow aspiration showed increase of atypical plasma cells with mildly enlarged nuclei and irregular nuclear contour. These atypical plasma cells were EBER-positive. Accordingly, a diagnosis of EBV-positive plasmacytic LPD was made. Most cases of LPDs are B-cell origin, and plasmacytic LPD is a rare subtype. The current report is the second case of plasmacytic LPD in patients with IST for AA. Therefore, detailed histopathological and immunohistochemical analyses are needed for correct diagnosis and treatment, and additional studies are needed to clarify the clinicopathological features of EBV-LPD after IST for AA. PMID:24817974

Nakanishi, Ryota; Ishida, Mitsuaki; Hodohara, Keiko; Okuno, Hiroko; Yoshii, Miyuki; Horinouchi, Akiko; Shirakawa, Ayaka; Harada, Ayumi; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Yoshida, Takashi; Okabe, Hidetoshi

2014-01-01

280

Rituximab for prevention and treatment of graft-versus-host disease.  

PubMed

Growing understanding of the important role of B lymphocytes in alloreactivity has paved the way for evaluating anti-B cell therapy with rituximab in patients undergoing allogeneic hematopoietic cell transplantation. Data suggesting a beneficial reduction in incidence and severity of acute graft-versus-host disease (GVHD) are limited to non-randomized studies from single institutions using higher than conventional doses of rituximab. Additionally, rituximab is used as an effective treatment of corticosteroid-refractory chronic GVHD with good responses, particularly in cases of dermatologic and mucosal involvement. Post-transplant administration of rituximab appears to reduce the rate of chronic GVHD in preliminary studies. PMID:21547615

Kharfan-Dabaja, Mohamed A; Cutler, Corey S

2011-05-01

281

Folliculocentric B-cell-rich follicular dendritic cells sarcoma: a hitherto unreported morphological variant mimicking lymphoproliferative disorders.  

PubMed

We report three cases of follicular dendritic cell sarcoma (FDCS) showing a hitherto undescribed histological pattern consisting of nodular tumor growth associated with small B lymphocytes. FDCS tumor cells consistently showed large epithelioid features and were intermingled with small lymphocytes in the nodules in two cases, whereas they formed cohesive aggregates surrounded by lymphocyte mantle in the other. These features were easily confused with lymphomatous proliferations and, in particular, subtypes of Hodgkin lymphoma, high-grade follicular lymphoma, and germinotropic large B-cell lymphomas. The diagnosis was established by the use of a broad panel of antibodies that showed a variable expression of the FDC markers CD21, CD23, CD35, clusterin, podoplanin, claudin 4, epidermal growth factor receptor, and CXCL13. The associated B lymphocytes revealed a mantle zone B phenotype, with expression of CD20 and PAX5, together with TCL1 and IgD. Of notice, in all cases, morphological features suggesting hyaline-vascular Castleman disease were recognized in the interfollicular areas, containing scattered epithelioid cells similar to those found in the nodules, thus providing a useful clue for FDCS diagnosis. Of the 3 cases, 1 presented multiple recurrences unresponsive to chemotherapy and radiotherapy and finally died of disease 14 years after diagnosis. This study further emphasizes the extreme variability of morphological presentation of FDCS and expands the spectrum of lesions showing a nodular growth pattern occurring in human lymph nodes. PMID:21835430

Lorenzi, Luisa; Lonardi, Silvia; Petrilli, Giulia; Tanda, Francesco; Bella, Michelangelo; Laurino, Licia; Rossi, Giuseppe; Facchetti, Fabio

2012-02-01

282

Castleman's Disease with Cutaneous Involvement Manifestating as Multiple Violaceous Plaques on Entire Body  

PubMed Central

Castleman's disease (CD) is an uncommon B-cell lymphoproliferative disorder characterized by lymph node hyperplasia with vascular proliferation. Cutaneous involvement in CD is rare. A 65-year-old man presented with a 7-year history of gradually developing multiple reddish to violaceous indurated plaques on the scalp, trunk, and legs. On physical examination, there were palpable enlarged cervical, axillary, and inguinal lymph nodes. Laboratory examination revealed anemia, thrombocytosis, hyperproteinemia, hypoalbuminemia, and polyclonal hypergammaglobulinemia. An inguinal lymph node biopsy and a skin biopsy were performed and the patient was diagnosed with the plasma cell type of CD. Chemotherapy was started and the lesions have responded to treatment. PMID:22148042

Park, Hyeon-Young; Lee, Je-Jung; Lee, Jee-Bum; Kim, Seong-Jin; Lee, Seung-Chul; Won, Young Ho

2011-01-01

283

Vascular and nonvascular complications of renal transplants: sonographic evaluation and correlation with other imaging modalities, surgery, and pathology.  

PubMed

Cadaveric or living donor renal transplantation is commonly performed in individuals with end-stage renal disease. In recent years, gray-scale sonography, coupled with color Doppler sonography (CDUS), power Doppler sonography (PDUS), or spectral Doppler sonography, has become the primary imaging modality for these patients. Postoperative serial sonography is performed to detect complications and aid in posttransplant management. In addition, sonography is used to guide percutaneous aspiration of fluid or biopsy to diagnose rejection or renal and perirenal masses. In this article we discuss the spectrum of sonographic findings, both vascular and nonvascular, of renal transplant complications, including but not limited to renal arterial and venous stenosis and thrombosis, peritransplant collections (lymphoceles, hematomas, urinomas, and seromas), posttransplant lymphoproliferative disorder, and postbiopsy complications (hematomas, pseudoaneurysms, and arteriovenous fistulas). We correlate sonographic findings with those from other imaging modalities (such as angiography, CT, and MRI) and findings at surgery and pathology when possible. PMID:15756666

Friedewald, Sarah M; Molmenti, Ernesto P; Friedewald, John J; Dejong, Marius R; Hamper, Ulrike M

2005-01-01

284

Infectious disease prophylaxis in renal transplant patients: a survey of US transplant centers.  

PubMed

Definitive approaches to most infectious diseases following renal transplantation have not been established, leading to different approaches at different transplant centers. To study the extent of these differences, we conducted a survey of the practices surrounding specific infectious diseases at US renal transplant centers. A survey containing 103 questions covering viral, bacterial, mycobacterial and protozoal infections was developed. Surveys were sent to program directors at all U.S. renal transplant centers. Responses were received from 147 of 245 (60%) transplant centers and were proportionately represented all centers with respect to program size and geographical location. Pre-transplant donor and recipient screening for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and cytomegalovirus (CMV) is uniform, but great discrepancy exists in the testing for other agents. HCV seropositive donors are used in 49% of centers. HIV seropositivity remains a contraindication to transplantation, although 13% of centers indicated they have experience with such patients. Post-transplant, there is wide variety in approach to CMV and Pneumocystis carinii (PCP) prophylaxis. Similarly divergent practices affect post-transplant vaccinations, with 54% of centers routinely vaccinating all patients according to customary guidelines in non-transplant populations. In contrast, 22% of centers indicated they do not recommend vaccination in any patients. We believe an appreciation of the differences in approaches to post-transplant infectious complications may encourage individual centers to analyse the results of their own practices. Such analysis may assist in the design of studies to answer widespread and important questions regarding the care of patients following renal transplantation. PMID:11982608

Batiuk, Thomas D; Bodziak, Kenneth A; Goldman, Mitch

2002-02-01

285

Methotrexate-related Epstein-Barr virus-associated lymphoproliferative disorder occurring in the gingiva of a patient with rheumatoid arthritis  

PubMed Central

It is well recognized that patients with immunodeficiency have a high risk of development of lymphoproliferative disorders (LPDs), and Epstein-Barr virus (EBV) is associated with the occurrence of LPDs. Methotrexate (MTX) is one of the common cause of iatrogenic-associated LPD, and approximately 40-50% of MTX-related LPD cases occur in extranodal sites. However, the occurrence of MTX-related LPD in the gingiva is extremely rare. Herein, we report the fourth documented case of MTX-related EBV-associated LPD occurring in the gingiva of a patient with rheumatoid arthritis (RA). A 76-year-old Japanese female with a 10-year history of RA, who was treated with MTX and infliximab, presented with a tumorous lesion in the gingiva. Biopsy of the gingiva tumor revealed diffuse proliferation of large-sized lymphoid cells with cleaved nuclei containing conspicuous nucleoli. These lymphoid cells were CD20- and EBER-positive. Therefore, a diagnosis of MTX-related EBV-associated LPD showing features of diffuse large B-cell lymphoma (DLBCL) that occurred in the gingiva was made. Although the occurrence of LPD in the oral region, as seen in the present case, is rare, the prevalence of this disorder may be on the rise due to the increased number of patients undergoing immunosuppression therapy. Moreover, immunosenescence can also be a cause of EBV-associated LPD. Therefore, recognition of the occurrence of this disorder in the oral cavity and consideration of the clinical history can facilitate the correct diagnosis. PMID:24133604

Ishida, Mitsuaki; Hodohara, Keiko; Yoshii, Miyuki; Okuno, Hiroko; Horinouchi, Akiko; Nakanishi, Ryota; Harada, Ayumi; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Yoshida, Takashi; Okabe, Hidetoshi

2013-01-01

286

Molecular cytogenetic delineation of a novel critical genomic region in chromosome bands 11q22.3-923.1 in lymphoproliferative disorders.  

PubMed Central

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

Stilgenbauer, S; Liebisch, P; James, M R; Schröder, M; Schlegelberger, B; Fischer, K; Bentz, M; Lichter, P; Döhner, H

1996-01-01

287

Pre-and-post transplant considerations in patients with nonalcoholic fatty liver disease  

PubMed Central

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

Khullar, Vikas; Dolganiuc, Angela; Firpi, Roberto J

2014-01-01

288

Pathophysiologic and treatment strategies for cardiovascular disease in end-stage renal disease and kidney transplantations.  

PubMed

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

Ghanta, Mythili; Kozicky, Mark; Jim, Belinda

2015-01-01

289

Clinical characteristics and healthcare utilization of patients with multicentric Castleman disease.  

PubMed

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disease. Little is known about how patient clinical features and healthcare utilization varies by human immunodeficiency virus (HIV) status and disease subtype. Data of MCD patients identified between 2000 and 2009 were collected from medical records at two United States treatment centres. Clinical, demographic, and biochemical characteristics, drug therapies and medical utilization were descriptively reported by HIV status and cell histology, and statistically compared with the Fisher's Exact and Kruskal-Wallis tests. Patients (n = 59) had a pathologically and clinically confirmed MCD diagnosis: plasmacytic (42%), hyaline vascular (29%) and mixed (15%); 10% had HIV infection. In the first year after diagnosis, MCD patients on average saw a healthcare provider more than six times, were hospitalized at least once and underwent frequent radiological and laboratory testing. Rituximab was the most commonly used drug therapy, followed by corticosteroids and conventional chemotherapy. One- and 2-year survival was excellent in HIV-negative patients (100% and 97%, respectively) but inferior for HIV-positive cases (67% and 67%, respectively). Heterogeneous treatment decisions were observed in this MCD study; HIV status was the only distinguishing clinical criteria associated with pharmacotherapies. Additional research is necessary to guide treatment of this rare lymphoproliferative disorder. PMID:25208471

Casper, Corey; Teltsch, Dana Y; Robinson, Don; Desrosiers, Marie-Pierre; Rotella, Philip; Dispenzieri, Angela; Qi, Ming; Habermann, Thomas; Reynolds, Matthew W

2015-01-01

290

Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning  

PubMed Central

Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies depends on graft-versus-tumor effects for eradication of cancer. Here, we estimated relapse risks according to disease characteristics. Between 1997 and 2006, 834 consecutive patients (median age, 55 years; range, 5-74 years) received related (n = 498) or unrelated (n = 336) HCT after 2 Gy total body irradiation alone (n = 171) or combined with fludarabine (90 mg/m2; n = 663). Relapse rates per patient year (PY) at risk, corrected for follow-up and competing nonrelapse mortality, were calculated for 29 different diseases and stages. The overall relapse rate per PY was 0.36. Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in remission (CR), low-grade or mantle cell non-Hodgkin lymphoma (NHL) (CR + partial remission [PR]), and high-grade NHL-CR had the lowest rates (0.00-0.24; low risk). In contrast, patients with advanced myeloid and lymphoid malignancies had rates of more than 0.52 (high risk). Patients with lymphoproliferative diseases not in CR (except Hodgkin lymphoma and high-grade NHL) and myeloid malignancies in CR had rates of 0.26-0.37 (standard risk). In conclusion, patients with low-grade lymphoproliferative disorders experienced the lowest relapse rates, whereas patients with advanced myeloid and lymphoid malignancies had high relapse rates after nonmyeloablative HCT. The latter might benefit from cytoreductive treatment before HCT. PMID:17595333

Kahl, Christoph; Storer, Barry E.; Sandmaier, Brenda M.; Mielcarek, Marco; Maris, Michael B.; Blume, Karl G.; Niederwieser, Dietger; Chauncey, Thomas R.; Forman, Stephen J.; Agura, Edward; Leis, Jose F.; Bruno, Benedetto; Langston, Amelia; Pulsipher, Michael A.; McSweeney, Peter A.; Wade, James C.; Epner, Elliot; Bo Petersen, Finn; Bethge, Wolfgang A.; Maloney, David G.

2007-01-01

291

HIV-associated Multicentric Castleman Disease  

PubMed Central

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

Reddy, Deepa; Mitsuyasu, Ronald

2015-01-01

292

Clonal rearrangement for immunoglobulin and T-cell receptor genes in systemic Castleman's disease. Association with Epstein-Barr virus.  

PubMed Central

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

Hanson, C. A.; Frizzera, G.; Patton, D. F.; Peterson, B. A.; McClain, K. L.; Gajl-Peczalska, K. J.; Kersey, J. H.

1988-01-01

293

Chronic Kidney Disease (CKD) after Liver Transplantation in HIV/ HCV Coinfected versus HIV/non-HCV Infected Recipients: Results from the NIH Multi-Site Study  

PubMed Central

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 versus HIV/non-HCV infected recipients. METHODS Data from the NIH Solid Organ Transplantation in HIV: Multi-Site Study of 116 OLT recipients (35 HIV/non-HCV and 81 HIV/HCV co-infected) from 2003 to 2010 were analyzed for pre-transplant CKD prevalence (estimated glomerular filtration rate (eGFR) < 60 ml/min for ? 3 months) and incidence of CKD up to 3 years post-transplant. Proportional hazards models were performed to assess predictors of post-transplant CKD. A contemporaneous cohort of HCV monoinfected transplant recipients from the SRTR database was also analyzed. RESULTS Median age at transplant was 48 years, serum creatinine was 1.1 mg/dl, and median eGFR was 77 ml/min. Thirty-four patients had suspected pre-transplant CKD; 20 of these (59%) had post-transplant CKD. Among the 82 patients without pre-transplant CKD (26 HIV/non-HCV and 56 HIV/HCV coinfected), the cumulative incidence of stage 3 CKD at 3 years post-OLT was 62% (55% HIV/non-HCV versus 65% HIV/HCV coinfected) and stage 4/5 CKD was 8% (0% HIV/non-HCV versus 12% HIV/HCV coinfected). In multivariate proportional hazards analysis, older age (HR 1.05 per year; p 0.03) and 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 adjustment for age on multivariate analysis. The cumulative incidence of stage 4/5 CKD was significantly higher in HIV/HCV coinfected patients compared to HIV/non-HCV and HCV monoinfected transplant recipients (p=0.001). CONCLUSIONS CKD occurs frequently in HIV infected transplant recipients. Predictors of post-transplant CKD include older age, and lower post-transplant CD4 count. HCV co-infection is associated with a higher incidence of stage 4/5 CKD. PMID:23512786

Bahirwani, Ranjeeta; Barin, Burc; Olthoff, Kim; Stock, Peter; Murphy, Barbara; Reddy, K. Rajender

2013-01-01

294

Dynamic International Prognostic Scoring System scores, pre-transplant therapy and chronic graft-versus-host disease determine outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis  

PubMed Central

Background Myelofibrosis is a myeloproliferative stem cell disorder curable exclusively by allogeneic hematopoietic stem cell transplantation and is associated with substantial mortality and morbidity. The aim of this study was to assess disease-specific and transplant-related risk factors that influence post-transplant outcome in patients with myelofibrosis. Design and Methods We retrospectively assessed 76 consecutive patients with primary (n=47) or secondary (n=29) myelofibrosis who underwent bone marrow (n=6) or peripheral blood stem cell (n=70) transplantation from sibling (n=30) or unrelated (n=46) donors between January 1994 and December 2010. The median follow-up of surviving patients was 55±7.5 months. Results Primary graft failure occurred in 5% and the non-relapse mortality rate at 1 year was 28%. The relapse-free survival rate was 50% with a relapse rate of 19% at 5 years. The use of pharmacological pre-treatment and the post-transplant occurrence of chronic graft-versus-host disease were significant independent unfavourable risk factors for post-transplant survival in multivariate analysis. Using the Dynamic International Prognostic Scoring System for risk stratification, low-risk patients had significantly better overall survival (P=0.014, hazard ratio 1.4) and relapse-free survival (P=0.02, hazard ratio 1.3) compared to the other risk groups of patients. The additional inclusion of thrombocytopenia, abnormal karyotype and transfusion need (Dynamic International Prognostic Scoring System Plus) resulted in a predicted 5-year overall survival of 100%, 51%, 54% and 30% for low, intermediate-1, intermediate-2 and high-risk groups, respectively. The relapse incidence was significantly higher in the absence of chronic graft-versus-host disease (P=0.006), and pharmacological pre-treatment (n=43) was associated with reduced relapse-free survival (P=0.001). Conclusions The data corroborate a strong correlation between alloreactivity and long-term post-transplant disease control and confirm an inverse relationship between disease stage, pharmacotherapy and outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis. The Dynamic International Prognostic Scoring System was demonstrated to be useful for risk stratification of patients with myelofibrosis who are to undergo hematopoietic stem cell transplantation. PMID:22491742

Ditschkowski, Markus; Elmaagacli, Ahmet H.; Trenschel, Rudolf; Gromke, Tanja; Steckel, Nina K.; Koldehoff, Michael; Beelen, Dietrich W.

2012-01-01

295

Successful Treatment of Castleman’s Disease with Interleukin-1 Receptor Antagonist (Anakinra)  

PubMed Central

Castleman’s disease (CD) is a very rare lymphoproliferative disorder whose underlying pathophysiology is not fully understood and for which no standard treatment exists. Because interleukin-1 (IL-1) might promote the production of interleukin-6 (IL-6), a key pathogenic factor for the disease, we hypothesized that blocking the IL-1 receptor would be a useful therapy for CD. We report the case of a 61-year-old woman with CD who had undergone multiple treatments, including cladribine, rituximab, steroids, etanercept, and anti-IL-6 monoclonal antibody, and whose disease was refractory to all of these treatments. She was started on the recombinant IL-1 receptor antagonist, Anakinra, at a subcutaneous dose of 100 mg daily. Within one week, her fatigue and anorexia markedly improved, and her laboratory abnormalities, including anemia, thrombocytosis, leukocytosis, and elevated markers of inflammation, all resolved. Our observation suggests that Anakinra may be an attractive therapeutic approach for refractory multicentric CD. PMID:20501803

El-Osta, Hazem; Janku, Filip; Kurzrock, Razelle

2011-01-01

296

Successful treatment of Castleman's disease with interleukin-1 receptor antagonist (Anakinra).  

PubMed

Castleman's disease (CD) is a very rare lymphoproliferative disorder whose underlying pathophysiology is not fully understood and for which no standard treatment exists. Because interleukin-1 (IL-1) might promote the production of interleukin-6 (IL-6), a key pathogenic factor for the disease, we hypothesized that blocking the interleukin-1 receptor would be a useful therapy for CD. We report the case of a 61-year-old woman with CD who had undergone multiple treatments, including cladribine, rituximab, steroids, etanercept, and anti-IL-6 monoclonal antibody, and whose disease was refractory to all of these treatments. She was started on the recombinant IL-1 receptor antagonist, Anakinra, at a subcutaneous dose of 100 mg daily. Within one week, her fatigue and anorexia markedly improved, and her laboratory abnormalities, including anemia, thrombocytosis, leukocytosis, and elevated markers of inflammation, all resolved. Our observation suggests that Anakinra may be an attractive therapeutic approach for refractory multicentric CD. PMID:20501803

El-Osta, Hazem; Janku, Filip; Kurzrock, Razelle

2010-06-01

297

Castleman disease mimicked pancreatic carcinoma: report of two cases.  

PubMed

Castleman disease (CD) is an uncommon benign lymphoproliferative disorder, which usually presents as solitary or multiple masses in the mediastinum. Peripancreatic CD was rarely reported. Herein, we report two cases of unicentric peripancreatic CD from our center. A 43-year-old man and a 58-year-old woman were detected to have a pancreatic mass in the routine medical examinations. Both of them were asymptomatic. The computed tomography and ultrasonographic examination revealed a mild enhancing solitary mass at the pancreatic head/neck. No definite preoperative diagnosis was established and Whipple operations were originally planned. The intraoperative frozen section diagnosis of both patients revealed lymphoproliferation. Then the local excisions of mass were performed. Histological examination revealed features of CD of hyaline-vascular type. No recurrence was found during the follow-up period. CD should be included in the differential diagnosis of pancreatic tumors. Local excision is a suitable surgical choice. PMID:22824621

Guo, Hua; Shen, Yan; Wang, Wei-Lin; Zhang, Min; Li, Hong; Wu, Ying-Sheng; Yan, Sheng; Xu, Xiao; Wu, Jian; Zheng, Shu-Sen

2012-01-01

298

Lymph node-based disease and HHV-8/KSHV infection in HIV seronegative patients: report of three new cases of a heterogeneous group of diseases.  

PubMed

We describe three cases of lymph proliferative diseases characterized by the presence of lymphoma cells expressing the KSHV/HHV-8 antigen with or without EBV expression. The patients were HIV seronegative without serous effusions. One case was diagnosed as KSHV-germinotropic lymphoproliferative disorder due to the presence of atypical plasmablasts involving germinal centers. These plasmablasts were positive for MUM1 and vIL6, co-expressed EBV and LNA-1 of HHV-8/KSHV, and showed a polyclonal pattern of Ig gene rearrangements on PCR. The disease was localized and the prognosis was good. In two other cases, a diagnosis of KSHV/HHV-8-related diffuse large cell B-lymphoma morphology was made. The lymphoma cells were anaplastic or frankly pleomorphic, expressed KSHV but not EBV, and were positive for CD20, MUM1, PAX-5, and vIL6. In both cases the prognosis was poor. On the basis of the features observed, we raise three considerations: (1) KSHV-related lymphoproliferative disorders represent a distinctive and heterogeneous group of diseases with variable clinico-pathologic findings and immunophenotypes (BCL6-/MUM1+/CD138- and BCL6+/MUM1+/CD138- or BCL6-/MUM1+/CD138+). (2) Although the pathogenic mechanism of HHV8 in lymphomagenesis is unclear, the presence the viral DNA in lymph nodes of HIV- patients is not a simply opportunistic infection, but is directly implicated in the pathogenesis of KSHV-related diseases; the activation of IL-6 receptor signalling may play an important role in most cases. (3) The different prognoses among different diseases with KSHV etiology may be related to the fact that the pathogenic potential appears to be constrained by a competent immune system. PMID:21509436

D'Antonio, Antonio; Addesso, Maria; Memoli, Domenico; Liguori, Pina; Cuomo, Roberto; Boscaino, Amedeo; Nappi, Oscar

2011-06-01

299

A unique description of stage IV extranodal marginal zone lymphoma (EMZL) in an adolescent associated with gamma heavy chain disease.  

PubMed

Extranodal Marginal zone lymphoma (EMZL) is a rare, usually localized disease in children. Advanced stage EMZL in adults is considered incurable, with prolonged remissions after chemotherapy. Gamma heavy chain disease (?HCD) is a rare disease of adults associated with lympho-proliferative processes with no comparable reports in children. A case of stage-IV EMZL with ?HCD in an adolescent is discussed including treatment with Bendamustine plus Rituximab. The patient remains disease free 18 months from diagnosis. This case highlights necessity for careful diagnostic work-up to identify indolent lymphomas in children which may respond to less toxic chemotherapy than used for common pediatric lymphomas. Pediatr Blood Cancer 2015;62:905-908. © 2015 Wiley Periodicals, Inc. PMID:25663537

Mittal, Nupur; Zhu, Bing; Gaitonde, Sujata; Lu, Yang; Schmidt, Mary Lou

2015-05-01

300

High-dose iodine-131-metaiodobenzylguanidine with haploidentical stem cell transplantation and posttransplant immunotherapy in children with relapsed/refractory neuroblastoma.  

PubMed

We evaluated the feasibility and efficacy of using high-dose iodine-131-metaiodobenzylguanidine ((131)I-MIBG) followed by reduced-intensity conditioning (RIC) and transplantation of T cell-depleted haploidentical peripheral blood stem cells (designated haplo-SCT) to treat relapsing/refractory neuroblastoma (RRNB). Five RRNB patients were enrolled: 4 with relapse (3 after autologous SCT) and 1 with induction therapy failure. The preparative regimen included high-dose (131)I-MIBG on day -20, followed by fludarabine (Flu), thiotepa, and melphalan (Mel) from day -8 to -1. Granulocyte-colony stimulating factor (G-CSF)-mobilized, T cell-depleted haploidentical paternal stem cells were infused on day 0 together with cultured donor mesenchymal stem cells. A single dose of rituximab was given on day +1. After cessation of short immunosuppression (mycophenolate, OKT3), 4 children received donor lymphocyte infusion (DLI). (131)I-MIBG infusion and RIC were well tolerated. All patients engrafted. No primary acute graft-versus-host disease (aGVHD) was observed. Four children developed aGVHD after DLI and were successfully treated. Analysis of immunologic recovery showed fast reappearance of potentially immunocompetent natural killer (NK) and T cells, which might have acted as effector cells responsible for the graft-versus-tumor (GVT) effect. Two children are alive and well, with no evidence of disease 40 and 42 months after transplantation. One patient experienced late progression with new bone lesions (sternum) 38 months after haplo-SCT, and is being treated with local irradiation and reinstituted DLI. One patient rejected the graft, was rescued with autologous backup, and died of progressive disease 5 months after transplantation. Another child relapsed 7 months after transplantation and died 5 months later. High-dose (131)I-MIBG followed by RIC and haplo-SCT for RRNB is feasible and promising, because 2 of 5 children on that regimen achieved long-lasting remission. Further studies are needed to evaluate targeted therapy and immune-mediated tumor control in high-risk neuroblastoma. PMID:19660720

Toporski, Jacek; Garkavij, Michael; Tennvall, Jan; Ora, Ingrid; Gleisner, Katarina Sjögreen; Dykes, Josefina H; Lenhoff, Stig; Juliusson, Gunnar; Scheding, Stefan; Turkiewicz, Dominik; Békássy, Albert N

2009-09-01

301

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

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

Cistaro, A; Pazè, F; Durando, S; Cogoni, M; Faletti, R; Vesco, S; Vallero, S; Quartuccio, N; Treglia, G; Ramenghi, U

2014-01-01

302

Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States  

PubMed Central

Chronic active EBV disease (CAEBV) is a lymphoproliferative disorder characterized by markedly elevated levels of antibody to EBV or EBV DNA in the blood and EBV RNA or protein in lymphocytes in tissues. We present our experience with CAEBV during the last 28 years, including the first 8 cases treated with hematopoietic stem cell transplantation in the United States. Most cases of CAEBV have been reported from Japan. Unlike CAEBV in Japan, where EBV is nearly always found in T or natural killer (NK) cells in tissues, EBV was usually detected in B cells in tissues from our patients. Most patients presented with lymphadenopathy and splenomegaly; fever, hepatitis, and pancytopenia were common. Most patients died of infection or progressive lymphoproliferation. Unlike cases reported from Japan, our patients often showed a progressive loss of B cells and hypogammaglobulinemia. Although patients with CAEBV from Japan have normal or increased numbers of NK cells, many of our patients had reduced NK-cell numbers. Although immunosuppressive agents, rituximab, autologous cytotoxic T cells, or cytotoxic chemotherapy often resulted in short-term remissions, they were not curative. Hematopoietic stem cell transplantation was often curative for CAEBV, even in patients with active lymphoproliferative disease that was unresponsive to chemotherapy. These studies are registered at http://www.clinicaltrials.gov as NCT00032513 for CAEBV, NCT00062868 and NCT00058812 for EBV-specific T-cell studies, and NCT00578539 for the hematopoietic stem cell transplantation protocol. PMID:21454450

Jaffe, Elaine S.; Dale, Janet K.; Pittaluga, Stefania; Heslop, Helen E.; Rooney, Cliona M.; Gottschalk, Stephen; Bollard, Catherine M.; Rao, V. Koneti; Marques, Adriana; Burbelo, Peter D.; Turk, Siu-Ping; Fulton, Rachael; Wayne, Alan S.; Little, Richard F.; Cairo, Mitchell S.; El-Mallawany, Nader K.; Fowler, Daniel; Sportes, Claude; Bishop, Michael R.; Wilson, Wyndham; Straus, Stephen E.

2011-01-01

303

Inhibitors of apoptosis (IAPs) regulate intestinal immunity and inflammatory bowel disease (IBD) inflammation.  

PubMed

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

Pedersen, Jannie; LaCasse, Eric C; Seidelin, Jakob B; Coskun, Mehmet; Nielsen, Ole H

2014-11-01

304

Castleman disease presenting with jaundice: a case with the multicentric hyaline vascular variant.  

PubMed

Castleman disease (CD) is a rare lymphoproliferative disorder of unknown etiology with different clinical manifestations. A previous healthy 50 year-old man was hospitalized for right upper quadrant (RUQ) abdominal pain. He had jaundice and a 1 cm-sized lymph node in the right supraclavicular area. Pancreas and biliary computed tomography (CT) showed masses at the right renal hilum and peripancreatic areas. Positron emission tomography (PET) showed widespread systemic lymphadenopathy. Excisional biopsy of the right supraclavicular node revealed a hyaline vascular variant of CD. Corticosteroid therapy was started and the extent of disease decreased. We here report a case of multicentric CD, the hyaline vascular variant, presenting with jaundice, diagnosed by excisional biopsy and successfully treated with corticosteroids. PMID:17616028

Park, Jun Bean; Hwang, Jin Hyeok; Kim, Haeryoung; Choe, Hyung Sim; Kim, Yu Kyeong; Kim, Hong Bin; Bang, Soo-Mee

2007-06-01

305

Real-time quantitative PCR using hairpin-shaped clone-specific primers for minimal residual disease assessment in an animal model of human non-Hodgkin lymphoma.  

PubMed

A multitude of molecular techniques for monitoring minimal residual disease in lymphoproliferative disorders have been described to date. Real-Time Quantitative PCR targeting Immunoglobulin Heavy chain patient-specific sequences is increasingly being used for molecular detection of residual neoplastic B-cells using allele-specific oligos. The establishment of individually tailored PCR assays with the extensive use of patient-specific fluorescent-labeled oligos may be cumbersome and expensive. The present study was aimed at evaluating the usefulness of recently described hairpin-shaped allele-specific primers, originally intended for typing single-nucleotide polymorphisms, for the assessment of minimal residual disease using SYBR Green intercalating dye. Three cloned and 2 sequenced clonogenic Ig heavy chain rearranged gene loci, obtained from 5 cases of canine spontaneous B-cell lymphoma, were used as an experimental model. Both standard linear and hairpin-shaped forward and reverse clone-specific primers were evaluated in terms of specificity, sensitivity and PCR efficiency. Hairpin-shaped primers were demonstrated to have achieved accurate results more consistently than the respective linear primers allowing the specific and sensitive quantification of minimal residual disease of lymphoproliferative disorders with fewer validation procedures and more flexibility on the assay design. PMID:19651205

Gentilini, Fabio; Turba, Maria Elena; Calzolari, Claudia; Cinotti, Stefano; Forni, Monica; Zannoni, Augusta

2010-02-01

306

Autoimmune BSEP Disease: Disease Recurrence After Liver Transplantation for Progressive Familial Intrahepatic Cholestasis.  

PubMed

Severe cholestasis may result in end-stage liver disease with the need of liver transplantation (LTX). In children, about 10 % of LTX are necessary because of cholestatic liver diseases. Apart from bile duct atresia, three types of progressive familial intrahepatic cholestasis (PFIC) are common causes of severe cholestasis in children. The three subtypes of PFIC are defined by the involved genes: PFIC-1, PFIC-2, and PFIC-3 are due to mutations of P-type ATPase ATP8B1 (familial intrahepatic cholestasis 1, FIC1), the ATP binding cassette transporter ABCB11 (bile salt export pump, BSEP), or ABCB4 (multidrug resistance protein 3, MDR3), respectively. All transporters are localized in the canalicular membrane of hepatocytes and together mediate bile salt and phospholipid transport. In some patients with PFIC-2 disease, recurrence has been observed after LTX, which mimics a PFIC phenotype. It could be shown by several groups that inhibitory anti-BSEP antibodies emerge, which most likely cause disease recurrence. The prevalence of severe BSEP mutations (e.g., splice site and premature stop codon mutations) is very high in this group of patients. These mutations often result in the complete absence of BSEP, which likely accounts for an insufficient auto-tolerance against BSEP. Although many aspects of this "new" disease are not fully elucidated, the possibility of anti-BSEP antibody formation has implications for the pre- and posttransplant management of PFIC-2 patients. This review will summarize the current knowledge including diagnosis, pathomechanisms, and management of "autoimmune BSEP disease." PMID:25342496

Kubitz, Ralf; Dröge, Carola; Kluge, Stefanie; Stross, Claudia; Walter, Nathalie; Keitel, Verena; Häussinger, Dieter; Stindt, Jan

2015-06-01

307

Gastrointestinal pathology in transplant patients.  

PubMed

The assessment of gastrointestinal (GI) specimens from transplant patients is complicated by the wide range of potentially rare pathologies that may be found in this clinical setting. Acute GI graft-versus-host disease (GvHD) is characterized by epithelial cell apoptosis, although there is increasing recognition that acute and/or chronic inflammation may also be present. By contrast, thus far there are no histological features known to be specific to chronic GI GvHD. Mycophenolate mofetil colitis may mimic both GvHD and inflammatory bowel disease, whereas both cytomegalovirus (CMV) and adenovirus infections can cause gland apoptosis. Post-transplant lymphoproliferative disorder should be considered if a Crohn's-like histological picture is seen, and granulomas in biopsies from umbilical cord blood recipients should raise a suspicion of cord colitis syndrome. Finally, the GI tract may be involved directly or indirectly by the disease that originally required haematopoietic stem cell or liver transplantation. PMID:25195803

Wong, Newton A C S

2015-03-01

308

Regression of cutaneous invasive squamous cell carcinoma in a patient with chronic cutaneous graft versus host disease.  

PubMed

Numerous complications can be observed in the post-transplant period among recipients of hematopoietic stem cells including graft-versus-host disease (GVHD), which is associated with significant morbidity and mortality. On the other hand, graft versus tumor (GVT) effect is a well-described phenomenon in patients with hematologic malignancies and has also been reported in renal cell cancer, ovarian cancer, breast carcinoma, and melanoma. We describe spontaneous regression of a cutaneous invasive squamous cell carcinoma and multifocal atypical intraepidermal proliferations in a patient with chronic graft-versus-host disease following initiation of extracorporeal photopheresis (ECP). This observation raises questions regarding the GVT in cutaneous neoplasms and potential immunomodulatory effects of ECP. PMID:24852774

Balagula, Yevgeniy; Taube, Janis M; Wang, Timothy; Dorafshar, Amir H; Sweren, Ronald J

2014-05-01

309

Parkinson's Disease  

MedlinePLUS

... 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 ...

310

Pick disease  

MedlinePLUS

Semantic dementia; Dementia - semantic; Frontotemporal dementia; Arnold Pick disease ... can help doctors tell Pick disease apart from Alzheimer disease. (Memory loss is often the main, and earliest, ...

311

Overexpression of Activation-Induced Cytidine Deaminase in MTX- and Age-Related Epstein-Barr Virus-Associated B-Cell Lymphoproliferative Disorders of the Head and Neck  

PubMed Central

Recent research has shown that activation-induced cytidine deaminase (AID) triggers somatic hypermutation and recombination, in turn contributing to lymphomagenesis. Such aberrant AID expression is seen in B-cell leukemia/lymphomas, including Burkitt lymphoma which is associated with c-myc translocation. Moreover, Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) increases genomic instability through early growth transcription response-1 (Egr-1) mediated upregulation of AID in B-cell lymphoma. However, few clinicopathological studies have focused on AID expression in lymphoproliferative disorders (LPDs). Therefore, we conducted an immunohistochemical study to investigate the relationship between AID and LMP-1 expression in LPDs (MTX-/Age-related EBV-associated), including diffuse large B-cell lymphomas (DLBCLs). More intense AID expression was detected in LPDs (89.5%) than in DLBCLs (20.0%), and the expression of LMP-1 and EBER was more intense in LPDs (68.4% and 94.7%) than in DLBCLs (10.0% and 20.0%). Furthermore, stronger Egr-1 expression was found in MTX/Age-EBV-LPDs (83.3%) than in DLBCLs (30.0%). AID expression was significantly constitutively overexpressed in LPDs as compared with DLBCLs. These results suggest that increased AID expression in LPDs may be one of the processes involved in lymphomagenesis, thereby further increasing the survival of genetically destabilized B-cells. AID expression may be a useful indicator for differentiation between LPDs and DLBCLs.

Kikuchi, Kentaro; Ishige, Toshiyuki; Ide, Fumio; Ito, Yumi; Saito, Ichiro; Hoshino, Miyako; Inoue, Harumi; Miyazaki, Yuji; Nozaki, Tadashige; Kojima, Masaru; Kusama, Kaoru

2015-01-01

312

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....

313

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 ...

314

Lyme Disease  

MedlinePLUS

... Is Lyme Disease? People get Lyme disease through tick bites. The disease is caused by a bacterium called ... a sesame seed. It's easy to overlook a tick bite. Many people who get Lyme disease don't ...

315

Japanese variant of multicentric castleman's disease associated with serositis and thrombocytopenia--a report of two cases: is TAFRO syndrome (Castleman- Kojima disease) a distinct clinicopathological entity?  

PubMed

Multicentric Castleman's disease (MCD) is a polyclonal lymphoproliferative disorder that manifests as marked hyper-?-globulinemia, severe inflammation, anemia, and thrombocytosis. Recently, Takai et al. reported a new disease concept, TAFRO syndrome, named from thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. Furthermore, Kojima et al. reported Japanese MCD cases with effusion and thrombocytopenia (Castleman-Kojima disease). Here, we report two cases of MCD associated with marked pleural effusion, ascites, and thrombocytopenia, and discuss the independence of the TAFRO syndrome (Castleman-Kojima disease). Case 1: A 57-year-old woman had fever, anemia, anasarca, and some small cervical lymphadenopathy. Although she had been administered steroid therapy, and full-coverage antibiotics, her general condition, including fever, systemic inflammation, and anasarca, deteriorated steadily. We administered chemotherapy [CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisolone) regimen], but despite a transient improvement, she died due to septic shock. Case 2: A 73-year-old man with a history of aplastic anemia and remission presented with fever, severe inflammation, and anasarca. Prednisolone was administered (15 mg daily), and his hyperinflammation once improved. Nevertheless, his general condition, including pleural effusion and ascites, worsened, and C-reactive protein and interleukin-6 levels showed marked increases. The patient died due to multiorgan failure. Cases of TAFRO syndrome (Castleman-Kojima disease) are still rare. Therefore, it is necessary to conduct multicenter clinical surveys including similar cases, such as ours, to reach a consensus regarding diagnostic criteria, therapeutic strategy, and pathophysiological etiology for this syndrome. PMID:23801138

Masaki, Yasufumi; Nakajima, Akio; Iwao, Haruka; Kurose, Nozomu; Sato, Tomomi; Nakamura, Takuji; Miki, Miyuki; Sakai, Tomoyuki; Kawanami, Takafumi; Sawaki, Toshioki; Fujita, Yoshimasa; Tanaka, Masao; Fukushima, Toshihiro; Okazaki, Toshiro; Umehara, Hisanori

2013-01-01

316

The Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) equation best characterizes kidney function in patients being considered for lung transplantation  

PubMed Central

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

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

317

Management of inflammatory bowel disease patients with a cancer history.  

PubMed

In inflammatory bowel disease (IBD) patients, thiopurines promote carcinogenesis of Epstein-Barr Virus (EBV)-related lymphomas, non-melanoma skin cancers and urinary tract cancers, while anti-TNF agents could promote carcinogenesis of melanomas. Patients with IBD and previous cancer are at a higher risk of developing new or recurrent cancer than IBD patients without a history of cancer, irrespective of the use of immunosuppressants. In transplant recipients, the use of thiopurines is associated with a high rate of cancer recurrence, particularly within the first two years following transplantation. In patients with chronic inflammatory disease, limited data suggest that no dramatic incidence of cancer recurrence is associated with the use of thiopurines or anti-TNF agents. However, there is a rationale for a two-year drug holiday from immunosuppressants after the diagnosis and treatment of the majority of incident cancers, as often as possible. Extending the duration of the immunosuppressant drug holiday to 5 years in patients with previous cancers associated with a high risk of recurrence in the post-transplant state should be considered. The immunosuppressants that can be initiated or resumed after cancer treatment should be chosen according to the type of the previous cancer. All individual decisions should be made on a case-by-case basis, together with the oncologist, according to characteristics and expected evolution of the index cancer, expected impact of the immunosuppressants on cancer evolution, and intrinsic severity of IBD, with its associated risks. PMID:25146698

Beaugerie, Laurent

2014-01-01

318

Chagas Disease  

MedlinePLUS

... Health Division of Parasitic Diseases and Malaria CS226359 Chagas Disease Fact Sheet What is Chagas disease? ? A disease that can cause serious heart ... benchuca,” “vinchuca,” “chinche,” or “barbeiro” Who can get Chagas disease? Anyone. However, people have a greater chance ...

319

VESICULAR DISEASES  

Technology Transfer Automated Retrieval System (TEKTRAN)

The principal vesicular diseases that affect swine are foot-and-mouth disease (FMD), vesicular stomatitis (VS), and swine vesicular diseases (SVD). There are other infectious diseases and conditions that can produce signs and pathologies in pigs similar to those seen in these three viral diseases, ...

320

Alzheimer's Disease  

MedlinePLUS

... version of this page please turn Javascript on. Alzheimer's Disease What Is Alzheimer's Disease? Alzheimer’s disease is a brain disease that slowly ... it has no cure. A Common Cause of Dementia Alzheimer’s disease is the most common cause of ...

321

Foodborne Diseases  

MedlinePLUS

... JavaScript on. Read more information on enabling JavaScript. Foodborne Diseases Top Banner Content Area Skip Content Marketing Share ... on a clean kitchen countertop. Credit: CDC. Understanding Foodborne Diseases Infectious diseases spread through food or beverages are ...

322

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 ...

323

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 ...

324

Infectious Diseases  

MedlinePLUS

Infectious diseases kill more people worldwide than any other single cause. Infectious diseases are caused by germs. Germs are tiny living ... live NIH: National Institute of Allergy and Infectious Diseases

325

Bone Diseases  

MedlinePLUS

... break Osteogenesis imperfecta makes your bones brittle Paget's disease of bone makes them weak Bone disease can make bones easy to break Bones can also develop cancer and infections Other bone diseases are caused by poor nutrition, genetic factors or ...

326

Behcet's Disease  

MedlinePLUS

... Old Silk Route,” which spans the region from Japan and China in the Far East to the ... the disease’s epidemiology is not well understood. In Japan, Behcet’s disease ranks as a leading cause of ...

327

Parkinson's Disease  

MedlinePLUS

... symptoms of something called Parkinson's disease. What Is Parkinson's Disease? You may have seen the actor Michael J. ... it needs to move normally. Continue What Causes Parkinson's Disease? Experts agree that low dopamine levels in the ...

328

Reportable diseases  

MedlinePLUS

... be reported to the U.S. Centers for Disease Control and Prevention (CDC). Reportable diseases are divided into several groups: Mandatory written reporting: A report of the disease must be made ...

329

Pompe Disease  

MedlinePLUS

... Manifestations of Pompe Disease, Acid Maltase Deficiency, Glycogen Storage Disease Table of Contents (click to jump to ... Clinical Trials Organizations Column1 Column2 Association for Glycogen Storage Disease P.O. Box 896 Durant, IA 52747 ...

330

Lyme Disease  

MedlinePLUS

... Lyme Disease Top Banner Content Area Skip Content Marketing Share this: Main Content Area Understanding Lyme Disease ... about NIAID Lyme disease research . Research at NIAID Diagnostic Research Co-Infection Antibiotic Therapy Vaccines Research in ...

331

Farber's Disease  

MedlinePLUS

... a group of inherited metabolic disorders called lipid storage diseases, in which excess amounts of lipids (oils, ... Institutes of Health (NIH), conducts research about lipid storage diseases such as Farber’s disease in laboratories at ...

332

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 ...

333

Krabbe Disease  

MedlinePLUS

... Krabbe Disease? Krabbe disease is a rare, inherited degenerative disorder of the central and peripheral nervous systems. ... receive umbilical cord blood stem cells prior to disease onset or early bone marrow transplantation. Persons with juvenile- or adult-onset ...

334

Treatment Options for Childhood Non-Hodgkin Lymphoma  

MedlinePLUS

... Web site . Lymphoproliferative Disease Associated with a Weakened Immune System Treatment of lymphoproliferative disease in children and adolescents with weakened immune systems may include the following: Surgery with or without ...

335

Targeting Marek's disease virus by RNA interference delivered from a herpesvirus vaccine.  

PubMed

Live attenuated herpesvirus vaccines such as herpesvirus of turkey (HVT) have been used since 1970 for the control of Marek's disease (MD), a highly infectious lymphoproliferative disease of poultry. Despite the success of these vaccines in reducing losses from the disease, Marek's disease virus (MDV) strains have shown a continuing increase in virulence, presumably due to the inability of the current vaccines in preventing MDV replication. The highly specific and effective nature of RNA interference (RNAi) makes this technology particularly attractive for new antiviral strategies. In order to exploit the power of RNAi-mediated suppression of MDV replication in vivo delivered through existing vaccines, we engineered recombinant HVT expressing short hairpin RNA (shRNA) against MDV genes gB and UL29. The levels of protection induced by the RNAi-expressing HVT against virulent virus challenge were similar to the parent pHVT3 virus. However, chickens vaccinated with recombinant HVT expressing shRNA showed moderate reduction of challenge virus replication in blood and feather samples. Delivery of RNAi-based gene silencing through live attenuated vaccines for reducing replication of pathogenic viruses is a novel approach for the control of infectious diseases. PMID:18977264

Lambeth, Luke S; Zhao, Yuguang; Smith, Lorraine P; Kgosana, Lydia; Nair, Venugopal

2009-01-01

336

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

337

Disease-causing mutations in the XIAP BIR2 domain impair NOD2-dependent immune signalling  

PubMed Central

X-linked Inhibitor of Apoptosis (XIAP) is an essential ubiquitin ligase for pro-inflammatory signalling downstream of the nucleotide-binding oligomerization domain containing (NOD)-1 and -2 pattern recognition receptors. Mutations in XIAP cause X-linked lymphoproliferative syndrome type-2 (XLP2), an immunodeficiency associated with a potentially fatal deregulation of the immune system, whose aetiology is not well understood. Here, we identify the XIAP baculovirus IAP repeat (BIR)2 domain as a hotspot for missense mutations in XLP2. We demonstrate that XLP2-BIR2 mutations severely impair NOD1/2-dependent immune signalling in primary cells from XLP2 patients and in reconstituted XIAP-deficient cell lines. XLP2-BIR2 mutations abolish the XIAP-RIPK2 interaction resulting in impaired ubiquitylation of RIPK2 and recruitment of linear ubiquitin chain assembly complex (LUBAC) to the NOD2-complex. We show that the RIPK2 binding site in XIAP overlaps with the BIR2 IBM-binding pocket and find that a bivalent Smac mimetic compound (SMC) potently antagonises XIAP function downstream of NOD2 to limit signalling. These findings suggest that impaired immune signalling in response to NOD1/2 stimulation is a general defect in XLP2 and demonstrate that the XIAP BIR2-RIPK2 interaction may be targeted pharmacologically to modulate inflammatory signalling. The X-linked lymphoproliferative syndrome type-2 is an immunodeficiency disease caused by mutations in the XIAP gene. BIR2 domain mutations in patients impair RIPK2 binding and NOD2-dependent innate immune signaling, explaining some of the pathology. PMID:23818254

Damgaard, Rune Busk; Fiil, Berthe Katrine; Speckmann, Carsten; Yabal, Monica; zur Stadt, Udo; Bekker-Jensen, Simon; Jost, Philipp J; Ehl, Stephan; Mailand, Niels; Gyrd-Hansen, Mads

2013-01-01

338

Unicentric mesenteric Castleman’s disease with littoral cell angioma, anemia, growth retardation and amenorrhea: A case report  

PubMed Central

Castleman’s disease (CD) is a rare lymphoproliferative disorder of unknown origin, and littoral cell angioma (LCA) is a rare vascular tumor of the spleen with an unknown etiology. The current study reports the case of a 28-year-old female who presented with anemia, growth retardation and amenorrhea. Physical examination revealed a mass in the mesentery, splenomegaly with multiple small nodules, hepatomegaly and an infantile uterus. Histopathological analysis of the resected mass and spleen confirmed the diagnosis of hyaline-vascular CD and LCA. The patient’s anemia resolved, and menstruation and breast development also commenced following surgery. To the best of our knowledge, this is the first report of CD accompanied by littoral cell angioma, anemia, growth retardation and amenorrhea. PMID:25789041

YANG, LING; ZHAO, SHUANG; LIU, RONG-BO

2015-01-01

339

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 ...

340

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 ...

341

Rare complications after second hematopoietic stem cell transplantation for thalassemia major.  

PubMed

We describe an 11-year-old girl with thalassemia major who underwent a second hematopoietic stem cell transplantation from a matched related donor and who subsequently developed posttransplant lymphoproliferative disorder complicated by severe ascending paralysis resembling Guillian-Barré syndrome. Six months later she developed a massive pericardial effusion. She received a multimodal treatment for these complications and currently, 18 months after transplantation, she is in a good clinical condition, is transfusion independent, with no evidence of graft-versus-host disease and off all treatment. This case highlights the dilemma surrounding second hematopoietic stem cell transplantations in hemoglobinopathies and the need for a careful, well informed, and collaborative decision-making process by patients, families, and medical professionals. PMID:22395220

Yanir, Asaf; Yatsiv, Ido; Braun, Jacques; Zilkha, Amir; Brooks, Rebecca; Bouhanna, Dalia; Weintraub, Michael; Stepensky, Polina

2012-07-01

342

Cytomegalovirus prophylaxis with ganciclovir and cytomegalovirus immune globulin in liver and intestinal transplantation.  

PubMed

Liver and intestinal transplant recipients at the University of Miami receive an intensive regimen of cytomegalovirus (CMV) prophylactic therapy consisting of a combination of CMV immune globulin intravenous (CMV-IGIV, CytoGam) and ganciclovir. The 5-year experience with this regimen in liver transplant patients showed effective CMV prophylaxis in this patient population. The importance of an effective prophylactic strategy was underscored by higher observed rates of chronic rejection and post-transplant lymphoproliferative disorder (PTLD) in CMV-infected patients. The use of CMV-positive donors for intestinal transplants did not increase the incidence of CMV disease. Intestinal transplant recipients had improved survival rates, reflecting an aggressive policy of monitoring, immunosuppression, and CytoGam plus ganciclovir prophylaxis. PMID:11926748

Tzakis, A G

2001-01-01

343

Prion Diseases  

Microsoft Academic Search

The modern history of the prion diseases is one of novel microbes, anthropological intrigue, and food safety mishaps. The\\u000a prion diseases, also called the transmissible spongiform encephalopathies, are fatal neurodegenerative diseases that can be\\u000a sporadic, inherited, or acquired. These multiple origins are unique among human disease. The basis of all prion diseases is\\u000a the misfolding of the host prion protein

Qingzhong Kong; Richard A. Bessen

344

Deletion of the meq gene significantly decreases immunosuppression in chickens caused by pathogenic marek's disease virus  

PubMed Central

Background Marek's disease virus (MDV) causes an acute lymphoproliferative disease in chickens, resulting in immunosuppression, which is considered to be an integral aspect of the pathogenesis of Marek's disease (MD). A recent study showed that deletion of the Meq gene resulted in loss of transformation of T-cells in chickens and a Meq-null virus, rMd5?Meq, could provide protection superior to CVI988/Rispens. Results In the present study, to investigate whether the Meq-null virus could be a safe vaccine candidate, we constructed a Meq deletion strain, GX0101?Meq, by deleting both copies of the Meq gene from a pathogenic MDV, GX0101 strain, which was isolated in China. Pathogenesis experiments showed that the GX0101?Meq virus was fully attenuated in specific pathogen-free chickens because none of the infected chickens developed Marek's disease-associated lymphomas. The study also evaluated the effects of GX0101?Meq on the immune system in chickens after infection with GX0101?Meq virus. Immune system variables, including relative lymphoid organ weight, blood lymphocytes and antibody production following vaccination against AIV and NDV were used to assess the immune status of chickens. Experimental infection with GX0101?Meq showed that deletion of the Meq gene significantly decreased immunosuppression in chickens caused by pathogenic MDV. Conclusion These findings suggested that the Meq gene played an important role not only in tumor formation but also in inducing immunosuppressive effects in MDV-infected chickens. PMID:21205328

2011-01-01

345

Hemophagocytic lymphohistiocytosis caused by primary Epstein-Barr virus in patient with Crohn's disease.  

PubMed

We present a case of a 19-year-old man with a 6-year history of Crohn's disease (CD), previously treated with 6-mercaptopurine, who was admitted to our department for Epstein-Barr virus (EBV) infection and subsequently developed a hemophagocytic lymphohistiocytosis (HLH). HLH is a rare disease which causes phagocytosis of all bone marrow derived cells. It can be a primary form as a autosomic recessive disease, or a secondary form associated with a variety of infections; EBV is the most common, the one with poorer prognosis. The incidence of lymphoproliferative disorders was increased in patients with inflammatory bowel disease (IBD) treated with thiopurines. Specific EBV-related clinical and virological management should be considered when treating a patient with IBD with immunosuppressive therapy. Moreover EBV infection in immunosuppressed patient can occur with more aggressive forms such as encephalitis and diffuse large B cell lymphoma. Our case confirms what is described in the literature; patients with IBD, particularly patients with CD receiving thiopurine therapy, who present 5 d of fever and cervical lymphadenopathy or previous evidence of lymphopenia should be screened for HLH. PMID:24520429

Virdis, Francesco; Tacci, Sara; Messina, Federico; Varcada, Massimo

2013-11-27

346

Marek?s disease: rapid progress in research with unclear biological implementations.  

PubMed

Here we would like to provide a brief overview of the modern history of Marek?s disease (MD) research with a focus on the most recent developments in experimental work and we will try to sum up their impact on the understanding of the biological properties of Marek?s disease type 1 (MDV-1), the only representative of the Mardivirus genus causing fatal lymphoproliferative disease in poultry. We will also compare MDV-1 with other serologically-related poultry herpesviruses, Marek?s disease virus type 2 (MDV-2) and herpesvirus of turkeys (HVT). Although MD was first described at the beginning of the last century, proper characterization of its biological impact on poultry production and utilization of molecular biology methods for detailed characterization of causative agent MDV-1 were introduced only in recent decades. However, many characteristics of MD infection, pathogenesis and vaccine protection mechanisms remain unclarified, though novel methods bring a challenge for better understanding of these unanswered questions. PMID:23600883

Zelník, V; Lapuníková, B; Kúdelová, M

2013-01-01

347

Liver transplantation in alcoholic liver disease current status and controversies  

PubMed Central

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

Singal, Ashwani K; Chaha, Khushdeep S; Rasheed, Khalid; Anand, Bhupinderjit S

2013-01-01

348

[Auto-immune diseases and cancers. Second part: auto-immune diseases complicating cancers and their treatment].  

PubMed

Autoimmune diseases may reveal or occur during the course of a neoplasia or its treatment. Autoimmune cytopenia, especially haemolytic anaemia, is common in lymphoproliferative disorders such as chronic lymphoid leukemia. The link between cancer and myositis is well established. Dermatomyositis is associated with an increased relative risk of cancer of 3.4 to 4.4. A combination of detection of antibodies against p155 and TEP-computed tomography may be the best approach to ascertain the presence of occult malignancy in patients with dermatomyositis. A cutaneous or a systemic vascularitis may reveal a cancer, most often a haematological malignancy such as hairy cell leukemia. Paraneoplastic polyarthritis have been described in particular with adenocardinoma of the lungs. Underlying neoplasia should be considered in male smokers patients with new onset polyarthritis and poor health status. The prevalence of autoimmune conditions in myelodysplastic syndromes is 10 to 30%. Vasculitis and relapsing polychondritis are the most commonly reported manifestations. Immune manifestations can also be related to treatment. The most common treatment complications are autoimmune haemolytic anaemia with fludarabine and thyroiditis related to interferon and cervical radiotherapy. PMID:25106665

Pasquet, F; Pavic, M; Ninet, J; Hot, A

2014-10-01

349

Binswanger's Disease  

MedlinePLUS

... Trials Organizations What is Binswanger's Disease? Binswanger's disease (BD), also called subcortical vascular dementia , is a type ... and brain tissue dies. A characteristic pattern of BD-damaged brain tissue can be seen with modern ...

350

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 ...

351

Gaucher's Disease  

MedlinePLUS

Gaucher's disease is a rare, inherited disorder in which you do not have enough of an enzyme called glucocerebrosidase. ... It usually starts in childhood or adolescence. Gaucher's disease has no cure. Treatment options for types 1 ...

352

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, ...

353

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 ...

354

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 ...

355

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 ...

356

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 ...

357

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 ...

358

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 ...

359

Parkinson's Disease  

MedlinePLUS

... and Parkinson’s disease illustrates value of exposome studies (Mar. 2014) Exploring the haunting legacy – benomyl and Parkinson’s ( ... 2011) Deciphering a Core Process in Parkinson's Disease (Mar. 2011) Workshop Examines the Role of Air Pollution ...

360

Lyme Disease  

MedlinePLUS

... wondered whether the European rash, called erythema migrans (EM), and Lyme disease might have the same cause. ... that a spirochete caused both Lyme disease and EM. The spirochete was later named Borrelia burgdorferi in ...

361

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 ...

362

Batten Disease  

MedlinePLUS

... The NINDS supports two national human brain specimen banks. These banks supply investigators around the world with tissue from patients with neurological and psychiatric diseases. Both banks need brain tissue from Batten disease patients to ...

363

Mycobacterial Diseases  

MedlinePLUS

... Differences Between Lab and Live Results . Related Links Tuberculosis Leprosy (Hansen's Disease) National Library of Medicine, MedlinePlus ... coats that can be found throughout the world. Tuberculosis and leprosy (Hansen’s disease) are the best known ...

364

Wildlife Diseases  

E-print Network

chronic diarrhea, abdominal cramps, bloating and fatigue. Giardiasis is not usually a life threatening disease, and once diag- nosed can be effectively treated with medication. To prevent the disease, avoid drinking or acci- dentally ingesting untreated...

Texas Wildlife Services

2007-03-13

365

Hirschsprung Disease  

MedlinePLUS

... For Kids For Parents MORE ON THIS TOPIC Digestive System Irritable Bowel Syndrome (IBS) Inflammatory Bowel Disease X- ... GI) Irritable Bowel Syndrome Inflammatory Bowel Disease Your Digestive System Constipation Upper GI (Video) Digestive System Inflammatory Bowel ...

366

Celiac Disease  

MedlinePLUS

... with celiac disease, a lifelong disorder of the digestive system, these foods aren't always the treats that ... commonly consumed ingredient. What Is Celiac Disease? The digestive system is the set of organs that digest food ...

367

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 ...

368

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, ...

369

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 ...

370

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 ...

371

Leigh's Disease  

MedlinePLUS

... Leigh's disease can be caused by mutations in mitochondrial DNA or by deficiencies of an enzyme called pyruvate ... kidney function. In Leigh’s disease, genetic mutations in mitochondrial DNA interfere with the energy sources that run cells ...

372

Alexander Disease  

MedlinePLUS

... may be other genetic or perhaps even non-genetic causes of Alexander disease. Current research is aimed at understanding the mechanisms by which the mutations cause disease, developing better animal models for the disorder, and exploring potential strategies ...

373

Lyme Disease  

MedlinePLUS

Lyme disease is a bacterial infection you get from the bite of an infected tick. The first symptom ... Muscle and joint aches A stiff neck Fatigue Lyme disease can be hard to diagnose because you may ...

374

Behcet's Disease  

MedlinePLUS

... other diseases of the digestive tract, such as ulcerative colitis and Crohn’s disease, careful evaluation is essential to ... is put directly on the affected body part. Ulcerative colitis. Inflammation of the colon. Symptoms include stomach pain ...

375

Autoimmune Diseases  

MedlinePLUS

... of the digestive tract. Crohn's (krohnz) disease and ulcerative colitis (UHL-sur-uh-tiv koh-LEYE-tuhss) are ... Crohn's disease) Painful or difficult bowel movements (in ulcerative colitis) Inflammatory myopathies (meye-OP-uh-theez) A group ...

376

Neurodegenerative Diseases  

Microsoft Academic Search

The neurodegenerative disorders, which include Amyotrophic Lateral Sclerosis (ALS), Alzheimer Disease (AD), Parkinson Disease\\u000a (PD), and Huntington Disease (HD), are clinically heterogeneous. Medications can ameliorate some symptoms, but none reverse\\u000a the relentless progression of the illnesses. The past several decades have seen a dramatic increase in the understanding of\\u000a the complex pathophysiology underlying the diseases. Overlapping features at the cellular

Jinsy A. Andrews; Paul H. Gordon

377

Umbilical cord blood transplantation: review of factors affecting the hospitalized patient.  

PubMed

The use of umbilical cord blood (UCB) as a stem cell donor source has dramatically increased over the last 2 decades. Patients undergoing UCB transplantation share medical management issues with patients receiving a hematopoietic stem cell transplantion using adult donor sources (peripheral blood stem cells or bone marrow stem cells) and may also have more complex medical issues that appear to be related to delayed immune recovery from UCB-derived stem cells. The interface with critical care providers is likely to occur in the transplant and posttransplant setting. Patients may experience UCB infusion reactions that range from mild to rarely severe. Following transplant, patients are transfusion dependent for long periods due to the prolonged engraftment of UCB cells. They are at high risk of infection, particularly viral. Once engrafted, UCB transplant patients have a lower rate of graft versus host disease compared to other donor sources. Some of the other complications that are seen in patients undergoing UCB transplant are posttransplant lymphoproliferative disease, diffuse alveolar hemorrhage, and posterior reversible encephalopathy will also be discussed. PMID:23753249

Delaney, Meghan; Ballen, Karen K

2015-01-01

378

Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies  

ClinicalTrials.gov

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

2014-08-13

379

Prion diseases  

Microsoft Academic Search

Human prion diseases are a rare and diverse group of neurodegenerative diseases that have long provoked interest from physicians and scientists. Initially, this related to the enigma of a group of diseases with inherited, sporadic and acquired forms, and then subsequently to the proposition that the infectious agent comprised an abnormally folded but widely expressed cell-surface protein. More recently, the

Diego Kaski; Simon Mead

2009-01-01

380

Prion diseases  

Microsoft Academic Search

Human prion diseases are a rare and diverse group of neurodegenerative diseases that have long provoked interest from physicians and scientists. Initially, this related to the enigma of a disease with inherited, sporadic and acquired forms, and the subsequent demonstration that the infectious agent comprised an abnormally folded but widely expressed cell-surface protein. More recently, the epidemic of bovine spongiform

Simon Mead

2005-01-01

381

Celiac Disease  

MedlinePLUS

... absorbing enough iron. Continue Why Do Kids Get Celiac Disease? No one is sure why celiac disease happens, but it appears to run in families. ... have a 5% to 10% chance of getting celiac disease if someone in your family has it. It's ...

382

Kawasaki disease  

PubMed Central

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.

Kawasaki, Tomisaku

2006-01-01

383

Sandhoff Disease  

MedlinePLUS

... body. Sandhoff disease is a severe form of Tay-Sachs disease--which is prevalent primarily in people of Eastern ... Worldwide NINDS Clinical Trials Organizations Column1 Column2 National Tay-Sachs and Allied Diseases Association 2001 Beacon Street Suite 204 Boston, MA ...

384

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...

385

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...

386

Meniere's Disease.  

ERIC Educational Resources Information Center

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…

Schessel, David A.

1997-01-01

387

Lyme Disease  

MedlinePLUS

... Most cases of Lyme disease occur in the spring and summer months. Lyme disease, in most cases, can be eliminated with antibiotics, especially if treatment is started when symptoms are first noted. Lyme disease is divided into 3 phases: Early localized : Symptoms start a few days to a ...

388

Prostate Diseases  

MedlinePLUS

Aging & Health A to Z Prostate Diseases Basic Facts & Information What are Prostate Diseases? The prostate—one of the components of a man's sex organs—is a ... out anything serious. The Most Common Types of Prostate Diseases Benign prostatic hyperplasia (BPH) Prostatitis Prostate cancer ...

389

Lyme Disease.  

ERIC Educational Resources Information Center

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…

Taylor, George C.

1991-01-01

390

Crohn's Disease  

MedlinePLUS

... Crohn’s disease are very similar to those of ulcerative colitis , except that Crohn’s disease can happen anywhere along ... tract, from the mouth to the anus , while ulcerative colitis is restricted to the colon . Crohn’s disease may ...

391

Follicular Lymphoma Presenting with Leptomeningeal Disease  

PubMed Central

Follicular lymphoma is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. Central nervous system metastasis is a very rare complication portending a very poor prognosis. We report a rare case of follicular lymphoma presenting with leptomeningeal involvement achieving a complete remission after initial therapy. PMID:25544910

Costa, Ricardo; Costa, Renata

2014-01-01

392

Liver Transplantation for Metabolic Liver Disease: Experience at a Living Donor Dominant Liver Transplantation Center  

PubMed Central

Purpose Metabolic liver disease (MLD) often progresses to life-threatening conditions. This study intends to describe the outcomes of liver transplantation (LTx) for MLD at a living donor-dominant transplantation center where potentially heterozygous carrier grafts are employed. Methods We retrospectively evaluated the medical records of 54 patients with MLD who underwent LTx between November 1995 and February 2012 at Asan Medical Center in Seoul, Korea. The cumulative graft and patient survival rates were analyzed according to patient age, and living or deceased donor LTx. Recurrence of the original disease was also investigated. Results The post-transplant cumulative patient survival rates at one, five, and 10 years were 90.7%, 87.5% and 87.5%, and the graft survival rates were 88.8%, 85.5%, and 85.5%, respectively. There were no differences in the patient survival rates according to the recipient age, human leukocyte antigen matching, and living or deceased donor LTx. There were also no differences in the patient survival rates between the MLD and the non-MLD groups for children. Recurrence of the original metabolic disease was not observed in any patient during the follow-up period. Conclusion Our results suggest that the living donor-dominant transplantation program is well-tolerated in MLD without recurrence of the original MLD using all types of transplantation. PMID:25866733

Kim, Jun Suk; Oh, Seak Hee; Kim, Hyun Jin; Cho, Jin Min; Yoo, Han-Wook; Namgoong, Jung-Man; Kim, Dae Yeon; Kim, Ki-Hun; Hwang, Shin; Lee, Sung-Gyu

2015-01-01

393

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

B-cell Adult Acute Lymphoblastic Leukemia; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma

2015-03-04

394

Cellular Immunotherapy Following Cyclophosphamide in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia or B-Cell Prolymphocytic Leukemia  

ClinicalTrials.gov

Post-transplant Lymphoproliferative Disorder; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell 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 Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Waldenström Macroglobulinemia

2015-01-29

395

Kawasaki disease.  

PubMed

Kawasaki disease (KD) is the archetypal pediatric vasculitis, exemplifying the unique aspects and challenges of vascular inflammation in children. The condition is almost unheard of in adults, is closely associated with infections, and is self-limited, with fever resolving after an average of 12 days even without treatment. Yet KD is also a potentially fatal disease and the most common cause of acquired heart disease in the developed world. Unraveling of the developmental, immunologic, and genetic secrets of Kawasaki disease promises to improve our understanding of vasculitis in particular, and perhaps also to provide a window on the fundamental mysteries of inflammatory diseases in general. PMID:25399940

Sundel, Robert P

2015-01-01

396

Biology and disease associations of Epstein-Barr virus.  

PubMed Central

Epstein-Barr virus (EBV) is a human herpesvirus which infects almost all of the world's population subclinically during childhood and thereafter remains in the body for life. The virus colonizes antibody-producing (B) cells, which, as relatively long-lived resting cells, are an ideal site for long-term residence. Here EBV evades recognition and destruction by cytotoxic T cells. EBV is passed to naive hosts in saliva, but how the virus gains access to this route of transmission is not entirely clear. EBV carries a set of latent genes that, when expressed in resting B cells, induce cell proliferation and thereby increase the chances of successful virus colonization of the B-cell system during primary infection and the establishment of persistence. However, if this cell proliferation is not controlled, or if it is accompanied by additional genetic events within the infected cell, it can lead to malignancy. Thus EBV acts as a step in the evolution of an ever-increasing list of malignancies which are broadly of lymphoid or epithelial cell origin. In some of these, such as B-lymphoproliferative disease in the immunocompromised host, the role of the virus is central and well defined; in others, such as Burkitt's lymphoma, essential cofactors have been identified which act in concert with EBV in the evolution of the malignant clone. However, in several diseases in which the presence of EBV has more recently been discovered, the role of the virus is unclear. This review describes recent views on the EBV life cycle and its interlinks with normal B-cell biology, and discusses how this interrelationship may be upset and result in EBV-associated disease. PMID:11313005

Crawford, D H

2001-01-01

397

Genetics Home Reference: Autoimmune lymphoproliferative syndrome  

MedlinePLUS

... nodes (lymphadenopathy), the liver (hepatomegaly), and the spleen (splenomegaly). People with ALPS have an increased risk of ... panniculitis ; platelets ; population ; prevalence ; protein ; recessive ; somatic mutation ; splenomegaly ; syndrome ; systemic lupus ; systemic lupus erythematosus ; thrombocytopenia ; uveitis ; ...

398

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

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.

Knight, Tyler; Schaefer, Caroline; Krasa, Holly; Oberdhan, Dorothee; Chapman, Arlene; Perrone, Ronald D

2015-01-01

399

[Wilson's disease].  

PubMed

Wilson's disease is an autosomal recessive disorder of copper metabolism. The Wilson disease protein is a copper-transporting P-type ATPase, ATP7B, the malfunction of which results in the toxic accumulation of copper in the liver and brain, causing the hepatic and/or neurological symptoms accompanying this disease. Patients present, generally between the ages of 10 and 40 years, with liver disease, neurological disease of a movement disorder type, or behavioral abnormalities, and often with a combination of these. Because Wilson's disease is effectively treated, it is extremely important for physicians to learn to recognize and diagnose the disease. The laboratory diagnosis of Wilson's disease is confirmed by decreased serum ceruloplasmin, increased urinary copper content, and elevated hepatic copper concentration. Molecular genetic analysis is complex as more than 200 unique mutations have been identified and most individuals are compound heterozygotes. The treatment of Wilson's disease must be life long. Copper chelation with penicillamine is an effective therapy in most patients. Another chelating agent which has been used successfully as the initial therapy is trientine. The search for new anticopper drugs for Wilson's disease is culminating in two excellent new drugs: zinc for maintenance therapy and ammonium tetrathiomolybdate (which is to date still an experimental drug) for initial therapy. Liver transplantation is indicated for the fulminant form and in those patients with severe disease not responding to optimal medical management. This paper reviews the pathogenesis, pathology, clinical presentation and diagnosis of the Wilson's disease as well as the most recent views on the molecular genetics and the treatment of this disease. PMID:14582469

Kovacevi?, Igor; Zekan, Mirta

2003-01-01

400

Lyme Disease  

PubMed Central

Synopsis Lyme disease, caused by spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States. The clinical presentation varies depending on the stage of the illness: early disease includes erthyma migrans, early disseminated disease includes multiple erythema migrans, meningitis, cranial nerve palsies and carditis; late disease is primarily arthritis. The symptoms and signs of infection resolve in the vast majority of patients after appropriate treatment with antimicrobials for from 2-4 weeks. Serologic testing should be used judiciously as it often results in misdiagnosis when performed on blood from patients with a low prior probability of disease and those with non-specific symptoms such as fatigue or arthralgia without signs of infection. PMID:20513553

Murray, Thomas S.; Shapiro, Eugene D.

2013-01-01

401

Prion Diseases  

NSDL National Science Digital Library

Prion Diseases is one of a set of lecture notes for Virology 335 by Shaun Heaphy of Leicester University (UK). It contains detailed information on its topic, along with selected links. Although prion research has been going on for over 25 years, the scientific and medical communities have only recently acknowledged the existence of prions and there remains serious debate over their role in a variety of neurological diseases. The name "prion" is derived from "proteinaceous infectious particles," and was coined by Dr. Stanley Prusiner, who discovered the agents and who recently received the Nobel Prize for Medicine for his work. Prions are thought to be the first transmissible and heritable disease-causing agents that lack DNA and RNA. They are composed solely of protein and appear to be the cause of such diseases as kuru and Creutzfeldt-Jakob disease in humans, and bovine spongiform encephalopathies, mad cow disease, and scrapie in sheep and goats.

Heaphy, Shaun.

1997-01-01

402

Infectious disease  

NASA Technical Reports Server (NTRS)

This is a collection of viewgraphs on the Johnson Space Center's work on infectious disease. It addresses their major concern over outbreaks of infectious disease that could jeopardize the health, safety and/or performance of crew members engaged in long duration space missions. The Antarctic environment is seen as an analogous location on Earth and a good place to carry out such infectious disease studies and methods for proposed studies as suggested.

Pierson, Duane L.

1990-01-01

403

Gaucher disease.  

PubMed

Gaucher disease is the commonest lysosomal storage disease seen in India and worldwide. It should be considered in any child or adult with an unexplained splenohepatomegaly and cytopenia which are seen in the three types of Gaucher disease. Type 1 is the non-neuronopathic form and type 2 and 3 are the neuronopathic forms. Type 2 is a more severe neuronopathic form leading to mortality by 2 years of age. Definitive diagnosis is made by a blood test-the glucocerebrosidase assay. There is no role for histological examination of the bone marrow, liver or spleen for diagnosis of the disease. Molecular studies for mutations are useful for confirming diagnosis, screening family members and prognosticating the disease. A splenectomy should not be performed except for palliation or when there is no response to enzyme replacement treatment or no possibility of getting any definitive treatment. Splenectomy may worsen skeletal and lung manifestations in Gaucher disease. Enzyme replacement therapy (ERT) has completely revolutionized the prognosis and is now the standard of care for patients with this disease. Best results are seen in type 1 disease with good resolution of splenohepatomegaly, cytopenia and bone symptoms. Neurological symptoms in type 3 disease need supportive care. ERT is of no benefit in type 2 disease. Monitoring of patients on ERT involves evaluation of growth, blood counts, liver and spleen size and biomarkers such as chitotriosidase which reflect the disease burden. Therapy with ERT is very expensive and though patients in India have so far got the drug through a charitable access programme, there is a need for the government to facilitate access to treatment for this potentially curable disease. Bone marrow transplantation is an inferior option but may be considered when access to expensive ERT is not possible. PMID:25755533

Nagral, Aabha

2014-03-01

404

Genetic Diseases  

Microsoft Academic Search

\\u000a Many dermatologic diseases have a genetic component, and so this group of diseases may be expanded as more evidence is unearthed.\\u000a Atopic dermatitis, for instance, is currently included in the dermatitis\\/eczema group. Filaggrin gene defects have been found\\u000a in approximately 50% of the patients with atopic dermatitis, but the relationship of this defect to the pathogenesis of this\\u000a disease has

Herbert B. Allen

405

Gaucher Disease  

PubMed Central

Gaucher disease is the commonest lysosomal storage disease seen in India and worldwide. It should be considered in any child or adult with an unexplained splenohepatomegaly and cytopenia which are seen in the three types of Gaucher disease. Type 1 is the non-neuronopathic form and type 2 and 3 are the neuronopathic forms. Type 2 is a more severe neuronopathic form leading to mortality by 2 years of age. Definitive diagnosis is made by a blood test–the glucocerebrosidase assay. There is no role for histological examination of the bone marrow, liver or spleen for diagnosis of the disease. Molecular studies for mutations are useful for confirming diagnosis, screening family members and prognosticating the disease. A splenectomy should not be performed except for palliation or when there is no response to enzyme replacement treatment or no possibility of getting any definitive treatment. Splenectomy may worsen skeletal and lung manifestations in Gaucher disease. Enzyme replacement therapy (ERT) has completely revolutionized the prognosis and is now the standard of care for patients with this disease. Best results are seen in type 1 disease with good resolution of splenohepatomegaly, cytopenia and bone symptoms. Neurological symptoms in type 3 disease need supportive care. ERT is of no benefit in type 2 disease. Monitoring of patients on ERT involves evaluation of growth, blood counts, liver and spleen size and biomarkers such as chitotriosidase which reflect the disease burden. Therapy with ERT is very expensive and though patients in India have so far got the drug through a charitable access programme, there is a need for the government to facilitate access to treatment for this potentially curable disease. Bone marrow transplantation is an inferior option but may be considered when access to expensive ERT is not possible. PMID:25755533

Nagral, Aabha

2014-01-01

406

Hodgkin's disease  

SciTech Connect

The outlook for patients with Hodgkin's disease has improved dramatically over the past 20 years. The question is no longer whether cure is possible, but rather, how can cure be best achieved. With better understanding of the biology of Hodgkin's disease and with continued evolution of treatment approaches, the goal of curing all patients with Hodgkin's disease is clearly within reach. This article provides a summary of current concepts in the biology and management of Hodgkin's disease. Staging, treatment options, and complications of therapy are discussed.

Portlock, C.S.

1984-05-01

407

Disease Detective  

NSDL National Science Digital Library

This activity (on pages 35-43) lets learners analyze a "herd of elk" to detect the spread of a bacterial disease called brucellosis. The activity simulates how wildilfe veterinarians study elk in the wild by sampling only a subset of the animals. Based on a brucellosis problem with elk in Yellowstone National Park, learners cut out representations for two herds and then pick some at random to "test" for disease (denoted as a plus sign on a diseased animal). The results indicate that elk fed in Wyoming over the winter have more disease than the wild elk that go north to Montana

University of Nebraska State Museum

2002-01-01

408

Management of hepatitis C in patients with chronic kidney disease.  

PubMed

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

Carvalho-Filho, Roberto J; Feldner, Ana Cristina C A; Silva, Antonio Eduardo B; Ferraz, Maria Lucia G

2015-01-14

409

Management of hepatitis C in patients with chronic kidney disease  

PubMed Central

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

Carvalho-Filho, Roberto J; Feldner, Ana Cristina CA; Silva, Antonio Eduardo B; Ferraz, Maria Lucia G

2015-01-01

410

A critical analysis of racial difference with mycophenolate mofetil (MMF) dosing, clinical outcomes and adverse effects in pediatric kidney transplant patients.  

PubMed

There is paucity in the data examining the differences in mycophenolate mofetil (MMF) dosing and outcomes among pediatric kidney transplant recipients (PKTX) between races. The aims of this study were as follows (i) to assess whether higher doses of MMF are being utilized in African American (AA) PKTX (ii) to determine whether there is a correlation between MMF dose and outcomes between races, and (iii) to assess the adverse effects of MMF between races. This study analyzed 109 PKTX who received MMF between 7/99 and 5/08. Demographics were similar between groups. Fewer AAs received kidneys from living donors (18% vs. 44%), spent more time on dialysis (1.0 vs. 0.5 yr), and had more human leukocyte antigen mismatches (4 vs. 3). MMF doses among AA patients were higher throughout the study, with statistical differences at week 4, month 3, and month 18. AA patients had significantly higher acute rejection rates and trended toward poorer graft survival; infections, adverse events from MMF and post-transplant lymphoproliferative disease tended to be lower in the AA patients. AA PKTX received higher MMF doses within the first three yr post-transplant compared to their non-AA counterparts, yet demonstrate significantly more acute rejection episodes. Importantly, MMF caused fewer adverse events in AA patients, despite these patients receiving higher doses. PMID:20636410

Jensen, C J; Shrivastava, S; Taber, D J; Weimert, N A; Shatat, I F; Orak, J; Chavin, K D; Baliga, P K

2011-01-01

411

Alzheimer's Disease  

Microsoft Academic Search

The proliferation of information regarding Alzheimer's disease in current years has had a tremendous impact on the literature being generated on this topic. Until fairly recently, Alzheimer's disease was believed to be incurable, and its progress inexorable. In recent years research has come up with encouraging results which give hope that new treatments and even a cure is possible in

Carol Gillen

1993-01-01

412

Cardiovascular Disease  

Technology Transfer Automated Retrieval System (TEKTRAN)

Cardiovascular disease (CVD), particularly CHD (coronary heart disease) and stroke, remain the leading causes of death of women in America and most developed countries. In recent years the rate of CVD has declined in men but not in women. This is contributed to by an under-recognition of women’s C...

413

Addison's Disease  

MedlinePLUS

... is Addison’s disease? Addison’s disease affects your body’s adrenal glands. The adrenal glands are part of the endocrine system. The endocrine ... your moods, growth, metabolism, and tissue function. The adrenal glands are located just above your kidneys. They produce ...

414

Mitochondrial Diseases  

PubMed Central

Mitochondria contain the respiratory chain enzyme complexes that carry out oxidative phosphorylation and produce the main part of cellular energy in the form of ATP. Although several proteins related with signalling, assembling, transporting, and enzymatic function can be impaired in mitochondrial diseases, most frequently the activity of the respiratory chain protein complexes is primarily or secondarily affected, leading to impaired oxygen utilization and reduced energy production. Mitochondrial diseases usually show a chronic, slowly progressive course and present with multiorgan involvement with varying onset between birth and late adulthood. Neuromuscular system is frequently affected in mitochondrial diseases. Although there is actually no specific therapy and cure for mitochondrial diseases, the understanding of the pathophysiology may further facilitate the diagnostic approach and open perspectives to future in mitochondrial diseases. PMID:24649452

Lee, Young-Mock

2012-01-01

415

[Graves' disease].  

PubMed

Genetic and environmental determinants inducing Graves' disease are still poorly defined, especially those leading to the appearance of TSH receptor antibodies, which are both the hallmark of the disease and the keystone of its diagnosis. The treatment of Graves' disease is based on the use of antithyroid drugs and no therapeutic protocol has proven superior to the other. Surgical or radiometabolic treatments, largely restricted to relapses and to patients with comorbidities could be considered earlier provided we had reliable predictive markers for relapse. The treatment of Graves' orbitopathy relies first on a rigorous analysis of severity and activity of the disease. Intravenous steroids appear as a reference treatment in active forms. Evaluation of new therapeutics is in process. Graves' disease during pregnancy requires a multidisciplinary approach and an expert ultrasound evaluation of the fetus. Because of a suspected teratogenicity of carbimazole and methimazole, propylthiouracyl is the preferred drug used during early pregnancy. PMID:25090772

Illouz, Frédéric; Rodien, Patrice

2014-06-01

416

Beryllium disease.  

PubMed Central

The increasing use of beryllium in a variety of industries continues to be a hazard. New cases are still being reported to the UK Beryllium Case Registry, now numbering 60 in the period 1945-1988. The majority of cases follow inhalation which results in acute beryllium disease (chemical pneumonitis) or more commonly chronic beryllium disease--a granulomatous pneumonitis. Granulomatous skin nodules also occur following local implantation. The clinical and radiological features are briefly described with the emphasis on pathology and immunology. Laser microprobe mass spectrometry analysis of tissue sections is a major advance in diagnosis. Detection of beryllium distinguishes the granulomas of chronic beryllium disease from other diseases, in particular sarcoidosis. The role of beryllium lymphocyte transformation tests is discussed. Chronic beryllium disease is steroid dependent and local excision of skin lesions appears to be curative. There is no evidence that beryllium is carcinogenic. Images Figure 1 PMID:3074283

Jones Williams, W.

1988-01-01

417

Potential advantages and limitations of applying the chronic kidney disease classification to kidney transplant recipients.  

PubMed

The National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) classification of Chronic Kidney Disease (CKD) characterizes patients by their level of kidney function and includes kidney transplant recipients (KTRs). Most KTRs have stage > or = 3 CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2) and may benefit from aggressive CKD care. Recent modifications to the K/DOQI CKD classification reflect the recognition of KTRs as a unique subset of CKD patients in whom the presentation, progression and implications of CKD may vary from those in nontransplant CKD populations. Currently, there is limited information about how adopting the CKD classification in KTRs will influence clinical management and outcomes. Appropriately designed studies are needed to develop transplant-specific CKD treatment recommendations, and to ensure patient, health provider and payer acceptance of the continued need for aggressive CKD care after transplantation. Education and implementation strategies will be required to ensure appropriate integration of the CKD classification and treatment guidelines into existing posttransplant care programs. The CKD classification thus represents an exciting potential strategy to improve clinical outcomes that should be adopted, further studied and modified to incorporate considerations unique to KTRs. PMID:17061995

Gill, J S

2006-12-01

418

Pharmacokinetics and pharmacodynamics of methotrexate in non-neoplastic diseases.  

PubMed

Low dose pulse methotrexate (LDMTX) therapy has become effective in the treatment of autoimmune and lymphoproliferative diseases. The pharmacokinetics of LDMTX is individually highly variable, resulting in a different systemic exposure to the drug and a variable therapeutic/toxic effect in patients. The improvements and exacerbations of disease activity in relation to the introductions and discontinuations of LDMTX therapy suggest the possible immunosuppresive and anti-inflammatory properties of the drug. Because of a strong correlation between the drug pharmacokinetics and the therapeutic outcomes (pharmacodynamics), it seems to be possible to individualise the LDMTX therapy according to the results of pharmacokinetic/pharmacodynamic analysis. In the case of psoriasis, pharmacokinetic/pharmacodynamic analysis in our local study revealed a highly significant inverse relationship between PASI (expressed as a percent of the initial value) and a steady-state AUC(MTX) (area under the curve of methotrexate plasma concentrations; r(8) = -0.65, p < 0.001). The considerable inter-individual variability and low intra-individual variability in MTX pharmacokinetics, supports a role for therapeutic monitoring and dose individualisation at the start of pharmacotherapy. The results of this study suggest that a steady-state AUC(MTX) value of 700 nmol x h/L and higher are associated with a significantly better success rate of antipsoriatic therapy than lower values. The preliminary results in our follow-up study suggest the statistically higher incidence of unwanted effects depending on maximum plasma concentration of the drug. Moreover, statistically significant correlation was found between the toxic effects and exposure to the drug regarding methotrexate plasma concentrations and intracellular storage in erythrocytes. However, the data are still in the process of being completed and are not yet published. PMID:12537514

Grim, Jirí; Chládek, Jaroslav; Martínková, Jirina

2003-01-01

419

Primary and secondary cutaneous CD301 lymphoproliferative disorders: a report from the Dutch Cutaneous Lymphoma Group on the long-term follow-up data of 219 patients and guidelines for diagnosis and treatment  

Microsoft Academic Search

LTCL were treated with radiotherapy or excision. All patients with skin-limited disease from groups 1 and 2 who were treated with multiagent chemotherapy had 1 or more skin relapses. The calcu- lated risk for systemic disease within 10 years of diagnosis was 4% for group 1, 16% for group 2, and 20% for group 3 (after initial therapy). Disease-related 5-year-survival

Marcel W. Bekkenk; Francoise A. M. J. Geelen; F. Heule; Marie-Louise Geerts; Willem A. van Vloten; Chris J. L. M. Meijer; Rein Willemze

420

[Peyronie's disease].  

PubMed

Peyronie's disease is caused by collagen deposits in the tunica albuginea of the corpus cavernosum following microtrauma. Symptoms may include a combination of penile curvature, a palpable plaque, painful erections and erectile dysfunction. Peyronie's disease can have a major impact on the quality of life. In the course of the disease two phases can be discerned. In the first, active phase there is penile curvature with painful erections. The second, stable phase is characterised by painless curvature of the penis. Treatment in the active phase is conservative and supportive. Surgical treatment is useful only in the stable phase and may consist of penile plication surgery or penile graft surgery. PMID:25004781

Ruiter, Annebeth E C; Meuleman, Eric J H

2014-01-01

421

Gaucher's disease  

PubMed Central

Gaucher's disease (GD) is the most common amongst the various disorders classified under the lysosomal storage disorders. GD is a model for applications of molecular medicine to clinical delineation, diagnosis, and treatment. The multiorgan and varied presentation of the disease makes it a challenge to diagnose GD early. The advent of enzyme replacement therapy in the early 1990s changed the management, and survival, of patients with GD. In addition to this, development of substrate reduction, pharmacological chaperone, and gene therapies has broadened the horizon for this rare disease. However, in resource-poor countries like ours, optimal management is still a distant dream. PMID:21897894

Bohra, Vijay; Nair, Velu

2011-01-01

422

Leishmaniasis Disease  

MedlinePLUS

... message, please visit this page: About CDC.gov . Parasites - Leishmaniasis Parasites Home Share Compartir Disease Ulcerative skin lesion, with ... with some of the species (types) of the parasite that cause cutaneous leishmaniasis in parts of Latin ...

423

Celiac Disease  

Microsoft Academic Search

Celiac disease is induced by the ingestion of gluten, which is derived from wheat, barley, and rye. The gluten protein is enriched in glutamine and proline and is poor- ly digested in the human upper gastrointestinal tract. The term \\

Peter H. R. Green; Christophe Cellier

2007-01-01

424

Kennedy's Disease  

MedlinePLUS

... of a group of disorders called lower motor neuron disorders (which involve disruptions in the transmission of nerve cell signals in the brain to nerve cells in the brain stem and spinal cord). Onset of the disease is ...

425

Meniere's Disease  

MedlinePLUS

... pressure in some cases of Ménière?s disease. The auditory brain stem response (ABR), a computerized test of ... has advantages and drawbacks. In many people, careful control of salt in the diet and the use ...

426

Menkes Disease  

MedlinePLUS

... defective gene named ATPTA 1 that regulates the metabolism of copper in the body. The disease primarily affects male infants. Copper accumulates at abnormally low levels in the liver and brain, but at higher than normal levels ...

427

Alzheimer's Disease  

MedlinePLUS

... progressive brain disease that slowly destroys memory and thinking skills, and eventually even the ability to carry ... people. Dementia is the loss of cognitive functioning—thinking, remembering, and reasoning—and behavioral abilities, to such ...

428

Canavan Disease  

MedlinePLUS

... brain responsible for making myelin sheaths, known as oligodendrocytes, cannot properly complete this critical developmental task. Myelin ... support for nerve cells. In Canavan disease, many oligodendrocytes do not mature and instead die, leaving nerve ...

429

Liver Diseases  

MedlinePLUS

Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis ...

430

Behcet's Disease  

MedlinePLUS

... of Behcet's disease include recurrent ulcers in the mouth (resembling canker sores) and on the genitals, and eye inflammation. The disorder may also cause various types of skin lesions, arthritis, bowel inflammation, meningitis (inflammation of the membranes ...

431

Meniere's disease.  

PubMed

Meniere's disease is a chronic illness that affects a substantial number of patients every year worldwide. The disease is characterised by intermittent episodes of vertigo lasting from minutes to hours, with fluctuating sensorineural hearing loss, tinnitus, and aural pressure. Although there is currently no cure, more than 85% of patients with Meniere's disease are helped by either changes in lifestyle and medical treatment, or minimally invasive surgical procedures such as intratympanic steroid therapy, intratympanic gentamicin therapy, and endolymphatic sac surgery. Vestibular neurectomy has a very high rate of vertigo control and is available for patients with good hearing who have failed all other treatments. Labyrinthectomy is undertaken as a last resort and is best reserved for patients with unilateral disease and deafness. PMID:18675691

Sajjadi, Hamed; Paparella, Michael M

2008-08-01

432

Diverticular Disease  

MedlinePLUS

... your large intestine. It is caused by small pouches (called diverticula) that can form anywhere in your ... disease are: Diverticulosis. People who have diverticulosis have pouches in the large intestine. Most people who have ...

433

Nail Diseases  

MedlinePLUS

... growth rate can be signs of lung, heart, kidney, and liver diseases, as well as diabetes and anemia. White spots and vertical ridges are harmless. Nail problems that sometimes require treatment include Bacterial and fungal infections Ingrown nails Tumors ...

434

Chagas disease  

MedlinePLUS

... help control the spread of the disease. Blood banks in Central and South America screen donors for ... discarded if the donor tests positive. Most blood banks in the United States began screening for Chagas ...

435

Fungal Diseases  

MedlinePLUS

... Chest & Lungs Chronic Conditions Developmental Disabilities Ear, Nose & Throat Emotional Problems Fever Genitals & Urinary Tract Head, Neck & Nervous System Obesity Skin Treatments View all Injuries & Emergencies Sports Injuries Vaccine Preventable Diseases Diphtheria Haemophilus ...

436

Graves' Disease  

MedlinePLUS

... Graves' disease can cause the following symptoms: Nervousness Insomnia Emotional swings Sweating Hand tremor Palpitations Unexplained weight ... medication such as propanolol (Inderal). For anxiety and insomnia, your doctor may prescribe diazepam (Valium), lorazepam (Ativan) ...

437

Alpers' Disease  

MedlinePLUS

... disease, failure to thrive, infection-associated encephalopathy, spasticity, myoclonus (involuntary jerking of a muscle or group of ... be difficult to control and unrelenting seizures can cause developmental regression as well. "Alpers-like" disorders without ...

438

Lung Disease  

MedlinePLUS

... Infections, such as influenza and pneumonia Lung cancer Sarcoidosis (sar-KOY-doh-sis) and pulmonary fibrosis Lung ... and can reduce oxygen flow into the blood. Sarcoidosis and pulmonary fibrosis. These inflammatory diseases cause stiffening ...

439

Alzheimer disease  

MedlinePLUS

Senile dementia - Alzheimer type (SDAT); SDAT ... The exact cause of Alzheimer disease (AD) is not known. Research shows that certain changes in the brain lead to AD developing. You are more likely ...

440

Lyme disease  

MedlinePLUS

Lyme disease is caused by bacteria called Borrelia burgdorferi ( B. burgdorferi) . Blacklegged ticks and other species of ticks can carry these bacteria. The ticks pick up the bacteria when they bite mice ...

441

Gaucher disease  

MedlinePLUS

... harmful substances to build up in the liver, spleen, bones, and bone marrow. The substances prevent cells ... common. It involves bone disease, anemia, an enlarged spleen and thrombocytopenia. Type I affects both children and ...

442

Ménière's Disease  

MedlinePLUS

... membranous labyrinth) filled with endolymph. Credit: NIH Medical Arts The symptoms of Ménière’s disease are caused by ... dizziness. Location of endolymphatic sac Credit: NIH Medical Arts Surgery. Surgery may be recommended when all other ...

443

Graves disease  

MedlinePLUS

... levels of TSH, T3, and free T4 Radioactive iodine uptake and scan This disease may also affect ... or more of the following: Antithyroid medications Radioactive iodine Surgery If you have had radioactive iodine treatment ...

444

Gaucher Disease  

MedlinePLUS

... problems and blood disorders. Is there any treatment? Enzyme replacement therapy is available for most people with types 1 ... and 3 Gaucher disease. What is the prognosis? Enzyme r