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Sample records for post-transplant lymphoproliferative disease

  1. Risk factors for post-transplant lymphoproliferative disease in patients with cystic fibrosis.

    PubMed

    Saueressig, Maurício G; Boussaud, Veronique; Amrein, Catherine; Guillemain, Romain; Souilamas, Jihane; Souilamas, Redha

    2011-01-01

    The objective of this study was to retrospectively analyze risk factors associated with post-transplant lymphoproliferative disease (PTLD) in a cohort of 112 lung transplant recipients with cystic fibrosis (CF). Prior to transplantation, patients were tested for Epstein-Barr virus (EBV), human herpesvirus (HHV types 1, 2, 3, 6, and 8), herpes zoster virus, and cytomegalovirus (CMV) serologies. PTLD diagnosis was established based on increased EBV viral charge plus clinical/radiographic findings and confirmed by biopsy. Negative EBV and HHV serologies at the time of lung transplantation (LTx) were significant risk factors associated with development of PTLD in patients with CF in the univariate logistic regression analysis (p < 0.05) and also in the multivariate analysis (odds ratio of 77.5 and 12.5, respectively). CMV serology, CMV mismatch, acute rejection in the first three months following LTx, HLA-A3 antigen expression, and female gender did not affect PTLD. Our study confirmed the presence of a strong association between negative EBV serology at the time of LTx and PTLD and suggested an independent effect of negative HHV serology on PTLD.

  2. Risk factors for post-transplant lymphoproliferative disease in patients with cystic fibrosis.

    PubMed

    Saueressig, Maurício G; Boussaud, Veronique; Amrein, Catherine; Guillemain, Romain; Souilamas, Jihane; Souilamas, Redha

    2011-01-01

    The objective of this study was to retrospectively analyze risk factors associated with post-transplant lymphoproliferative disease (PTLD) in a cohort of 112 lung transplant recipients with cystic fibrosis (CF). Prior to transplantation, patients were tested for Epstein-Barr virus (EBV), human herpesvirus (HHV types 1, 2, 3, 6, and 8), herpes zoster virus, and cytomegalovirus (CMV) serologies. PTLD diagnosis was established based on increased EBV viral charge plus clinical/radiographic findings and confirmed by biopsy. Negative EBV and HHV serologies at the time of lung transplantation (LTx) were significant risk factors associated with development of PTLD in patients with CF in the univariate logistic regression analysis (p < 0.05) and also in the multivariate analysis (odds ratio of 77.5 and 12.5, respectively). CMV serology, CMV mismatch, acute rejection in the first three months following LTx, HLA-A3 antigen expression, and female gender did not affect PTLD. Our study confirmed the presence of a strong association between negative EBV serology at the time of LTx and PTLD and suggested an independent effect of negative HHV serology on PTLD. PMID:21518001

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

    SciTech Connect

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

    2015-07-10

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

  4. Epstein-barr virus-negative post-transplant lymphoproliferative diseases: three distinct cases from a single center.

    PubMed

    Bakanay, Sule Mine; Kaygusuz, Gülşah; Topçuoğlu, Pervin; Sengül, Sule; Tunçalı, Timur; Keven, Kenan; Kuzu, Işınsu; Uysal, Akın; Arat, Mutlu

    2014-03-01

    Three cases of Epstein-Barr virus (EBV)-negative post-transplant lymphoproliferative disease that occurred 6 to 8 years after renal transplantation are reported. The patients respectively had gastric mucosa-associated lymphoid tissue lymphoma, gastric diffuse large B-cell lymphoma, and atypical Burkitt lymphoma. Absence of EBV in the tissue samples was demonstrated by both in situ hybridization for EBV early RNA and polymerase chain reaction for EBV DNA. Patients were treated with reduction in immunosuppression and combined chemotherapy plus an anti-CD20 monoclonal antibody, rituximab. Despite the reduction in immunosuppression, patients had stable renal functions without loss of graft functions. The patient with atypical Burkitt lymphoma had an abnormal karyotype, did not respond to treatment completely, and died due to disease progression. The other patients are still alive and in remission 5 and 3 years after diagnosis, respectively. EBV-negative post-transplant lymphoproliferative diseases are usually late-onset and are reported to have poor prognosis. Thus, reduction in immunosuppression is usually not sufficient for treatment and more aggressive approaches like rituximab with combined chemotherapy are required.

  5. Treatment Response and Outcomes in Post-transplantation Lymphoproliferative Disease vs Lymphoma in Immunocompetent Patients.

    PubMed

    Trusson, R; Serre, J E; Szwarc, I; Brunot, V; Garrigue, V; Delmas, S; Kanouni, T; Cartron, G; Mourad, G

    2016-01-01

    Posttransplantation lymphoproliferative disorder (PTLD) after solid organ transplantation may carry a poorer prognosis than lymphoma in immunocompetent individuals, but comparative data are lacking. In a retrospective, single-center, case-control study, 21 cases of PTLD were identified in patients undergoing kidney transplantation since 2000, and compared to 42 nontransplanted controls cared for in the same institution and matched for age, prognostic index, and cerebral localization. Two-year and 5-year overall survival was 57% and 44%, respectively, in PTLD patients and 71% and 58% in controls (log-rank test P = .20). On multivariable analysis, overall survival was similar for PTLD and control patients (hazard ratio 1.71, 95% confidence interval 0.81 to 3.61, P = .16). Response rate to first-line chemotherapy was similar between the 2 groups. Death was due to progression of the disease in 46% vs 94% of PTLD and control patients, respectively (P < .01), or sepsis in 31% vs 0% (P = .03). Treatment-related mortality was significantly higher in PTLD (19%) than in controls (0%, P = .03). In conclusion, response to first-line chemotherapy and overall survival are similar in PTLD and control patients, whereas causes of death were significantly different. Better prevention and management of infectious complications could improve the results in PTLD patients. PMID:27569924

  6. EBV-associated post-transplant lymphoproliferative disorder after umbilical cord blood transplantation in adults with hematological diseases.

    PubMed

    Sanz, J; Arango, M; Senent, L; Jarque, I; Montesinos, P; Sempere, A; Lorenzo, I; Martín, G; Moscardó, F; Mayordomo, E; Salavert, M; Cañigral, C; Boluda, B; Salazar, C; López-Hontangas, J L; Sanz, M A; Sanz, G F

    2014-03-01

    We analyzed the incidence, clinicopathological features, risk factors and prognosis of patients with EBV-associated post-transplant lymphoproliferative disorder (EBV-PTLD) in 288 adults undergoing umbilical cord blood transplantation (UCBT) at a single institution. Twelve patients developed proven EBV-PTLD at a median time of 73 days (range, 36-812). Three-year cumulative incidence (CI) of EBV-PTLD was 4.3% (95% CI: 1.9-6.7). All patients presented with extranodal involvement. Most frequently affected sites were the liver, spleen, central nervous system (CNS), Waldeyer's ring and BM in 7, 6, 4, 3 and 3 patients, respectively. One patient had polymorphic and 11 had monomorphic EBV-PTLD (7 diffuse large B-cell lymphomas not otherwise specified, 4 plasmablastic lymphomas). We confirmed donor origin and EBV infection in all histological samples. EBV-PTLD was the cause of death in 11 patients at a median time of 23 days (range, 1-84). The 3-year CI of EBV-PTLD was 12.9% (95% CI: 3.2-22.5) and 2.6% (95% CI: 0.5-4.7) for patients receiving reduced-intensity conditioning (RIC) and myeloablative conditioning, respectively (P<0.0001). In conclusion, adults with EBV-PTLD after UCBT showed frequent visceral and CNS involvement. The prognosis was poor despite routine viral monitoring and early intervention. An increased risk of EBV-PTLD was noted among recipients of RIC regimens.

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2015-08-01

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

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

    ClinicalTrials.gov

    2013-01-24

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

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

    PubMed

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

    2015-06-01

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

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

    PubMed

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

    2015-06-01

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

  12. Post-transplant lymphoproliferative disorder following kidney transplantation: a population-based cohort study.

    PubMed

    Maksten, Eva Futtrup; Vase, Maja Ølholm; Kampmann, Jan; d'Amore, Francesco; Møller, Michael Boe; Strandhave, Charlotte; Bendix, Knud; Bistrup, Claus; Thiesson, Helle Charlotte; Søndergaard, Esben; Hamilton-Dutoit, Stephen; Jespersen, Bente

    2016-04-01

    Post-transplant lymphoproliferative disorder (PTLD) incidence is difficult to determine, mainly because both early and other lesions may go unrecognized and unregistered. Few studies have included systematic pathology review to maximize case identification and decide more accurately PTLD frequency after long-term post-transplantation follow-up. A retrospective population-based cohort study including all kidney transplant recipients at two Danish centres (1990-2011; population covered 3.1 million; 2175 transplantations in 1906 patients). Pathology reports were reviewed for all patient biopsies to identify possible PTLDs. Candidate PTLDs underwent histopathological review and classification. Seventy PTLD cases were identified in 2175 transplantations (3.2%). The incidence rate (IR) after first transplantation was 5.4 cases per 1000 patient-years (95% CI: 4.0-7.3). Most PTLDs were monomorphic (58.5%), or early lesions (21.5%). Excluding early lesions and patients <18 years, IR was 3.7 (95% CI: 2.9-5.5). Ten patients with PTLD were retransplanted, 2 developing further PTLDs. Post-transplant patient survival was inferior in patients with PTLD, while death-censored graft survival was not. Using registry data together with extensive pathological review and long follow-up, a rather high incidence of PTLD was found. PMID:26749337

  13. Recent insights in the pathogenesis of post-transplantation lymphoproliferative disorders.

    PubMed

    Morscio, Julie; Tousseyn, Thomas

    2016-09-24

    Post-transplant lymphoproliferative disorder (PTLD) is an aggressive complication of solid organ and hematopoietic stem cell transplantation that arises in up to 20% of transplant recipients. Infection or reactivation of the Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, in combination with chronic immunosuppression are considered as the main predisposing factors, however insight in PTLD biology is fragmentary. The study of PTLD is complicated by its morphological heterogeneity and the lack of prospective trials, which also impede treatment optimization. Furthermore, the broad spectrum of underlying disorders and the graft type represent important confounding factors. PTLD encompasses different malignant subtypes that resemble histologically similar lymphomas in the general population. Post-transplant diffuse large B-cell lymphoma (PT-DLBCL), Burkitt lymphoma (PT-BL) and plasmablastic lymphoma (PT-PBL) occur most frequently. However, in many studies various EBV(+) and EBV(-) PTLD subtypes are pooled, complicating the interpretation of the results. In this review, studies of the gene expression pattern, the microenvironment and the genetic profile of PT-DLBCL, PT-BL and PT-PBL are summarized to better understand the mechanisms underlying post-transplantation lymphomagenesis. Based on the available findings we propose stratification of PTLD according to the histological subtype and the EBV status to facilitate the interpretation of future studies and the establishment of clinical trials. PMID:27683629

  14. Recent insights in the pathogenesis of post-transplantation lymphoproliferative disorders

    PubMed Central

    Morscio, Julie; Tousseyn, Thomas

    2016-01-01

    Post-transplant lymphoproliferative disorder (PTLD) is an aggressive complication of solid organ and hematopoietic stem cell transplantation that arises in up to 20% of transplant recipients. Infection or reactivation of the Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, in combination with chronic immunosuppression are considered as the main predisposing factors, however insight in PTLD biology is fragmentary. The study of PTLD is complicated by its morphological heterogeneity and the lack of prospective trials, which also impede treatment optimization. Furthermore, the broad spectrum of underlying disorders and the graft type represent important confounding factors. PTLD encompasses different malignant subtypes that resemble histologically similar lymphomas in the general population. Post-transplant diffuse large B-cell lymphoma (PT-DLBCL), Burkitt lymphoma (PT-BL) and plasmablastic lymphoma (PT-PBL) occur most frequently. However, in many studies various EBV+ and EBV- PTLD subtypes are pooled, complicating the interpretation of the results. In this review, studies of the gene expression pattern, the microenvironment and the genetic profile of PT-DLBCL, PT-BL and PT-PBL are summarized to better understand the mechanisms underlying post-transplantation lymphomagenesis. Based on the available findings we propose stratification of PTLD according to the histological subtype and the EBV status to facilitate the interpretation of future studies and the establishment of clinical trials. PMID:27683629

  15. Recent insights in the pathogenesis of post-transplantation lymphoproliferative disorders

    PubMed Central

    Morscio, Julie; Tousseyn, Thomas

    2016-01-01

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

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

    PubMed

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

    2000-10-01

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

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

    PubMed

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

    2016-01-01

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

  18. Post-transplant lymphoproliferative disorder after autologous peripheral stem cell transplantation in a pediatric patient.

    PubMed

    Lones, M A; Kirov, I; Said, J W; Shintaku, I P; Neudorf, S

    2000-11-01

    Post-transplant lymphoproliferative disorder (PTLD) is a complication of allogeneic bone marrow transplantation (BMT). Rare cases of PTLD after autologous BMT have been reported only in adults. This case report is the first to describe PTLD in a pediatric patient after autologous peripheral stem cell transplantation (PSCT). This 2-year-old male with stage IV neuroblastoma underwent autologous PSCT. The post-PSCT course was complicated by fever with hematochezia and a lung mass. On day 94 post PSCT, colonoscopy revealed an ulcer due to a PTLD, monomorphic type, B cell phenotype, associated with Epstein-Barr virus. Fine needle aspiration identified the lung mass as neuroblastoma. PTLD can occur in pediatric autologous PSCT recipients, and may occur more frequently in autologous grafts manipulated by T cell depletion or CD34+ cell selection.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  1. Post-transplant lymphoproliferative disorder in children: incidence, prognosis, and treatment options.

    PubMed

    Faye, Albert; Vilmer, Etienne

    2005-01-01

    Post-transplant lymphoproliferative disorder (PTLD) after solid organ or hematopoietic stem cell transplantation in children is a serious complication that has been responsible for high mortality rates over recent years. PTLDs are part of a clinically and histologically heterogeneous group of B-lymphocyte proliferations mostly induced by Epstein-Barr virus (EBV) in a context of immunosuppression. Major risk factors for PTLDs in solid organ transplantation are the EBV serostatus mismatch and the intensity, duration, and type of immunosuppression. T-cell depletion and the HLA-mismatched donor and recipient are the main risk factors following hematopoietic stem cell transplantation. For a long time, the only safe and effective therapeutic approach to PTLD was reduction of immunosuppression, with a risk of graft rejection. Based on a better knowledge of the pathophysiology and risk factors for PTLD, preventive and pre-emptive strategies have been recently proposed to control PTLD. New treatment modalities, such as anti-B-cell antibodies, cytokine inhibitor therapy, or anti-EBV cytotoxic T lymphocytes are promising and may improve the outcome of PTLD. These therapeutic approaches need to be further evaluated, especially in the context of pre-emptive strategies adapted to predictive markers of EBV-induced PTLD.

  2. Treatment options for post-transplant lymphoproliferative disorder and other Epstein-Barr virus-associated malignancies.

    PubMed

    Davis, J E; Moss, D J

    2004-04-01

    Epstein-Barr virus (EBV) is associated with a range of malignancies that largely arise from a defect in EBV-specific cytotoxic T lymphocyte (CTL) immunity and function. Much work has focused on the reconstitution of CTL immunity to EBV in transplant patients, in whom immunosuppression modalities render them susceptible to post-transplant lymphoproliferative disease (PTLD). Adoptive transfer of autologous CTLs is effective at both preventing and curing PTLD in solid organ transplant recipients and can produce a long-term memory response and protection against recurring disease. In this review, the benefits and restrictions of administering EBV-specific CTLs for the treatment of PTLD are discussed and compared with emerging therapies including the generation of allogeneic human leukocyte antigen-matched CTL banks and the anti-CD20 monoclonal antibody therapy, MabThera. Furthermore, studies involving other EBV-associated disorders have described the potential benefit of adoptive transfer of EBV-specific CTLs for Hodgkin's disease, nasopharyngeal carcinoma, chronic active EBV infection, and Burkitt's lymphoma. The challenges of tailor-making therapies for individual diseases and EBV antigen expression latencies are highlighted, in addition to considering vaccination strategies for optimal treatment. PMID:15009802

  3. EBV-negative monomorphic B-cell post-transplant lymphoproliferative disorders are pathologically distinct from EBV-positive cases and frequently contain TP53 mutations.

    PubMed

    Courville, Elizabeth L; Yohe, Sophia; Chou, David; Nardi, Valentina; Lazaryan, Aleksandr; Thakral, Beenu; Nelson, Andrew C; Ferry, Judith A; Sohani, Aliyah R

    2016-10-01

    Monomorphic post-transplant lymphoproliferative disorder commonly resembles diffuse large B-cell lymphoma or Burkitt lymphoma, and most are Epstein-Barr virus (EBV) positive. We retrospectively identified 32 cases of monomorphic post-transplant lymphoproliferative disorder from two institutions and evaluated EBV in situ hybridization; TP53 mutation status; p53, CD30, myc, and BCL2 expression by immunohistochemistry; proliferation index by Ki67; and germinal center vs non-germinal center immunophenotype by Hans criteria. Post-transplant lymphoproliferative disorder arose after hematopoietic stem cell transplant in five and solid organ transplant in 27 patients, a median of 4 and 96 months after transplant, respectively (overall median latency 71 months, range 2-295). The most common morphology was diffuse large B-cell lymphoma (28 cases), with three cases of Burkitt lymphoma, and one case of plasmablastic lymphoma. Ten cases (31%) were EBV negative. Of those with the morphology of diffuse large B-cell lymphoma, the EBV-negative cases were more frequently TP53-mutated (P<0.001), p53 positive by immunohistochemistry (P<0.001), CD30 negative (P<0.01), and of germinal center immunophenotype (P=0.01) compared with EBV-positive cases. No statistically significant difference in overall survival was identified based on EBV, TP53 mutation status, germinal center vs non-germinal center immunophenotype, or other immunohistochemical parameters evaluated. Patients who died of post-transplant lymphoproliferative disorder were older with a longer latency from time of transplant to diagnosis (P<0.05). Our study demonstrates that diffuse large B-cell lymphoma-related immunohistochemical prognostic markers have limited relevance in the post-transplant setting and underscores differences between EBV-positive and EBV-negative post-transplant lymphoproliferative disorder in terms of immunophenotype and TP53 mutation frequency, supporting an alternative pathogenesis for EBV-negative post-transplant

  4. Native kidney post-transplant lymphoproliferative disorder in a non-renal transplant patient.

    PubMed

    Araya, Carlos E; Mehta, Mansi B; González-Peralta, Regino P; Hunger, Stephen P; Dharnidharka, Vikas R

    2009-06-01

    PTLD is an important post-transplant complication. Although PTLD affects kidney allografts after renal transplantation, it has not been reported in native kidneys of other solid organ recipients. Herein, we report a child who underwent an orthotropic liver transplant for cryptogenic cholestatic hepatitis and developed fever, generalized lymphadenopathy, chronic EBV viremia, and lymphatic PTLD. Subsequently, she also developed gross hematuria and nephrotic range proteinuria. Kidney histology revealed EBV-positive mononuclear infiltrates within the renal parenchyma consistent with PTLD. Electron microscopy examination demonstrated subepithelial electron-dense deposits consistent with a membranous glomerulopathy pattern. The PTLD was successfully treated with reduced immunosuppression and cyclic cyclophosphamide, rituximab, and prednisone, but the renal disease progressed to end-stage renal failure within two yr. Repeat kidney histology showed chronic nephropathy and membranous glomerulopathy without PTLD infiltrates or detectable EBV staining, although chronic viremia persisted. To our knowledge, this is the first such child to be reported and highlights the importance of remaining vigilant for renal PTLD even in non-kidney organ recipients.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  7. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines.

    PubMed

    Styczynski, Jan; van der Velden, Walter; Fox, Christopher P; Engelhard, Dan; de la Camara, Rafael; Cordonnier, Catherine; Ljungman, Per

    2016-07-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged. PMID:27365460

  8. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines.

    PubMed

    Styczynski, Jan; van der Velden, Walter; Fox, Christopher P; Engelhard, Dan; de la Camara, Rafael; Cordonnier, Catherine; Ljungman, Per

    2016-07-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged.

  9. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines

    PubMed Central

    Styczynski, Jan; van der Velden, Walter; Fox, Christopher P.; Engelhard, Dan; de la Camara, Rafael; Cordonnier, Catherine; Ljungman, Per

    2016-01-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged. PMID:27365460

  10. Three different histological subtypes of Epstein-Barr virus-negative post-transplant lymphoproliferative disorder in a patient with hepatitis C infection.

    PubMed

    Kobayashi, Mikiko; Asano, Naoko; Fukushima, Mana; Honda, Takayuki

    2014-09-01

    We report a rare case in which Epstein-Barr virus (EBV)-negative polymorphic B-cell post-transplant lymphoproliferative disorder (PTLD) and EBV-negative monomorphic T-cell PTLD [anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL)] were observed simultaneously in the same cervical lymph node, 34 months after liver transplantation for hepatitis C liver cirrhosis. Although hepatitis C recurred after 2 months, he had no other complications until PTLD occurred 34 months post-transplantation. The patient underwent reduction of the immunosuppressive drug and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, and he was considered to have achieved complete remission. However, PTLD recurred, and he died 6 months after the initial diagnosis. Autopsy revealed only EBV-negative monomorphic T-cell PTLD (ALK-negative ALCL) that involved the liver, spleen, bilateral kidneys, stomach, bladder, heart, bone marrow, right ureter, and pons. Thus, recurrent PTLD may show a different histological type from the primary disorder, as PTLD has a multiclonal potentiality that causes various types of lymphomas. Therefore, it may be difficult to predict PTLD-related prognosis from the initial PTLD histological identification.

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

    PubMed Central

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

    2015-01-01

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

  12. Chimaeric anti-CD20 monoclonal antibody (rituximab) in post-transplant B-lymphoproliferative disorder following stem cell transplantation in children.

    PubMed

    Faye, A; Quartier, P; Reguerre, Y; Lutz, P; Carret, A S; Dehée, A; Rohrlich, P; Peuchmaur, M; Matthieu-Boué, A; Fischer, A; Vilmer, E

    2001-10-01

    Post-transplant lymphoproliferative disorder (PTLD) after haemopoietic stem cell transplantation is a serious complication that occurs in 8-22% of patients with high-risk factors. We retrospectively investigated tolerance and efficacy of humanized anti-CD20 monoclonal antibody (rituximab) as first-line treatment in 12 children with B-cell PTLD. At diagnosis, eight patients had tumoral involvement. The other four patients had fever, associated with raised Epstein-Barr virus (EBV) viral load and monoclonal gammopathy. Rituximab was given at the dose of 375 mg/m2 once a week by intravenous infusion (1-9 infusions). Only 1/48 infusions was associated with a grade 2 clinical adverse event. Eight out of 12 (66%) patients responded to the treatment and were in complete remission. All patients without tumoral involvement responded to the treatment. A rapid decrease in fever within 1 week was observed in all responders. Non-responders did not show any clinical response during the first week. Tumoral involvement and immunodepression seemed to be more marked in non-responders. Rituximab was an effective and well-tolerated treatment of B-cell PTLD. Early treatment before tumoral involvement seemed to be the most effective approach. Lack of rapid response should lead to intensification of PTLD treatment. Pre-emptive treatment should be considered and evaluated in further longitudinal multicentre studies.

  13. Detection of bone marrow involvement in newly diagnosed post-transplant lymphoproliferative disorder: (18)F-fluorodeoxyglucose positron emission tomography/computed tomography versus bone marrow biopsy.

    PubMed

    Gheysens, Olivier; Thielemans, Sanne; Morscio, Julie; Boeckx, Nancy; Goffin, Karolien E; Deroose, Christophe M; Sagaert, Xavier; Wlodarska, Iwona; Verhoef, Gregor; Dierickx, Daan; Tousseyn, Thomas

    2016-10-01

    Detecting bone marrow involvement (BMI) in lymphoma is important as it adversely affects stage. Bone marrow biopsy (BMB) remains the standard to detect BMI but is prone to sampling error. We retrospectively investigated whether (18)F-fluorodeoxyglucose positron emission tomography with computed tomography ((18)F-FDG-PET/CT) could identify BMI in patients with post-transplant lymphoproliferative disorder (PTLD) with sufficient accuracy in comparison with staging BMB. Twenty-five patients diagnosed with PTLD who underwent (18)F-FDG-PET/CT and BMB within one month were evaluated. Based on our criteria, six patients (24%) were considered positive for BMI on (18)F-FDG-PET/CT compared to one by BMB. Although we cannot completely exclude false positive results on (18)F-FDG-PET/CT, our data indicate a significantly higher sensitivity of (18)F-FDG-PET/CT compared to BMB (100% vs 17%) but similar specificity. These data confirm the high diagnostic performance of (18)F-FDG-PET/CT for detecting BMI, but prospective studies are needed to determine whether (18)F-FDG-PET/CT could indeed replace staging BMB in PTLD.

  14. Virus and Autoantigen-Specific CD4+ T Cells Are Key Effectors in a SCID Mouse Model of EBV-Associated Post-Transplant Lymphoproliferative Disorders

    PubMed Central

    Linnerbauer, Stefanie; Behrends, Uta; Adhikary, Dinesh; Witter, Klaus; Bornkamm, Georg W.; Mautner, Josef

    2014-01-01

    Polyclonal Epstein-Barr virus (EBV)-infected B cell line (lymphoblastoid cell lines; LCL)-stimulated T-cell preparations have been successfully used to treat EBV-positive post-transplant lymphoproliferative disorders (PTLD) in transplant recipients, but function and specificity of the CD4+ component are still poorly defined. Here, we assessed the tumor-protective potential of different CD4+ T-cell specificities in a PTLD-SCID mouse model. Injection of different virus-specific CD4+ T-cell clones showed that single specificities were capable of prolonging mouse survival and that the degree of tumor protection directly correlated with recognition of target cells in vitro. Surprisingly, some CD4+ T-cell clones promoted tumor development, suggesting that besides antigen recognition, still elusive functional differences exist among virus-specific T cells. Of several EBV-specific CD4+ T-cell clones tested, those directed against virion antigens proved most tumor-protective. However, enriching these specificities in LCL-stimulated preparations conferred no additional survival benefit. Instead, CD4+ T cells specific for unknown, probably self-antigens were identified as principal antitumoral effectors in LCL-stimulated T-cell lines. These results indicate that virion and still unidentified cellular antigens are crucial targets of the CD4+ T-cell response in this preclinical PTLD-model and that enriching the corresponding T-cell specificities in therapeutic preparations may enhance their clinical efficacy. Moreover, the expression in several EBV-negative B-cell lymphoma cell lines implies that these putative autoantigen(s) might also qualify as targets for T-cell-based immunotherapy of virus-negative B cell malignancies. PMID:24853673

  15. 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

    2014-01-01

    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

  16. Genetics Home Reference: X-linked lymphoproliferative disease

    MedlinePlus

    ... the development of specialized T cells called natural killer T cells. The SAP protein also helps control ... PubMed GeneReview: Lymphoproliferative Disease, X-Linked Latour S. Natural killer T cells and X-linked lymphoproliferative syndrome. Curr ...

  17. Negative outcomes after liver transplantation in patients with alcoholic liver disease beyond the fifth post-transplant year.

    PubMed

    Grąt, Michał; Lewandowski, Zbigniew; Grąt, Karolina; Wronka, Karolina Maria; Krasnodębski, Maciej; Barski, Krzysztof; Zborowska, Hanna; Patkowski, Waldemar; Zieniewicz, Krzysztof; Krawczyk, Marek

    2014-10-01

    Although up to 50% of patients with alcoholic liver disease (ALD) resume alcohol consumption after liver transplantation (LT), numerous studies indicate that long-term results are not compromised. This study focused on evaluating the impact of ALD on outcomes up to and beyond the fifth year after LT. Among the 432 primary LT recipients included in this study, 97 underwent transplantation for ALD. Alcohol relapse rate at 10 yr was 33.5%, with younger recipient age being the only independent predictor (p = 0.019). Survival of patients with ALD (77.0%) was similar to those without (79.0%) up to the fifth post-transplant year (p = 0.655) but worse during the five subsequent years among the five-yr survivors (70.6% vs. 92.9%; p = 0.002). ALD was an independent risk factor for poorer survival beyond the fifth post-transplant year (p = 0.049), but not earlier (p = 0.717). Conversely, alcohol relapse increased the risk of death only during the first five post-transplant years (p = 0.039). There were no significant differences regarding graft failure incidence between ALD and non-ALD recipients up to the fifth post-transplant year (7.3% vs. 11.6%; p = 0.255) and beyond (12.9% vs. 5.0%; p = 0.126). In conclusion, pre-transplant diagnosis of ALD yields negative effects on post-transplant outcomes beyond the fifth post-transplant year, not attributable to recidivism.

  18. 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 ...

  19. 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...

  20. Susceptibility-weighted imaging and diffusion-weighted imaging findings in central nervous system monomorphic B cell post-transplant lymphoproliferative disorder before and after treatment and comparison with primary B cell central nervous system lymphoma.

    PubMed

    Ginat, Daniel Thomas; Purakal, Alixandra; Pytel, Peter

    2015-11-01

    The purpose of this article is to review the MRI features of monomorphic central nervous system post-transplant lymphoproliferative disorder (CNS PTLD), including diffusion-weighted and susceptibility-weighted sequences before and after treatment and to compare the imaging findings with those of primary central nervous system B cell lymphoma (PCNS BCL). Retrospective review of the brain MRI characteristics in patients with pathology proven monomorphic CNS PTLD and PCNS BCL was performed. In particular, the enhancement, diffusion-weighted, susceptibility-weighted MRI characteristics of the lesions were evaluated. In addition, the diffusion-weighted, susceptibility-weighted MRI features after treatment for CNS PTLD were evaluated. A total of 12 lesions in six patients with CNS PTLD and 12 lesions in nine patients with PCNS BCL were identified on MRI. Among the CNS PTLD lesions with post-contrast images, 80 % demonstrated peripheral enhancement. All of the CNS PTLD lesions contained foci of intratumoral susceptibility signal (ITSS) and the average mean ADC values and ratios were 0.892 × 10(-3) mm(2)/s (standard deviation: 0.082 × 10(-3) mm(2)/s) and 1.19 (standard deviation: 0.15), respectively. On the other hand, 75 % of the PCNS BCL displayed diffuse enhancement, two cases (16.7 %) contained ITSS, and the mean ADC values and ratios were 0.721 × 10(-3) mm(2)/s (standard deviation: 0.093 × 10(-3) mm(2)/s), and 0.99 (standard deviation: 0.17), respectively. Thus, the presence of heterogeneous lesions with ITSS that do not necessarily have as extensive restricted diffusion as PCNS BCL is suggestive of CNS PTLD in the appropriate clinical setting. The preliminary data in this series suggests that diffusion-weighted imaging may serve as a useful biomarker for monitoring treatment response, in which successful treatment of CNS PTLD may result in increased ADC values. In addition, foci of susceptibility effect in CNS PTLD tend to persist or increase over the course of

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  2. Post-transplantation primary central nervous system lymphoma in a patient with systemic lupus erythematosus and prolonged use of immunosuppressant.

    PubMed

    Tse, Teresa P K; Chan, Allan N L; Chan, Tony K T; Po, Y C

    2014-12-01

    Post-transplantation primary central nervous system lymphoma is an uncommon and fatal post-transplant lymphoproliferative disorder. Such lymphomas have been described in only a few case series in the literature. The incidence of this condition is rising with improved survival after organ transplantation. A case of post-transplantation primary central nervous system lymphoma in a young Chinese woman with systemic lupus erythematosus is described here. She presented with right-sided weakness and memory loss after tooth extraction 2 weeks before admission. Contrast computed tomography of the brain demonstrated a contrast rim-enhancing lesion over the left frontal lobe. With a history of recent dental procedure, long-term immunosuppressive therapy and computed tomography findings, cerebral abscess was highly suspected. Emergency operation was performed. Histopathology showed post-transplantation primary central nervous system lymphoma, with cells positive for B-cell marker CD20. Immunosuppressant was stopped and she was treated with radiotherapy and rituximab (anti-CD20 monoclonal antibody). She remained disease-free at 16 months. Post-transplantation primary central nervous system lymphoma is rare with variable presentation and radiological features. We believe rituximab may have a role in the treatment of such lymphomas. PMID:25488034

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

    PubMed Central

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

    2013-01-01

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

  4. Cure of X-linked lymphoproliferative disease (XLP) with allogeneic hematopoietic stem cell transplantation (HSCT): report from the XLP registry.

    PubMed

    Gross, T G; Filipovich, A H; Conley, M E; Pracher, E; Schmiegelow, K; Verdirame, J D; Vowels, M; Williams, L L; Seemayer, T A

    1996-05-01

    Seven male patients in the David T Purtilo International X-linked Lymphoproliferative Disease (XLP) Registry have undergone allogeneic hematopoietic stem cell transplantation (HSCT). All patients received HSCT from HLA-identical donors: sibling BM, five; unrelated BM, one; and sibling umbilical cord blood, one. Ages at time of HSCT ranged from 5 to 30 years. Pre-HSCT clinical course varied, but four boys had a significant history of chronic and/or serious infections. Conditioning regimens varied: TBI containing regimens, four, chemotherapy only, three. All patients engrafted. Six developed grade I-II acute GVHD but no chronic GVHD. Four are alive and well with normal immune function greater than 3 years following HSCT. Three died within 100 days: disseminated adenovirus, one; polymicrobial sepsis, one; and multiple organ system failure and bleeding diathesis, one. No EBV-associated post-transplant complications were observed, even though all donors except the umbilical cord blood were EBV-seropositive. Unsuccessful HSCT was associated with age at HSCT (> 15 years), TBI-containing regimen and significant history for pre-HSCT infections. These results provide evidence that HSCT performed during childhood with HLA-identical sibling donors, regardless of EBV serostatus, offers the only curative therapy for XLP. PMID:8733691

  5. Neuroinflammation in the generation of post-transplantation dyskinesia in Parkinson's disease.

    PubMed

    Lane, E L; Soulet, D; Vercammen, L; Cenci, M A; Brundin, P

    2008-11-01

    The observation that neural grafts can induce dyskinesias has severely hindered the development of a transplantation therapy for Parkinson's disease (PD). We addressed the hypothesis that inflammatory responses within and around an intrastriatal graft containing dopamine neurons can trigger dyskinetic behaviors. We subjected rats to unilateral nigrostriatal lesions with 6-hydroxydopamine (6-OHDA) and treated them with L-DOPA for 21 days in order to induce abnormal involuntary movements (AIMs). Subsequently, we grafted the rats with allogeneic embryonic ventral mesencephalic tissue in the dopamine-denervated striatum. In agreement with earlier studies, the grafted rats developed dyskinesia-like AIMs in response to amphetamine. We then used two experimental approaches to induce an inflammatory response and examined if the amphetamine-induced AIMs worsened or if spontaneous AIMs developed. In one experiment, we challenged the neural graft hosts immunologically with an orthotopic skin allograft of the same genetic origin as the intracerebral neural allograft. In another experiment, we infused the pro-inflammatory cytokine interleukin 2 (IL-2) adjacent to the intrastriatal grafts using osmotic minipumps. The skin allograft induced rapid rejection of the mesencephalic allografts, leading to disappearance of the amphetamine-induced AIMs. Contrary to our hypothesis, the rejection process itself did not elicit AIMs. Likewise, the IL-2 infusion did not induce spontaneous AIMs, nor did it alter L-DOPA-induced AIMs. The IL-2 infusions did, however, elicit the predicted marked striatal inflammation, as evidenced by the presence of activated microglia and IL2Ralpha-positive cells. These results indicate that an inflammatory response in and around grafted dopaminergic neurons is not sufficient to evoke dyskinetic behaviors in experimental models of PD. PMID:18675359

  6. Characterization of post transplantation lymphoma in feline renal transplant recipients.

    PubMed

    Durham, A C; Mariano, A D; Holmes, E S; Aronson, L

    2014-01-01

    The development of malignant neoplasia following solid organ transplantation and immunosuppression is well recognized in man. Post-transplantation malignant tumours include non-melanoma skin cancers, non-Hodgkin's lymphoma and Kaposi's sarcoma and many of these cancers have a known or suspected viral cause. A similar increased incidence of cancer is seen in cats that have received a renal transplant and lymphoma is the predominant neoplasm in this population. This study examines a population of cats that received renal transplants at the University of Pennsylvania School of Veterinary Medicine and subsequently developed neoplasia. From 1998 to 2010, 111 cats were transplanted and 25 cats developed cancer (22.5%). Fourteen of the 25 cats were diagnosed with lymphoma (56%), making it the most common tumour in this patient population. The median interval between transplantation and diagnosis of lymphoma was 617 days and the median survival time (MST) following the diagnosis of lymphoma was 2 days. Tissues from seven of these cats were available for histopathological review as either samples collected at necropsy examination (n = 5) or biopsy submissions (n = 2). Five of these cats had multiorgan involvement with sites including the liver, spleen, peripheral and mesenteric lymph nodes, small intestine, urinary bladder, heart, mesenteric fat and body wall. Four of the cats with multiorgan disease had involvement of the renal allograft two of which also had lymphoma of the native kidney. All lymphomas were classified as mid to high grade, diffuse large B-cell lymphoma, which is also the most common lymphoma subtype in human cases of post-transplantation lymphoproliferative disorders.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2015-01-01

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

  9. Phase II Trial of Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide after Reduced-Intensity Busulfan/Fludarabine Conditioning for Hematological Malignancies.

    PubMed

    Alousi, Amin M; Brammer, Jonathan E; Saliba, Rima M; Andersson, Borje; Popat, Uday; Hosing, Chitra; Jones, Roy; Shpall, Elizabeth J; Khouri, Issa; Qazilbash, Muzaffar; Nieto, Yago; Shah, Nina; Ahmed, Sairah; Oran, Betul; Al Atrash, Gheath; Ciurea, Stefan; Kebriaei, Partow; Chen, Julianne; Rondon, Gabriela; Champlin, Richard E

    2015-05-01

    Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (CY) after ablative HLA-matched bone marrow (BM) transplantation has been reported to have comparable rates of acute GVHD with an apparent reduction in chronic GVHD and infections when compared to historical prophylaxis with a calcineurin-inhibitor (CNI) and methotrexate (MTX). We conducted a phase II trial of post-transplantation CY (post-CY) after reduced-intensity conditioning (RIC) using intravenous busulfan (area under the curve of 4000 micromolar minute), fludarabine (40 mg/m(2)) for 4 days, and CY 50 mg/kg on days +3 and +4 after BM or peripheral blood (PB) transplantations from matched related (MRD) or unrelated donors (MUD). MUD recipients received antithymocyte globulin (ATG); however, a later amendment removed ATG. Forty-nine patients were treated (acute myeloid leukemia/myelodysplastic syndrome, 82%). Median age was 62 years (range, 39 to 72). Fifteen patients received an MRD (9 PB/6 BM); 34 had a MUD (2 PB/32 BM). The cumulative incidence of grade II to IV acute GVHD, III to IV acute GVHD, and chronic GVHD was 58%, 22%, and 18%, respectively. A matched cohort analysis compared outcomes to tacrolimus/methotrexate GVHD prophylaxis and indicated higher rates of acute GVHD grade II to IV (46% versus 19%; hazard ratio [HR], 2.8; P = .02) and treatment-related mortality (HR, 3.3; P = .035) and worse overall survival (HR, 1.9; P = .04) with post-CY. The incidence of chronic GVHD and CMV reactivation did not differ. This study suggests that post-CY should not be used as sole GVHD prophylaxis after a RIC transplantation from HLA-matched donors. PMID:25667989

  10. Role of BK virus infection in end-stage renal disease patients waiting for kidney transplantation--viral replication dynamics from pre- to post-transplant.

    PubMed

    Mitterhofer, Anna Paola; Tinti, Francesca; Pietropaolo, Valeria; Umbro, Ilaria; Anzivino, Elena; Bellizzi, Anna; Zavatto, Assunta; Poli, Luca; Berloco, Pasquale Bartolomeo; Taliani, Gloria

    2014-03-01

    We report the prevalence of BK virus (BKV) infection before renal transplantation and the dynamics of BKV viremia from pre- to post-transplantation. We assessed 60 kidney transplanted patients from a single cohort in Italy, treated with identical immunosuppressive therapy, for BK viremia at pre-transplantation, 12 h, and three and six months post-transplantation. Polymerase chain reaction showed that the prevalence of plasma BKV replication--considered a marker of infection--was 20% in pre-transplant patients. All pre-transplant-positive patients remained positive post-transplant, whereas the majority of pre-transplant-negative patients remained negative. Viremia dynamics classification revealed three clusters of patients: Cluster A++, pre-transplant-positive patients (20%) who tested positive at least once post-transplant; Cluster B-+, pre-transplant-negative patients (28%) who tested positive at least once post-transplant; and Cluster C- -, pre-transplant-negative patients (52%) who remained negative throughout. These clusters presented significant differences related to the prevalence of substantially positive patients with high plasma viral load (>10(3) copies/mL) in cluster A, but not in donors' or grafts' characteristics. We suggest that pre-transplant viral status should be considered as an additional risk factor for post-transplant BKV replication. Therefore, pre-transplant BKV infection screening in kidney transplant patients should be performed for improving planning of personalized immunosuppressant schemes and specific post-transplant surveillance.

  11. Post-transplantation diabetes-state of the art.

    PubMed

    Sharif, Adnan; Cohney, Solomon

    2016-04-01

    With increasing success in overcoming the immunological and infectious challenges accompanying solid organ transplantation, susceptibility to post-transplant diabetes and cardiovascular disease has assumed increasing importance. Although some guidance is available from diabetes-related literature pertaining to the general population, some aspects are unique to solid organ allograft recipients. Both insulin resistance and β-cell dysfunction are generally agreed to contribute to development and manifestation of post-transplant diabetes, but controversy continues about which is most important and to what extent post-transplant diabetes is a distinct entity or simply a variant of type 2 diabetes with transplant-specific components. The optimum method and timing for detection and diagnosis of post-transplant diabetes remains an area of uncertainty. However, the greatest needs are to: address the absence of contemporary data for incidence and clinical outcomes associated with post-transplant diabetes; establish the role of glycaemic control; and assess the role of new diabetic therapies in prevention and management of post-transplant diabetes. We place the present knowledge base in the context of other advances in transplantation, challenge some existing ideas, and examine the potential role of emerging diabetes therapies. In highlighting existing deficiencies, we hope to provide direction for future research that will ultimately reduce incidence and improve management of post-transplant diabetes. PMID:26632096

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

    PubMed

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

    2014-11-01

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

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

    PubMed

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

    2014-11-01

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

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

    PubMed

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

    2013-08-01

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

  15. Short Course of Post-Transplantation Cyclophosphamide and Bortezomib for Graft-versus-Host Disease Prevention after Allogeneic Peripheral Blood Stem Cell Transplantation Is Feasible and Yields Favorable Results: A Phase I Study.

    PubMed

    Al-Homsi, Ahmad-Samer; Cole, Kelli; Bogema, Marlee; Duffner, Ulrich; Williams, Stephanie; Mageed, Aly

    2015-07-01

    An effective graft-versus-host disease (GVHD) preventative approach that preserves the graft-versus-tumor effect after allogeneic hematopoietic stem cell transplantation (HSCT) remains elusive. Standard GVHD prophylactic regimens suppress T cells indiscriminately and are suboptimal. Conversely, post-transplantation high-dose cyclophosphamide selectively destroys proliferating alloreactive T cells, allows the expansion of regulatory T cells, and induces long-lasting clonal deletion of intrathymic antihost T cells. It has been successfully used to prevent GVHD after allogeneic HSCT. Bortezomib has antitumor activity on a variety of hematological malignancies and exhibits a number of favorable immunomodulatory effects that include inhibition of dendritic cells. Therefore, an approach that combines post-transplantation cyclophosphamide and bortezomib seems attractive. Herein, we report the results of a phase I study examining the feasibility and safety of high-dose post-transplantation cyclophosphamide in combination with bortezomib in patients undergoing allogeneic peripheral blood HSCT from matched siblings or unrelated donors after reduced-intensity conditioning. Cyclophosphamide was given at a fixed dose (50 mg/kg on days +3 and +4). Bortezomib dose was started at .7 mg/m2, escalated up to 1.3 mg/m2, and was administered on days 0 and +3. Patients receiving grafts from unrelated donors also received rabbit antithymocyte globulin. The combination was well tolerated and allowed prompt engraftment in all patients. The incidences of acute GVHD grades II to IV and grades III and IV were 20% and 6.7%, respectively. With a median follow-up of 9.1 months (range, 4.3 to 26.7), treatment-related mortality was 13.5% with predicted 2-year disease-free survival and overall survival of 55.7% and 68%, respectively. The study suggests that the combination of post-transplantation cyclophosphamide and bortezomib is feasible and may offer an effective and practical GVHD prophylactic

  16. Pre- and post-transplant quantification of measurable ('minimal') residual disease via multiparameter flow cytometry in adult acute myeloid leukemia.

    PubMed

    Zhou, Y; Othus, M; Araki, D; Wood, B L; Radich, J P; Halpern, A B; Mielcarek, M; Estey, E H; Appelbaum, F R; Walter, R B

    2016-07-01

    Measurable ('minimal') residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n=63) or after (n=16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas two patients developed new evidence of disease. The 214 MRD(neg)/MRD(neg) patients had excellent outcomes, whereas both MRD(neg)/MRD(pos) patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was only observed among the 58 patients with decreasing but not the seven patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with overall survival and risk of relapse. These data indicate that MRD(pos) patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies.

  17. Pre- and post-transplant quantification of measurable ('minimal') residual disease via multiparameter flow cytometry in adult acute myeloid leukemia.

    PubMed

    Zhou, Y; Othus, M; Araki, D; Wood, B L; Radich, J P; Halpern, A B; Mielcarek, M; Estey, E H; Appelbaum, F R; Walter, R B

    2016-07-01

    Measurable ('minimal') residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n=63) or after (n=16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas two patients developed new evidence of disease. The 214 MRD(neg)/MRD(neg) patients had excellent outcomes, whereas both MRD(neg)/MRD(pos) patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was only observed among the 58 patients with decreasing but not the seven patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with overall survival and risk of relapse. These data indicate that MRD(pos) patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies. PMID:27012865

  18. Treatment of post-transplant premalignant skin disease: a randomized intrapatient comparative study of 5-fluorouracil cream and topical photodynamic therapy

    PubMed Central

    Perrett, C.M.; McGregor, J.M.; Warwick, J.; Karran, P.; Leigh, I.M.; Proby, C.M.; Harwood, C.A.

    2008-01-01

    Summary Background Organ transplant recipients (OTR) are at high risk of developing non-melanoma skin cancer and premalignant epidermal dysplasia (carcinoma in situ/Bowen’s disease and actinic keratoses). Epidermal dysplasia is often widespread and there are few comparative studies of available treatments. Objectives To compare topical methylaminolaevulinate (MAL) photodynamic therapy (PDT) with topical 5% fluorouracil (5-FU) cream in the treatment of post-transplant epidermal dysplasia. Methods Eight OTRs with epidermal dysplasia were recruited to an open-label, single-centre, randomized, intrapatient comparative study. Treatment with two cycles of topical MAL PDT 1 week apart was randomly assigned to one area of epidermal dysplasia, and 5-FU cream was applied twice daily for 3 weeks to a clinically and histologically comparable area. Patients were reviewed at 1, 3 and 6 months after treatment. The main outcome measures were complete resolution rate (CRR), overall reduction in lesional area, treatment-associated pain and erythema, cosmetic outcome and global patient preference. Results At all time points evaluated after completion of treatment, PDT was more effective than 5-FU in achieving complete resolution: eight of nine lesional areas cleared with PDT (CRR 89%, 95% CI: 0·52-0·99), compared with one of nine lesional areas treated with 5-FU (CRR 11%, 95% CI: 0·003-0·48) (P = 0·02). The mean lesional area reduction was also proportionately greater with PDT than with 5-FU (100% vs. 79% respectively). Cosmetic outcome and patient preference were also superior in the PDT-treated group. Conclusions Compared with topical 5-FU, MAL PDT was a more effective and cosmetically acceptable treatment for epidermal dysplasia in OTRs and was preferred by patients. Further studies are now required to confirm these results and to examine the effect of treating epidermal dysplasia with PDT on subsequent development of squamous cell carcinoma in this high risk population

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    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

    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

  1. [THE COMBINATION OF EXPRESSION OF MARKERS CR1 AND CR2 (CD35/CD21) IN DIAGNOSTIC OF B-CELL LYMPHOPROLIFERATIVE DISEASES].

    PubMed

    Chibisova, O N; Burtsev, D V; Galstian, K M; Lugovskaia, G I

    2015-04-01

    The study was carried out to analyze rate of expression of antigens CD35 and CD21 in norm and under different forms of B-cell lymphoproliferative diseases. The level of average intensity of fluorescence of antigens CD35, CD21 and CD200 is compared for different groups of patients with B-cell lymphoproliferative diseases. The established patterns of expression of antigens CD35 and CD21 under B-cell lymphoproliferative diseases permit considering expression of the given markers as a characteristic of differential diagnostic. PMID:26189291

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  5. Expression of Human Herpesvirus-6 Antigens in Benign and Malignant Lymphoproliferative Diseases

    PubMed Central

    Luppi, Mario; Barozzi, Patrizia; Garber, Richard; Maiorana, Antonio; Bonacorsi, Goretta; Artusi, Tullio; Trovato, Raffaella; Marasca, Roberto; Torelli, Giuseppe

    1998-01-01

    Immunohistochemistry was used to look for the expression of human herpesvirus-6 (HHV-6) antigens in a well characterized series of benign, atypical, and malignant lymphoid lesions, which tested positive for the presence of HHV-6 DNA. A panel of specific antibodies against HHV-6 antigens, characteristic either of the early (p41) or late (p101K, gp106, and gp116) phases of the viral cycle, was applied to the lymphoid tissues from 15 non-Hodgkin’s lymphomas, 14 Hodgkin’s disease cases, 5 angioimmunoblastic lymphadenopathies with dysproteinemia, 14 reactive lymphadenopathies, and 2 cases of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). In lymphomatous tissues, the expression of late antigens was documented only in reactive cells, and mainly in plasma cells. Of interest, the expression of the early p41 antigen was detected in the so-called “mummified” Reed-Sternberg cells, in two Hodgkin’s disease cases. In reactive lymphadenopathies, the HHV-6 late antigen-expressing cells were plasma cells, histiocytes, and rare granulocytes distributed in interfollicular areas. In both cases of Rosai-Dorfman disease, the p101K showed an intense staining in follicular dendritic cells of germinal centers, whereas the gp106 exhibited an intense cytoplasmic reaction in the abnormal histiocytes, which represent the histological hallmark of the disease. The expression of HHV-6 antigens is tightly controlled in lymphoid tissues. The lack of HHV-6 antigen expression in neoplastic cells and the limited expression in degenerating Reed-Sternberg cells argue against a major pathogenetic role of the virus in human lymphomagenesis. The detection of a rather unique pattern of viral late antigen expression in Rosai-Dorfman disease suggests a possible pathogenetic involvement of HHV-6 in some cases of this rare lymphoproliferative disorder. PMID:9736030

  6. Multi-Institutional Study of Post-Transplantation Cyclophosphamide As Single-Agent Graft-Versus-Host Disease Prophylaxis After Allogeneic Bone Marrow Transplantation Using Myeloablative Busulfan and Fludarabine Conditioning

    PubMed Central

    Kanakry, Christopher G.; O'Donnell, Paul V.; Furlong, Terry; de Lima, Marcos J.; Wei, Wei; Medeot, Marta; Mielcarek, Marco; Champlin, Richard E.; Jones, Richard J.; Thall, Peter F.; Andersson, Borje S.; Luznik, Leo

    2014-01-01

    Purpose The clinical safety and efficacy of intravenous busulfan and fludarabine (IV Bu/Flu) myeloablative conditioning as well as graft-versus-host disease (GVHD) prophylaxis with high-dose, post-transplantation cyclophosphamide (PTCy) have been demonstrated independently in several single-institutional studies. We hypothesized that combining these two promising approaches in a multi-institutional study of human leukocyte antigen (HLA) -matched bone marrow transplantation would provide low rates of severe acute and chronic GVHD, low toxicity, and effective disease control. Patients and Methods Ninety-two adult patients (median age, 49 years; range, 21 to 65 years) with high-risk hematologic malignancies were enrolled at three centers (clinical trial No. NCT00809276). Forty-five patients received related allografts, and 47 received unrelated allografts. GVHD prophylaxis was solely with PTCy at 50 mg/kg/day on post-transplantation days +3 and +4. Results The cumulative incidences of grades 2 to 4 acute, grades 3 to 4 acute, and chronic GVHD were 51%, 15%, and 14%, respectively. Nonrelapse mortality (NRM) at 100 days and 1 year were 9% and 16%, respectively. With a median follow-up period of 2.2 years, the 2-year disease-free survival (DFS) and overall survival (OS) rates were 62% and 67%, respectively. Donor relatedness did not affect NRM, DFS, or OS. Patients in complete remission (CR) without evidence of minimal residual disease (MRD) had markedly better DFS (80%) and OS (80%) than patients in CR with MRD or with active disease at the time of transplantation (DFS, P = .0005; OS, P = .019). Conclusion This multi-institutional study demonstrates that PTCy can be safely and effectively combined with IV Bu/Flu myeloablative conditioning and confirms PTCy's efficacy as single-agent, short-course GVHD prophylaxis for both acute and chronic GVHD after bone marrow transplantation from HLA-matched donors. PMID:25267759

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

    PubMed

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

    2015-12-01

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

  8. IgG4-related disease: a novel lymphoproliferative disorder discovered and established in Japan in the 21st century.

    PubMed

    Masaki, Yasufumi; Kurose, Nozomu; Umehara, Hisanori

    2011-01-01

    IgG4-related disease is a novel lymphoproliferative disorder that shows hyper-IgG4-γ-globulinemia and IgG4-producing plasma cell expansion in affected organs with fibrotic or sclerotic changes. Patients show systemic inflammatory conditions and various symptoms depending on the affected organ. Since the first report of patients with elevated serum IgG4 in sclerosing pancreatitis in 2001, various systemic disorders described by many names have been reported. Despite similarities in the organs involved in IgG4-related Mikulicz's disease and Sjögren's syndrome, there are marked clinical and pathological differences between these conditions. Most patients diagnosed with autoimmune pancreatitis in Japan have IgG4-related pancreatitis [Type 1 autoimmune pancreatitis (AIP), lymphoplasmacytic sclerosing pancreatitis (LPSP)], a disease distinct from some of the western type [Type 2 AIP, idiopathic duct-centric chronic pancreatitis (IDCP), autoimmune pancreatitis with granulocytic epithelial lesions (GEL)]. Diagnosis of IgG4-related disease is characterized by both elevated serum IgG4 (>135 mg/dL) and histopathological features including lymphocyte and IgG4(+) plasma cell infiltration (IgG4(+) plasma cells/IgG(+) plasma cells>40%). Differential diagnosis from other distinct disorders, such as sarcoidosis, Castleman's disease, Wegener's granulomatosis, lymphoma, cancer, and other existing conditions associated with high serum IgG4 level or abundant IgG4-bearing plasma cells in tissues is necessary. We have begun a clinical prospective study to establish a treatment strategy (Phase II prospective treatment study for IgG4-multiorgan lymphoproliferative syndrome: UMIN R000002311). PMID:21628856

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

    PubMed

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

    2005-11-01

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

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

    PubMed Central

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

    2014-01-01

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

  11. Pre- and Post-Transplant Quantification of Measurable (“Minimal”) Residual Disease via Multiparameter Flow Cytometry in Adult Acute Myeloid Leukemia

    PubMed Central

    Zhou, Yi; Othus, Megan; Araki, Daisuke; Wood, Brent L.; Radich, Jerald P.; Halpern, Anna B.; Mielcarek, Marco; Estey, Elihu H.; Appelbaum, Frederick R.; Walter, Roland B.

    2016-01-01

    Measurable (“minimal”) residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n=63) or after (n=16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas 2 patients developed new evidence of disease. The 214 MRDneg/MRDneg patients had excellent outcomes, whereas both MRDneg/MRDpos patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was observed among the 58 patients with decreasing but not the 7 patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with OS and RR. These data indicate that MRDpos patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies. PMID:27012865

  12. Oral Lesions and Lymphoproliferative Disorders

    PubMed Central

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

    2010-01-01

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

  13. Informational needs of liver transplant recipients during a two-year post transplant period

    PubMed Central

    Ko, Dami; Lee, Insook; Muehrer, Rebecca J

    2016-01-01

    Objectives To describe the informational needs of liver transplant (LTx) recipients, examine potential differences in informational needs by socio-demographic and clinical variables, and examine informational needs at various time points post-transplant. Methods This study used a descriptive, cross-sectional design. Informational needs were assessed by the INQ-liver, a new questionnaire developed to include LTx recipients’ perspective. In order to examine information needs at different post-transplant time points, participants were classified into four groups (0–1, 2–4, 5–9, and 10–24 months post-transplant). Results Participants (159) who were married, single, had higher levels of education, or higher monthly incomes had significantly greater informational needs. Informational needs related to disease and physical and emotional management remained high after transplant. Four subscales (medication, wound management, diet, and daily and social activities) indicated patients experience different informational needs across time. Participants who were 2–4 months post-transplant had higher informational needs related to wound management and daily and social activities. The highest informational needs related to medication and diet were reported by participants who were 5–9 months post-transplant. Discussion The findings indicated that informational needs vary among LTx recipients who are at different time points post-transplant. Marital status, education, and monthly income can influence informational needs. Conclusion Healthcare providers should tailor information given to LTx recipients to their needs at different time points. Longitudinal studies are needed to confirm the changing patterns of informational needs. PMID:26289361

  14. Risk assessment and management of post-transplant diabetes mellitus.

    PubMed

    Han, Eugene; Kim, Myoung Soo; Kim, Yu Seun; Kang, Eun Seok

    2016-10-01

    The success rate of organ transplantation has been increasing with advances in surgical and pharmacological techniques. However, the number of solid organ transplant recipients who require metabolic disease management is also growing. Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation and is associated with risks of graft loss, cardiovascular morbidity, and mortality. Other risk factors for PTDM include older age, genetic background, obesity, hepatitis C virus infection, hypomagnesemia, and use of immunosuppressant agents (corticosteroids, calcineurin inhibitors, and mammalian target of rapamycin inhibitor). Management of PTDM should be started before the transplantation plan to properly screen high-risk patients. Even though PTDM management is similar to that of general type 2 diabetes, therapeutic approaches must be made with consideration of drug interactions between immunosuppressive agents, glucose-lowering medications, and graft rejection and function.

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

    PubMed

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

    2016-06-01

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

  16. Risk assessment and management of post-transplant diabetes mellitus.

    PubMed

    Han, Eugene; Kim, Myoung Soo; Kim, Yu Seun; Kang, Eun Seok

    2016-10-01

    The success rate of organ transplantation has been increasing with advances in surgical and pharmacological techniques. However, the number of solid organ transplant recipients who require metabolic disease management is also growing. Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation and is associated with risks of graft loss, cardiovascular morbidity, and mortality. Other risk factors for PTDM include older age, genetic background, obesity, hepatitis C virus infection, hypomagnesemia, and use of immunosuppressant agents (corticosteroids, calcineurin inhibitors, and mammalian target of rapamycin inhibitor). Management of PTDM should be started before the transplantation plan to properly screen high-risk patients. Even though PTDM management is similar to that of general type 2 diabetes, therapeutic approaches must be made with consideration of drug interactions between immunosuppressive agents, glucose-lowering medications, and graft rejection and function. PMID:27621191

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

    MedlinePlus

    ... Related Links​ ALPS Unit, Laboratory of Immunology Autoimmune Diseases Immune System Primary Immune Deficiency Diseases National Library of ... Study Provides Insights Into Diagnosis, Treatment of Rare Immune Disease NIH Scientists Report Findings From 20 Years of ...

  18. SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease.

    PubMed

    Rivat, Christine; Booth, Claire; Alonso-Ferrero, Maria; Blundell, Michael; Sebire, Neil J; Thrasher, Adrian J; Gaspar, H Bobby

    2013-02-14

    X-linked lymphoproliferative disease (XLP1) arises from mutations in the gene encoding SLAM-associated protein (SAP) and leads to abnormalities of NKT-cell development, NK-cell cytotoxicity, and T-dependent humoral function. Curative treatment is limited to allogeneic hematopoietic stem cell (HSC) transplantation. We tested whether HSC gene therapy could correct the multilineage defects seen in SAP(-/-) mice. SAP(-/-) murine HSCs were transduced with lentiviral vectors containing either SAP or reporter gene before transplantation into irradiated recipients. NKT-cell development was significantly higher and NK-cell cytotoxicity restored to wild-type levels in mice receiving the SAP vector in comparison to control mice. Baseline immunoglobulin levels were significantly increased and T-dependent humoral responses to NP-CGG, including germinal center formation, were restored in SAP-transduced mice.We demonstrate for the first time that HSC gene transfer corrects the cellular and humoral defects in SAP(-/-) mice providing proof of concept for gene therapy in XLP1.

  19. Identifying predictive factors for posttransplant lymphoproliferative disease in pediatric solid organ transplant recipients with Epstein-Barr virus viremia.

    PubMed

    Weintraub, Lauren; Weiner, Chana; Miloh, Tamir; Tomaino, Juli; Joashi, Umesh; Benchimol, Corinne; Strauchen, James; Roth, Michael; Wistinghausen, Birte

    2014-11-01

    Epstein-Barr virus (EBV) viremia (EV) in pediatric solid organ transplant (SOT) recipients is a significant risk factor for posttransplant lymphoproliferative disease (PTLD) but not all patients with EV develop PTLD. We identify predictive factors for PTLD in patients with EV. We conducted a retrospective chart review of all pediatric SOT recipients (0 to 21 y) at a single institution between 2001 and 2009. A total of 350 pediatric patients received a SOT and 90 (25.7%) developed EV. Of EV patients, 28 (31%) developed PTLD. The median age at transplant was 11.5 months in the PTLD group and 21.5 months in the EV-only group (P=0.003). Twenty-three (37%) EV-only patients had immunosuppression increased before EV, compared with 28 (100%) of PTLD patients (P<0.001). The median peak EBV level was 3212 EBV copies/10 lymphocytes for EV-only and 8392.5 EBV copies/10 lymphocytes for PTLD (P=0.005). All patients who developed PTLD had ≥1 clinical symptoms. Younger age at transplant, increased immunosuppression before EV, higher peak EBV level, and presence of clinical symptoms have predictive value in the development of PTLD in SOT patients with EV.

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

    PubMed Central

    2014-01-01

    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

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

    PubMed

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

    2016-01-01

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

  2. Epstein-Barr Virus-Positive Posttransplant Lymphoproliferative Disease After Solid Organ Transplantation: Pathogenesis, Clinical Manifestations, Diagnosis, and Management.

    PubMed

    Nijland, Marieke L; Kersten, Marie José; Pals, Steven T; Bemelman, Frederike J; Ten Berge, Ineke J M

    2016-01-01

    Posttransplant lymphoproliferative disease (PTLD) is a potentially fatal complication after (solid organ) transplantation, which is highly associated with Epstein-Barr virus (EBV). The EBV-specific cytotoxic T cell response that is essential in controlling the virus in healthy individuals is suppressed in transplant recipients using immunosuppressive drugs. A primary EBV infection in EBV-seronegative patients receiving an EBV-seropositive donor organ or a reactivation in those who are already latently infected pretransplantation can lead to uninhibited growth of EBV-infected B cells and subsequently to PTLD. Effective preventive strategies, such as vaccines and antiviral agents, are lacking. Because not every transplant recipient with increasing EBV viral load develops PTLD, it is hard to decide how intensively these patients should be monitored and how and when a preemptive intervention should take place. There is a need for other tools to help predict the development of PTLD in patients at risk to make timing and strategy of preemptive intervention easier and more reliable. The cornerstone of the treatment of patients with PTLD is restoring the host's immunity by reduction of immunosuppressive drug therapy. American and British guidelines recommend to add rituximab monotherapy or rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisolone, depending on histology and clinical characteristics. Although response to these therapies is good, toxicity is a problem, and PTLD still has a relatively high mortality rate. An evolving therapy, especially in PTLD occurring in allogeneic stem cell transplantation, is restoring the host's immune response with infusion of EBV-specific cytotoxic T cells. This may also play a role in the future in both prevention and treatment of PTLD in SOT. PMID:27500242

  3. P-glycoprotein is expressed and causes resistance to chemotherapy in EBV-positive T-cell lymphoproliferative diseases.

    PubMed

    Yoshimori, Mayumi; Takada, Honami; Imadome, Ken-Ichi; Kurata, Morito; Yamamoto, Kouhei; Koyama, Takatoshi; Shimizu, Norio; Fujiwara, Shigeyoshi; Miura, Osamu; Arai, Ayako

    2015-10-01

    Epstein-Barr virus-positive T-cell lymphoproliferative diseases (EBV-T-LPDs) are rare lymphomas with poor prognosis. Although chemotherapeutic strategies such as CHOP have been often selected, they have exhibited only limited efficacy. To clarify the mechanism of chemoresistance, we examined P-glycoprotein (P-gp) expression. P-gp acts as an energy-dependent efflux pump that excretes drugs from the cytoplasm, resulting in low-intracellular drug concentrations and poor sensitivity to chemotherapy. We examined P-gp expression in EBV-positive cells by immunohistochemistry staining in three patients of EBV-T-LPDs and the expression was detected in all patients. We also examined mdr1 mRNA expression by reverse-transcriptase polymerase-chain reaction (RT-PCR) in EBV-positive tumor cells from these patients and additional three patients. The expression was detected in all examined patients. In five EBV-T-LPDs patients, P-gp function was detected by Rhodamine-123 efflux assay in these cells. The efflux was inhibited by treatment with a P-gp inhibitor, cyclosporine A (CsA). We also examined and detected P-gp expression in EBV-positive T-cell lines SNT8 and SNT16 established from EBV-T-LPDs patients, by RT-PCR and western blotting. The function was also detected by Rhodamine-123 efflux in these cell lines. Inhibition and knock down of P-gp by CsA and siRNA, respectively, enhanced etoposide- and doxorubicin-induced cell death in the EBV-positive T-cell lines. Finally, we infected the T-cell line MOLT4 with EBV, and found that mdr1 mRNA expression and Rhodamine 123 efflux were upregulated after infection. These results indicated that enhanced P-gp expression contributed to the chemoresistance of EBV-T-LPDs.

  4. Epstein-Barr Virus–Positive Posttransplant Lymphoproliferative Disease After Solid Organ Transplantation: Pathogenesis, Clinical Manifestations, Diagnosis, and Management

    PubMed Central

    Nijland, Marieke L.; Kersten, Marie José; Pals, Steven T.; Bemelman, Frederike J.; ten Berge, Ineke J.M.

    2016-01-01

    Abstract Posttransplant lymphoproliferative disease (PTLD) is a potentially fatal complication after (solid organ) transplantation, which is highly associated with Epstein-Barr virus (EBV). The EBV-specific cytotoxic T cell response that is essential in controlling the virus in healthy individuals is suppressed in transplant recipients using immunosuppressive drugs. A primary EBV infection in EBV-seronegative patients receiving an EBV-seropositive donor organ or a reactivation in those who are already latently infected pretransplantation can lead to uninhibited growth of EBV-infected B cells and subsequently to PTLD. Effective preventive strategies, such as vaccines and antiviral agents, are lacking. Because not every transplant recipient with increasing EBV viral load develops PTLD, it is hard to decide how intensively these patients should be monitored and how and when a preemptive intervention should take place. There is a need for other tools to help predict the development of PTLD in patients at risk to make timing and strategy of preemptive intervention easier and more reliable. The cornerstone of the treatment of patients with PTLD is restoring the host's immunity by reduction of immunosuppressive drug therapy. American and British guidelines recommend to add rituximab monotherapy or rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisolone, depending on histology and clinical characteristics. Although response to these therapies is good, toxicity is a problem, and PTLD still has a relatively high mortality rate. An evolving therapy, especially in PTLD occurring in allogeneic stem cell transplantation, is restoring the host's immune response with infusion of EBV-specific cytotoxic T cells. This may also play a role in the future in both prevention and treatment of PTLD in SOT. PMID:27500242

  5. Disclosing the CXCR4 expression in lymphoproliferative diseases by targeted molecular imaging.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-12-01

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

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

    PubMed Central

    1985-01-01

    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

  9. Adoptive transfer of the generalized lymphoproliferative disease (gld) syndrome in nude beige mice.

    PubMed Central

    Froidevaux, S; Rosenblatt, N; Loor, F

    1992-01-01

    C57BL/6 nude beige mice (B6 nubg) were used as recipients for the transfer of haematopoietic cells from either B6 wild as control mice, or systemic lupus erythematous B6 mice homozygous for the recessive generalized lymphadenopathy disease (gld) locus. Both gld and wild cell grafts prolonged survival of the short-living B6 nubg recipients and restored some T-cell functions, as monitored by the presence of T-dependent Ig isotypes in the serum and responsiveness of spleen cells to a T-cell mitogen. Moreover, the [gld----nubg] chimeras but not the [wild----nubg] chimeras showed several similarities with gld control mice, particularly, a spleen and lymph node hyperplasia, elevated anti-single-stranded DNA antibody titres and a hyperglobulinaemia. This hyperglobulinaemia was however qualitatively different from the gld-type hyperglobulinaemia with an important contribution of the IgG1 isotype; the lymph node hyperplasia was also less marked than in B6 gld mice. PMID:1592442

  10. A yeast artificial chromosome (YAC) contig encompassing the critical region of the X-linked lymphoproliferative disease (XLP) locus.

    PubMed

    Lanyi, A; Li, B; Li, S; Talmadge, C B; Brichacek, B; Davis, J R; Kozel, B A; Trask, B; van den Engh, G; Uzvolgyi, E; Stanbridge, E J; Nelson, D L; Chinault, C; Heslop, H; Gross, T G; Seemayer, T A; Klein, G; Purtilo, D T; Sumegi, J

    1997-01-01

    X-linked lymphoproliferative disease (XLP) is characterized by a marked vulnerability to Epstein-Barr virus (EBV) infection. Infection of XLP patients with EBV invariably results in fatal mononucleosis, agammaglobulinemia, or malignant lymphoma. Initially the XLP gene was assigned to a 10-cM region in Xq25 between DXS42 and DXS37. Subsequently, an interstitial, cytogenetically visible deletion in Xq25 was identified in one XLP family, 43. In this study we estimated the deletion in XLP patient 43-004 by dual-laser flow karyotyping to involve 2% of the X chromosome, or approximately 3 Mb of DNA sequence. From a human chromosome Xq25-specific yeast artificial chromosome (YAC) sublibrary, five YACs containing DNA sequences deleted in patient 43-004 have been isolated. Sequence-tagged sites (STSs) from these YACs have been used to identify interstitial deletions in unrelated XLP patients. Three more families with interstitial deletions were found. Two of the patients (63-003 and 73-032) carried an interstitial deletion of 3.0 Mb overlapping the 43-004 deletion. In one XLP patient (30-011) who exhibited the characteristic postinfectious mononucleosis phenotype of XLP with hypogammaglobulinemia and malignant lymphoma, a deletion of approximately 250 kb was detected overlapping the deletion detected in patients 43-004, 63-003, and 73-032. A YAC contig of 2.2 Mb spanning the XLP critical region, whose orientation on chromosome X was determined by double-color fluorescence in situ hybridization and which consists of 15 overlapping YAC clones, has been constructed. A detailed restriction enzyme map of the region has been constructed. YAC insert sizes were determined by counter-clamped homogenous electric field gel electrophoresis. Chimerism of YACs was determined by FISH and restriction mapping. On the basis of lambda subclones, YAC end-derived plasmids, and STSs with an average spacing of 100 kb, a long-range physical map was constructed using 5 rare-cutter restriction

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

    PubMed Central

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

    2015-01-01

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

  12. Haploidentical Hematopoietic Stem Cell Transplantation as Platform for Post-transplant Cellular Therapy

    PubMed Central

    Kongtim, Piyanuch; Lee, Dean A.; Cooper, Laurence J. N.; Kebriaei, Partow; Champlin, Richard E.; Ciurea, Stefan O.

    2016-01-01

    Haploidentical transplantation can extend the opportunity for transplantation to almost all patients who lack an HLA-matched donor. Advances in the field of haploidentical transplantation have led to a marked decrease in treatment-related mortality, allowing investigators to focus on developing rationale pre- and peri-remission therapies aimed at preventing disease relapse post-transplant. Due to widespread availability, low treatment-related mortality and cost, haploidentical donors may become the preferred “alternative” donors for allogeneic hematopoietic stem cell transplantation. One of the major advantages of using a related donor is the possibility to collect or generate additional cellular products from the same immediate available donor, which will not be rejected. Infusion of these cells in the peri-transplant period, derived from the same immune system, is opening the possibility to markedly enhance the anti-tumor effects of the graft and hasten immunologic reconstitution post-transplant. PMID:26172479

  13. Post-transplant Adjustment – The Later Years

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    2014-01-01

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

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

    PubMed

    Park, Chul Soo

    2015-06-14

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

  16. Production of genetically modified Epstein-Barr virus-specific cytotoxic T cells for adoptive transfer to patients at high risk of EBV-associated lymphoproliferative disease.

    PubMed

    Smith, C A; Ng, C Y; Heslop, H E; Holladay, M S; Richardson, S; Turner, E V; Loftin, S K; Li, C; Brenner, M K; Rooney, C M

    1995-04-01

    EBV-induced lymphoproliferative disease (EBV-LPD) is a disorder most commonly associated with the immunocompromise that follows allogeneic organ transplantation. In patients receiving T cell-depleted bone marrow from HLA-mismatched or HLA-matched unrelated donors, the incidence of EBV-LPD is particularly high, ranging from 5 to 30%. Administration of EBV-specific cytotoxic T lymphocytes may be one means of preventing and treating this disease. We now describe a method that allows the routine and timely preparation of large numbers of such cells to allow their safe administration to bone marrow transplant recipients. We also describe how these cells may be genetically marked before infusion, to determine their fate and disposition in vivo.

  17. Post-transplant hepatic complications: Imaging findings

    PubMed Central

    Drudi, F.M.; Pagliara, E.; Cantisani, V.; Arduini, F.; D'Ambrosio, U.; Alfano, G.

    2007-01-01

    Transplantation is considered definitive therapy for acute or chronic irreversible pathologies of the liver, and the increased survival rates are mainly due to improved immunosuppressive therapies and surgical techniques. However, early diagnosis of possible graft dysfunction is crucial to liver graft survival. Diagnostic imaging plays an important role in the evaluation of the liver before and after transplant and in the detection of complications such as vascular and biliary diseases, acute and chronic rejection and neoplastic recurrence. Integrated imaging using color-Doppler, CT, MRI and traditional x-ray reach a high level of sensitivity and specificity in the management of transplanted patients. PMID:23395917

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

    PubMed Central

    Agarwal, Arnav; Prasad, G V Ramesh

    2016-01-01

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

  19. Treatment options for post-transplantation diabetes mellitus.

    PubMed

    Sharif, Adnan

    2015-01-01

    Treatment options for management of post-transplantation diabetes mellitus (PTDM) are limited with regards to the availability of strong clinical evidence base. This is a concern as PTDM is common after solid organ transplantation and associated with poor clinical outcomes. PTDM and type 2 diabetes mellitus are distinct pathophysiological entities that have important differences with regards to aetiology, clinical course and management. Therefore, any clinical evidence of treatment benefit from the general population with type 2 diabetes mellitus may not be directly translated to the solid organ transplant recipient. In addition, the potential risk and benefit of using many of these therapeutic agents must take account of the complicated post-transplantation milieu of immunosuppression. While there is reasonable evidence base for treatment of diabetes mellitus in the general population, the same is not true in a post-transplantation setting. In this article the treatment options available for PTDM will be discussed, with a transplant-specific focus on the pros and cons of each particular component of the glucose lowering therapy armoury.

  20. Pediatric post-transplant metabolic syndrome: new clouds on the horizon.

    PubMed

    Nobili, Valerio; de Ville de Goyet, Jean

    2013-05-01

    Liver transplantation (LT) is a standard treatment for children with end-stage liver disease, standing at more than 90% survival rate after one yr, and at over a 70% survival rate after five yr. The majority of transplanted children enjoy an excellent quality of life but complications can occur in the long term, and can develop subclinically in otherwise well children; there are various underestimated nutritional and metabolic aspects, including the so-called post-transplant metabolic syndrome (PTMS). During the post-transplant period, the use of immunosuppressants, corticosteroids, calcineurin inhibitors, and the presence of risk factors, including non-alcoholic fatty liver disease (NAFLD), and kidney and bone complications have been largely implicated in PTMS development. Strategies to reduce the progression of PMTS should include careful screening of patients for diabetes, dyslipidemia, and obesity, and to support weight reduction with a carefully constructed program, particularly based on diet modification and exercise. With early identification and appropriate and aggressive management, excellent long-term health outcomes and acceptable graft survival can be achieved.

  1. NK-cell enteropathy: a benign NK-cell lymphoproliferative disease mimicking intestinal lymphoma: clinicopathologic features and follow-up in a unique case series.

    PubMed

    Mansoor, Adnan; Pittaluga, Stefania; Beck, Paul L; Wilson, Wyndham H; Ferry, Judith A; Jaffe, Elaine S

    2011-02-01

    Intestinal T-cell and natural killer (NK)-cell lymphomas are clinically aggressive and can be challenging to diagnose in small endoscopic biopsies. We describe 8 patients in whom atypical NK-cell lymphoproliferative lesions mimicked NK- or T-cell lymphoma. The patients (2 men; 6 women; ages 27-68 years) presented with vague gastrointestinal symptoms with lesions involving stomach, duodenum, small intestine, and colon. At endoscopy, the lesions exhibited superficial ulceration, edema, and hemorrhage. Biopsies revealed a mucosal infiltrate of atypical cells with an NK-cell phenotype (CD56(+)/TIA-1(+)/Granzyme B(+)/cCD3(+)), which displaced but did not invade the glandular epithelium. Epstein-Barr virus-encoded RNA in situ hybridization was negative, and T-cell receptor-γ gene rearrangement showed no evidence of a clonal process. Based on an original diagnosis of lymphoma, 3 patients received aggressive chemotherapy followed by autologous bone marrow transplantation in 2. Five patients were followed without treatment. However, no patient developed progressive disease or died of lymphoma (median follow-up, 30 months). Repeat endoscopies in 6 of 8 patients showed persistence or recurrence of superficial gastrointestinal lesions. This unique entity mimics intestinal and NK-/T-cell lymphomas on endoscopic biopsies and can result in erroneous diagnosis, leading to aggressive chemotherapy. We propose the term "NK-cell enteropathy" for this syndrome of as yet unknown etiology.

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

    PubMed

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

    2016-02-01

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

  3. Post-Transplant Recurrence of Hepatocellular Carcinoma and Elevated NLR

    PubMed Central

    Rustagi, Tarun

    2010-01-01

    interest in the systemic proinflammatory effects exerted by tumors. Several inflammatory markers such as C-reactive protein and neutrophil-lymphocyte ratio (NLR) have been suggested as surrogate markers of tumor biology. NLR is one such marker of inflammation that has been linked with several malignancies. NLR >5 has been shown to be a marker of survival in colorectal cancer patients. Similarly, a few studies have demonstrated the efficacy of NLR in predicting outcome in patients undergoing liver resection for HCC; however, none directly compared the incidence of elevated NLR in LT patients with and without HCC recurrence. Our study results indicate no statistical difference in incidence of elevated NLR between the two groups. We suggest that elevated NLR might not be closely correlated to recurrence of HCC post-transplant, although the small sample size might be a limiting factor. Larger studies are necessary to more definitively evaluate this relationship.

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

    PubMed

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

    2016-01-01

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

  5. Post-transplant lymphoproliferative disorders and other malignancies after pediatric intestinal transplantation: incidence, clinical features and outcome.

    PubMed

    Ramos, Esther; Hernández, Francisco; Andres, Ane; Martínez-Ojinaga, Eva; Molina, Manuel; Sarría, Jesús; Lopez-Santamaria, Manuel; Prieto, Gerardo

    2013-08-01

    PTLDs are a well-recognized and potentially fatal complication after intestinal transplantation. We analyzed the incidence, clinical features, and outcome in a 63 intestinal transplantation series performed in our unit between October 1999 and July 2011. Types of graft included ISB (n = 23), LSB (n = 20), and MV (n = 20). Patients were categorized into three groups of immunosuppression: I (n = 43) received basiliximab, tacrolimus, and steroids; II (n = 11) thymoglobulin and tacrolimus, and III (n = 9) alemtuzumab and tacrolimus. EBV status was serially assessed. All PTLD cases were biopsied to establish histopathological diagnosis. The incidence of PTLD was 14.2% (9/63). Median onset of PTLD after transplant was four months (range: 0.5-28), within first postoperative year in 6 (66.6%) patients. Fever was the most common symptom. Graft removal was needed in four patients (44%). The patient survival rate was 66.6% (6/9). We have not found any association between PTLD and immunosuppression regimen or transplant type. However, there was a statistical association with EBV active infection.

  6. Post-transplant lymphoproliferative disorders and other malignancies after pediatric intestinal transplantation: incidence, clinical features and outcome.

    PubMed

    Ramos, Esther; Hernández, Francisco; Andres, Ane; Martínez-Ojinaga, Eva; Molina, Manuel; Sarría, Jesús; Lopez-Santamaria, Manuel; Prieto, Gerardo

    2013-08-01

    PTLDs are a well-recognized and potentially fatal complication after intestinal transplantation. We analyzed the incidence, clinical features, and outcome in a 63 intestinal transplantation series performed in our unit between October 1999 and July 2011. Types of graft included ISB (n = 23), LSB (n = 20), and MV (n = 20). Patients were categorized into three groups of immunosuppression: I (n = 43) received basiliximab, tacrolimus, and steroids; II (n = 11) thymoglobulin and tacrolimus, and III (n = 9) alemtuzumab and tacrolimus. EBV status was serially assessed. All PTLD cases were biopsied to establish histopathological diagnosis. The incidence of PTLD was 14.2% (9/63). Median onset of PTLD after transplant was four months (range: 0.5-28), within first postoperative year in 6 (66.6%) patients. Fever was the most common symptom. Graft removal was needed in four patients (44%). The patient survival rate was 66.6% (6/9). We have not found any association between PTLD and immunosuppression regimen or transplant type. However, there was a statistical association with EBV active infection. PMID:23730927

  7. Reduced-intensity conditioning hematopoietic cell transplantation is an effective treatment for patients with SLAM-associated protein deficiency/X-linked lymphoproliferative disease type 1.

    PubMed

    Marsh, Rebecca A; Bleesing, Jack J; Chandrakasan, Shanmuganathan; Jordan, Michael B; Davies, Stella M; Filipovich, Alexandra H

    2014-10-01

    X-linked lymphoproliferative disease type 1 (XLP1) is a rare immune deficiency caused by mutations in SH2D1A. Allogeneic hematopoietic cell transplantation (HCT) is often performed because of the morbidity and mortality associated with XLP1. There is limited experience using reduced-intensity conditioning (RIC) regimens for these patients. Here we report our 8-year single-center experience. Sixteen consecutive patients diagnosed with XLP1 underwent allogeneic HCT between 2006 and 2013 after a RIC regimen consisting of alemtuzumab, fludarabine, and melphalan. Patient phenotypes included hemophagocytic lymphohistiocytosis (HLH) after Epstein-Barr virus (n = 5) or human herpesvirus 6 (n = 1), macrophage activation syndrome (n = 1), interstitial pneumonitis and encephalitis (n = 1), B cell lymphoma (n = 8), and hypogammaglobulinemia (n = 2). One patient was asymptomatic. Fourteen of 16 patients received 8/8 HLA-matched unrelated or related bone marrow grafts, whereas 2 patients received mismatched unrelated grafts. Acute graft-versus-host disease (GVHD) prophylaxis consisted of methylprednisolone and cyclosporine in all but 1 patient, who additionally received methotrexate. All patients had hematopoietic recovery. There were no cases of hepatic veno-occlusive disease or pulmonary hemorrhage. One patient (6%) developed acute GVHD and later also developed chronic GVHD (6%). Five patients (31%) developed mixed chimerism. Only 1 patient with mixed chimerism (6%) experienced a decline of donor chimerism to less than 50% but returned to full donor chimerism after infusion of donor lymphocytes and a CD34(+) selected stem cell boost. Infectious complications were frequent, particularly viral reactivation. One-year survival estimated by Kaplan-Meier analysis was 80%, with long-term survival estimated at 71%. Survival was similar for patients with or without a history of HLH (86% versus 75%, respectively, P = .70). There were no occurrences of lymphoma or HLH

  8. Gastrointestinal Side Effects of Post-Transplant Therapy.

    PubMed

    Lucan, Valerian Ciprian; Berardinelli, Luisa

    2016-09-01

    Modern immunosuppressive therapy has produced a real revolution in renal and organ transplantation but it comes with the price of multiple side effects. There are many gastrointestinal (GI) complications that are the consequence of transplant immunosuppressant medication. In fact, for any immunosuppressant therapy, certain standardized precepts and attitudes that aim to reduce the incidence and the impact of the medication side effects must be applied. Many patients undergo renal transplantation and the physicians have to be aware of the advantages and the risks associated. This article reviews the main GI complications that may arise as a consequence of immunosuppressive therapy after solid organ transplantation, focusing on renal and renal/pancreas transplantation, as well as the ways in which the incidence of these complications can be reduced. Management of the post-transplant therapy is mandatory in order to increase not only the grafts' and the patients' survival, but also their quality of life by the occurrence of fewer complications. PMID:27689202

  9. Chemoselection of Allogeneic HSC After Murine Neonatal Transplantation Without Myeloablation or Post-transplant Immunosuppression

    PubMed Central

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

    2012-01-01

    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 (MGMTP140K-2A-GFP-IRES-TK (MAGIT)). This vector contains P140K-O6-methylguanine-methyltransferase (MGMTP140K), HSV-thymidine kinase (TKHSV), 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 TKHSV 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 Hbbth3 heterozygous mice by correction of β-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

  10. Hepatitis C in Liver Allograft Recipients: Utility of One-Year Post-Transplantation Biopsy as an Indicator of Antiviral Therapy

    PubMed Central

    Habib, Shahid; Malik, Shahid; Fu, Bo; Chang, Joyce; Nalesnik, Michael; Humar, Abhinav; Shaikh, Obaid S.

    2015-01-01

    Background All-oral interferon-free regimens for hepatitis C viral (HCV) infection are highly efficacious; however, high cost is a barrier to applicability. Liver allograft recipients are particularly likely to benefit from therapy as HCV often leads to graft dysfunction and loss. In this study, we aimed to establish the utility of allograft biopsy at 1 year post-transplant as an indicator of treatment. Methods and Results Among 252 liver recipients enrolled, 136 (54%) developed severe disease (fibrosing cholestatic hepatitis (FCH) or fibrosis stage ≥ 2 at 1 year post-transplant). Multivariable analysis revealed younger recipient age and female gender, older donor age and T cell depletive therapy to be independent predictors of severe disease. Recipients with severe disease had higher rate of further graft loss compared to those with mild disease. Patients with mild disease and sustained virologic response (SVR) had the best survival rate, whereas those with severe disease and viremia had the worst survival (96% versus 63% at 5 years). Conclusion In conclusion, allograft biopsy at 1 year helps identify recipients at high risk of further graft dysfunction and loss. In view of high cost of therapy, treatment should be preferably directed to high-risk patients including those with FCH or fibrosis stage ≥ 2 by 1 year post-transplant.

  11. Alternative-Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Nonmalignant Disorders.

    PubMed

    Klein, Orly R; Chen, Allen R; Gamper, Christopher; Loeb, David; Zambidis, Elias; Llosa, Nicolas; Huo, Jeffrey; Dezern, Amy E; Steppan, Diana; Robey, Nancy; Holuba, Mary Jo; Cooke, Kenneth R; Symons, Heather J

    2016-05-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many nonmalignant pediatric disorders, including hemoglobinopathies, bone marrow failure syndromes, and immunodeficiencies. There is great success using HLA-matched related donors for these patients; however, the use of alternative donors has been associated with increased graft failure, graft-versus-host disease (GVHD), and transplant-related mortality (TRM). HSCT using alternative donors with post-transplantation cyclophosphamide (PT/Cy) for GVHD prophylaxis has been performed for hematologic malignancies with engraftment, GVHD, and TRM comparable with that seen with HLA-matched related donors. There are limited reports of HSCT in nonmalignant pediatric disorders other than hemoglobinopathies using alternative donors and PT/Cy. We transplanted 11 pediatric patients with life-threatening nonmalignant conditions using reduced-intensity conditioning, alternative donors, and PT/Cy alone or in combination with tacrolimus and mycophenolate mofetil. We observed limited GVHD, no TRM, and successful engraftment sufficient to eliminate manifestations of disease in all patients. Allogeneic HSCT using alternative donors and PT/Cy shows promise for curing nonmalignant disorders; development of prospective clinical trials to confirm these observations is warranted. PMID:26860634

  12. Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical BMT

    PubMed Central

    Luznik, Leo; O’Donnell, Paul V.; Ephraim, J. Fuchs

    2013-01-01

    Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potentially curative therapy for many hematologic and immunologic diseases. Further, partial or full donor hematopoietic chimerism following alloSCT may be sufficient to guarantee immunologic tolerance to solid organs from the same donor, obviating any requirement for prolonged pharmacologic immunosuppression. Despite alloSCT’s potential, the procedure is beset by two major limitations. The first relates to the procedure’s toxicity including conditioning regimen toxicity, graft-versus-host disease (GVHD), and infection. The second limitation is the lack of histocompatible donors. A human leukocyte antigen (HLA)-matched sibling or unrelated donor cannot be identified expeditiously for up to 40% of patients. Historically, alloSCT from partially HLA-mismatched or HLA-haploidentical relatives has been complicated by unacceptably high incidences of graft rejection, severe GVHD, and non-relapse mortality. Recently, our groups have developed a method to selectively deplete alloreactive cells in vivo by administering high doses of cyclophosphamide in a narrow window after transplantation. Using high-dose, post-transplantation cyclophosphamide (PT/Cy), crossing the HLA barrier in alloSCT is now feasible and donors can be found for nearly all patients. This review discusses the history of HLA-haploidentical SCT, recent clinical results and immunologic mechanisms of action of high-dose PT/Cy for prevention of graft rejection and GVHD. PMID:23206845

  13. Early post-transplant neopterin associated with one year survival and bacteremia in liver transplant recipients.

    PubMed

    Oweira, Hani; Lahdou, Imad; Daniel, Volker; Hofer, Stefan; Mieth, Markus; Schmidt, Jan; Schemmer, Peter; Opelz, Gerhard; Mehrabi, Arianeb; Sadeghi, Mahmoud

    2016-01-01

    Bacterial infections are the most common complications, and the major cause of mortality after liver transplantation (Tx). Neopterin, a marker of immune activation, is produced in monocyte/macrophages in response to inflammation. The aim of our study was to investigate whether early post-operation serum levels of neopterin were associated with post-transplant bacteremia and mortality in liver transplant recipients. We studied 162 of 262 liver Tx patients between January 2008 and February 2011 of whom pre- and early post-Tx sera samples were available. Pre- and early post-operative risk factors of infection and mortality were evaluated in 45 bacteremic patients and 117 non-bacteremic patients. During one-year follow-up, 28 of 262 patients died because of graft failure, septicemia and other diseases. Post-Tx serum neopterin on day 10 (p<0.001) were significantly higher in bacteriemic patients than in patients without bacteremia. Logistic regression analyses showed that day 10 post-Tx neopterin serum level ⩾40 nmol/l has a predictive value (OR=6.86: p<0.001) for bacteremia and mortality (OR=3.47: p=0.021). Our results suggest that early post-Tx neopterin serum levels are very sensitive predictive markers of one-year post-Tx bacteremia and mortality in liver Tx recipients.

  14. Post-transplant monitoring of chimerism by lineage-specific analysis.

    PubMed

    Preuner, Sandra; Lion, Thomas

    2014-01-01

    Molecular surveillance of hematopoietic chimerism is an important part of the routine diagnostic program in patients after allogeneic stem cell transplantation. Chimerism testing permits early prediction and documentation of successful engraftment and facilitates early risk assessment of impending graft rejection. In patients transplanted for treatment of malignant hematologic disorders, monitoring of chimerism can provide an early indication of incipient disease relapse. The investigation of chimerism has therefore become an indispensable tool for the management of patients during the post-transplant period. Increasing use of reduced-intensity conditioning, which is associated with prolonged duration of mixed hematopoietic chimerism, has further increased the clinical importance of chimerism analysis. At present, the most commonly used technical approach to the investigation of chimerism is microsatellite analysis by polymerase chain reaction. The investigation of chimerism within specific leukocyte subsets isolated from peripheral blood or bone marrow samples by flow sorting- or magnetic bead-based techniques provides more specific information on processes underlying the dynamics of donor/recipient chimerism. Moreover, cell subset-specific analysis permits the assessment of impending complications at a significantly higher sensitivity, thus providing a basis for earlier treatment decisions.

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

    PubMed

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

    2014-07-01

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

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

    PubMed Central

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

    2014-01-01

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

  17. Clinical Significance of Pre- and Post-Transplant BAFF Levels in Kidney Transplant Recipients

    PubMed Central

    Min, Ji Won; Kim, Kyoung Woon; Kim, Bo-Mi; Doh, Kyoung Chan; Choi, Min Seok; Choi, Bum Soon; Park, Cheol Whee; Yang, Chul Woo; Kim, Yong-Soo

    2016-01-01

    It is well known that pre-transplant B cell activating factor (BAFF) levels are associated with the development of de novo anti-HLA antibodies and antibody mediated rejection post-transplant. However, the clinical significance of BAFF values at allograft rejection has not been determined. In this study, we investigated the clinical significance of pre-transplant BAFF level as well as post-transplant BAFF levels measured when indication biopsy was done. We checked for anti-HLA antibodies in 115 kidney transplant recipients who required allograft biopsy due to an increase in serum creatinine. With the same serum specimen, we measured BAFF levels, and in 78 of these patients, pre-transplant BAFF and anti-HLA antibody levels were detected as well. Patients in each group were divided into tertiles according to BAFF levels. We investigated the relationship between BAFF levels and the occurrence of anti-HLA antibodies. Pre-transplant BAFF levels showed significant association with pre-transplant sensitization, and also with early rejection (Tertile 3, 26.9% vs. Tertile 1, 11.5%; P<0.05). Post-transplant BAFF levels showed significant association with pre-transplant sensitization, but did not show association with anti-HLA antibodies and positive donor-specific antibodies at the time of biopsy. We did not find any association between post-transplant BAFF levels and allograft biopsy results, Banff scores and microvascular inflammation scores. In conclusion, pre-transplant BAFF levels are associated with pre-transplant sensitization and are useful in predicting allograft rejection. But post-transplant BAFF levels measured at the time of indication biopsy are not associated with the appearance of de novo HLA-DSA, allograft rejection, biopsy findings and other allograft outcomes. PMID:27631619

  18. Clinical Significance of Pre- and Post-Transplant BAFF Levels in Kidney Transplant Recipients.

    PubMed

    Min, Ji Won; Kim, Kyoung Woon; Kim, Bo-Mi; Doh, Kyoung Chan; Choi, Min Seok; Choi, Bum Soon; Park, Cheol Whee; Yang, Chul Woo; Kim, Yong-Soo; Oh, Eun-Jee; Chung, Byung Ha

    2016-01-01

    It is well known that pre-transplant B cell activating factor (BAFF) levels are associated with the development of de novo anti-HLA antibodies and antibody mediated rejection post-transplant. However, the clinical significance of BAFF values at allograft rejection has not been determined. In this study, we investigated the clinical significance of pre-transplant BAFF level as well as post-transplant BAFF levels measured when indication biopsy was done. We checked for anti-HLA antibodies in 115 kidney transplant recipients who required allograft biopsy due to an increase in serum creatinine. With the same serum specimen, we measured BAFF levels, and in 78 of these patients, pre-transplant BAFF and anti-HLA antibody levels were detected as well. Patients in each group were divided into tertiles according to BAFF levels. We investigated the relationship between BAFF levels and the occurrence of anti-HLA antibodies. Pre-transplant BAFF levels showed significant association with pre-transplant sensitization, and also with early rejection (Tertile 3, 26.9% vs. Tertile 1, 11.5%; P<0.05). Post-transplant BAFF levels showed significant association with pre-transplant sensitization, but did not show association with anti-HLA antibodies and positive donor-specific antibodies at the time of biopsy. We did not find any association between post-transplant BAFF levels and allograft biopsy results, Banff scores and microvascular inflammation scores. In conclusion, pre-transplant BAFF levels are associated with pre-transplant sensitization and are useful in predicting allograft rejection. But post-transplant BAFF levels measured at the time of indication biopsy are not associated with the appearance of de novo HLA-DSA, allograft rejection, biopsy findings and other allograft outcomes. PMID:27631619

  19. Posttransplant lymphoproliferative disorders following liver transplantation: Where are we now?

    PubMed Central

    Dierickx, Daan; Cardinaels, Nina

    2015-01-01

    Liver transplantation has emerged as a life-saving treatment for several patients with acute liver failure, end stage liver disease and primary hepatic malignancies. However, long term immunosuppressive therapy aiming to reduce the risk of transplant rejection increases the incidence of several complications including malignancies. This is illustrated by the observation of a high ratio between observed and expected cases of lymphoproliferative disorders following liver transplantation. Despite a huge heterogeneity in morphological appearance of these disorders ranging from reactive-like lesions to real lymphomas, they are collectively termed posttransplant lymphoproliferative disorders. In this review we will provide an overview of this rare but challenging disorder as a complication of liver transplantation. PMID:26494960

  20. Timed Sequential Busulfan and Post Transplant Cyclophosphamide for Allogeneic Transplantation

    ClinicalTrials.gov

    2016-09-08

    Other Diseases of Blood and Blood-forming Organs; Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Chronic Myeloid Leukemia; Chronic Lymphocytic Leukemia; Myelodysplastic Syndrome; Myeloproliferative Syndrome; Non-Hodgkins Lymphoma; Hodgkins Lymphoma; Multiple Myeloma

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

    PubMed Central

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

    1988-01-01

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

  2. FGF23 is associated with early post-transplant hypophosphataemia and normalizes faster than iPTH in living donor renal transplant recipients: a longitudinal follow-up study

    PubMed Central

    Prasad, Narayan; Jaiswal, Akhilesh; Agarwal, Vikas; Kumar, Shashi; Chaturvedi, Saurabh; Yadav, Subhash; Gupta, Amit; Sharma, Raj K.; Bhadauria, Dharmendra; Kaul, Anupama

    2016-01-01

    Background We aimed to longitudinally analyse changes in the levels of serum fibroblast growth factor 23 (FGF23), intact parathyroid hormone (iPTH) and associated minerals in patients undergoing renal transplantation. Methods Sixty-three patients with end-stage renal disease (ESRD) who underwent living donor transplantation were recruited. Serum FGF23, iPTH, uric acid, inorganic phosphorous (iP), blood urea nitrogen and serum creatinine were measured pre-transplant and at 1 (M1), 3 (M3) and 12 months (M12) post-transplantation. Results FGF23 levels were decreased at M1, M3 and M12 by 93.81, 96.74 and 97.53%, respectively. iPTH levels were decreased by 67.95, 74.95 and 84.9%, respectively. The prevalence of hyperparathyroidism at M1, M3 and M12 post-transplantation was 63.5, 42.9 and 11.1%, respectively. FGF23 and iP levels remained above the normal range in 23 (36.5%) and 17 (27%) patients at M1, 10 (15.9%) and 5 (8%) at M3 and in none at M12 post-transplantation, respectively. A multivariate regression model revealed that, pre-transplant, iP was positively associated with iPTH (P = 0.016) but not with FGF 23; however, post-transplant, iP level was negatively associated with FGF23 (P < 0.001) but not with iPTH. Conclusions Post-transplant FGF23 levels settle faster than those of iPTH. However, 11% of patients continued to have hyperparathyroidism even after 12 months. PMID:27679713

  3. FGF23 is associated with early post-transplant hypophosphataemia and normalizes faster than iPTH in living donor renal transplant recipients: a longitudinal follow-up study

    PubMed Central

    Prasad, Narayan; Jaiswal, Akhilesh; Agarwal, Vikas; Kumar, Shashi; Chaturvedi, Saurabh; Yadav, Subhash; Gupta, Amit; Sharma, Raj K.; Bhadauria, Dharmendra; Kaul, Anupama

    2016-01-01

    Background We aimed to longitudinally analyse changes in the levels of serum fibroblast growth factor 23 (FGF23), intact parathyroid hormone (iPTH) and associated minerals in patients undergoing renal transplantation. Methods Sixty-three patients with end-stage renal disease (ESRD) who underwent living donor transplantation were recruited. Serum FGF23, iPTH, uric acid, inorganic phosphorous (iP), blood urea nitrogen and serum creatinine were measured pre-transplant and at 1 (M1), 3 (M3) and 12 months (M12) post-transplantation. Results FGF23 levels were decreased at M1, M3 and M12 by 93.81, 96.74 and 97.53%, respectively. iPTH levels were decreased by 67.95, 74.95 and 84.9%, respectively. The prevalence of hyperparathyroidism at M1, M3 and M12 post-transplantation was 63.5, 42.9 and 11.1%, respectively. FGF23 and iP levels remained above the normal range in 23 (36.5%) and 17 (27%) patients at M1, 10 (15.9%) and 5 (8%) at M3 and in none at M12 post-transplantation, respectively. A multivariate regression model revealed that, pre-transplant, iP was positively associated with iPTH (P = 0.016) but not with FGF 23; however, post-transplant, iP level was negatively associated with FGF23 (P < 0.001) but not with iPTH. Conclusions Post-transplant FGF23 levels settle faster than those of iPTH. However, 11% of patients continued to have hyperparathyroidism even after 12 months.

  4. New concepts and best practices for management of pre- and post-transplantation cancer.

    PubMed

    Campistol, Josep M; Cuervas-Mons, Valentín; Manito, Nicolás; Almenar, Luis; Arias, Manuel; Casafont, Fernando; Del Castillo, Domingo; Crespo-Leiro, María G; Delgado, Juan F; Herrero, J Ignacio; Jara, Paloma; Morales, José M; Navarro, Mercedes; Oppenheimer, Federico; Prieto, Martín; Pulpón, Luis A; Rimola, Antoni; Román, Antonio; Serón, Daniel; Ussetti, Piedad

    2012-10-01

    Solid-organ transplant recipients are at increased risk of developing cancer compared with the general population. Tumours can arise de novo, as a recurrence of a preexisting malignancy, or from the donated organ. The ATOS (Aula sobre Trasplantes de Órganos Sólidos; the Solid-Organ Transplantation Working Group) group, integrated by Spanish transplant experts, meets annually to discuss current advances in the field. In 2011, the 11th edition covered a range of new topics on cancer and transplantation. In this review we have highlighted the new concepts and best practices for managing cancer in the pre-transplant and post-transplant settings that were presented at the ATOS meeting. Immunosuppression plays a major role in oncogenesis in the transplant recipient, both through impaired immunosurveillance and through direct oncogenic activity. It is possible to transplant organs obtained from donors with a history of cancer as long as an effective minimization of malignancy transmission strategy is followed. Tumour-specific wait-periods have been proposed for the increased number of transplantation candidates with a history of malignancy; however, the patient's individual risk of death from organ failure must be taken into consideration. It is important to actively prevent tumour recurrence, especially the recurrence of hepatocellular carcinoma in liver transplant recipients. To effectively manage post-transplant malignancies, it is essential to proactively monitor patients, with long-term intensive screening programs showing a reduced incidence of cancer post-transplantation. Proposed management strategies for post-transplantation malignancies include viral monitoring and prophylaxis to decrease infection-related cancer, immunosuppression modulation with lower doses of calcineurin inhibitors, and addition of or conversion to inhibitors of the mammalian target of rapamycin.

  5. Associations of Pre-Transplant Serum Albumin with Post-Transplant Outcomes in Kidney Transplant Recipients

    PubMed Central

    Molnar, Miklos Z; Kovesdy, Csaba P; Bunnapradist, Suphamai; Streja, Elani; Mehrotra, Rajnish; Krishnan, Mahesh; Nissenson, Allen R; Kalantar-Zadeh, Kamyar

    2011-01-01

    The association between pre-transplant serum albumin concentration and post-transplant outcomes in kidney transplant recipients is unclear. We hypothesized that in transplant-waitlisted hemodialysis patients, lower serum albumin concentrations are associated with worse post-transplant outcomes. Linking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 8961 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (Odds ratio [OR]), respectively. Patients were 48±13 years old and included 37% women and 27% diabetics. The higher pre-transplant serum albumin was associated with lower mortality, graft failure and DGF risk even after multivariate adjustment for case-mix, malnutrition-inflammation complex and transplant related variable. Every 0.2 g/dL higher pre-transplant serum albumin concentration was associated with 13% lower all-cause mortality (HR=0.87 [95% confidence interval: 0.82-0.93]), 17% lower cardiovascular mortality (HR=0.83[0.74-0.93]), 7% lower combined risk of death or graft failure (HR=0.93[0.89-0.97]), and 4% lower DGF risk (OR=0.96[0.93-0.99]). Hence, lower pre-transplant serum albumin level is associated with worse post-transplant outcomes. Clinical trials to examine interventions to improve nutritional status in transplant-wait-listed hemodialysis patients and their impacts on post-transplant outcomes are indicated. PMID:21449945

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

    PubMed

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

    2016-03-01

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

  7. Post-Transplant Outcomes in High-Risk Compared with Non-High-Risk Multiple Myeloma: A CIBMTR Analysis.

    PubMed

    Scott, Emma C; Hari, Parameswaran; Sharma, Manish; Le-Rademacher, Jennifer; Huang, Jiaxing; Vogl, Dan; Abidi, Muneer; Beitinjaneh, Amer; Fung, Henry; Ganguly, Siddhartha; Hildebrandt, Gerhard; Holmberg, Leona; Kalaycio, Matt; Kumar, Shaji; Kyle, Robert; Lazarus, Hillard; Lee, Cindy; Maziarz, Richard T; Meehan, Kenneth; Mikhael, Joseph; Nishihori, Taiga; Ramanathan, Muthalagu; Usmani, Saad; Tay, Jason; Vesole, David; Wirk, Baldeep; Yared, Jean; Savani, Bipin N; Gasparetto, Cristina; Krishnan, Amrita; Mark, Tomer; Nieto, Yago; D'Souza, Anita

    2016-10-01

    Conventional cytogenetics and interphase fluorescence in situ hybridization (FISH) identify high-risk multiple myeloma (HRM) populations characterized by poor outcomes. We analyzed these differences among HRM versus non-HRM populations after upfront autologous hematopoietic cell transplantation (autoHCT). Between 2008 and 2012, 715 patients with multiple myeloma identified by FISH and/or cytogenetic data with upfront autoHCT were identified in the Center for International Blood and Marrow Transplant Research database. HRM was defined as del17p, t(4;14), t(14;16), hypodiploidy (<45 chromosomes excluding -Y) or chromosome 1 p and 1q abnormalities; all others were non-HRM. Among 125 HRM patients (17.5%), induction with bortezomib and immunomodulatory agents (imids) was higher compared with non-HRM (56% versus 43%, P < .001) with similar pretransplant complete response (CR) rates (14% versus 16%, P .1). At day 100 post-transplant, at least a very good partial response was 59% in HRM and 61% in non-HRM (P = .6). More HRM patients received post-transplant therapy with bortezomib and imids (26% versus 12%, P = .004). Three-year post-transplant progression-free (PFS) and overall survival (OS) rates in HRM versus non-HRM were 37% versus 49% (P < .001) and 72% versus 85% (P < .001), respectively. At 3 years, PFS for HRM patients with and without post-transplant therapy was 46% (95% confidence interval [CI], 33 to 59) versus 14% (95% CI, 4 to 29) and in non-HRM patients with and without post-transplant therapy 55% (95% CI, 49 to 62) versus 39% (95% CI, 32 to 47); rates of OS for HRM patients with and without post-transplant therapy were 81% (95% CI, 70 to 90) versus 48% (95% CI, 30 to 65) compared with 88% (95% CI, 84 to 92) and 79% (95% CI, 73 to 85) in non-HRM patients with and without post-transplant therapy, respectively. Among patients receiving post-transplant therapy, there was no difference in OS between HRM and non-HRM (P = .08). In addition to

  8. Post-Transplant Outcomes in High-Risk Compared with Non-High-Risk Multiple Myeloma: A CIBMTR Analysis.

    PubMed

    Scott, Emma C; Hari, Parameswaran; Sharma, Manish; Le-Rademacher, Jennifer; Huang, Jiaxing; Vogl, Dan; Abidi, Muneer; Beitinjaneh, Amer; Fung, Henry; Ganguly, Siddhartha; Hildebrandt, Gerhard; Holmberg, Leona; Kalaycio, Matt; Kumar, Shaji; Kyle, Robert; Lazarus, Hillard; Lee, Cindy; Maziarz, Richard T; Meehan, Kenneth; Mikhael, Joseph; Nishihori, Taiga; Ramanathan, Muthalagu; Usmani, Saad; Tay, Jason; Vesole, David; Wirk, Baldeep; Yared, Jean; Savani, Bipin N; Gasparetto, Cristina; Krishnan, Amrita; Mark, Tomer; Nieto, Yago; D'Souza, Anita

    2016-10-01

    Conventional cytogenetics and interphase fluorescence in situ hybridization (FISH) identify high-risk multiple myeloma (HRM) populations characterized by poor outcomes. We analyzed these differences among HRM versus non-HRM populations after upfront autologous hematopoietic cell transplantation (autoHCT). Between 2008 and 2012, 715 patients with multiple myeloma identified by FISH and/or cytogenetic data with upfront autoHCT were identified in the Center for International Blood and Marrow Transplant Research database. HRM was defined as del17p, t(4;14), t(14;16), hypodiploidy (<45 chromosomes excluding -Y) or chromosome 1 p and 1q abnormalities; all others were non-HRM. Among 125 HRM patients (17.5%), induction with bortezomib and immunomodulatory agents (imids) was higher compared with non-HRM (56% versus 43%, P < .001) with similar pretransplant complete response (CR) rates (14% versus 16%, P .1). At day 100 post-transplant, at least a very good partial response was 59% in HRM and 61% in non-HRM (P = .6). More HRM patients received post-transplant therapy with bortezomib and imids (26% versus 12%, P = .004). Three-year post-transplant progression-free (PFS) and overall survival (OS) rates in HRM versus non-HRM were 37% versus 49% (P < .001) and 72% versus 85% (P < .001), respectively. At 3 years, PFS for HRM patients with and without post-transplant therapy was 46% (95% confidence interval [CI], 33 to 59) versus 14% (95% CI, 4 to 29) and in non-HRM patients with and without post-transplant therapy 55% (95% CI, 49 to 62) versus 39% (95% CI, 32 to 47); rates of OS for HRM patients with and without post-transplant therapy were 81% (95% CI, 70 to 90) versus 48% (95% CI, 30 to 65) compared with 88% (95% CI, 84 to 92) and 79% (95% CI, 73 to 85) in non-HRM patients with and without post-transplant therapy, respectively. Among patients receiving post-transplant therapy, there was no difference in OS between HRM and non-HRM (P = .08). In addition to

  9. What is the impact of immunosuppressive treatment on the post-transplant renal osteopathy?

    PubMed

    Blaslov, Kristina; Katalinic, Lea; Kes, Petar; Spasovski, Goce; Smalcelj, Ruzica; Basic-Jukic, Nikolina

    2014-05-01

    Although glucocorticoid therapy is considered to be the main pathogenic factor, a consistent body of evidence suggests that other immunosuppressants might also play an important role in the development of the post-transplant renal osteopathy (PRO) through their pleiotropic pharmacological effects. Glucocorticoids seem to induce osteoclasts' activity suppressing the osteoblasts while data regarding other immunosuppressive drugs are still controversial. Mycophenolate mofetil and azathioprine appear to be neutral regarding the bone metabolism. However, the study analyzing any independent effect of antimetabolites on bone turnover has not been conducted yet. Calcineurin inhibitors (CNIs) induce trabecular bone loss in rodent, with contradictory results in renal transplant recipients. Suppression of vitamin D receptor is probably the underlying mechanism of renal calcium wasting in renal transplant recipients receiving CNI. In spite of an increased 1,25(OH)2 vitamin D level, the kidney is not able to reserve calcium, suggesting a role of vitamin D resistance that may be related to bone loss. More efforts should be invested to determine the role of CNI in PRO. In particular, data regarding the role of mammalian target of rapamycin inhibitors (mTORi), such as sirolimus and everolimus, in the PRO development are still controversial. Rapamycin markedly decreases bone longitudinal growth as well as callus formation in experimental models, but also lowers the rate of bone resorption markers and glomerular filtration in clinical studies. Everolimus potently inhibits primary mouse and human osteoclast activity as well as the osteoclast differentiation. It also prevents the ovariectomy-induced loss of cancellous bone by 60 %, an effect predominantly associated with a decreased osteoclast-mediated bone resorption, resulting in a partial preservation of the cancellous bone. At present, there is no clinical study analyzing the effect of everolimus on bone turnover in renal

  10. VITA-D: Cholecalciferol substitution in vitamin D deficient kidney transplant recipients: A randomized, placebo-controlled study to evaluate the post-transplant outcome

    PubMed Central

    Thiem, Ursula; Heinze, Georg; Segel, Rudolf; Perkmann, Thomas; Kainberger, Franz; Mühlbacher, Ferdinand; Hörl, Walter; Borchhardt, Kyra

    2009-01-01

    Background Vitamin D does not only regulate calcium homeostasis but also plays an important role as an immune modulator. It influences the immune system through the induction of immune shifts and regulatory cells resulting in immunologic tolerance. As such, vitamin D is thought to exert beneficial effects within the transplant setting, especially in kidney transplant recipients, considering the high prevalence of vitamin D deficiency in kidney transplant recipients. Methods/Design The VITA-D study, a randomized, placebo-controlled, double-blind study with two parallel groups including a total of 200 kidney transplant recipients, is designed to investigate the immunomodulatory and renoprotective effects of cholecalciferol (vitamin D3) within the transplant setting. Kidney transplant recipients found to have vitamin D deficiency defined as 25-hydroxyvitamin D3 < 50 nmol per liter will be randomly assigned to receive either oral cholecalciferol therapy or placebo and will be followed for one year. Cholecalciferol will be administered at a dose of 6800 International Units daily over a time period of one year. The objective is to evaluate the influence of vitamin D3 substitution in vitamin D deficient kidney transplant recipients on the post-transplant outcome. As a primary endpoint glomerular filtration rate calculated with the MDRD formula (modification of diet in renal disease) one year after kidney transplantation will be evaluated. Incidence of acute rejection episodes, and the number and severity of infections (analyzed by means of C-reactive protein) within the first year after transplantation will be monitored as well. As a secondary endpoint the influence of vitamin D3 on bone mineral density within the first year post-transplant will be assessed. Three DXA analyses will be performed, one within the first four weeks post-transplant, one five months and one twelve months after kidney transplantation. Trial Registration ClinicalTrials.gov NCT00752401 PMID

  11. Therapeutic drug monitoring for either oral or intravenous busulfan when combined with pre- and post-transplantation cyclophosphamide.

    PubMed

    Lombardi, Lindsey R; Kanakry, Christopher G; Zahurak, Marianna; Durakovic, Nadira; Bolaños-Meade, Javier; Kasamon, Yvette L; Gladstone, Douglas E; Matsui, William; Borrello, Ivan; Huff, Carol Ann; Swinnen, Lode J; Brodsky, Robert A; Ambinder, Richard F; Fuchs, Ephraim J; Rosner, Gary L; Jones, Richard J; Luznik, Leo

    2016-01-01

    Busulfan (Bu)/cyclophosphamide (Cy) is a standard conditioning platform for allogeneic transplantation. We developed a strategy separating the Cy into two pre/post-transplantation doses (PTCy), providing myeloablative conditioning and single-agent graft-versus-host disease (GVHD) prophylaxis. We investigated the impact of Bu route on treatment-related toxicity for 131 consecutive adult patients. Busulfan was administered in four daily divided doses either orally (n = 72) or intravenously (n = 59) with pharmacokinetics on the first-dose and as necessary on subsequent doses to achieve a target area-under-the-concentration-curve (AUC) of 800-1400 μmol*min/L per dose. BuCy/PTCy with pharmacokinetics is well-tolerated with low treatment-related toxicity. Hepatic veno-occlusive disease incidence was 6% with two fatal events. Bu administration route in the context of BuCy/PTCy did not statistically impact hepatotoxicity, GVHD, relapse, disease-free survival, or overall survival. The BuCy/PTCy platform has a low incidence of treatment-related toxicity, including hepatotoxicity, in hematologic malignancies when using pharmacokinetics for a target AUC of 800-1400 μmol*min/L, irrespective of Bu administration route.

  12. Myoglobinuria masquerading as acute rejection in a renal allograft recipient with recurrent post transplant diabetic nephropathy.

    PubMed

    Gupta, Pallav; Sharma, Amit; Khullar, Dinesh

    2014-08-01

    Rhabdomyolysis contributes to 7-10% of total AKI cases. Myoglobinuria as a cause of acute renal allograft dysfunction is extremely uncommon. Renal allograft recipient on cyclosporine or tacrolimus can develop myoglobinuria in presence of other precipitating factors. Present case describes an interesting report of myoglobinuria in a patient with post transplant diabetic nephropathy mimicking acute graft rejection. Clinically myoglobinuria presenting as renal allograft dysfunction is diagnosis of exclusion and renal biopsy is extremely important in making a correct diagnosis and planning optimal management in such cases.

  13. Updated Understanding of Autoimmune Lymphoproliferative Syndrome (ALPS).

    PubMed

    Li, Pu; Huang, Ping; Yang, Ye; Hao, Mu; Peng, Hongwei; Li, Fei

    2016-02-01

    Autoimmune lymphoproliferative syndrome (ALPS), a disorder characterized by immune dysregulation due to disrupted lymphocyte homeostasis, is mainly resulted from the mutations in FAS-mediated apoptotic pathway. In addition, other mutations of the genes such as Fas-ligand (FASLG), Caspase 10 (CASP10) and Caspase 8 (CASP8), NRAS and KRAS have also been observed in a small number of patients with ALPS or ALPS-related disorders. However, approximately 20-30% of patients with ALPS have unidentified defect. Its clinical manifestations observed in multiple family members include unexplained lymphadenopathy, hepatosplenomegaly, autoimmune cytopenias such as thrombocytopenia, neutropenia, and anemia due to excessive production of antibodies by lymphocytes, elevated number of double-negative T (DNT) cells, and increased risk of lymphoma. As a very rare disease, ALPS was first characterized in the early 1990s. More than 300 families with hereditary ALPS have been reported till now; nearly 500 patients from these families have been studied and followed worldwide over the last 20 years. ALPS has historically considered as a primary immune defect presenting in early childhood, however, recent studies have shown that it may be more common than previous thought because adult onset presentation is increasingly becoming recognized and more adult ALPS patients are diagnosed. The new genetic and biological insights have improved the understanding of ALPS and a number of targeted therapeutic strategies such as mycophenolate mofetil, sirolimus, and pentostatin have been successfully applied in ALPS patients with promising treatment efficacy. This article comprehensively reviews the clinical and laboratory manifestations, new research advances in the molecular pathogenesis, diagnosis and treatments of this disorder.

  14. Donor Monoclonal Gammopathy May Cause Lymphoproliferative Disorders in Solid Organ Transplant Recipients.

    PubMed

    Felldin, M; Ekberg, J; Polanska-Tamborek, D; Hansson, U; Sender, M; Rizell, M; Svanvik, J; Mölne, J

    2016-09-01

    Prior research on donor monoclonal gammopathy of undetermined significance (MGUS) has been inadequate regarding the risk for lymphoproliferative disease in solid organ transplantation recipients. Seven organ recipients from two different donors developed lymphoproliferative disease. The origin of the malignancy was determined by use of microsatellite analysis, and the plasma of the two donors was analyzed with the use of electrophoresis. The clinical courses of the seven recipients were followed for 36-60 months. One donor transmitted lymphoplasmacytic lymphoma to two kidney recipients and MGUS to a liver recipient, all IgMκ. A second donor caused IgGλ myeloma in two kidney and one liver recipient, and IgGλ gammopathy in a heart recipient. Transplant nephrectomy was performed in three kidney recipients and remission was achieved. The fourth kidney recipient has kept the graft and the disease has progressed. The liver recipient died from myeloma. There were no clinical signs of lymphoproliferative disease in the donors, but retrospective serum analyses showed M-components, IgMκ (37 g/L) and IgGλ (8 g/L). Donors with MGUS may cause donor-transmitted malignancies via passenger lymphocytes/plasma cells in solid organ recipients. The results call for a large register study of the incidence of donor MGUS and lymphoproliferative disease in their recipients. PMID:27575725

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

    PubMed

    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

    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.

  16. X-Linked Lymphoproliferative Disease (XLP)

    MedlinePlus

    ... Patients Procedure for Accessing Lab Services Data Package Requirements AIDS Therapies Resource Guide In Vitro Efficacy Evaluations ... Assurances to Users Application and Approval Process User Requirements Malaria Vaccine Production Services Data Sharing and Release ...

  17. Post-transplantation diabetes mellitus; frequency and related risk factors: a single center study.

    PubMed

    Ghafari, Ali; PourAli, Reza; Sepehrvand, Nariman; Hatami, Sanaz; Modarres, Vanooshe

    2010-09-01

    Post-transplantation diabetes mellitus (PTDM) is a serious complication after organ transplantation, which could lead to cardiovascular morbidity and mortality. The rate of PTDM increased in recent years, probably due to new immunosuppressive drugs such as Tacrolimus. In this study, we retrospectively evaluated the frequency of PTDM and related risk factors in 644 non diabetic patients who underwent renal transplantation. Data was analyzed by chi-square and Fisher's exact test in SPSS software ver11.5. Among 644 patients PTDM developed in 10.2% similar to literature. PTDM was significantly correlated to age (P value = 0.000), positive familial history (P= 0.003) and HBV infection (P= 0.046). In conclusion, PTDM is not uncommon in Iranian patients and a positive family history of diabetes, HBV infection and older age increases the likelihood to develop PTDM. PMID:20814117

  18. How do I manage hyperglycemia/post-transplant diabetes mellitus after allogeneic HSCT.

    PubMed

    Fuji, S; Rovó, A; Ohashi, K; Griffith, M; Einsele, H; Kapp, M; Mohty, M; Majhail, N S; Engelhardt, B G; Tichelli, A; Savani, B N

    2016-08-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients frequently develop glucose intolerance and post-transplant diabetes mellitus (PTDM). The clinical importance of PTDM and its detrimental impact on HSCT outcomes are under-recognized. After allo-HSCT, various mechanisms can contribute to the development of PTDM. Here we review information about hyperglycemia and PTDM after allo-HSCT as well as PTDM after solid organ transplantation and describe ways to manage hyperglycemia/PTDM after allogeneic HSCT. Taking into consideration a lack of well-established evidence in the field of allo-HSCT, more studies should be conducted in the future, which will require closer multidisciplinary collaboration between hematologists, endocrinologists and nutritionists. PMID:27042848

  19. Post-transplantation diabetes mellitus; frequency and related risk factors: a single center study.

    PubMed

    Ghafari, Ali; PourAli, Reza; Sepehrvand, Nariman; Hatami, Sanaz; Modarres, Vanooshe

    2010-09-01

    Post-transplantation diabetes mellitus (PTDM) is a serious complication after organ transplantation, which could lead to cardiovascular morbidity and mortality. The rate of PTDM increased in recent years, probably due to new immunosuppressive drugs such as Tacrolimus. In this study, we retrospectively evaluated the frequency of PTDM and related risk factors in 644 non diabetic patients who underwent renal transplantation. Data was analyzed by chi-square and Fisher's exact test in SPSS software ver11.5. Among 644 patients PTDM developed in 10.2% similar to literature. PTDM was significantly correlated to age (P value = 0.000), positive familial history (P= 0.003) and HBV infection (P= 0.046). In conclusion, PTDM is not uncommon in Iranian patients and a positive family history of diabetes, HBV infection and older age increases the likelihood to develop PTDM.

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

    PubMed

    Shivaswamy, Vijay; Boerner, Brian; Larsen, Jennifer

    2016-02-01

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

  1. Augmenting the post-transplantation growth and survivorship of juvenile scleractinian corals via nutritional enhancement.

    PubMed

    Toh, Tai Chong; Ng, Chin Soon Lionel; Peh, Jia Wei Kassler; Toh, Kok Ben; Chou, Loke Ming

    2014-01-01

    Size-dependent mortality influences the recolonization success of juvenile corals transplanted for reef restoration and assisting juvenile corals attain a refuge size would thus improve post-transplantation survivorship. To explore colony size augmentation strategies, recruits of the scleractinian coral Pocillopora damicornis were fed with live Artemia salina nauplii twice a week for 24 weeks in an ex situ coral nursery. Fed recruits grew significantly faster than unfed ones, with corals in the 3600, 1800, 600 and 0 (control) nauplii/L groups exhibiting volumetric growth rates of 10.65 ± 1.46, 4.69 ± 0.9, 3.64 ± 0.55 and 1.18 ± 0.37 mm3/week, respectively. Corals supplied with the highest density of nauplii increased their ecological volume by more than 74 times their initial size, achieving a mean final volume of 248.38 ± 33.44 mm3. The benefits of feeding were apparent even after transplantation to the reef. The corals in the 3600, 1800, 600 and 0 nauplii/L groups grew to final sizes of 4875 ± 260 mm3, 2036 ± 627 mm3, 1066 ± 70 mm3 and 512 ± 116 mm3, respectively. The fed corals had significantly higher survival rates than the unfed ones after transplantation (63%, 59%, 56% and 38% for the 3600, 1800, 600 and 0 nauplii/L treatments respectively). Additionally, cost-effectiveness analysis revealed that the costs per unit volumetric growth were drastically reduced with increasing feed densities. Corals fed with the highest density of nauplii were the most cost-effective (US$0.02/mm3), and were more than 12 times cheaper than the controls. This study demonstrated that nutrition enhancement can augment coral growth and post-transplantation survival, and is a biologically and economically viable option that can be used to supplement existing coral mariculture procedures and enhance reef restoration outcomes. PMID:24896085

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-05-01

    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.

  5. Vaccination strategies in lymphoproliferative disorders: Failures and successes.

    PubMed

    Allegra, A; Russo, S; Gerace, D; Calabrò, L; Maisano, V; Innao, V; Musolino, C

    2015-10-01

    Anti-tumor vaccines in lymphoproliferative disorders hold out the prospect of effective tumor therapies with minimal side effects. The addition of immunotherapy to old and new chemotherapy regimens has improved both response rates and disease-free survival, leading in many cases to an extended overall survival. Ideally, an antigen that is used for vaccination would be specifically expressed in the tumor; it must have an important, causal part in the multifactorial process that leads to cancer, and it must be expressed stably even after it is attacked by the immune system. Immunotherapies, which aim to activate the immune system to kill cancer cells, include strategies to increase the frequency or potency of antitumor T cells, to overcome suppressive factors in the tumor microenvironment, and to reduce T-cell suppression systemically. In this review, we focus on the results of clinical trials of vaccination in lymphoma, and discuss potential strategies to enhance the efficacy of immunotherapy in the future.

  6. Granulomatous Lymphoproliferative Disorders: Granulomatous Slack Skin and Lymphomatoid Granulomatosis.

    PubMed

    Gangar, Pamela; Venkatarajan, Sangeetha

    2015-07-01

    Granulomatous cutaneous T-cell lymphomas (CTCL) and lymphomatoid granulomatosis are considered granulomatous lymphoproliferative disorders. The most common types of granulomatous CTCL are granulomatous mycosis fungoides and granulomatous slack skin. Lymphomatoid granulomatosis is a rare Epstein-Barr virus driven lymphoproliferative disorder. This article reviews the etiopathogenesis, clinical presentation, systemic associations, and management of both granulomatous slack skin syndrome and lymphomatoid granulomatosis. PMID:26143428

  7. Live Donor Renal Anatomic Asymmetry and Post-Transplant Renal Function

    PubMed Central

    Tanriover, Bekir; Fernandez, Sonalis; Campenot, Eric S.; Newhouse, Jeffrey H.; Oyfe, Irina; Mohan, Prince; Sandikci, Burhaneddin; Radhakrishnan, Jai; Wexler, Jennifer J.; Carroll, Maureen A.; Sharif, Sairah; Cohen, David J.; Ratner, Lloyd E.; Hardy, Mark A.

    2014-01-01

    Background Relationship between live donor renal anatomic asymmetry and post-transplant recipient function has not been studied extensively. Methods We analyzed 96 live-kidney donors, who had anatomical asymmetry (>10% renal length and/or volume difference calculated from CT angiograms) and their matching recipients. Split function differences (SFD) were quantified with 99mTc-DMSA renography. Implantation biopsies at time-zero were semi-quantitatively scored. A comprehensive model utilizing donor renal volume adjusted to recipient weight (Vol/Wgt), SFD, and biopsy score was used to predict recipient estimated glomerular filtration rate (eGFR) at one-year. Primary analysis consisted of a logistic regression model of outcome (odds of developing eGFR>60ml/min/1.73 m2 at one-year), a linear regression model of outcome (predicting recipient eGFR at one-year, using the CKD-EPI formula), and a Monte Carlo simulation based on the linear regression model (N=10,000 iterations). Results In the study cohort, the mean Vol/Wgt and eGFR at one-year were 2.04 ml/kg and 60.4 ml/min/1.73m2, respectively. Volume and split ratios between two donor kidneys were strongly correlated (r=0.79, p-value<0.001). The biopsy scores among SFD categories (<5%, 5–10%, >10%) were not different (p=0.190). On multivariate models, only Vol/Wgt was significantly associated with higher odds of having eGFR>60ml/min/1.73 m2 (OR=8.94, 95% CI 2.47–32.25, p=0.001) and had a strong discriminatory power in predicting the risk of eGFR<60ml/min/1.73m2 at one-year (ROC curve=0.78, 95% CI 0.68–0.89). Conclusion In the presence of donor renal anatomic asymmetry, Vol/Wgt appears to be a major determinant of recipient renal function at one-year post-transplantation. Renography can be replaced with CT volume calculation in estimating split renal function. PMID:25719258

  8. Trisomy 12 is seen within a specific subtype of B-cell chronic lymphoproliferative disease affecting the peripheral blood/bone marrow and co-segregates with elevated expression of CD11a.

    PubMed

    Su'ut, L; O'Connor, S J; Richards, S J; Jones, R A; Roberts, B E; Davies, F E; Fegan, C D; Jack, A S; Morgan, G J

    1998-04-01

    In order to delineate the specific morphological and immunophenotypic features of B-cell lymphoproliferative disorders associated with trisomy 12, 172 sequential unselected cases of CD19+CD5+ B-cell disorders, primarily affecting the peripheral blood and bone marrow, were studied. Trisomy 12 was found in 24 cases (13.9%), with all cases morphologically classified as either CLL-PL or CLL-mixed by FAB criteria. Trisomy 12 was not found in any cases of typical CLL. Trisomy 12 cases demonstrated a significant higher expression of CD11a (P<0.0001) and CD20 (P<0.0006) when compared to cases with the equivalent morphology and immunophenotype, but without the chromosomal abnormality. Trisomy 12 cases also demonstrated a higher frequency of FMC7, CD38 expression and moderate to strong surface immunoglobulin staining. However, no correlation was detected between the percentages of trisomy 12 cells and cells expressing CD11a, CD38, FMC7 or sIg mean fluorescent intensity. Cells from trisomy 12 positive cases were sorted according to their CD11a expression using fluorescent activated cell sorting. There was a significant increase in the percentage of trisomy 12 cells within the CD11a+ sorted fraction compared to the unsorted population (P < 0.05), implying that trisomy 12 is associated with increased expression of CD11a. With the highly specific morphological and immunophenotypic features demonstrated by trisomy 12 cases in this study, it is highly likely that these cases constitute a specific group of B-cell lymphoproliferative disorders.

  9. Unperturbed vs. post-transplantation hematopoiesis: both in vivo but different

    PubMed Central

    Busch, Katrin; Rodewald, Hans-Reimer

    2016-01-01

    Purpose of review Hematopoietic stem cell (HSC) transplantation has yielded tremendous information on experimental properties of HSCs. Yet, it remains unclear whether transplantation reflects the physiology of hematopoiesis. A limitation is the difficulty in accessing HSC functions without isolation, in-vitro manipulation and readout for potential. New genetic fate mapping and clonal marking techniques now shed light on hematopoiesis under physiological conditions. Recent findings Transposon-based genetic marks were introduced across the entire hematopoietic system to follow the clonal dynamics of these tags over time. A polyclonal source downstream from stem cells was found responsible for the production of at least granulocytes. In independent experiments, HSCs were genetically marked in adult mice, and the kinetics of label emergence throughout the system was followed over time. These experiments uncovered that during physiological steady-state hematopoiesis large numbers of HSCs yield differentiated progeny. Individual HSCs were active only rarely, indicating their very slow periodicity of differentiation rather than quiescence. Summary Noninvasive genetic experiments in mice have identified a major role of stem and progenitor cells downstream from HSCs as drivers of adult hematopoiesis, and revealed that post-transplantation hematopoiesis differs quantitatively from normal steady-state hematopoiesis. PMID:27213498

  10. HLA-haploidentical blood or marrow transplantation with high-dose, post-transplantation cyclophosphamide.

    PubMed

    Fuchs, E J

    2015-06-01

    In the past, partially HLA-mismatched related donor, or HLA-haploidentical, blood or marrow transplantation (haploBMT), for hematologic malignancies has been complicated by unacceptably high incidences of graft rejection or GvHD resulting from intense bi-directional alloreactivity. Administration of high doses of cyclophosphamide early after haploBMT selectively kills proliferating, alloreactive T cells while sparing non-alloreactive T cells responsible for immune reconstitution and resistance to infection. In the clinic, haploBMT with high-dose, post-transplantation cyclophosphamide is associated with acceptably low incidences of fatal graft rejection, GvHD and non-relapse mortality, and provides an acceptable treatment option for hematologic malignancies patients lacking suitably HLA-matched donors. HaploBMT with PTCy is now being investigated as a treatment of hemoglobinopathy and as a method for inducing tolerance to solid organs transplanted from the same donor. Ongoing and future clinical trials will establish the hierarchy of donor preference for hematologic malignancy patients lacking an HLA-matched sibling.

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

    PubMed

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

    2013-01-01

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

  12. Fibrosing cholestatic hepatitis C in post-transplant adult recipients of liver transplantation

    PubMed Central

    Hori, Tomohide; Onishi, Yasuharu; Kamei, Hideya; Kurata, Nobuhiko; Ishigami, Masatoshi; Ishizu, Yoji; Ogura, Yasuhiro

    2016-01-01

    Hepatitis C recurrence continues to present a major challenge in liver transplantation (LT). Approximately 10% of hepatitis C virus (HCV)-positive recipients will develop fibrosing cholestatic hepatitis (FCH) after LT. FCH is clinically characterized as marked jaundice with cholestatic hepatic dysfunction and high titers of viremia. Pathologically, FCH manifests as marked hepatocyte swelling, cholestasis, periportal peritrabecular fibrosis and only mild inflammation. This progressive form usually involves acute liver failure, and rapidly results in graft loss. A real-time and precise diagnosis based on histopathological examination and viral measurement is indispensable for the adequate treatment of FCH. Typical pathological findings of FCH are shown. Currently, carefully selected combinations of direct-acting antivirals (DAAs) offer the potential for highly effective and safe regimens for hepatitis C, both in the pre- and post-transplant settings. Here, we review FCH caused by HCV in LT recipients, and current strategies for sustained virological responses after LT. Only a few cases of successfully treated FCH C after LT by DAAs have been reported. The diagnostic findings and therapeutic dilemma are discussed based on a literature review. PMID:27708510

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

    PubMed Central

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

    2016-01-01

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

  14. T cell lymphoproliferative disorder following bone marrow transplantation for severe aplastic anemia.

    PubMed

    Wang, L C; Lu, M Y; Yu, J; Jou, S T; Chiang, I P; Lin, K H; Lin, D T

    2000-10-01

    Post-transplant lymphoproliferative disorder (PTLD) is uncommonly of T cell origin, especially following BMT. We describe a 13-year-old boy with severe aplastic anemia (SAA) and no evidence of Fanconi's anemia who underwent BMT at 11 years of age using CY 10 mg/kg once daily i.v. on days -5, -4, antilymphocyte globulin (ALG) 30 mg/kg once daily i.v. on days -5 approximately -3 and CsA from day -1 as conditioning. The BMT failed and he received a further peripheral blood stem cell transplant (PBSCT) 240 days after BMT. Conditioning was with CY 50 mg/kg once daily i.v. on days -5 approximately -2, and ALG 15 mg/kg once daily i.v. on days -4 approximately -2. GVHD prophylaxis included CsA and MTX. Engraftment was later confirmed by cytogenetic studies. Desquamation and ulcers of the oral mucosa and mouth angle developed in the 13th month post PBSCT. A buccal mucosa biopsy on day +524 revealed only plasmacytosis. Immunosuppressants were discontinued at that point. Generalized lymphadenopathy, prolonged fever (waxing and waning) and facial swelling developed in the 18th month post PBSCT. A neck lymph node biopsy on day +601 showed T cell lymphoma of diffuse large cell type with monoclonal TCR gamma-chain gene rearrangement. A FISH study showed that the malignant T cells were of recipient origin. EBV in situ hybridization was negative. He did not receive further treatment apart from discontinuation of immunosuppressants. He was followed up in our out-patient clinic and showed good performance 1170 days post PBSCT. We speculate that a different mechanism was operating in the pathogenesis of T cell lymphoma in this case. Risk factors include SAA and two transplants, conditioned with CY and ALG, long term use of CsA and treatment with azathioprine. PMID:11081391

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

    PubMed

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

    2016-06-01

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

  16. Extra Y chromosome in chronic lymphoproliferative disorders.

    PubMed

    Xiao, H; Dadey, B; Block, A W; Han, T; Sandberg, A A

    1991-02-01

    Using separated lymphocytes from 95 male patients with B-cell lymphoproliferative disorders, we have established both Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and short-term cultures with polyclonal B-cell mitogens. Cytogenetic studies of these patients revealed an extra Y chromosome in 4 of 71 male cell lines examined. An extra Y chromosome appeared to be the sole karyotype change (47,XY, + Y) in 2 of these 4 patients. The extra Y chromosome was accompanied by extra copies of chromosomes 12 and 21 (48,XY, + Y, + 12 and 48,XY, + Y, + 21) in the other 2 patients, respectively. The possible oncological role of the extra Y chromosome in the initiation of leukemia is discussed. PMID:1847090

  17. Post-transplantation hepatocellular carcinoma recurrence: Patterns and relation between vascularity and differentiation degree

    PubMed Central

    Pecchi, Annarita; Besutti, Giulia; De Santis, Mario; Del Giovane, Cinzia; Nosseir, Sofia; Tarantino, Giuseppe; Di Benedetto, Fabrizio; Torricelli, Pietro

    2015-01-01

    AIM: To evaluate the relationship between hepatocellular carcinoma (HCC) vascularity and grade; to describe patterns and vascular/histopathological variations of post-transplantation recurrence. METHODS: This retrospective study included 165 patients (143 men, 22 women; median age 56.8 years, range 28-70.4 years) transplanted for HCC who had a follow-up period longer than 2 mo. Pre-transplantation dynamic computed tomography or magnetic resonance examinations were retrospectively reviewed, classifying HCC imaging enhancement pattern into hypervascular and hypovascular based on presence of wash-in during arterial phase. All pathologic reports of the explanted livers were reviewed, collecting data about HCC differentiation degree. The association between imaging vascular pattern and pathological grade was estimated using the Fisher exact test. All follow-up clinical and imaging data were reviewed for evidence of recurrence. Recurrence rate was calculated and imaging features of recurrent tumor were collected, classifying early and late recurrences based on timing (< or ≥ 2 years after transplantation) and intrahepatic, extrahepatic and both intrahepatic and extrahepatic recurrences based on location. All intrahepatic recurrences were classified as hypervascular or hypovascular and the differentiation degree was collected where available. The presence of variations in imaging enhancement pattern and pathological grade between the primary tumor and the intrahepatic recurrence was evaluated and the association between imaging and histopatholgical variations was estimated by using the χ2 test. RESULTS: Of the 163 patients with imaging evidence of viable tumor, 156 (95.7%) had hypervascular and 7 (4.3%) hypovascular HCC. Among the 125 patients with evidence of viable tumor in the explanted liver, 19 (15.2%) had grade 1, 56 (44.8%) grade 2, 40 (32%) grade 3 and 4 (3.2%) grade 4 HCC, while the differentiation degree was not assessable for 6 patients (4.8%). A significant

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

    PubMed

    Berio, A; Mangiante, G; Piazzi, A

    2014-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  1. Intralymphatic Spread Is a Common Finding in Cutaneous CD30+ Lymphoproliferative Disorders.

    PubMed

    Ferrara, Gerardo; Ena, Luca; Cota, Carlo; Cerroni, Lorenzo

    2015-11-01

    An intralymphatic variant of the cutaneous CD30 lymphoproliferative disorders (cutaneous anaplastic large cell lymphoma [ALCL] and lymphomatoid papulosis [LyP]) has been described recently. We retrieved 60 cases of ALCL of the skin (primary cutaneous: 37; cases with concomitant involvement of 1 regional lymph node: 4; skin involvement from systemic disease: 4; cases with staging results unknown: 15) and 16 cases of LyP, to evaluate the presence of lymphatic vessel involvement by neoplastic cells. A D2-40 immunohistochemical staining was used to highlight lymphatic vessels. Lymphatic vessel involvement was found in 36 cases (60%) of ALCL (primary cutaneous: 24; concomitant: 3; secondary cutaneous: 4; staging unknown: 5), and in 6 cases (37.5%) of LyP. Follow-up data, available in 28 patients with ALCL and 11 with LyP, suggested that lymphatic vessel involvement had no negative prognostic implication. Our study demonstrates that cutaneous CD30 lymphoproliferative disorders are frequently characterized by involvement of the lymphatic vessels. The intralymphatic variant of ALCL and LyP may be explained, at least in part, by a particular lymphotropism of the neoplastic cells of cutaneous CD30 lymphoproliferative disorders.

  2. Fine-needle aspiration cytology of lymphoproliferative lesions involving the major salivary glands.

    PubMed

    Chhieng, D C; Cangiarella, J F; Cohen, J M

    2000-04-01

    Fine-needle aspiration biopsy (FNA) is an accurate and cost-effective procedure for evaluating salivary gland lesions. Lymphoproliferative lesions may manifest as salivary gland enlargement. We report our experience with 43 cases of reactive and neoplastic lymphoproliferative lesions of the salivary glands evaluated by FNA, including 23 cases of reactive lymphoid hyperplasia and 20 neoplastic lymphoproliferative processes. The latter included 2 multiple myelomas and 18 non-Hodgkin lymphomas (small lymphocytic lymphoma/chronic lymphocytic leukemia, 1; small cleaved cell lymphoma, 1; lympho-plasmacytoid lymphoma, 1; mucosa-associated lymphoid tissue lymphoma, 2; mixed cell lymphoma, 4; lymphoblastic lymphoma, 1; and large cell lymphoma, 8). There were no false-negative diagnoses. Aspiration smears from 3 patients with reactive lymphoid hyperplasia and 4 patients with malignant lymphoma initially were interpreted as atypical lymphoid proliferations or as suggestive of malignant lymphoma. Thus, FNA had a sensitivity of 100% and a specificity of 87%. The majority of patients were treated medically without surgical intervention. Among the patients who underwent surgical resection of the salivary gland, 7 had an equivocal cytologic diagnosis and 2 had a benign cytologic diagnosis, but their parotid swelling failed to regress despite medical treatment. In most instances, FNA provides useful information for subsequent disease management and obviates surgical intervention.

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2016-05-01

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

  5. How I treat autoimmune lymphoproliferative syndrome

    PubMed Central

    Oliveira, João Bosco

    2011-01-01

    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

  6. Spleen Tyrosine Kinase: A Crucial Player and Potential Therapeutic Target in Renal Disease.

    PubMed

    Ma, Terry King-Wing; McAdoo, Stephen P; Tam, Frederick Wai-Keung

    2016-01-01

    Spleen tyrosine kinase (Syk), a 72 kDa cytoplasmic non-receptor protein-tyrosine kinase, plays an important role in signal transduction in a variety of cell types. Ever since its discovery in the early 1990s, there has been accumulating evidence to suggest a pathogenic role of Syk in various allergic disorders, autoimmune diseases and malignancies. Additionally, there is emerging data from both pre-clinical and clinical studies that Syk is implicated in the pathogenesis of proliferative glomerulonephritis (GN), including anti-glomerular basement membrane disease, anti-neutrophil cytoplasmic antibody-associated GN, lupus nephritis and immunoglobulin A nephropathy (IgAN). Moreover, recent animal studies have shed light on the importance of Syk in mediating acute renal allograft rejection, Epstein Barr virus-associated post-transplant lymphoproliferative disease and kidney fibrosis. Fostamatinib, an oral Syk inhibitor, has undergone clinical testing in rheumatoid arthritis, refractory immune thrombocytopenic purpura, leukemia and lymphoma. The recent STOP-IgAN trial showed that the addition of non-selective immunosuppressive therapy to intensive supportive care did not improve clinical outcomes in high-risk IgAN patients. A Syk-targeted approach may be beneficial and is currently being evaluated in a phase II randomized controlled trial. In this review, we will discuss the pathogenic role of Syk and potential use of Syk inhibitor in a variety of renal diseases. PMID:27476075

  7. Autoimmune Lymphoproliferative Syndrome: A Rare Cause of Disappearing HDL Syndrome.

    PubMed

    Sriram, Swetha; Joshi, Avni Y; Rodriguez, Vilmarie; Kumar, Seema

    2016-01-01

    The term disappearing HDL syndrome refers to development of severe high density lipoprotein cholesterol (HDL-C) deficiency in noncritically ill patients with previously normal HDL-C and triglyceride levels. Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of the immune system due to an inability to regulate lymphocyte homeostasis resulting in lymphadenopathy and hepatosplenomegaly. We describe a 17-year-old boy who was evaluated in the lipid clinic for history of undetectable or low HDL-C and low density lipoprotein cholesterol (LDL-C) levels. Past medical history was significant for ALPS IA diagnosed at 10 years of age when he presented with bilateral cervical adenopathy. He was known to have a missense mutation in one allele of the FAS protein extracellular domain consistent with ALPS type 1A. HDL-C and LDL-C levels had been undetectable on multiple occasions, though lipids had not been measured prior to the diagnosis of ALPS. He had been receiving sirolimus for immunosuppression. The HDL-C and LDL-C levels correlated with disease activity and improved to normal levels during times when the activity of ALPS was controlled. This case highlights the importance of considering ALPS as a cause of low HDL-C and LDL-C levels in a child with evidence of lymphoproliferation. PMID:27579193

  8. Autoimmune Lymphoproliferative Syndrome: A Rare Cause of Disappearing HDL Syndrome

    PubMed Central

    Sriram, Swetha; Joshi, Avni Y.; Rodriguez, Vilmarie

    2016-01-01

    The term disappearing HDL syndrome refers to development of severe high density lipoprotein cholesterol (HDL-C) deficiency in noncritically ill patients with previously normal HDL-C and triglyceride levels. Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of the immune system due to an inability to regulate lymphocyte homeostasis resulting in lymphadenopathy and hepatosplenomegaly. We describe a 17-year-old boy who was evaluated in the lipid clinic for history of undetectable or low HDL-C and low density lipoprotein cholesterol (LDL-C) levels. Past medical history was significant for ALPS IA diagnosed at 10 years of age when he presented with bilateral cervical adenopathy. He was known to have a missense mutation in one allele of the FAS protein extracellular domain consistent with ALPS type 1A. HDL-C and LDL-C levels had been undetectable on multiple occasions, though lipids had not been measured prior to the diagnosis of ALPS. He had been receiving sirolimus for immunosuppression. The HDL-C and LDL-C levels correlated with disease activity and improved to normal levels during times when the activity of ALPS was controlled. This case highlights the importance of considering ALPS as a cause of low HDL-C and LDL-C levels in a child with evidence of lymphoproliferation. PMID:27579193

  9. Tolerability and Clinical Activity of Post-Transplantation Azacitidine in Patients Allografted for Acute Myeloid Leukemia Treated on the RICAZA Trial.

    PubMed

    Craddock, Charles; Jilani, Nadira; Siddique, Shamyla; Yap, Christina; Khan, Josephine; Nagra, Sandeep; Ward, Janice; Ferguson, Paul; Hazlewood, Peter; Buka, Richard; Vyas, Paresh; Goodyear, Oliver; Tholouli, Eleni; Crawley, Charles; Russell, Nigel; Byrne, Jenny; Malladi, Ram; Snowden, John; Dennis, Mike

    2016-02-01

    Disease relapse is the major causes of treatment failure after allogeneic stem cell transplantation (SCT) in patients with acute myeloid leukemia (AML). As well as demonstrating significant clinical activity in AML, azacitidine (AZA) upregulates putative tumor antigens, inducing a CD8(+) T cell response with the potential to augment a graft-versus-leukemia effect. We, therefore, studied the feasibility and clinical sequelae of the administration of AZA during the first year after transplantation in 51 patients with AML undergoing allogeneic SCT. Fourteen patients did not commence AZA either because of transplantation complications or withdrawal of consent. Thirty-seven patients commenced AZA at a median of 54 days (range, 40 to 194 days) after transplantation, which was well tolerated in the majority of patients. Thirty-one patients completed 3 or more cycles of AZA. Sixteen patients relapsed at a median time of 8 months after transplantation. No patient developed extensive chronic graft-versus-host disease. The induction of a post-transplantation CD8(+) T cell response to 1 or more tumor-specific peptides was studied in 28 patients. Induction of a CD8(+) T cell response was associated with a reduced risk of disease relapse (hazard ratio [HR], .30; 95% confidence interval [CI], .10 to .85; P = .02) and improved relapse-free survival (HR, .29; 95% CI, .10 to .83; P = .02) taking into account death as a competing risk. In conclusion, AZA is well tolerated after transplantation and appears to have the capacity to reduce the relapse risk in patients who demonstrate a CD8(+) T cell response to tumor antigens. These observations require confirmation in a prospective clinical trial. PMID:26363443

  10. [Epstein-Barr virus infection - life cycle, methods of diagnosis, associated diseases].

    PubMed

    Bocian, Joanna; Januszkiewicz-Lewandowska, Danuta

    2011-01-01

    Epstein-Barr virus (EBV) is a ubiquitous virus that infects about 90–95% of the adult population. EBV establishes life-long latent persistence. The virus is found to be the major cause of infectious mononucleosis but it has also been associated with development of endemic Burkitt’s lymphoma. Result of EBV infection is the most common complication in patients after transplantation which is a post-transplant lymphoproliferative disease. Strong associations between EBV infection and Hodgkin’s lymphoma, nasopharyngeal carcinoma, gastric carcinoma and carcinomas derived from smooth muscle tissue also exist. There is a hypothesis that there is an association between EBV infection and autoimmune and allergic diseases. EBV is a Herpesvirus family member; its genetic material has dsDNA form. There are two strains of EBV: A and B. The only host for EBV is human with target cells: B cells and epithelial cells. The life cycle of EBV consists of lytic and latent phases. In the latent phase three different patterns of gene expression are possible. Due to some circumstances EBV can undergo reactivation, which is an important issue in transplantology. The main methods of diagnosis of EBV infections are serological methods that detect certain specific antibodies and recently more popular molecular biological methods such as PCR or in situ hybridization. PMID:21677354

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

    PubMed Central

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

    2014-01-01

    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

  12. Pharmacokinetic-pharmacodynamic assessment of tacrolimus in liver-transplant recipients during the early post-transplantation period.

    PubMed

    Blanchet, Benoît; Duvoux, Christophe; Costentin, Charlotte E; Barrault, Camille; Ghaleh, Bijan; Salvat, Annie; Jouault, Hélène; Astier, Alain; Tod, Michel; Hulin, Anne

    2008-08-01

    During the early post-transplantation period, the limitations of monitoring current tacrolimus dose with classic pharmacokinetics (PK) have been demonstrated in liver-transplant recipients. Evaluation of the pharmacodynamics (PD) using calcineurin activity (CNA) has been proposed to optimize tacrolimus dosing. The aim of the present study was to determine the time of maximal inhibition of CNA, to explore the relation between exposure to tacrolimus and CNA, and to analyze its variability. Blood was drawn from 14 patients 0, 2, 3, 4, 6, and 9 hours after tacrolimus intake on post-transplantation days 8, 21, and 90 to measure blood tacrolimus concentrations using the EMIT 2000 assay and CNA in peripheral blood mononuclear cells. Tacrolimus and CNA data were obtained for 33 blood-sample collection sessions and analyzed using a population approach. Three models were built to describe tacrolimus PK, CNA kinetics, and the relationships between the area under the CNA-time curve (AUC12effCNA) and AUC12Tacrolimus or CminTacrolimus. Coagulation factor V and whole/split liver graft were identified as covariates influencing tacrolimus clearance. Indeed, apparent tacrolimus clearance rose by 14% when factor V increased by 10% and was threefold higher in patients with whole-liver grafts. The median maximal inhibition of CNA was reached 4 hours after tacrolimus intake on days 8, 21, and 90 and represented an 18% drop in CNA compared with activity at drug intake. The variability of the PK-PD relationship was minimal when using AUC12Tacrolimus. The large variability of the PD parameters (coefficient of variation was 89%) that linked AUC12effCNA to AUC12Tacrolimus indicates that monitoring tacrolimus concentrations may not be adequate to control CNA. Measuring CNA in peripheral blood mononuclear cells 4 hours after tacrolimus intake during the first 3 months after liver transplantation could be a means to improve tacrolimus monitoring and thereby avoid acute graft-rejection episodes.

  13. [Four Cases of Other Iatrogenic Immunodeficiency-associated Lymphoproliferative Disorders in the Head and Neck Region].

    PubMed

    Fukasawa, Masahiko; Akazawa, Yoshihiro; Kasugai, Shigeru; Mikami, Koshi; Saito, Yoshimitsu; Akutsu, Masatoshi; Akashi, Aibi; Ido, Kojiro; Maeda, Ichiro; Hoshikawa, Masahiro; Koizuka, Izumi

    2016-05-01

    Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) comprise lymphoid proliferations or lymphomas that arise in patients treated with immunosuppressive drugs for autoimmune diseases, especially rheumatoid arthritis (RA) treated with methotrexate (MTX). MTX has been increasingly administered to patients with RA, resulting in methotrexate-associated lymphoproliferative disorder (MTX-LPD) in patients. We report herein on four cases of patients with RA, who diagnosed with head and neck region. In two cases (one case MTX and another case tacrolimus) drug therapy was discontinued, when the patients were diagnosed as having OIIA-LPD in only a few local findings. These patients have followed good clinical courses for 24 months. In the other two cases, consultations were performed for cervical lymphadenopathy by the Division of Rheumatology. In one case drug therapy was discontinued and a good clinical course was followed. In case of the other patient, however, who had undergone tacrolimus therapy after MTX therapy was discontinued, she relapsed and died. In the case of patients with an autoimmune disease such as RA who are taking MTX, tacrolimus, or anti TNF-α therapy, when cervical lymphadenopathy and extranodal disease are detected, OIIA-LPD should be suspected. We should cooperate with a hematologist-oncologist, a rheumatologist, and pathologist in such a case. PMID:27459820

  14. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    2016-04-22

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

  15. High-dose chemotherapy and autologous stem cell support followed by post-transplant doxorubicin and taxol as initial therapy for metastatic breast cancer: hematopoietic tolerance and efficacy.

    PubMed

    deMagalhaes-Silverman, M; Hammert, L; Lembersky, B; Lister, J; Rybka, W; Ball, E

    1998-06-01

    A multistep HDC regimen was designed as first-line chemotherapy for MBC. Twenty-four patients with MBC and no previous chemotherapy for metastatic disease were treated with high-dose cyclophosphamide (5000 mg/m2), and etoposide (1000 mg/m2) (CyVP16), followed by granulocyte colony-stimulating factor (G-CSF). Peripheral blood stem cells (PBSCs) were collected. Subsequently patients received cyclophosphamide (6000 mg/m2), thiotepa (500 mg/m2) and carboplatin (800 mg/m2) (CTCb) with hematopoietic rescue. Upon recovery from hematopoietic and gastrointestinal toxicity three cycles of doxorubicin (50 mg/m2) and taxol (150 mg/m2) were delivered. After CyVP16 42% of patients developed neutropenic fevers. There was one documented episode of bacteremia. Patients received CTCb 32 days after starting CyVP16. After CTCb the median number of days to ANC >5 x 10(9)/l was 10 and to a platelet count >20 x 10(9)/l was 14. Neutropenic fevers developed in 16 patients. There were no hemorrhagic episodes. A total of 69 cycles of doxorubicin and taxol were delivered (87% of planned). The median time from PBSC infusion to the first cycle was 38 days. The median time to the second cycle was 27 days and to the last cycle was 24 days. One patient developed congestive heart failure. Two episodes of neutropenic fevers were observed. No toxicity-related deaths were observed. Grafts are stable at 6 months post transplantation. This multistep regimen is feasible with acceptable toxicity. PMID:9674853

  16. Remission of late-onset post-heart transplantation lymphoproliferative disorder following treatment with rituximab and modified mini-CHOP chemotherapy: A case report

    PubMed Central

    HUANG, QIANG; YANG, TIANXIN; JIN, XING; NI, XUMING; QI, HAIYAN; YAN, ZHIKUN

    2016-01-01

    Post-transplant lymphoproliferative disorder (PTLD) is one of the most frequent secondary malignancies that can follow immunosuppressive therapy for solid organ transplantation, and may result in severe morbidities and even mortality. A middle-aged Han Chinese patient, prescribed with immunosuppressive cyclosporine and prednisone, developed PTLD that manifested as a painless cervical lymph node enlargement, 12 years following heart transplantation. Histology revealed monomorphic B-cell PTLD (diffuse large-cell lymphoma); as a result the immunosuppressive regimen of the patient was changed to tacrolimus and mycophenolate mofetil. In addition, the patient was changed to 6-cycle rituximab with a modified mini-CHOP (R-mini-CHOP) regimen for induction, and 8-cycle quarterly rituximab treatment and maintenance therapy. R-mini-CHOP therapy was well tolerated, and no allograft rejection occurred. The patient exhibited clinical remission as demonstrated by the results of the positron emission tomography-computed tomography at the 5-year follow-up visit following R-mini-CHOP therapy. In conclusion, R-mini-CHOP therapy following reduced immunosuppression is effective and safe for the treatment of late-onset PTLD following heart transplantation. PMID:27347047

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  19. Single-Fraction Radiotherapy for CD30+ Lymphoproliferative Disorders

    PubMed Central

    Gentile, Michelle S.; Martinez-Escala, Maria Estela; Thomas, Tarita O.; Guitart, Joan; Rosen, Steven; Kuzel, Timothy; Mittal, Bharat B.

    2015-01-01

    Objectives. CD30+ lymphoproliferative disorder is a rare variant of cutaneous T-cell lymphoma. Sustained complete response following first-line treatments is rare. This retrospective review evaluates the response of refractory or recurrent lesions to palliative radiation therapy. Methods. The records of 6 patients with 12 lesions, treated with radiation therapy, were reviewed. All patients received previous first-line treatments. Patients with clinical and pathological evidence of symptomatic CD30+ lymphoproliferative disorder, with no history of other cutaneous T-cell lymphoma variants, and with no prior radiation therapy to the index site were included. Results. The median age of patients was 50.5 years (range, 15–83 years). Median size of the treated lesions was 2.5 cm (range, 2–7 cm). Four sites were treated with a single fraction of 750–800 cGy (n = 3) and 8 sites were treated with 4000–4500 cGy in 200–250 cGy fractions (n = 3). Radiation therapy was administered with electrons and bolus. Median follow-up was 113 months (range, 16–147 months). For all sites, there was 100% complete response with acute grade 1-2 dermatitis. Conclusions. For recurrent and symptomatic radiation-naïve CD30+ lymphoproliferative disorder lesions, palliative radiation therapy shows excellent response. A single fraction of 750–800 cGy is as effective as a multifractionated course and more convenient. PMID:26504818

  20. Tumor-Infiltrating Macrophages in Post-Transplant, Relapsed Classical Hodgkin Lymphoma Are Donor-Derived

    PubMed Central

    Morsberger, Laura A.; Yonescu, Raluca; Thiess, Michele L.; Batista, Denise A. S.; Ning, Yi; Burns, Kathleen H.; Vuica-Ross, Milena; Borowitz, Michael J.; Gocke, Christopher D.; Ambinder, Richard F.; Duffield, Amy S.

    2016-01-01

    Tumor-associated inflammatory cells in classical Hodgkin lymphoma (CHL) typically outnumber the neoplastic Hodgkin/Reed-Sternberg (H/RS) cells. The composition of the inflammatory infiltrate, particularly the fraction of macrophages, has been associated with clinical behavior. Emerging work from animal models demonstrates that most tissue macrophages are maintained by a process of self-renewal under physiologic circumstances and certain inflammatory states, but the contribution from circulating monocytes may be increased in some disease states. This raises the question of the source of macrophages involved in human disease, particularly that of CHL. Patients with relapsed CHL following allogeneic bone marrow transplant (BMT) provide a unique opportunity to begin to address this issue. We identified 4 such patients in our archives. Through molecular chimerism and/or XY FISH studies, we demonstrated the DNA content in the post-BMT recurrent CHL was predominantly donor-derived, while the H/RS cells were derived from the patient. Where possible to evaluate, the cellular composition of the inflammatory infiltrate, including the percentage of macrophages, was similar to that of the original tumor. Our findings suggest that the H/RS cells themselves define the inflammatory environment. In addition, our results demonstrate that tumor-associated macrophages in CHL are predominantly derived from circulating monocytes rather than resident tissue macrophages. Given the association between tumor microenvironment and disease progression, a better understanding of macrophage recruitment to CHL may open new strategies for therapeutic intervention. PMID:27685855

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

    ERIC Educational Resources Information Center

    Klein, Susan D.; Simmons, Roberta G.

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

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

    PubMed

    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

    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.

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

    PubMed

    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

    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

  4. [Prophylaxis against Epstein Barr disease in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation].

    PubMed

    Catalán, Paula; Alba, Andrea

    2012-09-01

    Post transplant lymphoproliferative disease (PTLD) associated with EBV infection is one of the most life-threatening complications in SOT and HSCT. Risk factors for infection or reactivation of EBV in SOT are the use of greater immunosuppression, seronegative receptor and CMV infection. In HSCT, the risk factors are related to type of transplant, HLA disparity, the greater immunosuppression, T-cell depletion and severe GVHD. There is no scientific evidence to support the use of specific therapy for prophylaxis of EBV infection. Prophylaxis recommendations focus on avoid exposure of transplant recipients to sources of virus, through hygiene practices such as hand washing (A3), avoid sharing utensils (B3) and avoid contact with potentially infected secretions (respiratory or saliva) (A2). For PTLD prevention, the recommendation is regular EBV viral load monitoring by rtPCR. In SOT with logarithmic rising of EBV loads, it is recommended to reduce immunosuppression and periodically perform exams to diagnose PTLD. In HSCT, it is recommended to reduce immunosuppression whenever possible, and use rituximab according to speciic protocol. Acyclovir or gancyclovir have not proven to be of any eficacy in PTLD prophylaxis in SOT (C3) or HSCT (D2), so their administration as preemptive therapy is no recommended. PMID:23282553

  5. Induction of Adult T-Cell Leukemia-Like Lymphoproliferative Disease and Its Inhibition by Adoptive Immunotherapy in T-Cell-Deficient Nude Rats Inoculated with Syngeneic Human T-Cell Leukemia Virus Type 1-Immortalized Cells

    PubMed Central

    Ohashi, Takashi; Hanabuchi, Shino; Kato, Hirotomo; Koya, Yoshihiro; Takemura, Fumiyo; Hirokawa, Katsuiku; Yoshiki, Takashi; Tanaka, Yuetsu; Fujii, Masahiro; Kannagi, Mari

    1999-01-01

    Human T-cell leukemia virus type 1 (HTLV-1) has been shown to be the etiologic agent of adult T-cell leukemia (ATL), but the in vivo mechanism by which the virus causes the malignant transformation is largely unknown. In order to investigate the mechanisms of HTLV-1 leukemogenesis, we developed a rat model system in which ATL-like disease was reproducibly observed, following inoculation of various rat HTLV-1-immortalized cell lines. When previously established cell lines, F344-S1 and TARS-1, but not TART-1 or W7TM-1, were inoculated, systemic multiple tumor development was observed in adult nude (nu/nu) rats. FPM1 cells, newly established from a heterozygous (nu/+) rat syngeneic to nu/nu rats, caused transient tumors only at the injection site in adult nu/nu rats, but could progressively grow in newborn nu/nu rats and metastasize in lymph nodes. The derivative cell line (FPM1-V1AX) serially passed through newborn nu/nu rats acquired the potency to grow in adult nu/nu rats. These results indicated that only some with additional changes but not all of the in vitro HTLV-1-immortalized cell lines possessed in vivo tumorigenicity. Using the syngeneic system, we further showed the inhibition of tumor development by transferring splenic T cells from immunized rats, suggesting the involvement of T cells in the regression of tumors. This novel and reproducible nude rat model of human ATL would be useful for investigation of leukemogenesis and antitumor immune responses in HTLV-1 infection. PMID:10364355

  6. Transduction of Primary Lymphocytes with Epstein-Barr Virus (EBV) Latent Membrane Protein-Specific T-Cell Receptor Induces Lysis of Virus-Infected Cells: A Novel Strategy for the Treatment of Hodgkin’s Disease and Nasopharyngeal Carcinoma

    PubMed Central

    Jurgens, Lisa A.; Khanna, Rajiv; Weber, James; Orentas, Rimas J.

    2010-01-01

    Adoptive immunotherapy with in vitro expanded cytotoxic T lymphocytes specific for Epstein-Barr virus (EBV) can successfully treat post-transplant lymphoproliferative disease (PTLD). However, extension of a similar strategy to Hodgkin’s disease (HD) and nasopharyngeal carcinoma (NPC) is limited by the poor immunogenicity of the limited set of EBV latency antigens expressed in these malignancies, making T-cell expansion difficult. Retroviral transduction of LMP-specific T-cell receptors (TCR) into activated T lymphocytes may provide a universal, MHC-restricted, means to generate effector cells without the need for tissue culture based methods of CTL expansion. We report the transfer of two LMP2-specific TCRs from human T-cell clones (HLA-A2 and HLA-A23,24 restricted) that confer the ability to lyse EBV-immortalized B-lymphoblastoid cell lines (B-LCL). B-LCL are the best model for native expression of LMP2. We also demonstrate the rapid transfer of the TCR by nucleofection of primary T cells using a simple plasmid-based vector. The ability to detect nucleofected TCRVβ chain by antibody, fully assembled TCR by tetramer, and peptide-MHC-specific lytic activity indicates that nucleofection can serve as a tool for rapid screening of TCR specificity. PMID:16418800

  7. Studies on Erythropoiesis in Uremic and Post-Transplant (Renal) Patients Utilizing Radioactive Iron and Chromium

    PubMed Central

    Farooki, M. S.; Kimber, R. W.

    1971-01-01

    The association of anemia with chronic renal disease is well known. The striking hematologic improvement following a successful renal allotransplantation led to the present study. Using radioactive 59Fe, ferrokinetic measurements were carried out in nine uremic patients (seven with and two without anemia), four post-allotransplant cases, three patients with iron deficiency anemia and a group of five normal subjects. Erythrocyte life-span was calculated by 51Cr-labelled, autotransfused red cells in all patients who had had transplants and in three patients with renal anemia. The results showed that in patients with renal anemia the plasma radioiron clearance was slightly delayed but the 59Fe incorporation into the circulating erythrocytes was significantly decreased. Red cell life-span was moderately shortened in two out of three uremic patients investigated. The findings constitute evidence of ineffective erythropoiesis in patients with renal anemia. By comparison, the four transplant patients showed normal 59Fe plasma clearance and red cell incorporation; the 51Cr erythrocyte survival was normal in all four patients. PMID:4931770

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

    PubMed Central

    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

    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

  9. Regional evaluation of renal dynamics in post transplant kidneys with Tc-99m DTPA and scinti-camera

    SciTech Connect

    Suzuki, T.; Akuta, K.; Aoki, S.; Furunishi, H.; Yamazaki, T.; Yamazaki, T.; Nakane, Y.; Pak, K.

    1984-01-01

    The purpose of the study is to analyze the regional renal dynamic process (renal perfusion, accumulation and clearance) using Tc-99m DTPA and assess for the regional renal indices from this analysis early to detect acute tubular necrosis and acute rejection of post transplant kidneys. The subjects were 6 normal donors and 10 post renal transplant patients. Tc-99m DTPA (20 mCi) was injected into the vein by a bolus, and its activity change in the kidney was measured by a scintillation camera, and stored each 1 sec. for 20 sec. following each 15 sec. for 20 min. in the computer, to calculate the renal functional indices: the perfusion index, the blood flow mean transit time, the accumulation rate and the clearance rate in the cortex, medulla and pelvis, whose R.O.I. regions were separated in the early and late scinti-images. The accumulation ratio, a new parameter, which is the second upslope part of Tc-99m DTPA renogram, and the clearance rate were calculated from H/A method. The authors made the functional images of these indices to estimate their regional distribution. The accumulation rate and the clearance rate only in the cortex were markedly decreased in the acute tubular necrosis and the rejection, which functional images showed irregular distributions. It was possible to evaluate the renal perfusion with Tc-99m DTPA, separated from the renal accumulation and clearance process. The authors' method gave the assessment of the regional renal disorders with the functional images; the renal disorders in acute tubular necrosis and acute rejection exist mainly in the cortex.

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

    PubMed Central

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

    2016-01-01

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

  11. Advances in the management and understanding of autoimmune lymphoproliferative syndrome (ALPS)

    PubMed Central

    Teachey, David T.; Seif, Alix E.; Grupp, Stephan A.

    2010-01-01

    Summary Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of T cell dysregulation caused by defective Fas-mediated apoptosis. Patients with ALPS can develop a myriad of clinical manifestations including lymphadenopathy, hepatosplenomegaly, autoimmunity and increased rates of malignancy. ALPS may be more common that originally thought, and testing for ALPS should be considered in patients with unexplained lymphadenopathy, hepatosplenomegaly, and/or autoimmunity. As the pathophysiology of ALPS is better characterized, a number of targeted therapies are in preclinical development and clinical trials with promising early results. This review describes the clinical and laboratory manifestations found in ALPS patients, as well as the molecular basis for the disease and new advances in treatment. PMID:19930184

  12. Isolated Upper Extremity Posttransplant Lymphoproliferative Disorder in a Child.

    PubMed

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

    2015-01-01

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

  13. Impact of pretransplant minimal residual disease on the post-transplant outcome of pediatric acute lymphoblastic leukemia.

    PubMed

    Umeda, Katsutsugu; Hiramatsu, Hidefumi; Kawaguchi, Koji; Iwai, Atsushi; Mikami, Masamitsu; Nodomi, Seishiro; Saida, Satoshi; Heike, Toshio; Ohomori, Katsuyuki; Adachi, Souichi

    2016-08-01

    There are few reports on the clinical significance of MRD before HSCT in pediatric ALL. We retrospectively analyzed the clinical significance of FCM-based detection of MRD (FCM-MRD) before allogeneic HSCT in pediatric ALL. Of 38 pediatric patients who underwent allogeneic HSCT for the first time between 1998 and 2014, 33 patients were in CR and five patients were in non-CR. The CR group was further divided into two groups based on the pretransplant FCM-MRD level: the MRD(neg) (<0.01%; 30 patients) group and the MRD(pos) (≥0.01%; three patients) group. There were significant differences in the three-yr event-free survival rates between the CR and non-CR group, and between the MRD(neg) and MRD(pos) group. The three-yr cumulative RI in the MRD(neg) group were 27.3% ± 8.8%, whereas two of the three patients in the MRD(pos) group relapsed within one yr after HSCT. The clinical outcome of the MRD(pos) group was as poor as that of the non-CR group in pediatric ALL. Therefore, an improvement in pretransplant treatment that aims to achieve a more profound remission would contribute to reducing the risk of relapse.

  14. Spectrum of Radiological Manifestations in Lymphoproliferative Malignancies with Unusual Extra Nodal Soft Tissue Involvement

    PubMed Central

    Prasad, Kahila; Upreti, Lalendra; Garga, Umesh Chandra

    2016-01-01

    Lymphoproliferative malignancies constitute a wide spectrum of haematological malignancies and their prevalence is widely increasing. Non-Hodgkin lymphomas and Hodgkin disease, frequently involve extranodal soft tissue structures in the head and neck, thorax and abdomen. These malignancies may involve virtually any type of soft tissues to any extent; hence many different imaging manifestations are possible which may mimic other disorders. The imaging characteristics of extranodal lymphomatous soft tissue involvement are described and classified here according to the site of involvement in 6 cases (primary diseases with orbital, muscle, extra testicular, scalp, sinonasal and pachymeningeal/dural involvement). In majority of these cases at presentation we found a predominantly homogeneous soft tissue mass with mildly high attenuation on CT and a T2 intermediate signal on MRI at these sites without any manifestation of disease elsewhere but on follow-up two out of these six cases developed systemic disease elsewhere. Few consistent patterns were noticed on CT and MRI which might help to include lymphomas as an important differential diagnosis of soft tissue masses. Though a definitive diagnosis requires a biopsy (bone marrow, lymph node, or mass), and other laboratory tests, imaging primarily aims at staging of the disease and identification of new or recurrent disease. PMID:27630925

  15. Spectrum of Radiological Manifestations in Lymphoproliferative Malignancies with Unusual Extra Nodal Soft Tissue Involvement

    PubMed Central

    Prasad, Kahila; Upreti, Lalendra; Garga, Umesh Chandra

    2016-01-01

    Lymphoproliferative malignancies constitute a wide spectrum of haematological malignancies and their prevalence is widely increasing. Non-Hodgkin lymphomas and Hodgkin disease, frequently involve extranodal soft tissue structures in the head and neck, thorax and abdomen. These malignancies may involve virtually any type of soft tissues to any extent; hence many different imaging manifestations are possible which may mimic other disorders. The imaging characteristics of extranodal lymphomatous soft tissue involvement are described and classified here according to the site of involvement in 6 cases (primary diseases with orbital, muscle, extra testicular, scalp, sinonasal and pachymeningeal/dural involvement). In majority of these cases at presentation we found a predominantly homogeneous soft tissue mass with mildly high attenuation on CT and a T2 intermediate signal on MRI at these sites without any manifestation of disease elsewhere but on follow-up two out of these six cases developed systemic disease elsewhere. Few consistent patterns were noticed on CT and MRI which might help to include lymphomas as an important differential diagnosis of soft tissue masses. Though a definitive diagnosis requires a biopsy (bone marrow, lymph node, or mass), and other laboratory tests, imaging primarily aims at staging of the disease and identification of new or recurrent disease.

  16. Spectrum of Radiological Manifestations in Lymphoproliferative Malignancies with Unusual Extra Nodal Soft Tissue Involvement.

    PubMed

    Sanyal, Shantiranjan; Prasad, Kahila; Upreti, Lalendra; Garga, Umesh Chandra

    2016-07-01

    Lymphoproliferative malignancies constitute a wide spectrum of haematological malignancies and their prevalence is widely increasing. Non-Hodgkin lymphomas and Hodgkin disease, frequently involve extranodal soft tissue structures in the head and neck, thorax and abdomen. These malignancies may involve virtually any type of soft tissues to any extent; hence many different imaging manifestations are possible which may mimic other disorders. The imaging characteristics of extranodal lymphomatous soft tissue involvement are described and classified here according to the site of involvement in 6 cases (primary diseases with orbital, muscle, extra testicular, scalp, sinonasal and pachymeningeal/dural involvement). In majority of these cases at presentation we found a predominantly homogeneous soft tissue mass with mildly high attenuation on CT and a T2 intermediate signal on MRI at these sites without any manifestation of disease elsewhere but on follow-up two out of these six cases developed systemic disease elsewhere. Few consistent patterns were noticed on CT and MRI which might help to include lymphomas as an important differential diagnosis of soft tissue masses. Though a definitive diagnosis requires a biopsy (bone marrow, lymph node, or mass), and other laboratory tests, imaging primarily aims at staging of the disease and identification of new or recurrent disease. PMID:27630925

  17. Hematopoietic Neoplasias in Horses: Myeloproliferative and Lymphoproliferative Disorders

    PubMed Central

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

    2010-01-01

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

  18. A DNA hybridization system for labeling of neural stem cells with SPIO nanoparticles for MRI monitoring post-transplantation.

    PubMed

    Egawa, Edgar Y; Kitamura, Narufumi; Nakai, Ryusuke; Arima, Yusuke; Iwata, Hiroo

    2015-06-01

    detected by MRI in vitro as well in vivo. Cells transplanted into the rat brain striatum could be detected by MRI scanning up to 1 month post-transplantation.

  19. Haploidentical T Cell-Replete Transplantation with Post-Transplantation Cyclophosphamide for Patients in or above the Sixth Decade of Age Compared with Allogeneic Hematopoietic Stem Cell Transplantation from an Human Leukocyte Antigen-Matched Related or Unrelated Donor.

    PubMed

    Blaise, Didier; Fürst, Sabine; Crocchiolo, Roberto; El-Cheikh, Jean; Granata, Angela; Harbi, Samia; Bouabdallah, Reda; Devillier, Raynier; Bramanti, Stephania; Lemarie, Claude; Picard, Christophe; Chabannon, Christian; Weiller, Pierre-Jean; Faucher, Catherine; Mohty, Bilal; Vey, Norbert; Castagna, Luca

    2016-01-01

    It has recently been shown that a T cell-replete allogeneic (allo) hematopoietic stem cell transplantation (HSCT) from a haploidentical donor (haplo-ID) could be a valid treatment for hematological malignancies. However, little data exist concerning older populations. We provided transplantation to 31 patients over the age of 55 years from a haplo-ID and compared their outcomes with patients of the same ages who underwent transplantation from a matched related (MRD) or an unrelated donor (UD). All 3 groups were comparable, except for their conditioning. Patients in haplo-ID group received 2 days of post-transplantation high-dose cyclophosphamide followed by cyclosporine A and mycophenolate mofetil, whereas patients in other groups received pretransplantation antithymocyte globulin, cyclosporine A, and additional mycophenolate mofetil in case of 1-antigen mismatch. All patients but 1 in the haplo-ID group engrafted. The incidence of grades 2 to 4 acute graft-versus-host disease (GVHD) was not statistically different between recipients from haplo-ID (cumulative incidence, 23%) and MRD (cumulative incidence, 21%) transplantations but it was lower than after UD HSCT (cumulative incidence, 44%). No patient in the haplo-ID group developed severe chronic GVHD, compared with cumulative incidences of 16% and 14% after MRD (P = .02) and UD (P = .03) grafts, respectively. The cumulative incidences of relapse were similar in the 3 groups, whereas nonrelapse mortality after UD HSCT was 3-fold higher than after haplo-ID or MRD HSCT. Overall, 2-year overall survival (70%), progression-free survival (67%), and progression and severe chronic GVHD-free survival (67%) probabilities after haplo-ID did not statistically differ from MRD transplantation (78%, 64%, and 51%, respectively), although they were higher than after UD transplantation (51% [P = .08], 38% [P = .02], and 31% [P = .007]). We conclude that T cell-replete haplo-ID HSCT followed by post-transplantation high

  20. Improved Outcome of Refractory/Relapsed Acute Myeloid Leukemia after Post-Transplantation Cyclophosphamide-Based Haploidentical Transplantation with Myeloablative Conditioning and Early Prophylactic Granulocyte Colony-Stimulating Factor-Mobilized Donor Lymphocyte Infusions.

    PubMed

    Jaiswal, Sarita Rani; Zaman, Shamsuz; Chakrabarti, Aditi; Sen, Subrata; Mukherjee, Shashwata; Bhargava, Sneh; Ray, Kunal; O'Donnell, Paul V; Chakrabarti, Suparno

    2016-10-01

    We carried out post-transplantation cyclophosphamide (PTCy)-based haploidentical peripheral blood stem cell transplantation in 51 patients with refractory/relapsed acute myeloid leukemia not in remission. The first 10 patients received nonmyeloablative conditioning followed by planned granulocyte colony-stimulating factor (G-CSF)-mobilized donor lymphocyte infusions (DLIs) on days 35, 60, and 90. No patient developed graft-versus-host disease (GVHD), but 90% had disease progression between 3 and 6 months. A subsequent 41 patients received myeloablative conditioning (MAC); the first 20 patients did not receive DLIs (MAC group) and the next 21 patients received G-CSF-mobilized DLIs (G-DLI) on days 21, 35, and 60 (MAC-DLI group). The incidence of disease progression and progression-free survival at 18 months were 66% and 25% in the MAC group compared with 21.4% and 61.9% in the MAC-DLI group (P = .01). Chronic GVHD but not acute GVHD was increased in the MAC-DLI group (41.2% versus 11%, P = .05). Natural killer cell alloreactive donor was associated with lower incidence of disease progression in the MAC but not in MAC-DLI group. The only factor favorably influencing disease progression and progression-free survival was administration of G-DLI after myeloablative conditioning. Our study shows that early administration of G-DLI is feasible after PTCy-based haploidentical hematopoietic stem cell transplantation for refractory/relapsed acute myeloid leukemia and might be associated with improved survival after MAC. PMID:27470289

  1. Folliculotropic Mycosis Fungoides as a Posttransplant Lymphoproliferative Disorder.

    PubMed

    Spence-Shishido, Allyson; Streicher, Jenna L; George, Roshan P; Parker, Sareeta R; Lawley, Leslie P

    2015-09-01

    Posttransplant lymphoproliferative disorder (PTLD) is a known complication of solid organ transplantation. The majority are B cell in origin and related to Epstein-Barr virus infection. T-cell PTLD is much less common; most are Epstein-Barr virus negative and have a worse prognosis. Primary cutaneous T-cell lymphoma (CTCL) as a presentation of PTLD is rare. CTCL has a less favorable prognosis in transplant patients compared with that in immune-competent patients. Herein, we report a case of a 13-year-old boy who developed folliculotropic mycosis fungoides, a rare subtype of CTCL, subsequent to renal transplantation. To our knowledge, this is the first report of this type of PTLD in a pediatric patient. PMID:26283779

  2. Practical Management of CD30⁺ Lymphoproliferative Disorders.

    PubMed

    Hughey, Lauren C

    2015-10-01

    Primary cutaneous CD30⁺ lymphoproliferative disorders (LPDs) account for approximately 25% of cutaneous lymphomas. Although these LPDs are clinically heterogeneous, they can be indistinguishable histologically. Lymphomatoid papulosis rarely requires systemic treatment; however, multifocal primary cutaneous anaplastic large cell cutaneous lymphoma and large cell transformation of mycosis fungoides are typically treated systemically. As CD30⁺ LPDs are rare, there is little published evidence to support a specific treatment algorithm. Most studies are case reports, small case series, or retrospective reviews. This article discusses various treatment choices for each of the CD30⁺ disorders and offers practical pearls to aid in choosing an appropriate regimen. PMID:26433852

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

    PubMed Central

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

    2016-01-01

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

  4. Pre-transplant shedding of BK virus in urine is unrelated to post-transplant viruria and viremia in kidney transplant recipients.

    PubMed

    Bicalho, C S; Oliveira, R R; Pierrotti, L C; Fink, M C D S; Urbano, P R P; Nali, L H S; Luna, E J A; Romano, C M; David, D R; David-Neto, E; Pannuti, C S

    2016-07-01

    BK virus-(BKV) associated nephropathy (BKVN) is a major cause of allograft injury in kidney transplant recipients. In such patients, subclinical reactivation of latent BKV infection can occur in the pre-transplant period. The purpose of this study was to determine whether urinary BKV shedding in the immediate pre-transplant period is associated with a higher incidence of viruria and viremia during the first year after kidney transplantation. We examined urine samples from 34 kidney transplant recipients, using real-time quantitative polymerase chain reaction to detect BKV. Urine samples were obtained in the immediate pre-transplant period and during the first year after transplant on a monthly basis. If BKV viruria was detected, blood samples were collected and screened for BKV viremia. In the immediate pre-transplant period, we detected BKV viruria in 11 (32.3%) of the 34 recipients. During the first year after transplantation, we detected BKV viruria in all 34 patients and viremia in eight (23.5%). We found no correlation between pre-transplant viruria and post-transplant viruria or viremia (p = 0.2). Although reactivation of latent BKV infection in the pre-transplant period is fairly common among kidney transplant recipients, it is not a risk factor for post-transplant BKV viruria or viremia.

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

    PubMed Central

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

    2014-01-01

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

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

    ClinicalTrials.gov

    2015-12-09

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

  7. [EBV-associated B-cell lymphoproliferative disorder of the elderly successfully treated with autologous peripheral blood stem cell transplantation and locoregional radiotherapy].

    PubMed

    Sugino, Noriko; Nakamura, Chishiho; Fujii, Sumie; Matsui, Yusuke; Kaneko, Hitomi; Watanabe, Mitsumasa; Miura, Yasuo; Wakasa, Tomoko; Tsudo, Mitsuru

    2011-03-01

    Age-related EBV-associated B-cell lymphoproliferative disorder is a highly aggressive lymphoma, and a standard therapy for this disease has not yet been established. A 58-year-old male was admitted to our hospital because of fever and lymphadenopathy across the whole body. Neck lymph node biopsy showed hemorrhagic and geographic necrosis with Hodgkin-like large cells against a background of small lymphocytes. The large cells were positive for CD30 and EBER. The patient was diagnosed as having age-related EBV-associated B-cell lymphoproliferative disorder. Although there was no response to CHOP therapy, he obtained partial response after 3 courses of DeVIC therapy. Because his lymphoma was highly aggressive and chemotherapy-resistant, he underwent autologous stem cell transplantation with a conditioning regimen including ranimustine, etoposide, cytarabine, and melphalan. After stem cell transplantation and subsequent radiotherapy to the residual lesion, the patient achieved complete remission. This is the first report of successful autologous stem cell transplantation for a patient with age-related EBV-associated B-cell lymphoproliferative disorder. PMID:21471700

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

    ClinicalTrials.gov

    2016-05-11

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

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

    PubMed Central

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

    2015-01-01

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

  10. PHASE II TRIAL OF GVHD PROPHYLAXIS WITH POST-TRANSPLANTATION CYCLOPHOSPHAMIDE FOLLOWING REDUCED-INTENSITY BUSULFAN/FLUDARABINE (BU/FLU) CONDITIONING FOR HEMATOLOGICAL MALIGNANCIES

    PubMed Central

    Alousi, Amin M.; Brammer, Jonathan E.; Saliba, Rima M.; Andersson, Borje; Popat, Uday; Hosing, Chitra; Jones, Roy; Shpall, Elizabeth J; Khouri, Issa; Qazilbash, Muzaffar; Nieto, Yago; Shah, Nina; Ahmed, Sairah; Oran, Betul; Atrash, Gheath Al; Ciurea, Stefan; Kebriaei, Partow; Chen, Julianne; Rondon, Gabriela; Champlin, Richard

    2016-01-01

    GVHD-prophylaxis with post-transplant cyclophosphamide (CY) following ablative HLA-matched bone marrow (BM) transplantation has been reported to have comparable rates of acute GVHD with an apparent reduction in chronic GVHD and infections. We conducted a phase II trial of post-CY following reduced-intensity conditioning (RIC) using intravenous busulfan (AUC of 4,000 micromolar-minutes), Fludarabine (40mg/m2) for 4 days and CY 50mg/kg on days +3 and +4 following BM or peripheral blood (PB) transplants from matched related (MRD) or unrelated donors (MUD). MUD- recipients received anti-thymocyte globulin (ATG); however, a later amendment removed ATG. 49 patients were treated (AML/MDS: 82%). Median age was 62 years (range, 39–72). Fifteen patients received a MRD (9 PB/6 BM); 34 had a MUD (2 PB/32 BM). The cumulative incidence of grade II–IV, III–IV acute and chronic GVHD was 58%, 22% and 18%. A matched-cohort analysis compared outcomes to tacrolimus/methotrexate GVHD prophylaxis and indicated higher rates of acute GVHD grade II–IV (46% versus 19%, HR=2.8, p=0.02) and treatment-related mortality (HR 3.3, p=0.035) and worse overall survival (HR=1.9, p=0.04) with post-Cy. The incidence of chronic GVHD and CMV reactivation did not differ. This study suggests that post-transplant CY should not be used as sole GVHD-prophylaxis following a RIC transplant from HLA matched donors. PMID:25667989

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

    PubMed Central

    Rao, V. Koneti

    2015-01-01

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

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

    PubMed Central

    Geng, Lingyun; Wang, Xin

    2015-01-01

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

  13. LYMPHO-PROLIFERATIVE RESPONSES TO VARIOUS FASCIOLA HEPATICA WORM'S ANTIGENS: AN IN VITRO STUDY.

    PubMed

    Sharaf, Osama F; Amir, Elamir M; Hawash, Yousry A

    2016-04-01

    Fascioliasis is an important zoonotic disease with approximately 2-4 million people infected worldwide and a further 180 million at risk of infection. F. hepatica can survive within the bile ducts for many years through its ability to suppress the host immunity with Fasciola cathepsin L1 cysteine protease and Glutathione S transferase playing an important role. The aim of the present study is to investigate the in vitro lympho-proliferative responses of hepatic hilar lymphocytes (HLN) of infected sheep in response to different F. hepatica antigens. The suppressive effects of Fasciola excretory/secretory (ES) and tegument (TEG) and their fractions were also investigated. Our results showed that both ES and TEG had significant suppressive effects on lympho-proliferation, up to 74% and 92%, respectively. When these antigens were fractionated, fraction 3 (MW of >10000-30000) of both ES (64%) and TEG (59%) in addition to fraction 4 (MW of ≤ 10000) of TEG (38%) inherited the suppressive effects. Identification of the potential molecule(s) with such suppressive effects on lymphocytes in TEG fraction 4 could reveal vaccine candidates. PMID:27363058

  14. LYMPHO-PROLIFERATIVE RESPONSES TO VARIOUS FASCIOLA HEPATICA WORM'S ANTIGENS: AN IN VITRO STUDY.

    PubMed

    Sharaf, Osama F; Amir, Elamir M; Hawash, Yousry A

    2016-04-01

    Fascioliasis is an important zoonotic disease with approximately 2-4 million people infected worldwide and a further 180 million at risk of infection. F. hepatica can survive within the bile ducts for many years through its ability to suppress the host immunity with Fasciola cathepsin L1 cysteine protease and Glutathione S transferase playing an important role. The aim of the present study is to investigate the in vitro lympho-proliferative responses of hepatic hilar lymphocytes (HLN) of infected sheep in response to different F. hepatica antigens. The suppressive effects of Fasciola excretory/secretory (ES) and tegument (TEG) and their fractions were also investigated. Our results showed that both ES and TEG had significant suppressive effects on lympho-proliferation, up to 74% and 92%, respectively. When these antigens were fractionated, fraction 3 (MW of >10000-30000) of both ES (64%) and TEG (59%) in addition to fraction 4 (MW of ≤ 10000) of TEG (38%) inherited the suppressive effects. Identification of the potential molecule(s) with such suppressive effects on lymphocytes in TEG fraction 4 could reveal vaccine candidates.

  15. Donor or recipient origin of posttransplant lymphoproliferative disorders following solid organ transplantation.

    PubMed

    Kinch, A; Cavelier, L; Bengtsson, M; Baecklund, E; Enblad, G; Backlin, C; Thunberg, U; Sundström, C; Pauksens, K

    2014-12-01

    Previous studies of donor or recipient origin of posttransplant lymphoproliferative disorders (PTLDs) following solid organ transplantation (SOT) have either been small or with selected patient groups. We studied tumor origin in a population-based cohort of 93 patients with PTLD following SOT. Tumor origin of PTLD tissue was analyzed by fluorescence in situ hybridization of the sex chromosomes in cases of sex mismatch between donor and recipient (n = 41), or HLA genotyping in cases of identical sex but different HLA type (n = 52). Tumor origin of PTLD could be determined in 67 of the 93 cases. All 67 PTLDs were of recipient origin. They were found in recipients of kidney (n = 38), liver (n = 12), heart (n = 10) and lung (n = 7). The most common recipient-derived lymphomas were monomorphic B-cell PTLDs (n = 45), monomorphic T cell PTLDs (n = 9), indolent lymphomas (n = 6), and polymorphic PTLD (n = 4). Half of the recipient-derived PTLDs were Epstein-Barr virus-positive. Twelve of the recipient-derived PTLDs were located in the grafts: in four cases exclusively and in eight cases in combination with disseminated disease outside the graft. Tumor origin was indeterminable in 26 cases, probably due to low DNA quality. We conclude that the vast majority of PTLDs after SOT was of recipient origin.

  16. Breast Implant–Associated ALCL: A Unique Entity in the Spectrum of CD30+ Lymphoproliferative Disorders

    PubMed Central

    Story, Sara K.; Schowalter, Michael K.

    2013-01-01

    CD30+ lymphoproliferative disorders represent a spectrum of diseases with distinct clinical phenotypes ranging from reactive conditions to aggressive systemic anaplastic lymphoma kinase (ALK)− anaplastic large cell lymphoma (ALCL). In January 2011, the U.S. Food and Drug Administration (FDA) announced a possible association between breast implants and ALCL, which was likened to systemic ALCL and treated accordingly. We analyzed existing data to see if implant-associated ALCL (iALCL) may represent a distinct entity, different from aggressive ALCL. We conducted a systematic review of publications regarding ALCL and breast implantation for 1990–2012 and contacted corresponding authors to obtain long-term follow-up where available. We identified 44 unique cases of iALCL, the majority of which were associated with seroma, had an ALK− phenotype (97%), and had a good prognosis, different from the expected 40% 5-year survival rate of patients with ALK− nodal ALCL (one case remitted spontaneously following implant removal; only two deaths have been reported to the FDA or in the scientific literature since 1990). The majority of these patients received cyclophosphamide, doxorubicin, vincristine, and prednisolone with or without radiation, but radiation alone also resulted in complete clinical responses. It appears that iALCL demonstrates a strong association with breast implants, a waxing and waning course, and an overall good prognosis, with morphology, cytokine profile, and biological behavior similar to those of primary cutaneous ALCL. Taken together, these data are suggestive that iALCL may start as a reactive process with the potential to progress and acquire an aggressive phenotype typical of its systemic counterpart. A larger analysis and prospective evaluation and follow-up of iALCL patients are necessary to definitively resolve the issue of the natural course of the disease and best therapeutic approaches for these patients. PMID:23429741

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  19. Limited sampling strategy of mycophenolic acid in adult kidney transplant recipients: influence of the post-transplant period and the pharmacokinetic profile.

    PubMed

    Chaabane, Amel; Aouam, Karim; Ben Fredj, Nadia; Hammouda, Mouna; Chadly, Zohra; El May, Mezri; Boughattas, Naceur; Skhiri, Habib

    2013-09-01

    We aimed to develop an accurate and convenient LSS for predicting MPA-AUC(0-12 hours) in Tunisian adult kidney transplant recipients whose immunosuppressive regimen consisted of MMF and tacrolimus combination with regards to the post-transplant period and the pharmacokinetic profile. Each pharmacokinetic profile consisted of eight blood samples collected during the 12-hour dosing interval. The AUC(0-12 hours) was calculated according to the linear trapezoidal rule. The MPA concentrations at each sampling time were correlated by a linear regression analysis with the measured AUC(0-12). We analyzed all the developed models for their ability to estimate the MPA-AUC(0-12 hours). The best multilinear regression model for predicting the full MPA-AUC(0-12 hours) was found to be the combination of C1, C4, and C6. All the best correlated models and the most convenient ones were verified to be also applicable before 5 months after transplantation and thereafter. These models were also verified to be applicable for patients having or not the second peak in their pharmacokinetic profiles. For practical reasons we recommend a LSS using C0, C1, and C4 that provides a reasonable MPA-AUC(0-12 hours) estimation. PMID:23813362

  20. A Metabolomic Approach (1H HRMAS NMR Spectroscopy) Supported by Histology to Study Early Post-transplantation Responses in Islet-transplanted Livers

    PubMed Central

    Vivot, Kevin; Benahmed, Malika A.; Seyfritz, Elodie; Bietiger, William; Elbayed, Karim; Ruhland, Elisa; Langlois, Allan; Maillard, Elisa; Pinget, Michel; Jeandidier, Nathalie; Gies, Jean-Pierre; Namer, Izzie-Jacques; Sigrist, Séverine; Reix, Nathalie

    2016-01-01

    Intrahepatic transplantation of islets requires a lot of islets because more than 50% of the graft is lost during the 24 hours following transplantation. We analyzed, in a rat model, early post-transplantation inflammation using systemic inflammatory markers, or directly in islet-transplanted livers by immunohistochemistry. 1H HRMAS NMR was employed to investigate metabolic responses associated with the transplantation. Inflammatory markers (Interleukin-6, α2-macroglobulin) are not suitable to follow islet reactions as they are not islet specific. To study islet specific inflammatory events, immunohistochemistry was performed on sections of islet transplanted livers for thrombin (indicator of the instant blood-mediated inflammatory reaction (IBMIR)) and granulocytes and macrophages. We observed a specific correlation between IBMIR and granulocyte and macrophage infiltration after 12 h. In parallel, we identified a metabolic response associated with transplantation: after 12 h, glucose, alanine, aspartate, glutamate and glutathione were significantly increased. An increase of glucose is a marker of tissue degradation, and could be explained by immune cell infiltration. Alanine, aspartate and glutamate are inter-connected in a common metabolic pathway known to be activated during hypoxia. An increase of glutathione revealed the presence of antioxidant protection. In this study, IBMIR visualization combined with 1H HRMAS NMR facilitated the characterization of cellular and molecular pathways recruited following islet transplantation. PMID:27766032

  1. Chronic natural killer lymphoproliferative disorders: characteristics of an international cohort of 70 patients

    PubMed Central

    Poullot, E.; Zambello, R.; Leblanc, F.; Bareau, B.; De March, E.; Roussel, M.; Boulland, M. L.; Houot, R.; Renault, A.; Fest, T.; Semenzato, G.; Loughran, T.; Lamy, T.

    2014-01-01

    Background The 2008 World Health Organization (WHO) classification distinguishes three entities among the large granular lymphocytic leukemia (LGL leukemia): T-cell LGL leukemia (T-LGL leukemia), aggressive natural killer (NK) cell leukemia, and chronic NK lymphoproliferative disorders (LPD), the later considered as a provisional entity. Only a few and small cohorts of chronic NK LPD have been published. Patients and methods We report here clinicobiological features collected retrospectively from 70 cases of chronic NK LPD, and compared with those of T-LGL leukemia. Results There were no statistical differences between chronic NK LPD and T-LGL leukemia concerning median age [61 years (range 23–82 years)], organomegaly (26%), associated autoimmune diseases (24%), and associated hematological malignancies (11%). Patients with chronic NK LPD were significantly less symptomatic (49% versus 18%, P < 0.001) and the association with rheumatoid arthritis was more rarely observed (7% versus 17%, P = 0.03). The neutropenia (<0.5 × 109/l) was less severe in chronic NK LPD (33% versus 61%, P < 0.001) without difference in the rate of recurrent infections. STAT3 mutation was detected in 12% of the cohort, which is lower than the frequency observed in T-LGL leukemia. Thirty-seven percent of the patients required specific therapy. Good results were obtained with cyclophosphamide. Overall and complete response rates were, respectively, 69% and 56%. Overall survival was 94% at 5 years. Conclusion This study suggests very high similarities between chronic NK LPD and T-LGL leukemias. Since chronic NK LPD is still a provisional entity, our findings should be helpful when considering further revisions of the WHO classification. PMID:25096606

  2. Cell-engineered human elastic chondrocytes regenerate natural scaffold in vitro and neocartilage with neoperichondrium in the human body post-transplantation.

    PubMed

    Yanaga, Hiroko; Imai, Keisuke; Koga, Mika; Yanaga, Katsu

    2012-10-01

    cartilage. Using our multilayered culture system supplemented with FGF2, elastic chondrocytes produce an ECM and also exhibit an intercellular network; therefore, they are able to maintain tissue integrity post-transplantation. These findings realized a clinical application for generative cartilage surgery.

  3. Screening for cardiovascular disease before kidney transplantation

    PubMed Central

    Palepu, Sneha; Prasad, G V Ramesh

    2015-01-01

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

  4. Changes in Pre- and Post-Exercise Gene Expression among Patients with Chronic Kidney Disease and Kidney Transplant Recipients

    PubMed Central

    Coletta, Dawn K.; Campbell, Latoya E.; Weil, Jennifer; Kaplan, Bruce; Clarkson, Marie; Finlayson, Jean; Mandarino, Lawrence J.; Chakkera, Harini A.

    2016-01-01

    Introduction Decreased insulin sensitivity blunts the normal increase in gene expression from skeletal muscle after exercise. In addition, chronic inflammation decreases insulin sensitivity. Chronic kidney disease (CKD) is an inflammatory state. How CKD and, subsequently, kidney transplantation affects skeletal muscle gene expression after exercise are unknown. Methods Study cohort: non-diabetic male/female 4/1, age 52±2 years, with end-stage CKD who underwent successful kidney transplantation. The following were measured both pre-transplant and post-transplant and compared to normals: Inflammatory markers, euglycemic insulin clamp studies determine insulin sensitivity, and skeletal muscle biopsies performed before and within 30 minutes after an acute exercise protocol. Microarray analyses were performed on the skeletal muscle using the 4x44K Whole Human Genome Microarrays. Since nuclear factor of activated T cells (NFAT) plays an important role in T cell activation and calcineurin inhibitors are mainstay immunosuppression, calcineurin/NFAT pathway gene expression was compared at rest and after exercise. Log transformation was performed to prevent skewing of data and regression analyses comparing measures pre- and post-transplant performed. Result Markers of inflammation significantly improved post-transplantation. Insulin infusion raised glucose disposal slightly lower post-transplant compared to pre-transplant, but not significantly, thus concluding differences in insulin sensitivity were similar. The overall pattern of gene expression in response to exercise was reduced both pre-and post-transplant compared to healthy volunteers. Although significant changes were observed among NFAT/Calcineurin gene at rest and after exercise in normal cohort, there were no significant differences comparing NFAT/calcineurin pathway gene expression pre- and post-transplant. Conclusions Despite an improvement in serum inflammatory markers, no significant differences in glucose

  5. Role of Metabolism by Intestinal Bacteria in Arbutin-Induced Suppression of Lymphoproliferative Response in vitro

    PubMed Central

    Kang, Mi Jeong; Ha, Hyun Woo; Kim, Ghee Hwan; Lee, Sang Kyu; Ahn, Young Tae; Kim, Dong Hyun; Jeong, Hye Gwang; Jeong, Tae Cheon

    2012-01-01

    Role of metabolism by intestinal bacteria in arbutin-induced immunotoxicity was investigated in splenocyte cultures. Following an incubation of arbutin with 5 different intestinal bacteria for 24 hr, its aglycone hydroquinone could be produced and detected in the bacterial culture media with different amounts. Toxic effects of activated arbutin by intestinal bacteria on lymphoproliferative response were tested in splenocyte cultures from normal mice. Lipopolysaccharide and concanavalin A were used as mitogens for B- and T-cells, respectively. When bacteria cultured medium with arbutin was treated into the splenocytes for 3 days, the medium cultured with bacteria producing large amounts of hydroquinone induced suppression of lymphoproliferative responses, indicating that metabolic activation by intestinal bacteria might be required in arbutin-induced toxicity. The results indicated that the present testing system might be applied for determining the possible role of metabolism by intestinal bacteria in certain chemical-induced immunotoxicity in animal cell cultures. PMID:24116295

  6. Everolimus in combination with mycophenolate mofetil as pre- and post-transplantation immunosuppression after nonmyeloablative hematopoietic stem cell transplantation in canine littermates.

    PubMed

    Machka, Christoph; Lange, Sandra; Werner, Juliane; Wacke, Rainer; Killian, Doreen; Knueppel, Anne; Knuebel, Gudrun; Vogel, Heike; Lindner, Iris; Roolf, Catrin; Murua Escobar, Hugo; Junghanss, Christian

    2014-09-01

    The mammalian target of rapamycin inhibitor everolimus (RAD001) is a successfully used immunosuppressant in solid-organ transplantation. Several studies have already used RAD001 in combination with calcineurin inhibitors after hematopoietic stem cell transplantation (HSCT). We investigated calcineurin inhibitor-free pre- and post-transplantation immunosuppression of RAD001 combined with mycophenolate mofetil (MMF) in a nonmyeloablative HSCT setting. After nonmyeloablative conditioning with 2 Gy total body irradiation, 8 dogs received HSCT from dog leukocyte antigen-identical siblings. Immunosuppressives were given at doses of 1.5 mg RAD001 twice daily from day -1 to +49, then tapered until day +56, and 20 mg/kg MMF from day 0 to +28, then tapered until day +42. An historical cyclosporin A (CsA)/MMF regimen was used in the control group. All dogs engrafted. Median platelet nadir amounted in all dogs to 0 × 10(9)/L (median, day +10; duration <50 × 10(9)/L, 22 days) and median leukocyte nadir was 1.0 × 10(9)/L (range, .1 to 2.5 × 10(9)/L; median, day +13). Eventually, 5 of 8 (63%) animals rejected their grafts. Two dogs died of infections on day +19 and +25. Pharmacokinetics of RAD001 and MMF showed median trough levels of 19.1 (range, 10.5 to 43.2) μg/L and .3 (.1 to 1.3) mg/L, respectively. The median area under the curve was 325 (range, 178 to 593) μg/L × hour for RAD001 and 29.6 (range, 7.9 to 40.5) ng/L × hour for MMF. All dogs developed clinically mucosal viral infections during the clinical course. Compared with the control group, the level of toxicities for RAD001/MMF increased in all qualities. Combined immunosuppression of RAD001 and MMF after nonmyeloablative HSCT is associated with significant toxicities, including a prolonged platelet recovery time as well as increased infections compared to the CsA/MMF regimen. PMID:24923538

  7. Methotrexate-associated B-cell lymphoproliferative disorders presenting in the skin: A clinicopathologic and immunophenotypical study of 10 cases.

    PubMed

    Koens, Lianne; Senff, Nancy J; Vermeer, Maarten H; Willemze, Rein; Jansen, Patty M

    2014-07-01

    Methotrexate (MTX)-associated B-cell lymphoproliferative disorders (B-LPD) may first present in the skin, but their clinicopathologic features are still ill defined. Differentiation from primary cutaneous follicle center lymphoma and primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) is important, as MTX-associated B-LPD may show spontaneous regression after withdrawal of MTX therapy. In the present study, the clinicopathologic and phenotypical features of 10 patients with MTX-associated B-LPD first presenting in the skin, including 5 EBV(+) and 5 EBV(-) cases, were investigated. Six patients had skin-limited disease. Clinically, abrogation of MTX therapy resulted in a complete response in 4 cases and a partial response in another 2. The 5-year disease-specific survival was 90%. MTX-associated B-LPD differed from primary cutaneous follicle center lymphoma by the presence of ulcerating and/or generalized skin lesions, an infiltrate composed of centroblasts/immunoblasts rather than large centrocytes, reduced staining for CD79a, and expression of BCL2, IRF4, and FOXP1 in most cases. EBV(+) MTX-associated B-LPD differed from PCLBCL-LT by the presence ulcerative skin lesions, marked tumor cell polymorphism, reduced staining for CD79a, and expression of CD30 and EBV. EBV(-) cases showed morphologic and immunophenotypical similarities to PCLBCL-LT but differed by presentation with generalized skin lesions in 4 of 5 cases. The results of this study, showing a relatively good clinical outcome and spontaneous disease regression after only withdrawal of MTX in a considerable proportion of patients, underscores the importance of a careful wait-and-see policy before considering more aggressive therapies in patients with MTX-associated B-LPD of the skin.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Gitto, Stefano; Villa, Erica

    2016-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  13. No evidence of HTLV-I proviral integration in lymphoproliferative disorders associated with cutaneous T-cell lymphoma.

    PubMed Central

    Wood, G. S.; Schaffer, J. M.; Boni, R.; Dummer, R.; Burg, G.; Takeshita, M.; Kikuchi, M.

    1997-01-01

    Several recent studies have reported detection of HTLV-I genetic sequences in patients with cutaneous T-cell lymphoma (CTCL) including mycosis fungoides and Sezary syndrome. The purpose of this study was to determine whether HTLV-I was detectable in lesional tissues of patients suffering from diseases known to be associated with CTCL. Thirty-five cases were obtained from diverse geographical locations including Ohio, California, Switzerland, and Japan. Six of them had concurrent CTCL. Cases were analyzed using a combination of genomic polymerase chain reaction (PCR)/ Southern blot, dot blot, and Southern blot analyses. All assays were specific for HTLV-I provirus. Sensitivity ranged from approximately 10(-6) for PCR-based studies to 10(-2) for unamplified genomic blotting. Lesional DNA from patients with lymphomatoid papulosis (fourteen cases), Hodgkin's disease (twelve cases), and CD30+ large-cell lymphoma (nine cases) was tested for the HTLV-I proviral pX region using a genomic PCR assay followed by confirmatory Southern blot analysis with a nested oligonucleotide pX probe. All cases were uniformly negative. All of the Hodgkin's disease cases, eight of the large-cell lymphoma cases, and six of the lymphomatoid papulosis cases were then subjected to dot blot analysis of genomic DNA using a full-length HTLV-I proviral DNA probe that spans all regions of the HTLV-I genome. Again, all cases were negative. Finally, eleven of the Hodgkin's disease cases were also subjected to Southern blot analysis of EcoRI-digested genomic DNA using the same full-length HTLV-I probe. Once again, all cases were negative. These findings indicated that, despite utilization of a variety of sensitive and specific molecular biological methods, HTLV-I genetic sequences were not detectable in patients with CTCL-associated lymphoproliferative disorders. These results strongly suggest that the HTLV-I retrovirus is not involved in the pathogenesis of these diseases. Images Figure 1 Figure 2

  14. Clinical and In Vitro Studies on Impact of High-Dose Etoposide Pharmacokinetics Prior Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia on the Risk of Post-Transplant Leukemia Relapse.

    PubMed

    Sobiak, Joanna; Kazimierczak, Urszula; Kowalczyk, Dariusz W; Chrzanowska, Maria; Styczyński, Jan; Wysocki, Mariusz; Szpecht, Dawid; Wachowiak, Jacek

    2015-10-01

    The impact of etoposide (VP-16) plasma concentrations on the day of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on leukemia-free survival in children with acute lymphoblastic leukemia (ALL) was studied. In addition, the in vitro effects of VP-16 on the lymphocytes proliferation, cytotoxic activity and on Th1/Th2 cytokine responses were assessed. In 31 children undergoing allo-HSCT, VP-16 plasma concentrations were determined up to 120 h after the infusion using the HPLC-UV method. For mentioned in vitro studies, VP-16 plasma concentrations observed on allo-HSCT day were used. In 84 % of children, VP-16 plasma concentrations (0.1-1.5 μg/mL) were quantifiable 72 h after the end of the drug infusion, i.e. when allo-HSCT should be performed. In 20 (65 %) children allo-HSCT was performed 4 days after the end of the drug infusion, and VP-16 was still detectable (0.1-0.9 μg/mL) in plasma of 12 (39 %) of them. Post-transplant ALL relapse occurred in four children, in all of them VP-16 was detectable in plasma (0.1-0.8 μg/mL) on allo-HSCT day, while there was no relapse in children with undetectable VP-16. In in vitro studies, VP-16 demonstrated impact on the proliferation activity of stimulated lymphocytes depending on its concentration and exposition time. The presence of VP-16 in plasma on allo-HSCT day may demonstrate an adverse effect on graft-versus-leukemia (GvL) reaction and increase the risk of post-transplant ALL relapse. Therefore, if 72 h after VP-16 administration its plasma concentration is still above 0.1 μg/mL then the postponement of transplantation for next 24 h should be considered to protect GvL effector cells from transplant material.

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

    PubMed

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

    2014-11-01

    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.

  16. Lymphoproliferative Disease and Hepatitis B Reactivation: Challenges in the Era of Rapidly Evolving Targeted Therapy.

    PubMed

    Phipps, Colin; Chen, Yunxin; Tan, Daryl

    2016-01-01

    Reactivation of hepatitis B virus (HBV) is a known complication that occurs in patients receiving chemotherapy especially for malignant lymphoma. The increased risk in lymphoma patients parallels the potency of the immunosuppressive treatment regimens that are provided. B-cell-depleting therapy such as anti-CD20 monoclonal antibodies, especially when combined with conventional chemotherapy, significantly increases the risk of HBV reactivation, even in patients with resolved HBV infection. The first reports of HBV reactivation with anti-CD20 therapy emerged only 4 years after its US Food and Drug Administration approval. Today, these drugs carry alert warnings on the risk of hepatic dysfunction and reactivation of HBV infection. Many other new/novel agents active against lymphoma have emerged since then, targeting the different pathways involved in lymphoma pathogenesis, including histone deacetylase inhibitors, antibody-drug conjugates, and proteasome inhibitors. These various drugs have differing depths and mechanisms of immunosuppression, necessitating due diligence when administrating these compounds to prevent infective complications such as HBV reactivation, which can lead to liver failure and death. This review focuses on HBV reactivation with non-Hodgkin lymphoma treatment, in particular with the various approved novel agents. We also discuss the current recommendations for screening non-Hodgkin lymphoma patients for HBV and the role of prophylactic antiviral therapy during and after immunosuppressive treatment.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

    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

    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

  19. A 47-year-old stem cell transplant recipient with fever, cough and chest pain

    PubMed Central

    Salh, Omar S; Nadhem, Omar N; Thakore, Sanket R; Halloush, Ruba A; Khasawneh, Faisal A

    2015-01-01

    Infections and malignancies are among the most serious complications that follow organ or stem cell transplantation. They may have a mild course, and nonspecific and overlapping manifestations. The present article describes a case of symptomatic nodular pulmonary disease that complicated hematopoietic stem cell transplantation. It was diagnosed to be post-transplant lymphoproliferative disorder, a potential sequela of immunosuppression and a very difficult entity to treat in profoundly immunosuppressed patients. PMID:26057372

  20. What can happen after lung transplantation and the importance of the time since transplantation: radiological review of post-transplantation complications.

    PubMed

    Daimiel Naranjo, I; Alonso Charterina, S

    2016-01-01

    Lung transplantation is the best treatment option in the final stages of diseases such as cystic fibrosis, pulmonary hypertension, chronic obstructive pulmonary disease, or idiopathic pulmonary fibrosis. Better surgical techniques and advances in immunosuppressor treatments have increased survival in lung transplant recipients, making longer follow-up necessary because complications can occur at any time after transplantation. For practical purposes, complications can be classified as early (those that normally occur within two months after transplantation), late (those that normally occur more than two months after transplantation), or time-independent (those that can occur at any time after transplantation). Many complications have nonspecific clinical and radiological manifestations, so the time factor is key to narrow the differential diagnosis. Imaging can guide interventional procedures and can detect complications early. This article aims to describe and illustrate the complications that can occur after lung transplantation from the clinical and radiological viewpoints so that they can be detected as early as possible.

  1. Hepatitis C virus infection and risk of posttransplantation lymphoproliferative disorder among solid organ transplant recipients

    PubMed Central

    Landgren, Ola; Chatterjee, Nilanjan; Castenson, David; Parsons, Ruth; Hoover, Robert N.; Engels, Eric A.

    2007-01-01

    Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. Hepatitis C virus (HCV) infection has been linked to increased risk of lymphoma among immunocompetent individuals. We therefore investigated the association between HCV infection and PTLD in a retrospective cohort study of all individuals in the United States who received their first solid organ transplant from 1994 to 2005 (N = 210 763) using Scientific Registry of Transplant Recipients data. During follow-up, 1630 patients with PTLD were diagnosed. HCV prevalence at transplantation was 11.3%. HCV infection did not increase PTLD risk in the total cohort (Cox regression model, hazard ratio [HR] = 0.84; 95% confidence interval [CI] 0.68-1.05), even after adjustment for type of organ transplanted, indication for transplantation, degree of HLA mismatch, donor type, or use of immunosuppression medications. Additional analyses also revealed no association by PTLD subtype (defined by site, pathology, cell type, and tumor Epstein-Barr virus [EBV] status). HCV infection did increase PTLD risk among the 2.8% of patients (N = 5959) who were not reported to have received immunosuppression maintenance medications prior to hospital discharge (HR = 3.09; 95% CI, 1.14-8.42; P interaction = .007). Our findings suggest that HCV is not a major risk factor for PTLD, which is consistent with the model in which an intact immune system is necessary for development of HCV-related lymphoproliferation. PMID:17855632

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

    PubMed Central

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

    2014-01-01

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

  3. Hyperactive mTOR pathway promotes lymphoproliferation and abnormal differentiation in autoimmune lymphoproliferative syndrome.

    PubMed

    Völkl, Simon; Rensing-Ehl, Anne; Allgäuer, Andrea; Schreiner, Elisabeth; Lorenz, Myriam Ricarda; Rohr, Jan; Klemann, Christian; Fuchs, Ilka; Schuster, Volker; von Bueren, André O; Naumann-Bartsch, Nora; Gambineri, Eleonora; Siepermann, Kathrin; Kobbe, Robin; Nathrath, Michaela; Arkwright, Peter D; Miano, Maurizio; Stachel, Klaus-Daniel; Metzler, Markus; Schwarz, Klaus; Kremer, Anita N; Speckmann, Carsten; Ehl, Stephan; Mackensen, Andreas

    2016-07-14

    Autoimmune lymphoproliferative syndrome (ALPS) is a human disorder characterized by defective Fas signaling, resulting in chronic benign lymphoproliferation and accumulation of TCRαβ(+) CD4(-) CD8(-) double-negative T (DNT) cells. Although their phenotype resembles that of terminally differentiated or exhausted T cells, lack of KLRG1, high eomesodermin, and marginal T-bet expression point instead to a long-lived memory state with potent proliferative capacity. Here we show that despite their terminally differentiated phenotype, human ALPS DNT cells exhibit substantial mitotic activity in vivo. Notably, hyperproliferation of ALPS DNT cells is associated with increased basal and activation-induced phosphorylation of serine-threonine kinases Akt and mechanistic target of rapamycin (mTOR). The mTOR inhibitor rapamycin abrogated survival and proliferation of ALPS DNT cells, but not of CD4(+) or CD8(+) T cells in vitro. In vivo, mTOR inhibition reduced proliferation and abnormal differentiation by DNT cells. Importantly, increased mitotic activity and hyperactive mTOR signaling was also observed in recently defined CD4(+) or CD8(+) precursor DNT cells, and mTOR inhibition specifically reduced these cells in vivo, indicating abnormal programming of Fas-deficient T cells before the DNT stage. Thus, our results identify the mTOR pathway as a major regulator of lymphoproliferation and aberrant differentiation in ALPS.

  4. Lymphoproliferative response and its relationship with histological lesions in experimental ovine paratuberculosis and its diagnostic implications.

    PubMed

    Kurade, N P; Tripathi, B N

    2008-01-01

    Lymphoproliferative response (LPR) was studied in 19 lambs orally infected (Group I) with Mycobacterium avium subsp. paratuberculosis (MAP) with in vitro lymphocyte stimulation test using MTT dye reduction assay. The non-specific LPR against Con A and specific LPR against sonicated antigen and johnin PPD (purified protein derivatives) were estimated on preinfection (0 day) and various days postinfection period (15 to 330 dpi) in the animals, which were classified according to histological and bacteriological evidence of paratuberculosis infection. Of the two antigens used, johnin PPD was found to be superior in terms of consistency and uniformity of response over an observation period of about a year. Significantly (P<0.05) higher LPR were observed in the infected sheep during postinfection period, as compared with preinfection values and values from uninfected control sheep. It was evident from the present study that the LPR in histologically infected animals fluctuated during the long course of infection and had a definite relationship with the gut pathology and the mycobacterial load. The LPR were stronger but variable in sheep with grades 1, 2 and 3 lesions (paucibacillary) and increased progressively from 30 dpi onwards. The sheep with the advanced lesions (grade 4, multibacillary) showed progressive decline in LPR till 120 dpi after initial stronger response at 30 dpi. Most of the animals were detected by LPR before initiation of faecal shedding of MAP. The results suggested that repeated testing was required while screening an infected flock for detecting most of the positive animals. PMID:17619156

  5. HIV-specific lymphoproliferative responses in asymptomatic HIV-infected individuals.

    PubMed Central

    Pontesilli, O; Carlesimo, M; Varani, A R; Ferrara, R; Guerra, E C; Bernardi, M L; Ricci, G; Mazzone, A M; D'Offizi, G; Aiuti, F

    1995-01-01

    In vitro lymphoproliferative responses to HIV-1 recombinant antigens (gp160, p24, and Rev protein) were studied in 83 patients with asymptomatic HIV-1 infection (CDC groups II and III) and circulating CD4 lymphocyte numbers > 400/mm3. Significant response to at least one of the three antigens was detected in 52.4% of the subjects, but the responses were weak, and concordance of the response to the three antigens was rare, the frequency of individuals responding to each antigen not exceeding 22.4%. Increasing frequencies of response were observed when recall antigens (tetanus toxoid and Candida albicans glycomannoprotein) (65.5%) and anti-CD3 MoAb (76.6%) were used as stimuli. Although a significant association between lymphocyte response to p24, but not gp160, and steadiness of CD4 lymphocyte numbers before the assay was observed, no predictive value for lack of CD4 cell decrease was confirmed for either antigen, and fluctuation of the responses to HIV antigens was seen during subsequent follow up. The panel of T cell assays used could be regarded as appropriate for monitoring both HIV-specific responses and T lymphocyte function during immunotherapy with soluble HIV antigens. PMID:7774051

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

    PubMed

    de Bielke, María Gabriela Simesen; Perez, Laura; Yancoski, Judith; Oliveira, João Bosco; Danielian, Silvia

    2015-11-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. Liver transplantation in the Nordic countries – An intention to treat and post-transplant analysis from The Nordic Liver Transplant Registry 1982–2013

    PubMed Central

    Fosby, Bjarte; Melum, Espen; Bjøro, Kristian; Bennet, William; Rasmussen, Allan; Andersen, Ina Marie; Castedal, Maria; Olausson, Michael; Wibeck, Christina; Gotlieb, Mette; Gjertsen, Henrik; Toivonen, Leena; Foss, Stein; Makisalo, Heikki; Nordin, Arno; Sanengen, Truls; Bergquist, Annika; Larsson, Marie E.; Soderdahl, Gunnar; Nowak, Greg; Boberg, Kirsten Muri; Isoniemi, Helena; Keiding, Susanne; Foss, Aksel; Line, Pål-Dag; Friman, Styrbjörn; Schrumpf, Erik; Ericzon, Bo-Göran; Höckerstedt, Krister; Karlsen, Tom H.

    2015-01-01

    Abstract Aim and background. The Nordic Liver Transplant Registry (NLTR) accounts for all liver transplants performed in the Nordic countries since the start of the transplant program in 1982. Due to short waiting times, donor liver allocation has been made without considerations of the model of end-stage liver disease (MELD) score. We aimed to summarize key outcome measures and developments for the activity up to December 2013. Materials and methods. The registry is integrated with the operational waiting-list and liver allocation system of Scandiatransplant (www.scandiatransplant.org) and accounted at the end of 2013 for 6019 patients out of whom 5198 were transplanted. Data for recipient and donor characteristics and relevant end-points retransplantation and death are manually curated on an annual basis to allow for statistical analysis and the annual report. Results. Primary sclerosing cholangitis, acute hepatic failure, alcoholic liver disease, primary biliary cirrhosis and hepatocellular carcinoma are the five most frequent diagnoses (accounting for 15.3%, 10.8%, 10.6%, 9.3% and 9.0% of all transplants, respectively). Median waiting time for non-urgent liver transplantation during the last 10-year period was 39 days. Outcome has improved over time, and for patients transplanted during 2004–2013, overall one-, five- and 10-year survival rates were 91%, 80% and 71%, respectively. In an intention-to-treat analysis, corresponding numbers during the same time period were 87%, 75% and 66%, respectively. Conclusion. The liver transplant program in the Nordic countries provides comparable outcomes to programs with a MELD-based donor liver allocation system. Unique features comprise the diagnostic spectrum, waiting times and the availability of an integrated waiting list and transplant registry (NLTR). PMID:25959101

  9. Marek’s disease virus induces transient atrophy of cecal tonsils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens caused by an immunosupperessive alpha herpesvirus, Marek’s disease virus (MDV). Clinical signs of MD include bursal/thymic atrophy and neurological disorders. The cecal tonsils (CT) are the largest lymphoid aggregates of avia...

  10. Marek’s disease virus-induced transient cecal tonsil atrophy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens that is caused by a highly cell-associated oncogenic '-herpesvirus, Marek’s disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latent infection within CD4+ T cells. MD is characterized by bursal/th...

  11. HLA Associations and Risk of Posttransplant Lymphoproliferative Disorder in a Danish Population-Based Cohort

    PubMed Central

    Vase, Maja Ølholm; Maksten, Eva Futtrup; Strandhave, Charlotte; Søndergaard, Esben; Bendix, Knud; Hamilton-Dutoit, Stephen; Andersen, Claus; Møller, Michael Boe; Sørensen, Søren Schwartz; Kampmann, Jan; Eiskjær, Hans; Iversen, Martin; Weinreich, Ilse Duus; Møller, Bjarne; Jespersen, Bente; d'Amore, Francesco

    2015-01-01

    Background Posttransplant lymphoproliferative disorder (PTLD) is a feared complication to organ transplantation, associated with substantial morbidity and inferior survival. Risk factors for PTLD include T cell–depleting induction therapy and primary infection or reactivation of Epstein-Barr virus. Possible associations between certain HLA types and the risk of developing PTLD have been reported by other investigators; however, results are conflicting. Methods We conducted a retrospective, population-based study on 4295 Danish solid organ transplant patients from the Scandiatransplant database. Having identified 93 PTLD patients in the cohort, we investigated the association of HLA types with PTLD, Epstein-Barr virus status and time to PTLD onset. The outcomes survival and PTLD were evaluated using Cox regression; mismatching, and the PTLD-specific mortality were evaluated in a competing risk analysis. Results Risk of PTLD was associated with male sex (odds ratio, 1.70; 95% confidence interval, 1.07-2.71), and, in women, HLA-DR13 conferred an increased risk (odds ratio, 3.22; 95% confidence interval, 1.41-7.31). In multivariate analysis, HLA-B45 and HLA-DR13 remained independent predictive factors of PTLD. Mismatching in the B locus was associated with a reduced risk of PTLD (P < 0.001). Overall survival was poor after a PTLD diagnosis and was significantly worse than that in the remaining transplant cohort (P < 0.001). Conclusions Our data indicate risk-modifying HLA associations, which can be clinically useful after transplantation in personalized monitoring schemes. Given the strong linkage disequilibrium in the HLA region, the associations must be interpreted carefully. The large size, virtually complete ascertainment of cases and no loss to follow-up remain important strengths of the study. PMID:27500227

  12. Cell sizing in chronic lymphoproliferative disorders: an aid to differential diagnosis.

    PubMed Central

    Alexander, H D; Markey, G M; Nolan, R L; Morris, T C

    1992-01-01

    AIMS: To determine if leucocyte volume distribution analysis (LVDA), obtained using a Coulter Counter Model S Plus IV, can be used to aid differentiation of chronic lymphoproliferative disorder (CLPD) subtypes. METHODS: Mean lymphocyte volume and lymphocyte distribution width were measured on each patient (n = 90) using a hard copy of an amplified LVDA histogram. The mean lymphocyte volume was taken as the mean of the values on either side of the peak at half maximum height. The lymphocyte distribution width was taken as the range of cell values between the two values used to calibrate the mean lymphocyte volume. A template showing typical histograms from commonly occurring CLPD was also produced on an acetate sheet. This was used to examine the histogram from each new patient to evaluate its usefulness as an alternative to the calculation of mean lymphocyte volume and lymphocyte distribution width. RESULTS: Mean lymphocyte volume and lymphocyte distribution width were significantly higher in B cell lymphocytic leukaemia of mixed cell type (B CLL/PL), B cell non-Hodgkin's lymphoma with peripheral blood spill, hairy cell leukaemia and T cell prolymphocytic leukaemia than in B cell chronic lymphocytic leukaemia (B CLL). The mean lymphocyte volume, but not the lymphocyte distribution width, was also significantly higher in T cell chronic lymphocytic leukaemia than in B CLL. The template gave an immediate preliminary indication of possible subtype(s) of disorder and could be used as an alternative to measurement of mean lymphocyte volume and lymphocyte distribution width. CONCLUSIONS: Electronic haematology analysers producing an LVDA provide a useful, cost effective cell sizing analysis which can aid the differentiation of subtypes of CLPD. Images PMID:1430257

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2013-07-25

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

  15. A case of multicentric Castleman's disease in HIV infection with the rare complication of acquired angioedema.

    PubMed

    Fernando, I; Scott, G

    2014-06-01

    Multicentric Castleman's disease (MCD), a polyclonal lymphoproliferative disorder of unknown aetiology, is a well-recognised complication of HIV disease. We present a case of MCD in an HIV-positive patient that is unusual on two counts: our patient's MCD first presented in the context of an immune restoration inflammatory syndrome (IRIS), following the initiation of highly active antiretroviral therapy (HAART). In addition, her MCD was associated with the unusual complication of acquired angioedema (AAE), which resolved following treatment of the MCD. While AAE is frequently found to have an underlying diagnosis of a lymphoproliferative disease, this is the first reported case linking AAE to MCD.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2014-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2011-01-01

    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

  20. Challenges in transplantation for alcoholic liver disease.

    PubMed

    Berlakovich, Gabriela A

    2014-07-01

    Transplantation for the treatment of alcoholic cirrhosis is more controversially discussed than it is for any other indication. The crucial aspect in this setting is abstinence before and after liver transplantation. We established pre-transplant selection criteria for potential transplant candidates. Provided that the underlying disease can be treated, there is no reason to withhold liver transplantation in a patient suffering from alcoholic cirrhosis. Evaluation of the patient by a multidisciplinary team, including an addiction specialist, is considered to be the gold standard. However, several centers demand a specified period of abstinence - usually 6 mo- irrespective of the specialist's assessment. The 6-mo rule is viewed critically because liver transplantation was found to clearly benefit selected patients with acute alcoholic hepatitis; the benefit was similar to that achieved for other acute indications. However, the discussion may well be an academic one because the waiting time for liver transplantation exceeds six months at the majority of centers. The actual challenge in liver transplantation for alcoholic cirrhosis may well be the need for lifelong post-transplant follow-up rather than the patient's pre-transplant evaluation. A small number of recipients experience a relapse of alcoholism; these patients are at risk for organ damage and graft-related death. Post-transplant surveillance protocols should demonstrate alcohol relapse at an early stage, thus permitting the initiation of adequate treatment. Patients with alcoholic cirrhosis are at high risk of developing head and neck, esophageal, or lung cancer. The higher risk of malignancies should be considered in the routine assessment of patients suffering from alcoholic cirrhosis. Tumor surveillance protocols for liver transplant recipients, currently being developed, should become a part of standard care; these will improve survival by permitting diagnosis at an early stage. In conclusion, the key

  1. Protective efficacy of a recombinant bacterial artificial chromosome clone of a very virulent Marek’s disease virus containing a reticuloendotheliosis virus long terminal repeat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease virus (MDV), an alphaherpesvirus, causes Marek’s disease (MD), a lymphoproliferative disease in poultry characterized by T-cell lymphomas, nerve lesions and mortality. Vaccination is used worldwide to control MD, but increasingly virulent field strains can overcome this protection, d...

  2. Composite Epstein-Barr Virus-Associated B-Cell Lymphoproliferative Disorder and Tubular Adenoma in a Rectal Polyp.

    PubMed

    Lo, Amy A; Gao, Juehua; Rao, M Sambasivia; Yang, Guang-Yu

    2016-02-01

    Composite tumors are formed when there is intermingling between two components of separate tumors seen histologically. Cases demonstrating composite tubular adenoma with other types of tumors in the colon are rare. Composite tubular adenomas with nonlymphoid tumors including carcinoids, microcarcinoids, and small cell undifferentiated carcinoma have been reported in the literature. The occurrence of composite lymphoma and tubular adenoma within the colorectal tract is extremely rare. Only three cases have been reported and include one case of mantle cell lymphoma and two cases of diffuse large B-cell lymphoma arising in composite tubular adenomas. We present the first case of composite Epstein-Barr virus-associated B-cell lymphoproliferative disorder and tubular adenoma in a rectal polyp with a benign endoscopic appearance.

  3. Leishmanin skin test lymphoproliferative responses and cytokine production after symptomatic or asymptomatic Leishmania major infection in Tunisia

    PubMed Central

    SASSI, A; LOUZIR, H; BEN SALAH, A; MOKNI, M; BEN OSMAN, A; DELLAGI, K

    1999-01-01

    Resistance to Leishmania parasite infection requires the development of a cellular immune response that activates macrophage leishmanicidal activity. In this study we have investigated the lymphoproliferative responses and in vitro cytokine production of peripheral blood mononuclear cells (PBMC) from individuals living in an endemic area for L. major infection in Tunisia. The results were compared with the DTH reaction of the leishmanin skin test (LST). Sixty-seven individuals were included in the study: 22 persons (age range 9–60 years) who developed, 2 years before the present study, a parasitologically confirmed localized cutaneous leishmaniasis (LCL) that healed spontaneously, and 45 individuals (age range 18–20 years) born and living in the same area, with no previous history of LCL. LST was positive (skin induration ≥ 5 mm) in 20/22 cured cases of LCL and in 75% of healthy individuals without history of LCL. LST+ individuals expressed vigorous Leishmania-specific lymphoproliferative responses associated with in vitro production of interferon-gamma (IFN-γ) but not IL-4. Interestingly, IL-10 was detected in parallel with the highest levels of IFN-γ in PBMC supernatants from 3/20 cured LCL and 8/25 individuals without history of LCL. Our results showed a 98% concordance between the DTH reaction assessed by LST and the in vitro proliferative assay induced by soluble leishmanial antigens. Moreover, proliferative assays as well as cytokine analysis did not show any significant difference of the immune memory to parasite antigens developed by patients who had overt cutaneous leishmaniasis and those who had apparently asymptomatic infection. PMID:10209516

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  5. Marek's disease virus immunosuppression alters host cellular responses and immune gene expression in the skin of infected chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a highly contagious lymphoproliferative and neuropathic disease of chickens. The feather follicle epithelium (FFE) is the only anatomical site within the host where infectious enveloped cell-free MD virus (MDV) particles are produced and disseminated into the environment. MD ...

  6. Chest neoplasms with infectious etiologies.

    PubMed

    Restrepo, Carlos S; Chen, Melissa M; Martinez-Jimenez, Santiago; Carrillo, Jorge; Restrepo, Catalina

    2011-12-28

    A wide spectrum of thoracic tumors have known or suspected viral etiologies. Oncogenic viruses can be classified by the type of genomic material they contain. Neoplastic conditions found to have viral etiologies include post-transplant lymphoproliferative disease, lymphoid granulomatosis, Kaposi's sarcoma, Castleman's disease, recurrent respiratory papillomatosis, lung cancer, malignant mesothelioma, leukemia and lymphomas. Viruses involved in these conditions include Epstein-Barr virus, human herpes virus 8, human papillomavirus, Simian virus 40, human immunodeficiency virus, and Human T-lymphotropic virus. Imaging findings, epidemiology and mechanism of transmission for these diseases are reviewed in detail to gain a more thorough appreciation of disease pathophysiology for the chest radiologist.

  7. 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...

  8. [Castleman disease].

    PubMed

    Sánchez de Toledo Sancho, J; Fàbrega Sabaté, J; Marhuenda Irastorza, C; Lucaya Layret, X; Torán Fuentes, N; Gros Subias, L; Sábado Alvarez, C

    2005-07-01

    Castleman disease or angiofollicular hyperplasia is a rare disorder included in the group of lymphoproliferative disorders. This entity was originally described by Castleman in 1956. The etiology remains unknown but it is postulated to be a reactive lymphoid hyperplasia due to chronic antigenic stimulation caused by a viral infection. The disease presents in young adults and is more frequent in women; it is exceptionally rare in the pediatric age group. It is classified into two clinical groups (localized disease and disseminated disease) and there are two histologic variants (hyaline-vascular and plasma cell Castleman disease). Localized disease is usually asymptomatic, has a good prognosis, and is the most common presentation in pediatric patients, usually corresponding to highly vascularized mediastinal masses. Resection of the mass, which is curative, is associated with a high risk of blood loss. Recently, preoperative arteriography with embolization has been used satisfactorily in the preoperative management of these tumors. We present a case of localized Castleman disease in a 12-year-old girl satisfactorily treated with embolization before curative resection.

  9. Salvia Hispanica Seed in Reducing Risk of Disease Recurrence in Patients With Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-08-26

    Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Adult T-Cell Leukemia/Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; B Lymphoblastic Leukemia/Lymphoma; Blastic Plasmacytoid Dendritic Cell Neoplasm; Burkitt Leukemia; Central Nervous System Lymphoma; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Diffuse Large B-Cell Lymphoma; Enteropathy-Associated T-Cell Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3 Follicular Lymphoma; Hepatosplenic T-Cell Lymphoma; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Mycosis Fungoides; Nasal Type Extranodal NK/T-Cell Lymphoma; Nodal Marginal Zone Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Post-Transplant Lymphoproliferative Disorder; Primary Cutaneous Anaplastic Large Cell Lymphoma; Primary Effusion Lymphoma; Sezary Syndrome; Splenic Marginal Zone Lymphoma; Subcutaneous Panniculitis-Like T-Cell Lymphoma; Systemic Anaplastic Large Cell Lymphoma; T Lymphoblastic Leukemia/Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  10. [Analyses of the rearrangement of T-cell receptor- and immunoglobulin genes in the diagnosis of lymphoproliferative disorders].

    PubMed

    Griesser, D H

    1995-01-01

    Rearrangements are developmentally regulated genetic recombinations in T and B cells which generate functional T cell receptor (TcR) and immunoglobulin genes, respectively. Different variable, sometimes diversity, and joining gene segments which are discontinuously spread out within their chromosomal location in germline configuration, are randomly assembled in individual lymphocytes. These rearrangements can be detected by Southern Blot analysis if more than 5% of a total lymphocyte population in a biopsy specimen carries the same clonal rearrangement. We analyzed DNA from 324 snap-frozen biopsy specimens from lympho-proliferative disorders. None of the 20 reactive lesions and four malignant myelomonocytic tumors had a clonal antigen receptor gene rearrangement. All 117 malignant B cell lymphomas of different subtypes and 95 of 97 malignant T cell lymphomas showed a clonal gene rearrangement. Only two angioimmunoblastic lymphadenopathy(AILD)-type T cell lymphomas did not have immune receptor gene rearrangements. They were morphologically indistinguishable from the other 47 T/AILD lymphomas with clonal rearrangement patterns. In most cases TcR beta and immunoglobulin heavy chain (IgH) gene probes were sufficient for lineage assignment of the clonal T or B lymphocyte population. In 18% of B lymphomas, however, a cross-lineage rearrangement of TcR beta genes, and in 20% of the T cell lymphomas a clonal IgH gene rearrangement was detected. After exclusion of centrocytic, large cell anaplastic lymphomas (LCAL) of B-type, and T/AILD lymphomas which are overrepresented in our study, only 10% of the remaining 147 T and B cell lymphomas had aberrant rearrangements. TcR rearrangements other than those of the beta chain genes were extremely rare in B cell lymphomas, as were Ig kappa rearrangements in T lymphomas. Only two T/AILD lymphomas had IgH and Ig kappa rearrangement in addition to their clonal T cell receptor gene rearrangements. Both samples likely contain a clonal B

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

    PubMed

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

    2015-08-01

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

  12. Severe necrotic dermatitis in the combs of line 6-3 chickens is associated with Marek's disease virus-induced immunosuppression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD), a lymphoproliferative disorder of domestic chickens is characterized by bursal–thymic atrophy and rapid onset of T-cell lymphomas that infiltrate lymphoid tissues, visceral organs, and peripheral nerves. Marek’s disease virus (MDV), the etiological agent of MD, is a highly cel...

  13. Hepatitis C virus upregulates B-cell receptor signaling: a novel mechanism for HCV-associated B-cell lymphoproliferative disorders

    PubMed Central

    Dai, B; Chen, A Y; Corkum, C P; Peroutka, R J; Landon, A; Houng, S; Muniandy, P A; Zhang, Y; Lehrmann, E; Mazan-Mamczarz, K; Steinhardt, J; Shlyak, M; Chen, Q C; Becker, K G; Livak, F; Michalak, T I; Talwani, R; Gartenhaus, R B

    2016-01-01

    B-cell receptor (BCR) signaling is essential for the development of B cells and has a critical role in B-cell neoplasia. Increasing evidence indicates an association between chronic hepatitis C virus (HCV) infection and B-cell lymphoma, however, the mechanisms by which HCV causes B-cell lymphoproliferative disorder are still unclear. Herein, we demonstrate the expression of HCV viral proteins in B cells of HCV-infected patients and show that HCV upregulates BCR signaling in human primary B cells. HCV nonstructural protein NS3/4A interacts with CHK2 and downregulates its activity, modulating HuR posttranscriptional regulation of a network of target mRNAs associated with B-cell lymphoproliferative disorders. Interestingly, the BCR signaling pathway was found to have the largest number of transcripts with increased association with HuR and was upregulated by NS3/4A. Our study reveals a previously unidentified role of NS3/4A in regulation of host BCR signaling during HCV infection, contributing to a better understanding of the molecular mechanisms underlying HCV-associated B-cell lymphoproliferative disorders. PMID:26434584

  14. High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

    ClinicalTrials.gov

    2016-07-08

    Post-Transplant Lymphoproliferative Disorder; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

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

    ClinicalTrials.gov

    2013-01-16

    AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma

  16. Subclinical pulmonary function defects following autologous and allogeneic bone marrow transplantation: relationship to total body irradiation and graft-versus-host disease

    SciTech Connect

    Tait, R.C.; Burnett, A.K.; Robertson, A.G.; McNee, S.; Riyami, B.M.; Carter, R.; Stevenson, R.D. )

    1991-06-01

    Pulmonary function results pre- and post-transplant, to a maximum of 4 years, were analyzed in 98 patients with haematological disorders undergoing allogeneic (N = 53) or autologous bone marrow transplantation (N = 45) between 1982 and 1988. All received similar total body irradiation based regimens ranging from 9.5 Gy as a single fraction to 14.4 Gy fractionated. FEV1/FVC as a measure of airway obstruction showed little deterioration except in patients experiencing graft-versus-host disease in whom statistically significant obstructive ventilatory defects were evident by 6 months post-transplant (p less than 0.01). These defects appeared to be permanent. Restrictive ventilatory defects, as measured by reduction in TLC, and defects in diffusing capacity (DLCO and KCO) were also maximal at 6 months post-transplant (p less than 0.01). Both were related, at least in part, to the presence of GVHD (p less than 0.01) or use of single fraction TBI with absorbed lung dose of 8.0 Gy (p less than 0.05). Fractionated TBI resulted in less marked restricted ventilation and impaired gas exchange, which reverted to normal by 2 years, even when the lung dose was increased from 11.0 Gy to between 12.0 and 13.5 Gy. After exclusion of patients with GVHD (30% allografts) there was no significant difference in pulmonary function abnormalities between autograft and allograft recipients.

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

    PubMed

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

    2015-12-15

    Currently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for clonality, in the diagnostic work-up of chronic lymphoproliferative disorders of NK cells (CLPD-NK). For this purpose, a large panel of markers was evaluated by multiparametric flow cytometry on peripheral blood (PB) CD56(low) NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56(low) NK-cell expansions, and 37 with CLPD-NK of undetermined clonality; also, PB samples from 10 healthy adults were included. Clonality was established using the human androgen receptor (HUMARA) assay. Clonal NK cells were found to show decreased expression of CD7, CD11b and CD38, and higher CD2, CD94 and HLADR levels vs. normal NK cells, together with a restricted repertoire of expression of the CD158a, CD158b and CD161 killer-associated receptors. In turn, NK cells from both clonal and polyclonal CLPD-NK showed similar/overlapping phenotypic profiles, except for high and more homogeneous expression of CD94 and HLADR, which was restricted to clonal CLPD-NK. We conclude that the CD94(hi)/HLADR+ phenotypic profile proved to be a useful surrogate marker for NK-cell clonality.

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

    PubMed Central

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

    2015-01-01

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

  19. Characterization of EBV-related lymphoproliferative lesions arising in donor lymphocytes of transplanted human tumor tissues in the NOG mouse.

    PubMed

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

    2014-01-01

    Human tumor tissue line models established in the severely immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Sug)/Jic (NOD/Shi-scid, IL-2Rγ(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.

  20. Age-related Epstein-Barr Virus-positive lymphoproliferative disorders of the orbit and maxillary sinus : a case report.

    PubMed

    Mitsui, Takeki; Mawatari, Momoko; Koiso, Hiromi; Yokohama, Akihiko; Uchiumi, Hideki; Saitoh, Takayuki; Handa, Hiroshi; Hirato, Junko; Karasawa, Masamitsu; Murakami, Hirokazu; Kojima, Masaru; Nakamura, Shigeo; Nojima, Yoshihisa; Tsukamoto, Norifumi

    2012-01-01

    We report a rare case of age-related Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disorder (aEBVBLPD) primarily involving the orbit and maxillary sinus. Lesions in the left orbit and maxillary sinus were observed in a 59-year-old man presenting with pain in the left orbit and maxilla. Owing to the presence of Reed-Sternberg-like cells, the initial diagnosis was nodular sclerosis-type Hodgkin's lymphoma. Clinical stage was IIAE, and response to chemotherapy and radiotherapy was favorable. Further immunohistochemical and in situ hybridization analyses of the Reed-Sternberg-like giant cells revealed CD30, CD15, CD20, Bob-1, Oct-2, EBV-encoded RNAs (EBERs) and latent membrane protein-1 (LMP-1) expression. The characteristics of the present case, which included immunohistochemical findings, sites of primary lesions, absence of other lymph node lesions and relatively old age, suggested aEBVBLPD. Owing to the similarity in morphology, higher frequency at extranodal sites and poor prognosis, aEBVBLPD represents a differential diagnostic issue from classical Hodgkin's lymphoma when Reed-Sternberg cells are positive for EBV.

  1. Cytogenetics in the management of lymphomas and lymphoproliferative disorders in adults and children: an update by the Groupe francophone de cytogénétique hématologique (GFCH).

    PubMed

    Lefebvre, Christine; Callet-Bauchu, Evelyne; Chapiro, Elise; Nadal, Nathalie; Penther, Dominique; Poirel, Hélène-Antoine

    2016-10-01

    Non-Hodgkin's lymphomas and lymphoproliferative disorders include a high number of heterogeneous entities, described in the 2008 WHO classification. This classification reflects the crucial role of a multidisciplinary approach which integrates cytogenetic results both for the notion of clonality and for differential diagnosis between these entities. The prognostic impact of some cytogenetic abnormalities or genome complexity is also confirmed for many of these entities. Novel provisional entities have been described, such as BCLU (B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma) for which karyotype is critical to distinguish BCLU from Burkitt's lymphoma. The karyotype can be established from any tumour or liquid infiltrated by lymphoma cells. Recent adaptations of technics for cellular cultures according to the subtype of known (or suspected) lymphoma have significantly improved the percentage of informative karyotypes. Conventional karyotypes remain the best technical approach recommended for most of these subtypes. Interphase and/or metaphase FISH also represents a solid and rapid approach, because of the significant number of recurrent (sometimes specific) rearrangements of these entities. Next generation sequencing technologies contribute to enrich genomic data and substantially improve the understanding of oncogenic mechanisms underlying these lymphoid malignancies. Some molecular biomarkers are already part of the diagnostic process (for example, somatic mutation of MYD88 in Waldenström disease) thus reinforcing the essential principle of a multidisciplinary approach for the diagnosis of all the mature lymphoid malignancies.

  2. Diseases of the tongue.

    PubMed

    Mangold, Aaron R; Torgerson, Rochelle R; Rogers, Roy S

    2016-01-01

    The tongue is a complex organ involved in speech and expression as well as in gustation, mastication, and deglutition. The oral cavity, along with the tongue, are sites of neoplasms, reactive processes, and infections, and may be a harbinger of systemic diseases. This review includes both common and rare diseases that occur on the tongue, including: vascular and lymphatic lesions (infantile hemangiomas and oral varices), reactive and inflammatory processes (hairy tongue, pigmented fungiform papillae of the tongue, benign migratory glossitis, and fissured tongue), infections (oral hairy leukoplakia, herpes simplex and varicella-zoster virus infections, human papillomavirus, and candidiasis), premalignant lesions (leukoplakia and erythroplakia), malignant lesions (squamous cell carcinoma, Kaposi sarcoma, and lymphoproliferative diseases), and signs of systemic disease (nutritional deficiency and systemic amyloidosis). PMID:27343960

  3. Posttransplant Lymphoproliferative Disorder of the Thorax: CT and FDG-PET Features in a Single Tertiary Referral Center

    PubMed Central

    Yoon, Ga Young; Kim, Mi Young; Huh, Joo Rryung; Jo, Kyung-Wook; Shim, Tae Sun

    2015-01-01

    Abstract To investigate the chest computed tomography (CT) and F-18 fluoro-2-deoxy-d-glucose positron emission tomographic (FDG-PET) findings of posttransplant lymphoproliferative disorder (PTLD) in the thorax. From November 2004 to February 2013, the cases of 12 adult patients (3 female and 9 male, age range 34–68, and median age 46 years) with proven PTLD were retrospectively reviewed. The transplanted organs included the kidney (5/12), liver (4/12), heart (1/12), combined kidney and pancreas (1/12), and hematopoietic stem cell (1/12). We investigated the relationship of the Epstein–Barr virus (EBV) to the patients’ long-term follow-up, and evaluated the characteristics of the lesions on the chest CT and FDG-PET. The lesions were classified into 2 patterns: that of lymph node and lung involvement. The interval between the transplantation and the onset of PTLD was 2 to 128 months (median, 49). Positive EBV-encoded RNA in the pathologic specimens was found in 10 patients (83.3%). Eight patients were positive for EBV PCR in their blood, and 3 patients showed seroconversion without antiviral therapy. The responses to treatment were complete in 7 cases (58.3%), partial remission in 4 cases (33.3%), and undetermined in 1 case (8.3%). The more common chest CT patterns showed lymph node involvement (10/12) rather than lung involvement (3/12). The median maximum-standardized uptake value on the FDG-PET scans was 7.7 (range, 2.7–25.5). In patients with PTLD involving the thorax, lymphadenopathy was the more common manifestation on the chest CT rather than lung involvement. The lesions showed hypermetabolism on FDG-PET. PMID:26252295

  4. Three Rwandan Children With Massive Splenomegaly and Epstein-Barr Virus-associated Lymphoproliferative Disorders: Case Presentations and the Literature Review.

    PubMed

    Friedman-Klabanoff, DeAnna; Ball, Allison; Rutare, Samuel; McCall, Natalie; Blackall, Douglas P

    2016-07-01

    This report describes 3 Rwandan children with massive splenomegaly and pancytopenia who underwent splenectomy. Each was diagnosed with Epstein-Barr virus-associated lymphoproliferative disorder (EBV LPD) based on lymphocyte morphology, lymphocyte immunophenotype, and the results of EBV in situ hybridization studies. The differential diagnosis of splenomegaly, with a special emphasis on the sub-Saharan African context, is discussed along with EBV and associated disorders. These cases serve as a call to consider EBV LPD in the differential diagnosis of splenomegaly in children in whom common causes have been ruled out. PMID:27352192

  5. Candidates for liver transplantation with alcoholic liver disease: Psychosocial aspects

    PubMed Central

    Telles-Correia, Diogo; Mega, Inês

    2015-01-01

    In Europe, 30% to 50% of liver transplantations are currently due to alcoholic liver disease (ALD). In the United States, this percentage is 17.2%. Post-transplant survival and other predictors of clinical course do not differ significantly from those in other types of transplanted patients, as long as there is no relapse of drinking. However, 20%-25% of these patients lapse or relapse to heavy drinking post-operatively, which has been associated with an increased risk of liver damage and mortality. It is therefore crucial to design specific selection and follow-up strategies aimed at this particular type of patient. Several good and poor prognosis factors that could help to predict a relapse have been suggested, among them the duration of abstinence, social support, a family history of alcoholism, abuse diagnosis versus alcohol dependence, non-acceptance of diagnosis related to alcohol use, presence of severe mental illness, non-adherence in a broad sense, number of years of alcoholism, and daily quantity of alcohol consumption. In this article, we discuss these and other, more controversial factors in selecting ALD patients for liver transplantation. Abstinence should be the main goal after transplantation in an ALD patient. In this article, we review the several definitions of post-transplant relapse, its monitoring and the psychopharmacological and psychotherapeutic treatment. PMID:26494959

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

    PubMed

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

    1999-08-01

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

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

    SciTech Connect

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

    2014-09-10

    -3 kinase inhibitors reverse the lymphoproliferative phenotype in vivo. - Highlights: • First genetic evidence that PTEN controls LPS/TLR4 signaling in B lymphocytes. • Evidence that PTEN regulates LPS induced lymphoproliferation in vivo. • PI-3 kinase inhibitors block LPS induced lymphoproliferation in vivo.

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

    PubMed Central

    2011-01-01

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

  9. Castleman Disease of the Parotid Gland: A Report of a Case.

    PubMed

    Abo-Alhassan, Fawaz; Faras, Fatemah; Bastaki, Jassem; Al-Sihan, Mutlaq K

    2015-01-01

    Castleman disease is an extremely rare benign lymphoproliferative disorder of unknown etiology. It affects the lymphatic chain in anybody region, although the commonest site is the mediastinum. The head and neck region is the second most common site; however, the salivary glands are rarely affected. We report a case of a 29-year-old Asian lady who presented with a 2-year history of an enlarging left parotid mass. Histopathology of the excisional biopsy confirmed the diagnosis of Castleman disease.

  10. Castleman's Disease: An Interesting Cause of Hematuria

    PubMed Central

    Tolofari, Sotonye Karl; Chow, Wai-Man; Hussain, Basharat

    2015-01-01

    Castleman's disease is a rare benign lymphoproliferative disorder, characterized by benign growths of the lymph node tissue. It is associated with a number of malignancies, including Kaposi sarcoma, non-Hodgkin's and Hodgkins lymphoma, and POEMS syndrome. This report describes the case of a 38 year old gentleman, presenting with painless hematuria. Initial investigations, including flexible cystoscopy were unremarkable. However, subsequent imaging including CT Urogram and MR pelvis revealed multiple prevesical lesions. Histology obtained from excision biopsy revealed histological features consistent with Castleman's disease. In this report we discuss the nature, presentation and treatment modalities of this rare condition. PMID:26793490

  11. Castleman's Disease: An Interesting Cause of Hematuria.

    PubMed

    Tolofari, Sotonye Karl; Chow, Wai-Man; Hussain, Basharat

    2015-03-01

    Castleman's disease is a rare benign lymphoproliferative disorder, characterized by benign growths of the lymph node tissue. It is associated with a number of malignancies, including Kaposi sarcoma, non-Hodgkin's and Hodgkins lymphoma, and POEMS syndrome. This report describes the case of a 38 year old gentleman, presenting with painless hematuria. Initial investigations, including flexible cystoscopy were unremarkable. However, subsequent imaging including CT Urogram and MR pelvis revealed multiple prevesical lesions. Histology obtained from excision biopsy revealed histological features consistent with Castleman's disease. In this report we discuss the nature, presentation and treatment modalities of this rare condition. PMID:26793490

  12. 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

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

    2014-12-01

    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-κB1) 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

  13. Monocytes promote tumor cell survival in T-cell lymphoproliferative disorders and are impaired in their ability to differentiate into mature dendritic cells

    PubMed Central

    Wilcox, Ryan A.; Wada, David A.; Ziesmer, Steven C.; Elsawa, Sherine F.; Comfere, Nneka I.; Dietz, Allan B.; Novak, Anne J.; Witzig, Thomas E.; Feldman, Andrew L.; Pittelkow, Mark R.

    2009-01-01

    A variety of nonmalignant cells present in the tumor microenvironment promotes tumorigenesis by stimulating tumor cell growth and metastasis or suppressing host immunity. The role of such stromal cells in T-cell lymphoproliferative disorders is incompletely understood. Monocyte-derived cells (MDCs), including professional antigen-presenting cells such as dendritic cells (DCs), play a central role in T-cell biology. Here, we provide evidence that monocytes promote the survival of malignant T cells and demonstrate that MDCs are abundant within the tumor microenvironment of T cell–derived lymphomas. Malignant T cells were observed to remain viable during in vitro culture with autologous monocytes, but cell death was significantly increased after monocyte depletion. Furthermore, monocytes prevent the induction of cell death in T-cell lymphoma lines in response to either serum starvation or doxorubicin, and promote the engraftment of these cells in nonobese diabetic/severe combined immunodeficient mice. Monocytes are actively recruited to the tumor microenvironment by CCL5 (RANTES), where their differentiation into mature DCs is impaired by tumor-derived interleukin-10. Collectively, the data presented demonstrate a previously undescribed role for monocytes in T-cell lymphoproliferative disorders. PMID:19671921

  14. Hydrogen, a potential safeguard for graft-versus-host disease and graft ischemia-reperfusion injury?

    PubMed

    Yuan, Lijuan; Shen, Jianliang

    2016-09-01

    Post-transplant complications such as graft-versus-host disease and graft ischemia-reperfusion injury are crucial challenges in transplantation. Hydrogen can act as a potential antioxidant, playing a preventive role against post-transplant complications in animal models of multiple organ transplantation. Herein, the authors review the current literature regarding the effects of hydrogen on graft ischemia-reperfusion injury and graft-versus-host disease. Existing data on the effects of hydrogen on ischemia-reperfusion injury related to organ transplantation are specifically reviewed and coupled with further suggestions for future work. The reviewed studies showed that hydrogen (inhaled or dissolved in saline) improved the outcomes of organ transplantation by decreasing oxidative stress and inflammation at both the transplanted organ and the systemic levels. In conclusion, a substantial body of experimental evidence suggests that hydrogen can significantly alleviate transplantation-related ischemia-reperfusion injury and have a therapeutic effect on graft-versus-host disease, mainly via inhibition of inflammatory cytokine secretion and reduction of oxidative stress through several underlying mechanisms. Further animal experiments and preliminary human clinical trials will lay the foundation for hydrogen use as a drug in the clinic. PMID:27652837

  15. Hydrogen, a potential safeguard for graft-versus-host disease and graft ischemia-reperfusion injury?

    PubMed Central

    Yuan, Lijuan; Shen, Jianliang

    2016-01-01

    Post-transplant complications such as graft-versus-host disease and graft ischemia-reperfusion injury are crucial challenges in transplantation. Hydrogen can act as a potential antioxidant, playing a preventive role against post-transplant complications in animal models of multiple organ transplantation. Herein, the authors review the current literature regarding the effects of hydrogen on graft ischemia-reperfusion injury and graft-versus-host disease. Existing data on the effects of hydrogen on ischemia-reperfusion injury related to organ transplantation are specifically reviewed and coupled with further suggestions for future work. The reviewed studies showed that hydrogen (inhaled or dissolved in saline) improved the outcomes of organ transplantation by decreasing oxidative stress and inflammation at both the transplanted organ and the systemic levels. In conclusion, a substantial body of experimental evidence suggests that hydrogen can significantly alleviate transplantation-related ischemia-reperfusion injury and have a therapeutic effect on graft-versus-host disease, mainly via inhibition of inflammatory cytokine secretion and reduction of oxidative stress through several underlying mechanisms. Further animal experiments and preliminary human clinical trials will lay the foundation for hydrogen use as a drug in the clinic. PMID:27652837

  16. Hydrogen, a potential safeguard for graft-versus-host disease and graft ischemia-reperfusion injury?

    PubMed Central

    Yuan, Lijuan; Shen, Jianliang

    2016-01-01

    Post-transplant complications such as graft-versus-host disease and graft ischemia-reperfusion injury are crucial challenges in transplantation. Hydrogen can act as a potential antioxidant, playing a preventive role against post-transplant complications in animal models of multiple organ transplantation. Herein, the authors review the current literature regarding the effects of hydrogen on graft ischemia-reperfusion injury and graft-versus-host disease. Existing data on the effects of hydrogen on ischemia-reperfusion injury related to organ transplantation are specifically reviewed and coupled with further suggestions for future work. The reviewed studies showed that hydrogen (inhaled or dissolved in saline) improved the outcomes of organ transplantation by decreasing oxidative stress and inflammation at both the transplanted organ and the systemic levels. In conclusion, a substantial body of experimental evidence suggests that hydrogen can significantly alleviate transplantation-related ischemia-reperfusion injury and have a therapeutic effect on graft-versus-host disease, mainly via inhibition of inflammatory cytokine secretion and reduction of oxidative stress through several underlying mechanisms. Further animal experiments and preliminary human clinical trials will lay the foundation for hydrogen use as a drug in the clinic.

  17. Recurrence of diabetic kidney disease in a type 1 diabetic patient after kidney transplantation.

    PubMed

    Nyumura, Izumi; Honda, Kazuho; Babazono, Tetsuya; Horita, Shigeru; Murakami, Toru; Fuchinoue, Shohei; Uchigata, Yasuko

    2015-07-01

    Post-transplant hyperglycaemia of diabetic patients may cause recurrent diabetic kidney disease (DKD) in kidney allografts. We report a patient with slowly progressive DKD with calcineurin inhibitor toxicity (CNI) toxicity after the kidney transplantation. A 28-year-old female with type 1 diabetes mellitus underwent successful kidney transplantation from her mother in April 2003, and the kidney graft survived for more than 10 years. She was treated with combined immunosuppressive therapy consisting of cyclosporine and mycophenolate mofetil. After transplantation, she continued to take insulin injection four times per day, but her glycosylated haemoglobin (HbA1c) was above 10%. Protocol allograft kidney biopsies performed 5 and 10 years after transplantation revealed the recurrence of slowly progressive diabetic kidney disease. In addition, arteriolar hyalinosis partly associated with calcineurin inhibitor toxicity (CNI) was detected with progression. Post-transplant hyperglycaemia causes recurrent diabetic kidney disease (DKD) in kidney allografts, but its progression is usually slow. For long-term management, it is important to prevent the progression of the calcineurin inhibitor arteriolopathy, as well as maintain favourable glycaemic control.

  18. Autoimmune Lymphoproliferative Syndrome (ALPS)

    MedlinePlus

    ... Patients Procedure for Accessing Lab Services Data Package Requirements AIDS Therapies Resource Guide In Vitro Efficacy Evaluations ... Assurances to Users Application and Approval Process User Requirements Malaria Vaccine Production Services Data Sharing and Release ...

  19. Recognizing Weber-Christian disease.

    PubMed

    Khan, G A; Lewis, F I

    1996-12-01

    The eponym Weber-Christian Disease (WCD) defines a chronic disorder characterized by relapsing febrile episodes and panniculitis. Systemic manifestations due to visceral involvement may be present. WCD is associated with no identifiable cause, although chronic panniculitis may be due to definable underlying disorders. A variety of distinctive disease entities, such as systemic lupus erythematosus (SLE), pancreatic disease, alpha-I-antitrypsin disease, lymphoproliferative neoplasia, infections, or trauma are associated with chronic panniculitis. The accurate diagnosis of panniculitis requires an adequate deep skin biopsy showing inflammation of the subcutaneous layers. We describe a white woman with fever and recurrent episodes of painful nodules of the lower extremities, excisional biopsy of which confirmed panniculitis. The febrile episodes and skin lesions responded dramatically with the use of oral corticosteroids. PMID:8987390

  20. Marek's disease--the disease and its prevention by vaccination.

    PubMed Central

    Biggs, P. M.

    1975-01-01

    Marek's disease (MD) is a common lymphoproliferative disease of the domestic chicken caused by a cell associated herpesvirus. Vaccines used for the prophylaxis of MD have been derived from non-pathogenic field Marek's disease virus (MDV), pathogenic MDV and the herpesvirus of turkeys (HVT). Vaccines derived from MDV have been developed by attenuation of virus strains which produce the acute form of MD and virus strains which produce the classical form. They have also been developed by suitable modification, where necessary, of non-pathogenic MDV. All MDV derived vaccines have to be used in the cell associated form. The turkey herpesvirus vaccine can be used in either the cell associated or cell free lyophilized form. All these types of vaccine appear to be safe and to provide significant levels of protection under field conditions. PMID:170953

  1. CD8-positive T-cell lymphoproliferative disorder associated with Epstein-Barr virus-infected B-cells in a rheumatoid arthritis patient under methotrexate treatment.

    PubMed

    Koji, Hitoshi; Yazawa, Takuya; Nakabayashi, Kimimasa; Fujioka, Yasunori; Kamma, Hiroshi; Yamada, Akira

    2016-01-01

    We report a 48-year-old female who developed lymphoproliferative disorder (LPD) during treatment of rheumatoid arthritis (RA) with methotrexate (MTX). She presented with multiple tumors in the cervical lymph nodes (LNs), multiple lung shadows and round shadows in both kidneys with pancytopenia and a high CRP level. The LN showed CD8-positive T-cell LPD associated with Epstein-Barr (EB) virus-infected B-cells. Clonality assays for immunoglobulin (Ig) heavy chain and T-cell receptor gamma (TCRγ) were negative. The cessation of MTX without chemotherapy resulted in the complete disappearance of the tumors and abnormal clinical features. We compared this case with previously published ones and discuss the pathological findings, presuming that the proliferation of CD8 T-cells was a reactive manifestation to reactivated EB virus-infected B-cells.

  2. Effect of liver transplantation on the hypothalamic-pituitary-gonadal axis of chronic alcoholic men with advanced liver disease.

    PubMed

    Van Thiel, D H; Kumar, S; Gavaler, J S; Tarter, R E

    1990-06-01

    The hormones testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) were assayed in blood obtained from men with alcoholic liver disease before and after successful liver transplantation. The frequency and severity of self reported impotence, intercourse, and paternity were assessed before and 18 +/- 3 months post-transplantation. The results obtained were compared with those of age-matched males transplanted within the same month by the same surgical teams for advanced hepatocellular disease other than alcoholism. Little change for any parameter assessed pre- and post-transplantation was noted for the nonalcoholics. In contrast, the FSH, LH, and testosterone levels of the alcoholic men all increased significantly following successful transplantation. These data suggest that the liver disease associated with alcoholism contributes to some of the endocrine effects of alcohol-associated cirrhosis but not all. Because the transplanted alcoholics remain less adequate than controls, it is further suggested that some residual alcohol-induced injury to the hypothalamic-pituitary-gonadal axis persists despite successful liver transplantation.

  3. Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation

    PubMed Central

    2013-01-01

    Viral infections are important causes of morbidity and mortality after allogeneic stem cell hematopoietic transplantation (allo-HSCT). Although most viral infections present with asymptomatic or subclinical manifestations, viruses may result in fatal complications in severe immunocompromised recipients. Reactivation of latent viruses, such as herpesviruses, is frequent during the immunosuppression that occurs with allo-HSCT. Viruses acquired from community, such as the respiratory and gastrointestinal viruses, are also important pathogens of post-transplant viral diseases. Currently, molecular diagnostic methods have replaced or supplemented traditional methods, such as viral culture and antigen detection, in diagnosis of viral infections. The utilization of polymerase chain reaction facilitates the early diagnosis. In view of lacking efficacious agents for treatment of viral diseases, prevention of viral infections is extremely valuable. Application of prophylactic strategies including preemptive therapy reduces viral infections and diseases. Adoptive cellular therapy for restoring virus-specific immunity is a promising method in the treatment of viral diseases. PMID:24341630

  4. Spirochetes in the spleen of a patient with chronic Lyme disease.

    PubMed

    Cimmino, M A; Azzolini, A; Tobia, F; Pesce, C M

    1989-01-01

    A 54-year-old man had intermittent evening fever, arthralgia, transient erythematous macular eruption on the skin, and splenomegaly of two year's duration. Immunofluorescence tests for Borrelia burgdorferi serum antibodies had positive results, but G-penicillin treatment was ineffective. Splenectomy with lymph node biopsy was performed to rule out lymphoproliferative disorders. Borrelia-like spirochetes were identified histologically in the spleen; this finding was consistent with persistence of B. burgdorferi organisms in inner organs in chronic Lyme disease.

  5. Persistent Legionnaire's disease in an adult with hairy cell leukemia successfully treated with prolonged levofloxacin therapy.

    PubMed

    Cunha, Burke A; Munoz-Gomez, Sigridh; Gran, Arthur; Raza, Muhammad; Irshad, Nadia

    2015-01-01

    Legionnaire's disease (LD) manifests most commonly as an atypical community acquired pneumonia (CAP) with systemic extrapulmonary manifestations. Disorders associated with impaired cell mediated immunity (CMI) are particularly predisposed to LD. Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative leukemia associated with decreased CMI. LD has only rarely been reported in HCL. We present a most interesting case of persistent LD in a elderly male with HCL who required prolonged antibiotic therapy.

  6. The management of perioperative nutrition in patients with end stage liver disease undergoing liver transplantation.

    PubMed

    Zhang, Qi-Kun; Wang, Meng-Long

    2015-10-01

    Malnutrition is found in almost 100% of patients with end stage liver disease (ESLD) awaiting transplantation and malnutrition before transplantation leads to higher rates of post-transplant complications and worse graft survival outcomes. Reasons for protein energy malnutrition include several metabolic alterations such as inadequate intake, malabsorption, and overloaded expenditure. And also, stress from surgery, gastrointestinal reperfusion injury, immunosuppressive therapy and corticosteriods use lead to delayed bowl function recovery and disorder of nutrients absorption. In the pretransplant phase, nutritional goals include optimization of nutritional status and treatment of nutrition-related symptoms induced by hepatic decompensation. During the acute post-transplant phase, adequate nutrition is required to help support metabolic demands, replenish lost stores, prevent infection, arrive at a new immunologic balance, and promote overall recovery. In a word, it is extremely important to identify and correct nutritional deficiencies in this population and provide an adequate nutritional support during all phases of liver transplantation (LT). This study review focuses on prevalence, nutrition support, evaluation, and management of perioperative nutrition disorder in patients with ESLD undergoing LT.

  7. Cutaneous necrotizing vasculitis. Relation to systemic disease.

    PubMed

    Lotti, T M; Comacchi, C; Ghersetich, I

    1999-01-01

    Cutaneous necrotizing vasculitis (CNV) is a complex multisystem disease generally involving the skin and mucous membranes, often accompanied by renal, gastrointestinal, pericardial, neurological, and articular signs and symptoms. CNV may be idiopatical or occur in association with a drug, infection, or underlying disease. CNV has been shown in patients with chronic infections (viral, bacterial, protozoa, helminthic), serum sickness, a variety of collagen vascular diseases (systemic lupus erythematous, Sjögren's syndrome, rheumatoid arthritis, Behçet's disease) hyperglobulinemic states, cryoglobulinemia, bowel bypass syndrome, ulcerative colitis, cystic fibrosis, primary biliary cirrhosis and HIV infection. Association with malignancies is not frequent. Lymphoproliferative disorders (Hodgkin's disease, mycosis fungoides, lymphosarcoma, adult T-cell leukemia, multiple mieloma) and solid tumors (lung cancer, colon carcinoma, renal, prostate, head and neck cancer and breast cancer) may be associated with CNV. Whenever possible, treatment is directed at the elimination of the cause. In other cases after adequate laboratory screening local and systemic therapy are recommended. PMID:10599332

  8. Localized Castleman's Disease in the Breast in a Young Woman

    PubMed Central

    Guio, José Ismael; López-Correa, Patricia

    2016-01-01

    Castleman's disease (CD) is a rare lymphoproliferative disorder of unknown etiology. It typically occurs in adulthood but it may also develop in childhood. Clinically, this disease may be classified as localized (unicentric) or systemic (multicentric). Six cases of breast CD have been described in the literature, and all have been reported in adults. Herein we describe the case of a 15-year-old female who presented with a slow-growing tumor in the right breast. The tumor was excised and histopathological examination demonstrated hyaline vascular variant CD. After two years of follow-up, the patient was asymptomatic without evidence of cervical or axillary lymphadenopathy. PMID:27073709

  9. Rituximab in post-transplant pediatric recurrent focal segmental glomerulosclerosis

    PubMed Central

    Shatat, Ibrahim F.; Skversky, Amy L.; Woroniecki, Robert P.; Del Rio, Marcela; Perelstein, Eduardo M.; Johnson, Valerie L.; Mahesh, Shefali

    2012-01-01

    Background Focal segmental glomerulosclerosis (FSGS) recurs in 20–40 % of allografts. Plasmapheresis (TPE) has been one of the mainstays of treatment with variable results. Rituximab (RTX), a monoclonal antibody to the protein CD20, is being used for treatment of recurrent FSGS (recFSGS) but pediatric experience is limited. Methods We conducted a retrospective review of eight patients with recFSGS, treated with RTX (1–4 doses) after having minimal response to TPE. Complete response was defined as a decrease in urine protein creatinine ratio (Up/c) to less than 0.2 and partial response was a decrease in Up/c ratio by 50 % of baseline and in the sub-nephrotic range (U p/c <2). Results Complete response was seen in two of eight patients, and partial response was seen in four of eight patients. Two patients had no response. At last follow-up, all the partial responders had sub-nephrotic range proteinuria (Up/c ratios ranging from 0.29 to 1.6). Delayed response, up to 9 months post-RTX, was also seen in some of the patients. Significant complications such as rituximab-associated lung injury (RALI), acute tubular necrosis, and central nervous system (CNS) malignancy were also observed in our case series. Conclusions Rituximab can be used with caution as a treatment for recFSGS. Efficacy is variable from none to complete response. Even partial reduction in proteinuria is of benefit in prolonging the life of the allograft. Long-term, multicenter studies are needed to prove its sustained efficacy in those who respond and to monitor for serious adverse effects. PMID:23052653

  10. Voriconazole-induced periostitis in two post-transplant patients.

    PubMed

    Bucknor, Matthew D; Gross, Andrew J; Link, Thomas M

    2013-08-01

    While drug-related periostitis has been known of for many years, the specific association of diffuse periostitis with voriconazole (most frequently in transplant patients) has only been recently explicitly addressed in the literature. Recognition of the radiologic and clinical manifestations of voriconazole-related periostitis is important for helping to narrow an otherwise broad differential diagnosis. We present two cases that illustrate different radiologic presentations of this painful cause of diffuse periostitis. Case 1 features a 60 year-old woman with a history of orthotopic heart transplant who was hospitalized for "full body pain" with progressively worsening bone tenderness involving the humeri, knees, femurs, hips, and hands. Case 2 describes a 48 year-old man with a history of acute lymphoblastic leukemia status post stem cell transplant who presented with diffuse arthralgias involving bilateral ankles, knees, wrists, and elbows.

  11. Voriconazole-induced periostitis in two post-transplant patients

    PubMed Central

    Bucknor, Matthew D.; Gross, Andrew J.; Link, Thomas M.

    2013-01-01

    While drug-related periostitis has been known of for many years, the specific association of diffuse periostitis with voriconazole (most frequently in transplant patients) has only been recently explicitly addressed in the literature. Recognition of the radiologic and clinical manifestations of voriconazole-related periostitis is important for helping to narrow an otherwise broad differential diagnosis. We present two cases that illustrate different radiologic presentations of this painful cause of diffuse periostitis. Case 1 features a 60 year-old woman with a history of orthotopic heart transplant who was hospitalized for “full body pain” with progressively worsening bone tenderness involving the humeri, knees, femurs, hips, and hands. Case 2 describes a 48 year-old man with a history of acute lymphoblastic leukemia status post stem cell transplant who presented with diffuse arthralgias involving bilateral ankles, knees, wrists, and elbows. PMID:24421948

  12. A marker chromosome in post-transplant bone marrow.

    PubMed

    Morsberger, Laura; Powell, Kerry; Ning, Yi

    2016-01-01

    Detection of small supernumerary marker chromosomes in karyotype analysis represents a diagnostic challenge. While such markers are usually detected during cytogenetic studies of constitutional chromosome abnormalities, they have also been found in specimens submitted from patients with acquired malignancies. We report here the detection of a marker chromosome in a bone marrow specimen from a patient who received a bone marrow transplantation. We discuss the importance of proper characterization and interpretation of marker chromosomes in clinical practice. PMID:27252781

  13. Deletion of receptor for advanced glycation end products exacerbates lymphoproliferative syndrome and lupus nephritis in B6-MRL Fas lpr/j mice.

    PubMed

    Goury, Antoine; Meghraoui-Kheddar, Aïda; Belmokhtar, Karim; Vuiblet, Vincent; Ortillon, Jeremy; Jaisson, Stéphane; Devy, Jerôme; Le Naour, Richard; Tabary, Thierry; Cohen, Jacques H M; Schmidt, Ann-Marie; Rieu, Philippe; Touré, Fatouma

    2015-04-15

    The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that interacts with advanced glycation end products, but also with C3a, CpG DNA oligonucleotides, and alarmin molecules such as HMGB1 to initiate a proinflammatory reaction. Systemic lupus erythematosus is an autoimmune disorder associated with the accumulation of RAGE ligands. We generated mice invalidated for RAGE in the lupus-prone B6-MRL Fas lpr/j background to determine the role of RAGE in the pathogenesis of systemic lupus erythematosus. We compared the phenotype of these mice with that of their wild-type and B6-MRL Fas lpr/j littermates. Lymphoproliferative syndrome, production of anti-dsDNA Abs, lupus nephritis, and accumulation of CD3(+)B220(+)CD4(-)CD8(-) autoreactive T cells (in the peripheral blood and the spleen) were significantly increased in B6-MRL Fas lpr/j RAGE(-/-) mice compared with B6-MRL Fas lpr/j mice (respectively p < 0.005, p < 0.05, p < 0.001, and p < 0.001). A large proportion of autoreactive T cells from B6-MRL Fas lpr/j mice expressed RAGE at their surface. Time course studies of annexin V expression revealed that autoreactive T cells in the spleen of B6-MRL Fas lpr/j-RAGE(-/-) mice exhibited a delay in apoptosis and expressed significantly less activated caspase 3 (39.5 ± 4.3%) than T cells in B6-MRL Fas lpr/j mice (65.5 ± 5.2%) or wild-type mice (75.3 ± 2.64%) (p = 0.02). We conclude that the deletion of RAGE in B6-MRL Fas lpr/j mice promotes the accumulation of autoreactive CD3(+)B220(+)CD4(-)CD8(-) T cells, therefore exacerbating lymphoproliferative syndrome, autoimmunity, and organ injury. This suggests that RAGE rescues the apoptosis of T lymphocytes when the death receptor Fas/CD95 is dysfunctional.

  14. Deletion of receptor for advanced glycation end products exacerbates lymphoproliferative syndrome and lupus nephritis in B6-MRL Fas lpr/j mice.

    PubMed

    Goury, Antoine; Meghraoui-Kheddar, Aïda; Belmokhtar, Karim; Vuiblet, Vincent; Ortillon, Jeremy; Jaisson, Stéphane; Devy, Jerôme; Le Naour, Richard; Tabary, Thierry; Cohen, Jacques H M; Schmidt, Ann-Marie; Rieu, Philippe; Touré, Fatouma

    2015-04-15

    The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that interacts with advanced glycation end products, but also with C3a, CpG DNA oligonucleotides, and alarmin molecules such as HMGB1 to initiate a proinflammatory reaction. Systemic lupus erythematosus is an autoimmune disorder associated with the accumulation of RAGE ligands. We generated mice invalidated for RAGE in the lupus-prone B6-MRL Fas lpr/j background to determine the role of RAGE in the pathogenesis of systemic lupus erythematosus. We compared the phenotype of these mice with that of their wild-type and B6-MRL Fas lpr/j littermates. Lymphoproliferative syndrome, production of anti-dsDNA Abs, lupus nephritis, and accumulation of CD3(+)B220(+)CD4(-)CD8(-) autoreactive T cells (in the peripheral blood and the spleen) were significantly increased in B6-MRL Fas lpr/j RAGE(-/-) mice compared with B6-MRL Fas lpr/j mice (respectively p < 0.005, p < 0.05, p < 0.001, and p < 0.001). A large proportion of autoreactive T cells from B6-MRL Fas lpr/j mice expressed RAGE at their surface. Time course studies of annexin V expression revealed that autoreactive T cells in the spleen of B6-MRL Fas lpr/j-RAGE(-/-) mice exhibited a delay in apoptosis and expressed significantly less activated caspase 3 (39.5 ± 4.3%) than T cells in B6-MRL Fas lpr/j mice (65.5 ± 5.2%) or wild-type mice (75.3 ± 2.64%) (p = 0.02). We conclude that the deletion of RAGE in B6-MRL Fas lpr/j mice promotes the accumulation of autoreactive CD3(+)B220(+)CD4(-)CD8(-) T cells, therefore exacerbating lymphoproliferative syndrome, autoimmunity, and organ injury. This suggests that RAGE rescues the apoptosis of T lymphocytes when the death receptor Fas/CD95 is dysfunctional. PMID:25762779

  15. Diffuse Cystic Lung Disease. Part II.

    PubMed

    Gupta, Nishant; Vassallo, Robert; Wikenheiser-Brokamp, Kathryn A; McCormack, Francis X

    2015-07-01

    The diffuse cystic lung diseases have a broad differential diagnosis. A wide variety of pathophysiological processes spanning the spectrum from airway obstruction to lung remodeling can lead to multifocal cyst development in the lung. Although lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis are perhaps more frequently seen in the clinic, disorders such as Birt-Hogg-Dubé syndrome, lymphocytic interstitial pneumonia, follicular bronchiolitis, and light-chain deposition disease are increasingly being recognized. Obtaining an accurate diagnosis can be challenging, and management approaches are highly disease dependent. Unique imaging features, genetic tests, serum studies, and clinical features provide invaluable clues that help clinicians distinguish among the various etiologies, but biopsy is often required for definitive diagnosis. In part II of this review, we present an overview of the diffuse cystic lung diseases caused by lymphoproliferative disorders, genetic mutations, or aberrant lung development and provide an approach to aid in their diagnosis and management.

  16. EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma*

    PubMed Central

    Pfaltz, Katrin; Vermeer, Maarten H.; Cozzio, Antonio; Ortiz-Romero, Pablo L.; Bagot, Martine; Olsen, Elise; Kim, Youn H.; Dummer, Reinhard; Pimpinelli, Nicola; Whittaker, Sean; Hodak, Emmilia; Cerroni, Lorenzo; Berti, Emilio; Horwitz, Steve; Prince, H. Miles; Guitart, Joan; Estrach, Teresa; Sanches, José A.; Duvic, Madeleine; Ranki, Annamari; Dreno, Brigitte; Ostheeren-Michaelis, Sonja; Knobler, Robert; Wood, Gary; Willemze, Rein

    2011-01-01

    Primary cutaneous CD30+ lymphoproliferative disorders (CD30+ LPDs) are the second most common form of cutaneous T-cell lymphomas and include lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Despite the anaplastic cytomorphology of tumor cells that suggest an aggressive course, CD30+ LPDs are characterized by an excellent prognosis. Although a broad spectrum of therapeutic strategies has been reported, these have been limited mostly to small retrospective cohort series or case reports, and only very few prospective controlled or multicenter studies have been performed, which results in a low level of evidence for most therapies. The response rates to treatment, recurrence rates, and outcome have not been analyzed in a systematic review. Moreover, international guidelines for staging and treatment of CD30+ LPDs have not yet been presented. Based on a literature analysis and discussions, recommendations were elaborated by a multidisciplinary expert panel of the Cutaneous Lymphoma Task Force of the European Organization for Research and Treatment of Cancer, the International Society for Cutaneous Lymphomas, and the United States Cutaneous Lymphoma Consortium. The recommendations represent the state-of-the-art management of CD30+ LPDs and include definitions for clinical endpoints as well as response criteria for future clinical trials in CD30+ LPDs. PMID:21841159

  17. Rearrangement of the rheumatoid factor-related germline gene Vg and bcl-2 expression in lymphoproliferative disorders in patients with Sjögren's syndrome.

    PubMed

    Sugai, S; Saito, I; Masaki, Y; Takeshita, S; Shimizu, S; Tachibana, J; Miyasaka, N

    1994-08-01

    Of 250 patients with Sjögren's syndrome (SS) (190 with 1 degree SS and 60 with 2 degrees SS), 60 patients demonstrated lymphoproliferative disorders (LPD): 41 patients had monoclonal gammopathy (MG), 4 had pseudolymphoma, 3 had in situ monoclonal lymphoproliferation, and 12 had malignant lymphoma. Rearrangement of the rheumatoid factor (RF)-related germline gene Vg (associated with the monoclonal RF SF18/2) was demonstrated in 24 of 50 genomic DNAs from the peripheral blood leukocytes of SS patients. It was found in none of 20 DNAs from normal subjects. This suggests an almost 50% incidence of a germline Ig gene rearrangement in SS patients without clinical MG. Lymphocytes composing the lymphoepithelial lesion (LEL) in the major salivary glands of SS patients expressed the oncogene bcl-2 protein in 4 out of 6 patients. The progression of SS from benign to malignant lymphoproliferation may be related to suppression of apoptotic death by bcl-2. These findings suggest that (i) RF clones are activated in SS with little or no somatic mutation resulting in monoclonal proliferation and (ii) the LEL in the salivary gland is one site for monoclonal B cell proliferation and emerging malignant lymphoma.

  18. Use of biologics and chemotherapy in patients with inflammatory bowel diseases and cancer.

    PubMed

    Jauregui-Amezaga, Aranzazu; Vermeire, Séverine; Prenen, Hans

    2016-01-01

    Patients with inflammatory bowel disease have an additional risk of developing cancer compared with the general population. This is due to local chronic inflammation that leads to the development of gastrointestinal cancers and the use of thiopurines, associated with a higher risk of lymphoproliferative disorders, skin cancers, or uterine cervical cancers. Similar to the general population, a previous history of cancer in inflammatory bowel disease patients increases the risk of developing a secondary cancer. Large studies have not shown an increased risk of cancer in patients treated with biologics. In this review we discuss the prevention and treatment of cancer in patients with inflammatory bowel disease. PMID:27065724

  19. Use of biologics and chemotherapy in patients with inflammatory bowel diseases and cancer

    PubMed Central

    Jauregui-Amezaga, Aranzazu; Vermeire, Séverine; Prenen, Hans

    2016-01-01

    Patients with inflammatory bowel disease have an additional risk of developing cancer compared with the general population. This is due to local chronic inflammation that leads to the development of gastrointestinal cancers and the use of thiopurines, associated with a higher risk of lymphoproliferative disorders, skin cancers, or uterine cervical cancers. Similar to the general population, a previous history of cancer in inflammatory bowel disease patients increases the risk of developing a secondary cancer. Large studies have not shown an increased risk of cancer in patients treated with biologics. In this review we discuss the prevention and treatment of cancer in patients with inflammatory bowel disease. PMID:27065724

  20. Castleman's disease of a submandibular mass diagnosed on Fine Needle Cytology: Report of a case with histopathological, immunocytochemical and imaging correlations

    PubMed Central

    Malzone, Maria Gabriella; Campanile, Anna Cipolletta; Sanna, Veronica; Ionna, Franco; Longo, Francesco; De Chiara, Annarosaria; Setola, Sergio Venanzio; Botti, Gerardo; Fulciniti, Franco

    2016-01-01

    Summary Castleman's disease (CD) is an unusual inflammatory lymphoproliferative disorder of uncertain aetiology, mainly involving lymphatic tissue in the mediastinum, but also occurring in the neck, lung, abdomen, pelvis, skeletal muscle and retroperitoneum. Fine Needle Cytology (FNC) is a quick, cost-effective and safe diagnostic modality to investigate on organs involved by CD, also providing a guide to treatment and management of patients with lymphoadenopathy. We report a case of a 44-year-old man who underwent FNC of a submandibular mass with subsequent surgical excision. Cytology revealed an atypical lymphoproliferative process, which arose the suspicion of CD. Histopathological study of the excised masses combined with immunhistochemistry and imaging of the submandibular and neck areas, confirmed the suspicion. A final diagnosis of Unicentric Castleman's disease, hyaline-vascular type, was made. PMID:26989647

  1. Castleman's disease of a submandibular mass diagnosed on Fine Needle Cytology: Report of a case with histopathological, immunocytochemical and imaging correlations.

    PubMed

    Malzone, Maria Gabriella; Campanile, Anna Cipolletta; Sanna, Veronica; Ionna, Franco; Longo, Francesco; De Chiara, Annarosaria; Setola, Sergio Venanzio; Botti, Gerardo; Fulciniti, Franco

    2016-02-01

    Castleman's disease (CD) is an unusual inflammatory lymphoproliferative disorder of uncertain aetiology, mainly involving lymphatic tissue in the mediastinum, but also occurring in the neck, lung, abdomen, pelvis, skeletal muscle and retroperitoneum. Fine Needle Cytology (FNC) is a quick, cost-effective and safe diagnostic modality to investigate on organs involved by CD, also providing a guide to treatment and management of patients with lymphoadenopathy. We report a case of a 44-year-old man who underwent FNC of a submandibular mass with subsequent surgical excision. Cytology revealed an atypical lymphoproliferative process, which arose the suspicion of CD. Histopathological study of the excised masses combined with immunhistochemistry and imaging of the submandibular and neck areas, confirmed the suspicion. A final diagnosis of Unicentric Castleman's disease, hyaline-vascular type, was made.

  2. Radiotherapy of unicentric mediastinal Castleman's disease

    PubMed Central

    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

    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

  3. CASTLEMAN'S DISEASE PRESENTING AS A TUMOROUS PARACARDIAC FORMATION.

    PubMed

    Vuković, Ivica; Brešković, Toni; Duplancić, Darko; Batinić, Tonci; Štula, Ivana; Bulat, Cristian; Tomić, Snježana

    2016-03-01

    Castleman's disease (in the literature also known as angiofollicular hyperplasia) is a rare benign lymphoproliferative disease. Clinically, it can manifest as unicentric or multicentric disease. Unicentric disease is most often diagnosed by accident or by symptomatology resulting from compression upon the adjoining anatomical structures. Considering its lymphatic origin, tumor mass can theoretically occur in any body region. We present a case of paracardiac localization of unicentric Castleman's disease in a previously healthy 24-year-old woman. In such clinical cases, the specific localization of the tumor and its radiological properties can pose a differential diagnostic dilemma. Correct diagnosis is only possible after complete surgical excision and histopathologic analysis, which is the optimal therapeutic approach in this disease. PMID:27333732

  4. Castleman Disease: An Unexpected Cause of a Solitary Pleural Mass

    PubMed Central

    Moloney, Fiachra; Twomey, Maria; Hinchion, John; Maher, Michael

    2013-01-01

    Castleman disease (CD) is a rare benign lymphoproliferative disorder, the etiology of which is unclear. Clinically it may manifest as localized disease (unicentric) or disseminated disease (multicentric). CD occurs in the thorax in 70% of cases, abdomen and pelvis in 15%, and in the neck in 10–15% of cases. We present a case of a pleural mass located posteriorly in a paraspinal location, which was discovered incidentally in a 50-year-old man and was subsequently resected followed by an unexpected diagnosis of Castleman disease on histological examination. In this report, we review the clinical and histological findings in a rare presentation of Castleman disease and discuss the findings in this case as part of an overall review of the typical radiological findings seen in Castleman disease. PMID:24106632

  5. Methotrexate-associated primary cutaneous CD30-positive cutaneous T-cell lymphoproliferative disorder: a case illustration and a brief review.

    PubMed

    Claudino, Wederson M; Gibson, Bradley; Tse, William; Krem, Maxwell; Grewal, Jaspreet

    2016-01-01

    Methotrexate (MTX) is a commonly used anti-metabolite agent. Increased risk of lymphoproliferative disorders (LPD) in patients with rheumatoid arthritis (RA) has been documented with the prolonged use of immunosuppressive medications such as MTX. This is thought to be the result of immune dysregulation and/or chronic immune stimulation. Most cases of LPDs regress following withdrawal of the offending immunosuppressive agent. We present an interesting and rare case of CD30 and EBV positive CD8 primary cutaneous anaplastic large cell lymphoma (PC-ALCL) in a 66-year-old African American woman. Patient had been on MTX for rheumatoid arthritis (RA) which was stopped after the patient was evaluated at our institution. Patient had an incredible response to stopping immunosuppression with spontaneous regression of skin lesions and disappearance of clonal malignant cell population as evidenced on serial biopsy specimens. Primary cutaneous CD30+ LPDs constitute about 30% of the primary cutaneous T-cell lymphomas (CTLs) and includes entities such as lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (PC-ALCL) and other CD30+ borderline LPDs. Histopathological criteria in addition to CD30 positivity is important for identification of these conditions. Treatment options include "wait and see", phototherapy, radiotherapy, topical agents, systemic therapy and surgical resection. Prognosis is excellent and most cases resolve spontaneously on withdrawal of immunosuppression. Refractory cases may require aggressive local treatment or systemic therapy. Brentuximab Vedontin, an anti-CD30 antibody drug conjugate (ADC), may provide additional therapeutic option in refractory cases. PMID:27335685

  6. Methotrexate-associated primary cutaneous CD30-positive cutaneous T-cell lymphoproliferative disorder: a case illustration and a brief review

    PubMed Central

    Claudino, Wederson M; Gibson, Bradley; Tse, William; Krem, Maxwell; Grewal, Jaspreet

    2016-01-01

    Methotrexate (MTX) is a commonly used anti-metabolite agent. Increased risk of lymphoproliferative disorders (LPD) in patients with rheumatoid arthritis (RA) has been documented with the prolonged use of immunosuppressive medications such as MTX. This is thought to be the result of immune dysregulation and/or chronic immune stimulation. Most cases of LPDs regress following withdrawal of the offending immunosuppressive agent. We present an interesting and rare case of CD30 and EBV positive CD8 primary cutaneous anaplastic large cell lymphoma (PC-ALCL) in a 66-year-old African American woman. Patient had been on MTX for rheumatoid arthritis (RA) which was stopped after the patient was evaluated at our institution. Patient had an incredible response to stopping immunosuppression with spontaneous regression of skin lesions and disappearance of clonal malignant cell population as evidenced on serial biopsy specimens. Primary cutaneous CD30+ LPDs constitute about 30% of the primary cutaneous T-cell lymphomas (CTLs) and includes entities such as lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (PC-ALCL) and other CD30+ borderline LPDs. Histopathological criteria in addition to CD30 positivity is important for identification of these conditions. Treatment options include “wait and see”, phototherapy, radiotherapy, topical agents, systemic therapy and surgical resection. Prognosis is excellent and most cases resolve spontaneously on withdrawal of immunosuppression. Refractory cases may require aggressive local treatment or systemic therapy. Brentuximab Vedontin, an anti-CD30 antibody drug conjugate (ADC), may provide additional therapeutic option in refractory cases. PMID:27335685

  7. The influence of class II HLA type on the lymphoproliferative response of normal donors to a bcr-abl fusion peptide.

    PubMed

    MacIntyre, A R; Christmas, S E; Clark, R E

    1996-09-01

    Chronic myelogenous leukemia (CML) is characterized by a t(9;22) chromosomal translocation resulting in the expression of a novel bcr-abl fusion protein. The region spanning the fusion point is novel to the immune system and hence represents a potential leukemia-specific antigen. The ability of a 21-mer b3a2 fusion peptide to induce an in vitro lymphoproliferative response in a panel of 54 normal donors has been tested. This gave a mean stimulation index of 2.73 (95% CI 2.42-3.05) and 50/54 (93%) of donors gave responses that were greater than those with bcr or abl control peptides. The mean stimulation index relative to that of the control peptides was 1.80 (95% CI 1.63-1.97; p < 0.001). Responses were optimal at concentrations ranging from 0.3-150 micrograms/mL and in most cases peaked at 9 days. There was no clear relationship between level of responsiveness to the b3a2 fusion peptide and the presence of any single HLA-A, -B, -DR, or -DQ allele. HIA-DRB1*0404 was the only allele that was not associated with responsiveness. It is therefore likely that the b3a2 fusion peptide can be presented to T cells during a primary immune response in the context of several different class II HLA allelic products, albeit at low efficiency. The implications for specific active immunotherapy of CML patients are discussed.

  8. Comparison of chimerism and minimal residual disease monitoring for relapse prediction after allogeneic stem cell transplantation for adult acute lymphoblastic leukemia.

    PubMed

    Terwey, Theis Helge; Hemmati, Philipp Georg; Nagy, Marion; Pfeifer, Heike; Gökbuget, Nicola; Brüggemann, Monika; Le Duc, Tanja Melinh; le Coutre, Philipp; Dörken, Bernd; Arnold, Renate

    2014-10-01

    Little data are available on the relative merits of chimerism and minimal residual disease (MRD) monitoring for relapse prediction after allogeneic hematopoietic stem cell transplantation (HCT). We performed a retrospective analysis of serial chimerism assessments in 101 adult HCT recipients with acute lymphoblastic leukemia (ALL) and of serial MRD assessments in a subgroup of 22 patients. All patients had received myeloablative conditioning. The cumulative incidence of relapse was significantly higher in the patients with increasing mixed chimerism (in-MC) compared with those with complete chimerism, low-level MC, and decreasing MC, but the sensitivity of in-MC detection with regard to relapse prediction was only modest. In contrast, MRD assessment was highly sensitive and specific. Patients with MRD positivity after HCT had the highest incidence of relapse among all prognostic groups analyzed. The median time from MRD positivity to relapse was longer than the median time from detection of in-MC, but in some cases in-MC preceded MRD positivity. We conclude that MRD assessment is a powerful prognostic tool that should be included in the routine post-transplantation monitoring of patients with ALL, but chimerism analysis may provide additional information in some cases. Integration of these tools and clinical judgment should allow optimal decision making with regard to post-transplantation therapeutic interventions.

  9. Optimal time-points for minimal residual disease monitoring change on the basis of the method used in patients with acute myeloid leukemia who underwent allogeneic stem cell transplantation: a comparison between multiparameter flow cytometry and Wilms' tumor 1 expression.

    PubMed

    Rossi, Giovanni; Carella, Angelo Michele; Minervini, Maria Marta; di Nardo, Francesco; Waure, Chiara de; Greco, Michele Mario; Merla, Emanuela; Cillis, Giovanni Pio de; Di Renzo, Nicola; Melpignano, Angela; Capalbo, Silvana; Palumbo, Gaetano; Pisapia, Giovanni; Cascavilla, Nicola

    2015-02-01

    Minimal residual disease (MRD) of 30 adult AML patients was monitored by multiparameter flow cytometry (MFC) and WT1 expression before and after allogeneic stem cell transplantation (allo-SCT). Diagnostic performance of pre-transplant MRD measured by MFC was higher than that obtained by WT1 expression. Comparable results were displayed at day +30 post-transplant, while better values by WT1 compared to MFC were found at day +90. Positive MRD by MFC predicted a shorter disease free survival (DFS) before and 1 month after transplant (p=0.006 and p=0.005), while only high WT1 levels at 1 month from the transplant significantly impacted on DFS (p=0.010). Our results support the idea that MRD monitoring by MFC should be suggested before and 30 days after the transplant, while WT1 expression should be preferred after this procedure. The assessment of MRD at day +30 from allo-SCT is recommended as post transplant check-point for the predictive role displayed, independently of the method used.

  10. Dissociation between lymphoproliferative responses and virus replication in mice with different sensitivities to retrovirus-induced immunodeficiency.

    PubMed Central

    Pozsgay, J M; Reid, S; Pitha, P M

    1993-01-01

    Murine AIDS (MAIDS) is induced by a replication-defective virus (BM5d). In susceptible mice (C57BL/6J), inoculation with LP-BM5 murine leukemia virus, which consists of the BM5d virus and replication-competent B-tropic ecotropic (BM5e) and milk cell focus-inducing (BM5-MCF) helper viruses results in the polyclonal proliferation of T and B cells, immunodeficiency, and the expansion of B cells containing the BM5d provirus followed by the development of B-cell lymphomas. Several strains of mice that are resistant to LP-BM5-induced murine AIDS have been identified, and major histocompatibility complex genes as well as non-major histocompatibility complex genes were shown to play a role in this resistance. In the present study, we have examined and compared the replication of the BM5d and BM5e viruses after inoculation of LP-BM5 into sensitive (C57BL/6J) and resistant (C57BL/KSJ) mice. Using a specific polymerase chain reaction, we could detect the BM5d and BM5e proviruses as early as 1 week postinfection in the sensitive mice, and the levels of both viruses increased significantly with the progression of the disease. In contrast, in the resistant C57BL/KSJ mice, replication of BM5d and BM5e was restricted and no BM5d and only very low levels of the BM5e provirus could be detected either at early or late times postinoculation with the LP-BM5 virus mixture. Inoculation with LP-BM5 did not lead to the production of antibodies that could recognize the BM5d-encoded Pr60gag in either the sensitive or resistant mice; however, production of antibodies recognizing the env-related proteins of the helper virus was detected in the resistant but not in the sensitive mice at late times postinfection. Interestingly, inoculation with LP-BM5 increased polyclonal stimulation of spleen cells and decreased mitogen stimulation in both strains of mice. This stimulation of splenocytes persisted in the sensitive mice but decreased after a few weeks in the resistant mice. These results show an

  11. Dry Eye Disease Incidence Associated with Chronic Graft-Host Disease: Nonconcurrent Cohort Study (An American Ophthalmological Society Thesis)

    PubMed Central

    Mian, Shahzad I.; De la Parra-Colín, Paola; De Melo-Franco, Rafael; Johnson, Christopher; Barrientos-Gutierrez, Tonatiuh

    2015-01-01

    Purpose: To determine if chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with stable or progressive dry eye disease and to determine the true incidence in patients with no prior history of dry eye disease. Methods: A nonconcurrent cohort study at a single institution with 136 patients who had no previous history of dry eye disease before HSCT. Survival analysis was used to estimate dry eye disease incidence. The incidence rate was calculated using life tables as the number of observed dry eye disease cases divided by the person-time at risk accumulated by the cohort. Transition probabilities were calculated from time of transplant to time of diagnosis, and then to last recorded visit. Results: Incidence rate was 0.8 cases of dry eye disease per person-year, and half of the population at risk developed dry eye disease during the first 10 months post transplant. Time to develop dry eye disease was 2.5 months for mild dry eye disease, 9.6 months for moderate dry eye disease, and 13.2 months for severe dry eye disease. In terms of cumulative incidence, 73% of subjects developed dry eye disease (50% mild, 16% moderate, and 7% severe) at the time of diagnosis. Conclusions: Our findings suggest that dry eye disease associated with cGVHD is an extremely frequent event and shows a wide spectrum of severity, with a mild form presenting early and a moderate to severe form presenting later after HSCT. These findings need to be studied further to elucidate if these are two different pathophysiological entities or just different expressions of the same pathology. PMID:27507907

  12. A Rare Consequence of Chronic Graft Versus Host Disease - Peyronie's Disease

    PubMed Central

    Jain, Natasha A; Venkatesan, Krishnan; Anandi, Prathima; Ito, Sawa; Kumar, Dhruv; Lu, Kit; Battiwalla, Minoo; Barrett, A. John

    2015-01-01

    Chronic graft versus host disease (GvHD) after allogeneic stem cell transplantation (SCT) may involve any organ system, but male genital involvement is rare. Peyronie’s Disease (PD) is an acquired, localized fibrotic disorder of the tunica albuginea, which leads to penile deformity, pain, and eventually to erectile dysfunction. We report the case of a 52 year old African American male with Acute Myeloid Leukemia who underwent human leucocyte antigen (HLA) matched sibling allogeneic peripheral blood SCT. His post transplant course was complicated by development of acute and multi-organ chronic GvHD requiring prolonged immunosuppression. He developed progressive dorsal curvature of the penis with erections within 1 year of ultra low dose interleukin -2 (IL2) treatment for his chronic GvHD but concealed symptoms for several months. Color Doppler Duplex ultrasound evaluation of the erect penis revealed a 75-degree curvature and appropriate hemodynamic response to prostaglandin injection. He underwent successful incision and grafting of the penile plaque. There is no significant residual curvature and is now able to engage in intercourse. A strong temporal association between GVHD (or its treatment) and Peyronie's is documented here. Awareness of the possible link between PD and chronic GVHD is required in this era of rapid growth in numbers of SCT. PMID:26770907

  13. Immunotherapy for Epstein-Barr virus-associated cancers in children.

    PubMed

    Straathof, Karin C M; Bollard, Catherine M; Rooney, Cliona M; Heslop, Helen E

    2003-01-01

    Latent Epstein-Barr virus (EBV) infection is associated with several malignancies, including Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma, and post-transplant lymphoproliferative disease (LPD). The presence of EBV antigens in these tumors provides a target for immunotherapy approaches, and immunotherapy with EBV-specific cytotoxic T cells (CTLs) has proved effective in post-transplant LPDs, which are highly immunogenic tumors expressing type III latency. The malignant cells in Hodgkin's disease and nasopharyngeal carcinoma express type II latency and hence a more restricted pattern of EBV antigens. Trials with autologous EBV-specific CTL responses are under way in both of these diseases, and while some activity has been seen, no patient has yet been cured. This reduced CTL efficacy may reflect either downregulation of immunodominant EBV proteins, which are major CTL targets, or the ability of these tumors to evade the immune response by secreting inhibitory cytokines. Further improvement of EBV-specific CTL therapy for these type II latency tumors will require improved methods to activate and expand CTLs specific for the subdominant EBV genes expressed and to genetically modify the expanded CTLs to render them resistant to inhibitory cytokines. If these strategies to improve the therapeutic potential of immunotherapy for EBV-associated tumors prove successful, this type of treatment may be adapted to other tumors expressing known (viral) antigens. PMID:12604735

  14. Castleman Disease of the Thorax: Clinical, Radiologic, and Pathologic Correlation: From the Radiologic Pathology Archives.

    PubMed

    Kligerman, Seth J; Auerbach, Aaron; Franks, Teri J; Galvin, Jeffrey R

    2016-01-01

    Castleman disease is a complex lymphoproliferative disease pathologically divided into two subtypes, the hyaline vascular variant (HVV) and the plasma cell variant (PCV). The HVV is the most common, is thought to represent a benign neoplasm of lymph node stromal cells, and is treated with surgical resection. It is most commonly found in the mediastinum, where it classically appears as a unicentric, avidly enhancing mass at computed tomography (CT) and magnetic resonance imaging. This appearance can mimic other avidly enhancing mediastinal masses, and location, clinical history, laboratory data, and nuclear medicine single photon emission CT (SPECT) and positron emission tomography (PET) studies can help narrow the differential diagnosis. Multicentric Castleman disease (MCD), which in the majority of cases is composed of the PCV, is an aggressive lymphoproliferative disorder associated with human herpesvirus infection, interleukin 6 dysregulation, and other systemic disorders. While it can be difficult to differentiate MCD from lymphoma, the presence of avidly enhancing lymph nodes can suggest the diagnosis. The purpose of this article is to review the clinical, immunologic, and pathologic findings associated with both unicentric Castleman disease and MCD and discuss how the imaging findings correlate with the pathophysiology of the disease. PMID:27618318

  15. A survey of human T-cell leukaemia virus type I antibodies in patients with malignant disease in the Witwatersrand area.

    PubMed

    Dansey, R D; Mansoor, N; Cohn, R J; MacDougall, L G; Bezwoda, W R

    1986-10-11

    The prevalence of antibodies to human T-cell leukaemia virus type I in Africa ranges from 2% to 21% according to the geographical area surveyed. Most studies suggest that the background infection rate in children is low. In paediatric patients with malignant disease in the Witwatersrand area the prevalence is low (1%), whereas a seemingly high rate is found in healthy black children from a restricted rural area (7%). Further, the antibody prevalence in adult whites with lymphoproliferative disease is low (1%) compared with that in blacks with malignant disease (6%). There also appears to be a higher prevalence of positive results in black women (7%) than in black men (4%).

  16. A Palpable Painless Axillary Mass as the Clinical Manifestation of Castleman's Disease in a Patient with Hepatitis C Disease

    PubMed Central

    Papazafiropoulou, Athanasia K.; Angelidi, Angeliki M.; Kousoulis, Antonis A.; Christofilidis, Georgios; Sagia, Chariklia; Kaftanidou, Liountmila; Manoloudaki, Kassiani; Tsavari, Aikaterini; Kranidiotis, Georgios; Kamaratos, Alexandros; Melidonis, Andreas

    2016-01-01

    Introduction. Castleman's disease (CD) is a rare lymphoproliferative disorder. CD is divided into two clinical subtypes: the most common unicentric and the less usual multicentric subtype. The majority of unicentric CD affects the mediastinum, while neck, abdomen, and axilla are less common locations. Case Presentation. Herein, we describe a rare case of unicentric CD in the right axilla in a 36-year-old white male with a medical history of hepatitis C virus infection admitted to our hospital due to palpation of a painless mass in the right axilla. Complete excision of the lesion was performed and, one year after the diagnosis, patient was free of the disease. Conclusions. Although infrequent, it is important to include CD in the differential diagnosis when evaluating axillary lymphadenopathy particularly in young patients with a low-grade inflammation process and chronic disease even in the absence of an abnormal blood picture or organomegaly. PMID:27313621

  17. A Palpable Painless Axillary Mass as the Clinical Manifestation of Castleman's Disease in a Patient with Hepatitis C Disease.

    PubMed

    Papazafiropoulou, Athanasia K; Angelidi, Angeliki M; Kousoulis, Antonis A; Christofilidis, Georgios; Sagia, Chariklia; Kaftanidou, Liountmila; Manoloudaki, Kassiani; Tsavari, Aikaterini; Kranidiotis, Georgios; Kamaratos, Alexandros; Melidonis, Andreas

    2016-01-01

    Introduction. Castleman's disease (CD) is a rare lymphoproliferative disorder. CD is divided into two clinical subtypes: the most common unicentric and the less usual multicentric subtype. The majority of unicentric CD affects the mediastinum, while neck, abdomen, and axilla are less common locations. Case Presentation. Herein, we describe a rare case of unicentric CD in the right axilla in a 36-year-old white male with a medical history of hepatitis C virus infection admitted to our hospital due to palpation of a painless mass in the right axilla. Complete excision of the lesion was performed and, one year after the diagnosis, patient was free of the disease. Conclusions. Although infrequent, it is important to include CD in the differential diagnosis when evaluating axillary lymphadenopathy particularly in young patients with a low-grade inflammation process and chronic disease even in the absence of an abnormal blood picture or organomegaly. PMID:27313621

  18. [Castleman's disease: a case report].

    PubMed

    Cammisuli, E; Catania, V; Santuccio, A; Pennisi, S

    2003-01-01

    Castlemans disease (CD) was described from Benjamin Castleman in 1954. The disease today is enumerated among lymphoproliferative disorders and has unknown etiology, but a interleukin-6 (IL-6) dysregulation and a reaction to viral antigens (HHV8) especially in patients with immunodeficiency is suspected. It is observed in adult and young people, in male or female with equal frequency; the appearance in childhood is extremely rare. The disease shows various clinical and histological pictures, with a localized type (involvement of one lymph node group) described more frequently than the multicentric one. Histological examination distinguish a "hyaline-vascular type" that represents approximately the 91%, a plasma cell type" that represents approximately the 9% has an aggressive clinical outcome, and the "mixed types". Initial symptoms are nearly absent, but not for the plasma cell type. We describe the clinical case of a female patient 21 years old. She reached our observation in May 1999, referring us for pelvic pains and amenorrhoea from four years. During 1996 she underwent to a laparoscopy that diagnosed an endometrial cyst on left ovary. A year later a new retroperitoneal mass was discovered and a second laparoscopy was performed with a little partial excision of the tumor. In our Institute the us and the TC showed a retroperitoneal mass of 4.5 cm of diameter, next to the uterus and the iliac left vessels. The patient underwent surgical laparotomic excision and histological examination showed hyaline vascular type of CD. Three years after surgery the patient is still free of any symptoms.

  19. Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma Involving the Colon in a Patient With Ulcerative Pancolitis and Polymyositis on Long-Term Methotrexate Therapy

    PubMed Central

    Chang, Michael D.; Markham, Merry-Jennifer; Liu, Xiuli

    2016-01-01

    The link between immunosuppressive therapy and increased lymphoma risk is well established in patients with solid organ transplantation. Epstein-Barr virus-positive (EBV) diffuse large B-cell lymphoma (DLBCL) is known to be a complication in patients receiving methotrexate for rheumatoid arthritis, and the risk of lymphoma in inflammatory bowel disease (IBD) has raised concerns regarding the lymphoproliferative potential of immunomodulatory therapy. In this report, we describe a case of EBV-positive DLBCL arising within the colon of a patient affected by ulcerative pancolitis. The patient is a 73-year-old man with a history of IBD and polymyositis on long-term methotrexate therapy. Increasing age and long-term methotrexate therapy may simulate post-transplantation immunosuppression and contribute to lymphoma tumorigenesis in a segment of chronically inflamed colon. PMID:27785332

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

    PubMed

    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; Storb, Rainer

    2007-10-01

    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/m(2); 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.

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

    PubMed Central

    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

    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

  2. Antimicrobial prophylaxis in allogeneic bone marrow transplantation. Guidelines of the infectious diseases working party (AGIHO) of the german society of haematology and oncology.

    PubMed

    Krüger, W H; Bohlius, J; Cornely, O A; Einsele, H; Hebart, H; Massenkeil, G; Schüttrumpf, S; Silling, G; Ullmann, A J; Waldschmidt, D T; Wolf, H-H

    2005-08-01

    Patients undergoing allogeneic stem cell transplantation are at high risk for infection with a variety of pathogens during different phases of the procedure. Bacteria and fungi predominate the first phase until engraftment. During the second phase, from engraftment to about day 100, major infectious problems are caused by fungi and cytomegalovirus. Both pathogens remain important under continued immunosuppression, however, in the late post-transplantation period infections with encapsulated bacteria may become a problem. In this review the Infectious Diseases Working Party of the DGHO gives recommendations for prophylaxis of infections under allogeneic stem cell transplantation with drugs and other measures. The aim of the group was to do this on an evidence-based-medicine rating, if possible.

  3. De novo therapy with everolimus and reduced-exposure cyclosporine following pediatric kidney transplantation: a prospective, multicenter, 12-month study.

    PubMed

    Grushkin, Carl; Mahan, John D; Mange, Kevin C; Hexham, J Mark; Ettenger, Robert

    2013-05-01

    Prospective data regarding the de novo use of everolimus following kidney transplantation in children are sparse. In a prospective, 12-month, single-arm, open-label study, pediatric kidney transplant patients received everolimus (target trough concentration ≥3 ng/mL) with reduced-exposure CsA and corticosteroids, with or without basiliximab induction. Sixteen of the 18 patients completed the study on-treatment. Age range was 2-16 yr (mean 10.9 yr); eight patients received a living donor graft. Mean (s.d.) everolimus level was 7.4 (3.1) ng/mL during the first 12 months post-transplant. There were no cases of BPAR, graft loss, or death during the study. Protocol biopsies were performed at month 12 in seven patients, with subclinical (untreated) acute rejection diagnosed in one case. Mean (s.d.) estimated GFR (Schwartz formula) was 98 (34) mL/min/1.73 m(2) at month 12. Three patients experienced one or more serious adverse events with a suspected relation to study medication. One patient discontinued study medication due to post-transplant lymphoproliferative disease (5.6%). Everolimus with reduced-dose CsA and corticosteroids achieved good efficacy and renal function and was well tolerated in this small cohort of pediatric kidney transplant patients. Controlled trials are required to answer remaining questions about the optimal use of everolimus in this setting.

  4. Roles of mTOR complexes in the kidney: implications for renal disease and transplantation.

    PubMed

    Fantus, Daniel; Rogers, Natasha M; Grahammer, Florian; Huber, Tobias B; Thomson, Angus W

    2016-10-01

    The mTOR pathway has a central role in the regulation of cell metabolism, growth and proliferation. Studies involving selective gene targeting of mTOR complexes (mTORC1 and mTORC2) in renal cell populations and/or pharmacologic mTOR inhibition have revealed important roles of mTOR in podocyte homeostasis and tubular transport. Important advances have also been made in understanding the role of mTOR in renal injury, polycystic kidney disease and glomerular diseases, including diabetic nephropathy. Novel insights into the roles of mTORC1 and mTORC2 in the regulation of immune cell homeostasis and function are helping to improve understanding of the complex effects of mTOR targeting on immune responses, including those that impact both de novo renal disease and renal allograft outcomes. Extensive experience in clinical renal transplantation has resulted in successful conversion of patients from calcineurin inhibitors to mTOR inhibitors at various times post-transplantation, with excellent long-term graft function. Widespread use of this practice has, however, been limited owing to mTOR-inhibitor- related toxicities. Unique attributes of mTOR inhibitors include reduced rates of squamous cell carcinoma and cytomegalovirus infection compared to other regimens. As understanding of the mechanisms by which mTORC1 and mTORC2 drive the pathogenesis of renal disease progresses, clinical studies of mTOR pathway targeting will enable testing of evolving hypotheses. PMID:27477490

  5. Basiliximab treatment for autoimmune bowel disease in a pediatric heart transplant patient.

    PubMed

    Puri, K; Kocoshis, S; Risma, K; Perez, L; Hart, C; Chin, C; Ryan, T D; Jefferies, J L; Schumacher, K R; Castleberry, C

    2015-11-01

    Autoimmune-mediated bowel disease has been reported after pediatric heart transplantation. Recognition and treatment of these patients has been difficult. We describe a patient who responded to steroids and basiliximab therapy after an inflammatory process secondary to abnormal T-cell activation. Our patient is a 28-month-old female who received a heart transplant at five wk of age. At 24 months post-transplant, she developed fever and bloody stools. Initial investigations were significant for an elevated ESR (>120) and CRP (15.2). Symptoms persisted despite bowel rest and mycophenolate discontinuation. Endoscopic evaluation revealed discontinuous ulcerative disease involving esophagus, terminal ileum, right and left colon, necessitating extensive bowel resection. She had additional airway inflammation leading to a TEF at the site of esophageal ulceration, requiring tracheostomy. Immune evaluation revealed autoimmune dysregulation that responded to parenteral methylprednisolone. Chronic basiliximab therapy allowed for successful weaning of steroids with sustained remission. She has been transitioned to sirolimus and tacrolimus maintenance immunosuppression with plans to discontinue basiliximab once off steroids. In conclusion, bowel disease in the setting of pediatric heart transplantation can be severe and refractory to traditional treatment methods. Tailoring immune therapy to activated T cells can result in remission. Basiliximab therapy was used in our patient to maintain steroid-induced remission, but long-term complications of this disease process are unknown.

  6. Non-alcoholic fatty liver disease and liver transplantation.

    PubMed

    Khan, Reenam S; Newsome, Philip N

    2016-08-01

    Cirrhosis secondary to non-alcoholic steatohepatitis (NASH) is a common indication for liver transplant. In comparison to other cirrhotic patients, patients with NASH cirrhosis are more likely to be older and have the metabolic syndrome. Pre-transplant, patients require careful evaluation of cardiovascular risk. As the incidence of non-alcoholic fatty liver disease (NAFLD) is rising, a greater proportion of donor grafts have steatosis greater than 30%, which is associated with poor outcomes. Grafts with steatosis greater than 60% are unsuitable for transplant. Overall, post-transplant survival outcomes for patients with NASH cirrhosis are similar to those with cirrhosis without NASH. However, NASH cirrhosis is associated with a higher 30-day mortality, predominantly from an increase in cardiovascular events and infections. Following liver transplant, there is a significant risk of NASH recurrence, although this seldom results in allograft loss. Furthermore, a significant number of patients who had a liver transplant for other reasons develop NASH de novo. When patients with NASH cirrhosis are considered for transplant, one of the major challenges lies in identifying which patients are too high risk for surgery. This review aims to provide information to aid this decision making process, and to provide guidance on the peri-operative care strategies that can modify risk. PMID:26997540

  7. Selenite benefits embryonic stem cells therapy in Parkinson's disease.

    PubMed

    Tian, L-P; Zhang, S; Xu, L; Li, W; Wang, Y; Chen, S-D; Ding, J-Q

    2012-09-01

    Embryonic stem cells (ESC) transplantation is a potential therapeutic approach for Parkinson's disease (PD). However, one of the main challenges to this therapy is the post-transplantation survival of dopaminergic (DA) neurons. In this study, mouse ESC were differentiated into DA neurons by a modified serum free protocol. These ESC-derived neurons were then transplanted into striatum of 6-OHDA lesioned rat. The viability of grafted DA neurons was decreased, accompanied by activated microglia and high levels of proinflammatory factors, such as TNF-α and iNOS, in the graft niche. This suggested that the local neuroinflammation might be involved in the reduced cells viability. Selenite, the source of essential micronutrient selenium, could inhibit NF-κB p65 nuclear translocation and subsequently reduce iNOS, COX-2 and TNF-α expression in LPS-treated BV2 cells in a dose dependant manner. Before the transplantation of ESC-derived DA neurons, 6-OHDA lesioned rats were intraperitoneally injected with selenite. The expression levels of TNF-α and iNOS were decreased by 30% and 50%, respectively, in selenite treated group. The survival of implanted DA neurons and the rotational behavior of transplanted rats were also remarkably improved by selenite treatment. To sum up, selenite might benefit ESCs transplantation therapy in PD through anti-inflammation effects.

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

    PubMed Central

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

    1988-01-01

    Castleman's disease is a morphologically and clinically heterogeneous lymphoproliferative disorder. Both a localized benign variant and an aggressive form with systemic manifestations have been described. To investigate the differences between these variants of Castleman's disease, the authors analyzed lymph node DNA from 4 patients with the localized type and 4 with the systemic type of Castleman's disease for immunoglobulin and T-cell receptor gene rearrangements. The role of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) was also studied by viral genomic DNA probes. They detected clonal rearrangements in 3 of the 4 patients with the systemic variant of Castleman's; no patients with localized disease had rearrangements. Copies of EBV genome were also detected in 2 of the 3 patients with clonal rearrangements. These results suggest that systemic Castleman's disease is a disorder distinct from the classical localized variant in that it may evolve into a clonal lymphoproliferation. Images Figure 1 PMID:2833104

  9. Retroviral insertional activation of the c-myb proto-oncogene in a Marek's disease T-lymphoma cell line.

    PubMed Central

    Le Rouzic, E; Perbal, B

    1996-01-01

    Marek's disease virus (MDV) is an avian herpesvirus that causes, in chickens, a lymphoproliferative disease characterized by malignant transformation of T lymphocytes. The rapid onset of polyclonal tumors indicates the existence of MDV-encoded oncogenic products. However, the molecular basis of MDV-induced lymphoproliferative disease and latency remains largely unclear. Several lines of evidence suggest that MDV and Rous-associated virus (RAV) might cooperate in the development of B-cell lymphomas induced by RAV. Our present results indicate for the first time that MDV and RAV might also act synergistically in the development of T-cell lymphomas. We report an example of an MDV-transformed T-lymphoblastoid cell line (T9) expressing high levels of a truncated C-MYB protein as a result of RAV integration within one c-myb allele. The chimeric RAV-c-myb mRNA species initiated in the 5' long terminal repeat of RAV are deprived of sequences corresponding to c-myb exons 1 to 3. The attenuation of MDV oncogenicity has been strongly related to structural changes in the MDV BamHI-D and BamHI-H DNA fragments. We have established that both DNA restriction fragments are rearranged in the T9 MDV-transformed cells. Our results suggest that retroviral insertional activation of the c-myb proto-oncogene is a critical factor involved in the maintenance of the transformed phenotype and the tumorigenic potential of this T-lymphoma cell line. PMID:8892859

  10. Minimal change disease: A case report of an unusual relationship.

    PubMed

    Edrees, Fahad; Black, Robert M; Leb, Laszlo; Rennke, Helmut

    2016-01-01

    Kidney injury associated with lymphoproliferative disorders is rare, and the exact pathogenetic mechanisms behind it are still poorly understood. Glomerular involvement presenting as a nephrotic syndrome has been reported, usually secondary to membranoproliferative glomerulonephritis. We report a case of a 63-year-old male who presented with bilateral leg swelling due to nephrotic syndrome and acute kidney injury. A kidney biopsy showed minimal change disease with light chain deposition; however, no circulating light chains were present. This prompted a bone marrow biopsy, which showed chronic lymphocytic leukemia (CLL) with deposition of the same kappa monoclonal light chains. Three cycles of rituximab and methylprednisolone resulted in remission of both CLL and nephrotic syndrome, without recurrence during a three-year follow-up.

  11. Rosai-Dorfman Disease of the Central Nervous System

    PubMed Central

    Sandoval-Sus, Jose D.; Sandoval-Leon, Ana C.; Chapman, Jennifer R.; Velazquez-Vega, Jose; Borja, Maria J.; Rosenberg, Shai; Lossos, Alexander; Lossos, Izidore S.

    2014-01-01

    Abstract Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy (SHML), is an uncommon benign idiopathic lymphoproliferative disorder. The histologic hallmark of RDD is the finding of emperipolesis displayed by lesional histiocytes. While RDD most commonly affects lymph nodes, extranodal involvement of multiple organs has been reported, including the central nervous system (CNS). However, CNS involvement in RDD is rare and is not well characterized. As a result, therapeutic approaches to CNS involvement in RDD are not well established. Herein we report 6 cases of RDD with isolated CNS involvement and review the literature on RDD with CNS involvement. One of the presented cases exhibited intramedullary involvement of the spinal cord—a very rare form of RDD with CNS involvement. PMID:24797172

  12. Emerging treatments in Castleman disease – a critical appraisal of siltuximab

    PubMed Central

    Koff, Jean L; Lonial, Sagar

    2016-01-01

    Castleman disease (CD) is a rare, heterogeneous lymphoproliferative disorder for which no standard of care currently exists. Evidence that the pathophysiology of CD is fueled by excessive interleukin-6 (IL-6) has led to considerable interest in therapeutic targeting of this cytokine. Siltuximab, a chimeric monoclonal antibody to IL-6, has thus emerged as a promising treatment option in a disease lacking efficacious therapy. Here, we review the findings of recent studies evaluating single-agent siltuximab treatment in CD, including the first-ever randomized clinical trial in this disease. Although much more work is needed to establish a standardized treatment approach, siltuximab appears to be a safe and effective treatment for patients with newly diagnosed and previously treated CD. PMID:26869762

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

    ClinicalTrials.gov

    2015-08-04

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Myeloid Leukemia in Remission; Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell

  14. Outcomes after Hematopoietic Stem Cell Transplant for Children with I-Cell Disease

    PubMed Central

    Lund, Troy C.; Cathey, Sara S.; Miller, Weston P.; Eapen, Mary; Andreansky, Martin; Dvorak, Christopher C.; Davis, Jeffrey H.; Dalal, Jignesh D.; Devine, Steven M.; Eames, Gretchen M.; Ferguson, William S.; Giller, Roger H.; He, Wensheng; Kurtzberg, Joanne; Krance, Robert; Katsanis, Emmanuel; Lewis, Victor A.; Sahdev, Indira; Orchard, Paul J.

    2014-01-01

    Mucolipidosis type II (MLII), or I-Cell Disease, is a rare, but severe disorder affecting localization of enzymes to the lysosome, generally resulting in death before the 10th birthday. Although hematopoietic stem cell transplant (HSCT) has been used to successfully treat some lysosomal storage diseases, there have been only two case reports in the use of HSCT to treat MLII. For the first time, we describe the combined international experience in the use of HSCT for MLII in 22 patients. Although 95% of the patients engrafted, the overall survival was low with only 6 patients (27%) alive at last follow-up. The most common cause of death post-transplant was cardiovascular complications, most likely due to disease progression. Survivors were globally delayed in development, and often required complex medical support such as gastrostomy tubes for nutrition, and tracheostomy with mechanical ventilation. Although HSCT has demonstrated efficacy in treating some lysosomal storage disorders, the neurologic outcome and survival for patents with MLII were poor. Therefore new medical and cellular therapies should be sought for these patients. PMID:25016194

  15. Successful cord blood transplantation in an adult acute lymphoblastic leukemia patient with congenital heart disease.

    PubMed

    Kowata, Shugo; Fujishima, Yukiteru; Suzuki, Yuzo; Tsukushi, Yasuhiko; Oyake, Tatsuo; Togawa, Ryou; Oyama, Kotaro; Ikai, Akio; Ito, Shigeki; Ishida, Yoji

    2016-08-01

    Recent advances in surgical corrections and supportive care for congenital heart disease have resulted in increasing numbers of adult survivors who may develop hematological malignancies. Treatments including chemotherapy for such patients may cause serious hemodynamic or cardiac complications, especially in those receiving stem cell transplantation. We present a 29-year-old woman with acute lymphoblastic leukemia and congenital heart disease. She had been diagnosed with pulmonary atresia with an intact ventricular septum at birth, and the anomaly was surgically corrected according to the Fontan technique at age 9 years. Her induction chemotherapy required modifications due to poor cardiac status with Fontan circulation. However, after surgical procedures including total cavopulmonary connection and aortic valve replacement at first complete remission, her cardiac status was significantly improved. Subsequently, she underwent cord blood stem cell transplantation at the third complete remission. She required intensive supportive care for circulatory failure as a pre-engraftment immune reaction and stage III acute graft versus host disease of the gut, but recovered from these complications. She was discharged on day 239, and remained in complete remission at 1-year post-transplantation. PMID:27599417

  16. BK virus disease after allogeneic stem cell transplantation: a cohort analysis.

    PubMed

    Rorije, Nienke M G; Shea, Margaret M; Satyanarayana, Gowri; Hammond, Sarah P; Ho, Vincent T; Baden, Lindsey R; Antin, Joseph H; Soiffer, Robert J; Marty, Francisco M

    2014-04-01

    The clinical epidemiology of BK virus (BKV) disease after allogeneic hematopoietic stem cell transplantation (HSCT) is not well defined. We evaluated 491 patients transplanted from January 2010 to December 2011 at a single transplant center to assess incidence, severity, and risk factors for BKV disease after HSCT. BKV disease was defined as BKV detection in urine by PCR testing in association with genitourinary symptoms without other concurrent genitourinary conditions. BKV disease occurred in 78 patients (15.9%), for an incidence rate of .47/1000 patient-days (95% confidence interval [CI], .37 to .59); BKV disease was considered severe in 27 patients (5.5%). In multivariate Cox modeling, time-dependent acute graft-versus-host disease (aGVHD) grades II to IV (adjusted hazard ratio [aHR] 4.25; 95% CI, 2.51 to 7.21), cord blood HSCT (aHR 2.28; 95% CI, 1.01 to 5.15), post-transplant mycophenolate use (aHR 3.31; 95% CI, 1.83 to 5.99), and high-dose cyclophosphamide conditioning (aHR 2.34, 95% CI 1.45 to 3.77) were significant predictors of BKV disease. Time-dependent aGVHD grades III to IV (aHR 10.5; 95% CI, 4.44 to 25.0) and cord blood HSCT (aHR 5.40; 95% CI, 1.94 to 15.0) were independent risk factors for severe BKV disease. BKV disease is common and is associated with significant and prolonged morbidity after HSCT. Prospective studies are needed to better define the morbidity of post-HSCT BKV disease and inform the design of prophylaxis and treatment trials.

  17. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease.

    PubMed

    Holler, Ernst; Butzhammer, Peter; Schmid, Karin; Hundsrucker, Christian; Koestler, Josef; Peter, Katrin; Zhu, Wentao; Sporrer, Daniela; Hehlgans, Thomas; Kreutz, Marina; Holler, Barbara; Wolff, Daniel; Edinger, Matthias; Andreesen, Reinhard; Levine, John E; Ferrara, James L; Gessner, Andre; Spang, Rainer; Oefner, Peter J

    2014-05-01

    Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from serial stool specimens collected from 31 patients receiving allogeneic stem cell transplantation (SCT) was performed to elucidate variations in the composition of the intestinal microbiome in the course of allogeneic SCT. Metagenomic analysis was complemented by strain-specific enterococcal PCR and indirect assessment of bacterial load by liquid chromatography-tandem mass spectrometry of urinary indoxyl sulfate. At the time of admission, patients showed a predominance of commensal bacteria. After transplantation, a relative shift toward enterococci was observed, which was more pronounced under antibiotic prophylaxis and treatment of neutropenic infections. The shift was particularly prominent in patients that developed subsequently or suffered from active gastrointestinal (GI) graft-versus-host disease (GVHD). The mean proportion of enterococci in post-transplant stool specimens was 21% in patients who did not develop GI GVHD as compared with 46% in those that subsequently developed GI GVHD and 74% at the time of active GVHD. Enterococcal PCR confirmed predominance of Enterococcus faecium or both E. faecium and Enterococcus faecalis in these specimens. As a consequence of the loss of bacterial diversity, mean urinary indoxyl sulfate levels dropped from 42.5 ± 11 μmol/L to 11.8 ± 2.8 μmol/L in all post-transplant samples and to 3.5 ± 3 μmol/L in samples from patients with active GVHD. Our study reveals major microbiome shifts in the course of allogeneic SCT that occur in the period of antibiotic treatment but are more prominent in association with GI GVHD. Our data indicate early microbiome shifts and a loss of diversity of the intestinal microbiome that may affect intestinal inflammation in the setting of allogeneic SCT.

  18. Heart transplantation for congenital heart disease in the first year of life.

    PubMed

    Chinnock, Richard E; Bailey, Leonard L

    2011-05-01

    Successful infant heart transplantation has now been performed for over 25 years. Assessment of long term outcomes is now possible. We report clinical outcomes for322 patients who received their heart transplant during infancy. Actuarial graft survival for newborn recipients is 59% at 25 years. Survival has improved in the most recent era. Cardiac allograft vasculopathy is the most important late cause of death with an actuarial incidence at 25 years of 35%. Post-transplant lymphoma is estimated to occur in 20% of infant recipients by25 years. Chronic kidney disease grade 3 or worse is present in 31% of survivors. The epidemiology of infant heart transplantation has changed through the years as the results for staged repair improved and donor resources remained stagnant. Most centers now employ staged repair for hypoplastic left heart syndrome and similar extreme forms of congenital heart disease. Techniques for staged repair, including the hybrid procedure, are described. The lack of donors is described with particular note regarding decreased donors due to newer programs for appropriate infant sleep positioning and infant car seats. ABO incompatible donors are a newer resource for maximizing donor resources, as is donation after circulatory determination of death and techniques to properly utilize more donors by expanding the criteria for what is an acceptable donor. An immunological advantage for the youngest recipients has long been postulated, and evaluation of this phenomenon may provide clues to the development of accommodation and/or tolerance. PMID:22548030

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

    PubMed

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

    2014-11-01

    The inhibitor of apoptosis (IAP) family members, notably cIAP1, cIAP2, and XIAP, are critical and universal regulators of tumor necrosis factor (TNF) mediated survival, inflammatory, and death signaling pathways. Furthermore, IAPs mediate the signaling of nucleotide-binding oligomerization domain (NOD)1/NOD2 and other intracellular NOD-like receptors in response to bacterial pathogens. These pathways are important to the pathogenesis and treatment of inflammatory bowel disease (IBD). Inactivating mutations in the X-chromosome-linked IAP (XIAP) gene causes an immunodeficiency syndrome, X-linked lymphoproliferative disease type 2 (XLP2), in which 20% of patients develop severe intestinal inflammation. In addition, 4% of males with early-onset IBD also have inactivating mutations in XIAP. Therefore, the IAPs play a greater role in gut homeostasis, immunity and IBD development than previously suspected, and may have therapeutic potential.

  20. Perivesical unicentric Castleman disease initially suspected to be metastatic prostate cancer

    PubMed Central

    Guthrie, Patrick J.; Thomas, John V.; Peker, Deniz; Turkbey, Baris; Rais-Bahrami, Soroush

    2016-01-01

    Unicentric Castleman disease (UCD) is a relatively rare lymphoproliferative disease, which commonly presents as a mediastinal mass and less frequently involves abdomen, pelvis, and retroperitoneum. We report a case of a 64-year-old man with newly diagnosed low-volume, Gleason 3 + 3 = 6 prostate adenocarcinoma, who in considering active surveillance versus treatment was found to have a left perivesical and iliac chain lymphadenopathy concerning for potential metastatic involvement. He underwent magnetic resonance imaging with ferumoxytol to assist in the diagnostic evaluation to better characterize his lymphadenopathy. Subsequently, he underwent robotic-assisted laparoscopic bilateral pelvic lymph node dissection and resection of left perivesical mass exhibiting hyaline vascular variant of UCD. PMID:27141204

  1. Regulatory T-Cells in Chronic Lymphocytic Leukemia and Autoimmune Diseases

    PubMed Central

    D’Arena, Giovanni; Rossi, Giovanni; Vannata, Barbara; Deaglio, Silvia; Mansueto, Giovanna; D’Auria, Fiorella; Statuto, Teodora; Simeon, Vittorio; De Martino, Laura; Marandino, Aurelio; Del Poeta8, Giovanni; De Feo, Vincenzo; Musto, Pellegrino

    2012-01-01

    Regulatory T-cells (Tregs) constitute a small subset of cells that are actively involved in maintaining self-tolerance, in immune homeostasis and in antitumor immunity. They are thought to play a significant role in the progression of cancer and are generally increased in patient with chronic lymphocytic leukemia (CLL). Their number correlates with more aggressive disease status and is predictive of the time to treatment, as well. Moreover, it is now clear that dysregulation in Tregs cell frequency and/or function may result in a plethora of autoimmune diseases, including multiple sclerosis, type 1 diabetes mellitus, myasthenia gravis, systemic lupus erythematosus, autoimmune lymphoproliferative disorders, rheumatoid arthritis, and psoriasis. Efforts are made aiming to develop approaches to deplete Tregs or inhibit their function in cancer and autoimmune disorders, as well. PMID:22973497

  2. Objective Radiological Assessment of Body Composition in Patients with End-Stage Liver Disease: Going Beyond the BMI

    PubMed Central

    Cruz, Ruy J.; Dew, Mary Amanda; Myaskovsky, Larissa; Goodpaster, Bret; Fox, Kristen; Fontes, Paulo; DiMartini, Andrea

    2015-01-01

    Body Mass Index is a commonly used but likely inexact measure of body composition for patients with end-stage liver disease. For this reason, we examined whether body composition measurements from direct visualization on computerized tomography (CT) scans provide new insights both into the degree of malnutrition and also discordant combinations such as obesity with muscle mass loss. This technology is widely used in other medically ill populations but not yet in liver transplantation. Methods We examined actual body composition using abdominal CT scan data and software designed to measure fat and muscle compartments. Results In 234 liver transplant candidates we found BMI was highly and significantly correlated to subcutaneous and visceral fat. However we additionally found that even among obese patients, cachexia, as defined by muscle mass, was common with 56% of those with BMIs over 30 being cachexic. We also found that patients with non-alcoholic steatohepatitis, compared to other types of liver diseases, were significantly more likely to have larger amounts of visceral fat while also having less muscle. In an exploratory analysis muscle mass corrected for height was a significant predictor of post-transplant survival. Conclusions Body composition by CT scan data provides a specific method to identify obesity and muscle wasting for end-stage liver disease patients. Whether these data can aid in the prognostication of outcomes and survival requires further investigation. PMID:23348896

  3. A Phase I Dose-Finding Trial of Recombinant Interleukin-21 and Rituximab in Relapsed and Refractory Low Grade B-cell Lymphoproliferative Disorders

    PubMed Central

    Timmerman, John M.; Byrd, John C.; Andorsky, David J.; Yamada, Reiko E.; Kramer, Janet; Muthusamy, Natarajan; Hunder, Naomi; Pagel, John M.

    2015-01-01

    Purpose We performed a phase I study to determine the safety, maximum tolerated dose (MTD), and efficacy of weekly bolus recombinant human interleukin-21 (rIL-21) plus rituximab in patients with indolent B-cell malignancies. Experimental Design One week after a lead-in rituximab dose, cohorts of 3 patients were treated with 30, 100, or 150 μg/kg rIL-21 weekly for 4 weeks, concurrent with 4 weekly doses of rituximab. Patients with stable disease or better were eligible for a second course of therapy. Results Twenty-one patients with relapsed small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL, n=11), follicular lymphoma (n=9), or marginal zone lymphoma (n=1) were enrolled, with 19 completing at least 1 course of therapy. The MTD for rIL-21 was 100 μg/kg, based on observed toxicities including nausea, vomiting, diarrhea, hypotension, edema, and hypophosphatemia. Clinical responses were seen in 8 of 19 evaluable patients (42%; 3 CR/CRu, 5 PR), with 4 of longer duration than the patient’s previous response to rituximab-based treatment (median 9 versus 3 months). Conclusions Outpatient therapy of indolent B-cell malignancies with rituximab and weekly rIL-21 was well-tolerated and clinically-active, with durable complete remissions in a small subset of patients. Additional studies of rIL-21 and anti-CD20 antibodies in lymphoma and SLL/CLL are warranted. PMID:22893631

  4. Management of hepatitis C in patients with chronic kidney disease

    PubMed Central

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

    2015-01-01

    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

  5. Renal Primordia Activate Kidney Regenerative Events in a Rat Model of Progressive Renal Disease

    PubMed Central

    Imberti, Barbara; Corna, Daniela; Rizzo, Paola; Xinaris, Christodoulos; Abbate, Mauro; Longaretti, Lorena; Cassis, Paola; Benedetti, Valentina; Benigni, Ariela; Zoja, Carlamaria; Remuzzi, Giuseppe; Morigi, Marina

    2015-01-01

    New intervention tools for severely damaged kidneys are in great demand to provide patients with a valid alternative to whole organ replacement. For repairing or replacing injured tissues, emerging approaches focus on using stem and progenitor cells. Embryonic kidneys represent an interesting option because, when transplanted to sites such as the renal capsule of healthy animals, they originate new renal structures. Here, we studied whether metanephroi possess developmental capacity when transplanted under the kidney capsule of MWF male rats, a model of spontaneous nephropathy. We found that six weeks post-transplantation, renal primordia developed glomeruli and tubuli able to filter blood and to produce urine in cyst-like structures. Newly developed metanephroi were able to initiate a regenerative-like process in host renal tissues adjacent to the graft in MWF male rats as indicated by an increase in cell proliferation and vascular density, accompanied by mRNA and protein upregulation of VEGF, FGF2, HGF, IGF-1 and Pax-2. The expression of SMP30 and NCAM was induced in tubular cells. Oxidative stress and apoptosis markedly decreased. Our study shows that embryonic kidneys generate functional nephrons when transplanted into animals with severe renal disease and at the same time activate events at least partly mimicking those observed in kidney tissues during renal regeneration. PMID:25811887

  6. Renal primordia activate kidney regenerative events in a rat model of progressive renal disease.

    PubMed

    Imberti, Barbara; Corna, Daniela; Rizzo, Paola; Xinaris, Christodoulos; Abbate, Mauro; Longaretti, Lorena; Cassis, Paola; Benedetti, Valentina; Benigni, Ariela; Zoja, Carlamaria; Remuzzi, Giuseppe; Morigi, Marina

    2015-01-01

    New intervention tools for severely damaged kidneys are in great demand to provide patients with a valid alternative to whole organ replacement. For repairing or replacing injured tissues, emerging approaches focus on using stem and progenitor cells. Embryonic kidneys represent an interesting option because, when transplanted to sites such as the renal capsule of healthy animals, they originate new renal structures. Here, we studied whether metanephroi possess developmental capacity when transplanted under the kidney capsule of MWF male rats, a model of spontaneous nephropathy. We found that six weeks post-transplantation, renal primordia developed glomeruli and tubuli able to filter blood and to produce urine in cyst-like structures. Newly developed metanephroi were able to initiate a regenerative-like process in host renal tissues adjacent to the graft in MWF male rats as indicated by an increase in cell proliferation and vascular density, accompanied by mRNA and protein upregulation of VEGF, FGF2, HGF, IGF-1 and Pax-2. The expression of SMP30 and NCAM was induced in tubular cells. Oxidative stress and apoptosis markedly decreased. Our study shows that embryonic kidneys generate functional nephrons when transplanted into animals with severe renal disease and at the same time activate events at least partly mimicking those observed in kidney tissues during renal regeneration.

  7. Recurrent hepatitis C and non-alcoholic fatty liver disease in transplanted patients: a review.

    PubMed

    Testino, G; Sumberaz, A; Leone, S; Borro, P

    2013-04-01

    Non-alcoholic fatty liver disease (NAFLD) is a common occurrence after orthotopic liver transplantation (OLT). The association steatosis/HCV determines important implications for clinical practice: steatosis accelerates the progression of fibrosis and reduces the likelihood of obtaining a sustained virological response (SVR) with antiviral therapy. In post-transplant HCV patients we have evidenced a strong correlation between body mass index (BMI), cholesterol, triglycerides (TGC) and hepatic percentage of steatosis. In subjects with BMI <25 and TGC <160 ng/mL, the chance of SVR was 48 times higher than that of non response. The chances of SVR and sustained biochemical response for patients with percentage of steatosis <15 were 12 times higher than that with higher percentage of steatosis. We can conclude how the amount of steatosis be noted specifically in biopsy examination reports of patients with relapse chronic hepatitis C and how the management of dismetabolism, diet and exercise therapy can improve BMI, liver histology and the response to antiviral therapy. PMID:23514999

  8. Memory CD4+ T cells do not induce graft-versus-host disease.

    PubMed

    Anderson, Britt E; McNiff, Jennifer; Yan, Jun; Doyle, Hester; Mamula, Mark; Shlomchik, Mark J; Shlomchik, Warren D

    2003-07-01

    Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation (alloSCT). Donor T cells that accompany stem cell grafts cause GVHD by attacking recipient tissues; therefore, all patients receive GVHD prophylaxis by depletion of T cells from the allograft or through immunosuppressant drugs. In addition to providing a graft-versus-leukemia effect, donor T cells are critical for reconstituting T cell-mediated immunity. Ideally, immunity to infectious agents would be transferred from donor to host without GVHD. Most donors have been exposed to common pathogens and have an increased precursor frequency of memory T cells against pathogenic antigens. We therefore asked whether memory CD62L-CD44+ CD4+ T cells would induce less GVHD than unfractionated or naive CD4+ T cells. Strikingly, we found that memory CD4 cells induced neither clinical nor histologic GVHD. This effect was not due to the increased number of CD4+CD25+ regulatory T cells found in the CD62L-CD44+ fraction because memory T cells depletion of these cells did not cause GVHD. Memory CD4 cells engrafted and responded to antigen both in vivo and in vitro. If these murine results are applicable to human alloSCT, selective administration of memory T cells could greatly improve post-transplant immune reconstitution.

  9. Autoimmunity Including Intestinal Behçet Disease Bearing the KRAS Mutation in Lymphocytes: A Case Report.

    PubMed

    Moritake, Hiroshi; Takagi, Masatoshi; Kinoshita, Mariko; Ohara, Osamu; Yamamoto, Shojiro; Moriguchi, Sayaka; Nunoi, Hiroyuki

    2016-03-01

    We experienced the case of a 3-year-old male with a very rare combination of autoimmunity, including immune thrombocytopenia, recurrent Henoch-Schönlein purpura and intestinal Behçet disease. Exome sequencing of the patient's peripheral blood mononuclear cells identified a KRAS G13C mutation. Interestingly, the KRAS G13C mutation was observed in T and B lymphocytes, as well as natural killer cells, but not granulocytes. Our case was completely phenotypically different from RASopathies and did not meet the criteria for Ras-associated lymphoproliferative disease or juvenile myelomonocytic leukemia. This is the first reported case in which the KRAS mutation existed only in the lymphoid lineage. Based on the findings of our case and the current literature, it is clear that the RAS mutation in lymphoid cells is tightly linked with various autoimmune symptoms. The presence of the RAS mutation in lymphocytes should be reconsidered as a pathogenesis in cases of autoimmunity.

  10. The clinical significance of EBV DNA in the plasma and peripheral blood mononuclear cells of patients with or without EBV diseases.

    PubMed

    Kanakry, Jennifer A; Hegde, Aparna M; Durand, Christine M; Massie, Allan B; Greer, Amy E; Ambinder, Richard F; Valsamakis, Alexandra

    2016-04-21

    Epstein-Barr virus (EBV) is a ubiquitous virus that establishes a latent infection within the host and in some cases can lead to the development of EBV-associated lymphomas, lymphoproliferative disorders, hemophagocytic lymphohistiocytosis, solid tumors, and other diseases. We studied the clinical significance of detecting EBV DNA in the plasma and peripheral blood mononuclear cells (PBMCs) of 2146 patients who had blood specimens sent to the Johns Hopkins Hospital clinical laboratory for viral quantitative real-time polymerase chain reaction assay over a 5-year period. Within this largely immunocompromised and hospitalized cohort, 535 patients (25%) had EBV detected in plasma or PBMCs. When EBV was detected in the absence of an EBV(+)disease (n = 402), it was present only in PBMCs in 69% of cases. Immunocompromised patients were less likely to have EBV in plasma than in PBMCs in the absence of EBV(+)disease. In patients with active, systemic EBV(+)diseases (n = 105), EBV was detected in plasma in 99% of cases but detected in PBMCs in only 54%. Across a range of copy number cutoffs, EBV in plasma had higher specificity and sensitivity for EBV(+)disease as compared with EBV in PBMCs. EBV copy number in plasma distinguished untreated, EBV(+)lymphoma from EBV(+)lymphoma in remission and EBV(-)lymphoma, and also distinguished untreated, EBV(+)posttransplantation lymphoproliferative disorder (PTLD) from EBV(+)PTLD in remission and EBV(-)PTLD. EBV copy number quantification is a useful diagnostic marker across the spectrum of EBV(+)diseases, even among immunocompromised patients, with plasma specimens more indicative of EBV(+)disease than PBMCs.

  11. Unicentric Castleman Disease: An Unusual Cause of An Isolated Neck Mass.

    PubMed

    Kumar, Anjay; Aggarwal, Krittika; Agrawal, Himanshu; Sharma, Sonal; Garg, Pankaj Kumar

    2016-07-01

    Castleman disease (CD) is a rare lymphoproliferative disorder of unknown aetiology. It manifests in two distinct clinical presentations: unicentric and multicentric. Unicentric CD is rare and may present as an isolated neck mass. A 22-year-old man presented with a 6-month history of right neck swelling that occupied the posterior triangle of the right neck region. After surgical exploration, a solitary, well defined, and hyper vascular mass was excise. A histopathological examination confirmed the lesion as CD, hyaline-vascular variant. CD of the neck is a diagnosis that is usually not taken into consideration while evaluating neck masses due to its rarity and unassuming presentation. It should be keep in the differential diagnosis of neck masses as the clinical and radiological features evade a firm diagnosis. The treatment of unicentric CD is complete surgical excision, which cures the patient. PMID:27660550

  12. Diseases diagnosed in wild turkeys (Meleagris gallopavo) of the southeastern United States.

    PubMed

    Davidson, W R; Nettles, V F; Couvillion, C E; Howerth, E W

    1985-10-01

    Diagnostic findings are presented on 139 sick or dead wild turkeys examined during the period 1972 through 1984. Turkeys originated from eight southeastern states (Alabama, Arkansas, Florida, Georgia, South Carolina, Tennessee, Virginia, West Virginia) and included 31 turkeys categorized as capture-related mortalities and 108 turkeys categorized as natural mortalities. Frequent diagnoses (greater than or equal to 10% of case accessions) in the natural mortality group were trauma, avian pox, and histomoniasis. Less frequent diagnoses (less than or equal to 4% of case accessions) included malnutrition/environmental stress syndrome, coligranuloma-like condition, crop impaction, bumblefoot, organophosphate toxicosis, infectious sinusitis, a lympho-proliferative disease, salmonellosis, aspergillosis, toxoplasmosis, crop trichomoniasis, and melorheostosis.

  13. Unicentric Castleman Disease: An Unusual Cause of An Isolated Neck Mass

    PubMed Central

    Kumar, Anjay; Aggarwal, Krittika; Agrawal, Himanshu; Sharma, Sonal; Garg, Pankaj Kumar

    2016-01-01

    Castleman disease (CD) is a rare lymphoproliferative disorder of unknown aetiology. It manifests in two distinct clinical presentations: unicentric and multicentric. Unicentric CD is rare and may present as an isolated neck mass. A 22-year-old man presented with a 6-month history of right neck swelling that occupied the posterior triangle of the right neck region. After surgical exploration, a solitary, well defined, and hyper vascular mass was excise. A histopathological examination confirmed the lesion as CD, hyaline-vascular variant. CD of the neck is a diagnosis that is usually not taken into consideration while evaluating neck masses due to its rarity and unassuming presentation. It should be keep in the differential diagnosis of neck masses as the clinical and radiological features evade a firm diagnosis. The treatment of unicentric CD is complete surgical excision, which cures the patient. PMID:27660550

  14. Safe and cost-effective control of post-transplantation recurrence of hepatitis B

    PubMed Central

    Takaki, Akinobu; Yagi, Takahito; Yamamoto, Kazuhide

    2015-01-01

    A combination of hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide analogs (NUC) is the current standard of care for controlling hepatitis B recurrence after orthotopic liver transplantation (OLT). However, long-term HBIG administration is associated with several unresolved issues, including limited availability and extremely high cost, and thus several protocols for treatment with low-dose HBIG combined with NUC or HBIG-free regimens have been developed. This article reviews recent advances in post-OLT hepatitis B virus (HBV) control and future methodological directions. New NUC such as entecavir, tenofovir or lamivudine plus adefovir dipivoxil combinations induce a very low frequency of viral resistance. The withdrawal of HBIG after several months of OLT under new NUC continuation also has permissible effects. Even after HBV reactivation, NUC can usually achieve viral control when viral markers are strictly followed up. Another approach is to induce self-producing anti-HBV antibodies via vaccination with a hepatitis B surface antigen vaccine. However, HBV vaccination is not sufficiently effective in patients to treat liver cirrhosis type B after OLT because immune tolerance to the virus has already continued for several decades. Trials of its safety and cost-effectiveness are required. This review advocates a safe and economical approach to controlling post-OLT HBV recurrence. PMID:24905970

  15. Management of post transplant hepatitis C in the direct antiviral agents era.

    PubMed

    Coilly, Audrey; Roche, Bruno; Duclos-Vallée, Jean-Charles; Samuel, Didier

    2015-04-01

    Hepatitis C virus (HCV) infection is one of the main indications for liver transplantation. Viral recurrence occurs in all patients with detectable serum HCV RNA at the time of transplantation leading to cirrhosis in 20-30% of patients within 5 years. Viral eradication using antiviral therapy has been shown to improve patient and graft survival. Pegylated interferon (PEG-IFN) and ribavirin (RBV) antiviral therapy achieved SVR in around 30% of transplant recipients. In the non-transplant setting, first generation NS3/4 protease inhibitors, boceprevir or telaprevir associated with PEG-IFN and RBV, has improved the SVR rates to 75% in genotype 1 infected patients. However, tolerability and drug-drug interactions with calcineurin inhibitors are both limiting factors of their use in transplant recipients. In the non-transplant patients, using new direct-acting antiviral therapy has dramatically improved the efficacy of antiviral C therapy over recent years leading to SVR rates over 90% in phase II and III clinical trials, without PEG-IFN and/or RBV. Preliminary results in transplant patients showed better efficacy, better tolerability and less drug-drug interactions. PMID:25820797

  16. CXCR2 modulates bone marrow vascular repair and haematopoietic recovery post-transplant.

    PubMed

    Hale, Sarah J M; Hale, Ashley B H; Zhang, Youyi; Sweeney, Dominic; Fisher, Nita; van der Garde, Mark; Grabowska, Rita; Pepperell, Emma; Channon, Keith; Martin-Rendon, Enca; Watt, Suzanne M

    2015-05-01

    Murine models of bone marrow transplantation show that pre-conditioning regimens affect the integrity of the bone marrow endothelium and that the repair of this vascular niche is an essential pre-requisite for successful haematopoietic stem and progenitor cell engraftment. Little is known about the angiogenic pathways that play a role in the repair of the human bone marrow vascular niche. We therefore established an in vitro humanized model, composed of bone marrow stromal and endothelial cells and have identified several pro-angiogenic factors, VEGFA, ANGPT1, CXCL8 and CXCL16, produced by the stromal component of this niche. We demonstrate for the first time that addition of CXCL8 or inhibition of its receptor, CXCR2, modulates blood vessel formation in our bone marrow endothelial niche model. Compared to wild type, Cxcr2(-/-) mice displayed a reduction in bone marrow cellularity and delayed platelet and leucocyte recovery following myeloablation and bone marrow transplantation. The delay in bone marrow recovery correlated with impaired bone marrow vascular repair. Taken together, our data demonstrate that CXCR2 regulates bone marrow blood vessel repair/regeneration and haematopoietic recovery, and clinically may be a therapeutic target for improving bone marrow transplantation.

  17. Safe and cost-effective control of post-transplantation recurrence of hepatitis B.

    PubMed

    Takaki, Akinobu; Yagi, Takahito; Yamamoto, Kazuhide

    2015-01-01

    A combination of hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide analogs (NUC) is the current standard of care for controlling hepatitis B recurrence after orthotopic liver transplantation (OLT). However, long-term HBIG administration is associated with several unresolved issues, including limited availability and extremely high cost, and thus several protocols for treatment with low-dose HBIG combined with NUC or HBIG-free regimens have been developed. This article reviews recent advances in post-OLT hepatitis B virus (HBV) control and future methodological directions. New NUC such as entecavir, tenofovir or lamivudine plus adefovir dipivoxil combinations induce a very low frequency of viral resistance. The withdrawal of HBIG after several months of OLT under new NUC continuation also has permissible effects. Even after HBV reactivation, NUC can usually achieve viral control when viral markers are strictly followed up. Another approach is to induce self-producing anti-HBV antibodies via vaccination with a hepatitis B surface antigen vaccine. However, HBV vaccination is not sufficiently effective in patients to treat liver cirrhosis type B after OLT because immune tolerance to the virus has already continued for several decades. Trials of its safety and cost-effectiveness are required. This review advocates a safe and economical approach to controlling post-OLT HBV recurrence.

  18. Comparison of Tpe Changing on ECG, in Pre and Post Dialysis and Post Transplantation

    PubMed Central

    Monfared, Ali; Assadian Rad, Mohammad; Feizkhah, Mohammadreza; Kazemnezhad, Ehsan; Esmaeili, Samaneh; Rastjou Herfeh, Nadia; Hedayatsafa, Razieh

    2016-01-01

    Background High incidence of premature ventricular contractions (PVCS) and arrhythmia during and soon after dialysis have been demonstrated by Holter monitoring. Objectives In this study, the effects of dialysis and renal transplantation on Tpe, Tpec (corrected Tpe), QTc (corrected QT), QTd (QT dispersion), and Tpe/QT parameters as known factors in arrhythmogenicity, and also the correlation between electrolyte and arterial blood gas changing within these parameters will be assessed. Patients and Methods In a retrospective study, 42 renal transplant recipients were selected. Under the supervision of an electrophysiologist, information related to Tpe, Tpec, Tpe/QT, QTd, and QTc parameters before dialysis (pre-HD), after dialysis (post-HD), and two weeks after transplantation (RTX) were analyzed. Electrolyte and arterial blood gas information were also recorded. Bonferroni adjustment, repeated measures ANOVA, generalized linear models, and generalized estimating equations were used for analysis. Results Two weeks after transplantation, the mean Tpe decreased to 0.052 ± 0.002, which was significant compared to pre-HD (P < 0.001) and Post-HD (P = 0.019). The mean Tpec was 0.059 ± 0.002, which, just in comparison to pre-HD, was significant (P = 0.005). In addition, the mean Tpe/QT decreased to 0.143 ± 0.005, which was significant compared to pre-HD (P = 0.018). The mean QTd was 0.066 ± 0.004, which wasn’t significant compared to before or after dialysis. The mean QTc decreased to 0.386 ± 0.004, which was significant compared to post-HD (P = 0.0003). Conclusions Taking the role of Tpe and Tpe/QT in arrhythmia into account and amending it by a successful transplantation can be considered as a factor that decreases arrhythmia after renal transplantation compared to ESRD patients. PMID:27570753

  19. HLA-Mismatched Unrelated Donor Bone Marrow Transplantation With Post-Transplantation Cyclophosphamide

    ClinicalTrials.gov

    2016-10-21

    Myelodysplastic Syndrome (MDS); Chronic Lymphocytic Leukemia (CLL); Chemotherapy-sensitive Lymphoma; Acute Lymphoblastic Leukemia (ALL)/T Lymphoblastic Lymphoma; Acute Myelogenous Leukemia (AML); Acute Biphenotypic Leukemia (ABL); Acute Undifferentiated Leukemia (AUL)

  20. Endoplasmic Reticulum Stress is a Mediator of Post-Transplant Injury in Severely Steatotic Liver Allografts

    PubMed Central

    Anderson, Christopher D.; Upadhya, Gundumi; Conzen, Kendra D.; Jia, Jianlou; Brunt, Elizabeth M.; Tiriveedhi, Venkataswarup; Xie, Yan; Ramachandran, Sabarinathan; Mohanakumar, Thalachallour; Davidson, Nicholas O.; Chapman, William C.

    2010-01-01

    Hepatic steatosis continues to present a major challenge in liver transplantation. These organs have been shown to have an increased susceptibility to cold ischemia and reperfusion (CIR) injury compared to otherwise comparable lean livers; the mechanisms governing this increased susceptibility to CIR injury are not fully understood. Endoplasmic reticulum (ER) stress is an important link between hepatic steatosis, insulin resistance and the metabolic syndrome. In this study, we investigated ER stress signaling and blockade in the mediation of CIR injury in severely steatotic rodent allografts. Steatotic allografts from genetically leptin-resistant rodents had increased ER stress responses and increased markers of hepatocellular injury following liver transplantation into strain-matched lean recipients. ER stress response components were decreased by the chemical chaperone, TUDCA, resulting in improvement of the allograft injury. TUDCA treatment decreased NF-κB activation, and the pro-inflammatory cytokines IL-6 and IL-1β. However, the predominant response was decreased expression of the ER stress cell death mediator, CHOP. Further, activation of the inflammation-associated caspase 11 was decreased linking ER Stress/CHOP to pro-inflammatory cytokine production following steatotic liver transplantation. These data confirm ER stress in steatotic allografts, and implicate this as a mediating mechanism of inflammation and hepatocyte death in the steatotic liver allograft. PMID:21280192

  1. Correlation between CMV Infection and Post-transplantation New-onset Diabetes Mellitus

    PubMed Central

    Dedinská, I.; Laca, Ľ.; Miklušica, J.; Kantárová, D.; Galajda, P.; Mokáň, M.

    2016-01-01

    Background: New-onset diabetes mellitus after transplantation (NODAT) is a well-known complication of transplantation. Objective: To determine the correlation between CMV infection and NODAT. Methods: Retrospectively, we detected CMV replication (PCR) in every month after renal transplantation in the first 12 months of the procedure in a homogenous group of patients from the immunosuppression point of view. Results: In 167 patients (64 with NODAT and 103 in the control group), the average amount of CMV viremia was not significantly different between the NODAT and the control group (p=0.929). In the 10th month of transplantation, we recorded a significantly higher CMV viremia in the NODAT group (p<0.0001), however, in the multivariant analysis, the observed statistical difference vanished. The survival of patients and grafts was 12 months after kidney transplantation without any statistically significant difference between the studied groups (p=0.611 and p=0.538, respectively). Conclusion: CMV is not a risk factor for NODAT. PMID:27721964

  2. Voriconazole-induced periostitis post transplant: an illustrative review of thoracic computed tomography imaging manifestations.

    PubMed

    Rheinboldt, M; Delproposto, Z; Agarwal, R

    2015-12-01

    Voriconazole, first commercially approved in 2002 as a second-generation antifungal agent, is commonly used in the immunocompromised setting as both a therapeutic and prophylactic agent. Since 2009, scattered case reports and small case series have detailed a secondary drug-related hyperfluorosis-induced painful periostitis that can occur in the treated patient population. We present a pictorial review of the thoracic imaging manifestations utilizing 3 illustrative cases in the setting of both solid organ and bone marrow transplantation. Knowledge of the relatively characteristic radiographic appearance and distribution, when coupled with the appropriate clinical context and associated laboratory findings, is important in narrowing an otherwise relatively broad differential diagnosis.

  3. Psychosocial needs assessment post kidney transplant: Feasibility of a post-transplant specific support group.

    PubMed

    Brijmohan, Angela; Famure, Olusegun; Sihota, Kiren; Shea, Mary; Marzario, Barbara; Mitchell, Margot

    2015-01-01

    This project assessed unmet psychosocial needs of kidney transplant recipients and the feasibility of a support group located at an urban Canadian hospital to meet those needs. A survey assessed transplant recipient concerns about psychosocial issues related to transplantation, interest in a support group, desired group composition, facilitation, leadership, barriers and alternative forms of support. Most respondents were more than two years since transplant and were more concerned about medical complications, returning to normalcy, and had a greater desire to talk to other transplant recipients. Forty per cent of respondents indicated they would be interested in a support group. However, 60% indicated that a support group hosted in the hospital setting would be a deterrent to attending, citing time and transportation as the greatest barriers. More research is needed to assess the feasibility of post-kidney transplant support groups closer to recipients' homes and the feasibility of alternative forms of support. PMID:26882632

  4. Post-transplant lymphocele: an unusual cause of acute urinary retention mimicking urethral injury.

    PubMed

    Hwang, Eu Chang; Kang, Taek Won; Koh, Yang Seok; Kim, Jung Chul; Ma, Seong-Kwon; Kwon, Dong Deuk; Park, Kwangsung; Ryu, Soo Bang

    2006-04-01

    Retroperitoneal pelvic lymphoceles are one of the most common complications following renal transplantation, and usually present with a palpable mass, ipsilateral leg edema, hydronephrosis caused by ureteral obstruction, decreased renal function and cutaneous lymphatic fistula. However, lymphocele rarely causes acute urinary retention. In this study, we describe a case of a patient who developed acute urinary retention after renal transplantation mimicking urethral injury. When a transplanted patient demonstrates the inability to void, one should consider bladder outlet obstruction resulting from lymphocele as a possible cause.

  5. Pre-transplant thymic function is associated with the risk of cytomegalovirus disease after solid organ transplantation.

    PubMed

    Gracia-Ahufinger, I; Ferrando-Martínez, S; Montejo, M; Muñoz-Villanueva, M C; Cantisán, S; Rivero, A; Solana, R; Leal, M; Torre-Cisneros, J

    2015-05-01

    Cytomegalovirus (CMV) disease is an important complication in solid organ transplant recipients. Thymic function in adults is associated with specific T-cell immunity. Pre-transplant thymic function was analysed in 75 solid organ transplant patients by the use of nested PCR. The primary outcome was the incidence of CMV disease 12 months after transplantation. Using multivariable logistic regression, we studied whether pre-transplant thymic function is an independent risk factor for CMV disease after transplantation. Thymic function was related to the risk of CMV disease in CMV-seropositive recipients. In these recipients, pre-transplant thymic function of <9.5 (OR 11.27, 95% CI 1.11-114.43, p 0.040) and the use of thymoglobulin (OR 8.21, 95% CI 1.09-61.84, p 0.041) were independent risk factors for CMV disease at 12 months after transplantation. Patients with pre-transplant thymic function values of <9.5 had a higher subsequent incidence of CMV disease (24%) than patients with values of ≥ 9.5 (3%) (log-rank test: 5.727; p 0.017). The positive and negative predictive values of these pre-transplant thymic function cut-offs were 0.24 (95% CI 0.10-0.45) and 0.97 (95% CI 0.82-1.00), respectively. Pre-transplant thymic function in CMV-seropositive candidates could be useful in determining the risk of post-transplant CMV disease in solid organ transplant patients, selecting a group of low-risk candidates.

  6. Higher Dose of Mycophenolate Mofetil Reduces Acute Graft-Versus-Host Disease in Reduced Intensity Conditioning Double Umbilical Cord Blood Transplantation

    PubMed Central

    Bejanyan, Nelli; Rogosheske, John; DeFor, Todd; Lazaryan, Aleksandr; Esbaum, Kelli; Holtan, Shernan; Arora, Mukta; MacMillan, Margaret L.; Weisdorf, Daniel; Jacobson, Pamala; Wagner, John; Brunstein, Claudio G.

    2016-01-01

    Mycophenolate mofetil (MMF) is frequently used in hematopoietic cell transplantation (HCT) for graft-versus-host disease (GVHD) prophylaxis and to facilitate engraftment. We previously reported that a higher level of mycophenolic acid can be achieved with an MMF dose of 3 g/day as compared to 2g/day. Here, we retrospectively compared clinical outcomes of reduced intensity conditioning (RIC) double umbilical cord blood (dUCB) HCT recipients receiving cyclosporine A with MMF 2g (n=93) vs. 3g (n=175) daily. Multiple regression analysis adjusted for ATG in the conditioning revealed that MMF 3g/day led to a 49% relative risk reduction in grade II–IV acute GVHD rate (RR=0.51, 95%CI 0.36–0.72; p<0.01). However, the higher MMF dose was not protective for chronic GVHD. Additionally, MMF dose was not an independent predictor of neutrophil engraftment, treatment-related mortality at 6 months, or 2-year post-transplant disease relapse, disease-free survival, or overall survival. Higher MMF dose did not increase risk of infectious complications and infection-related mortality was similar for both MMF doses. Our data indicate that MMF 3g/day reduces the risk of acute GVHD without affecting other clinical outcomes and should be used for GVHD prophylaxis after RIC dUCBT. PMID:25655791

  7. Bortezomib and Azacitidine in Treating Patients With Relapsed or Refractory T-Cell Lymphoma

    ClinicalTrials.gov

    2013-12-02

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Prolymphocytic Leukemia; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Small Intestine Lymphoma; T-cell Large Granular Lymphocyte Leukemia

  8. Whole-body UVB irradiation during allogeneic hematopoietic cell transplantation is safe and decreases acute graft-versus-host disease.

    PubMed

    Kreutz, Marina; Karrer, Sigrid; Hoffmann, Petra; Gottfried, Eva; Szeimies, Rolf-Markus; Hahn, Joachim; Edinger, Matthias; Landthaler, Michael; Andreesen, Reinhard; Merad, Miriam; Holler, Ernst

    2012-01-01

    Depletion of host Langerhans cells (LCs) prevents cutaneous graft-versus-host disease (GvHD) in mice. We analyzed whether UVB irradiation is tolerated during the course of human allogeneic hematopoietic cell transplantation and whether depletion of LCs by broadband UVB could improve GvHD outcome. A total of 17 patients received six whole-body UVB irradiations with 75% of the individually determined minimal erythemal dose after conditioning with a reduced intensity protocol. LCs, dermal dendritic cells (DCs), and macrophages were analyzed before and after UVB irradiation by immunohistochemical analysis. Circulating blood cells and serum factors were analyzed in parallel. In striking contrast to previous data, our irradiation protocol was well tolerated in all patients. UVB treatment decreased the number of LCs and also affected dermal DCs. UVB-treated patients also had significantly higher 25-hydroxyvitamin D3 serum levels and higher numbers of circulating CD4+ FoxP3+ regulatory T cells. Strikingly, nine out of nine patients with complete LC depletion (<1 LC per field) developed only grade I GvHD or no GvHD up to day 100. Our results strongly suggest that prophylactic UVB irradiation post transplant is safe and should be further explored as a clinical strategy to prevent acute (skin) GvHD.

  9. Human olfactory bulb neural stem cells expressing hNGF restore cognitive deficit in Alzheimer's disease rat model.

    PubMed

    Marei, Hany E S; Farag, Amany; Althani, Asma; Afifi, Nahla; Abd-Elmaksoud, Ahmed; Lashen, Samah; Rezk, Shaymaa; Pallini, Roberto; Casalbore, Patrizia; Cenciarelli, Carlo

    2015-01-01

    In this study, we aim to demonstrate the fate of allogenic adult human olfactory bulb neural stem/progenitor cells (OBNSC/NPCs) transplanted into the rat hippocampus treated with ibotenic acid (IBO), a neurotoxicant specific to hippocampal cholinergic neurons that are lost in Alzheimer's disease. We assessed their possible ability to survive, integrate, proliferate, and differentiate into different neuronal and glial elements: we also evaluate their possible therapeutic potential, and the mechanism(s) relevant to neuroprotection following their engraftment into the CNS milieu. OBNSC/NPCs were isolated from adult human olfactory bulb patients, genetically engineered to express GFP and human nerve growth factor (hNGF) by lentivirus-mediated infection, and stereotaxically transplanted into the hippocampus of IBO-treated animals and controls. Stereological analysis of engrafted OBNSCs eight weeks post transplantation revealed a 1.89 fold increase with respect to the initial cell population, indicating a marked ability for survival and proliferation. In addition, 54.71 ± 11.38%, 30.18 ± 6.00%, and 15.09 ± 5.38% of engrafted OBNSCs were identified by morphological criteria suggestive of mature neurons, oligodendrocytes and astrocytes respectively. Taken together, this work demonstrated that human OBNSCs expressing NGF ameliorate the cognitive deficiencies associated with IBO-induced lesions in AD model rats, and the improvement can probably be attributed primarily to neuronal and glial cell replacement as well as the trophic influence exerted by the secreted NGF.

  10. Nonmyeloablative Stem Cell Transplantation with Alemtuzumab/Low-Dose Irradiation to Cure and Improve the Quality of Life of Adults with Sickle Cell Disease.

    PubMed

    Saraf, Santosh L; Oh, Annie L; Patel, Pritesh R; Jalundhwala, Yash; Sweiss, Karen; Koshy, Matthew; Campbell-Lee, Sally; Gowhari, Michel; Hassan, Johara; Peace, David; Quigley, John G; Khan, Irum; Molokie, Robert E; Hsu, Lewis L; Mahmud, Nadim; Levinson, Dennis J; Pickard, A Simon; Garcia, Joe G N; Gordeuk, Victor R; Rondelli, Damiano

    2016-03-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is rarely performed in adult patients with sickle cell disease (SCD). We utilized the chemotherapy-free, alemtuzumab/total body irradiation 300 cGy regimen with sirolimus as post-transplantation immunosuppression in 13 high-risk SCD adult patients between November 2011 and June 2014. Patients received matched related donor (MRD) granulocyte colony-stimulating factor-mobilized peripheral blood stem cells, including 2 cases that were ABO incompatible. Quality-of-life (QoL) measurements were performed at different time points after HSCT. All 13 patients initially engrafted. A stable mixed donor/recipient chimerism was maintained in 12 patients (92%), whereas 1 patient not compliant with sirolimus experienced secondary graft failure. With a median follow-up of 22 months (range, 12 to 44 months) there was no mortality, no acute or chronic graft-versus-host disease (GVHD), and no grades 3 or 4 extramedullary toxicities. At 1 year after transplantation, patients with stable donor chimerism have normalized hemoglobin concentrations and improved cardiopulmonary and QoL parameters including bodily pain, general health, and vitality. In 4 patients, sirolimus was stopped without rejection or SCD-related complications. These results underscore the successful use of a chemotherapy-free regimen in MRD HSCT for high-risk adult SCD patients and demonstrates a high cure rate, absence of GVHD or mortality, and improvement in QoL including the applicability of this regimen in ABO mismatched cases (NCT number 01499888). PMID:26348889

  11. Multicentric Castleman's disease developing during follow-up of sarcoidosis.

    PubMed

    Sawata, Tetsuro; Bando, Masashi; Nakayama, Masayuki; Mato, Naoko; Takemura, Tamiko; Sugiyama, Yukihiko

    2016-07-01

    Pulmonary sarcoidosis is reported to have complication of lymphoproliferative disease such as malignant lymphoma, but the complication of multicentric Castleman's disease (MCD) is rarely reported. In our case of a 60-year-old woman, bilateral hilar lymphadenopathy was noted in her chest X-ray. We performed a transbronchial lung biopsy. She was diagnosed as having pulmonary sarcoidosis (Stage II). The shadow on chest X-ray disappeared without treatment. However, after 8 years, swelling of the mediastinal and abdominal lymph node, thickened bronchovascular bundle, and multiple nodular shadows were identified, and a thoracoscopic lung biopsy was performed. Based on the histopathological findings and elevated serum interleukin-6 level (75.7 pg/mL), she was diagnosed with pulmonary sarcoidosis complicated by MCD. When a change in chest X-ray findings are found during monitoring of pulmonary sarcoidosis, it is important to proceed with a thoracoscopic lung biopsy, because of the possibility of the rare complication of MCD. PMID:27512568

  12. A HHV-8 positive, HIV negative multicentric Castleman disease treated with R-CEOP chemotherapy and valganciclovir combination.

    PubMed

    Kantarci, Fatma Eda Nuhoglu; Eren, Rafet; Gündoğan, Cihan; Huq, Gülben Erdem; Doğu, Mehmet Hilmi; Suyanı, Elif

    2016-07-01

    Multicentric Castleman disease (MCD) is a lymphoproliferative disorder characterized by systemic symptoms like recurrent lymphadenopathy, fever and hepatosplenomegaly. Human herpes virus 8 (HHV-8) can be associated with MCD whether the patient is infected with human immunodeficiency virus (HIV) or not. A 59-year-old male patient presented with fatigue, drowsiness and enlarged lymph nodes. Thoracic and abdominal computed tomography showed enlarged mediastinal, axillary, paracardiac, paraaortic, celiac, mesenteric, obturator and inguinal lymph nodes concomitant with enlarged liver and spleen. Cervical lymph node biopsy revealed HHV-8 positive plasma cell MCD. The patient's tests were negative for HIV. R-CEOP (rituximab, cyclophosphamide, etoposide, vincristin, prednisolone) and valganciclovir treatments were started simultaneously. After sixth cycle of R-CEOP, the patient achieved unconfirmed complete remission. Rituximab combined with CEOP protocol and antiviral therapy against HHV-8 might be an effective therapeutic approach without a considerable side effect for HHV-8-positive HIV-negative MCD patients. PMID:26948831

  13. Rosai-Dorfman disease of the central nervous system: report of 6 cases and review of the literature.

    PubMed

    Sandoval-Sus, Jose D; Sandoval-Leon, Ana C; Chapman, Jennifer R; Velazquez-Vega, Jose; Borja, Maria J; Rosenberg, Shai; Lossos, Alexander; Lossos, Izidore S

    2014-05-01

    Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy (SHML), is an uncommon benign idiopathic lymphoproliferative disorder. The histologic hallmark of RDD is the finding of emperipolesis displayed by lesional histiocytes. While RDD most commonly affects lymph nodes, extranodal involvement of multiple organs has been reported, including the central nervous system (CNS). However, CNS involvement in RDD is rare and is not well characterized. As a result, therapeutic approaches to CNS involvement in RDD are not well established. Herein we report 6 cases of RDD with isolated CNS involvement and review the literature on RDD with CNS involvement. One of the presented cases exhibited intramedullary involvement of the spinal cord--a very rare form of RDD with CNS involvement.

  14. Use of a claims database to characterize and estimate the incidence rate for Castleman disease.

    PubMed

    Munshi, Nikhil; Mehra, Maneesha; van de Velde, Helgi; Desai, Avinash; Potluri, Ravi; Vermeulen, Jessica

    2015-05-01

    Castleman disease (CD) is a rare lymphoproliferative disorder affecting single (unicentric; UCD) or multiple (multicentric; MCD) lymph nodes. The incidence of this difficult to diagnose disease is poorly understood, as no International Classification of Diseases, Ninth Revision (ICD-9) code is available. This study utilized a unique strategy to estimate its incidence using two commercial claims databases, IMS LifeLink™ and Truven Health Analytics MarketScan(®). Patients with an index diagnosis of lymphadenopathy (ICD-9 code 785.6) were followed longitudinally for 1 year prior to and 2 years post-index diagnosis date. An algorithm that identifies potential patients with CD was developed to determine the incidence rate in person-years. The incidence rate for CD was calculated as 21 (IMS LifeLink™) and 25 (MarketScan(®)) per million person-years. Additionally, 23% of patients with CD were identified as potentially suffering from MCD. These results are consistent with the definition of an orphan disease, and the low incidence of the disease estimated in the literature.

  15. Epstein-Barr virus and human diseases: recent advances in diagnosis.

    PubMed Central

    Okano, M; Thiele, G M; Davis, J R; Grierson, H L; Purtilo, D T

    1988-01-01

    Since the discovery of Epstein-Barr virus (EBV) from a cultured Burkitt's lymphoma cell line in 1964, the virus has been associated with Burkitt's lymphoma, nasopharyngeal carcinoma, and infectious mononucleosis. During the recent decade, EBV has been etiologically implicated in a broad spectrum of human diseases. The precise role of this virus in these diseases is not well understood, but clearly, defective immunosurveillance against the virus may permit an uncontrolled proliferation of EBV-infected cells. As a result, a growing number of cases of EBV-associated B-cell proliferative diseases or lymphoma have been noted in patients with primary and acquired immunodeficiencies. These lymphoproliferative diseases and others, such as chronic mononucleosis syndrome, are leading to new areas of investigation which are providing information regarding the pathogenetic mechanisms of EBV-induced diseases. The early accurate diagnosis of EBV infection can be achieved by performing EBV-specific serology, detecting for EBV-determined nuclear antigen in tissues, establishing spontaneous lymphoid cell lines, and using molecular hybridization techniques for demonstrating the presence of viral genome in affected lesions. Images PMID:2848624

  16. CUBN as a novel locus for end-stage renal disease: insights from renal transplantation.

    PubMed

    Reznichenko, Anna; Snieder, Harold; van den Born, Jacob; de Borst, Martin H; Damman, Jeffrey; van Dijk, Marcory C R F; van Goor, Harry; Hepkema, Bouke G; Hillebrands, Jan-Luuk; Leuvenink, Henri G D; Niesing, Jan; Bakker, Stephan J L; Seelen, Marc; Navis, Gerjan

    2012-01-01

    Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage renal disease (ESRD) and proteinuria. First, a total of 1142 patients with ESRD, admitted for renal transplantation, and 1186 donors were genotyped for SNPs rs7918972 and rs1801239 (case-control study). The rs7918972 minor allele frequency (MAF) was higher in ESRD patients comparing to kidney donors, implicating an increased risk for ESRD (OR 1.39, p = 0.0004) in native kidneys. Second, after transplantation recipients were followed for 5.8 [3.8-9.2] years (longitudinal study) documenting ESRD in transplanted kidneys--graft failure (GF). During post-transplant follow-up 92 (9.6%) cases of death-censored GF occurred. Donor rs7918972 MAF, representing genotype of the transplanted kidney, was 16.3% in GF vs 10.7% in cases with functioning graft. Consistently, a multivariate Cox regression analysis showed that donor rs7918972 is a predictor of GF, although statistical significance was not reached (HR 1.53, p = 0.055). There was no association of recipient rs7918972 with GF. Rs1801239 was not associated with ESRD or GF. In line with an association with the outcome, donor rs7918972 was associated with elevated proteinuria levels cross-sectionally at 1 year after transplantation. Thus, we identified CUBN rs7918972 as a novel risk variant for renal function loss in two independent settings: ESRD in native kidneys and GF in transplanted kidneys. PMID:22574174

  17. Impacts of graft-versus-host disease on outcomes after allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia: A nationwide retrospective study.

    PubMed

    Itonaga, Hidehiro; Iwanaga, Masako; Aoki, Kazunari; Aoki, Jun; Ishiyama, Ken; Ishikawa, Takayuki; Sakura, Toru; Fukuda, Takahiro; Najima, Yuho; Yujiri, Toshiaki; Mori, Takehiko; Kurokawa, Mineo; Nawa, Yuichiro; Uchida, Naoyuki; Morishita, Yoshihisa; Hashimoto, Hisako; Eto, Tetsuya; Hirokawa, Makoto; Morishima, Yasuo; Nagamura-Inoue, Tokiko; Atsuta, Yoshiko; Miyazaki, Yasushi

    2016-02-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a therapeutic option that may lead to improved outcomes in patients with chronic myelomonocytic leukemia (CMML). However, few studies have examined the impact of the grade of graft-versus-host disease (GVHD) on post-transplant outcomes for CMML. We retrospectively analyzed the outcomes of 141 patients with CMML who underwent allo-HSCT between 1987 and 2010, and achieved neutrophil engraftment. The effects of acute GVHD (aGVHD) or chronic GVHD (cGVHD) on overall survival (OS), leukemia-associated mortality (LAM), and transplant-related mortality were evaluated by hazards regression models, in which the onset date of aGVHD or cGVHD was treated as a time-dependent covariate. Grade I aGVHD was associated with better OS and lower LAM (P=0.042, P=0.033, respectively) than no GVHD in univariate analyses, but not in the multivariate analyses. The multivariate analyses demonstrated that extensive cGVHD significantly associated with better OS (Hazard Ratio [HR] 0.35 [95% confidence intervals (CI), 0.16-0.74]; P=0.007) and lower LAM (HR 0.36 [95% CI, 0.14-0.92]; P=0.033) in patients who were not in complete remission at transplantation. In conclusion, the occurrence of cGVHD may be an important factor affecting the outcomes of CMML patients who received transplantation. PMID:26754557

  18. Eculizumab Treatment in a Patient with Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy and Steroid-Refractory Acute Graft Versus Host Disease.

    PubMed

    Fernández, Cristina; Lario, Ana; Forés, Rafael; Cabrera, Rafael

    2015-11-23

    A 30-year-old man with acquired aplastic anemia underwent an HLA-identical bone marrow transplant. He developed a grade III acute graft versus host disease (GVHD) refractory to various lines of treatment. On post-transplant day 196, he was diagnosed with stem cell transplantation-associated thrombotic micro-angiopathy (HSCT-TMA) and he received treatment with eculizumab 900 mg iv weekly for 4 doses followed by a single dose of 1200 mg 2 weeks later. After the first dose of eculizumab, the patient ceased to require transfusions and a progressive improvement in analytical parameters for microangiopathy was observed until their complete normalization. Coinciding with the improved of HSCT-TMA, the patient presented a clear response to his acute GVHD with disappearance of the diarrhea and bilirubin normalization. He was discharged eight weeks after the start of treatment. Unfortunately, one month later, the patient was readmitted for a GVHD relapse and he died two weeks later by an acute respiratory distress syndrome. In our case, the rapid clinical and analytical response to early treatment with eculizumab supports the implication of the complement in HSCT-TMA and suggests that the drug has a beneficial effect when used as coadjuvant therapy in acute GVHD.

  19. [History of resaerch on Epstein-Barr virus--target cells of infection, and disease].

    PubMed

    Ohga, Shouichi

    2014-01-01

    Half a century has passed since Epstein-Barr virus (EBV) particles were isolated from the cultured lymphoblasts of Burkitt lymphoma. During the period, molecular biology, hematology/immunology, and transplantation medicine made amazing progress, that clarified the mode of infection and pathophysiology of the virus in human diseases. Research strategies on the relationship between EBV and human have expanded to the epidemiology, structures and functions of both genomes, regulatory genes including microRNA, and the nature of epigenetics. Although no animal models of EBV infection long hampered the completion of in vivo experiments, humanized mice have broken through a barrier of in vitro study on EBV-infected cell lines. Our understanding of the life cycle of EBV has continued to deepen about the infection via the CD21 receptor expressed on B cells, the latency, reactivation/reinfection, and transformation, and also the dynamics of T-cell immune response and the intracellular immunosurveillance beyond acquired and innate immunity. On the other hand, the disease entity of life-threatening lymphoproliferative disease of EBV-infected T cells or NK cells is on controversial. The other parts of this special issue include the recent topics of the basic and clinical researches of EBV as the oncogenic virus. Then, we herewith overview the research history of EBV with special reference to the infected cells and host immune responses in EBV-associated diseases. PMID:25765982

  20. Is MELD score failing patients with liver disease and hepatorenal syndrome?

    PubMed Central

    Sibulesky, Lena; Leca, Nicolae; Blosser, Christopher; Rahnemai-Azar, Amir A; Bhattacharya, Renuka; Reyes, Jorge

    2016-01-01

    There is a need to reassess the application of MELD and the impact of renal insufficiency with consideration for developing an algorithm with exception points that would lead to timely allocation of livers to patients with hepatorenal syndrome prior to occurrence of permanent renal damage without jeopardizing post-transplant survival.

  1. A2-3: Impact of Mild Chronic Kidney Disease Stage on Outcomes after Total Hip or Knee Arthroplasty

    PubMed Central

    Graham, Jove; Deegan, Brian; Bowen, Thomas; Richard, Raveesh; Perkins, Robert; Foltzer, Michael

    2014-01-01

    Background/Aims Dialysis and kidney transplantation adversely impact outcomes of total hip or knee arthroplasty (THA, TKA), but complication rates have not been reported for patients with less advanced stages of chronic kidney disease (CKD). Surgeons lack the data necessary to have informed discussions regarding anticipated outcomes of joint replacement for these patients. Methods We retrospectively reviewed electronic health records of 779 adults with stages 1, 2, and 3 CKD not requiring dialysis or transplantation who underwent THA or TKA from 2004–2011, to assess infection, revision, 90-day readmission and mortality rates. Patients with less than 12 months follow-up, open fracture, prior joint surgery, pregnancy, or acute kidney injury were excluded. Chi-square analysis and Cox survival analysis compared these outcomes between the stage 1–2 and stage 3 groups, stratified by joint replaced (THA vs TKA). All models adjusted for age, sex and BMI at surgery. Results No statistically different rates of revision or infection between Stage 3 vs. Stages 1–2 were seen, although there was a trend toward increased infections in Stage 3. THA patients with Stage 3 showed a significantly increased mortality rate compared to Stage 1–2 THA patients (HR 3.40, 95% CI = 1.25–9.23, P = 0.02). Conclusions CKD affects nearly 15% of the U.S. population many of whom undergo joint replacement. End stage kidney disease (patients post-transplant or on hemodialysis) has been consistently associated with increased rates of infection and revision in excess of our observed outcomes, but the overall rate of infection/revision in our study population was only slightly higher than reported rates in the general population (2–7% vs. 1–2%, respectively). CKD should not preclude joint replacement, but these data can help clinicians engage in meaningful informed discussions with patients with mild kidney disease regarding risks for infection, revision and death following joint

  2. Combination of immunoglobulins and natural killer cells in the context of CMV and EBV infection.

    PubMed

    Frenzel, K; Lehmann, J; Krüger, D H; Martin-Parras, L; Uharek, L; Hofmann, J

    2014-04-01

    Cytomegalovirus (CMV)-specific hyperimmunoglobulin (CMV-HIG) is used to treat and prevent CMV infection in immunocompromised patients, and anti-CD20 monoclonal antibody is successfully used in the treatment for post-transplant lymphoproliferative disease caused by Epstein-Barr virus (EBV). Two immunological approaches have been suggested to further improve the control of viral reproduction in patients with active disease: first, the use of monoclonal antibodies with specificity against viral epitopes and second, coadministration of cells with the capacity to promote antibody-dependent cell-mediated cytotoxicity. Here, we have evaluated the effectiveness of these strategies in vitro (alone and in combination) with neutralization and cytotoxicity assays. Our results indicate that monoclonal antibodies (in particular SM5-1) can be as effective as CMV-HIG in neutralizing-cell-free CMV. Moreover, our data indicate that antibody-mediated elimination (either by moAb or by HIG) of EBV-infected cells can be significantly enhanced by NK cells. Using human NK cells that have been purified, cultured and expanded under GMP conditions, we were able to demonstrate that the combination of NK cells and antibodies could represent a feasible and highly effective clinical approach to achieve control of EBV infections. Especially in leukopenic patients with low numbers of ADCC-promoting cells, the combination of adoptively transferred NK cells and antiviral antibodies offers a promising strategy that should be tested in clinical trials.

  3. Intestinal and multivisceral transplantation

    PubMed Central

    Meira, Sérgio Paiva; Guardia, Bianca Della; Evangelista, Andréia Silva; Matielo, Celso Eduardo Lourenço; Neves, Douglas Bastos; Pandullo, Fernando Luis; Felga, Guilherme Eduardo Gonçalves; Alves, Jefferson André da Silva; Curvelo, Lilian Amorim; Diaz, Luiz Gustavo Guedes; Rusi, Marcela Balbo; Viveiros, Marcelo de Melo; de Almeida, Marcio Dias; Epstein, Marina Gabrielle; Pedroso, Pamella Tung; Salvalaggio, Paolo; Meirelles, Roberto Ferreira; Rocco, Rodrigo Andrey; de Almeida, Samira Scalso; de Rezende, Marcelo Bruno

    2015-01-01

    Intestinal transplantation has shown exceptional growth over the past 10 years. At the end of the 1990’s, intestinal transplantation moved out of the experimental realm to become a routine practice in treating patients with severe complications related to total parenteral nutrition and intestinal failure. In the last years, several centers reported an increasing improvement in survival outcomes (about 80%), during the first 12 months after surgery, but long-term survival is still a challenge. Several advances led to clinical application of transplants. Immunosuppression involved in intestinal and multivisceral transplantation was the biggest gain for this procedure in the past decade due to tacrolimus, and new inducing drugs, mono- and polyclonal anti-lymphocyte antibodies. Despite the advancement of rigid immunosuppression protocols, rejection is still very frequent in the first 12 months, and can result in long-term graft loss. The future of intestinal transplantation and multivisceral transplantation appears promising. The major challenge is early recognition of acute rejection in order to prevent graft loss, opportunistic infections associated to complications, post-transplant lymphoproliferative disease and graft versus host disease; and consequently, improve results in the long run. PMID:25993080

  4. Neurologic Diseases

    MedlinePlus

    ... muscular dystrophy Problems with the way the nervous system develops, such as spina bifida Degenerative diseases, where nerve cells are damaged or die, such as Parkinson's disease and Alzheimer's disease Diseases of the blood vessels that supply ...

  5. Recent concepts of autoimmune pancreatitis and IgG4-related disease.

    PubMed

    Okazaki, Kazuichi; Uchida, Kazushige; Miyoshi, Hideaki; Ikeura, Tsukasa; Takaoka, Makoto; Nishio, Akiyoshi

    2011-10-01

    Recent studies suggested the existence of two subtypes of autoimmune pancreatitis (AIP): type 1 related with IgG4 (lymphoplasmacytic sclerosing pancreatitis; LPSP) and type 2 related with a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis; IDCP). Apart from type 2 AIP, the pathological features of type 1 AIP with increased serum IgG4/IgE levels, abundant infiltration of IgG4+ plasmacytes and lymphocytes, fibrosis, and steroid responsiveness are suggestive of abnormal immunity such as allergy or autoimmunity. Moreover, the patients with type 1 AIP often have extrapancreatic lesions such as sclerosing cholangitis, sclerosing sialadenitis, or retroperitoneal fibrosis showing similar pathological features. Based on these findings, many synonyms have been proposed for these conditions, such as "multifocal idiopathic fibrosclerosis", "IgG4-related autoimmune disease", "IgG4-related sclerosing disease", "IgG4-related plasmacytic disease", and "IgG4-related multiorgan lymphoproliferative syndrome", all of which may refer to the same conditions. Therefore, the Japanese Research Committee for "Systemic IgG4-related Sclerosing Disease" proposed a disease concept and clinical diagnostic criteria based on the concept of multifocal fibrosclerosis in 2009, in which the term "IgG4-related disease" was appointed as a minimal consensus on these conditions. Although the significance of IgG4 in the development of "IgG4-related disease" remains unclear, we have proposed a hypothesis for the development of type 1 AIP, one of the IgG4-related disease. The concept and diagnostic criteria of "IgG4-related disease" will be changed in accordance with future studies. PMID:21170607

  6. Contribution of chemotherapy mobilization to disease control in multiple myeloma treated with autologous hematopoietic cell transplantation

    PubMed Central

    Uy, Geoffrey L.; Costa, Luciano J.; Hari, Parameswaran N.; Zhang, Mei-Jie; Huang, Jia-Xing; Anderson, Kenneth C.; Bredeson, Christopher N.; Callander, Natalie S.; Cornell, Robert Frank; Perez, Miguel Angel Diaz; Dispenzieri, Angela; Freytes, César O.; Gale, Robert Peter; Garfall, Alfred; Gertz, Morie A.; Gibson, John; Hamadani, Mehdi; Lazarus, Hillard M.; Kalaycio, Matt E.; Kamble, Rammurti T.; Kharfan-Dabaja, Mohamed A.; Krishnan, Amrita Y.; Kumar, Shaji K.; Kyle, Robert A.; Landau, Heather J.; Lee, Cindy H.; Maiolino, Angelo; Marks, David I.; Mark, Tomer M.; Munker, Reinhold; Nishihori, Taiga; Olsson, Richard F.; Ramanathan, Muthalagu; Rodriguez, Tulio E.; Saad, Ayman A.; Savani, Bipin N.; Schiller, Gary J.; Schouten, Harry C.; Schriber, Jeffrey R.; Scott, Emma; Seo, Sachiko; Sharma, Manish; Ganguly, Siddhartha; Stadtmauer, Edward A.; Tay, Jason; To, L. Bik; Vesole, David H.; Vogl, Dan T.; Wagner, John L.; Wirk, Baldeep; Wood, William A.; D’Souza, Anita

    2015-01-01

    In patients with multiple myeloma (MM) undergoing autologous hematopoietic cell transplantation (auto-HCT), peripheral blood progenitor cells (PBPCs) may be collected following mobilization with growth factor alone (GF) or cytotoxic chemotherapy plus GF ( (CC+GF). It is uncertain whether the method of mobilization affects post-transplant outcomes. We compared these mobilization strategies in a retrospective analysis of 968 patients with MM from the Center for International Blood and Marrow Transplant Research database who received an auto-HCT in the US and Canada between 2007 and 2012. The kinetics of neutrophil engraftment (≥ 0.5 × 109/L) was similar between groups (13 vs. 13 days, P=0.69) while platelet engraftment (≥ 20 × 109/L) was slightly faster with CC+GF (19 vs. 18 days, P=0.006). Adjusted 3-years PFS was 43% (95% C.I. 38–48) in GF and 40% (95% C.I. 35–45) in CC+GF, P=0.33. Adjusted 3-years OS was 82% (95% C.I. 78–86) vs. 80% (95% C.I. 75–84), P=0.43 and adjusted 5-year OS was 62% (95C.I. 54–68) vs. 60% (95% C.I. 52–67), P=0.76, for GF and CC+GF respectively. We conclude that MM patients undergoing auto-HCT have similar outcomes irrespective of the method of mobilization and found no evidence that the addition of chemotherapy to mobilization contributes to disease control. PMID:26301967

  7. Hepatic Overexpression of Hemopexin Inhibits Inflammation and Vascular Stasis in Murine Models of Sickle Cell Disease

    PubMed Central

    Vercellotti, Gregory M; Zhang, Ping; Nguyen, Julia; Abdulla, Fuad; Chen, Chunsheng; Nguyen, Phong; Nowotny, Carlos; Steer, Clifford J; Smith, Ann; Belcher, John D

    2016-01-01

    Sickle cell disease (SCD) patients have low serum hemopexin (Hpx) levels due to chronic hemolysis. We hypothesized that in SCD mice, hepatic overexpression of hemopexin would scavenge the proximal mediator of vascular activation, heme, and inhibit inflammation and microvascular stasis. To examine the protective role of Hpx in SCD, we transplanted bone marrow from NY1DD SCD mice into Hpx-/- or Hpx+/+ C57BL/6 mice. Dorsal skin fold chambers were implanted 13 wks post-transplant, and microvascular stasis (% nonflowing venules) was evaluated in response to heme infusion. Hpx-/- sickle mice had significantly greater microvascular stasis in response to heme infusion than Hpx+/+ sickle mice (p < 0.05), demonstrating the protective effect of Hpx in SCD. We utilized Sleeping Beauty (SB) transposon-mediated gene transfer to overexpress wild-type rat Hpx (wt-Hpx) in NY1DD and Townes-SS SCD mice. Control SCD mice were treated with lactated Ringer’s solution (LRS) or a luciferase (Luc) plasmid. Plasma and hepatic Hpx were significantly increased compared with LRS and Luc controls. Microvascular stasis in response to heme infusion in NY1DD and Townes-SS mice overexpressing wt-Hpx had significantly less stasis than controls (p < 0.05). Wt-Hpx overexpression markedly increased hepatic nuclear Nrf2 expression, HO-1 activity and protein, and the heme-Hpx binding protein and scavenger receptor CD91/LRP1, and decreased NF-κB activation. Two missense (ms)-Hpx SB constructs that bound neither heme nor the Hpx receptor CD91/LRP1 did not prevent heme-induced stasis. In conclusion, increasing Hpx levels in transgenic sickle mice via gene transfer activates the Nrf2/HO-1 antioxidant axis and ameliorates inflammation and vasoocclusion. PMID:27451971

  8. Successful Treatment of Autoimmune Pulmonary Alveolar Proteinosis in a Pediatric Patient.

    PubMed

    Trukalj, Mirjana; Perica, Marija; Ferenčić, Željko; Erceg, Damir; Navratil, Marta; Redžepi, Gzim; Nogalo, Boro

    2016-01-01

    BACKGROUND Pulmonary alveolar proteinosis (PAP) is a rare condition characterized by the intra-alveolar accumulation of surfactant-derived material, which impairs gas exchange and results in respiratory insufficiency. Two major subtypes of PAP are autoimmune and non-autoimmune PAP. The diagnosis relies on clinical presentation, ground glass opacities on CT scan, bronchoscopy with PAS stain of BAL fluid (BALF), lung biopsy with PAS-positive material in the alveoli, and the presence of anti GM-CSF antibodies in serum or BALF for an autoimmune subtype. The therapeutic approach to pediatric cases varies according to age and the general clinical state of the child; however, whole lung lavage (WLL) and inhaled or subcutaneous GM-CSF are generally first-line therapy. CASE REPORT We report a unique case of an autoimmune type of PAP in a 12-year-old boy, who underwent successful bilateral lung transplantation after inefficacious treatment with GM-CSF, and who developed post-transplant lymphoproliferative disease (PTLD) and was successfully treated with a chemotherapeutic protocol. CONCLUSIONS Although lung transplantation is a rarely used therapeutic approach for patients with an autoimmune subtype of PAP, in cases of inefficacious treatment with other modalities, lung transplantation should be considered. PMID:27592713

  9. The porcine lymphotropic herpesvirus 1 encodes functional regulators of gene expression

    SciTech Connect

    Lindner, I.; Ehlers, B. . E-mail: ehlersb@rki.de; Noack, S.; Dural, G.; Yasmum, N.; Bauer, C.; Goltz, M.

    2007-01-20

    The porcine lymphotropic herpesviruses (PLHV) are discussed as possible risk factors in xenotransplantation because of the high prevalence of PLHV-1, PLHV-2 and PLHV-3 in pig populations world-wide and the fact that PLHV-1 has been found to be associated with porcine post-transplant lymphoproliferative disease. To provide structural and functional knowledge on the PLHV immediate-early (IE) transactivator genes, the central regions of the PLHV genomes were characterized by genome walking, sequence and splicing analysis. Three spliced genes were identified (ORF50, ORFA6/BZLF1{sub h}, ORF57) encoding putative IE transactivators, homologous to (i) ORF50 and BRLF1/Rta (ii) K8/K-bZIP and BZLF1/Zta and (iii) ORF57 and BMLF1 of HHV-8 and EBV, respectively. Expressed as myc-tag or HA-tag fusion proteins, they were located to the cellular nucleus. In reporter gene assays, several PLHV-promoters were mainly activated by PLHV-1 ORF50, to a lower level by PLHV-1 ORFA6/BZLF1{sub h} and not by PLHV-1 ORF57. However, the ORF57-encoded protein acted synergistically on ORF50-mediated activation.

  10. Adoptive T-cell Immunotherapy

    PubMed Central

    Gottschalk, Stephen; Rooney, Cliona

    2015-01-01

    Epstein-Barr virus (EBV) is associated with a range of malignancies involving B-cells, T-cells, natural killer (NK)-cells, epithelial cells and smooth muscle. All of these are associated with the latent life cycles of EBV, but the pattern of latency-associated viral antigens expressed in tumor cells depends on the type of tumor. EBV-specific T cells (EBVSTs) have been explored as prophylaxis and therapy for EBV-associated malignancies for more than two decades. EBVSTs have been most successful as prophylaxis and therapy for post-transplant lymphoproliferative disease (PTLD), which expresses the full array of latent EBV antigens (type 3 latency), in hematopoietic stem cell transplant recipients. While less effective, clinical studies have also demonstrated their therapeutic potential for PTLD post solid organ transplant, and for EBV-associated malignancies such as Hodgkin’s Lymphoma, Non-Hodgkin’s Lymphoma, and nasopharyngeal carcinoma that express a limited array of latent EBV antigens (type 2 latency),. Several approaches are actively being pursued to improve the antitumor activity of EBVSTs including activation and expansion of T cells specific for the EBV antigens expressed in type 2 latency, genetic approaches to render EBVSTs resistant to the immunosuppressive tumor environment and combination approaches with other immune-modulating modalities. Given the recent advances and renewed interest in cell therapy, we hope that EBVSTs will become an integral part of our treatment armamentarium against EBV-positive malignancies in the near future. PMID:26428384

  11. EBV-negative aggressive B-cell lymphomas of donor origin after allogeneic hematopoietic stem cell transplantation: a report of three cases.

    PubMed

    Federmann, Birgit; Bonzheim, Irina; Schittenhelm, Jens; Quintanilla-Martínez, Leticia; Mankel, Barbara; Vogel, Wichard; Faul, Christoph; Bethge, Wolfgang; Fend, Falko

    2016-11-01

    Post-transplant lymphoproliferative disorders (PTLD) develop as a consequence of iatrogenic immunosuppression, and the majority is associated with EBV. PTLD after allogeneic hematopoietic stem cell transplantation (allo-HCT) are rare. Most cases are donor-derived, reflecting immune reconstitution by malignant transformed donor cells, and are EBV-positive. We report three unusual cases of aggressive EBV-negative PTLD of monomorphic type after allo-HCT. All cases were of donor origin and arose with long latency, 4-12 years after HCT. The patients had a history of severe graft-versus-host disease (GVHD) resulting in prolonged immunosuppression before the diagnosis of lymphoma. In one case, the temporal evolution of the malignant clone was analyzed by clone-specific PCR targeting the immunoglobulin heavy chain rearrangement. A tumor-specific product was already detected 3 years before lymphoma development. This indicates that chronic antigenic stimulation and reduced immune surveillance, may promote the outgrowth of premalignant donor-derived clones after acquisition of additional genetic alterations.

  12. Celiac Disease

    MedlinePlus

    ... small intestine. People with celiac disease cannot eat gluten, a protein found in wheat, barley, and rye. ... Disease Doctors treat celiac disease by prescribing a gluten-free diet. Symptoms significantly improve for most people ...

  13. Huntington's Disease

    MedlinePlus

    Huntington's disease (HD) is an inherited disease that causes certain nerve cells in the brain to waste ... express emotions. If one of your parents has Huntington's disease, you have a 50 percent chance of ...

  14. Wilson Disease

    MedlinePlus

    ... Share External Link Disclaimer Digestive Diseases Wilson Disease Alternate Versions Wilson Disease (444 KB) You can also ... things psychosis—when a person loses contact with reality Other Signs and Symptoms Other signs and symptoms ...

  15. Crohn's Disease

    MedlinePlus

    ... is one of a group of diseases called inflammatory bowel disease. Crohn's can affect any area from the mouth to the anus. It often affects the lower part of the small intestine called the ileum. The cause of Crohn's disease ...

  16. Pick disease

    MedlinePlus

    Semantic dementia; Dementia - semantic; Frontotemporal dementia; FTD; Arnold Pick disease; 3R tauopathy ... can help doctors tell Pick disease apart from Alzheimer disease. (Memory loss is often the main, and earliest, ...

  17. Inactivation of the IL-6 gene prevents development of multicentric Castleman's disease in C/EBP beta-deficient mice

    PubMed Central

    1996-01-01

    Castleman's disease is a lymphoproliferative disorder thought to be related to deregulated production of IL-6. We have previously shown that mice lacking the trans-acting factor C/EBP beta, a transcriptional regulator of IL-6 and a mediator of IL-6 intracellular signaling, develop a pathology nearly identical to multicentric Castleman's disease, together with increasingly high levels of circulating IL-6. We describe here how the simultaneous inactivation of both IL-6 and C/EBP beta genes prevents the development of pathological traits of Castleman's disease observed in C/EBP beta-deficient mice. Histological and phenotypic analysis of lymph nodes and spleen of double mutant mice did not show either the lymphoadenopathy and splenomegaly or the abnormal expansion of myeloid, B and plasma cell compartments observed in C/EBP beta-/- mice, while B cell development, although delayed, was normal. Our data demonstrate that IL-6 is essential for the development of multicentric Castleman's disease in C/EBP beta-/- mice. PMID:8879230

  18. 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

  19. Survival, frost susceptibility, growth, and disease resistance of corkbark and subalpine fir grown for landscape and Christmas trees

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Trees from six corkbark fir (Abies lasiocarpa var. arizonica) and 10 subalpine fir (A. lasiocarpa var. lasiocarpa) seed sources were grown at the University of Idaho Sandpoint Research and Extension Center (SREC) and two commercial nurseries in Idaho and Oregon. Post transplant mortality was highest...

  20. Seed Source Significantly Influences Growth Rates and Disease Resistance of Abies Lasiocarpa Grown for Ornamental Nursery Stock and Christmas Trees

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Trees from six corkbark fir (Abies lasiocarpa var. arizonica) and 10 subalpine fir (Abies lasiocarpa var. lasiocarpa) seed sources were grown at the University of Idaho (SREC) and three commercial nurseries in northern Idaho and northeastern Oregon. Post transplant mortality was highest during the f...

  1. European Transplant Registry of Senior Renal Transplant Recipients on Advagraf

    ClinicalTrials.gov

    2016-08-11

    Graft Failure; Death; Acute Rejection of Renal Transplant; Infections; Bone Disease; Post Transplant Diabetes Mellitus; Quality of Life; HLA Antibody Production; Cardiovascular Risk Factors; Non-HLA Antibody Production

  2. Congenital Erythropoietic Porphyria (CEP)

    MedlinePlus

    ... patients now over 10 years post-transplantation. Hematopoietic stem cell cord blood transplantation has also been successful. The Rare Diseases Clinical Research Network (RDCRN), funded by the National Institute of ...

  3. Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing MUD SCT

    ClinicalTrials.gov

    2009-01-22

    Chronic Myeloid Leukemia; Acute Myelogenous Leukemia; Myelodysplasia; Acute Lymphocytic Leukemia; Severe Aplastic Anemia; Non-Hodgkin's Lymphoma; Lymphoproliferative Disease; Multiple Myeloma; Advanced Myeloproliferative Disease

  4. Infectious serologies and autoantibodies in hepatitis C and autoimmune disease-associated mixed cryoglobulinemia.

    PubMed

    Lidar, Merav; Lipschitz, Noga; Agmon-Levin, Nancy; Langevitz, Pnina; Barzilai, Ori; Ram, Maya; Porat-Katz, Bat-Sheba; Bizzaro, Nicola; Damoiseaux, Jan; Tervaert, Jan Willem Cohen; deVita, Salvatore; Bombardieri, Stefano; Shoenfeld, Yehuda

    2012-04-01

    Mixed cryoglobulinemia (MC) syndrome is an immune complex-mediated vasculitis characterized by the clinical triad of purpura, weakness, and arthralgias, the morbidity of which is mainly related to kidney and peripheral nervous system dysfunction as well as to the development of a secondary lymphoma (Ferri et al. Autoimmun Rev 7:114-120, 2007, Lidar et al. Ann N Y Acad Sci 1173:649-657, 2009, Trejo et al. Semin Arthritis Rheum 33:19-28, 2003). MC is associated with infectious and systemic disorders, principally autoimmune and lymphoproliferative diseases. Since the 1990s, a striking association (>90%) between MC and hepatitis C virus (HCV) infection has been established (Ferri and Bombardieri 2004; Pascual et al. J Infect Dis 162:569-570, 1990). However, information regarding the etiopathogenesis of HCV-negative MC is scant (Mascia et al. Dig Liver Dis 39:61-64, 2007). We hereby present our findings, as well as previously published data, regarding the presence of antibodies against infectious agents and autoantibodies in patients with MC in an attempt to establish novel associations which may shed light on the etiopathogenesis of this disease.

  5. Heart Diseases

    MedlinePlus

    ... re like most people, you think that heart disease is a problem for others. But heart disease is the number one killer in the U.S. ... disability. There are many different forms of heart disease. The most common cause of heart disease is ...

  6. Kimura disease

    PubMed Central

    AlGhamdi, Fares E.; Al-Khatib, Talal A.; Marzouki, Hani Z.; AlGarni, Mohammed A

    2016-01-01

    Kimura disease is a chronic inflammatory disease that mainly manifests as a lump in the cervical region. Although the underlying pathophysiology is not clear yet, the diagnosis can be established based on specific histopathological characteristics. The first case of this disease was described in China, as well as the majority of subsequent cases that were also described in the Far East countries made Kimura disease traditionally a disease of adult patients of Asian descent. This report describes the occurrence of Kimura disease in pediatric non-Asian patient with a similar clinicopathologic presentation. PMID:26905356

  7. [Effects of myeloid antigen expression on hematopoietic reconstitution and disease prognosis in acute lymphocytic leukemia patients after allogeneic stem cell transplantation].

    PubMed

    Wang, Xiao-Ning; Liu, Hua-Sheng; Zhang, Mei

    2014-08-01

    This study was aimed to investigate the effects of myeloid antigen expression on hematopoietic reconstitution and disease prognosis in acute lymphocytic leukemia patients post-allogeneic stem cell transplantation (allo-HSCT). Clinical data of 20 patients with acute lymphocytic leukemia in Department of Hematology of the First Affiliated Hospital of Xi'an Jiaotong University from 2008 January to 2014 April were retrospectively analyzed, in which 5 cases were with myeloid antigen (My(+) ALL), while 15 patients were without myeloid antigen expression (My(-) ALL). Differences in prognosis and hematopoietic reconstitution post-allo-HSCT were observed in My(+) ALL and My(-) ALL patients. The results showed that the poor platelet engraftment in patients with My(+) ALL was found more than that in My(-)ALL patients. Three My(+) ALL patients experienced skin chronic graft versus host disease (cGVHD) including local in 2 cases and extensive in one case, and 3 My(-) ALL patients developed grade I-II acute GVHD, while five patients of My(-) ALL experienced cGVHD including local in 3 cases, extensive in 2 cases. One and two year overall survival rate of My(+) ALL and My(-) ALL patients was 80% and 85.7%, 53% and 69.8% respectively, one and two year progress-free survival rate was 53.3% and 54.7%, 26% and 27.4%, respectively. And there was no significant statistical difference between two groups (P > 0.05). It is concluded that the myeloid antigen expression may impact the platelet engraftment post-transplantation. There is no significant difference between one and two year overall survival rate and progress-free survival rate of My(+) ALL and My(-) ALL patients after allogeneic stem cell transplantation.

  8. Outcomes of donor lymphocyte infusion for treatment of mixed donor chimerism after a reduced-intensity preparative regimen for pediatric patients with nonmalignant diseases.

    PubMed

    Haines, Hilary L; Bleesing, Jack J; Davies, Stella M; Hornung, Lindsey; Jordan, Michael B; Marsh, Rebecca A; Filipovich, Alexandra H

    2015-02-01

    Mixed donor chimerism is increasingly common in the pediatric hematopoietic stem cell transplantation (HSCT) setting because of the increased use of reduced-intensity preparative regimens for nonmalignant diseases. Donor lymphocyte infusion (DLI) is potentially useful in the treatment of mixed donor chimerism, but little are data available on the use of DLI in this setting. We conducted a retrospective review of 27 pediatric patients who received DLI for mixed donor chimerism between January 2006 and December 2010 after receiving a preparative regimen of alemtuzumab, fludarabine, and melphalan. Twenty-one patients (78%) were alive at a median of 35 months post-transplant. Seven patients (26%) sustained full donor chimerism after DLI only at a median of 35 months post-HSCT. Nine patients (33%) continued with mixed donor chimerism (median, 38% [range, 18% to 70%]) at a median of 37 months after DLI only. Five patients underwent unconditioned stem cell boosts or second conditioned transplants after no improvement in donor chimerism was seen following DLI. Donor source appeared to contribute to outcomes after DLI; patients with mismatched unrelated donors had earlier first decline in chimerism and timing of first DLI, a higher response rate to DLI, and an increased rate of graft-versus-host disease (GVHD). There was no response to DLI in patients with matched sibling donors. Ten patients, all with improvement in chimerism after DLI, developed acute GVHD after DLI, with 3 having grade III GVHD. Three patients developed chronic GVHD after DLI. These data illustrate the potential efficacy of DLI in the treatment of mixed donor chimerism after a reduced-intensity preparative regimen.

  9. Outcomes of donor lymphocyte infusion for treatment of mixed donor chimerism after a reduced-intensity preparative regimen for pediatric patients with nonmalignant diseases.

    PubMed

    Haines, Hilary L; Bleesing, Jack J; Davies, Stella M; Hornung, Lindsey; Jordan, Michael B; Marsh, Rebecca A; Filipovich, Alexandra H

    2015-02-01

    Mixed donor chimerism is increasingly common in the pediatric hematopoietic stem cell transplantation (HSCT) setting because of the increased use of reduced-intensity preparative regimens for nonmalignant diseases. Donor lymphocyte infusion (DLI) is potentially useful in the treatment of mixed donor chimerism, but little are data available on the use of DLI in this setting. We conducted a retrospective review of 27 pediatric patients who received DLI for mixed donor chimerism between January 2006 and December 2010 after receiving a preparative regimen of alemtuzumab, fludarabine, and melphalan. Twenty-one patients (78%) were alive at a median of 35 months post-transplant. Seven patients (26%) sustained full donor chimerism after DLI only at a median of 35 months post-HSCT. Nine patients (33%) continued with mixed donor chimerism (median, 38% [range, 18% to 70%]) at a median of 37 months after DLI only. Five patients underwent unconditioned stem cell boosts or second conditioned transplants after no improvement in donor chimerism was seen following DLI. Donor source appeared to contribute to outcomes after DLI; patients with mismatched unrelated donors had earlier first decline in chimerism and timing of first DLI, a higher response rate to DLI, and an increased rate of graft-versus-host disease (GVHD). There was no response to DLI in patients with matched sibling donors. Ten patients, all with improvement in chimerism after DLI, developed acute GVHD after DLI, with 3 having grade III GVHD. Three patients developed chronic GVHD after DLI. These data illustrate the potential efficacy of DLI in the treatment of mixed donor chimerism after a reduced-intensity preparative regimen. PMID:25464116

  10. Endoscopic retrograde cholangiopancreatography is safe and effective for the diagnosis and treatment of pancreaticobiliary disease following abdominal organ transplant in children.

    PubMed

    Otto, Alana K; Neal, Matthew D; Mazariegos, George V; Slivka, Adam; Kane, Timothy D

    2012-12-01

    ERCP is a diagnostic and therapeutic imaging modality widely used in adult pancreaticobiliary disease, including the treatment of anastomotic strictures following liver and small bowel transplant. We have previously reported a large series of ERCP in children and demonstrated its safety and utility in pediatric disease. The aim of this study was to evaluate the safety of and indications for ERCP following abdominal organ transplant among pediatric patients by performing a subgroup analysis of our large cohort. Forty-eight ERCPs were performed on 25 children ages 62 days to 20 yr following isolated liver, isolated small bowel, or composite graft transplant. Mean time from transplantation at the time of ERCP was 18 months. The most common indication for ERCP was the evaluation of non-specific hepatobiliary complaints, including abdominal pain and elevated liver enzymes. ERCP was also commonly performed for the evaluation or treatment of known or suspected biliary tree strictures. Seventy-seven percent of cases included therapeutic intervention, including sphincterotomy in 40%, stent placement in 29%, and stone extraction in 19%. The overall complication rate among post-transplant patients was low (2.9%) and not significantly different than the complication rate reported in our previous study. A history of abdominal organ transplant was not associated with an increased risk of complication following ERCP (OR = 0.41, 95% CI = 0.05-3.33). In our experience, ERCP can be safely performed in children following liver, small bowel, and composite graft transplant with outcomes similar to those seen in a general pediatric population and may be especially useful for the diagnosis and treatment for biliary strictures following transplant. Further investigation of the relationship between the timing of ERCP relative to transplant and the safety of the procedure is needed. PMID:22905881

  11. A simple and accurate grading system for orthoiodohippurate renal scans in the assessment of post-transplant renal function

    SciTech Connect

    Zaki, S.K.; Bretan, P.N.; Go, R.T.; Rehm, P.K.; Streem, S.B.; Novick, A.C. )

    1990-06-01

    Orthoiodohippurate renal scanning has proved to be a reliable, noninvasive method for the evaluation and followup of renal allograft function. However, a standardized system for grading renal function with this test is not available. We propose a simple grading system to distinguish the different functional phases of hippurate scanning in renal transplant recipients. This grading system was studied in 138 patients who were evaluated 1 week after renal transplantation. There was a significant correlation between the isotope renographic functional grade and clinical correlates of allograft function such as the serum creatinine level (p = 0.0001), blood urea nitrogen level (p = 0.0001), urine output (p = 0.005) and need for hemodialysis (p = 0.007). We recommend this grading system as a simple and accurate method to interpret orthoiodohippurate renal scans in the evaluation and followup of renal allograft recipients.

  12. [Study and prevalence of post-transplant diabetes mellitus; analysis on a group of kidney transplant recipients].

    PubMed

    Fernández Castillo, Rafael; Fernandez Gallegos, Ruth; Gomez Urquiza, Jose Luis; Cañadas de la Fuente, Guillermo A; Esteban de la Rosa, Rafael Jose; Peña Amaro, Maria Pilar

    2014-10-01

    Introducción: La aparición de la diabetes mellitus postrasplante (DMPT) entre los receptores renales se asocia con un mayor riesgo de fracaso del injerto y altas tasas de morbimortalidad. Minimizar el riesgo de DMPT es una prioridad para la mejora a largo plazo de las tasas de supervivencia. Objetivos: Este estudio tiene como objetivo evaluar la prevalencia de DMPT en una población de paciente trasplantados renales, para identificar los factores de riesgo y evaluar el injerto y supervivencia de los pacientes. Métodos: La muestras estuvo formada por 112 pacientes trasplantados renales, 69 hombres y 43 mujeres, trasplantados renales, que asistieron durante cinco años a la consulta postrasplante. Se analizaron como posibles factores de riesgo para DMPT: edad, sexo, índice de masa corporal (IMC), sobrepeso, hepatitis C, hipertensión, dislipemia, colesterol total (CT), triglicéridos en suero y terapia inmunosupresora (Ciclosporina, tacrolimus, micofenolato mofetil y sirolimus), también se evaluó la prevalencia de episodios de rechazo agudo. Resultados: La prevalencia de PTDM fue del 24,2%, frente a 85 pacientes (75,8%) con glucosa normalizada (PGN). Los pacientes con DMPT mostraron un IMC mayor, un porcentaje mayor de sobrepeso, dislipemias, niveles colesterol total, triglicéridos y se presento un mayor porcentaje de pacientes con PDMPT entre los que se administraron Micofenolato mofetil. Conclusiones: Existe una alta incidencia de DMPT en receptores renales, la importancia del control de peso y de un seguimiento estricto para todos los factores de riesgo identificados, asi como una minimización en las dosis de tratamientos inmunosupresores para prevenir la aparición de DMPT.

  13. High Emergency Lung Transplantation: dramatic decrease of waiting list death rate without relevant higher post-transplant mortality.

    PubMed

    Roux, Antoine; Beaumont-Azuar, Laurence; Hamid, Abdul Monem; De Miranda, Sandra; Grenet, Dominique; Briend, Guillaume; Bonnette, Pierre; Puyo, Philippe; Parquin, François; Devaquet, Jerome; Trebbia, Gregoire; Cuquemelle, Elise; Douvry, Benoit; Picard, Clément; Le Guen, Morgan; Chapelier, Alain; Stern, Marc; Sage, Edouard

    2015-09-01

    Many candidates for lung transplantation (LT) die on the waiting list, raising the question of graft availability and strategy for organ allocation. We report the experience of the new organ allocation program, "High Emergency Lung Transplantation" (HELT), since its implementation in our center in 2007. Retrospective analysis of 201 lung transplant patients, of whom 37 received HELT from 1st July 2007 to 31th May 2012. HELT candidates had a higher impairment grade on respiratory status and higher Lung Allocation Score (LAS). HELT patients had increased incidence of perioperative complications (e.g., perioperative bleeding) and extracorporeal circulatory assistance (75% vs. 36.6%, P = 0.0005). No significant difference was observed between HELT and non-HELT patients in mechanical ventilation duration (15.5 days vs. 11 days, P = 0.27), intensive care unit length of stay (15 days vs. 10 days, P = 0.22) or survival rate at 12 (81% vs. 80%), and 24 months post-LT (72.9% vs. 75.0%). Lastly, mortality on the waiting list was spectacularly reduced from 19% to 2% when compared to the non-HELT 2004-2007 group. Despite a more severe clinical status of patients on the waiting list, HELT provided similar results to conventional LT. These results were associated with a dramatic reduction in the mortality rate of patients on the waiting list.

  14. Analyses of the spleen proteome of chickens infected with Marek's disease virus

    SciTech Connect

    Thanthrige-Don, Niroshan; Abdul-Careem, Mohamed F.; Shack, L. Allen; Burgess, Shane C.; Sharif, Shayan

    2009-08-01

    Marek's disease virus (MDV), which causes a lymphoproliferative disease in chickens, is known to induce host responses leading to protection against disease in a manner dependent on genetic background of chickens and virulence of the virus. In the present study, changes in the spleen proteome at 7, 14 and 21 days post-infection in response to MDV infection were studied using two-dimensional polyacrylamide gel electrophoresis. Differentially expressed proteins were identified using one-dimensional liquid chromatography electrospray ionization tandem mass spectrometry (1D LC ESI MS/MS). Comparative analysis of multiple gels revealed that the majority of changes had occurred at early stages of the disease. In total, 61 protein spots representing 48 host proteins were detected as either quantitatively (false discovery rate (FDR) <= 0.05 and fold change >= 2) or qualitatively differentially expressed at least once during different sampling points. Overall, the proteins identified in the present study are involved in a variety of cellular processes such as the antigen processing and presentation, ubiquitin-proteasome protein degradation (UPP), formation of the cytoskeleton, cellular metabolism, signal transduction and regulation of translation. Notably, early stages of the disease were characterized by changes in the UPP, and antigen presentation. Furthermore, changes indicative of active cell proliferation as well as apoptosis together with significant changes in cytoskeletal components that were observed throughout the experimental period suggested the complexity of the pathogenesis. The present findings provide a basis for further studies aimed at elucidation of the role of these proteins in MDV interactions with its host.

  15. [Kikuchi-Fujimoto disease prior to childhood-systemic lupus erythematosus diagnosis].

    PubMed

    Martins, Sofia S; Buscatti, Izabel M; Freire, Pricilla S; Cavalcante, Erica G; Sallum, Adriana M; Campos, Lucia M A; Silva, Clovis A

    2014-01-01

    Kikuchi-Fujimoto disease (KFD) is a self-limiting histiocytic necrotizing lymphadenitis of unknown origin. Of note, KFD was infrequently reported in adult systemic lupus erythematosus (SLE), with rare occurrence in childhood-SLE (C-SLE) patients. To our knowledge, the prevalence of KFD in the paediatric lupus population was not studied. Therefore, in a period of 29 consecutive years, 5,682 patients were followed at our institution and 289 (5%) met the American College of Rheumatology classification criteria for SLE, one had isolated KFD (0.03) and only one had KFD associated to C-SLE diagnoses, which case was reported herein. A 12 year-old female patient had high fever, fatigue and cervical and axillary lymphadenopathy. The antinuclear antibodies (ANA) were negative, with positive IgM and IgG herpes simplex virus type 1 and type 2 serologies. Fluorine-18-fluoro-deoxy-glucose positron emission tomography/computed tomography (PET/CT) imaging demonstrated diffuse lymphadenopathy. The axillary lymph node biopsy showed necrotizing lymphadenitis with histiocytes, without lymphoproliferative disease, compatible with KFD. After 30 days, she presented spontaneous regression and no therapy was required. Nine months later, she developed malar rash, photosensitivity, oral ulcers, lymphopenia and ANA 1:320 (homogeneous nuclear pattern). At that moment the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 10 and she was treated with prednisone (1.0mg/kg/day) and hidroxychloroquine showing progressive improvement of hers signs and symptoms. In conclusion, KFD is a benign and rare disease in our paediatric lupus population. We also would like to reinforce the relevance of autoimmune diseases diagnosis during the follow-up of patients with KFD.

  16. 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 ...

  17. Menkes Disease

    MedlinePlus

    ... therapy approaches to Menkes disease. 3 1. Kaler, SG. The neurology of STPAT copper transporter disease: emerging ... Reviews Neurology , 2001:7:15-19.. 2. Kaler SG, et al. Neonatal Diagnosis and Treatment of Menkes ...

  18. Sandhoff Disease

    MedlinePlus

    ... Sandhoff Disease? Sandhoff disease is a rare, inherited lipid storage disorder that progressively destroys nerve cells in ... results in the harmful accumulation of certain fats (lipids) in the brain and other organs of the ...

  19. Gaucher Disease

    MedlinePlus

    ... one of the inherited metabolic disorders known as lipid storage diseases. Lipids are fatty materials that include oils, fatty acids, ... research to find ways to treat and prevent lipid storage disorders such as Gaucher disease. For example, ...

  20. Huntington disease

    MedlinePlus

    Huntington chorea ... Huntington disease is caused by a genetic defect on chromosome 4. The defect causes a part of ... 10 to 28 times. But in persons with Huntington disease, it is repeated 36 to 120 times. ...

  1. Digestive diseases

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/007447.htm Digestive diseases To use the sharing features on this page, please enable JavaScript. Digestive diseases are disorders of the digestive tract, which ...

  2. Tickborne Diseases

    MedlinePlus

    ... for tickborne diseases ranges from studying the basic biology of the microbes that cause these diseases to ... Nucleotide Polymorphism Phylogenetics & Ontology Proteomics & Protein Analysis Systems Biology Data Portals Software Applications BCBB Mobyle Interface Designer ( ...

  3. Graves' Disease

    MedlinePlus

    ... our online catalog. ​ Additional Links Hashimoto's Disease Hyperthyroidism Hypothyroidism Pregnancy & Thyroid Disease Thyroid Tests Find a Specialist ... everyone who receives radioactive iodine treatment eventually develops hypothyroidism, which occurs when the thyroid does not make ...

  4. 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 ...

  5. Celiac Disease

    MedlinePlus

    ... having celiac disease? Yes, you can have gluten sensitivity without the immune system attack on the small ... gluten causes in celiac disease. Symptoms of gluten sensitivity are generally milder than those seen in celiac ...

  6. Kawasaki disease

    MedlinePlus

    ... pubmed/23283289 . Mason JC. Rheumatic diseases of the cardiovascular system. In: Mann DL, Zipes DP, Libby P, Bonow RO, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine . 10th ed. Philadelphia, PA: Elsevier Saunders; 2014: ...

  7. Bone Diseases

    MedlinePlus

    ... avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds ... break Osteogenesis imperfecta makes your bones brittle Paget's disease of bone makes them weak Bones can also ...

  8. Gaucher Disease

    MedlinePlus

    Gaucher disease is a rare, inherited disorder. It is a type of lipid metabolism disorder. If you have it, ... It usually starts in childhood or adolescence. Gaucher disease has no cure. Treatment options for types 1 ...

  9. 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 ...

  10. Meniere's Disease

    MedlinePlus

    Meniere's disease is a disorder of the inner ear. It can cause severe dizziness, a roaring sound in your ... together over several days. Some people with Meniere's disease have "drop attacks" during which the dizziness is ...

  11. 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 ...

  12. 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 ...

  13. Mitochondrial Diseases

    MedlinePlus

    ... disorder, something goes wrong with this process. Mitochondrial diseases are a group of metabolic disorders. Mitochondria are ... cells and cause damage. The symptoms of mitochondrial disease can vary. It depends on how many mitochondria ...

  14. Kidney Diseases

    MedlinePlus

    ... until you go to the bathroom. Most kidney diseases attack the nephrons. This damage may leave kidneys ... medicines. You have a higher risk of kidney disease if you have diabetes, high blood pressure, or ...

  15. Parasitic Diseases

    MedlinePlus

    ... a bug bite, or sexual contact. Some parasitic diseases are easily treated and some are not. Parasites ... be seen with the naked eye. Some parasitic diseases occur in the United States. Contaminated water supplies ...

  16. Liver Diseases

    MedlinePlus

    ... remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, ... the skin, can be one sign of liver disease. Cancer can affect the liver. You could also ...

  17. Endocrine Diseases

    MedlinePlus

    ... low, you may have a hormone disorder. Hormone diseases also occur if your body does not respond ... In the United States, the most common endocrine disease is diabetes. There are many others. They are ...

  18. 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 ...

  19. 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, ...

  20. 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 ...

  1. Parkinson's Disease

    MedlinePlus

    Parkinson's disease (PD) is a type of movement disorder. It happens when nerve cells in the brain don't ... coordination As symptoms get worse, people with the disease may have trouble walking, talking, or doing simple ...

  2. 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 ...

  3. Binswanger's Disease

    MedlinePlus

    ... and Information 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 ...

  4. Kidney Disease

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Kidney Disease KidsHealth > For Teens > Kidney Disease Print A ... Syndrome Coping With Kidney Conditions What Do the Kidneys Do? You might never think much about some ...

  5. Addison disease

    MedlinePlus

    ... the adrenal glands (autoimmune disease) Infections such as tuberculosis , HIV, or fungal infections Hemorrhage into the adrenal glands Tumors Risk factors for the autoimmune type of Addison disease include ...

  6. Behcet's Disease

    MedlinePlus

    ... neurological disorders such as Behcet's disease. The National Human Genome Research Institute, another Institute of the National Institutes of Health, conducts research into the genomic basis of Behcet's disease. This research is aimed ...

  7. Lyme disease

    MedlinePlus

    ... The same disease occurs in many parts of Europe and Asia. In the United States, most Lyme ... Risk factors for Lyme disease include: Doing outside activities that increase tick exposure (for example, gardening, hunting, ...

  8. 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 ...

  9. Colonic Diseases

    MedlinePlus

    ... where your body makes and stores stool. Many disorders affect the colon's ability to work properly. Some ... abdominal cramping and other symptoms Treatment for colonic diseases varies greatly depending on the disease and its ...

  10. Pneumococcal Disease

    MedlinePlus

    ... pneumococcal disease. Quick Facts About Pneumococcal Disease and Vaccination According to WHO, pneumococcal pneumonia and meningitis are ... of antibiotic treatment. (9, 10, 11) Conjugate pneumococcal vaccination is safe and effective for preventing severe childhood ...

  11. Gilbert disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000301.htm Gilbert disease To use the sharing features on this page, please enable JavaScript. Gilbert disease is a common disorder passed down through ...

  12. Liver disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the liver ...

  13. Music in Reducing Anxiety and Pain in Adult Patients Undergoing Bone Marrow Biopsy for Hematologic Cancers or Other Diseases

    ClinicalTrials.gov

    2012-07-12

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Psychosocial Effects of Cancer and Its Treatment

  14. Parkinson Disease.

    PubMed

    Capriotti, Teri; Terzakis, Kristina

    2016-06-01

    Parkinson disease (PD) is a progressive neurodegenerative disease that affects one million people in the United States. This article reviews the etiology and pathophysiology of PD, risk factors, clinical manifestations, diagnostic criteria, and treatment of this common disease. Implications for home care clinicians are included.

  15. 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...

  16. Rare Diseases

    MedlinePlus

    ... Are often very complex Are often caused by changes in genes It can be hard to find a specialist who knows how to treat your rare disease. Disease advocacy groups, rare disease organizations, and genetics clinics may help you to find ...

  17. Behcet's Disease

    MedlinePlus

    ... with Behçet’s disease keep their joints strong and flexible. What Is the Prognosis for a Person With Behçet’s Disease? Most people with Behçet’s disease can lead productive lives and control symptoms with proper medicine, rest, and exercise. Doctors ...

  18. Lyme Disease.

    ERIC Educational Resources Information Center

    Taylor, George C.

    1991-01-01

    This overview of the public health significance of Lyme disease includes the microbiological specifics of the infectious spirochete, the entomology and ecology of the ticks which are the primary disease carrier, the clinical aspects and treatment stages, the known epidemiological patterns, and strategies for disease control and for expanded public…

  19. Meniere's Disease.

    ERIC Educational Resources Information Center

    Schessel, David A.

    1997-01-01

    Meniere's disease is characterized by unpredictable spells of severe vertigo and fluctuations in hearing and tinnitus. This article discusses the incidence of Meniere's disease, the present status of our understanding of this disease, controversies in its diagnosis, and the multiple therapeutic modalities recruited in its treatment. (Contains…

  20. Prion Diseases

    PubMed Central

    Geschwind, Michael D.

    2016-01-01

    Purpose of Review This article presents an update on the clinical aspects of human prion disease, including the wide spectrum of their presentations. Recent Findings Prion diseases, a group of disorders caused by abnormally shaped proteins called prions, occur in sporadic (Jakob-Creutzfeldt disease), genetic (genetic Jakob-Creutzfeldt disease, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia), and acquired (kuru, variant Jakob-Creutzfeldt disease, and iatrogenic Jakob-Creutzfeldt disease) forms. This article presents updated information on the clinical features and diagnostic methods for human prion diseases. New antemortem potential diagnostic tests based on amplifying prions in order to detect them are showing very high specificity. Understanding of the diversity of possible presentations of human prion diseases continues to evolve, with some genetic forms progressing slowly over decades, beginning with dysautonomia and neuropathy and progressing to a frontal-executive dementia with pathology of combined prionopathy and tauopathy. Unfortunately, to date, all human prion disease clinical trials have failed to show survival benefit. A very rare polymorphism in the prion protein gene recently has been identified that appears to protect against prion disease; this finding, in addition to providing greater understanding of the prionlike mechanisms of neurodegenerative disorders, might lead to potential treatments. Summary Sporadic Jakob-Creutzfeldt disease is the most common form of human prion disease. Genetic prion diseases, resulting from mutations in the prion-related protein gene (PRNP), are classified based on the mutation, clinical phenotype, and neuropathologic features and can be difficult to diagnose because of their varied presentations. Perhaps most relevant to this Continuum issue on neuroinfectious diseases, acquired prion diseases are caused by accidental transmission to humans, but fortunately, they are the least common form and

  1. Glomerular disease.

    PubMed

    Vaden, Shelly L

    2011-08-01

    Glomerular diseases are a leading cause of chronic kidney disease in dogs but seem to be less common in cats. Glomerular diseases are diverse, and a renal biopsy is needed to determine the specific glomerular disease that is present in any animal. Familial glomerulopathies occur in many breeds of dogs. However, most dogs with glomerular disease have acquired glomerular injury that is either immune-complex mediated or due to systemic factors, both of which are believed to be the result of a disease process elsewhere in the body (i.e., neoplastic, infectious, and noninfectious inflammatory disorders). A thorough clinical evaluation is indicated in all dogs suspected of having glomerular disease and should include an extensive evaluation for potential predisposing disorders. Nonspecific management of dogs with glomerular disease can be divided into 3 major categories: (1) treatment of potential predisposing disorders, (2) management of proteinuria, and (3) management of uremia and other complications of glomerular disease and chronic kidney disease. Specific management of specific glomerular diseases has not been fully studied in dogs. However, it may be reasonable to consider immunosuppressive therapy in dogs that have developed a form of glomerulonephritis secondary to a steroid-responsive disease (e.g., systemic lupus erythematosus) or have immune-mediated lesions that have been documented in renal biopsy specimens. Appropriate patient monitoring during therapy is important for maximizing patient care. The prognosis for dogs and cats with glomerular disease is variable and probably dependent on a combination of factors. The purpose of this article is to discuss the general diagnosis and management of dogs with glomerular disease. PMID:21782143

  2. High-throughput sequencing detects minimal residual disease in acute T lymphoblastic leukemia.

    PubMed

    Wu, David; Sherwood, Anna; Fromm, Jonathan R; Winter, Stuart S; Dunsmore, Kimberly P; Loh, Mignon L; Greisman, Harvey A; Sabath, Daniel E; Wood, Brent L; Robins, Harlan

    2012-05-16

    High-throughput sequencing (HTS) of lymphoid receptor genes is an emerging technology that can comprehensively assess the diversity of the immune system. Here, we applied HTS to the diagnosis of T-lineage acute lymphoblastic leukemia/lymphoma. Using 43 paired patient samples, we then assessed minimal residual disease (MRD) at day 29 after treatment. The variable regions of TCRB and TCRG were sequenced using an Illumina HiSeq platform after performance of multiplexed polymerase chain reaction, which targeted all potential V-J rearrangement combinations. Pretreatment samples were used to define clonal T cell receptor (TCR) complementarity-determining region 3 (CDR3) sequences, and paired posttreatment samples were evaluated for MRD. Abnormal T lymphoblast identification by multiparametric flow cytometry was concurrently performed for comparison. We found that TCRB and TCRG HTS not only identified clonality at diagnosis in most cases (31 of 43 for TCRB and 27 of 43 for TCRG) but also detected subsequent MRD. As expected, HTS of TCRB and TCRG identified MRD that was not detected by flow cytometry in a subset of cases (25 of 35 HTS compared with 13 of 35, respectively), which highlights the potential of this technology to define lower detection thresholds for MRD that could affect clinical treatment decisions. Thus, next-generation sequencing of lymphoid receptor gene repertoire may improve clinical diagnosis and subsequent MRD monitoring of lymphoproliferative disorders.

  3. [Social diseases, civilization diseases or lifestyle diseases?].

    PubMed

    Betlejewski, Stansław

    2007-01-01

    In general, the development of civilization is viewed as a positive step for the well-being of the human species, leading to an increased duration and quality of life. The accelerated progress of civilization (mainly industrialization, urbanization and nutrition) has lead to new possibilities for adverse effects on human health. In former high civilization--like old Egypt, Greece, Roman, Chinese, Indian, Maya civilizations--the "modem civilization diseases" were unknown. Modem science through improved sanitation, vaccination and antibiotics as well as improved social and economical conditions, has eliminated the threat of death from most infectious diseases. In the years after World War II the social, economic and health conditions changed. Most deaths have resulted from heart disease, stroke, cancer and other diseases as a result of an inappropriate relationship of people with their environment and changed lifestyle. Lifestyle diseases are different from other diseases because they are potentially preventable and can be lowered with changes in diet, lifestyle and environment. PMID:18350729

  4. Quantitative PCR detection of NPM/ALK fusion gene and CD30 gene expression in patients with anaplastic large cell lymphoma--residual disease monitoring and a correlation with the disease status.

    PubMed

    Kalinova, Marketa; Krskova, Lenka; Brizova, Helena; Kabickova, Edita; Kepak, Tomas; Kodet, Roman

    2008-01-01

    Anaplastic large cell lymphoma (ALCL) represents a heterogeneous group of malignant lymphoproliferative diseases with a consistent expression of the cytokine receptor CD30. ALCL is frequently associated with a NPM/ALK fusion gene which is found in up to 75% of pediatric ALCLs. Real-time quantitative RT-PCR (RQ-RT-PCR) of NPM/ALK and CD30 gene expression was employed to analyze minimal residual disease (MRD) in 10 patients with NPM/ALK positive ALCL in 79 follow-up bone marrow (BM) and/or peripheral blood (PB) samples. In all BM samples from relapses and/or closely before a relapse, BM samples revealed NPM/ALK and CD30 positivity in at least one of the iliac BM trephines. Five out of nine relapses were preceded or were accompanied by minimally half log increased NPM/ALK levels in the BM. We found that RQ-RT-PCR of the CD30 expression is not suitable for MRD detection--only two relapses were accompanied by an increase of the CD30 level above a level which was detected in BM/PB samples from healthy individuals. RQ-RT-PCR of NPM/ALK expression is a promising and rapid approach for monitoring MRD.

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

    PubMed Central

    2011-01-01

    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, rMd5ΔMeq, 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, GX0101ΔMeq, by deleting both copies of the Meq gene from a pathogenic MDV, GX0101 strain, which was isolated in China. Pathogenesis experiments showed that the GX0101ΔMeq 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 GX0101ΔMeq on the immune system in chickens after infection with GX0101ΔMeq 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 GX0101ΔMeq 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

  6. Revaccination with Marek's disease vaccines induces productive infection and superior immunity.

    PubMed

    Wu, Changxin; Gan, Junji; Jin, Qiao; Chen, Chuangfu; Liang, Ping; Wu, Yantao; Liu, Xuefen; Ma, Li; Davison, Fred

    2009-02-01

    The most common lymphoproliferative disease in chickens is Marek's disease (MD), which is caused by the oncogenic herpesvirus Marek's disease virus (MDV). The emergence of hypervirulent pathotypes of MDV has led to vaccine failures, which have become common and which have resulted in serious economic losses in some countries, and a revaccination strategy has been introduced in practice. The mechanism by which revaccination invokes superior immunity against MD is unknown. After field trials which showed that revaccination provided protection superior to that provided by a single vaccination were performed, experiments were conducted to explore the interaction between revaccinated chickens and MDV. The results showed that the chickens in the revaccination groups experienced two consecutive productive infections but that the chickens in the single-vaccination groups experienced one productive infection, demonstrating that revaccination of viruses caused the chickens to have productive and then latent infections. Revaccination of the virus induced in the chickens a higher and a longer temporary expansion of the CD8(+), CD4(+), and CD3(+) T-lymphocyte subpopulations, stronger peripheral blood lymphocyte proliferative activity; and higher levels of neutralizing antibody than single vaccination. These findings disagree with the postulate that MDV antigens persist, stimulate the immune system, and maintain a high level immunity after vaccination. The suppression of productive infection by maternal antibodies in chickens receiving the primary vaccination and a lower level of productive infection in the revaccination groups challenged with MDV were observed. The information obtained in this study suggests that the productive infection with revaccinated MDV in chickens plays a crucial role in the induction of superior immunity. This finding may be exploited for the development of a novel MD vaccine that results in the persistence of the antigen supply and that maintains a

  7. Revaccination with Marek's Disease Vaccines Induces Productive Infection and Superior Immunity▿

    PubMed Central

    Wu, Changxin; Gan, Junji; Jin, Qiao; Chen, Chuangfu; Liang, Ping; Wu, Yantao; Liu, Xuefen; Ma, Li; Davison, Fred

    2009-01-01

    The most common lymphoproliferative disease in chickens is Marek's disease (MD), which is caused by the oncogenic herpesvirus Marek's disease virus (MDV). The emergence of hypervirulent pathotypes of MDV has led to vaccine failures, which have become common and which have resulted in serious economic losses in some countries, and a revaccination strategy has been introduced in practice. The mechanism by which revaccination invokes superior immunity against MD is unknown. After field trials which showed that revaccination provided protection superior to that provided by a single vaccination were performed, experiments were conducted to explore the interaction between revaccinated chickens and MDV. The results showed that the chickens in the revaccination groups experienced two consecutive productive infections but that the chickens in the single-vaccination groups experienced one productive infection, demonstrating that revaccination of viruses caused the chickens to have productive and then latent infections. Revaccination of the virus induced in the chickens a higher and a longer temporary expansion of the CD8+, CD4+, and CD3+ T-lymphocyte subpopulations, stronger peripheral blood lymphocyte proliferative activity; and higher levels of neutralizing antibody than single vaccination. These findings disagree with the postulate that MDV antigens persist, stimulate the immune system, and maintain a high level immunity after vaccination. The suppression of productive infection by maternal antibodies in chickens receiving the primary vaccination and a lower level of productive infection in the revaccination groups challenged with MDV were observed. The information obtained in this study suggests that the productive infection with revaccinated MDV in chickens plays a crucial role in the induction of superior immunity. This finding may be exploited for the development of a novel MD vaccine that results in the persistence of the antigen supply and that maintains a high

  8. Unresolved problems concerning optimal therapy of puberty in children with chronic renal diseases.

    PubMed

    Hokken-Koelega, A C; Saenger, P; Cappa, M; Greggio, N

    2001-07-01

    Many children with chronic renal insufficiency (CRI) show growth retardation and severely delayed pubertal development. Successful renal transplantation (RTx) also rarely results in full growth rehabilitation. Pubertal height gain in CRI patients is only 58% and 48% of that observed in late-maturing boys and girls, respectively. Growth retardation in both CRI and RTx patients is not the result of abnormal GH secretion or decreased levels of IGF-I, but rather of elevated levels of IGFBPs inhibiting the bioavailability of the IGFs. In RTx patients prednisone may also inhibit growth directly via inhibition of bone matrix formation. Several studies have convincingly shown that GH therapy at a dose of 4 IU/m2/day results in a sustained improvement of growth in prepubertal and pubertal children with CRI and in growth-retarded prepubertal and pubertal post-transplant patients. The following consensus was reached concerning optimal therapy of puberty in children with chronic renal disease. GH therapy does not lead to an earlier start of puberty. It is safe to give GH to RTx patients if transplant function is stable. GH therapy will not accelerate bone maturation and can improve the final height of children with CRI and after RTx. Increasing the GH dose above 4 IU/m2/day in pubertal RTx patients does not increase height gain or final height and is not advised as it may increase insulin resistance. GH should best be started before the start of the pubertal growth spurt but will still be effective in RTx patients with advanced bone age. GH testing should not be a prerequisite for starting GH therapy. It is important to optimise other therapies during puberty. During GH therapy of RTx patients use minimum daily, not alternate-day, steroid dosing. Further research is still required on the possible long-term effects of GH therapy in children with chronic diseases. Two studies demonstrated improved long-term growth and final height within the target height range, without

  9. Pivotal roles of CD8+ T cells restricted by MHC class I–like molecules in autoimmune diseases

    PubMed Central

    Das, Gobardhan; Das, Jyoti; Eynott, Paul; Zhang, Yingyu; Bothwell, Alfred L.M.; Kaer, Luc Van; Shi, Yufang

    2006-01-01

    Unlike T cells restricted by major histocompatibility complex (MHC) class Ia or class II molecules, T cells restricted by MHC class I–like molecules demonstrate properties of both innate and adaptive immunity and are therefore considered innate-like lymphocytes (ILLs). ILLs are believed to have immunoregulatory functions, but their roles in autoimmunity and defense against infections remain elusive. To study the properties of ILLs, we generated mice expressing only MHC class I–like molecules by crossing CIITA−/− with Kb−/−Db−/− mice. Surprisingly, these mice developed a lymphoproliferative syndrome and autoimmunity, most notably inflammatory bowel disease (IBD) and insulitis. The CD8+ ILLs in these mice exhibit a constitutively activated phenotype, and depletion of these cells abolished the autoimmune disorders. In addition, adoptive transfer of CD8+ ILLs from Kb−/−Db−/−CIITA−/− mice to Rag-1−/−pfn−/− mice also resulted in IBD and insulitis. These findings provide direct evidence that CD8+ ILLs are sufficient to initiate and mediate autoimmune diseases. PMID:17088432

  10. Gaucher disease.

    PubMed

    Nagral, Aabha

    2014-03-01

    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

  11. Parathyroid disease.

    PubMed

    Wen, Hong Yan; Schumacher, H Ralph; Zhang, Li Yun

    2010-11-01

    Patients with parathyroid disease can have important musculoskeletal problems.Hypoparathyroidism can cause subcutaneous calcifications, tetany, muscle cramps,and paresthesias, but also myopathies and an ankylosing spondylitis-like back disease. Hypoparathyroidism can occur in SLE caused by antiparathyroid antibodies.Patients with hyperparathyroidism can develop bone disease with cysts, erosions,and deformities. They can also develop pseudogout, gout, myopathies, and tendon ruptures.

  12. Infectious disease

    NASA Technical Reports Server (NTRS)

    Pierson, Duane L.

    1990-01-01

    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.

  13. Huntington's Disease

    PubMed Central

    Finkbeiner, Steven

    2011-01-01

    Huntington's disease (HD) is the most common inherited neurodegenerative disease and is characterized by uncontrolled excessive motor movements and cognitive and emotional deficits. The mutation responsible for HD leads to an abnormally long polyglutamine (polyQ) expansion in the huntingtin (Htt) protein, which confers one or more toxic functions to mutant Htt leading to neurodegeneration. The polyQ expansion makes Htt prone to aggregate and accumulate, and manipulations that mitigate protein misfolding or facilitate the clearance of misfolded proteins tend to slow disease progression in HD models. This article will focus on HD and the evidence that it is a conformational disease. PMID:21441583

  14. [Wilson's disease].

    PubMed

    Moilanen, Veikko; Mäkisalo, Heikki

    2010-01-01

    Wilson's disease is a disorder of the liver's copper metabolism. Accumulation of copper causes liver and central nervous system damage. Wilson's disease should always be suspected, when a liver disease is detected in a child or an adolescent. The disease may also manifest itself as severe neurological or neuropsychiatric disorders. The diagnosis is often delayed despite the fact that the accumulation of copper in the body can be shown by various means. Early started medication will stop the accumulation of copper into the body. If the treatment is delayed or ineffective, liver transplantation is required.

  15. Siltuximab (Sylvant). Castleman's disease: good symptomatic efficacy in some patients.

    PubMed

    2016-03-01

    Multicentric Castleman's disease is a rare lymphoproliferative disorder characterised by disseminated lymphadenopathy. Symptoms and outcomes differ widely from one patient to another. The median survival time is about 2.5 years. There is no consensus on treatment. Siltuximab, a monoclonal antibody that antagonises interleukin-6, has been authorised in the European Union for patients with multicentric Castleman's disease who are not infected with HIV or HHV-8. In a randomised, double-blind trial in 79 patients, most of whom had mild or moderate symptoms, the estimated one-year survival rate was 100% in the siltuximab group versus 92% in the placebo group after a median follow-up of 60 weeks. However, half of the patients in the placebo group received siltuximab after disease progression. Symptoms disappeared for at least 18 weeks in one-quarter of patients in the siltuximab group versus none of those in the placebo group; the median symptom-free period in the siltuximab group was about 16 months. The known adverse effects of siltuximab are related to its immunosuppressive effect. They include frequent infections, neutropenia and thrombocytopenia. Reactions can occur during the infusion, and mouth sores have been reported. Other adverse events that appear to be more frequent with siltuximab include cutaneous disorders, oedema, renal and cardiac disorders, and peripheral neuropathy. Cases of gastrointestinal perforation have been reported in trials in other clinical settings. Siltuximab can mask the signs and symptoms of acute inflammation, in particular by suppressing fever and acute-phase markers such as C-reactive protein. Interleukin-6 is a cytochrome P450 inhibitor. Siltuximab activates its isoenzymes and can thus reduce the effectiveness of the numerous drugs that are substrates of this enzyme system. This risk of interactions is likely to persist up to several weeks after siltuximab withdrawal, because of its long plasma elimination half-life (about 16 days

  16. Reduced Intensity Preparative Regimen Followed by Stem Cell Transplant (FAB)

    ClinicalTrials.gov

    2016-03-29

    Myelodysplastic and Myeloproliferative Disorders; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia; Multiple Myeloma; Plasma Cell Dyscrasia; Lymphoproliferative Disorders; Hematologic Diseases

  17. Pilot Study of Unrelated Donor Hematopoietic Stem Cell Transplantation in Patients With Life Threatening Hemophagocytic Disorders

    ClinicalTrials.gov

    2005-06-23

    Chediak-Higashi Syndrome; Graft Versus Host Disease; X-Linked Lymphoproliferative Syndrome; Familial Erythrophagocytic Lymphohistiocytosis; Hemophagocytic Lymphohistiocytosis; Virus-Associated Hemophagocytic Syndrome

  18. Telaprevir- and Boceprevir-Based Triple Therapy for Hepatitis C in Liver Transplant Recipients with Advanced Recurrent Disease: A Multicenter Study

    PubMed Central

    Verna, Elizabeth C.; Saxena, Varun; Burton, James R.; O’Leary, Jacqueline G.; Dodge, Jennifer L.; Stravitz, Richard T.; Levitsky, Joshua; Trotter, James F.; Everson, Gregory T.; Brown, Robert S.; Terrault, Norah A.

    2016-01-01

    Background Antiviral treatment with sustained virologic response (SVR) improves survival in liver transplant (LT) recipients, and is especially relevant to patients with advanced recurrent hepatitis C virus (HCV). We assessed the safety and efficacy of protease inhibitor (PI)-based triple therapy in patients with recurrent advanced fibrosis and cholestatic hepatitis. Methods LT recipients with genotype 1 HCV and advanced fibrosis (F3-4/4) or cholestatic hepatitis treated with telaprevir or boceprevir-based triple therapy at 6 centers (CRUSH-C consortium) were retrospectively assessed. The primary endpoints were sustained virologic response at 12 weeks (SVR12) and safety. Results 45 patients with advanced fibrosis and 9 with cholestatic hepatitis (74% male, 57% with genotype 1a, and 63% prior non-responders) were included. SVR12 occurred in 51% of those with advanced fibrosis and 44% with cholestatic hepatitis, and eRVR was highly predictive of SVR12. Previous null/partial response (OR 0.09, p=0.003), low platelet count (OR 1.02, p=0.004), and steroid use (OR 0.16, p=0.03) were negatively associated with SVR12 in multivariable models. Six (11%) patients died during or after treatment, and hepatic decompensation during treatment occurred in 22% of patients with advanced fibrosis and 33% of patients with cholestatic hepatitis. Hispanic ethnicity (OR 9.37, p=0.03) and low albumin at treatment start (OR 0.01, p=0.001) were predictive of death or decompensation in multivariable models. Conclusions For LT recipients with recurrent advanced HCV and at highest need of effective treatment, PI-based triple therapy achieved sustained viral clearance in ~50% of patients. However, there is significant risk of serious adverse events including hepatic decompensation, arguing for earlier therapeutic intervention. The availability of antiviral drug combinations with higher efficacy and improved safety are of particular importance for post-transplant patients with advanced disease

  19. Long-Term Stable Mixed Chimerism after Hematopoietic Stem Cell Transplantation in Patients with Non-Malignant Disease, Shall We Be Tolerant?

    PubMed Central

    Stikvoort, Arwen; Sundin, Mikael; Uzunel, Mehmet; Gertow, Jens; Sundberg, Berit; Schaffer, Marie; Mattsson, Jonas; Uhlin, Michael

    2016-01-01

    Long-term stable mixed chimerism is a rare and poorly understood phenomenon post hematopoietic stem cell transplantation. This study aims to shed light on whether the two hematopoietic systems in patients with mixed chimerism remain functional. Additionally, we investigate possible immunologic differences in these individuals compared to patients with only donor derived immune cells. Patients with donor and mixed chimerism, at median 10 (5–16) years post-HSCT for non-malignant diseases, were assessed regarding clinical situation and immune system (phenotypical and functional). No difference in long-term outcome was seen in terms of general wellbeing, central phenotypic immune system features (e.g., differentiation status, CD4/CD8 ratio, B and NK-cell frequency) and antibody responses to immunizations. At a median of 10 years post transplantation, patients with mixed chimerism had significantly higher IgG3 and platelet levels. Additionally, these patients had higher NKT-cell levels (CD94+CD8+ and CD56+CD8+) than patients with donor chimerism. In depth phenotypic analysis of patients with mixed chimerism demonstrated recipient-derived fractions in most immune cell lineages (e.g., T-cell, B-cell and NK-cell subsets). Recipient cells were also capable of responding to mitogenic stimulation with production of several cytokines. In conclusion, long-term mixed chimerism did not negatively affect patient wellbeing and long-term outcome. Moreover, recipient-derived immunity may still be functional in these patients, suggesting an active state of tolerance and immunologic dependence on both hematopoietic systems. PMID:27152621

  20. Long-Term Stable Mixed Chimerism after Hematopoietic Stem Cell Transplantation in Patients with Non-Malignant Disease, Shall We Be Tolerant?

    PubMed

    Stikvoort, Arwen; Sundin, Mikael; Uzunel, Mehmet; Gertow, Jens; Sundberg, Berit; Schaffer, Marie; Mattsson, Jonas; Uhlin, Michael

    2016-01-01

    Long-term stable mixed chimerism is a rare and poorly understood phenomenon post hematopoietic stem cell transplantation. This study aims to shed light on whether the two hematopoietic systems in patients with mixed chimerism remain functional. Additionally, we investigate possible immunologic differences in these individuals compared to patients with only donor derived immune cells. Patients with donor and mixed chimerism, at median 10 (5-16) years post-HSCT for non-malignant diseases, were assessed regarding clinical situation and immune system (phenotypical and functional). No difference in long-term outcome was seen in terms of general wellbeing, central phenotypic immune system features (e.g., differentiation status, CD4/CD8 ratio, B and NK-cell frequency) and antibody responses to immunizations. At a median of 10 years post transplantation, patients with mixed chimerism had significantly higher IgG3 and platelet levels. Additionally, these patients had higher NKT-cell levels (CD94+CD8+ and CD56+CD8+) than patients with donor chimerism. In depth phenotypic analysis of patients with mixed chimerism demonstrated recipient-derived fractions in most immune cell lineages (e.g., T-cell, B-cell and NK-cell subsets). Recipient cells were also capable of responding to mitogenic stimulation with production of several cytokines. In conclusion, long-term mixed chimerism did not negatively affect patient wellbeing and long-term outcome. Moreover, recipient-derived immunity may still be functional in these patients, suggesting an active state of tolerance and immunologic dependence on both hematopoietic systems.