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Transplantation Sep 2017Posttransplant lymphoproliferative disorder (PTLD) is a serious complication in organ transplant recipients and is most often associated with the Epstein Barr virus... (Review)
Review
Posttransplant lymphoproliferative disorder (PTLD) is a serious complication in organ transplant recipients and is most often associated with the Epstein Barr virus (EBV). EBV is a common gammaherpes virus with tropism for B lymphocytes and infection in immunocompetent individuals is typically asymptomatic and benign. However, infection in immunocompromised or immunosuppressed individuals can result in malignant B cell lymphoproliferations, such as PTLD. EBV+ PTLD can arise after primary EBV infection, or because of reactivation of a prior infection, and represents a leading malignancy in the transplant population. The incidence of EBV+ PTLD is variable depending on the organ transplanted and whether the recipient has preexisting immunity to EBV but can be as high as 20%. It is generally accepted that impaired immune function due to immunosuppression is a primary cause of EBV+ PTLD. In this overview, we review the EBV life cycle and discuss our current understanding of the immune response to EBV in healthy, immunocompetent individuals, in transplant recipients, and in PTLD patients. We review the strategies that EBV uses to subvert and evade host immunity and discuss the implications for the development of EBV+ PTLD.
Topics: Animals; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Host-Pathogen Interactions; Humans; Immunity, Humoral; Immunocompromised Host; Immunosuppressive Agents; Killer Cells, Natural; Lymphoproliferative Disorders; Opportunistic Infections; Organ Transplantation; Risk Assessment; Risk Factors; T-Lymphocytes; Treatment Outcome; Virus Replication
PubMed: 28376031
DOI: 10.1097/TP.0000000000001767 -
The Israel Medical Association Journal... Mar 2006
Topics: DNA, Viral; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Incidence; Liver Transplantation; Lymphoproliferative Disorders; Postoperative Complications; Risk Factors
PubMed: 16599060
DOI: No ID Found -
Experimental and Clinical... Aug 2011Owing to the rare incidence of posttransplant lymphoproliferative disorder of the heart, there is a paucity of data concerning it. In this study, we pooled data from... (Review)
Review
OBJECTIVES
Owing to the rare incidence of posttransplant lymphoproliferative disorder of the heart, there is a paucity of data concerning it. In this study, we pooled data from posttransplant lymphoproliferative disorder patients from the existing literature. We sought to analyze and compare characteristics, predictors, and prognoses of patients with posttransplant lymphoproliferative disorder of the heart.
MATERIALS AND METHODS
A comprehensive search was made to gather data by PubMed and Google for reports of lymphoproliferative disorders occurring in transplant patients occurring within the heart, the heart allograft, and surrounding tissues. Pooled data were reanalyzed.
RESULTS
Overall, 206 patients were entered into the analysis. Transplant recipients with cardiac posttransplant lymphoproliferative disorders were significantly more likely to represent multivisceral and disseminated posttransplant lymphoproliferative disorder (P = .01 and P < .001). Posttransplant lymphoproliferative disorder in patients with heart involvement were more likely to involve the genitalia (P = .035), the adrenals (P = .035), the liver (P = .007), and the kidneys (P < .001). Patients with cardiac posttransplant lympho proliferative disorder had significantly shorter time from transplant to development of posttransplant lymphoproliferative disorder (P = .029). A log-rank test showed a significant inferior patient survival for transplant recipients with cardiac complications (P = .031). Patients with a cardiac allograft posttransplant lymphoproliferative disorder were significantly older at the time of transplant (55.3 ± 8.4 vs 38.5 ± 21.8 y; P = .002).
CONCLUSIONS
Because cardiac posttransplant lymphoproliferative disorder is associated with multiorgan and disseminated posttransplant lymphoproliferative disorder, all transplant recipients who represent posttransplant lymphoproliferative disorder in the heart should be evaluated for other organs involvement most especially in the kidneys, liver, and adrenals. Further prospective studies with a larger patient population are needed to confirm our results.
Topics: Adolescent; Adult; Chi-Square Distribution; Female; Heart Diseases; Humans; Kaplan-Meier Estimate; Kidney Transplantation; Lymphoproliferative Disorders; Male; Middle Aged; Risk Assessment; Risk Factors; Transplantation, Homologous; Treatment Outcome; Young Adult
PubMed: 21819371
DOI: No ID Found -
Journal of Clinical and Experimental... 2019Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs) with a T- or NK-cell phenotype are markedly rare, with only a limited number of... (Review)
Review
Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs) with a T- or NK-cell phenotype are markedly rare, with only a limited number of cases having been reported thus far. Methotrexate (MTX) is the most common agent used for OIIA-LPD patients, and 43 cases of MTX-associated T-LPDs (MTX T-LPDs) and five cases of MTX-associated NK/T-LPDs (MTX NK-LPDs) have been described. In addition to MTX T-LPDs and MTX NK/T-LPDs, T-LPD and NK/T-LPDs have been reported in patients receiving other immunosuppressive agents such as thiopurines, TNF antagonists, and cyclosporine. Hepatosplenic T-cell lymphoma (HSTL) is specifically associated with iatrogenic immunodeficiency, and 10% of HSTL cases develop in patients receiving thiopurines and/or TNF antagonists for inflammatory bowel disease (IBD). In this review, we focused on MTX T-LPD, MTX NK/T-LPD, and HSTL in patients with IBD. These T- and NK/T-cell associated OIIA-LPDs are the most common in daily medical practice.
Topics: Animals; Humans; Iatrogenic Disease; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphoproliferative Disorders; Methotrexate; Natural Killer T-Cells; T-Lymphocytes
PubMed: 31257346
DOI: 10.3960/jslrt.19013 -
American Journal of Transplantation :... Aug 2021EBV-positive and EBV-negative posttransplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct...
EBV-positive and EBV-negative posttransplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct pathophysiologies. To examine this hypothesis, we conducted a multicentric prospective study with 56 EBV-positive and 39 EBV-negative PTLD patients of the K-VIROGREF cohort, recruited at PTLD diagnosis and before treatment (2013-2019), and compared them to PTLD-free Transplant Controls (TC, n = 21). We measured absolute lymphocyte counts (n = 108), analyzed NK- and T cell phenotypes (n = 49 and 94), and performed EBV-specific functional assays (n = 16 and 42) by multiparameter flow cytometry and ELISpot-IFNγ assays (n = 50). EBV-negative PTLD patients, NK cells overexpressed Tim-3; the 2-year progression-free survival (PFS) was poorer in patients with a CD4 lymphopenia (CD4 <300 cells/mm , p < .001). EBV-positive PTLD patients presented a profound NK-cell lymphopenia (median = 60 cells/mm ) and a high proportion of NK cells expressing PD-1 (vs. TC, p = .029) and apoptosis markers (vs. TC, p < .001). EBV-specific T cells of EBV-positive PTLD patients circulated in low proportions, showed immune exhaustion (p = .013 vs. TC) and poorly recognized the N-terminal portion of EBNA-3A viral protein. Altogether, this broad comparison of EBV-positive and EBV-negative PTLDs highlight distinct patterns of immunopathological mechanisms between these two diseases and provide new clues for immunotherapeutic strategies and PTLD prognosis.
Topics: Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Lymphoproliferative Disorders; Organ Transplantation; Prospective Studies
PubMed: 33621411
DOI: 10.1111/ajt.16547 -
Cytometry. Part B, Clinical Cytometry Mar 2019This article provides an overview of the role of flow cytometry in the diagnosis, prognosis, and follow-up of T and NK-cell lymphoproliferative disorders. For each... (Review)
Review
This article provides an overview of the role of flow cytometry in the diagnosis, prognosis, and follow-up of T and NK-cell lymphoproliferative disorders. For each category, we will briefly discuss the immunophenotypic features of normal T and NK cells, and address technical issues in flow cytometry, the approach to diagnosis in various contexts, pitfalls in interpretation, and its use in follow-up and post-therapy management. In addition to reviewing the diagnostic, prognostic, and therapeutic utility of flow cytometric immunophenotyping in several of specific T and NK cell entities, we will also cover some of the new immunophenotypic markers. Furthermore, we will touch upon incorporation of flow cytometry in the final diagnosis, including correlation with other ancillary tests. © 2019 International Clinical Cytometry Society.
Topics: Flow Cytometry; Humans; Immunophenotyping; Killer Cells, Natural; Lymphoproliferative Disorders; T-Lymphocytes
PubMed: 30729667
DOI: 10.1002/cyto.b.21768 -
Journal of Clinical and Experimental... 2011IgG4-related disease is a novel lymphoproliferative disorder that shows hyper-IgG4-γ-globulinemia and IgG4-producing plasma cell expansion in affected organs with... (Review)
Review
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).
Topics: Diagnosis, Differential; History, 21st Century; Humans; Immunoglobulin G; Japan; Lymphoproliferative Disorders; Mikulicz' Disease; Sjogren's Syndrome
PubMed: 21628856
DOI: 10.3960/jslrt.51.13 -
Current Oncology (Toronto, Ont.) Dec 2021CD5-negative, CD10-negative low-grade B-cell lymphoproliferative disorders (CD5-CD10-LPD) of the spleen comprise a fascinating group of indolent, neoplastic, mature... (Review)
Review
CD5-negative, CD10-negative low-grade B-cell lymphoproliferative disorders (CD5-CD10-LPD) of the spleen comprise a fascinating group of indolent, neoplastic, mature B-cell proliferations that are essential to accurately identify but can be difficult to diagnose. They comprise the majority of B-cell LPDs primary to the spleen, commonly presenting with splenomegaly and co-involvement of peripheral blood and bone marrow, but with little to no involvement of lymph nodes. Splenic marginal zone lymphoma is one of the prototypical, best studied, and most frequently encountered CD5-CD10-LPD of the spleen and typically involves white pulp. In contrast, hairy cell leukemia, another well-studied CD5-CD10-LPD of the spleen, involves red pulp, as do the two less common entities comprising so-called splenic B-cell lymphoma/leukemia unclassifiable: splenic diffuse red pulp small B-cell lymphoma and hairy cell leukemia variant. Although not always encountered in the spleen, lymphoplasmacytic lymphoma, a B-cell lymphoproliferative disorder consisting of a dual population of both clonal B-cells and plasma cells and the frequent presence of the MYD88 L265P mutation, is another CD5-CD10-LPD that can be seen in the spleen. Distinction of these different entities is possible through careful evaluation of morphologic, immunophenotypic, cytogenetic, and molecular features, as well as peripheral blood and bone marrow specimens. A firm understanding of this group of low-grade B-cell lymphoproliferative disorders is necessary for accurate diagnosis leading to optimal patient management.
Topics: B-Lymphocytes; Humans; Immunophenotyping; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoproliferative Disorders; Spleen
PubMed: 34940069
DOI: 10.3390/curroncol28060430 -
Cancer Jun 2018Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation. Histologic heterogeneity and a lack of treatment...
BACKGROUND
Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation. Histologic heterogeneity and a lack of treatment standards have made evaluating clinical outcomes in specific patient populations difficult. This systematic literature review investigated the impact of the PTLD histologic subtype on survival in a large data set.
METHODS
Case series were identified on PubMed with the search terms post-transplant lymphoproliferative disorder/disease, PTLD, and solid organ transplantation, with additional publications identified through reference lists. The patient characteristics, immunosuppressive regimen, treatment, survival, and follow-up time for 306 cases were extracted from 94 articles, and these cases were combined with 11 cases from Emory University Hospital. Patients with a recorded subtype were included in a Kaplan-Meier survival analysis (n = 234). Cox proportional hazards regression analyses identified predictors of overall survival (OS) for each subtype and B-cell subgroup.
RESULTS
OS differed significantly between monomorphic T-cell neoplasms (median, 9 months) and polymorphic, monomorphic B-cell, and Hodgkin-type neoplasms, for which the median OS was not reached (P = .0001). Significant differences in OS among B subgroups were not detected, but there was a trend toward decreased survival for patients with Burkitt-type PTLD. Kidney transplantation and a reduction of immunosuppression were associated with increased OS for patients with B-cell neoplasms in a multivariate analysis. Immunosuppression with azathioprine was associated with decreased OS for patients with T-cell neoplasms, whereas radiotherapy was associated with improved OS for patients with that subtype.
CONCLUSIONS
The histologic subtype represents an important prognostic factor in PTLD, with patients with T-cell neoplasms exhibiting very poor OS. Possibly lower survival for certain subsets of patients with B-cell PTLD should be explored further and suggests the need for subtype-specific therapies to improve outcomes. Cancer 2018;124:2327-36. © 2018 American Cancer Society.
Topics: Antineoplastic Agents, Immunological; Chemoradiotherapy; Graft Rejection; Humans; Immunocompromised Host; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Kaplan-Meier Estimate; Lymphoproliferative Disorders; Organ Transplantation; Postoperative Complications; Progression-Free Survival; Risk Factors
PubMed: 29579330
DOI: 10.1002/cncr.31339 -
Clinical Transplantation May 2018A systematic review of papers in English on post-transplant lymphoproliferative disorder (PTLD) in lung transplant recipients (LTR) using MEDLINE, EMBASE, SCOPUS, and... (Meta-Analysis)
Meta-Analysis
A systematic review of papers in English on post-transplant lymphoproliferative disorder (PTLD) in lung transplant recipients (LTR) using MEDLINE, EMBASE, SCOPUS, and Cochrane databases was performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were strictly adhered to. Pooled odds ratios (pOR) were calculated from a random-effects model, and heterogeneity among studies was quantitated using I values. Fourteen studies published from 2005 to 2015 were included in the meta-analysis. One hundred and sixty-four lung transplant recipients were included. LTRs who received single vs bilateral were associated with a 7.67-fold risk of death after PTLD (6 studies with 64 LTRs; pOR 7.67 95% CI 1.98-29.70; P = .003). pOR of death for early onset PTLD (<1 year post-LT) vs late onset (>1 year post-LT) was not different (3 studies with 72 LTRS; pOR 0.62, 95% CI 0.20-1.86, P = .39). Standardized mean difference (SMD) in time from transplant to PTLD onset between LTRs who died vs alive was not different (9 studies with 109 LTRs; SMD 0.03, 95% CI -0.48-0.53, P = .92). Survival in polymorphic vs monomorphic PTLD and extranodal vs nodal disease was similar (4 studies with 31 LTRs; pOR 0.44, 95% CI 0.08-2.51; P = .36. 6 studies with 81 LTRs; pOR 1.05 95% CI 0.31-3.52, P = .94). This meta-analysis demonstrates that single LTRs are at a higher risk of death vs bilateral LTRs after the development of PTLD.
Topics: Graft Rejection; Humans; Lung Diseases; Lung Transplantation; Lymphoproliferative Disorders; Postoperative Complications
PubMed: 29517815
DOI: 10.1111/ctr.13235