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Journal of Clinical and Experimental... 2021Adult T-cell leukemia/lymphoma (ATLL) is a malignancy caused by the human T-cell leukemia virus type 1. Aggressive ATLL is refractory to conventional chemotherapy and... (Review)
Review
Adult T-cell leukemia/lymphoma (ATLL) is a malignancy caused by the human T-cell leukemia virus type 1. Aggressive ATLL is refractory to conventional chemotherapy and has a poor prognosis. Better therapeutic approaches, including cancer immunotherapy, are required to improve survival and prognosis. The genetic landscape of ATLL reveals frequent genetic alterations in genes associated with immune surveillance, including major histocompatibility complex (MHC) class I, CD58 antigen, and programmed cell death ligand 1. Clinicopathological investigations also revealed tumor immunity mechanisms in ATLL, including immune checkpoint molecules, MHC molecules, tumor-associated macrophages, and chemokines. However, the tumor microenvironment of ATLL remains complex because ATLL itself originates from T-cells, usually expressing regulatory T-cell markers. In this review, we discuss the recent literature describing the tumor microenvironment of ATLL.
Topics: Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; Lymphoma; Prognosis; Tumor Microenvironment
PubMed: 34937829
DOI: 10.3960/jslrt.21007 -
Frontiers in Immunology 2022Due to the various clinical and pathological manifestations of kidney involvement in lymphoproliferative disorder (LPD), the whole spectrum of kidney disease in LPD is...
BACKGROUND
Due to the various clinical and pathological manifestations of kidney involvement in lymphoproliferative disorder (LPD), the whole spectrum of kidney disease in LPD is still unclear, and data on kidney prognosis is scarce.
METHODS
We retrospectively reviewed the renal pathology profiles from January 2010 to December 2021, and 28 patients with B-cell LPD combined with intact renal biopsy data were included.
RESULTS
There were 20 men and eight women aging 41 to 79 years at the time of renal biopsy (median age 62 years). According to hematological diagnosis, patients were classified into four groups: chronic lymphocytic leukemia (CLL) (group1, n=7), Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) (group 2, n=8; WM, n=6; LPL, n=2), Other non-Hodgkin's lymphomas (NHL) (group3, n=7; diffuse large B-cell lymphoma (DLBCL), n=2; mucosa-associated lymphoid tissue (MALT) lymphoma, n=4; Low grade B-cell lymphoma, n=1), and monoclonal gammopathy of undetermined significance/monoclonal gammopathy of renal significance (MGUS/MGRS) (group 4, n=6). Median serum creatinine (Scr) level was 129 (range,59-956) umol/L. Eight patients (29%) were presented with acute kidney injury (AKI), and five patients (18%) required hemodialysis upon admission. Twenty-three patients (82%) presented with proteinuria (median protein excretion, 2.14 g/d), 11(39%) of whom had the nephrotic syndrome. Interstitial malignant infiltration was the most frequent renal lesion (n=6). Eight patients underwent immunohistochemistry of renal tissues, of which three patients (CLL, n=1; LPL, n=1; WM, n=1) had confirmed lymphoma infiltrates, and the infiltrating cells in the remaining five patients (CLL, n=1; MALT lymphoma, n=2; MGUS, n=2) were considered unrelated to lymphoma. The most common glomerular diseases were renal amyloidosis (n=4) and membranous nephropathy (n=4). Only 20 patients were treated, 13 of whom were treated with rituximab separately or in combination. The median follow-up time was 11 months. Of these, six had achieved hematological response, complete response in five cases. Eight had achieved renal response. At the end-of-study visit, four patients died and two progressed to end stage kidney disease (ESKD).
CONCLUSION
In conclusion, the clinicopathological spectrum of renal involvement in BLPD is diverse. Renal biopsy and immunohistochemistry are required for early diagnosis and prognostic assessment.
Topics: Acute Kidney Injury; Creatinine; Female; Humans; Kidney; Leukemia, Lymphocytic, Chronic, B-Cell; Leukocyte Disorders; Lymphoma, B-Cell, Marginal Zone; Lymphoproliferative Disorders; Male; Middle Aged; Monoclonal Gammopathy of Undetermined Significance; Retrospective Studies; Rituximab; Waldenstrom Macroglobulinemia
PubMed: 36172352
DOI: 10.3389/fimmu.2022.903315 -
Scientific Reports Nov 2020Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is a rare Epstein-Barr virus (EBV)-associated lymphoproliferative disease. The disease course of HVLPD...
Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is a rare Epstein-Barr virus (EBV)-associated lymphoproliferative disease. The disease course of HVLPD varies from an indolent course to progression to aggressive lymphoma. We investigated the characteristics of HVLPD in Korean patients. HVLPD patients at Seoul National University Hospital between 1988 and 2019 were retrospectively analyzed. This study included 26 HVLPD patients who all presented with recurrent papulovesicular and necrotic eruption on the face, neck, and extremities. EBV was detected from the skin tissues of all patients. HVLPD was diagnosed during childhood (age < 18 years) in seven patients (26.9%) and in adulthood (age ≥ 18 years) in 19 cases (73.1%). The median age at diagnosis was 24.0 years (range 7-70 years). HVLPD has various clinical courses, from an indolent course to progression to systemic lymphoma. Fourteen patients (53.8%) developed lymphoma: systemic EBV-positive T-cell lymphoma (n = 9, 34.6%); extranodal natural killer/T-cell lymphoma, nasal type (n = 3, 11.5%); aggressive natural killer/T-cell leukemia (n = 1, 3.8%); and EBV-positive Hodgkin lymphoma (n = 1, 3.8%). Mortality due to HVLPD occurred in five patients (26.3%) in the adult group, while it was one patient (14.3%) in the child group. As lymphoma progression and mortality occur not only in childhood but also in adulthood, adult-onset cases may need more careful monitoring.
Topics: Adolescent; Adult; Aged; Child; Disease Progression; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Hydroa Vacciniforme; Lymphoma, T-Cell; Lymphoproliferative Disorders; Male; Middle Aged; Necrosis; Republic of Korea; Retrospective Studies; Skin; Skin Neoplasms; Young Adult
PubMed: 33168864
DOI: 10.1038/s41598-020-76345-2 -
Journal of Hematology & Oncology Sep 2023Diagnosing post-transplant lymphoproliferative disorder (PTLD) is challenging and often requires invasive procedures. Analyses of cell-free DNA (cfDNA) isolated from... (Observational Study)
Observational Study
Diagnosing post-transplant lymphoproliferative disorder (PTLD) is challenging and often requires invasive procedures. Analyses of cell-free DNA (cfDNA) isolated from plasma is minimally invasive and highly effective for genomic profiling of tumors. We studied the feasibility of using cfDNA to profile PTLD and explore its potential to serve as a screening tool. We included seventeen patients with monomorphic PTLD after solid organ transplantation in this multi-center observational cohort study. We used low-coverage whole genome sequencing (lcWGS) to detect copy number variations (CNVs) and targeted next-generation sequencing (NGS) to identify Epstein-Barr virus (EBV) DNA load and somatic single nucleotide variants (SNVs) in cfDNA from plasma. Seven out of seventeen (41%) patients had EBV-positive tumors, and 13/17 (76%) had stage IV disease. Nine out of seventeen (56%) patients showed CNVs in cfDNA, with more CNVs in EBV-negative cases. Recurrent gains were detected for 3q, 11q, and 18q. Recurrent losses were observed at 6q. The fraction of EBV reads in cfDNA from EBV-positive patients was 3-log higher compared to controls and EBV-negative patients. 289 SNVs were identified, with a median of 19 per sample. SNV burden correlated significantly with lactate dehydrogenase levels. Similar SNV burdens were observed in EBV-negative and EBV-positive PTLD. The most commonly mutated genes were TP53 and KMT2D (41%), followed by SPEN, TET2 (35%), and ARID1A, IGLL5, and PIM1 (29%), indicating DNA damage response, epigenetic regulation, and B-cell signaling/NFkB pathways as drivers of PTLD. Overall, CNVs were more prevalent in EBV-negative lymphoma, while no difference was observed in the number of SNVs. Our data indicated the potential of analyzing cfDNA as a tool for PTLD screening and response monitoring.
Topics: Humans; DNA Copy Number Variations; Epigenesis, Genetic; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Lymphoproliferative Disorders; Cell-Free Nucleic Acids; Genomics
PubMed: 37705050
DOI: 10.1186/s13045-023-01500-x -
Advances in Chronic Kidney Disease Mar 2022Cancer is a leading cause of death in patients with kidney transplantation. Patients with kidney transplants are 10- to 200-times more likely to develop cancers after... (Review)
Review
Cancer is a leading cause of death in patients with kidney transplantation. Patients with kidney transplants are 10- to 200-times more likely to develop cancers after transplant than the general population, depending on the cancer type. Recent advances in cancer therapies have dramatically improved survival outcomes; however, patients with kidney transplants face unique challenges of immunosuppression management, cancer screening, and recurrence of cancer after transplant. Patients with a history of cancer tend to be excluded from transplant candidacy or are required to have long cancer-free wait time before wait-listing. The strategy of pretransplant wait time management may need to be revisited as cancer therapies improve, which is most applicable to patients with a history of multiple myeloma. In this review, we discuss several important topics in transplant onconephrology: the current recommendations for pretransplant wait times for transplant candidates with cancer histories, cancer screening post-transplant, post-transplant lymphoproliferative disorder, strategies for transplant patients with a history of multiple myeloma, and novel therapies for patients with post-transplant malignancies. With emerging novel cancer treatments, it is critical to have multidisciplinary discussions involving patients, caregivers, transplant nephrologists, and oncologists to achieve patient-oriented goals.
Topics: Humans; Kidney Transplantation; Multiple Myeloma
PubMed: 35817526
DOI: 10.1053/j.ackd.2021.09.002 -
Current Opinion in Infectious Diseases Dec 2021Management of Epstein-Barr virus posttransplant lymphoproliferative disorder (EBV PTLD) is complex, involving risk stratification, prevention and/or preemptive measures... (Review)
Review
PURPOSE OF REVIEW
Management of Epstein-Barr virus posttransplant lymphoproliferative disorder (EBV PTLD) is complex, involving risk stratification, prevention and/or preemptive measures involving monitoring EBV DNAemia and balancing treatment options, using a combination of reduction of immune suppression, anti-B cell therapy, and cytotoxic T lymphocytes (CTLs).
RECENT FINDINGS
The highest risk factor for the development of EBV PTLD in hematopoietic cell transplant (HCT) remains T cell depletion, with increasing use of antithymocyte globulin (ATG) or alemtuzumab in conditioning. In solid organ transplantation (SOT), the incidence of PTLD is highest among EBV seronegative recipients who are at risk for primary EBV infection following transplant in the first 12 months. Prevention is a critical component of the management of EBV PTLD. Although preemptive therapy remains standard of care, there continues to be heterogenicity and debate over the optimal choice of EBV DNA quantification and the threshold to use. Novel therapies such as donor-derived multipathogen and EBV specific CTLs for the prevention and third party CTLs for the treatment of EBV PTLD are promising, with rapidly expanding evidence, including large scale Phase III trials currently underway.
SUMMARY
With an increasing number of risk groups for developing EBV PTLD in HCT and SOT, management strategies using prophylaxis or preemptive therapy remain standard of care, however the use of prophylactic or preemptive EBV specific or multipathogen CTLs show promising results and safety profiles.
Topics: Epstein-Barr Virus Infections; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human; Humans; Lymphoproliferative Disorders; Organ Transplantation
PubMed: 34751183
DOI: 10.1097/QCO.0000000000000787 -
Pathologica Sep 2020The gastrointestinal tract (GI) is the primary site of lymphoproliferative lesions, spanning from reactive lymphoid hyperplasia to overt lymphoma. The diagnosis of these... (Review)
Review
The gastrointestinal tract (GI) is the primary site of lymphoproliferative lesions, spanning from reactive lymphoid hyperplasia to overt lymphoma. The diagnosis of these diseases is challenging and an integrated approach based on clinical, morphological, immunohistochemical and molecular data is needed. To reach to confident conclusions, a stepwise approach is highly recommended. Histological evaluation should first assess the benign neoplastic nature of a given lymphoid infiltrate. Morphological and phenotypic analyses should then be applied to get to a definite diagnosis. This review addresses the key histological features and diagnostic workup of the most common GI non-Hodgkin lymphomas (NHLs). Differential diagnoses and possible pitfalls are discussed by considering distinct groups of lesions ( small to medium B-cell NHLs; medium to large B-cell NHLs; T-cell NHLs; and mimickers of Hodgkin lymphoma). The key clinical and epidemiological features of each entity are also described.
Topics: Diagnosis, Differential; Gastrointestinal Neoplasms; Gastrointestinal Tract; Hodgkin Disease; Humans; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoproliferative Disorders
PubMed: 33179624
DOI: 10.32074/1591-951X-161 -
Acta Ophthalmologica Aug 2022The aim of this study is to describe the involvement of Epstein-Barr Virus (EBV) in the diseases of the ocular anterior segment. This is a narrative review designed... (Review)
Review
The aim of this study is to describe the involvement of Epstein-Barr Virus (EBV) in the diseases of the ocular anterior segment. This is a narrative review designed using the PUBMED, SCOPE and Web of Science databases, searching for reported literature on findings in the anterior ocular segment related to EBV between 1990 and 2020. Epstein-Barr Virus (EBV) is implicated in the development of salmon-coloured conjunctival masses in the context of acute mononucleosis and lymphoproliferative disorders. Moreover, EBV can cause haemorrhagic conjunctivitis and its corneal implications appear as different types of keratitis patterns. The involvement of EBV in the pathogenesis of anterior segment inflammation is not well-defined. Current evidence regarding anterior segment disease caused by EBV infection has been proved by positive viral detection through polymerase chain reaction test in eyes with lymphoproliferative disorders known to be caused by EBV, as B- and NK/T-cell lymphoid tumours. Antiviral treatment (oral Aciclovir or Valaciclovir) in anterior segment disease caused by EBV remains controversial.
Topics: Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Lymphoma; Lymphoproliferative Disorders
PubMed: 34766457
DOI: 10.1111/aos.15061 -
Blood Jun 2019
Topics: Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Hydroa Vacciniforme; Lymphoproliferative Disorders
PubMed: 31248873
DOI: 10.1182/blood.2019001031 -
Annales de Biologie Clinique Feb 2020Immunosuppression is a well known risk factor for the development of lymphoid pathologies. The classification of these neoplasias is becoming more precise and complex,... (Review)
Review
Immunosuppression is a well known risk factor for the development of lymphoid pathologies. The classification of these neoplasias is becoming more precise and complex, some features being common to all immunocompromised patients, primarily the important influence of Epstein-Barr virus. Whatever the origin of the immunodepression, these lymphoid proliferations are very heterogeneous, constituting a wide range between polymorphic aspects and clearly lymphomatous morphologies indistinguishable from those observed in immunocompetent subjects. It is important to detect precisely these different categories of proliferation within each group of immunosuppression, to better individualize the prognosis and the management of patients.
Topics: Cell Transformation, Viral; HIV; HIV Infections; Humans; Immunocompromised Host; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Lymphoma; Lymphoproliferative Disorders; Organ Transplantation; Transplantation Conditioning
PubMed: 32108583
DOI: 10.1684/abc.2020.1521