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European Journal of Haematology Oct 2022Posttransplant lymphoproliferative disorder (PTLD) in solid organ transplant recipients has a high mortality and may present early (<2 years) or late (≥2 years)...
OBJECTIVES
Posttransplant lymphoproliferative disorder (PTLD) in solid organ transplant recipients has a high mortality and may present early (<2 years) or late (≥2 years) posttransplantation. We investigated the clinical characteristics of early and late PTLD among kidney and liver transplant recipients.
METHODS
Recipients, transplanted at Rigshospitalet, with PTLD development as adults from January 2010 to August 2020, were included. Clinical characteristics, laboratory parameters, and pathology of early and late PTLD were compared.
RESULTS
Thirty-one PTLD cases were detected where 10 (32%) were early and 21 (68%) were late PTLD. EBV DNA in plasma was detected in 78% versus 28% in early and late PTLD (p = .037). None of the recipients with early PTLD and nine recipients with late PTLD (47%) had Ann Arbor stage IV at the time of their diagnosis (p = .006). Cyclophosphamid-Hydroxyrubicin-Oncovin-Prednisolon was used for treatment in 10 (48%) recipients with late PTLD (p = 0.032) only. There was no difference in mortality between the two groups.
CONCLUSIONS
Recipients with late PTLD had a lower prevalence of detectable EBV DNA in plasma, were diagnosed with more advanced disease, and were more frequently treated with chemotherapy compared to recipients with early PTLD.
Topics: Adult; Epstein-Barr Virus Infections; Humans; Incidence; Kidney; Liver Transplantation; Lymphoproliferative Disorders; Retrospective Studies; Risk Factors; Transplant Recipients
PubMed: 35719018
DOI: 10.1111/ejh.13815 -
British Journal of Haematology Feb 2021The application of therapeutic T cells for a number of conditions has been developed over the past few decades with notable successes including donor lymphocyte... (Review)
Review
The application of therapeutic T cells for a number of conditions has been developed over the past few decades with notable successes including donor lymphocyte infusions, virus-specific T cells and more recently CAR-T cell therapy. Primary immunodeficiencies are monogenetic disorders leading to abnormal development or function of the immune system. Haematopoietic stem cell transplantation and, in specific candidate diseases, haematopoietic stem cell gene therapy has been the only definitive treatment option so far. However, autologous gene-modified T cell therapy may offer a potential cure in conditions primarily affecting the lymphoid compartment. In this review we will highlight several T cell gene addition or gene-editing approaches in different target diseases with a focus on what we have learnt from clinical experience and promising preclinical studies in primary immunodeficiencies. Functional T cells are required not only for normal immune responses to infection (affected in CD40 ligand deficiency), but also for immune regulation [disrupted in IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-Linked) due to dysfunctional FOXP3 and CTLA4 deficiency] or cytotoxicity [defective in X-lymphoproliferative disease and familial haemophagocytic lymphohistiocytosis (HLH) syndromes]. In all these candidate diseases, restoration of T cell function by gene therapy could be of great value.
Topics: Animals; Diabetes Mellitus, Type 1; Diarrhea; Gene Editing; Genetic Diseases, X-Linked; Genetic Therapy; Hematopoietic Stem Cell Transplantation; Humans; Immune System Diseases; Immunotherapy, Adoptive; Lymphohistiocytosis, Hemophagocytic; Lymphoproliferative Disorders; T-Lymphocytes
PubMed: 33280098
DOI: 10.1111/bjh.17070 -
Current Oncology (Toronto, Ont.) Apr 2023Multiple myeloma (MM) is a malignant clonal plasma cell disorder in the bone marrow and is the second-most common hematologic malignancy in adults. Although patients... (Review)
Review
Multiple myeloma (MM) is a malignant clonal plasma cell disorder in the bone marrow and is the second-most common hematologic malignancy in adults. Although patients with MM have a moderate life expectancy, it remains a heterogeneous disease that often requires multiple lines of chemotherapy for durable control and long-term survival. This review outlines current management strategies for both transplant-eligible and transplant-ineligible patients as well as for relapsed and refractory disease. Advances in drug therapies have widened management options and improved survival. In this paper, we also discuss implications for special populations and survivorship care.
Topics: Adult; Humans; Multiple Myeloma; General Practitioners; Hematologic Neoplasms
PubMed: 37232792
DOI: 10.3390/curroncol30050334 -
Cancers Jun 2021iTLPD-GI is a low-grade clonal T-cell lymphoproliferative disease arising in GI organs. It is an uncommon disease, and only recently has it been enlisted as a distinct... (Review)
Review
iTLPD-GI is a low-grade clonal T-cell lymphoproliferative disease arising in GI organs. It is an uncommon disease, and only recently has it been enlisted as a distinct provisional entity in the current WHO Classification. Data from the literature disclose high heterogeneity in terms of pathological and molecular features; on the other hand, establishing an accurate diagnosis of iTLPD-GI is of pivotal importance, since treatment options are different from that of other, more frequent lymphomas that arise in the gastrointestinal tract. In this review, we aimed to better define this novel entity, and to identify useful diagnostic biomarkers; moreover, we provide a biomarker-based approach to the diagnosis and describe the most common issues in differentiating iTLPD-GI from other neoplastic and non-neoplastic disorders.
PubMed: 34205136
DOI: 10.3390/cancers13112790 -
JAMA Dermatology Oct 2022There is a knowledge gap about subcutaneous panniculitis-like T-cell lymphoma (SPTCL) owing to its rarity and diagnostic difficulty, resulting in an absence of...
Clinical and Pathological Characteristics and Outcomes Among Patients With Subcutaneous Panniculitis-like T-Cell Lymphoma and Related Adipotropic Lymphoproliferative Disorders.
IMPORTANCE
There is a knowledge gap about subcutaneous panniculitis-like T-cell lymphoma (SPTCL) owing to its rarity and diagnostic difficulty, resulting in an absence of well-documented large case series published to date.
OBJECTIVE
To generate consensus knowledge by a joint multi-institutional review of SPTCL and related conditions.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective clinical and pathological review included cases initially diagnosed as SPTCL at 6 large US academic centers. All cases were reviewed by a group of pathologists, dermatologists, and oncologists with expertise in cutaneous lymphomas. Through a process of group consensus applying defined clinical and pathological diagnostic criteria, the cohort was classified as (1) SPTCL or (2) adipotropic lymphoproliferative disorder (ALPD) for similar cases with incomplete histopathological criteria for SPTCL designation.
EXPOSURES
Cases of SPTCL diagnosed between 1998 and 2018.
MAIN OUTCOMES AND MEASURES
The main outcome was disease presentation and evolution, including response to therapy, disease progression, and development of hemophagocytic lymphohistiocytosis.
RESULTS
The cohort of 95 patients (median [range] age, 38 [2-81] years; female-to-male ratio, 2.7) included 75 cases of SPTCL and 20 cases of ALPD. The clinical presentation was similar for both groups with multiple (61 of 72 [85%]) or single (11 of 72 [15%]) tender nodules mostly involving extremities, occasionally resulting in lipoatrophy. Hemophagocytic lymphohistiocytosis (HLH) was only observed in SPTCL cases. With a mean follow-up of 56 months, 60 of 90 patients (67%) achieved complete remission with a median (range) of 3 (1-7) cumulative therapies. Relapse was common. None of the patients died of disease progression or HLH. Two patients with ALPD eventually progressed to SPTCL without associated systemic symptoms or HLH.
CONCLUSIONS AND RELEVANCE
In this case series of patients initially diagnosed as having SPTCL, results showed no evidence of systemic tumoral progression beyond the adipose tissue. The SPTCL experience in this study confirmed an indolent course and favorable response to a variety of treatments ranging from immune modulation to chemotherapy followed by hematopoietic stem cell transplantation. Morbidity was primarily associated with HLH.
Topics: Humans; Male; Female; Adult; Lymphohistiocytosis, Hemophagocytic; Retrospective Studies; Neoplasm Recurrence, Local; Panniculitis; Lymphoma, T-Cell; Disease Progression
PubMed: 36001337
DOI: 10.1001/jamadermatol.2022.3347 -
Cancer Science Sep 2023Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a troublesome problem in patients receiving MTX for rheumatoid arthritis (RA). However, its...
Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a troublesome problem in patients receiving MTX for rheumatoid arthritis (RA). However, its incidence, prognosis, and risk factors remain unclear. In this retrospective study, we evaluated the actual incidence, prognostic impact, and risk factors of MTX-LPD. Of the 986 patients with RA treated with MTX, 90 patients experienced 95 new malignancies (NMs), with LPD as the most frequent in 26 patients. The cumulative LPD incidences were 1.3% and 4.7% at 5 and 10 years after MTX initiation, respectively. Among the 24 patients who discontinued MTX after developing LPD, 15 showed sustained regression, without difference in overall survival between patients with LPD and without NM. Inflammatory markers and absolute lymphocyte counts were not useful for early LPD development detection, but most of the patients with LPD had persistently elevated erythrocyte sedimentation ratios. Regarding concomitant drugs, tacrolimus increased the risk only if patients were not receiving biological disease-modifying antirheumatic drugs (bDMARDs). bDMARDs did not increase the risk for any of the drugs or the number of classes used. The number of LPD cases was lower in patients with IL-6A even after a long period after MTX, although with no statistically significant difference. Thus, approximately 1 in 20 patients with RA developed MTX-LPD over the 10 years of MTX treatment, but it did not affect the survival of patients with RA. Tacrolimus increased the risk of developing LPD for certain patients and should be used with caution.
Topics: Humans; Methotrexate; Retrospective Studies; Tacrolimus; Arthritis, Rheumatoid; Antirheumatic Agents; Lymphoproliferative Disorders
PubMed: 37365854
DOI: 10.1111/cas.15894 -
Cancer Medicine Oct 2021Epstein-Barr virus (EBV) is detected in a variety of B-cell lymphomas (BCLs) and B-cell lymphoproliferative disorders (B-LPDs). Immunodeficiency has been considered to... (Review)
Review
BACKGROUND
Epstein-Barr virus (EBV) is detected in a variety of B-cell lymphomas (BCLs) and B-cell lymphoproliferative disorders (B-LPDs). Immunodeficiency has been considered to play a key role in the pathogenesis of these diseases. In addition, immune escape of tumor cells may also contribute to the development of EBV BCLs and B-LPDs. The PD-1/PD-L1 pathway is particularly important for immune escape of tumor cells that contribute to development of lymphoma through suppression of cytotoxic T-cell function. We now consider PD-L1 immunohistochemistry (IHC) a very useful method for predicting whether tumor cells of lymphoid malignancies are characterized by the immune escape mechanism.
METHODS
We reviewed articles of EBV BCLs and B-LPDs from the perspective of immune escape and immunodeficiency, particularly focusing on PD-L1 IHC.
RESULTS
Based on PD-L1 IHC, we consider that EBV BCL and B-LPD can be classified into three types: "immunodeficiency", "immune escape", and "immunodeficiency + immune escape" type. The immunodeficiency type includes EBV diffuse large BCL (DLBCL) of the elderly, EBV sporadic Burkitt lymphoma, EBV mucocutaneous ulcer, and methotrexate (MTX)-associated B-LPD. The immune escape type includes EBV classic Hodgkin lymphoma (CHL) and EBV DLBCL of the young. The immunodeficiency + immune escape type includes CHL type MTX-associated LPD and a minor subset of EBV DLBCL of the elderly.
CONCLUSIONS
Recently, good results have been reported for immune check-point inhibitors in treating lymphoma. Lymphomas and LPDs characterized by immune escape are regarded as good candidates for PD1/PD-L1 blockade therapy. Therefore, from both the clinical and pathological perspective, we suggest that lymphoma diagnosis should be made considering immune escape and immunodeficiency.
Topics: Female; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoproliferative Disorders; Male; Middle Aged; Primary Immunodeficiency Diseases; Tumor Escape
PubMed: 34387382
DOI: 10.1002/cam4.4198 -
The Journal of Dermatology Sep 2021Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a rare cutaneous disease associated with Epstein-Barr virus infection. We retrospectively analyzed the...
Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a rare cutaneous disease associated with Epstein-Barr virus infection. We retrospectively analyzed the clinical presentation, histopathological characteristics, and prognostic study of HV-LPD in 24 Chinese patients. All patients presented with recurrent papulovesicular and necrotic eruptions on the face, neck, and extremities, with 11 showing systemic symptoms. Twenty patients were diagnosed with HV-LPD in childhood (age < 18 years) and four in adulthood (age ≥ 18 years). The median age at diagnosis was 8.5 years old (range, 2-50). Histopathology revealed variably dense lymphocyte infiltration throughout the dermis. All cases were strongly positive for CD3 and Epstein-Barr encoding region based on in situ hybridization. Of 18 cases with a T-cell phenotype, 15 harbored monoclonal rearrangements in T-cell receptor (TCR) genes. Four cases with a natural killer cell phenotype carried polyclonal rearrangements in TCR genes. Among 24 patients, eight (33.3%) received chemotherapy, two (8.3%) allogeneic hematopoietic stem cell transplantation, and both are currently alive without disease. The median follow-up period was 24 months (range, 7-120) and 23 patients were available: 15 (62.5%) were alive, and eight (33.3%) had died. Fourteen cases had a relapse of disease and three developed lymphoma within 24 months of diagnosis. The mean survival time of childhood-onset patients was longer than that of adult-onset patients (36.4 vs. 20.8 months). In summary, the wide clinical course and representative presentation of cases in our center reflect the pedigree characteristics of HV-LPD. Allogeneic hematopoietic stem cell transplantation should be a preferred choice for relapse and refractory patients due to the poor effect of chemotherapy. Adult-onset and high serum EBV DNA loads may indicate an increased risk of aggressive disease in patients with HV-LPD.
Topics: Adolescent; Adult; Child; China; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Hydroa Vacciniforme; Lymphoma; Lymphoproliferative Disorders; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies
PubMed: 33982815
DOI: 10.1111/1346-8138.15944 -
Frontiers in Immunology 2021Epstein-Barr virus (EBV) is a human herpesvirus that is common among the global population, causing an enormous disease burden. EBV can directly cause infectious... (Review)
Review
Epstein-Barr virus (EBV) is a human herpesvirus that is common among the global population, causing an enormous disease burden. EBV can directly cause infectious mononucleosis and is also associated with various malignancies and autoimmune diseases. In order to prevent primary infection and subsequent chronic disease, efforts have been made to develop a prophylactic vaccine against EBV in recent years, but there is still no vaccine in clinical use. The outbreak of the COVID-19 pandemic and the global cooperation in vaccine development against SARS-CoV-2 provide insights for next-generation antiviral vaccine design and opportunities for developing an effective prophylactic EBV vaccine. With improvements in antigen selection, vaccine platforms, formulation and evaluation systems, novel vaccines against EBV are expected to elicit dual protection against infection of both B lymphocytes and epithelial cells. This would provide sustainable immunity against EBV-associated malignancies, finally enabling the control of worldwide EBV infection and management of EBV-associated diseases.
Topics: Animals; COVID-19; COVID-19 Vaccines; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Lymphoproliferative Disorders; Pre-Exposure Prophylaxis; SARS-CoV-2; Viral Vaccines
PubMed: 34168649
DOI: 10.3389/fimmu.2021.677027 -
Current Oncology (Toronto, Ont.) Nov 2021Primary splenic lymphoma (PSL) is a rare malignancy representing about 1% of all lymphoproliferative disorders, when using a strict definition that allows only... (Review)
Review
Primary splenic lymphoma (PSL) is a rare malignancy representing about 1% of all lymphoproliferative disorders, when using a strict definition that allows only involvement of spleen and hilar lymph nodes. In contrast, secondary low-grade B-cell lymphomas in the spleen, such as follicular lymphomas (FL), lymphoplasmacytic lymphoma and chronic lymphocytic leukemia/ small lymphocytic lymphoma, particularly as part of advanced stage disease, are more common. Indolent B cell lymphomas expressing CD10 almost always represent FL, which in its primary splenic form is the focus of this review. Primary splenic follicular lymphoma (PSFL) is exceedingly infrequent. This type of lymphoproliferative disorder is understudied and, in most cases, clinically characterized by splenomegaly or cytopenias related to hypersplenism. The diagnosis requires correlation of histopathology of spleen, blood and/or bone marrow with the correct immunophenotype (determined by flow cytometry and/or immunohistochemistry) and if necessary, additional molecular profiling. Management of this incurable disease is evolving, and splenectomy remains the mainstream treatment for stage I PSFL.
Topics: Humans; Immunohistochemistry; Immunophenotyping; Lymphoma, B-Cell; Lymphoma, Follicular; Spleen
PubMed: 34898578
DOI: 10.3390/curroncol28060407