scholarly journals Demographics of PTLD Patients Who Died during 2010-2017 Period: A NCDB Based Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4998-4998
Author(s):  
Sai Giridhar Gundepalli ◽  
Hussain I Rangoonwala ◽  
Peter Silberstein
Keyword(s):  
T Cell ◽  
Epstein Barr Virus ◽  
Demographic Factors ◽  
Demographic Characteristics ◽  
Solid Organ ◽  
Median Income ◽  
Hematopoietic Stem ◽  
Vital Status ◽  
Barr Virus ◽  
Epstein Barr

Abstract Background: Post-transplant lymphoproliferative disease (PTLD) is a rare, but well-known complication of solid organ transplants and hematopoietic stem cell transplantation. . In most affected patients, PTLD is an Epstein-Barr virus (EBV)-positive B cell proliferation occurring in the setting of immunosuppression and decreased T cell immune surveillance. PTLDs are among the most serious complications of transplantation. The principal risk factors underlying the development of PTLD are the degree of T cell immunosuppression and the Epstein-Barr virus (EBV) serologic status of the recipient. Early lesions of PTLD are treated with reduction in immunosuppression alone and those who do not have a complete response to this intervention have been treated with chemotherapy, immunotherapy, and occasionally surgical resection. Utilizing the NCDB, we aim to study the clinical and demographic characteristics of PTLD patients who were declared dead during period of 2010-2017. Methods A total of 425 patients diagnosed with PTLD above the age of 18 years between 2010 and 2017 were identified utilizing the National Cancer Database (NCDB). Patients were identified with ICD-O-3 morphologic code 9971/3 and data extracted from PUF using SPSS. Demographic factors (Race, gender, facility location, annual household income, facility type, Charlson-Deyo score, treatment received, age at diagnosis) were studied in relation to patient's vital status (alive or dead). We have separated data for patients declared dead during this period and formulated a table stating the demographic characteristics. We have excluded people whose vital status was unknown or missing (60 patients). Results Of the 365 patients diagnosed with PTLD between 2010-2017, 215 patients were alive during the entire period and 150 (41%) were declared dead in this time frame. Of these, 62.7% were in the age group less than 60 years and 37.3% above 60 years. 9.3% (14/150) received no treatment at all and 88% received some form of treatment, of which 39.3% (59/150) received immunotherapy (34 received immunotherapy alone and 23 received Immuno+chemo). Amongst these, 80% were Caucasians and 13.4% were African Americans. 41.6% (57/137) belonged to median income quartile >=$63,333, whereas 16% (22/137) belonged to median quartile income <$40,227 (Median Quartiles 2012-2016). 83.2% received care at an academic/research program and 8.8% in a Comprehensive community cancer program. 64.7% (97/150) of patient's had Charlson-Deyo score of 0 whereas 14% (21/150) had a score of 3. Conclusion This study contains largest cohort of patients diagnosed with PTLD, identifying clinical and demographic factors of patients with PTLD who were declared dead during the period of 2010-2017. The data shows significant variations in the populations stratified based on age, income quartiles, treatment received and race. These data may provide insight into identifying the factors influencing mortality of patients diagnosed with PTLD. The major limitations of our study include no data on specific therapy received, reasons for choosing the treatment modality used, no data on the cause of mortality and age at death. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Management of post-transplant Epstein-Barr virus-related lymphoproliferative disease in solid organ and hematopoietic stem cell recipients

2014 ◽  
Vol 47 (5) ◽  
pp. 543-546 ◽  
Author(s):  
Heloisa Helena de Sousa Marques ◽  
Maria Aparecida Shikanai-Yasuda ◽  
Luiz Sérgio Fonseca de Azevedo ◽  
Hélio Helh Caiaffa-Filho ◽  
Lígia Camera Pierrotti ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Solid Organ ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals T-cell lymphoma with a granulomatous lesion of the lungs after autologous hematopoietic stem cell transplantation for Epstein–Barr virus-positive diffuse large B-cell lymphoma: a unique rare case of metachronous B-cell and T-cell lymphoma

2020 ◽  
Author(s):  
Yusuke Kajimoto ◽  
Yasuhiro Terasaki ◽  
Mika Terasaki ◽  
Shinobu Kunugi ◽  
Yugo Okabe ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Hematopoietic Stem ◽  
Barr Virus ◽  
Large B Cell Lymphoma ◽  
Epstein Barr

Abstract Background: Epstein–Barr virus (EBV) is associated with the pathogenesis of a variety of malignancies, most notably lymphomas. Especially in the background of immunodeficiency, such as primary immunodeficiency disorder (PID) and post-transplant lymphoproliferative disorder (PTLD), the role of EBV might be crucial. PIDs are rare heterogeneous diseases affecting the development and/or the function of the innate and adaptive immune system. Malignancy is the second-highest cause of death after infection, and lymphoma accounts for about half of malignancies. The most frequently reported lymphoma type is diffuse large B-cell lymphoma (DLBCL) and the incidence of T-cell lymphoma is rare. PTLDs are also rare serious lymphoid and/or plasmacytic proliferation disorders that occur after undergoing solid organ or hematopoietic stem cell transplantation (HSCT). In the context of HSCT, most reported PTLDs have occurred in patients who received allogenic HSCT, but only a few cases have been reported in autologous HSCT (AutoHSCT) recipients.Case presentation: A 53-year-old female patient initially presented with enlargement of the left cervical lymph nodes and was diagnosed with EBV-positive DLBCL. She was treated with R-CHOP, R-ACES, and AutoHSCT and went into remission. Four years later, computed tomography results revealed multiple lung nodules and abnormal infiltration, and sustained and progressing hypogammaglobulinemia was observed. The pathological specimen of video-assisted thoracoscopic surgical lung biopsy demonstrated extensive invasion of lymphocytes with notable granuloma findings. Flow cytometric immunophenotyping analysis showed that lymphocytes were positive for CD3 and CD5; especially, CD3 was expressed in the cytoplasm. Southern blot analysis revealed rearrangements of the T-cell receptor Cb1 gene. She was diagnosed with peripheral T-cell lymphoma, not otherwise specified, accompanied by notable granulomatous lesions.Conclusion: Here, as a unique case of metachronous B-cell and T-cell lymphoma, we report a rare case of T-cell lymphoma that mainly affected the lungs with the presentation of notable granulomatous findings following AutoHSCT for EBV-positive DLBCL at the age of 53 years. These lung lesions of granulomatous T-cell lymphoma could be related to the underlying primary immunodeficiency background associated with sustained hypogammaglobulinemia.

scholarly journals Analysis of Post-Transplant Lymphoproliferative Disorder (PTLD) Outcomes with Epstein–Barr Virus (EBV) Assessments—A Single Tertiary Referral Center Experience and Review of Literature

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 899
Author(s):  
Eric Lau ◽  
Justin Tyler Moyers ◽  
Billy Chen Wang ◽  
Il Seok Daniel Jeong ◽  
Joanne Lee ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Allogeneic Bone ◽  
Hematopoietic Stem ◽  
Tertiary Referral Center ◽  
Post Transplant ◽  
Barr Virus ◽  
Significant Difference ◽  
Epstein Barr

Post-transplant lymphoproliferative disorders (PTLDs) are lymphoid or plasmacytic proliferations ranging from polyclonal reactive proliferations to overt lymphomas that develop as consequence of immunosuppression in recipients of solid organ transplantation (SOT) or allogeneic bone marrow/hematopoietic stem cell transplantation. Immunosuppression and Epstein–Barr virus (EBV) infection are known risk factors for PTLD. Patients with documented histopathologic diagnosis of primary PTLD at our institution between January 2000 and October 2019 were studied. Sixty-six patients with PTLD following SOT were followed for a median of 9.0 years. The overall median time from transplant to PTLD diagnosis was 5.5 years, with infant transplants showing the longest time to diagnosis at 12.0 years, compared to pediatric and adolescent transplants at 4.0 years and adult transplants at 4.5 years. The median overall survival (OS) was 19.0 years. In the monomorphic diffuse large B-cell (M-DLBCL-PTLD) subtype, median OS was 10.7 years, while median OS for polymorphic subtype was not yet reached. There was no significant difference in OS in patients with M-DLBCL-PTLD stratified by quantitative EBV viral load over and under 100,000 copies/mL at time of diagnosis, although there was a trend towards worse prognosis in those with higher copies.

Skewed TCR Repertoire of Vδ1+ γδT Cells in Recipients of Allogeneic Hematopoietic Stem Cell Grafts and Possible Involvement of Epstein-Barr Virus in Clonal Expansion of Vδ1+ T Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2230-2230
Author(s):  
Masumi Fujishima ◽  
Makoto Hirokawa ◽  
Naohito Fujishima ◽  
Hirobumi Saitoh ◽  
Yoshikazu Ichikawa ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Clinical Outcome ◽  
Epstein Barr Virus ◽  
Clonal Expansion ◽  
Hematopoietic Stem ◽  
Barr Virus ◽  
Cdr3 Region ◽  
Epstein Barr

Abstract Background: We previously demonstrated that stable clonal expansion of Vδ1+ γδT lymphocytes persisted for several years after human allogeneic hematopoietic stem cell transplantation (allo-HSCT). These Vδ1+ T cells are derived from mature T cells in the graft. In the present study, we have extended our observation to learn whether oligoclonal expansions of Vδ1+ γδT lymphocytes might be associated with clinical outcome and GVHD, and whether consensus sequences of the CDR3 region of clonally expanded Vδ1+ T cells would be observed among different individuals. We also examined the possible role for Epstein-Barr virus (EBV) in clonal expansion of Vδ1+ T cells. Methods: Forty-two patients receiving allo-HSCT for hematological malignancies were included in this study. Grafts included bone marrow (n=33), G-CSF mobilized peripheral blood stem cells (n=7) and cord blood (n=2). Clonality of the Vδ1+ T cell subset was determined by CDR3 size spectratyping analysis. Junctional sequences were determined by DNA sequencing. In some experiments, PBMCs from healthy volunteer donors were stimulated with autologous EBV-LCL and were analyzed for clonality of TCRs. Results: CDR3 size spectratyping analysis revealed that twenty-three out of forty-two patients had highly skewed TCR repertoires of the Vδ1+ T cells. There was no apparent association between the oligoclonality of Vδ1+ TCRs and clinical outcome such as GVHD and leukemia relapse. In eight out of seventeen patients examined, the -WGI- amino acid sequence was observed in the CDR3 region of TCRs of clonally expanded Vδ1+ T cells. The -YWG- sequence was observed in four patients. All recipients examined were serologically positive for EBV-VCA IgG and EBNA. Bacterial or fungal components failed to stimulate Vδ1+ T cells to proliferate in vitro, but autologous EBV transformed B cells could induce the expansion of Vδ1+ T cells. The CDR3 size distribution patterns of Vδ1+ TCRs became skewed after stimulation with autologous EBV-LCL, and the T cell clone with the -LEEYWGLPH- CDR3 sequence predominated in the culture with autologous EBV-LCL, whereas this clone was not detectable before culture. Moreover, allogeneic EBV-positive Raji cells also induced the oligoclonal expansion of Vδ1+ T cells carrying the -WGI- or -YWG- junctional sequence. These results suggest the CDR3 structure may contribute to recognition of EBV-associated antigens by Vδ1+ T cells Conclusion: Skewing of the Vδ1+ TCR after allo-HSCT may be the result of the response to infectious antigens widely existing in humans such as EBV. Table 1. Junctional diversity of Vδ1 TCR of γδ T cells expanded in response to autologous EBV-LCL and allogeneic Burkitt lymphoma cells Stimulation δV1 N-D-N Jδ Colony frequency T cell clones appearing more than once are presented. Nil CALGE GLPHALIMWGDLAY TDKLIFGKG 3/20 EBV-LCL CALGE LEEYWGLPH TDKLIFGKG 10/27 CALGE GLPHALIMWGDLAY TDKLIFGKG 7/27 CALG GVLYWGIRR TDKLIFGKG 2/27 CALGE SLWGIRY TDKLIFGKG 2/27 CALGE LGETTPLLGGYSFA LTAQLFFGKG 2/27 Raji CALG VSGLARGGSL KLIFGKG 6/25 CALGE ADWGIRARILY TDKLIFGKG 4/25 CALGE PRAILGDTRIKRMY TDKLIFGKG 4/25 CALGE LEEYWGLPH TDKLIFGKG 3/25 CALGE DPGLPFLWY TDKLIFGKG 2/25 CALG DLNLLWGIRSILPG TDKLIFGKG 2/25

scholarly journals T-cell lymphoma with a granulomatous lesion of the lungs after autologous hematopoietic stem cell transplantation for Epstein–Barr virus-positive diffuse large B-cell lymphoma: a unique rare case of metachronous B-cell and T-cell lymphoma

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Yusuke Kajimoto ◽  
Yasuhiro Terasaki ◽  
Mika Terasaki ◽  
Shinobu Kunugi ◽  
Yugo Okabe ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Hematopoietic Stem ◽  
Barr Virus ◽  
Large B Cell Lymphoma ◽  
Epstein Barr

Abstract Background Epstein–Barr virus (EBV) is associated with the pathogenesis of a variety of malignancies, most notably lymphomas. Especially in the background of immunodeficiency, such as primary immunodeficiency disorder (PID) and post-transplant lymphoproliferative disorder (PTLD), the role of EBV might be crucial. PIDs are rare heterogeneous diseases affecting the development and/or the function of the innate and adaptive immune system. Malignancy is the second-highest cause of death after infection, and lymphoma accounts for about half of malignancies. The most frequently reported lymphoma type is diffuse large B-cell lymphoma (DLBCL) and the incidence of T-cell lymphoma is rare. PTLDs are also rare serious lymphoid and/or plasmacytic proliferative disorders that occur after undergoing solid organ or hematopoietic stem cell transplantation (HSCT). In the context of HSCT, most reported PTLDs have occurred in patients who received allogenic HSCT, but only a few cases have been reported in autologous HSCT (AutoHSCT) recipients. Case presentation A 53-year-old female patient initially presented with enlargement of the left cervical lymph nodes and was diagnosed with EBV-positive DLBCL. She was treated with R-CHOP, R-ACES, and AutoHSCT and went into remission. Four years later, computed tomography results revealed multiple lung nodules and abnormal infiltration, and sustained and progressing hypogammaglobulinemia was observed. The pathological specimen of video-assisted thoracoscopic surgical lung biopsy demonstrated extensive invasion of lymphocytes with notable granuloma findings. Flow cytometric immunophenotyping analysis showed that lymphocytes were positive for CD3 and CD5; especially, CD3 was expressed in the cytoplasm. Southern blot analysis revealed rearrangements of the T-cell receptor Cβ1 gene. She was diagnosed with peripheral T-cell lymphoma, not otherwise specified, accompanied by notable granulomatous lesions. Conclusion Here, as a unique case of metachronous B-cell and T-cell lymphoma, we report a rare case of T-cell lymphoma that mainly affected the lungs with the presentation of notable granulomatous findings following AutoHSCT for EBV-positive DLBCL at the age of 53 years. These lung lesions of granulomatous T-cell lymphoma could be related to the underlying primary immunodeficiency background associated with sustained hypogammaglobulinemia.

scholarly journals The Epstein-Barr Virus Major Tegument Protein BNRF1 Is a Common Target of Cytotoxic CD4+ T Cells

2020 ◽  
Vol 94 (15) ◽  
Author(s):  
Dinesh Adhikary ◽  
Julia Damaschke ◽  
Josef Mautner ◽  
Uta Behrends
Keyword(s):  
T Cells ◽  
T Cell ◽  
Epstein Barr Virus ◽  
Response Rates ◽  
T Cell Response ◽  
Tegument Protein ◽  
Hematopoietic Stem ◽  
Barr Virus ◽  
Health And Disease ◽  
Epstein Barr

ABSTRACT Cellular immunotherapy is a proven approach against Epstein-Barr virus (EBV)-driven lymphoproliferation in recipients of hematopoietic stem cells. Extending the applicability and improving the response rates of such therapy demands improving the knowledge base. We studied 23 healthy donors for specific CD4+ T cell responses against the viral tegument protein BNRF1 and found such T cells in all seropositive donors, establishing BNRF1 as an important immune target in EBV. We identified 18 novel immune epitopes from BNRF1, all of them generated by natural processing of the full-length protein from virus-transformed lymphoblastoid cell lines (LCL). BNRF1-specific CD4+ T cells were measured directly ex vivo by a cytokine-based method, thus providing a tool to study the interaction between immunity and infection in health and disease. T cells of the cytotoxic Th1 type inhibited the proliferation of autologous LCL as well as virus-driven transformation. We infer that they are important in limiting reactivations to subclinical levels during health and reducing virus propagation during disease. The information obtained from this work will feed into data sets that are indispensable in the design of patient-tailored immunotherapeutic approaches, thereby enabling the stride toward broader application of T cell therapy and improving clinical response rates. IMPORTANCE Epstein-Barr virus is carried by most humans and can cause life-threatening diseases. Virus-specific T cells have been used in different clinical settings with variable success rates. One way to improve immunotherapy is to better suit T cell generation protocols to viral targets available in different diseases. BNRF1 is present in viral particles and therefore likely available as a target for T cells in diseases with virus amplification. Here, we studied healthy Epstein-Barr virus (EBV) carriers for BNRF1 immunogenicity and report our results indicating BNRF1 to be a dominant target of the EBV-specific CD4+ T cell response. BNRF1-specific CD4+ T cells were found to be cytotoxic and capable of limiting EBV-driven B cell transformation in vitro. The findings of this work contribute to forwarding our understanding of host-virus interactions during health and disease and are expected to find direct application in the generation of specific T cells for immunotherapy.

scholarly journals How I treat T-cell chronic active Epstein-Barr virus disease

Blood ◽  
2018 ◽  
Vol 131 (26) ◽  
pp. 2899-2905 ◽  
Author(s):  
Catherine M. Bollard ◽  
Jeffrey I. Cohen
Keyword(s):  
T Cells ◽  
T Cell ◽  
Epstein Barr Virus ◽  
Histone Deacetylase Inhibitors ◽  
Virus Disease ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Curative Therapy ◽  
Barr Virus ◽  
Epstein Barr

Abstract T-cell chronic active Epstein-Barr virus (CAEBV) is a rare disease in which EBV is present predominantly in T cells that infiltrate the tissues; patients have high levels of EBV in the blood. If untreated, patients often develop liver failure, hemophagocytic lymphohistiocytosis, coronary artery aneurysms, EBV infiltrating T cells impairing organ function, or T-cell lymphomas refractory to treatment. At present, hematopoietic stem-cell transplantation is the only curative therapy, and it is critical to make a proper diagnosis and initiate transplantation before the disease progresses to an irreversible stage. Specific medications such as high-dose systemic corticosteroids or ganciclovir combined with either histone deacetylase inhibitors or bortezomib may temporarily reduce systemic toxicity associated with T-cell CAEBV and allow the patient time to receive a transplant. Relapses of the disease after transplantation have also occurred, and the use of donor-derived virus-specific T cells may help to treat these relapses.

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