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1
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Chen Y, Chen Y, He Y, Mu Q, Ouyang G. A Rare Case of Post-Transplant Lymphoproliferative Disorder Presenting as Hodgkin Lymphoma After Autologous Hematopoietic Stem Cell Transplantation: A Case Report and Literature Review. Onco Targets Ther 2025; 18:27-33. [PMID: 39830922 PMCID: PMC11742566 DOI: 10.2147/ott.s490591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 01/06/2025] [Indexed: 01/22/2025] Open
Abstract
Post-transplant lymphoproliferative disorder (PTLD) is a rare complication following hematopoietic stem cell transplantation (HSCT), with its occurrence post-autologous hematopoietic stem cell transplantation (auto-HSCT) being even rarer. Research on PTLD following auto-HSCT is exceedingly scarce. Here, we present a noteworthy instance wherein a patient with diffuse large B-cell lymphoma (DLBCL) developed PTLD, manifesting as classical Hodgkin lymphoma (cHL) two years after auto-HSCT. Additionally, we conducted an extensive review of existing literature, exploring the current research on PTLD following auto-HSCT and illuminating this scarcely examined area.
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Affiliation(s)
- Yuzhan Chen
- Department of Hematology, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, People’s Republic of China
- Health Science Center, Ningbo University, Ningbo, 315000, People’s Republic of China
| | - Ying Chen
- Laboratory of Stem Cell Transplantation, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, People’s Republic of China
| | - Yimin He
- Department of Radiology, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, People’s Republic of China
| | - Qitian Mu
- Laboratory of Stem Cell Transplantation, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, People’s Republic of China
| | - Guifang Ouyang
- Department of Hematology, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, People’s Republic of China
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2
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Carbone A, Chadburn A, Gloghini A, Vaccher E, Bower M. Immune deficiency/dysregulation -associated lymphoproliferative disorders. Revised classification and management. Blood Rev 2024; 64:101167. [PMID: 38195294 DOI: 10.1016/j.blre.2023.101167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 12/13/2023] [Accepted: 12/30/2023] [Indexed: 01/11/2024]
Abstract
Significant advances in the field of lymphoma have resulted in two recent classification proposals, the International Consensus Classification (ICC) and the 5th edition WHO. A few entities are categorized differently in the ICC compared to the WHO. Nowhere is this more apparent than the immunodeficiency lymphoproliferative disorders. The three previous versions of the WHO classification (3rd, 4th and revised 4th editions) and the ICC focused on four clinical settings in which these lesions arise for primary categorization. In contrast the 2023 WHO 5th edition includes pathologic characteristics including morphology and viral status, in addition to clinical setting, as important information for lesion classification. In addition, the 2023 WHO recognizes a broader number of clinical scenarios in which these lesions arise, including not only traditional types of immune deficiency but also immune dysregulation. With this classification it is hoped that new treatment strategies will be developed leading to better patient outcomes.
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Affiliation(s)
- Antonino Carbone
- Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico, National Cancer Institute, Aviano, Italy.
| | - Amy Chadburn
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States of America.
| | - Annunziata Gloghini
- Department of Advanced Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
| | - Emanuela Vaccher
- Infectious Diseases and Tumors Unit, Department of Medical Oncology, Centro di Riferimento Oncologico (CRO), IRCCS, National Cancer Institute, Aviano, Italy.
| | - Mark Bower
- Department of Oncology and National Centre for HIV Malignancy, Chelsea & Westminster Hospital, London SW109NH, UK.
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3
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Shahid S, Prockop SE. Epstein-Barr virus-associated post-transplant lymphoproliferative disorders: beyond chemotherapy treatment. CANCER DRUG RESISTANCE (ALHAMBRA, CALIF.) 2021; 4:646-664. [PMID: 34485854 PMCID: PMC8415721 DOI: 10.20517/cdr.2021.34] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 05/10/2021] [Accepted: 05/19/2021] [Indexed: 12/30/2022]
Abstract
Post-transplant lymphoproliferative disorder (PTLD) is a rare but life-threatening complication of both allogeneic solid organ (SOT) and hematopoietic cell transplantation (HCT). The histology of PTLD ranges from benign polyclonal lymphoproliferation to a lesion indistinguishable from classic monoclonal lymphoma. Most commonly, PTLDs are Epstein-Barr virus (EBV) positive and result from loss of immune surveillance over EBV. Treatment for PTLD differs from the treatment for typical non-Hodgkin lymphoma because prognostic factors are different, resistance to treatment is unique, and there are specific concerns for organ toxicity. While recipients of HCT have a limited time during which they are at risk for this complication, recipients of SOT have a lifelong requirement for immunosuppression, so approaches that limit compromising or help restore immune surveillance are of high interest. Furthermore, while EBV-positive and EBV-negative PTLDs are not intrinsically resistant to chemotherapy, the poor tolerance of chemotherapy in the post-transplant setting makes it essential to minimize potential treatment-related toxicities and explore alternative treatment algorithms. Therefore, reduced-toxicity approaches such as single-agent CD20 monoclonal antibodies or bortezomib, reduced dosing of standard chemotherapeutic agents, and non-chemotherapy-based approaches such as cytotoxic T cells have all been explored. Here, we review the chemotherapy and non-chemotherapy treatment landscape for PTLD.
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Affiliation(s)
| | - Susan E. Prockop
- Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
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4
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Shah N, Eyre TA, Tucker D, Kassam S, Parmar J, Featherstone C, Andrews P, Asgari E, Chaganti S, Menne TF, Fox CP, Pettit S, Suddle A, Bowles KM. Front-line management of post-transplantation lymphoproliferative disorder in adult solid organ recipient patients - A British Society for Haematology Guideline. Br J Haematol 2021; 193:727-740. [PMID: 33877688 DOI: 10.1111/bjh.17421] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Nimish Shah
- Norfolk & Norwich University Hospitals NHS Foundation Trust, Norwich, UK
| | - Toby A Eyre
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | | | - Shireen Kassam
- King's College Hospital NHS Foundation Trust, London, UK
| | - Jasvir Parmar
- Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK
| | | | - Peter Andrews
- Epsom and St Helier University Hospitals NHS Trust, Surrey, UK
| | - Elham Asgari
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | | | - Tobias F Menne
- The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
| | | | - Stephen Pettit
- Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK
| | - Abid Suddle
- King's College Hospital NHS Foundation Trust, London, UK
| | - Kristian M Bowles
- Norfolk & Norwich University Hospitals NHS Foundation Trust, Norwich, UK
- Norwich Medical School, University of East Anglia, Norwich, UK
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5
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Sprangers B, Riella LV, Dierickx D. Posttransplant Lymphoproliferative Disorder Following Kidney Transplantation: A Review. Am J Kidney Dis 2021; 78:272-281. [PMID: 33774079 DOI: 10.1053/j.ajkd.2021.01.015] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 01/02/2021] [Indexed: 12/13/2022]
Abstract
Posttransplant lymphoproliferative disorder (PTLD) is one of the most feared complications following kidney transplantation. Over a 10-year period, the risk of PTLD in kidney transplant recipients (KTRs) is 12-fold higher than in a matched nontransplanted population. Given the number of kidney transplants performed, KTRs who experience PTLD outnumber other organ transplant recipients who experience PTLD. Epstein-Barr virus infection is one of the most important risk factors for PTLD, even though 40% of PTLD cases in contemporary series are not Epstein-Barr virus-associated. The overall level of immunosuppression seems to be the most important driver of the increased occurrence of PTLD in solid organ transplant recipients. Reduction in immunosuppression is commonly accepted to prevent and treat PTLD. Although the cornerstone of PTLD treatment had been chemotherapy (typically cyclophosphamide-doxorubicin-vincristinr-prednisone), the availability of rituximab has changed the treatment landscape in the past 2 decades. The outcome of PTLD in KTRs has clearly improved as a result of the introduction of more uniform treatment protocols, improved supportive care, and increased awareness and use of positron emission tomography combined with computed tomography in staging and response monitoring. In this review, we will focus on the most recent data on epidemiology, presentation, risk factors, and management of PTLD in KTRs.
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Affiliation(s)
- Ben Sprangers
- Department of Microbiology, Immunology and Transplantation, Laboratory of Molecular Immunology (Rega Institute for Medical Research), KU Leuven; Division of Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - Leonardo V Riella
- Division of Nephrology and Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Daan Dierickx
- Laboratory of Experimental Hematology, Department of Oncology, KU Leuven; Department of Hematology, University Hospitals Leuven, Leuven, Belgium.
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6
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Montes de Jesus F, Dierickx D, Vergote V, Noordzij W, Dierckx RAJO, Deroose CM, Glaudemans AWJM, Gheysens O, Kwee TC. Prognostic superiority of International Prognostic Index over [ 18F]FDG PET/CT volumetric parameters in post-transplant lymphoproliferative disorder. EJNMMI Res 2021; 11:29. [PMID: 33738643 PMCID: PMC7973341 DOI: 10.1186/s13550-021-00769-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 03/03/2021] [Indexed: 11/19/2022] Open
Abstract
Background Post-transplant lymphoproliferative disorders (PTLDs) are a spectrum of hematological malignancies occurring after solid organ and hematopoietic stem cell transplantation. [18F]FDG PET/CT is routinely performed at PTLD diagnosis, allowing for both staging of the disease and quantification of volumetric parameters, such as whole-body metabolic tumor volume (MTV) and total lesion glycolysis (TLG). In this retrospective study, we aimed to determine the prognostic value of MTV and TLG in PTLD patients, together with other variables of interest, such as the International Prognostic Index (IPI), organ transplant type, EBV tumor status, time after transplant, albumin levels and PTLD morphology. Results A total of 88 patients were included. The 1-, 3-, 5- year overall survival rates were 67%, 58% and 43% respectively. Multivariable analysis indicated that a high IPI (HR: 1.56, 95% CI: 1.13–2.16) and an EBV-negative tumor (HR: 2.71, 95% CI: 1.38–5.32) were associated with poor overall survival. Patients with a kidney transplant had a longer overall survival than any other organ recipients (HR: 0.38 95% CI: 0.16–0.89). IPI was found to be the best predicting parameter of overall survival in our cohort. Whole-body MTV, TLG, time after transplant, hypoalbuminemia and PTLD morphology were not associated with overall survival. Conclusion [18F]FDG PET/CT whole-body volumetric quantitative parameters were not predictive of overall survival in PTLD. In our cohort, high IPI and an EBV-negative tumor were found to predictors of worse overall survival while kidney transplant patients had a longer overall survival compared to other organ transplant recipients
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Affiliation(s)
- F Montes de Jesus
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
| | - D Dierickx
- Department of Hematology, University Hospitals Leuven, Leuven, Belgium
| | - V Vergote
- Department of Hematology, University Hospitals Leuven, Leuven, Belgium
| | - W Noordzij
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands
| | - R A J O Dierckx
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands
| | - C M Deroose
- Department of Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium
| | - A W J M Glaudemans
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands
| | - O Gheysens
- Department of Nuclear Medicine, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - T C Kwee
- Department of Radiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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7
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Song H, Guja KE, Iagaru A. 18F-FDG PET/CT for Evaluation of Post-Transplant Lymphoproliferative Disorder (PTLD). Semin Nucl Med 2021; 51:392-403. [PMID: 33455722 DOI: 10.1053/j.semnuclmed.2020.12.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Post-transplant lymphoproliferative disorders (PTLD) are a spectrum of heterogeneous lymphoproliferative conditions that are serious and possibly fatal complications after solid organ or allogenic hematopoietic stem cell transplantation. Most PTLD are attributed to Epstein-Barr virus reactivation in B-cells in the setting of immunosuppression after transplantation. Early diagnosis, accurate staging, and timely treatment are of vital importance to reduce morbidity and mortality. Given the often nonspecific clinical presentation and disease heterogeneity of PTLD, tissue biopsy and histopathological analysis are essential to establish diagnosis and most importantly, determine the subtype of PTLD, which guides treatment options. Advanced imaging modalities such as 18F-FDG PET/CT have played an increasingly important role and have shown high sensitivity and specificity in detection, staging, and assessing treatment response in multiple clinical studies over the last two decades. However, larger multicenter prospective validation is still needed to further establish the clinical utility of PET imaging in the management of PTLD. Significantly, new hybrid imaging modalities such as PET/MR may help reduce radiation exposure, which is especially important in pediatric transplant patients.
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Affiliation(s)
- Hong Song
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, 300 Pasteur Dr, H2200, Stanford, 94305, USA
| | - Kip E Guja
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, 300 Pasteur Dr, H2200, Stanford, 94305, USA
| | - Andrei Iagaru
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, 300 Pasteur Dr, H2200, Stanford, 94305, USA.
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8
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Abbas F, El Kossi M, Shaheen IS, Sharma A, Halawa A. Post-transplantation lymphoproliferative disorders: Current concepts and future therapeutic approaches. World J Transplant 2020; 10:29-46. [PMID: 32226769 PMCID: PMC7093305 DOI: 10.5500/wjt.v10.i2.29] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 10/21/2019] [Accepted: 12/14/2019] [Indexed: 02/05/2023] Open
Abstract
Transplant recipients are vulnerable to a higher risk of malignancy after solid organ transplantation and allogeneic hematopoietic stem-cell transplant. Post-transplant lymphoproliferative disorders (PTLD) include a wide spectrum of diseases ranging from benign proliferation of lymphoid tissues to frank malignancy with aggressive behavior. Two main risk factors of PTLD are: Firstly, the cumulative immunosuppressive burden, and secondly, the oncogenic impact of the Epstein-Barr virus. The latter is a key pathognomonic driver of PTLD evolution. Over the last two decades, a considerable progress has been made in diagnosis and therapy of PTLD. The treatment of PTLD includes reduction of immunosuppression, rituximab therapy, either isolated or in combination with other chemotherapeutic agents, adoptive therapy, surgical intervention, antiviral therapy and radiotherapy. In this review we shall discuss the prevalence, clinical clues, prophylactic measures as well as the current and future therapeutic strategies of this devastating disorder.
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Affiliation(s)
- Fedaey Abbas
- Nephrology Department, Jaber El Ahmed Military Hospital, Safat 13005, Kuwait
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
| | - Mohsen El Kossi
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Doncaster Royal Infirmary, Doncaster DN2 5LT, United Kingdom
| | - Ihab Sakr Shaheen
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Department of Paediatric Nephrology, Royal Hospital for Children, Glasgow G51 4TF, United Kingdom
| | - Ajay Sharma
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Department of Transplant Surgery, Royal Liverpool University Hospitals, Liverpool L7 8XP, United Kingdom
| | - Ahmed Halawa
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Department of Transplantation, Sheffield Teaching Hospitals, Sheffield S57AU, United Kingdom
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9
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Fujimoto A, Suzuki R. Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disorders after Hematopoietic Stem Cell Transplantation: Pathogenesis, Risk Factors and Clinical Outcomes. Cancers (Basel) 2020; 12:cancers12020328. [PMID: 32024048 PMCID: PMC7072403 DOI: 10.3390/cancers12020328] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 01/27/2020] [Accepted: 01/30/2020] [Indexed: 02/07/2023] Open
Abstract
Epstein-Barr virus (EBV) is a ubiquitous virus belonging to the human γ-herpes virus subfamily. After primary infection, EBV maintains a life-long latent infection. A major concern is that EBV can cause a diverse range of neoplasms and autoimmune diseases. In addition, patients undergoing hematopoietic stem cell transplantation or solid organ transplantation can experience post-transplant lymphoproliferative disorders (PTLDs) due to dysfunction or suppression of host’s immune system, or uncontrolled proliferation of EBV-infected cells. In recent years, the number of EBV-associated PTLD cases has increased. This review focuses on the current understandings of EBV-associated PTLD pathogenesis, as well as the risk factors and clinical outcomes for patients after allogeneic stem cell transplantation.
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Affiliation(s)
| | - Ritsuro Suzuki
- Correspondence: ; Tel.: +81-853-20-2517; Fax: +81-853-20-2525
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10
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Kim HB, Hong R, Na YS, Choi WY, Park SG, Lee HJ. Isolated peritoneal lymphomatosis defined as post-transplant lymphoproliferative disorder after a liver transplant: A case report. World J Clin Cases 2019; 7:4299-4306. [PMID: 31911911 PMCID: PMC6940333 DOI: 10.12998/wjcc.v7.i24.4299] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 10/31/2019] [Accepted: 11/15/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Post-transplant lymphoproliferative disorder (PTLD) is a fatal complication of solid organ transplantation or allogenic hematopoietic stem cell transplantation that is associated with immunosuppressive therapy. Potential manifestations are diverse, ranging from reactive lymphoid hyperplasia to high-grade lymphoma. PTLD is usually of B-cell origin and associated with Epstein-Barr virus (EBV) infection. Herein, we describe a case of PTLD involving the peritoneal omentum. There has been only case of PTLD as a diffuse large B-cell lymphoma (DLBCL) in the peritoneum.
CASE SUMMARY The patient was a 62-year-old man who had been receiving immunosuppressive therapy with tacrolimus since undergoing a liver transplant 15 years prior. He reported that he had experienced abdominal discomfort and anorexia 1 month prior to the current admission. Abdominal pelvic computed tomography (CT) revealed peritoneal and omental mass-like lesions without bowel obstruction. Ultrasonography-guided biopsy was performed, and he was histologically diagnosed with EBV-negative DLBCL. Positron emission tomography (PET)-CT depicted peritoneum and omentum involvement only, without any lymphadenopathy or organ masses, including in the gastrointestinal tract. Six cycles of chemotherapy with a “R-CHOP“ regimen (rituximab-cyclophosphamide, doxorubicin, vincristine, prednisolone) were administered, and PET-CT performed thereafter indicated complete remission.
CONCLUSION This is the first report of isolated peritoneal lymphomatosis defined as PTLD in a liver transplant recipient.
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Affiliation(s)
- Hong Beum Kim
- Department of Premedical Course, Chosun University School of Medicine, Gwangju 501-717, South Korea
| | - Ran Hong
- Department of Pathology, Chosun University Hospital, 365 Pilmun-daero, Dong-gu, Gwangju 501-717, South Korea
| | - Yung Sub Na
- Department of Internal Medicine, Pulomonology, Chosun University Hospital, Gwangju 501-717, South Korea
| | - Woo Young Choi
- Department of Plastic and Reconstructive Surgery, Chosun University Hospital, Gwangju 501-717, South Korea
| | - Sang Gon Park
- Department of Internal Medicine, Hemato-oncology, Chosun University Hospital, Gwangju 501-717, South Korea
| | - Hee Jeong Lee
- Department of Internal Medicine, Hemato-oncology, Chosun University Hospital, Gwangju 501-717, South Korea
- MD, PhD, Department of HematoOncology, Chosun University Hospital, 365 Pilmun-daero, Dong-gu, Gwangju 501-717, South Korea
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11
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Allen UD, Preiksaitis JK. Post-transplant lymphoproliferative disorders, Epstein-Barr virus infection, and disease in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33:e13652. [PMID: 31230381 DOI: 10.1111/ctr.13652] [Citation(s) in RCA: 213] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 06/19/2019] [Indexed: 02/06/2023]
Abstract
PTLD with the response-dependent sequential use of RIS, rituximab, and cytotoxic chemotherapy is recommended. Evidence gaps requiring future research and alternate treatment strategies including immunotherapy are highlighted.
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Affiliation(s)
- Upton D Allen
- Division of Infectious Diseases, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.,Research Institute, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.,Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, ON, Canada
| | - Jutta K Preiksaitis
- Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, AB, Canada
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12
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Crombie JL, LaCasce AS. Epstein Barr Virus Associated B-Cell Lymphomas and Iatrogenic Lymphoproliferative Disorders. Front Oncol 2019; 9:109. [PMID: 30899698 PMCID: PMC6416204 DOI: 10.3389/fonc.2019.00109] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Accepted: 02/05/2019] [Indexed: 12/17/2022] Open
Abstract
Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, affecting up to 90% of the population. EBV was first identified as an oncogenic virus in a Burkitt lymphoma cell line, though subsequently has been found to drive a variety of malignancies, including diffuse large B-cell lymphoma (DLBCL) and other lymphoma subtypes. EBV has a tropism for B-lymphocytes and has the unique ability to exist in a latent state, evading the host immune response. In cases of impaired cell mediated immunity, as in patients with advanced age or iatrogenic immune suppression, the virus is able to proliferate in an unregulated fashion, expressing viral antigens that predispose to transformation. EBV-positive DLBCL not otherwise specified, which has been included as a revised provisional entity in the 2016 WHO classification of lymphoid malignancies, is thought to commonly occur in older patients with immunosenescence. Similarly, it is well-established that iatrogenic immune suppression, occurring in both transplant and non-transplant settings, can predispose to EBV-driven lymphoproliferative disorders. EBV-positive lymphoproliferative disorders are heterogeneous, with variable clinical features and prognoses depending on the context in which they arise. While DLBCL is the most common subtype, other histologic variants, including Burkitt lymphoma, NK/T-cell lymphoma, and Hodgkin lymphoma can occur. Research aimed at understanding the underlying biology and disease prevention strategies in EBV-associated lymphoproliferative diseases are ongoing. Additionally, personalized treatment approaches, such as immunotherapy and adoptive T-cell therapies, have yielded encouraging results, though randomized trials are needed to further define optimal management.
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Affiliation(s)
- Jennifer L Crombie
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
| | - Ann S LaCasce
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
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13
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Affiliation(s)
- Daan Dierickx
- From the Department of Hematology, University Hospitals Leuven, and the Laboratory for Experimental Hematology, Department of Oncology, University of Leuven, Leuven, Belgium (D.D.); and the Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN (T.M.H.)
| | - Thomas M Habermann
- From the Department of Hematology, University Hospitals Leuven, and the Laboratory for Experimental Hematology, Department of Oncology, University of Leuven, Leuven, Belgium (D.D.); and the Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN (T.M.H.)
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14
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Heyes R, Northfelt DW, Lott DG. Posttransplant Lymphoproliferative Disorder: Otolaryngological Manifestations and Management. Otolaryngol Head Neck Surg 2017; 157:750-759. [DOI: 10.1177/0194599817707208] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Objective Posttransplant lymphoproliferative disorder (PTLD) is a unifying term for a spectrum of lymphoid expansion entities brought about by immunosuppression and is strongly associated with Epstein-Barr virus (EBV). Otolaryngological findings tend to present early in the clinical course; therefore, disease awareness among otolaryngologists is of utmost importance. This review synthesizes the body of literature pertaining to PTLD involving the head and neck, summarizes contemporary management, and highlights areas for future research. Data Sources PubMed/Medline. Review Methods Primary literature search of the Medline database was performed for all titles published in the past 10 years pertaining to PTLD. The database search included PTLD combined with a collection of otolaryngological MeSH terms. Full manuscripts were reviewed based on relevance of their title and abstract. Selection into this review was according to clinical and scientific relevance. Conclusion Adenotonsillar focus is common in children in whom adenotonsillectomy may be diagnostic and prevents potentially morbid airway obstruction. Sinonasal PTLD may mimic fungal infection. Laryngotracheal involvement predominately presents in children with symptoms of airway obstruction. PTLD limited to the esophagus is rare. Oral PTLD is rare and phenotypically varied. Cutaneous presentation of PTLD is infrequent, yet one-third of cases affects the head and neck. PTLD may present as cervical lymphadenopathy. Implications for Practice PTLD consideration is vital when evaluating posttransplant patients. Children and EBV-seronegative patients should receive otolaryngological follow-up after transplant. PTLD treatment is multidisciplinary and typically led by lymphoma specialists. Formal partnerships between otolaryngologists and transplant centers may improve patient care and research quality.
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Affiliation(s)
- Richard Heyes
- Department of Otorhinolaryngology–Head and Neck Surgery, Mayo Clinic Arizona, Phoenix, Arizona, USA
| | | | - David G. Lott
- Department of Otorhinolaryngology–Head and Neck Surgery, Mayo Clinic Arizona, Phoenix, Arizona, USA
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Dierickx D, Cardinaels N. Posttransplant lymphoproliferative disorders following liver transplantation: Where are we now? World J Gastroenterol 2015; 21:11034-11043. [PMID: 26494960 PMCID: PMC4607903 DOI: 10.3748/wjg.v21.i39.11034] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Revised: 06/22/2015] [Accepted: 09/02/2015] [Indexed: 02/06/2023] Open
Abstract
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.
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How I treat posttransplant lymphoproliferative disorders. Blood 2015; 126:2274-83. [PMID: 26384356 DOI: 10.1182/blood-2015-05-615872] [Citation(s) in RCA: 116] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Accepted: 09/13/2015] [Indexed: 01/13/2023] Open
Abstract
Posttransplant lymphoproliferative disorder (PTLD) is a potentially fatal disorder arising after solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). Iatrogenically impaired immune surveillance and Epstein-Barr virus (EBV) primary infection/reactivation are key factors in the pathogenesis. However, current knowledge on all aspects of PTLD is limited due to its rarity, morphologic heterogeneity, and the lack of prospective trials. Furthermore, the broad spectrum of underlying immune disorders and the type of graft represent important confounding factors. Despite these limitations, several reviews have been written aimed at offering a guide for pathologists and clinicians in diagnosing and treating PTLD. Rather than providing another classical review on PTLD, this "How I Treat" article, based on 2 case reports, focuses on specific challenges, different perspectives, and novel insights regarding the pathogenesis, diagnosis, and treatment of PTLD. These challenges include the wide variety of PTLD presentation (making treatment optimization difficult), the impact of EBV on pathogenesis and clinical behavior, and the controversial treatment of Burkitt lymphoma (BL)-PTLD.
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