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Sneyers F, Rocha‐Iraizos A, Vergote VKJ, Dierickx D. Delving deeper into the pathogenesis and genomics of posttransplant diffuse large B-cell lymphoma. Hemasphere 2025; 9:e70123. [PMID: 40236504 PMCID: PMC11997454 DOI: 10.1002/hem3.70123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 02/13/2025] [Accepted: 03/14/2025] [Indexed: 04/17/2025] Open
Abstract
Posttransplant lymphoproliferative disorders (PTLDs) are a well-known complication of solid organ transplantation and allogeneic hematopoietic stem cell transplantation. The diffuse large B-cell lymphoma subtype (PT-DLBCL) is the most frequent monomorphic PTLD and is associated with poor prognosis. Transplant recipients have an increased risk of abnormal proliferation of lymphoid cells because of diminished immune surveillance. In about 60% of the cases, Epstein-Barr virus infection seems to contribute to the cancer phenotype. Although clinical and research interest in the disorder has increased during the last two decades, the pathology of the disease remains largely elusive. In this review, we summarize current knowledge of PT-DLBCL pathogenesis, and we discuss how a better understanding of PT-DLBCL can lead to improved diagnostics and therapeutic strategies.
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Affiliation(s)
- Flore Sneyers
- Department of OncologyLaboratory of Experimental HematologyKU LeuvenLeuvenBelgium
- Department of Human GeneticsLaboratory of Molecular Biology of LeukemiaKU LeuvenLeuvenBelgium
- Center for Cancer Biology, VIBLeuvenBelgium
- Leuven Kankerinstituut (LKI), KU Leuven – UZ LeuvenLeuvenBelgium
| | - Ana‐Lucía Rocha‐Iraizos
- Department of OncologyLaboratory of Experimental HematologyKU LeuvenLeuvenBelgium
- Department of Human GeneticsLaboratory of Molecular Biology of LeukemiaKU LeuvenLeuvenBelgium
- Center for Cancer Biology, VIBLeuvenBelgium
- Leuven Kankerinstituut (LKI), KU Leuven – UZ LeuvenLeuvenBelgium
| | - Vibeke K. J. Vergote
- Leuven Kankerinstituut (LKI), KU Leuven – UZ LeuvenLeuvenBelgium
- Department of HematologyUZ LeuvenLeuvenBelgium
| | - Daan Dierickx
- Department of OncologyLaboratory of Experimental HematologyKU LeuvenLeuvenBelgium
- Leuven Kankerinstituut (LKI), KU Leuven – UZ LeuvenLeuvenBelgium
- Department of HematologyUZ LeuvenLeuvenBelgium
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Mah JK, Tam PCK, Chang YC, Saullo JH, Baker AW, Maziarz EK, Messina JA, Sim B, Abusalem L, Hanna S, Pipeling MR, Snyder LD, Reynolds JM, Wolfe CR, Lee MJ, Alexander BD, Heldman MR. Limited utility of Epstein-Barr virus (EBV) surveillance for predicting post-transplant lymphoproliferative disorders in adult EBV seropositive lung transplant recipients. J Clin Virol 2025; 176:105758. [PMID: 39700902 PMCID: PMC11975427 DOI: 10.1016/j.jcv.2024.105758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 11/15/2024] [Accepted: 12/12/2024] [Indexed: 12/21/2024]
Abstract
BACKGROUND EBV DNAemia surveillance, with reduction of immunosuppression at certain viral load (VL) thresholds, is a common practice for mitigating progression from EBV DNAemia to post-transplant lymphoproliferative disorder (PTLD) in lung transplant recipients (LTRs). The utility of EBV surveillance in adult EBV seropositive LTRs is unknown. METHODS We performed a retrospective cohort study of EBV seropositive adult LTRs who underwent lung transplant between 1/1/19 and 12/31/20 and received whole blood (WB) EBV PCR surveillance. We compared peak WB EBV VLs among 3 groups: 1) asymptomatic LTRs who developed PTLD, before PTLD was clinically suspected, 2) LTRs who developed PTLD, after PTLD was clinically suspected, and 3) LTRs who did not develop PTLD. We calculated the positive predictive value (PPV) of moderate-grade DNAemia (2840 to 11,360 IU/mL) and high-grade DNAemia (≥ 11,360 IU/mL) for identifying active or future PTLD. RESULTS Six (2.6 %) of 229 LTRs developed PTLD. Among LTRs who developed PTLD, median peak EBV VL was significantly higher after PTLD was suspected than before clinical signs of PTLD were present (16,004 IU/mL vs. ≤568 IU/mL, p = 0.016). Median peak EBV VLs were similar between asymptomatic LTRs who later developed PTLD and LTRs who did not develop PTLD (median peak EBV VL ≤568 IU/mL vs. ≤568 IU/mL, p = 0.62). The PPVs for moderate- and high-grade DNAemia were 14.7 % and 33.3 %, respectively. CONCLUSIONS EBV surveillance did not accurately identify EBV seropositive LTRs at risk for progressing to PTLD. EBV PCR testing in asymptomatic EBV seropositive transplant recipients may represent an opportunity for diagnostic stewardship.
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Affiliation(s)
- Jordan K Mah
- Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA.
| | - Patrick C K Tam
- Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA
| | - Yeh-Chung Chang
- Division of Infectious Diseases, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX USA
| | - Jennifer H Saullo
- Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA
| | - Arthur W Baker
- Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA
| | - Eileen K Maziarz
- Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA
| | - Julia A Messina
- Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA
| | - Beatrice Sim
- Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA
| | - Lana Abusalem
- Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA
| | - Sandrine Hanna
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University, Durham, NC, USA
| | - Matthew R Pipeling
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University, Durham, NC, USA
| | - Laurie D Snyder
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University, Durham, NC, USA
| | - John M Reynolds
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University, Durham, NC, USA
| | - Cameron R Wolfe
- Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA
| | - Mark J Lee
- Division of Microbiology, Department of Pathology, Duke University, Durham, NC, USA
| | - Barbara D Alexander
- Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA
| | - Madeleine R Heldman
- Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA.
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Srivastava S, Jilhare P, Nazar AH, Ora M, Gambhir S. Isolated Muscular NK/T Cell Lymphoma: A Rare Presentation of Post-Transplant Lymphoproliferative Disorders. Indian J Nucl Med 2024; 39:457-459. [PMID: 40291359 PMCID: PMC12020975 DOI: 10.4103/ijnm.ijnm_108_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 10/26/2024] [Accepted: 11/01/2024] [Indexed: 04/30/2025] Open
Abstract
Posttransplant lymphoproliferative disorders (PTLDs) represent a spectrum of malignancies occurring in transplant recipients under immunosuppression, often linked with Epstein-Barr Virus infection. PTLD has a varied presentation, and isolated muscular involvement is infrequent. Here, we present the case of a 47-year-old female renal transplant recipient presenting with acute left knee joint swelling, initially suggestive of an infective or inflammatory etiology. Biopsy revealed high-grade non-Hodgkin lymphoma of natural killer/T-cell lymphoma. F-18 Fluorodeoxyglucose positron emission tomography-computed tomography scan revealed metabolically active soft tissue mass lesions isolated to thigh muscles. The patient was on a modified chemotherapy regimen tailored to accommodate renal function. This case underscores the necessity for heightened vigilance in diagnosing PTLD, particularly considering its atypical presentations.
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Affiliation(s)
| | - Parag Jilhare
- Department of Nuclear Medicine, SGPGIMS, Lucknow, Uttar Pradesh, India
| | - Aftab Hasan Nazar
- Department of Nuclear Medicine, SGPGIMS, Lucknow, Uttar Pradesh, India
| | - Manish Ora
- Department of Nuclear Medicine, SGPGIMS, Lucknow, Uttar Pradesh, India
| | - Sanjay Gambhir
- Department of Nuclear Medicine, SGPGIMS, Lucknow, Uttar Pradesh, India
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Badia X, Calleja MÁ, Escudero-Vilaplana V, Pérez-Martínez A, Piñana JL, Poveda JL, Vallès JA. The value of the reflective discussion in decision-making using multi-criteria decision analysis (MCDA): an example of determining the value contribution of tabelecleucel for the treatment of the Epstein Barr virus-positive post-transplant lymphoproliferative disease (EBV + PTLD). Orphanet J Rare Dis 2024; 19:308. [PMID: 39180132 PMCID: PMC11342625 DOI: 10.1186/s13023-024-03324-5] [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: 01/15/2024] [Accepted: 08/08/2024] [Indexed: 08/26/2024] Open
Abstract
BACKGROUND The aim of this study was to assess the contribution of the reflective multidisciplinary discussion in determining the value contribution of innovative drugs through the multi-criteria decision analysis (MCDA). This methodology considers all relevant criteria for healthcare decision-making in a global, transparent, and systematic manner and from the perspective of relevant stakeholders. The determination of value contribution of tabelecleucel for the treatment of Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD) compared to salvage therapy was used as an example. RESULTS Tabelecleucel obtained a value contribution score of 0.63 and increased to 0.75 after the reflective discussion. EBV+ PTLD was considered a life-threatening disease (5.0 ± 0.0), with a significant unmet need for an approved treatment (5.0 ± 0.0). Tabelecleucel was perceived as bringing improvements in terms of efficacy (4.2 ± 0.8) and safety (3.8 ± 0.8) compared to the salvage therapy. Most experts considered that the high efficacy and safety results could represent an improvement in the quality of life of patients (2.3 ± 1.2) along with savings in medical costs (2.3 ± 2.0) and non-medical costs (2.7 ± 1.6) compared to the salvage therapy. However, others emphasized the need of more evidence to confirm these improvements and savings over time. Tabelecleucel was regarded as potentially modifying the clinical course of the disease (4.3 ± 0.8) and supported by high-quality evidence (3.2 ± 0.4). All contextual criteria were valued highly positively for tabelecleucel. "Safety/Tolerability" and "Other medical costs" were the criteria that experienced the highest change in the re-test conducted after the reflective discussion. The reflective discussion allowed resolving doubts or misinterpretations of the experts, so the re-test obtained more accurate and consistent results of the value contribution of tabelecleucel. CONCLUSIONS The study shows that the MCDA methodology is a useful tool for decision-making on innovative treatments for the management of rare diseases. It also highlights the importance of reflective multidisciplinary discussion for its ability to resolve doubts or misinterpretations of experts, subsequently allowing to obtain more consistent and reliable results on the value contribution of the drug, being potentially more positive.
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Affiliation(s)
- Xavier Badia
- Omakase Consulting S.L., Barcelona y Madrid, Spain.
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Allen UD, L'Huillier AG, Bollard CM, Gross TG, Hayashi RJ, Höcker B, Maecker-Kolhoff B, Marks SD, Mazariegos GV, Smets F, Trappe RU, Visner G, Chinnock RE, Comoli P, Danziger-Isakov L, Dulek DE, Dipchand AI, Ferry JA, Martinez OM, Metes DM, Michaels MG, Preiksaitis J, Squires JE, Swerdlow SH, Wilkinson JD, Dharnidharka VR, Green M, Webber SA, Esquivel CO. The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: IV-consensus guidelines for the management of post-transplant lymphoproliferative disorders in children and adolescents. Pediatr Transplant 2024; 28:e14781. [PMID: 38808744 DOI: 10.1111/petr.14781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 04/29/2024] [Accepted: 04/30/2024] [Indexed: 05/30/2024]
Abstract
The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti-CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision-making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted.
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Affiliation(s)
- Upton D Allen
- Division of Infectious Diseases, Department of Paediatrics, Transplant and Regenerative Medicine Center, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Arnaud G L'Huillier
- Pediatric Infectious Diseases Unit and Laboratory of Virology, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Catherine M Bollard
- Center for Cancer and Immunology Research, Children's National Hospital, The George Washington University, Washington, District of Columbia, USA
| | - Thomas G Gross
- Center for Cancer and Blood Diseases, Children's Hospital Colorado, Aurora, Colorado, USA
| | - Robert J Hayashi
- Division of Pediatric Hematology/Oncology, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Britta Höcker
- Department of Pediatrics I, Medical Faculty, University Children's Hospital, Heidelberg University, Heidelberg, Germany
| | | | - Stephen D Marks
- Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK
| | - George Vincent Mazariegos
- Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Francoise Smets
- Pediatric Gastroenterology and Hepatology, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium
| | - Ralf U Trappe
- Department of Hematology and Oncology, DIAKO Ev. Diakonie-Krankenhaus Bremen, Bremen, Germany
- Department of Internal Medicine II: Hematology and Oncology, University Medical Centre Schleswig-Holstein, Kiel, Germany
| | - Gary Visner
- Division of Pulmonary Medicine, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | | | - Patrizia Comoli
- Cell Factory & Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Lara Danziger-Isakov
- Division of Infectious Disease, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA
| | - Daniel E Dulek
- Division of Pediatric Infectious Diseases, Monroe Carell Junior Children's Hospital at Vanderbilt and Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Anne I Dipchand
- Department of Paediatrics, Labatt Family Heart Centre, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Judith A Ferry
- Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Olivia M Martinez
- Department of Surgery and Program in Immunology, Stanford University School of Medicine, Stanford, California, USA
| | - Diana M Metes
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Marian G Michaels
- Division of Pediatric Infectious Diseases, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Jutta Preiksaitis
- Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - James E Squires
- Division of Gastroenterology, Hepatology and Nutrition, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Steven H Swerdlow
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - James D Wilkinson
- Department of Pediatrics, Vanderbilt School of Medicine, Nashville, Tennessee, USA
| | - Vikas R Dharnidharka
- Division of Pediatric Nephrology, Hypertension & Apheresis, Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, Missouri, USA
| | - Michael Green
- Division of Pediatric Infectious Diseases, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Steven A Webber
- Department of Pediatrics, Vanderbilt School of Medicine, Nashville, Tennessee, USA
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Chaganti S, Maycock S, McIlroy G, Jackson A, Bishop R, Johnson S, Kanfer E, Kassam S, Cwynarski K, Wrench D, Arumainathan A, Fox CP, Johnson R, McKay P, Paneesha S, Rowntree C, Balotis C, Collins GP, Davies A, Wright J, Burns S, Laurence A, Wheatley K, Menne T. Ibrutinib as part of risk-stratified treatment for posttransplant lymphoproliferative disorder: the phase 2 TIDaL trial. Blood 2024; 144:392-401. [PMID: 38643491 DOI: 10.1182/blood.2024023847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 03/18/2024] [Accepted: 04/02/2024] [Indexed: 04/23/2024] Open
Abstract
ABSTRACT Posttransplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation, and cytotoxic chemotherapy is associated with treatment-related morbidity and mortality. Current treatment takes a sequential, risk-stratified approach, and patients with low-risk disease after initial immunotherapy can avoid escalation to immunochemotherapy. TIDaL is a prospective, single-arm phase 2 trial investigating the activity and tolerability of ibrutinib combined with risk-stratified therapy for first-line treatment of PTLD. Eligible patients were adults with newly diagnosed CD20+ B-cell PTLD after solid organ transplant and performance status 0 to 2. Initial treatment comprised 49 days of ibrutinib 560 mg once daily, with 4 doses of weekly rituximab. Treatment response on interim scan and baseline International Prognostic Index were used to allocate patients to either a low-risk arm (who continued ibrutinib, alongside 4 further doses of 3-weekly rituximab) or high-risk (escalation to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] immunochemotherapy, with ibrutinib continuing in patients aged <65 years). The primary outcome was complete response on interim scan, achieved by 11 of 38 patients (29%; 95% confidence interval [CI], 15-46). This did not reach the prespecified threshold for clinically significant activity. Secondary outcomes included allocation to the low-risk arm (41% of patients), 2-year progression-free survival (58%; 95% CI, 44-76), and 2-year overall survival (76%; 95% CI, 63-91). Adverse events were mostly hematological, gastrointestinal, and infective. Although TIDaL does not support adding ibrutinib into first-line treatment of PTLD, increasing the proportion of patients who can be treated without cytotoxic chemotherapy remains an important aim of future research. This trial was registered at www.clinicaltrials.gov as #ISRCTN32667607.
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Affiliation(s)
- Sridhar Chaganti
- Centre for Clinical Haematology, University Hospitals Birmingham National Health System Foundation Trust, Birmingham, United Kingdom
| | - Shanna Maycock
- Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Cancer, University of Birmingham, Birmingham, United Kingdom
| | - Graham McIlroy
- Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Cancer, University of Birmingham, Birmingham, United Kingdom
| | - Aimee Jackson
- Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Cancer, University of Birmingham, Birmingham, United Kingdom
| | - Rebecca Bishop
- Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Cancer, University of Birmingham, Birmingham, United Kingdom
| | - Sarah Johnson
- Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Cancer, University of Birmingham, Birmingham, United Kingdom
| | - Edward Kanfer
- Department of Haematology, Hammersmith Hospital, Imperial College Healthcare National Health System Trust, London, United Kingdom
| | - Shireen Kassam
- Department of Haematology, King's College Hospital, King's College Hospital National Health System Foundation Trust, London, United Kingdom
| | - Kate Cwynarski
- Department of Haematology, University College London Hospital, University College London Hospitals National Health System Foundation Trust, London, United Kingdom
| | - David Wrench
- Department of Haematology, Guy's Hospital, Guy's and St Thomas' National Health System Foundation Trust, London, United Kingdom
| | - Arvind Arumainathan
- Department of Haematology, Clatterbridge Cancer Centre, The Clatterbridge Cancer Centre National Health System Foundation Trust, Liverpool, United Kingdom
| | - Christopher P Fox
- School of Medicine, University of Nottingham, Nottingham, United Kingdom
| | - Rod Johnson
- Department of Clinical Haematology, St James's University Hospital, Leeds Teaching Hospitals National Health System Trust, Leeds, United Kingdom
| | - Pam McKay
- Department of Haemato-oncology, Beatson West of Scotland Cancer Centre, National Health System Greater Glasgow and Clyde, Glasgow, Scotland
| | - Shankara Paneesha
- Centre for Clinical Haematology, University Hospitals Birmingham National Health System Foundation Trust, Birmingham, United Kingdom
| | - Clare Rowntree
- Department of Haematology, University Hospital of Wales, Cardiff and Vale University Health Board, Cardiff, United Kingdom
| | - Constantine Balotis
- Clinical Haematology Service, Leicester Royal Infirmary, University Hospitals of Leicester National Health System Trust, Leicester, United Kingdom
| | - Graham P Collins
- Department of Haematology, Oxford Cancer and Hematology Centre, Churchill Hospital, Oxford University Hospitals National Health System Foundation Trust, Oxford, United Kingdom
| | - Andrew Davies
- Department of Haematology, Southampton General Hospital, University Hospital Southampton National Health System Foundation Trust, Southampton, United Kingdom
| | - Josh Wright
- Clinical Haematology Service, Royal Hallamshire Hospital, Sheffield Teaching Hospitals National Health System Foundation Trust, Sheffield, United Kingdom
| | - Sarah Burns
- Department of Haematology, Manchester Royal Infirmary, Manchester University National Health System Foundation Trust, Manchester, United Kingdom
| | - Arian Laurence
- Department of Haematology, University College London Hospital, University College London Hospitals National Health System Foundation Trust, London, United Kingdom
| | - Keith Wheatley
- Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Cancer, University of Birmingham, Birmingham, United Kingdom
| | - Tobias Menne
- Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne Hospitals National Health System Foundation Trust, Newcastle upon Tyne, United Kingdom
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Ranawaka R, Dayasiri K, Sandamali E, Gamage M. Management strategies for common viral infections in pediatric renal transplant recipients. World J Transplant 2024; 14:89978. [PMID: 38576764 PMCID: PMC10989477 DOI: 10.5500/wjt.v14.i1.89978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 12/19/2023] [Accepted: 01/04/2024] [Indexed: 03/15/2024] Open
Abstract
Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort. Children are at high risk of acquiring virus-related complications due to immunological immaturity and the enhanced alloreactivity risk that led to maintenance of high immunosuppressive regimes. Hence, prevention, early detection, and prompt treatment of such infe ctions are of paramount importance. Among all viral infections, herpes viruses (herpes simplex virus, varicella zoster virus, Epstein-Barr virus, cytomegalovirus), hepatitis B and C viruses, BK polyomavirus, and respiratory viruses (respiratory syncytial virus, parainfluenza virus, influenza virus and adenovirus) are common in kidney transplant recipients. These viruses can cause systemic disease or allograft dysfunction affecting the clinical outcome. Recent advances in tech nology and antiviral therapy have improved management strategies in screening, monitoring, adoption of prophylactic or preemptive therapy and precise trea tment in the immunocompromised host, with significant impact on the outcome. This review discusses the etiology, screening and monitoring, diagnosis, pre vention, and treatment of common viral infections in pediatric renal transplant recipients.
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Affiliation(s)
- Randula Ranawaka
- Department of Paediatrics, Faculty of Medicine, University of Colombo and Lady Ridgeway Hospital for Children, Colombo 0094, Sri Lanka
| | - Kavinda Dayasiri
- Department of Paediatrics, Facullty of Medicine, University of Kelaniya, Ragama 0094, Sri Lanka
| | - Erandima Sandamali
- Department of Nursing, Faculty of Allied Health Sciences, University of Ruhuna, Galle 0094, Sri Lanka
| | - Manoji Gamage
- Division of Nutrition, Ministry of Health, Colombo 0094, Sri Lanka
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Stefanelli LF, Alessi M, Di Bella C, Billo ME, Viola L, Gnappi M, Bettin E, Cacciapuoti M, Calò LA. EBV Reactivation in Transplant Recipients following SARS-CoV-2 Infection: A Retrospective Study. Pathogens 2023; 12:1435. [PMID: 38133317 PMCID: PMC10748065 DOI: 10.3390/pathogens12121435] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/05/2023] [Accepted: 12/08/2023] [Indexed: 12/23/2023] Open
Abstract
Reactivation and primary infection with a high Epstein Barr Virus (EBV) DNA level in kidney transplant patients could cause severe complications, including the development of Post-Transplantation Lymphoproliferative Disease (PTLD). While in the general population the reactivation of EBV after SARS-CoV-2 infection has been reported, very few data are available in transplant recipients. Our retrospective study aimed to evaluate a possible EBV reactivation in kidney transplant patients following SARS-CoV-2 infection and a possible impairment of the immune system. In addition, the effects of changes in immunosuppressive therapy on EBV DNA reactivation and vaccination were also evaluated. A total of 166 kidney transplant patients followed at the Kidney-Pancreas Transplant Ambulatory Nephrology Unit at Padova University Hospital were retrospectively considered for an observation period of 6 months from January 2020 to April 2023. EBV DNA level was measured by Rt-PCR and evaluated 6 months before and after SARS-CoV-2 infection. Patients' serological states were established via quantification of anti-VCA and anti-EBNA (chemiluminescence). Patients' immune systems were characterized by CD4+/CD8+ lymphocyte ratio (flow cytometry). EBV DNA was reactivated in 50% of the 166 patients with COVID-19 who completed the study. Older patients with more severe forms of COVID-19 had higher EBV reactivation (p < 0.05). EBV reactivation significantly increased in patients with severe SARS-CoV-2 infection requiring hospitalization compared to patients managed at home (p < 0.001). CD4+/CD8+ lymphocyte ratio was reduced in patients with a younger age of transplant (p < 0.01) and on a higher dose of steroids (p < 0.01). The results of our study confirm the role of immunodepression, especially in recent transplant patients and those on high steroids, in EBV reactivation. These results combined with the few available in the literature might contribute to providing an optimal management of immunosuppressive treatment for these patients in order to obtain an immune state unfavorable to the activation of latent viruses, including EBV.
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Affiliation(s)
- Lucia Federica Stefanelli
- Nephrology, Dialysis and Transplantation Unit, Department of Medicine, Padova University Hospital, 35128 Padova, Italy (M.A.); (M.E.B.); (L.V.); (M.G.); (E.B.); (M.C.)
| | - Marianna Alessi
- Nephrology, Dialysis and Transplantation Unit, Department of Medicine, Padova University Hospital, 35128 Padova, Italy (M.A.); (M.E.B.); (L.V.); (M.G.); (E.B.); (M.C.)
| | - Caterina Di Bella
- Kidney and Pancreas Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, 35128 Padova, Italy;
| | - Maria Elena Billo
- Nephrology, Dialysis and Transplantation Unit, Department of Medicine, Padova University Hospital, 35128 Padova, Italy (M.A.); (M.E.B.); (L.V.); (M.G.); (E.B.); (M.C.)
| | - Ludovica Viola
- Nephrology, Dialysis and Transplantation Unit, Department of Medicine, Padova University Hospital, 35128 Padova, Italy (M.A.); (M.E.B.); (L.V.); (M.G.); (E.B.); (M.C.)
| | - Maddalena Gnappi
- Nephrology, Dialysis and Transplantation Unit, Department of Medicine, Padova University Hospital, 35128 Padova, Italy (M.A.); (M.E.B.); (L.V.); (M.G.); (E.B.); (M.C.)
| | - Elisabetta Bettin
- Nephrology, Dialysis and Transplantation Unit, Department of Medicine, Padova University Hospital, 35128 Padova, Italy (M.A.); (M.E.B.); (L.V.); (M.G.); (E.B.); (M.C.)
| | - Martina Cacciapuoti
- Nephrology, Dialysis and Transplantation Unit, Department of Medicine, Padova University Hospital, 35128 Padova, Italy (M.A.); (M.E.B.); (L.V.); (M.G.); (E.B.); (M.C.)
| | - Lorenzo A. Calò
- Nephrology, Dialysis and Transplantation Unit, Department of Medicine, Padova University Hospital, 35128 Padova, Italy (M.A.); (M.E.B.); (L.V.); (M.G.); (E.B.); (M.C.)
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9
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Zhang Y, Lv Y, Wang B, Liu C, Wu R, Zhang X, Li Y, Tian M. Diagnosis and treatment of adult patients with PTLD at different sites after liver transplantation: A three-case report and literature review. Transpl Immunol 2023; 80:101881. [PMID: 37392897 DOI: 10.1016/j.trim.2023.101881] [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: 09/27/2022] [Revised: 06/07/2023] [Accepted: 06/28/2023] [Indexed: 07/03/2023]
Abstract
Post-transplant lymphoproliferative disease (PTLD) is a rare complication accompanying organ transplantation. Herein, we presented 3 cases of PTLD with different primary sites. All three patients presented with symptoms in the corresponding organs or sites and the latter two patients started with atypical symptoms of infections. The first two patients who developed the disease about a year after liver transplantation both had EBV infections. All three patients received immunosuppressant reduction and antiviral therapy. In case 2, remission occurred midway. Adult liver transplantation recipients are at high risk for PTLD, and screening for EBV infection should be intensified in such recipients within 1 year after liver transplantation. Patients should be highly alert for the development of PTLD when new unidentified masses appear, for whom enhanced CT and tissue biopsy should be performed as early as possible.
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Affiliation(s)
- Yanchao Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Yi Lv
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Bo Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Chang Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Rongqian Wu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Xiaogang Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Yu Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Min Tian
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
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10
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Lee M, Abousaud A, Harkins RA, Marin E, Balasubramani D, Churnetski MC, Peker D, Singh A, Koff JL. Important Considerations in the Diagnosis and Management of Post-transplant Lymphoproliferative Disorder. Curr Oncol Rep 2023; 25:883-895. [PMID: 37162742 PMCID: PMC10390257 DOI: 10.1007/s11912-023-01418-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/20/2023] [Indexed: 05/11/2023]
Abstract
PURPOSE OF REVIEW A relative lack of molecular and clinical studies compared to other lymphoid cancers has historically made it difficult to determine optimal management approaches in post-transplant lymphoproliferative disorder (PTLD). We sought to better define the "state of the science" in PTLD by examining recent advances in risk assessment, genomic profiling, and trials of PTLD-directed therapy. RECENT FINDINGS Several major clinical trials highlight risk-stratified sequential therapy incorporating rituximab with or without chemotherapy as a rational treatment strategy in patients with CD20+ PTLD who do not respond to reduction of immunosuppression alone. Epstein Barr virus (EBV)-targeted cytotoxic lymphocytes are a promising approach in patients with relapsed/refractory EBV+ PTLD, but dedicated clinical trials should determine how autologous chimeric antigen receptor T cell therapy (CAR-T) may be safely administered to PTLD patients. Sequencing studies underscore the important effect of EBV infection on PTLD pathogenesis, but comprehensive genomic and tumor microenvironment profiling are needed to identify biomarkers that predict response to treatment in this clinically heterogeneous disease.
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Affiliation(s)
| | - Aseala Abousaud
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | | | - Ellen Marin
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | | | - Michael C Churnetski
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Deniz Peker
- Department of Pathology, Emory University, Atlanta, GA, USA
| | - Ankur Singh
- Georgia Institute of Technology, Atlanta, GA, USA
| | - Jean L Koff
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
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11
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Ong SJ, Sharkey LM, Low KE, Cheow HK, Butler AJ, Buscombe JR. Clinical Utility of 18Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography ( 18F-FDG PET/CT) in Multivisceral Transplant Patients. J Imaging 2023; 9:114. [PMID: 37367462 DOI: 10.3390/jimaging9060114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 05/29/2023] [Accepted: 05/31/2023] [Indexed: 06/28/2023] Open
Abstract
Multivisceral transplant (MVTx) refers to a composite graft from a cadaveric donor, which often includes the liver, the pancreaticoduodenal complex, and small intestine transplanted en bloc. It remains rare and is performed in specialist centres. Post-transplant complications are reported at a higher rate in multivisceral transplants because of the high levels of immunosuppression used to prevent rejection of the highly immunogenic intestine. In this study, we analyzed the clinical utility of 28 18F-FDG PET/CT scans in 20 multivisceral transplant recipients in whom previous non-functional imaging was deemed clinically inconclusive. The results were compared with histopathological and clinical follow-up data. In our study, the accuracy of 18F-FDG PET/CT was determined as 66.7%, where a final diagnosis was confirmed clinically or via pathology. Of the 28 scans, 24 scans (85.7%) directly affected patient management, of which 9 were related to starting of new treatments and 6 resulted in an ongoing treatment or planned surgery being stopped. This study demonstrates that 18F-FDG PET/CT is a promising technique in identifying life-threatening pathologies in this complex group of patients. It would appear that 18F-FDG PET/CT has a good level of accuracy, including for those MVTx patients suffering from infection, post-transplant lymphoproliferative disease, and malignancy.
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Affiliation(s)
- Shao Jin Ong
- Addenbrookes Hospital, Cambridge Universities Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
| | - Lisa M Sharkey
- Addenbrookes Hospital, Cambridge Universities Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
| | - Kai En Low
- Addenbrookes Hospital, Cambridge Universities Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
| | - Heok K Cheow
- Addenbrookes Hospital, Cambridge Universities Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
| | - Andrew J Butler
- Addenbrookes Hospital, Cambridge Universities Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
| | - John R Buscombe
- Addenbrookes Hospital, Cambridge Universities Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
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12
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Abstract
In addition to being the primary target of infections such as viral hepatitis, the liver may also be affected by systemic disease. These include bacterial, mycotic, and viral infections, as well as autoimmune and infiltrative diseases. These conditions generally manifest as abnormal liver biochemistries, often with a cholestatic profile, and may present with additional signs/symptoms such as jaundice and fever. A high index of suspicion and familiarity with potential causal entities is necessary to guide appropriate testing, diagnosis, and treatment.
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Affiliation(s)
- Humberto C Gonzalez
- Division of Gastroenterology and Hepatology, Henry Ford Health, 2799 West Grand Boulevard, Detroit, MI 48202, USA; Wayne State University School of Medicine, 540 E Canfield St, Detroit, MI 48201, USA.
| | - Stuart C Gordon
- Division of Gastroenterology and Hepatology, Henry Ford Health, 2799 West Grand Boulevard, Detroit, MI 48202, USA; Wayne State University School of Medicine, 540 E Canfield St, Detroit, MI 48201, USA
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13
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Puckrin R, Peters A. Rituximab monotherapy following surgical resection of gastrointestinal post-transplant lymphoproliferative disorder in solid organ transplant recipients. Clin Transplant 2023; 37:e14910. [PMID: 36629389 DOI: 10.1111/ctr.14910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 01/04/2023] [Accepted: 01/05/2023] [Indexed: 01/12/2023]
Affiliation(s)
- Robert Puckrin
- Tom Baker Cancer Centre and University of Calgary, Calgary, Canada
| | - Anthea Peters
- Cross Cancer Institute and University of Alberta, Edmonton, Canada
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14
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Thieme CJ, Schulz M, Wehler P, Anft M, Amini L, Blàzquez-Navarro A, Stervbo U, Hecht J, Nienen M, Stittrich AB, Choi M, Zgoura P, Viebahn R, Schmueck-Henneresse M, Reinke P, Westhoff TH, Roch T, Babel N. In vitro and in vivo evidence that the switch from calcineurin to mTOR inhibitors may be a strategy for immunosuppression in Epstein-Barr virus-associated post-transplant lymphoproliferative disorder. Kidney Int 2022; 102:1392-1408. [PMID: 36103953 DOI: 10.1016/j.kint.2022.08.025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 08/02/2022] [Accepted: 08/12/2022] [Indexed: 01/12/2023]
Abstract
Post-transplant lymphoproliferative disorder is a life-threatening complication of immunosuppression following transplantation mediated by failure of T cells to control Epstein-Barr virus (EBV)-infected and transformed B cells. Typically, a modification or reduction of immunosuppression is recommended, but insufficiently defined thus far. In order to help delineate this, we characterized EBV-antigen-specific T cells and lymphoblastoid cell lines from healthy donors and in patients with a kidney transplant in the absence or presence of the standard immunosuppressants tacrolimus, cyclosporin A, prednisolone, rapamycin, and mycophenolic acid. Phenotypes of lymphoblastoid cell-lines and T cells, T cell-receptor-repertoire diversity, and T-cell reactivity upon co-culture with autologous lymphoblastoid cell lines were analyzed. Rapamycin and mycophenolic acid inhibited lymphoblastoid cell-line proliferation. T cells treated with prednisolone and rapamycin showed nearly normal cytokine production. Proliferation and the viability of T cells were decreased by mycophenolic acid, while tacrolimus and cyclosporin A were strong suppressors of T-cell function including their killing activity. Overall, our study provides a basis for the clinical decision for the modification and reduction of immunosuppression and adds information to the complex balance of maintaining anti-viral immunity while preventing acute rejection. Thus, an immunosuppressive regime based on mTOR inhibition and reduced or withdrawn calcineurin inhibitors could be a promising strategy for patients with increased risk of or manifested EBV-associated post-transplant lymphoproliferative disorder.
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Affiliation(s)
- Constantin J Thieme
- BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany; Berlin Center for Advanced Therapies (BeCAT), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Malissa Schulz
- Hochschule für Technik und Wirtschaft Berlin (HTW), Berlin, Germany
| | - Patrizia Wehler
- BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Moritz Anft
- Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany
| | - Leila Amini
- BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany; Berlin Center for Advanced Therapies (BeCAT), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Arturo Blàzquez-Navarro
- BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany; Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany
| | - Ulrik Stervbo
- Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany
| | - Jochen Hecht
- Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain; Experimental and Health Sciences Department, Universitat Pompeu Fabra, Barcelona, Spain
| | - Mikalai Nienen
- Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | | | - Mira Choi
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Panagiota Zgoura
- Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany
| | - Richard Viebahn
- Department of Surgery, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Michael Schmueck-Henneresse
- BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany; Berlin Center for Advanced Therapies (BeCAT), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Petra Reinke
- BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany; Berlin Center for Advanced Therapies (BeCAT), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Timm H Westhoff
- Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany
| | - Toralf Roch
- BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany; Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany
| | - Nina Babel
- BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany; Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany.
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15
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Reiche W, Tauseef A, Sabri A, Mirza M, Cantu D, Silberstein P, Chandan S. Gastrointestinal manifestations, risk factors, and management in patients with post-transplant lymphoproliferative disorder: A systematic review. World J Transplant 2022; 12:268-280. [PMID: 36159076 PMCID: PMC9453293 DOI: 10.5500/wjt.v12.i8.268] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 03/24/2022] [Accepted: 08/05/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Patients with a history of solid organ transplantation (SOT) or hematopoietic stem cell transplantation (HSCT) are at an increased risk of developing post-transplant lymphoproliferative disorder (PTLD). The gastrointestinal (GI) tract is commonly affected as it has an abundance of B and T cells. AIM To determine typical GI-manifestations, risk factors for developing PTLD, and management. METHODS Major databases were searched until November 2021. RESULTS Non-case report studies that described GI manifestations of PTLD, risk factors for developing PTLD, and management of PTLD were included. Nine articles written within the last 20 years were included in the review. All articles found that patients with a history of SOT, regardless of transplanted organ, have a propensity to develop GI-PTLD. CONCLUSION GI tract manifestations may be nonspecific; therefore, consideration of risk factors is crucial for identifying GI-PTLD. Like other lymphoma variants, PTLD is very aggressive making early diagnosis key to prognosis. Initial treatment is reduction of immunosuppression which is effective in more than 50% of cases; however, additional therapy including rituximab, chemotherapy, and surgery may also be required.
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Affiliation(s)
- William Reiche
- Department of Medicine, CHI Creighton University Medical Center, Omaha, NE 68124, United States
| | - Abubakar Tauseef
- Department of Medicine, CHI Creighton University Medical Center, Omaha, NE 68124, United States
| | - Ahmed Sabri
- Department of Pathology, CHI Creighton University Medical Center, Omaha, NE 68124, United States
| | - Mohsin Mirza
- Department of Medicine, CHI Creighton University Medical Center, Omaha, NE 68124, United States
| | - David Cantu
- Department of Pathology, CHI Creighton University Medical Center, Omaha, NE 68124, United States
| | - Peter Silberstein
- Division of Hematology and Oncology, Department of Medicine, CHI Creighton University Medical Center, Omaha, NE 68124, United States
| | - Saurabh Chandan
- Division of Gastroenterology and Hepatology, Department of Medicine, CHI Creighton University Medical Center, Omaha, NE 68124, United States
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16
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Grenda R. Non-Hodgkin lymphoma after pediatric kidney transplantation. Pediatr Nephrol 2022; 37:1759-1773. [PMID: 34633534 PMCID: PMC9239945 DOI: 10.1007/s00467-021-05205-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 05/27/2021] [Accepted: 06/24/2021] [Indexed: 11/18/2022]
Abstract
Non-Hodgkin lymphoma (NHL) that develops after kidney transplantation belongs to post-transplant lymphoproliferative disorders (PTLD) occurring with an incidence of 2-3%. Most pediatric cases are related to primary infection with Epstein-Barr virus (EBV), able to transform and immortalize B cells and widely proliferate due to the lack of relevant control of cytotoxic T cells in patients receiving post-transplant immunosuppression. NHL may develop as a systemic disease or as a localized lesion. The clinical pattern is variable, from non-symptomatic to fulminating disease. Young age of transplant recipient, seronegative EBV status at transplantation, and EBV mismatch between donor and recipient (D+/R-) are regarded as risk factors. Immunosuppression impacts the development of both early and late NHLs. Specific surveillance protocols, including monitoring of EBV viral load, are used in patients at risk; however, detailed histopathology diagnosis and evaluation of malignancy staging is crucial for therapeutic decisions. Minimizing of immunosuppression is a primary management, followed by the use of rituximab in B-cell NHLs. Specific chemotherapeutic protocols, adjusted to lymphoma classification and staging, are used in advanced NHLs. Radiotherapy and/or surgical removal of malignant lesions is limited to the most severe cases. Outcome is variable, depending on risk factors and timing of diagnosis, however is positive in pediatric patients in terms of graft function and patient survival. Kidney re-transplantation is possible in survivors who lost the primary graft due to chronic rejection, however may be performed after at least 2-3 years of waiting time, careful verification of malignancy-free status, and gaining immunity against EBV.
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Affiliation(s)
- Ryszard Grenda
- Department of Nephrology, Kidney Transplantation & Hypertension, Children's Memorial Health Institute, Warsaw, Poland.
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17
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Watson C, Gadikota H, Barlev A, Beckerman R. A review of the risks of long-term consequences associated with components of the CHOP chemotherapy regimen. J Drug Assess 2022; 11:1-11. [PMID: 35693477 PMCID: PMC9176678 DOI: 10.1080/21556660.2022.2073101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
A common chemotherapy regimen in post-transplant lymphoproliferative disease (PTLD) following solid organ transplants (SOT) is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). This study reviews the quantitative evidence for long-term consequences associated with components of CHOP identified from the Children's Oncology Group Long-Term Follow-Up Guidelines. Cited references were screened using prespecified criteria (English, systematic review, randomized controlled trial n > 100, observation study n > 100, case series n > 20). Relevant data were extracted and synthesized. Of 61 studies, 66% were retrospective cohort studies, 28% were in the US, and 95% enrolled pediatric patients. No study focused specifically on the CHOP regimen. Long-term consequences for CHOP components observed in >3 studies included cardiac toxicity (n = 14), hormone deficiencies/infertility (n = 14), secondary leukemia (n = 7), osteonecrosis (n = 6), and bladder cancer (n = 4). These effects are significant, impact a high percentage of patients, and occur as early as one year after treatment. Although none of the studies focused specifically on the CHOP regimen, 30%, 23%, and 15% evaluated alkylating agents (e.g. cyclophosphamide), anthracyclines (e.g. doxorubicin), and corticosteroids (e.g. prednisone), respectively. All three product classes had a dose-dependent risk of long-term consequences with up to 13.2-fold, 27-fold, 16-fold, 14.5-fold, and 6.2-fold increase in risk of heart failure, early menopause, secondary leukemia, bladder cancer, and osteonecrosis, respectively. Lymphoma patients had significantly elevated risks of cardiac toxicity (up to 12.2-fold), ovarian failure (up to 3.8-fold), and osteonecrosis (up to 6.7-fold). No studies were found in PTLD or SOT. Safe and effective PTLD treatments that potentially avoid these long-term consequences are urgently needed.
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Affiliation(s)
- Crystal Watson
- Atara Biotherapeutics Inc., South San Francisco, CA, USA
| | | | - Arie Barlev
- Atara Biotherapeutics Inc., South San Francisco, CA, USA
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18
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Asleh R, Alnsasra H, Habermann TM, Briasoulis A, Kushwaha SS. Post-transplant Lymphoproliferative Disorder Following Cardiac Transplantation. Front Cardiovasc Med 2022; 9:787975. [PMID: 35282339 PMCID: PMC8904724 DOI: 10.3389/fcvm.2022.787975] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 02/01/2022] [Indexed: 11/24/2022] Open
Abstract
Post-transplant lymphoproliferative disorder (PTLD) is a spectrum of lymphoid conditions frequently associated with the Epstein Barr Virus (EBV) and the use of potent immunosuppressive drugs after solid organ transplantation. PTLD remains a major cause of long-term morbidity and mortality following heart transplantation (HT). Epstein-Barr virus (EBV) is a key pathogenic driver in many PTLD cases. In the majority of PTLD cases, the proliferating immune cell is the B-cell, and the impaired T-cell immune surveillance against infected B cells in immunosuppressed transplant patients plays a key role in the pathogenesis of EBV-positive PTLD. Preventive screening strategies have been attempted for PTLD including limiting patient exposure to aggressive immunosuppressive regimens by tailoring or minimizing immunosuppression while preserving graft function, anti-viral prophylaxis, routine EBV monitoring, and avoidance of EBV seromismatch. Our group has also demonstrated that conversion from calcineurin inhibitor to the mammalian target of rapamycin (mTOR) inhibitor, sirolimus, as a primary immunosuppression was associated with a decreased risk of PTLD following HT. The main therapeutic measures consist of immunosuppression reduction, treatment with rituximab and use of immunochemotherapy regimens. The purpose of this article is to review the potential mechanisms underlying PTLD pathogenesis, discuss recent advances, and review potential therapeutic targets to decrease the burden of PTLD after HT.
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Affiliation(s)
- Rabea Asleh
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, United States
- Heart Institute, Hadassah University Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Hilmi Alnsasra
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, United States
- Soroka University Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel
| | - Thomas M. Habermann
- Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, United States
| | - Alexandros Briasoulis
- Division of Cardiovascular Disease, University of Iowa Hospitals and Clinics, Iowa City, IA, United States
| | - Sudhir S. Kushwaha
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, United States
- *Correspondence: Sudhir S. Kushwaha
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19
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Cytomegalovirus and other herpesviruses after hematopoietic cell and solid organ transplantation: From antiviral drugs to virus-specific T cells. Transpl Immunol 2022; 71:101539. [PMID: 35051589 DOI: 10.1016/j.trim.2022.101539] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 01/11/2022] [Accepted: 01/11/2022] [Indexed: 12/13/2022]
Abstract
Herpesviruses can either cause primary infection or may get reactivated after both hematopoietic cell and solid organ transplantations. In general, viral infections increase post-transplant morbidity and mortality. Prophylactic, preemptive, or therapeutically administered antiviral drugs may be associated with serious side effects and may induce viral resistance. Virus-specific T cells represent a valuable addition to antiviral treatment, with high rates of response and minimal side effects. Even low numbers of virus-specific T cells manufactured by direct selection methods can reconstitute virus-specific immunity after transplantation and control viral replication. Virus-specific T cells belong to the advanced therapy medicinal products, and their production is regulated by appropriate legislation; also, strict safety regulations are required to minimize their side effects.
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20
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Munting A, Manuel O. Viral infections in lung transplantation. J Thorac Dis 2022; 13:6673-6694. [PMID: 34992844 PMCID: PMC8662465 DOI: 10.21037/jtd-2021-24] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 06/21/2021] [Indexed: 12/15/2022]
Abstract
Viral infections account for up to 30% of all infectious complications in lung transplant recipients, remaining a significant cause of morbidity and even mortality. Impact of viral infections is not only due to the direct effects of viral replication, but also to immunologically-mediated lung injury that may lead to acute rejection and chronic lung allograft dysfunction. This has particularly been seen in infections caused by herpesviruses and respiratory viruses. The implementation of universal preventive measures against cytomegalovirus (CMV) and influenza (by means of antiviral prophylaxis and vaccination, respectively) and administration of early antiviral treatment have reduced the burden of these diseases and potentially their role in affecting allograft outcomes. New antivirals against CMV for prophylaxis and for treatment of antiviral-resistant CMV infection are currently being evaluated in transplant recipients, and may continue to improve the management of CMV in lung transplant recipients. However, new therapeutic and preventive strategies are highly needed for other viruses such as respiratory syncytial virus (RSV) or parainfluenza virus (PIV), including new antivirals and vaccines. This is particularly important in the advent of the COVID-19 pandemic, for which several unanswered questions remain, in particular on the best antiviral and immunomodulatory regimen for decreasing mortality specifically in lung transplant recipients. In conclusion, the appropriate management of viral complications after transplantation remain an essential step to continue improving survival and quality of life of lung transplant recipients.
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Affiliation(s)
- Aline Munting
- Infectious Diseases Service, Lausanne University Hospital, Lausanne, Switzerland
| | - Oriol Manuel
- Infectious Diseases Service, Lausanne University Hospital, Lausanne, Switzerland.,Transplantation Center, Lausanne University Hospital, Lausanne, Switzerland
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21
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Vazirani J, Crowhurst T, Morrissey CO, Snell GI. Management of Multidrug Resistant Infections in Lung Transplant Recipients with Cystic Fibrosis. Infect Drug Resist 2021; 14:5293-5301. [PMID: 34916813 PMCID: PMC8670859 DOI: 10.2147/idr.s301153] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 11/26/2021] [Indexed: 12/12/2022] Open
Abstract
Cystic fibrosis (CF) is an inherited multisystem disease characterised by bronchiectasis and chronic respiratory infections which eventually cause end stage lung disease. Lung transplantation (LTx) is a well-established treatment option for patients with CF-associated lung disease, improving survival and quality of life. Navigating recurrent infections in the setting of LTx is often difficult, where immune suppression must be balanced against the constant threat of infection. Sepsis/infections are one of the major contributors to post-LTx mortality and multiresistant organisms (eg, Burkholderia cepacia complex, Mycobacterium abscessus complex, Scedosporium spp. and Lomentospora spp.) pose a significant threat to survival. This review will summarize current and novel therapies to assist with the management of multiresistant bacterial, mycobacterial, viral and fungal infections which threaten the CF LTx cohort.
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Affiliation(s)
- Jaideep Vazirani
- Lung Transplant Service, Department of Respiratory Medicine, The Alfred Hospital and Monash University, Melbourne, VIC, Australia
| | - Thomas Crowhurst
- Lung Transplant Service, Department of Respiratory Medicine, The Alfred Hospital and Monash University, Melbourne, VIC, Australia
- Department of Medicine, The University of Adelaide, Adelaide, SA, Australia
| | - C Orla Morrissey
- Department of Infectious Diseases, The Alfred Hospital and Monash University, Melbourne, Vic, Australia
| | - Gregory I Snell
- Lung Transplant Service, Department of Respiratory Medicine, The Alfred Hospital and Monash University, Melbourne, VIC, Australia
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22
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Dashti-Khavidaki S, Saidi R, Lu H. Current status of glucocorticoid usage in solid organ transplantation. World J Transplant 2021; 11:443-465. [PMID: 34868896 PMCID: PMC8603633 DOI: 10.5500/wjt.v11.i11.443] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 09/16/2021] [Accepted: 11/03/2021] [Indexed: 02/06/2023] Open
Abstract
Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades, due to their potent effects on innate immunity and tissue protective effects. However, some SOT centers are reluctant to administer GCs long-term because of the various related side effects. This review summarizes the advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes covering “transplantation” and “glucocorticoids”. GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients, GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute antibody- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols, to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors, such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells, are new methods of GC application in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects involving different non-targeted organs/tissues, such as bone, cardiovascular, neuromuscular, skin and gastrointestinal tract, have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.
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Affiliation(s)
- Simin Dashti-Khavidaki
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14155, Iran
| | - Reza Saidi
- Department of Surgery, SUNY Upstate Medical University, Syracuse, NY 13210, United States
| | - Hong Lu
- Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States
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23
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Feng G, Li Q, Zhu H, Jiang Y, Yuan J, Fu Y, Deng Q. Safety and Efficacy of Anti-CD19-Chimeric Antigen Receptor T Cell Combined With Programmed Cell Death 1 Inhibitor Therapy in a Patient With Refractory Post-Transplant Lymphoproliferative Disease: Case Report and Literature Review. Front Oncol 2021; 11:726134. [PMID: 34604065 PMCID: PMC8481808 DOI: 10.3389/fonc.2021.726134] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 08/27/2021] [Indexed: 12/12/2022] Open
Abstract
Post-transplant lymphoproliferative disease (PTLD) often exhibits poor prognosis and high mortality, and there are no uniform guidelines for the treatment of this disease. Anti-CD19 chimeric antigen receptor (CAR) T cells show significant efficacy in treatment of relapse/refractory diffuse large B-cell lymphoma (DLBCL). Treatment using anti-CD19-CAR T-cell therapy in PTLD has been limited by immunosuppressants and has not been widely employed. In this study, a refractory post kidney transplant DLBCL patient with a high tumor burden was enrolled in a clinical trial of anti-CD19-CAR T-cell therapy. The tacrolimus dose was not decreased during combination chemotherapy, as the creatinine level of the patient increased. To improve the function of autologous T cells, combination therapy with anti-CD19-CAR T cells and programmed cell death 1 (PD-1) inhibitors was selected. After treatment with the combination therapy, the patient was diagnosed with grade 1 cytokine release syndrome and grade 3 immune effector cell-associated neurotoxicity syndrome. The amplification peak of anti-CD19-CAR T cells reached 9.01% on day 7. With PD-1 inhibitor maintenance therapy, his disease was maintained in partial remission for 18 weeks. However, his tumor suddenly increased in size, and he discontinued the treatment, including radiation therapy. The anti-CD19-CAR T cell and PD-1 inhibitors have a combined effect on PTLD, and this combination therapy needs to be further explored.
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Affiliation(s)
- Gang Feng
- Department of Kidney Transplantation, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Qing Li
- Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Haibo Zhu
- Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Yanyu Jiang
- Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Jijun Yuan
- Shanghai Genbase Biotechnology Co. Ltd., Shanghai, China
| | - Yingxin Fu
- Department of Kidney Transplantation, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Qi Deng
- Department of Kidney Transplantation, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
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24
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Ali S, Haji N, Pulipati P, Wahashi EA, Ramamurthi K. Occurrence of Post-Transplant Lymphoproliferative Disease in a Renal Transplant Patient. Cureus 2021; 13:e17930. [PMID: 34532199 PMCID: PMC8436725 DOI: 10.7759/cureus.17930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/13/2021] [Indexed: 11/30/2022] Open
Abstract
Post-transplant lymphoproliferative diseases (PTLD) are a group of lymphoid disorders that occur in the setting of solid organ or hematopoietic transplantation. Risk factors for the development of PTLD include type of organ transplanted, degree/duration of T-cell immunosuppression, and Epstein-Barr virus (EBV) status. After initial infection, EBV lies dormant in memory B-cells and persists at low levels throughout the lifetime. In an environment of chronic T-cell immunosuppression, the underlying EBV infection remains uncontrolled, resulting in malignant B-cell lymphoproliferations that causes PTLD. While PTLD is the most common malignancy associated with solid organ transplants, they are a serious complication and require a low threshold of suspicion for diagnosis. Oftentimes symptoms are nonspecific, such as weight loss and malaise, and many patients present without associated lymphadenopathy. We present the case of a 30-year-old Asian American female who developed PTLD, specifically large B-cell non-Hodgkin's lymphoma, five years after receiving a deceased-donor renal transplant.
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Affiliation(s)
- Sofiah Ali
- Internal Medicine, St. Joseph Mercy Oakland, Pontiac, USA
| | - Nahel Haji
- Internal Medicine, St. Joseph Mercy Oakland Hospital, Pontiac , USA
| | | | - Emad A Wahashi
- Internal Medicine, St. Joseph Mercy Oakland Hospital, Pontiac, USA
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25
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Camerini C, Sant'Antonio E, Ginori A, Pellegri M, De Gaudio C, Banti E, Ciliberti V, Parrini M, Bozzoli L, Simonetti F, Capochiani E. Unusual presentation of extranodal diffuse large B-cell lymphoma in a solid-organ recipient during long-term immunosuppressive treatment. TUMORI JOURNAL 2021; 107:NP127-NP130. [PMID: 34423702 DOI: 10.1177/03008916211040862] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
INTRODUCTION Posttransplant lymphoproliferative disorders (PTLDs) refer to a group of diseases, including diffuse large B-cell lymphoma (DLBCL), that develop after solid organ transplantation or hematopoietic stem cell transplantation. Extranodal involvement in PTLDs is common. Reports about exclusive bone marrow involvement are rare. CASE DESCRIPTION A 70-year-old woman, who had undergone kidney transplantation in 2018, was diagnosed with exclusively extranodal, Epstein-Barr virus-negative DLBCL, with bone marrow and spleen involvement, during long-term immunosuppression. She achieved complete remission with combined immunochemotherapy and temporary hold of immunosuppression. CONCLUSIONS This case shows an uncommon clinical presentation of DLBCL, which was challenging to diagnose, being entirely extranodal. The favorable clinical course relied on timely diagnosis and a multidisciplinary approach. Long-term consequences of posttransplant immunosuppression require a high level of suspicion for an appropriate management, aimed at preserving the graft while eradicating the lymphoproliferative disorder.
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Affiliation(s)
- C Camerini
- Hematology Unit, Center for Translational Medicine, Azienda USL Toscana Nord-Ovest, Livorno-Lucca-Viareggio, Italy
| | - E Sant'Antonio
- Hematology Unit, Center for Translational Medicine, Azienda USL Toscana Nord-Ovest, Livorno-Lucca-Viareggio, Italy
| | - A Ginori
- Pathology Unit, "Monterosso" Polyspecialistic Center, Carrara, Italy
| | - M Pellegri
- Nuclear Medicine Unit, Ospedale San Luca, Lucca, Italy
| | - C De Gaudio
- Nuclear Medicine Unit, Ospedale San Luca, Lucca, Italy
| | - E Banti
- Nuclear Medicine Unit, Ospedale San Luca, Lucca, Italy
| | - V Ciliberti
- Nuclear Medicine Unit, Ospedale San Luca, Lucca, Italy
| | - M Parrini
- Nephrology Unit, Ospedale San Luca, Lucca, Italy
| | - L Bozzoli
- Nephrology Unit, Ospedale San Luca, Lucca, Italy
| | - F Simonetti
- Hematology Unit, Center for Translational Medicine, Azienda USL Toscana Nord-Ovest, Livorno-Lucca-Viareggio, Italy
| | - E Capochiani
- Hematology Unit, Center for Translational Medicine, Azienda USL Toscana Nord-Ovest, Livorno-Lucca-Viareggio, Italy
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26
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Oitani Y, Kato F, Ikeno K, Ishido M, Nakanishi T, Sugihara S, Nunoda S. Complete remission from post-heart transplant lymphoproliferative disorder: A case report. J Cardiol Cases 2021; 24:60-63. [PMID: 34354779 DOI: 10.1016/j.jccase.2020.12.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 11/27/2020] [Accepted: 12/16/2020] [Indexed: 01/04/2023] Open
Abstract
We report a case of Burkitt's lymphoma, post-transplant lymphoproliferative disorder (BL-PTLD) that was treated with intensive chemotherapy. The patient was a 4-year-old boy who underwent heart transplantation at 7 months of age for refractory heart failure due to dilated cardiomyopathy. He was admitted to our hospital with a chief complaint of abdominal pain associated with an abdominal mass. Computed tomography was notable for a bulky mass arising from the terminal ileum. Fluorodeoxyglucose-positron emission tomography revealed multiple lesions in brain, bone, and lymph nodes. He was diagnosed with BL-PTLD stage III by pathological and clinical scoring. He was Epstein-Barr virus (EBV)-seronegative with a low EBV viral DNA load. No EBV-encoded small RNAs were in his intra-abdominal lymph nodes by in situ hybridization. On cytogenetic examination, the intra-abdominal lymph nodes revealed both a MYC rearrangement and a t(8;14)(q24;32), t(16;19)(q24;q13.1) translocation. Administration of tacrolimus and mycophenolate mofetil was discontinued; immunosuppression was maintained with everolimus. Intensive chemotherapy based on the modified LMB 96 protocol for BL was initiated, resulting in complete remission achieved. During the intensive chemotherapy and immunosuppressive switching period, cardiac dysfunction and allograft rejection had not been shown. The patient has remained well for two years after the treatment with no evidence of relapse. <Learning objective: Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication that can develop after heart transplantation and result in significant morbidity and mortality. In the case presented here, intensive chemotherapy and modified immunosuppressive therapy are among the most effective treatments for PTLD patients with an otherwise poor prognosis. Maintaining a fine balance between management of the PTLD and preventing allograft rejection is critically important.>.
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Affiliation(s)
- Yoshiki Oitani
- Department of Pediatrics, Tokyo Women's Medical University Medical Center East, Tokyo, Japan
| | - Fumiyo Kato
- Department of Pediatrics, Tokyo Women's Medical University Medical Center East, Tokyo, Japan
| | - Kaoru Ikeno
- Department of Pediatrics, Tokyo Women's Medical University Medical Center East, Tokyo, Japan
| | - Mikiko Ishido
- Department of Pediatric Cardiology, Tokyo Women's Medical University, Tokyo, Japan
| | - Toshio Nakanishi
- Department of Pediatric Cardiology, Tokyo Women's Medical University, Tokyo, Japan
| | - Shigetaka Sugihara
- Department of Pediatrics, Tokyo Women's Medical University Medical Center East, Tokyo, Japan
| | - Shinichi Nunoda
- Department of Therapeutic Strategy for Severe Heart Failure, Tokyo Women's Medical University Graduate School of Medical Science, Tokyo, Japan
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27
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Rubinstein JD, Shah R, Breese EH, Burns KC, Mangino JL, Norris RE, Lee L, Mizukawa B, O'Brien MM, Phillips CL, Perentesis JP, Pommert L, Absalon MJ. Treatment of posttransplant lymphoproliferative disorder with poor prognostic features in children and young adults: Short-course EPOCH regimens are safe and effective. Pediatr Blood Cancer 2021; 68:e29126. [PMID: 34019326 DOI: 10.1002/pbc.29126] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/20/2021] [Accepted: 05/07/2021] [Indexed: 12/30/2022]
Abstract
No guidelines exist for which intensive chemotherapy regimen is best in pediatric or young adult patients with high-risk posttransplant lymphoproliferative disorder (PTLD). We retrospectively reviewed patients with PTLD who received interval-compressed short-course etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (SC-EPOCH) regimens at our institution. Eight patients were included with median age of 12 years. All patients achieved a complete response with a manageable toxicity profile. Two patients developed second, clonally unrelated, EBV-positive PTLD and one patient had recurrence at 6 months off therapy. No graft rejection occurred during therapy. All eight patients are alive with median follow-up of 29 months.
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Affiliation(s)
- Jeremy D Rubinstein
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Rachana Shah
- Division of Hematology, Oncology and Blood and Marrow Transplantation, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California, USA.,Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Erin H Breese
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Karen C Burns
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Jennifer L Mangino
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Robin E Norris
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Lynn Lee
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Benjamin Mizukawa
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Maureen M O'Brien
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Christine L Phillips
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - John P Perentesis
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Lauren Pommert
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Michael J Absalon
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
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28
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Robinson C, Chanchlani R, Kitchlu A. Malignancies after pediatric solid organ transplantation. Pediatr Nephrol 2021; 36:2279-2291. [PMID: 33057766 DOI: 10.1007/s00467-020-04790-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 07/28/2020] [Accepted: 09/18/2020] [Indexed: 12/19/2022]
Abstract
As life expectancy among pediatric solid organ transplant recipients (SOTRs) improves, the risk of comorbid conditions such as malignancy post-transplantation has also increased. SOTRs are at elevated risks of post-transplantation lymphoproliferative disorders (PTLDs), and skin and solid cancers. PTLDs typically occur early following transplantation, while skin and solid cancers frequently arise in young adulthood (25-40 years). By 30 years following transplantation, 26-41% of pediatric SOTRs have developed cancer. Different risk factors exist for PTLD, and skin and solid cancers, which are modified by cumulative immunosuppression, infections, transplanted organ, and the underlying disease process associated with initial organ failure (e.g., kidney failure). Optimal cancer treatment strategies depend on the specific cancer type, stage, and patient comorbidities. Immunosuppression reduction may be beneficial for certain cancers but must be considered against the risks of acute and chronic rejection and allograft loss. Lifestyle counseling regarding smoking avoidance and sun protection, as well as human papillomavirus vaccination, is an important aspect of cancer prevention. Currently, no cancer screening guidelines exist specifically for pediatric SOTRs. Adult population screening guidelines have not been validated in transplant populations. Therefore, an individualized approach should be taken to cancer screening for pediatric SOTRs, accounting for other cancer risk factors.
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Affiliation(s)
- Cal Robinson
- Division of Paediatric Nephrology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
| | - Rahul Chanchlani
- Division of Pediatric Nephrology, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- ICES McMaster, Hamilton, Ontario, Canada
| | - Abhijat Kitchlu
- Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, 200 Elizabeth Street, 8 Eaton North, 8 N-842, Toronto, Ontario, M5G 2C4, Canada.
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29
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Patil R, Prashar R, Patel A. Heterogeneous Manifestations of Posttransplant Lymphoma in Renal Transplant Recipients: A Case Series. Transplant Proc 2021; 53:1519-1527. [PMID: 34134932 DOI: 10.1016/j.transproceed.2021.04.020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 04/05/2021] [Accepted: 04/19/2021] [Indexed: 01/07/2023]
Abstract
Posttransplant lymphoproliferative disorder (PTLD) occurs in 1% to 3% of adult renal transplant recipients (RTRs). PTLD has a heterogeneous presentation and is often associated with Epstein-Barr virus (EBV) and immunosuppression. We present a descriptive case series of 16 RTRs who demonstrate a variety of PTLD manifestations. Fifty-six percent received rabbit antithymocyte globulin induction, and 37.5% received basiliximab. Maintenance immunosuppression included glucocorticoids, tacrolimus, and mycophenolate mofetil. Median time from transplantation to PTLD diagnosis was 96.5 months. PTLD involved a single site in 44% of RTRs and multiple sites in 56%. PTLD was localized to the gastrointestinal tract in 9 RTRs, in lymph nodes in 9, central nervous system in 4, bone marrow in 3, skin in 3, lungs in 2, perinephric space in 2, mediastinum in 1, and native kidney in 1. PTLD was EBV positive in 8 RTRs, monomorphic/monoclonal in 14, and of B-cell lineage in 13. Three RTRs had T-cell PTLD. Immunosuppressive agents, except glucocorticoids, were discontinued at diagnosis. Treatment was chemotherapy either alone (in 14 RTRs) or in combination with radiation. Complete remission was achieved in 62.5% of RTRs. Renal dysfunction developed in 62.5% of RTRs, and 4 received dialysis. The overall mortality rate was 62.5%, with median time of death 6.5 months after diagnosis. PTLD that was EBV negative and had T-cell involvement presented with aggressive disease and a higher mortality. Clinicians should be aware of the various PTLD manifestations. Early diagnosis and a multidisciplinary approach to treatment is crucial for improved patient outcomes.
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Affiliation(s)
- Rujuta Patil
- Wayne State University School of Medicine, Detroit, Michigan
| | - Rohini Prashar
- Kidney and Pancreas Transplant Program, Henry Ford Transplant Institute, Detroit, Michigan
| | - Anita Patel
- Kidney and Pancreas Transplant Program, Henry Ford Transplant Institute, Detroit, Michigan.
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30
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Zimmermann H, Nitsche M, Pott C, Reinke P, Babel N, Hermann RM, Hauser IA, Hahn D, Ritgen M, Pietschmann C, Klapper W, Anagnostopoulos I, Trappe RU. Reduction of immunosuppression combined with whole-brain radiotherapy and concurrent systemic rituximab is an effective yet toxic treatment of primary central nervous system post-transplant lymphoproliferative disorder (pCNS-PTLD): 14 cases from the prospective German PTLD registry. Ann Hematol 2021; 100:2043-2050. [PMID: 33973053 DOI: 10.1007/s00277-021-04548-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 05/01/2021] [Indexed: 01/10/2023]
Abstract
Post-transplant lymphoproliferative disorders (PTLD) exclusively affecting the central nervous system-primary CNS-PTLD (pCNS-PTLD)-are rare. There is no standard therapy, and previous case series have included heterogeneous treatment approaches. We performed a retrospective, multi-centre analysis of 14 patients with pCNS-PTLD after solid organ transplantation (SOT) treated in the prospective German PTLD registry with reduction of immunosuppression (RI), whole-brain radiotherapy (WBRT), and concurrent systemic rituximab between 2001 and 2018. Twelve of fourteen patients were kidney transplant recipients and median age at diagnosis was 65 years. Thirteen of fourteen cases (93%) were monomorphic PTLD of the diffuse large B-cell lymphoma type, and 12/13 were EBV-associated. The median dose of WBRT administered was 40 Gy with a median fraction of 2 Gy. The median number of administered doses of rituximab (375 mg/m2) IV was four. All ten patients evaluated responded to treatment (100%). Median OS was 2.5 years with a 2-year Kaplan-Meier estimate of 63% (95% confidence interval 30-83%) without any recorded relapses after a median follow-up of 2.6 years. Seven of fourteen patients (50%) suffered grade III/IV infections under therapy (fatal in two cases, 14%). During follow-up, imaging demonstrated grey matter changes interpreted as radiation toxicity in 7/10 evaluated patients (70%). The combination of RI, WBRT, and rituximab was an effective yet toxic treatment of pCNS-PTLD in this series of 14 patients. Future treatment approaches in pCNS-PTLD should take into account the significant risk of infections as well as radiation-induced neurotoxicity.
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Affiliation(s)
- Heiner Zimmermann
- Department of Haematology and Oncology, DIAKO Ev. Diakonie-Krankenhaus Bremen, Gröpelinger Heerstr. 406-408, 28239, Bremen, Germany
| | | | - Christiane Pott
- Department of Internal Medicine II: Haematology and Oncology, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Petra Reinke
- Department of Nephrology and Intensive Care, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Nina Babel
- Center for Translational Medicine and Department of Internal Medicine I, Marien Hospital Herne, Ruhr-University Bochum University Hospital, Herne, Germany
| | - Robert M Hermann
- Center of Radiotherapy, Bremen, Germany
- Department of Radiotherapy and Special Oncology, Hannover Medical School, Hannover, Germany
| | - Ingeborg A Hauser
- Department of Nephrology, UKF, Goethe University Frankfurt, Frankfurt/Main, Germany
| | - Dennis Hahn
- Department of Haematology, Oncology and Palliative Care, Katharinen hospital, Stuttgart, Germany
| | - Matthias Ritgen
- Department of Internal Medicine II: Haematology and Oncology, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | | | - Wolfram Klapper
- Department of Haematopathology, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | | | - Ralf U Trappe
- Department of Haematology and Oncology, DIAKO Ev. Diakonie-Krankenhaus Bremen, Gröpelinger Heerstr. 406-408, 28239, Bremen, Germany.
- Department of Internal Medicine II: Haematology and Oncology, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany.
- Department of Haematology and Oncology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
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31
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Small S, Barnea Slonim L, Williams C, Karmali R. B Cell Lymphomas of the GI Tract. Curr Gastroenterol Rep 2021; 23:9. [PMID: 33963950 DOI: 10.1007/s11894-021-00811-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/24/2021] [Indexed: 06/12/2023]
Abstract
PURPOSE OF THE REVIEW Primary GI lymphomas of B cell origin are a diverse group of lymphomas. In this article, we provide an overview of the diagnosis, pathologic and molecular features, and management of these varied lymphomas. RECENT FINDINGS The most common primary GI lymphomas are diffuse large B cell lymphoma (DLBCL) and marginal zone lymphomas (MZL), but follicular lymphomas (FL), mantle cell lymphomas (MCL), post-transplant lymphoproliferative disorders (PTLD), and Burkitt lymphoma of the GI tract also occur. Many features of these lymphomas are similar to their nodal counterparts, but certain clinical and biological aspects are unique. Diagnostic and treatment strategies for these lymphomas continue to evolve over time. There are ongoing discoveries about the unique pathophysiology, molecular characteristics, and complications of primary B cell GI lymphomas that are already leading to improvements in management of this histologically diverse set of lymphomas.
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Affiliation(s)
- Sara Small
- Division of Hematology/Oncology, Northwestern University, Chicago, IL, USA
| | | | - Corinne Williams
- Robert H. Lurie Comprehensive Cancer Center, 675 N. St. Clair St.Fl 21 Ste. 100, Chicago, IL, 60611, USA
| | - Reem Karmali
- Division of Hematology/Oncology, Northwestern University, Chicago, IL, USA.
- Robert H. Lurie Comprehensive Cancer Center, 675 N. St. Clair St.Fl 21 Ste. 100, Chicago, IL, 60611, USA.
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32
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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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33
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Post-transplantation lymphoproliferative disorder after haematopoietic stem cell transplantation. Ann Hematol 2021; 100:865-878. [PMID: 33547921 DOI: 10.1007/s00277-021-04433-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Accepted: 01/18/2021] [Indexed: 12/19/2022]
Abstract
Post-transplantation lymphoproliferative disorder (PTLD) is a severe complication of haematopoietic stem cell transplantation (HSCT), occurring in a setting of immune suppression and dysregulation. The disease is in most cases driven by the reactivation of the Epstein-Barr virus (EBV), which induces B cell proliferation through different pathomechanisms. Beyond EBV, many factors, variably dependent on HSCT-related immunosuppression, contribute to the disease development. PTLDs share several features with primary lymphomas, though clinical manifestations may be different, frequently depending on extranodal involvement. According to the WHO classification, histologic examination is required for diagnosis, allowing also to distinguish among PTLD subtypes. However, in cases of severe and abrupt presentation, a diagnosis based on a combination of imaging studies and EBV-load determination is accepted. Therapies include prophylactic and pre-emptive interventions, aimed at eradicating EBV proliferation before symptoms onset, and targeted treatments. Among them, rituximab has emerged as first-line option, possibly combined with a reduction of immunosuppression, while EBV-specific cytotoxic T lymphocytes are effective and safe alternatives. Though prognosis remains poor, survival has markedly improved following the adoption of the aforementioned treatments. The validation of innovative, combined approaches is the future challenge.
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34
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Leeaphorn N, Thongprayoon C, Chewcharat A, Hansrivijit P, Jadlowiec CC, Cummings LS, Katari S, Mao SA, Mao MA, Cheungpasitporn W. Outcomes of kidney retransplantation in recipients with prior posttransplant lymphoproliferative disorders: An analysis of the 2000-2019 UNOS/OPTN database. Am J Transplant 2021; 21:846-853. [PMID: 33128832 DOI: 10.1111/ajt.16385] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 10/13/2020] [Accepted: 10/25/2020] [Indexed: 01/25/2023]
Abstract
This study utilized the UNOS database to assess clinical outcomes after kidney retransplantation in patients with a history of posttransplant lymphoproliferative disease (PTLD). Among second kidney transplant patients from 2000 to 2019, 254 had history of PTLD in their first kidney transplant, whereas 28,113 did not. After a second kidney transplant, PTLD occurred in 2.8% and 0.8% of patients with and without history of PTLD, respectively (p = .001). Over a median follow-up time of 4.5 years after a second kidney transplant, 5-year death-censored graft failure was 9.5% vs. 12.6% (p = .21), all-cause mortality was 8.3% vs. 11.8% (p = .51), and 1-year acute rejection was 11.0% vs. 9.3% (p = .36) in the PTLD vs. non-PTLD groups, respectively. There was no significant difference in death-censored graft failure, mortality, and acute rejection between PTLD and non-PTLD groups in adjusted analysis and after propensity score matching. We conclude that graft survival, patient survival, and acute rejection after kidney retransplantation are comparable between patients with and without history of PTLD, but PTLD occurrence after kidney retransplantation remains higher in patients with history of PTLD.
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Affiliation(s)
- Napat Leeaphorn
- Renal Transplant Program, University of Missouri-Kansas City School of Medicine/Saint Luke's Health System, Kansas City, Missouri
| | - Charat Thongprayoon
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Api Chewcharat
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Panupong Hansrivijit
- Department of Internal Medicine, University of Pittsburgh Medical Center Pinnacle, Harrisburg, Pennsylvania
| | | | - Lee S Cummings
- Renal Transplant Program, University of Missouri-Kansas City School of Medicine/Saint Luke's Health System, Kansas City, Missouri
| | - Sreelatha Katari
- Renal Transplant Program, University of Missouri-Kansas City School of Medicine/Saint Luke's Health System, Kansas City, Missouri
| | - Shennen A Mao
- Division of Transplant Surgery, Mayo Clinic, Jacksonville, Florida
| | - Michael A Mao
- Division of Nephrology and Hypertension, Mayo Clinic, Jacksonville, Florida
| | - Wisit Cheungpasitporn
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota
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35
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Watson C, Barlev A, Worrall J, Duff S, Beckerman R. Exploring the burden of short-term CHOP chemotherapy adverse events in post-transplant lymphoproliferative disease: a comprehensive literature review in lymphoma patients. J Drug Assess 2020; 10:18-26. [PMID: 33489434 PMCID: PMC7782278 DOI: 10.1080/21556660.2020.1854561] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Purpose Cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) is a treatment for post-transplant lymphoproliferative disease (PTLD) following solid organ transplant (SOT) after failing rituximab, an aggressive and potentially fatal lymphoma. This study explores the humanistic and economic burden of CHOP-associated adverse events (AEs) in PTLD patients. Since PTLD is rare, searches included lymphoproliferative disease with lymphoma patients. Design This comprehensive literature review used the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) protocol, pre-specifying the search strategy and criteria. CHOP-associated short-term AEs with an incidence of >4% were sourced from published literature and cancer websites to inform the search strategy. PubMed and EMBASE searches were used to identify humanistic and economic burden studies. Results PubMed and EMBASE searches identified 3946 citations with 27 lymphoma studies included. Studies were methodologically heterogeneous. Febrile neutropenia (FN) was the AE most encountered, followed by chemotherapy-induced (CI) anemia (A), infection, CI-nausea and vomiting, thrombocytopenia, and CI-peripheral neuropathy (PN). FN and infections were associated with significant disutility, increased hospitalization, and extended length of stay (LOS). Infections and CIPN significantly impacted the utility of patients and CIA-related fatigue showed reductions in quality of life (QoL). Many patients continue to have QoL deficits continued even after AEs were treated. Management costs varied greatly, ranging from nominal (CIPN) to over $100,000 in the USA for infections, EUR 10,290 in Europe for infections, or CAN$1012 in Canada for FN. Cost of outpatient care varied but had a lower economic impact compared to hospitalizations. Conclusions Short-term AEs from CHOP in the lymphoma population were associated with substantial humanistic and economic burden.
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Affiliation(s)
- Crystal Watson
- Atara Biotherapeutics, Inc, South San Francisco, CA, USA
| | - Arie Barlev
- Atara Biotherapeutics, Inc, South San Francisco, CA, USA
| | | | - Steve Duff
- Veritas Health Economics Consulting, Carlsbad, CA, USA
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36
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Pan K, Franke AJ, Skelton WP, Bishnoi R, Shah C, Dang NH, Alquadan K. Reduction of immunosuppression for post-transplant lymphoproliferative disorder (PTLD): a single-center experience of allograft survival outcomes. Leuk Lymphoma 2020; 62:1123-1128. [PMID: 33327817 DOI: 10.1080/10428194.2020.1861266] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication of hematopoietic stem cell transplant and solid organ transplant. While reduction in immunosuppression (RIS) is the first-line treatment for PTLD, outcomes of allograft function as a result of RIS remain understudied. In this retrospective study, we examine rates of allograft rejection and graft failure after RIS in 141 patients diagnosed with PTLD at the University of Florida. Compared to prior literature demonstrating around 32-40% rate of allograft rejection as result of RIS, our institutional analysis revealed a much lower treatment-related allograft rejection rate of 18.4%. Out of the patients who experienced acute allograft rejection, 23.1% ultimately progressed to allograft failure. Interestingly, acute allograft rejection episodes during PTLD treatment were not statistically found to impact overall survival. RIS remains an overall beneficial treatment modality of PTLD due to its low allograft rejection rate relative to treatment rate.
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Affiliation(s)
- Kelsey Pan
- Department of Internal Medicine, University of Florida, Gainesville, FL, USA
| | - Aaron J Franke
- Department of Internal Medicine, University of Florida, Gainesville, FL, USA.,Department of Hematology & Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - William Paul Skelton
- Department of Internal Medicine, University of Florida, Gainesville, FL, USA.,Department of Hematology & Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Rohit Bishnoi
- Department of Medicine, Division of Hematology & Oncology, University of Florida, Gainesville, FL, USA
| | - Chintan Shah
- Department of Medicine, Division of Hematology & Oncology, University of Florida, Gainesville, FL, USA
| | - Nam H Dang
- Department of Medicine, Division of Hematology & Oncology, University of Florida, Gainesville, FL, USA
| | - Kawther Alquadan
- Division of Nephrology, Hypertension & Renal Transplantation, University of Florida, Gainesville, FL, USA
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37
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Role of Radiotherapy in Post-transplant Lymphoproliferative Disorders: Three Case Reports and Review of the Literature. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2020; 21:e309-e316. [PMID: 33257284 DOI: 10.1016/j.clml.2020.11.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 11/05/2020] [Indexed: 12/22/2022]
Abstract
Post-transplant lymphoproliferative disorder (PTLD) is an aggressive malignancy that occurs in patients who have undergone solid organ transplantation or hematopoietic stem cell transplantation. It develops as the result of uncontrolled cell proliferations owing to reduced immunological surveillance. PTLD may occur with a various spectrum of clinical presentations, including both localized and extensive disease. Management can be significantly variable according both to the clinical presentation and to the histologic features. The most important systemic treatment strategies are reduction of immunosuppressive therapy, chemotherapy, anti B-cell antibodies, especially rituximab and cytokine-based therapies. The localized form of PTLD could be efficiently treated, and potentially cured, with surgery or radiotherapy (RT). Involved site RT may be a feasible effective option for the treatment of patients with PTLD, given the excellent radio-sensitivity of lymphoid disorders. In this report, we describe 3 adult patients with PTLD treated with moderate-dose RT (24-36 Gy) having a good local control with negligible toxicity. We also review the literature data on the role of radiation therapy in this particular setting.
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38
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Malyszko J, Basak G, Batko K, Capasso G, Capasso A, Drozd-Sokolowska J, Krzanowska K, Kulicki P, Matuszkiewicz-Rowinska J, Soler MJ, Sprangers B, Malyszko J. Haematological disorders following kidney transplantation. Nephrol Dial Transplant 2020; 37:409-420. [PMID: 33150431 DOI: 10.1093/ndt/gfaa219] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Indexed: 01/19/2023] Open
Abstract
Transplantation offers cure for some haematological cancers, end-stage organ failure, but at the cost of long-term complications. Renal transplantation is the best-known kidney replacement therapy and it can prolong end-stage renal disease patient lives for decades. However, patients after renal transplantation are at a higher risk of developing different complications connected not only with surgical procedure but also with immunosuppressive treatment, chronic kidney disease progression and rejection processes. Various blood disorders can develop in post-transplant patients ranging from relatively benign anaemia through cytopenias to therapy-related myelodysplasia and acute myeloid leukaemia (AML) and post-transplant lymphoproliferative disorders followed by a rare and fatal condition of thrombotic microangiopathy and haemophagocytic syndrome. So far literature mainly focused on the post-transplant lymphoproliferative disease. In this review, a variety of haematological problems after transplantation ranging from rare disorders such as myelodysplasia and AML to relatively common conditions such as anaemia and iron deficiency are presented with up-to-date diagnosis and management.
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Affiliation(s)
| | - Grzegorz Basak
- Department of Hematology, Oncology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Krzysztof Batko
- Department of Nephrology, Collegium Medicum, Jagiellonian University, Cracow, Poland
| | - Giavambatista Capasso
- Department of Translational Medical Sciences, University Luigi Vanvitelli, Naples, Italy
| | - Anna Capasso
- Department of Oncology, Livestrong Cancer Institutes, Dell Medical School, The University of Texas, Austin, TX, USA
| | - Joanna Drozd-Sokolowska
- Department of Hematology, Oncology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Katarzyna Krzanowska
- Department of Nephrology, Collegium Medicum, Jagiellonian University, Cracow, Poland
| | - Pawel Kulicki
- Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | | | - Maria Jose Soler
- Department of Nephrology, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Ben Sprangers
- Department of Microbiology, Immunology, and Transplantation, Laboratory of Molecular Immunology, Rega Institute, Katholieke Universiteit Leuven, Belgium.,Division of Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - Jacek Malyszko
- 1st Department of Nephrology and Transplantology, Medical University of Bialystok, Bialystok, Poland
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39
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Affiliation(s)
- Peter Cosgrove
- Department of Emergency Medicine, Boston Children's Hospital, Boston, MA
| | - Kartik Pillutla
- Department of Pediatric Nephrology, Dell Children's Medical Center, Austin, Texas
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40
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Bunchorntavakul C, Reddy KR. Epstein-Barr Virus and Cytomegalovirus Infections of the Liver. Gastroenterol Clin North Am 2020; 49:331-346. [PMID: 32389366 DOI: 10.1016/j.gtc.2020.01.008] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections are common and are associated with a variety of liver manifestations. EBV and CMV infections, in immunocompetent hosts, commonly manifest as acute hepatitis, with severity varying from asymptomatic, self-limited icteric hepatitis to acute liver failure. Atypical manifestations, such as cholestasis, chronic hepatitis, precipitation of acute-on-chronic liver failure, and autoimmune hepatitis, are reported with EBV infection, whereas cholestasis, portal vein thrombosis, and Budd-Chiari syndrome are reported with CMV infection. In the setting of liver transplantation, CMV is the most common infectious complication and carries significant morbidity; EBV is the major cause of post-transplant lymphoproliferative disorders.
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Affiliation(s)
- Chalermrat Bunchorntavakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, 2 Phayathai Road, Ratchathewi, Bangkok 10400, Thailand
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, Philadelphia, PA 19104, USA.
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41
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Silva JT, Fernández-Ruiz M, Aguado JM. Prevention and therapy of viral infections in patients with solid organ transplantation. Enferm Infecc Microbiol Clin 2020; 39:87-97. [PMID: 32143894 DOI: 10.1016/j.eimc.2020.01.021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 01/13/2020] [Accepted: 01/16/2020] [Indexed: 12/28/2022]
Abstract
Solid organ transplantation (SOT) is the best treatment option for end-stage organ disease. The number of SOT procedures has been steadily increasing worldwide during the past decades. This trend has been accompanied by the continuous incorporation of new antimicrobial drugs and by the refinement of strategies aimed at minimizing the risk of opportunistic infection. Nonetheless, viral infections, which can occur at any stage of the post-transplant period, remain a clinical challenge that negatively impacts both patient and graft outcomes. This review offers an overview of the most relevant viral infections in the SOT population, with a focus on herpesviruses (cytomegalovirus, Epstein-Barr virus, varicella-zoster virus, and herpes simplex virus 1 and 2) and polyomaviruses (human BK polyomavirus). In addition, the currently recommended prophylactic and treatment approaches are summarized, as well as the new antiviral agents in different phases of clinical development.
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Affiliation(s)
- Jose Tiago Silva
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), School of Medicine, Universidad Complutense, Madrid, Spain
| | - Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), School of Medicine, Universidad Complutense, Madrid, Spain
| | - José María Aguado
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), School of Medicine, Universidad Complutense, Madrid, Spain.
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42
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Abstract
Lung transplantation is an established therapeutic option for selected patients with advanced lung diseases. As early outcomes after lung transplantation have improved, chronic medical illnesses have emerged as significant obstacles to long-term survival. Among them is post-transplant malignancy, currently representing the 2nd most common cause of death 5–10 years after transplantation. Chronic immunosuppressive therapy and resulting impairment of anti-tumor immune surveillance is thought to have a central role in cancer development after solid organ transplantation (SOT). Lung transplant recipients receive more immunosuppression than other SOT populations, likely contributing to even higher risk of cancer among this group. The most common cancers in lung transplant recipients are non-melanoma skin cancers, followed by lung cancer and post-transplant lymphoproliferative disorder (PTLD). The purpose of this review is to outline the common malignancies following lung transplant, their risk factors, prognosis and current means for both prevention and treatment.
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Affiliation(s)
- Osnat Shtraichman
- Pulmonary, Allergy and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.,Pulmonary Institute, Rabin Medical Center, Affiliated with Sackler School of Medicine Tel Aviv University, Petach Tikva, Israel
| | - Vivek N Ahya
- Pulmonary, Allergy and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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43
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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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44
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Nimitpanya P, Limpanavongsaen P, Udomkarnjananun S, Jutivorakool K, Vanichanan J. Post-transplant Lymphoproliferative Disorder of Naso-orbital Region in Adult Renal Transplant Recipients: A Case Report and Literature Review. Transplant Proc 2020; 52:2731-2735. [PMID: 32089317 DOI: 10.1016/j.transproceed.2020.01.047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 01/22/2020] [Indexed: 10/25/2022]
Abstract
Post-transplant lymphoproliferative disorder (PTLD) is an uncommon but fatal complication following both solid organ and hematologic stem cell transplantations. Epstein-Barr virus (EBV) has been considered a main etiologic agent causing PTLD, especially in the first year after transplantation. Extranodal manifestations are frequently found in PTLD; however, naso-orbital involvement in adults is rare. We report a case of EBV-associated PTLD of the naso-orbital region in a 72-year-old patient that occurred 10 years after kidney transplant. Six additional adults with naso-orbital PTLD were identified after completing this literature review, including 2 cases with eyelid swelling, 3 cases with proptosis, and 1 case with facial numbness. The majority of cases occurred after 1 year of transplantation and were associated with EBV. This report emphasizes recognizing PTLD as differential diagnosis in transplant recipients who present with naso-orbital symptoms.
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Affiliation(s)
| | | | - Suwasin Udomkarnjananun
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Kamonwan Jutivorakool
- Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Jakapat Vanichanan
- Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
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45
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Retransplantation after post transplant lymphoproliferative disorder: overcoming the obstacles! CEN Case Rep 2020; 9:200-203. [DOI: 10.1007/s13730-020-00455-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 01/24/2020] [Indexed: 10/25/2022] Open
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46
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Griffin DB, Hajar T, Simpson E, White KP, Shinohara MM. Management of Cutaneous T-Cell Lymphoma/Mycosis Fungoides Occurring in the Setting of Solid Organ Transplantation: Report of 2 Cases. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2020; 20:e39-e42. [PMID: 31924574 DOI: 10.1016/j.clml.2019.12.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 12/07/2019] [Accepted: 12/14/2019] [Indexed: 11/28/2022]
Affiliation(s)
| | - Tamar Hajar
- Department of Dermatology, Oregon Health Science University, Portland, OR
| | - Eric Simpson
- Department of Dermatology, Oregon Health Science University, Portland, OR
| | - Kevin P White
- Department of Dermatology, Oregon Health Science University, Portland, OR
| | - Michi M Shinohara
- Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA.
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47
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Malignancy After Lung Transplantation: How to Manage Immunosuppression? Transplant Proc 2020; 52:315-320. [DOI: 10.1016/j.transproceed.2019.09.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 08/29/2019] [Accepted: 09/26/2019] [Indexed: 02/07/2023]
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48
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Kedi W, Dongjiang X, Zhi L, Yan G, Kun J, Jianrong S. The rational specimen for the quantitative detection of Epstein-Barr virus DNA load. Clin Chem Lab Med 2019; 57:759-765. [PMID: 30267627 DOI: 10.1515/cclm-2018-0733] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 08/28/2018] [Indexed: 12/15/2022]
Abstract
Background Epstein-Barr virus (EBV) DNA load monitoring in blood is essential for the diagnosis of EBV-associated diseases. However, the best-suited blood compartment for detection is still under discussion. The aim of this study was to evaluate the diagnostic value of EBV-DNA load in peripheral blood mononuclear cells (PBMC), plasma and whole blood (WB) samples. Methods A total of 156 patients, including 45 patients with infectious mononucleosis (IM), 57 patients with EBV-associated hemophagocytic lymphohistiocytosis (HLH) and 54 patients with post-transplant lymphoproliferative disorders (PTLD), were enrolled in this study. The EBV-DNA load in PBMC, plasma and WB samples were measured with real-time quantitative polymerase chain reaction (PCR). Results EBV-DNA load of patients with HLH showed no statistical difference in PBMC, plasma and WB samples, while patients with IM and PTLD showed a higher viral load in PBMC samples. The strongest correlation of EBV-DNA level was found between PBMC and WB samples among patients with IM, HLH and PTLD. The follow-up of EBV-DNA showed that the viral load became negative along with the recovery from the disease, while that in WB and PBMC would remain positive for a long time. Conclusions For the diagnosis and monitoring of EBV-DNA, the type of specimen should be chosen reasonably according to the disease. As for IM and HLH, plasma is recommended to quantify the EBV-DNA load, while PBMC and plasma are preferred in PTLD.
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Affiliation(s)
- Wang Kedi
- Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China
| | - Xu Dongjiang
- Clinical Laboratory, Beijing Jishuitan Hospital, Peking University, Beijing, P.R. China
| | - Lv Zhi
- Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China
| | - Gao Yan
- Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China
| | - Jia Kun
- Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China
| | - Su Jianrong
- Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China
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49
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Comparison of Clinical Features and Outcome of Pediatric Posttransplant Lymphoproliferative Disorder in Recipients of Small Bowel Allograft Versus Isolated Liver Transplantation. Transplantation 2019; 104:1429-1436. [DOI: 10.1097/tp.0000000000003004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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50
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Malyszko J. Post-transplant lymphoproliferative disorder: risk factors and management. Nephrol Dial Transplant 2019; 36:gfz207. [PMID: 31598720 DOI: 10.1093/ndt/gfz207] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Indexed: 11/15/2022] Open
Affiliation(s)
- Jolanta Malyszko
- Department of Nephrology, Dialysis and Internal Medicine, Warsaw Medical University, Warsaw, Poland
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