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Arsenault A, Sharma P, Buckley J, Braun A, Ewing E, Rhakra S, Cummings L, Bansal D. Transmission of Lung Adenocarcinoma From a Single Donor in 2 Transplant Recipients: A Case Report With Literature Review. Transplant Proc 2023; 55:1888-1892. [PMID: 37714809 DOI: 10.1016/j.transproceed.2023.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 08/16/2023] [Indexed: 09/17/2023]
Abstract
Malignancies transmitted to recipients during solid organ transplants carry significant morbidity and mortality. We present 2 cases of adenocarcinoma of donor lung origin transmitted via liver and kidney transplant from a single donor. Both recipients developed metastatic adenocarcinoma of lung origin with p.L858R mutation in the epidermal growth factor receptor gene and a microsatellite signature of donor origin. Osimertinib was trialed in the liver recipient; however, it was discontinued because of hepatotoxicity and disease progression. Standard donor screening protocols limit malignancy transmission but do not include multicancer detection assays. As these technologies evolve, they may be implemented in donor screening.
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Affiliation(s)
- Andre Arsenault
- Oncology Hematology, University of Missouri at Kansas City, Kansas City, Missouri, USA.
| | - Parth Sharma
- Internal Medicine, University of Missouri at Kansas City, Kansas City, Missouri
| | - Jennifer Buckley
- Department of Pathology St Lukes Hospital, Kansas City, Missouri
| | - Alex Braun
- Department of Pathology St Lukes Hospital, Kansas City, Missouri
| | - Eric Ewing
- Department of Pathology St Lukes Hospital, Kansas City, Missouri
| | - Sunpreet Rhakra
- Department of Radiation Oncology, St Lukes Hospital, Kansas City, Missouri
| | - Lee Cummings
- Department of Hepatobiliary Surgery, University of Missouri Kansas City, Kansas City, Missouri
| | - Dhruv Bansal
- Department of Oncology and Hematology, University of Missouri Kansas City, Kansas City, Missouri
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2
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Lee BT, Ganjoo N, Fiel MI, Hechtman JF, Sarkar SA, Kim-Schluger L, Florman SS, Schiano TD. Recurrent Liver Allograft Injury in Patients With Donor-Derived Malignancy Treated With Immunosuppression Cessation and Retransplantation. Am J Clin Pathol 2022; 158:199-205. [PMID: 35285881 DOI: 10.1093/ajcp/aqac026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 01/28/2022] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES Donor-derived malignancy of the liver allograft is a rare but serious condition in the setting of necessary immunosuppression. Retransplantation after abrupt immunosuppression cessation has been performed with durable cancer-free survival. METHODS We present 2 cases of patients with donor-derived malignancy who were treated with complete immunosuppression cessation, which induced rapidly progressive liver allograft rejection and failure, with a need for subsequent retransplantation. We reviewed all serial liver biopsies and explants from both patients and performed C4d immunostaining. RESULTS Initial explants of both patients showed severe allograft rejection, with unusual features of sinusoidal obstruction syndrome and C4d positivity. Malignant tumors in the explants were necrotic, related to rejection of donor-derived cancer cells and tissue. Follow-up of both patients has shown long-term cancer-free survival but issues with recurrent allograft failure requiring a third transplant. The reasons for retransplantation in both cases were related to allograft failure from antibody-mediated rejection. CONCLUSIONS Clinicians should be aware of a potentially increased risk of rejection and recurrent allograft failure when strategizing treatment of donor-derived malignancy with immunosuppression cessation and retransplantation.
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Affiliation(s)
- Brian T Lee
- Division of Gastroenterology and Transplantation Institute, Loma Linda University Health, Loma Linda, CA, USA
- Recanati/Miller Transplantation Institute, Division of Liver Diseases, Department of Medicine, New York, NY, USA
| | - Naveen Ganjoo
- Recanati/Miller Transplantation Institute, Division of Liver Diseases, Department of Medicine, New York, NY, USA
| | - M Isabel Fiel
- Department of Pathology, Molecular and Cell-Based Medicine, New York, NY, USA
| | | | - Suparna A Sarkar
- Department of Pathology, New York University School of Medicine, New York, NY, USA
| | - Leona Kim-Schluger
- Recanati/Miller Transplantation Institute, Division of Liver Diseases, Department of Medicine, New York, NY, USA
| | - Sander S Florman
- Recanati/Miller Transplantation Institute, Division of Abdominal Transplantation, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Thomas D Schiano
- Recanati/Miller Transplantation Institute, Division of Liver Diseases, Department of Medicine, New York, NY, USA
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Greenhall GHB, Ibrahim M, Dutta U, Doree C, Brunskill SJ, Johnson RJ, Tomlinson LA, Callaghan CJ, Watson CJE. Donor-Transmitted Cancer in Orthotopic Solid Organ Transplant Recipients: A Systematic Review. Transpl Int 2022; 35:10092. [PMID: 35185366 PMCID: PMC8842379 DOI: 10.3389/ti.2021.10092] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 12/07/2021] [Indexed: 01/18/2023]
Abstract
Donor-transmitted cancer (DTC) has major implications for the affected patient as well as other recipients of organs from the same donor. Unlike heterotopic transplant recipients, there may be limited treatment options for orthotopic transplant recipients with DTC. We systematically reviewed the evidence on DTC in orthotopic solid organ transplant recipients (SOTRs). We searched MEDLINE, EMBASE, PubMed, Scopus, and Web of Science in January 2020. We included cases where the outcome was reported and excluded donor-derived cancers. We assessed study quality using published checklists. Our domains of interest were presentation, time to diagnosis, cancer extent, management, and survival. There were 73 DTC cases in liver (n = 51), heart (n = 10), lung (n = 10) and multi-organ (n = 2) recipients from 58 publications. Study quality was variable. Median time to diagnosis was 8 months; 42% were widespread at diagnosis. Of 13 cases that underwent re-transplantation, three tumours recurred. Mortality was 75%; median survival 7 months. Survival was worst in transmitted melanoma and central nervous system tumours. The prognosis of DTC in orthotopic SOTRs is poor. Although re-transplantation offers the best chance of cure, some tumours still recur. Publication bias and clinical heterogeneity limit the available evidence. From our findings, we suggest refinements to clinical practice. Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020165001, Prospero Registration Number: CRD42020165001.
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Affiliation(s)
- George H. B. Greenhall
- Department of Statistics and Clinical Research, NHS Blood and Transplant, Bristol, United Kingdom
- School of Immunology and Microbial Sciences, King’s College London, London, United Kingdom
- *Correspondence: George H. B. Greenhall,
| | - Maria Ibrahim
- Department of Statistics and Clinical Research, NHS Blood and Transplant, Bristol, United Kingdom
- School of Immunology and Microbial Sciences, King’s College London, London, United Kingdom
| | - Utkarsh Dutta
- GKT School of Medical Education, King’s College London, London, United Kingdom
| | - Carolyn Doree
- Systematic Review Initiative, NHS Blood and Transplant, Oxford, United Kingdom
| | - Susan J. Brunskill
- Systematic Review Initiative, NHS Blood and Transplant, Oxford, United Kingdom
| | - Rachel J. Johnson
- Department of Statistics and Clinical Research, NHS Blood and Transplant, Bristol, United Kingdom
| | - Laurie A. Tomlinson
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Chris J. Callaghan
- School of Immunology and Microbial Sciences, King’s College London, London, United Kingdom
- Department of Nephrology and Transplantation, Guy’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom
| | - Christopher J. E. Watson
- Department of Surgery, University of Cambridge, Cambridge, United Kingdom
- The Cambridge NIHR Biomedical Research Centre, Cambridge, United Kingdom
- NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, University of Cambridge, Cambridge, United Kingdom
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Abstract
Hepatic retransplant accounts for 5% to 15% of liver transplants in most series and is associated with significantly increased hospital costs and inferior patient survival when compared with primary liver transplant. Early retransplants are usually due to primary graft nonfunction or vascular thrombosis, whereas later retransplants are most commonly necessitated by chronic rejection or recurrent primary liver disease. Hepatic retransplant remains the sole option for survival in many patients facing allograft failure after liver transplant. With improved techniques to match retransplant candidates with appropriate donor grafts, it is hoped that the outcomes of retransplant will continue to improve in future.
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Desai R, Neuberger J. Donor transmitted and de novo cancer after liver transplantation. World J Gastroenterol 2014; 20:6170-6179. [PMID: 24876738 PMCID: PMC4033455 DOI: 10.3748/wjg.v20.i20.6170] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2013] [Revised: 12/02/2013] [Accepted: 01/05/2014] [Indexed: 02/06/2023] Open
Abstract
Cancers in solid organ recipients may be classified as donor transmitted, donor derived, de novo or recurrent. The risk of donor-transmitted cancer is very low and can be reduced by careful screening of the donor but cannot be abolished and, in the United Kingdom series is less than 0.03%. For donors with a known history of cancer, the risks will depend on the nature of the cancer, the interventions given and the interval between diagnosis and organ donation. The risks of cancer transmission must be balanced against the risks of death awaiting a new graft and strict adherence to current guidelines may result increased patient death. Organs from selected patients, even with high-grade central nervous system (CNS) malignancy and after a shunt, can, in some circumstances, be considered. Of potential donors with non-CNS cancers, whether organs may be safely used again depends on the nature of the cancer, the treatment and interval. Data are scarce about the most appropriate treatment when donor transmitted cancer is diagnosed: sometimes substitution of agents and reduction of the immunosuppressive load may be adequate and the impact of graft removal should be considered but not always indicated. Liver allograft recipients are at increased risk of some de novo cancers, especially those grafted for alcohol-related liver disease and hepatitis C virus infection. The risk of lymphoproliferative disease and cancers of the skin, upper airway and bowel are increased but not breast. Recipients should be advised to avoid risk behavior and monitored appropriately.
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6
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Donor-transmitted malignancy in a liver transplant recipient: a case report and review of literature. Dig Dis Sci 2013; 58:1185-90. [PMID: 23242807 DOI: 10.1007/s10620-012-2501-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2012] [Accepted: 11/20/2012] [Indexed: 12/21/2022]
Abstract
Donor-transmitted malignancy is a rare complication of organ transplantation. This case illustrates a donor-transmitted adenocarcinoma in a patient 11 months after an orthotopic liver transplant for cryptogenic cirrhosis and hepatocellular carcinoma (HCC). Diagnosis of donor-transmitted malignancy may be challenging and can be confused with HCC recurrence. A timely diagnosis is crucial as a delay may limit treatment options. Biopsy of newly found liver lesions and the use of karyotypic and microsatellite analysis may be essential for diagnosis. Protocols should be in place to help recognize and limit the incidence of donor-transmitted malignancy.
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Begum R, Harnois D, Satyanarayana R, Krishna M, Halling KC, Kim GP, Nguyen JH, Keaveny AP. Retransplantation for donor-derived neuroendocrine tumor. Liver Transpl 2011; 17:83-7. [PMID: 21254348 DOI: 10.1002/lt.22196] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Although tumor transmission through liver transplantation (LT) is a rare occurrence, the consequences can be devastating, even when a very aggressive management approach is adopted. We report the case of a donor-derived small cell neuroendocrine tumor (NET) in a patient who underwent LT for cholangiocarcinoma. Despite locoregional therapy, chemotherapy and ultimately retransplantation, the patient died from metastases. The high grade nature of the NET was the most important determinant of prognosis in this case. Our experience suggests that retransplantation for donor-derived NET should only be considered when tumor biology is favorable.
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Affiliation(s)
- Rehana Begum
- Department of Transplant, Mayo Clinic, Jacksonville, FL 32224, USA
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Tan HH, Fiel MI, del Rio Martin J, Schiano TD. Graft rejection occurring in post-liver transplant patients receiving cytotoxic chemotherapy: a case series. Liver Transpl 2009; 15:634-9. [PMID: 19479807 DOI: 10.1002/lt.21727] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Liver transplant recipients are known to be at increased risk for the development of de novo neoplasms or the recurrence of preexisting malignancies, and this is possibly related to the use of immunosuppressive medication. Little is known about the effects of cytotoxic chemotherapy on graft function after transplantation. A retrospective chart and pathology database review was undertaken to identify post-liver transplant patients developing rejection during chemotherapy. All liver biopsies were reviewed by a hepatopathologist. Three patients were identified. All patients were diagnosed with cancer within 7 years of liver transplantation; two-thirds died soon after the diagnosis of malignancy. Rejection occurred soon after chemotherapy was started. All patients were receiving prednisone and tacrolimus (trough levels: 2.1-4.8 ng/mL). One patient developed plasma cell hepatitis (de novo autoimmune hepatitis). There was no histologic evidence of hepatotoxicity due to the chemotherapeutic agents. Cytotoxic chemotherapy should be used in liver transplant recipients with caution, and immunosuppressant doses should be maintained at therapeutic levels, as patients may be at risk for allograft rejection. Treatment of rejection or plasma cell hepatitis in this setting should be undertaken in a timely and aggressive fashion to prevent chronic ductopenic rejection.
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Affiliation(s)
- Hui-Hui Tan
- Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA
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Abstract
Chronic allograft nephropathy (CAN) is the leading cause of renal allograft loss in paediatric renal transplant recipients. CAN is the result of immunological and nonimmunological injury, including acute rejection episodes, hypoperfusion, ischaemia reperfusion, calcineurin toxicity, infection and recurrent disease. The development of CAN is often insidious and may be preceded by subclinical rejection in a well-functioning allograft. Classification of CAN is histological using the Banff classification of renal allograft pathology with classic findings of interstitial fibrosis, tubular atrophy, glomerulosclerosis, fibrointimal hyperplasia and arteriolar hyalinosis. Although improvement in immunosuppression has led to greater 1-year graft survival rates, chronic graft loss remains relatively unchanged and opportunistic infectious complications remain a problem. Protocol biopsy monitoring is not current practice in paediatric transplantation for CAN monitoring but may have a place if new treatment options become available. Newer immunosuppression regimens, closer monitoring of the renal allograft and management of subclinical rejection may lead to reduced immune injury leading to CAN in the paediatric population but must be weighed against the risk of increased immunosuppression and calcineurin inhibitor nephrotoxicity.
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10
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Snape K, Izatt L, Ross P, Ellis D, Mann K, O'Grady J. Donor-transmitted malignancy confirmed by quantitative fluorescence polymerase chain reaction genotype analysis: a rare indication for liver retransplantation. Liver Transpl 2008; 14:155-8. [PMID: 18236388 DOI: 10.1002/lt.21347] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Affiliation(s)
- Katie Snape
- Department of Neurology, Guy's and St Thomas' National Health Service Foundation Trust, London, United Kingdom.
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11
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Wente MN, Sauer P, Mehrabi A, Weitz J, Büchler MW, Schmidt J, Schemmer P. Review of the clinical experience with a modified release form of tacrolimus [FK506E (MR4)] in transplantation. Clin Transplant 2006; 20 Suppl 17:80-4. [PMID: 17100706 DOI: 10.1111/j.1399-0012.2006.00605.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Non-compliance in solid transplantation recipients is a major factor in acute graft rejection, which influences patient survival. Nowadays, tacrolimus is one of the most widely used immunosuppressant agents together with cyclosporine following kidney and liver transplantation with a standardized twice-daily dosing regimen. To improve the patients' compliance to the prescribed immunosuppressive therapy, FK506E (MR4), a modified release (MR) oral dosage form of tacrolimus has been developed for a once-daily dosing regimen. This report reviews the most recent results of clinical trials with MR tacrolimus after kidney and liver transplantation.
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Affiliation(s)
- Moritz N Wente
- Department of General Surgery, Ruprecht-Karls-University, Heidelberg, Heidelberg, Germany
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12
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Abstract
The major causes of renal transplant loss are death from vascular, malignant or infectious disease, and loss of the allograft from chronic renal dysfunction associated with the development of graft fibrosis and glomerulosclerosis. Chronic allograft nephropathy (CAN) is the histologic description of the fibrosis, vascular and glomerular damage occurring in renal allografts. Clinical programs rely on monitoring change in serum creatinine for identification of patients at risk of CAN, but this change occurs late in the course of the disease, and underestimates the severity of pathologic change. CAN has several causes: ischemia-reperfusion injury, ineffectively or untreated clinical and subclinical rejection, and superimposed calcineurin inhibitor nephrotoxicity, exacerbating pre-existing donor disease. Once established, interstitial fibrosis and arteriolar hyalinosis lead to progressive glomerulosclerosis over the subsequent years. There have been a number of approaches to treatment aimed at reducing the impact of CAN, mostly centered around avoidance of calcineurin inhibitors through their elimination in all, or just selected, patients. These immunosuppression strategies combine corticosteroids with azathioprine or mycophenolate mofetil, and/or sirolimus and everolimus. Late identification of CAN in individual patients has meant that strategies for intervening to prevent chronic renal allograft dysfunction and subsequent graft loss tend to be "too little and far too late."
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Affiliation(s)
- Jeremy R Chapman
- Department of Renal Medicine, Westmead Hospital, Westmead, New South Wales 2145, Australia.
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Detry O, De Roover A, de Leval L, Herens C, Delwaide J, Honoré P, Meurisse M. Transmission of an undiagnosed sarcoma to recipients of kidney and liver grafts procured in a non-heart beating donor. Liver Transpl 2005; 11:696-9. [PMID: 15915495 DOI: 10.1002/lt.20457] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Transmission of an undiagnosed cancer with solid organ transplantation is a rare but dreadful event. In this paper the authors report the transmission of an undiagnosed sarcoma to recipients of kidney and liver grafts procured in a Maastricht category 3 non-heart beating donor. To the authors' knowledge this case is the first report of such a transmission with a liver graft procured in a non-heart beating donor. The cancer transferal was diagnosed 1 year after transplantation in the recipients of the liver and of one kidney. The liver recipient died from multiple organ failure after a failed attempt of tumor resection. The kidney recipient underwent immunosuppression withdrawal and transplantectomy. Non-heart beating donors should not be particularly at risk for undiagnosed cancer transmission if the procurement is performed according to the same rules of careful inspection of the abdominal and thoracic organs. After diagnosis of donor cancer transmission, kidney recipients should have the graft removed, and immunosuppression should be interrupted. The management of liver graft recipients is very difficult in this setting, and long-term survival was very rarely reported.
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Affiliation(s)
- Olivier Detry
- Department of Abdominal Surgery, University of Liège, CHU Sart Tilman, Liège, Belgium.
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Seda Neto J, Macedo C, Jaffe R, Mazariegos GV, Sindhi R, Bond GJ, Abu-Elmagd K, Reyes J. Carcinoma of donor origin after liver-intestine transplantation in a child. Pediatr Transplant 2005; 9:244-8. [PMID: 15787801 DOI: 10.1111/j.1399-3046.2005.00252.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Tumor-related complications after intestinal transplantation in children have been principally EBV driven post-transplant disorders. We describe the clinical course of a child, with a diagnosis of microvillus inclusion disease who received a liver and intestine allograft at the age of 9 months. His postoperative course was significant for multiple episodes of acute intestinal allograft rejection and eventually the development of post-transplant lymphoproliferative disorder (PTLD), which resolved. At 8 yr post-transplant he presented with masses in the intestine allograft mesentery and in the right lobe of the allograft liver, biopsy of which revealed a relatively undifferentiated tumor, suggestive of a carcinoma. In situ hybridization for X and Y chromosomes, revealed his tumor to be of donor origin. Treatment included debulking of the mesenteric mass with segmental enterectomy of the intestinal allograft, and stopping his immunosuppression for a period of 4 months; this resulted in complete resolution of his malignancy. Immunosuppression with tacrolimus and steroids was restarted because of intestinal allograft rejection; he died suddenly of unknown causes at 17 months post-diagnosis of carcinoma. The severely immunosuppressed state produced in this patient allowed for the development of an unusual donor derived carcinoma, which resolved spontaneously with withdrawal of immunosuppression. The mechanism of such regression of tumor may be related to restitution of immunologic competence, but is yet to be determined.
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Affiliation(s)
- Joao Seda Neto
- Thomas E. Starzl Transplantation Institute, Pittsburgh, PA, USA
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