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Baysal S, Şahin D, Sezer S, Yayla ME, Uslu E, Ateş A, Turgay TM, Kinikli G. Malignancy-associated risk factors in patients with systemic sclerosis. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2025:23971983251322841. [PMID: 40124982 PMCID: PMC11924055 DOI: 10.1177/23971983251322841] [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: 12/22/2024] [Accepted: 02/06/2025] [Indexed: 03/25/2025]
Abstract
Background and Aim Systemic sclerosis was found to be associated with an increase in cancer incidence. The target of this study was to investigate the most common malignancies and to identify factors that increase the cancer risk in systemic sclerosis patients. Materials and Methods In this single-centre retrospective study, we screened 252 patients attending our outpatient clinic between January 2005 and December 2021. Results A total of 252 systemic sclerosis patients were included in the study. Data for the patients were obtained by evaluating their medical records retrospectively. A total of 252 patients with systemic sclerosis were analysed. Nineteen patients were diagnosed with malignancies. Lung cancer was the most common malignancy among patients. Malignancies were not correlated with sex, follow-up period, type of systemic sclerosis, organ involvement, smoking history, serological tests, comorbidities, dose and duration of disease-modifying antirheumatic drugs (DMARDs), but advanced age at systemic sclerosis diagnosis increased the risk of malignancy (p = 0.017) in systemic sclerosis patients. Conclusion In the current study, advanced age at systemic sclerosis diagnosis was determined to be an extra risk factor for the initiation of cancer in systemic sclerosis patients. Particularly in this patient group, additional screenings might be helpful for early diagnosis. Treatments such as methotrexate, cyclophosphamide, azathioprine, and mycophenolate mofetil can be used without additional cancer risk.
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Affiliation(s)
- Serdar Baysal
- Department of Internal Medicine, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Didem Şahin
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Serdar Sezer
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Müçteba E Yayla
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Emine Uslu
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Aşkın Ateş
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Tahsin M Turgay
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Gülay Kinikli
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Ankara University, Ankara, Turkey
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Xu X, Zhang S, Luo Z, Zheng Y, Kong T, Huang C, Qiu Z. Frontiers and Controversies in De Novo Gastrointestinal Tumors After Organ Transplantation: Current Progress and Future Directions. Ann Surg Oncol 2025:10.1245/s10434-025-16975-w. [PMID: 40035907 DOI: 10.1245/s10434-025-16975-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 01/21/2025] [Indexed: 03/06/2025]
Abstract
The increasing success of organ transplantation has significantly improved survival for patients with end-stage diseases, yet it introduces a complex dilemma: the elevated risk for the development of de novo gastrointestinal (GI) tumors. The sustained immunosuppression required to maintain graft function paradoxically undermines the body's natural defenses against cancer, leading to a higher incidence, aggressive progression, and atypical presentations of GI tumors among transplant recipients compared with the general population. This presents a pressing challenge: balancing the dual imperatives of preventing graft rejection and effectively managing malignancies. Current treatment paradigms, including surgical approaches, chemotherapy, radiation therapy, and the emerging role of immunotherapy, are fraught with complexities due to the altered immune landscape in these patients. This review underscores the critical need to understand the multifaceted relationship between post-transplantation immunosuppression and tumorigenesis, providing a comprehensive exploration of epidemiologic shifts, pathophysiologic insights, and the intricacies of the tumor microenvironment in this unique patient population. Understanding and managing GI tumors in transplant recipients is not only a clinical challenge, but also a necessary frontier in transplant oncology, promising to refine therapeutic strategies and improve the longevity and quality of life for this growing patient cohort.
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Affiliation(s)
- Ximo Xu
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shaopeng Zhang
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zai Luo
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yan Zheng
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tingting Kong
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chen Huang
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Zhengjun Qiu
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Kong D, Duan J, Chen S, Wang Z, Ren J, Lu J, Chen T, Song Z, Wu D, Chang Y, Yin Z, Shen Z, Zheng H. Transplant oncology and anti-cancer immunosuppressants. Front Immunol 2025; 15:1520083. [PMID: 39840041 PMCID: PMC11747528 DOI: 10.3389/fimmu.2024.1520083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 12/12/2024] [Indexed: 01/23/2025] Open
Abstract
Organ transplantation is a life-saving intervention that enhances the quality of life for patients with end-stage organ failure. However, long-term immunosuppressive therapy is required to prevent allogeneic graft rejection, which inadvertently elevates the risk of post-transplant malignancies, especially for liver transplant recipients with a prior history of liver cancer. In response, the emerging field of transplant oncology integrates principles from oncology and immunology to improve outcomes for patients at high risk of tumor occurrence or recurrence following transplantation. Therefore, it is of substantial clinical significance to develop immunosuppressants that possess both immunosuppressive and anti-tumor properties. For instance, mTOR inhibitors demonstrate anti-tumor effects among antimetabolite immunosuppressive drugs, and recent studies indicate that capecitabine, an antimetabolite chemotherapeutic, may also exhibit immunosuppressive activity in the clinic for liver transplants suffering from hepatocellular carcinoma. This review systematically explores potential immunosuppressants with dual anti-tumor and immunosuppressive effects to support the management of transplant patients at elevated risk of tumor occurrence or recurrence.
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Affiliation(s)
- Dejun Kong
- Nankai University School of Medicine, Tianjin, China
| | - Jinliang Duan
- Nankai University School of Medicine, Tianjin, China
| | - Shaofeng Chen
- Nankai University School of Medicine, Tianjin, China
| | - Zhenglu Wang
- Tianjin Organ Transplantation Research Center, Tianjin First Central Hospital, Nankai University School of Medicine, Tianjin, China
- Key Laboratory of Transplant Medicine, Chinese Academy of Medical Sciences, Tianjin, China
| | - Jiashu Ren
- Tianjin First Central Clinical College, Tianjin, China
| | - Jianing Lu
- Tianjin First Central Clinical College, Tianjin, China
| | - Tao Chen
- Nankai University School of Medicine, Tianjin, China
| | - Zhuolun Song
- Tianjin Organ Transplantation Research Center, Tianjin First Central Hospital, Nankai University School of Medicine, Tianjin, China
| | - Di Wu
- Tianjin Organ Transplantation Research Center, Tianjin First Central Hospital, Nankai University School of Medicine, Tianjin, China
| | - Yuan Chang
- Nankai University School of Medicine, Tianjin, China
| | - Zhongqian Yin
- Tianjin First Central Clinical College, Tianjin, China
| | - Zhongyang Shen
- Tianjin Organ Transplantation Research Center, Tianjin First Central Hospital, Nankai University School of Medicine, Tianjin, China
- Key Laboratory of Transplant Medicine, Chinese Academy of Medical Sciences, Tianjin, China
- Research Institute of Transplant Medicine, Nankai University, Tianjin, China
- Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Hong Zheng
- Tianjin Organ Transplantation Research Center, Tianjin First Central Hospital, Nankai University School of Medicine, Tianjin, China
- Key Laboratory of Transplant Medicine, Chinese Academy of Medical Sciences, Tianjin, China
- Research Institute of Transplant Medicine, Nankai University, Tianjin, China
- Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
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Okumi M, Inoue Y, Miyashita M, Ueda T, Fujihara A, Hongo F, Ukimua O. Genitourinary malignancies in kidney transplant recipients. Int J Urol 2024; 31:1321-1329. [PMID: 39316503 DOI: 10.1111/iju.15588] [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: 07/15/2023] [Accepted: 09/09/2024] [Indexed: 09/26/2024]
Abstract
Advances in immunosuppressive therapy and postoperative management have greatly improved the graft and patient survival rates after kidney transplantation; however, the incidence of post-transplant malignant tumors is increasing. Post-renal transplantation malignant tumors are associated with renal failure, immunosuppression, and viral infections. Moreover, the risk of developing cancer is higher in kidney transplant recipients than in the general population, and the tendency to develop cancer is affected by the background and environment of each patient. Recently, cancer after kidney transplantation has become the leading cause of death in Japan. Owing to the aggressive nature and poor prognosis of genitourinary malignancies, it is crucial to understand their epidemiology, risk factors, and best practices in kidney transplant recipients. This review has a special emphasis on the epidemiology, risk factors, and treatment protocols of genitourinary malignancies in kidney transplant recipients to enhance our understanding of the appropriate management strategies. Optimal immunosuppressive therapy and cancer management for these patients remain controversial, but adherence to the general guidelines is recommended.
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Affiliation(s)
- Masayoshi Okumi
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yuta Inoue
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masatsugu Miyashita
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takashi Ueda
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Atsuko Fujihara
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Fumiya Hongo
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Osamu Ukimua
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Bigotte Vieira M, Arai H, Nicolau C, Murakami N. Cancer Screening and Cancer Treatment in Kidney Transplant Recipients. KIDNEY360 2024; 5:1569-1583. [PMID: 39480669 PMCID: PMC11556922 DOI: 10.34067/kid.0000000000000545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Abstract
As the population ages and post-transplant survival improves, pretransplant and post-transplant malignancy are becoming increasingly common. In addition, rapid advances in cancer therapies and improving outcomes prompt us to rethink pretransplant cancer-free wait time and screening strategies. Although kidney transplant recipients (KTRs) are at higher risk of developing cancer, epidemiological data on how to best screen and treat cancers in KTRs are incomplete. Thus, current recommendations are still largely on the basis of studies in the general population, and their validity in KTRs is uncertain. Kidney transplant candidates without prior cancer should be evaluated for latent malignancies even in the absence of symptoms. Conversely, individuals with a history of malignancy require thorough monitoring to detect potential recurrences or de novo malignancies. When treating KTRs with cancer, reducing immunosuppression can enhance antitumor immunity, yet this also increases the risk of graft rejection. Optimal treatment and immunosuppression management remains undefined. As the emergence of novel cancer therapies adds complexity to this challenge, individualized risk-benefit assessment is crucial. In this review, we discuss up-to-date data on pretransplant screening and cancer-free wait time, as well as post-transplant cancer screening, prevention strategies, and treatment, including novel therapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell therapies.
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Affiliation(s)
- Miguel Bigotte Vieira
- Nephrology Department, Hospital Curry Cabral, Unidade Local de Saúde São José, Lisbon, Portugal
- NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
| | - Hiroyuki Arai
- Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Carla Nicolau
- Nephrology Department, Hospital Curry Cabral, Unidade Local de Saúde São José, Lisbon, Portugal
| | - Naoka Murakami
- Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts
- Harvard Medical School, Boston, Massachusetts
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Alouani E, Laparra A, Perret A, Sakkal M, Messayke S, Danlos FX, Ouali K, Hollebecque A, Even C, Ammari S, Baldini C, Champiat S, Besse B, Robert C, Guettier C, Samuel D, Lambotte O, De Martin E, Michot JM. Immunosuppressant mycophenolate mofetil for patients with steroid-refractory immune-related hepatitis induced by checkpoint inhibitors in oncology. Eur J Cancer 2023; 193:113313. [PMID: 37748398 DOI: 10.1016/j.ejca.2023.113313] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 08/11/2023] [Accepted: 08/22/2023] [Indexed: 09/27/2023]
Abstract
BACKGROUND Immune-checkpoint inhibitor (ICI) hepatitis, which does not improve with steroids and requires additional immunosuppressant, is defined as steroid-refractory ICI hepatitis. The outcome of patients with steroid-refractory ICI hepatitis remains poorly determined. Herein, we investigated the incidence, clinical features, and outcome of patients treated with second-line immunosuppressant for steroid-refractory ICI hepatitis. METHODS This is a retrospective analysis of patients who presented ICI hepatitis from 1st June 2016 to 30th September 2022. Steroid-refractory ICI hepatitis was defined as no clinical and biological improvement after systemic steroid therapy ≥1 mg/kg/d. Main objectives were to assess the frequency and risk factors associated with steroid-refractory ICI hepatitis and to evaluate the efficacy of second-line immunosuppressants. RESULTS In total, 130 patients with grade ≥3 ICI hepatitis were screened, of them 60 (46.2%) were treated with systemic steroids. In total, 11/130 (8.5%) had steroid-refractory hepatitis. Statistically significant factors associated with steroid-refractory hepatitis included previous liver comorbidities (54.5% versus 11.6%; p < 0.01), hyperbilirubinemia (p < 0.001), and general symptoms (fever, jaundice, ascites, and/or encephalopathy) associated with hepatitis (72.7% versus 30.8%; p = 0.015). The 11 patients with steroid-refractory hepatitis were treated with mycophenolate mofetil. In total, resolution or return to grade ≤1 for hepatitis was observed in 81.8% (9/11) of patients. CONCLUSIONS Steroid-refractory ICI hepatitis accounted for 8.5% of patients with grade ≥3 immune-related hepatitis and was statistically associated with previous liver comorbidities, hyperbilirubinemia, and general symptoms. Mycophenolate mofetil was a suitable option of therapy for steroid-refractory ICI hepatitis.
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Affiliation(s)
- Emily Alouani
- Département d'Innovation Thérapeutique et Essais Précoces, Gustave Roussy - Paris-Saclay University, Villejuif, France; Digestive Medical Oncology Department, IUCT-Rangueil, Toulouse Hospital University, Toulouse, France
| | - Ariane Laparra
- Département Interdisciplinaire d'Organisation des Parcours Patients, Gustave Roussy - Paris-Saclay University, Villejuif, France
| | - Audrey Perret
- Département Interdisciplinaire d'Organisation des Parcours Patients, Gustave Roussy - Paris-Saclay University, Villejuif, France
| | - Madonna Sakkal
- Département d'Innovation Thérapeutique et Essais Précoces, Gustave Roussy - Paris-Saclay University, Villejuif, France
| | - Sabine Messayke
- Pharmacovigilance Unit, Gustave Roussy - Paris-Saclay University, Villejuif, France
| | - Francois-Xavier Danlos
- Département d'Innovation Thérapeutique et Essais Précoces, Gustave Roussy - Paris-Saclay University, Villejuif, France; INSERM U1015 and CIC1428 BIOTHERIS, Gustave Roussy, Villejuif, France
| | - Kaissa Ouali
- Département d'Innovation Thérapeutique et Essais Précoces, Gustave Roussy - Paris-Saclay University, Villejuif, France
| | - Antoine Hollebecque
- Département d'Innovation Thérapeutique et Essais Précoces, Gustave Roussy - Paris-Saclay University, Villejuif, France
| | - Caroline Even
- Department of Medical Oncology, Gustave Roussy - Paris-Saclay University, Villejuif, France
| | - Samy Ammari
- ELSAN Department of Radiology, Institut de Cancérologie Paris Nord, Sarcelles, France; Department of Radiology, Gustave Roussy Cancer Campus, Biomaps, UMR1281 INSERM, CEA, CNRS, Université Paris-Saclay, Villejuif, France
| | - Capucine Baldini
- Département d'Innovation Thérapeutique et Essais Précoces, Gustave Roussy - Paris-Saclay University, Villejuif, France
| | - Stéphane Champiat
- Département d'Innovation Thérapeutique et Essais Précoces, Gustave Roussy - Paris-Saclay University, Villejuif, France
| | - Benjamin Besse
- Department of Medical Oncology, Gustave Roussy - Paris-Saclay University, Villejuif, France
| | - Caroline Robert
- Department of Medical Oncology, Gustave Roussy - Paris-Saclay University, Villejuif, France
| | - Catherine Guettier
- Department of Pathology, Bicêtre Hospital, Assistance Publique - Hôpitaux de Paris, Paris-Saclay University, UMR-S 1193, Le Kremlin Bicêtre, France
| | - Didier Samuel
- Department of Hepatology, Paul-Brousse Hospital, Assistance Publique - Hôpitaux de Paris, Centre Hépato-Biliaire, INSERM 1193, Villejuif, France
| | - Olivier Lambotte
- Internal Médecine Department, Bicêtre Hospital, Assistance Publique - Hôpitaux de Paris, Paris-Saclay University, Le Kremlin-Bicêtre, France; IDMIT Department, IBFJ, Centre Immunology of Viral Infections and Autoimmune Diseases, INSERM, CEA, Université Paris Saclay, Le Kremlin Bicêtre, France
| | - Eleonora De Martin
- Department of Hepatology, Paul-Brousse Hospital, Assistance Publique - Hôpitaux de Paris, Centre Hépato-Biliaire, INSERM 1193, Villejuif, France
| | - Jean-Marie Michot
- Département d'Innovation Thérapeutique et Essais Précoces, Gustave Roussy - Paris-Saclay University, Villejuif, France; INSERM U1170, Université Paris-Saclay, Gustave Roussy, Villejuif, France.
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Sinha T, Mishra H, Thomas R, Karpe SP, Waghmare S, Nair JP, Thorve SM. A case of post renal transplant PTLD of lung. Lung India 2023; 40:465-468. [PMID: 37787363 PMCID: PMC10553785 DOI: 10.4103/lungindia.lungindia_94_23] [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: 03/03/2023] [Revised: 03/06/2023] [Accepted: 04/08/2023] [Indexed: 10/04/2023] Open
Abstract
Post Transplant Lymphoproliferative Disorder (PTLD) is a heterogeneous group of Lymphoid proliferative disorders that occur in patients post Hematogenous or Solid organ transplants. They are closely associated with Ebstein-Barr Virus and can range from polyclonal lesions to frank lymphomas. PTLD is usually a rare post-transplant complication, with the incidence being higher post Lung or Heart Transplantation and less commonly seen post-renal transplantation. The incidence post renal transplantation is less than 1%, with most of the cases being limited to the Gastro-Intestinal Tract and Lymph nodes, and incidence in the lungs being extremely rare. Here we present a case report of PTLD of the lung in a post-renal transplant recipient.
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Affiliation(s)
- Tanay Sinha
- Department of Respiratory Medicine, Lokmanya Tilak Municipal Medical College, Sion, Maharashtra, India
| | - Harshita Mishra
- Department of Respiratory Medicine, Lokmanya Tilak Municipal Medical College, Sion, Maharashtra, India
| | - Rosna Thomas
- Department of Respiratory Medicine, Lokmanya Tilak Municipal Medical College, Sion, Maharashtra, India
| | - Sonal P. Karpe
- Department of Respiratory Medicine, Lokmanya Tilak Municipal Medical College, Sion, Maharashtra, India
| | - Siddharth Waghmare
- Department of Respiratory Medicine, Lokmanya Tilak Municipal Medical College, Sion, Maharashtra, India
| | - Jairaj P. Nair
- Department of Respiratory Medicine, Lokmanya Tilak Municipal Medical College, Sion, Maharashtra, India
| | - Swapnil M. Thorve
- Department of Respiratory Medicine, Lokmanya Tilak Municipal Medical College, Sion, Maharashtra, India
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Bhat R, Tonutti A, Timilsina S, Selmi C, Gershwin ME. Perspectives on Mycophenolate Mofetil in the Management of Autoimmunity. Clin Rev Allergy Immunol 2023:10.1007/s12016-023-08963-3. [PMID: 37338709 DOI: 10.1007/s12016-023-08963-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/03/2023] [Indexed: 06/21/2023]
Abstract
Before becoming a cornerstone in the treatment of numerous immune-mediated diseases, mycophenolate mofetil (MMF) was first introduced as an immunosuppressive agent in transplant immunology and later received the attention of rheumatologists and clinicians involved in the management of autoimmune diseases. MMF is now a widespread immunosuppressive drug for the treatment of several conditions, including lupus nephritis, interstitial lung disease associated with systemic sclerosis, and anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis while being efficacious also as rescue therapy in various orphan diseases, including dermatomyositis and IgA-associated nephropathy. Similarly, case reports or series support a possible use of MMF in other rare autoimmune diseases. Beyond modulating lymphocyte activation, MMF acts on other immune and non-immune cells and these effects may explain the therapeutic profile of this medication. The effects of MMF are broadly characterized by the impact on the immune system and the antiproliferative and antifibrotic changes induced. In this latter case, mechanistic data on fibroblasts may in the future allow to reevaluate the use of MMF in selected patients with inflammatory arthritis or systemic sclerosis. Attention must be paid towards the possible occurrence of adverse events, such as gastrointestinal complaints and teratogenicity, while the risk of infections and cancer related to MMF needs to be further investigated.
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Affiliation(s)
- Rithika Bhat
- Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, USA
| | - Antonio Tonutti
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Suraj Timilsina
- Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, USA
| | - Carlo Selmi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
| | - M Eric Gershwin
- Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, USA.
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Xu YC, Wang JX, Chu YR, Qian H, Wang HY, Wang F. Diseases of the musculoskeletal system and connective tissue and risk of breast cancer: Mendelian randomization study in European and East Asian populations. Front Oncol 2023; 13:1170119. [PMID: 37182186 PMCID: PMC10169740 DOI: 10.3389/fonc.2023.1170119] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 04/10/2023] [Indexed: 05/16/2023] Open
Abstract
Objective Associations between diseases of the musculoskeletal system and connective tissue (MSCTD) and breast cancer (BC) have not been elucidated completely. The purpose of this study was to investigate the associations of MSCTD, rheumatoid arthritis (RA), Sjogren syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM), polymyositis (PM), osteoarthritis (OA) of hip or knee, and ankylosing spondylitis (AS) with BC in European populations and East Asian populations using Mendelian randomized (MR) analysis. Methods The genetic instruments linked to MSCTD, RA, SS, SLE, SSc, DM, PM, OA, and AS were chosen from the EBI database of complete genome-wide association studies (GWAS) summary data and the FinnGen consortium. The associations of genetic variants with BC were extracted from the Breast Cancer Association Consortium (BCAC). Two Sample MR was performed using summary data from GWAS, principally using the inverse variant weighted (IVW) method. Heterogeneity, pleiotropy, and sensitivity analyses were performed to evaluate the robustness of the results by weighted median, MR Egger, simple mode, weighted mode, and leave-one-out analysis. Results In the European population, causal relationships between RA and BC (OR=1.04, 95%CI: 1.01-1.07, P=0.023), AS and BC (OR=1.21, 95%CI: 1.06-1.36, P=0.013) were confirmed. IVW analysis showed DM (OR=0.98, 95%CI: 0.96-0.99, P=0.026) and PM (OR=0.98, 95%CI: 0.97-0.99, P=0.002) were associated with slightly decreased risks of estrogen receptor (ER)+ BC, and MSCTD was associated with an increased risk of ER- BC (OR=1.85, 95%CI: 1.27-2.44, P=0.039). There was no causal relationship between SLE, SS, SSc, OA, and BC, neither ER+ BC nor ER- BC. However, in the East Asian population, IVW analysis showed that RA (OR=0.94, 95%CI: 0.89-0.99, P=0.0096) and SLE (OR=0.95, 95%CI: 0.92-0.99, P=0.0058) was associated with decreased risks of BC. Conclusions This study suggests that causal relationships between patients with MSCTD and BC in the European population are different from those in the East Asian population, patients with RA and AS in the European population have an increased risk of BC, patients with MSCTD have increased risk of ER- BC in the European population, while patients with RA and SLE in the East Asian population have decreased risk of BC.
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Affiliation(s)
- Yue-chen Xu
- Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jian-xiong Wang
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yi-ran Chu
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Han Qian
- Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Hong-yan Wang
- Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Fan Wang
- Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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Chiodo Ortiz A, Petrossian G, Addonizio K, Hsiao A, Koizumi N, Yu Y, Plews R, Conti D, Ortiz J. Short-term decreased post transplant lymphoproliferative disorder risk after kidney transplantation using two novel regimens. Transpl Immunol 2023; 76:101774. [PMID: 36528248 DOI: 10.1016/j.trim.2022.101774] [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: 08/12/2022] [Revised: 12/06/2022] [Accepted: 12/11/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND Belatacept is employed alongside calcineurin inhibitor (CNI) therapy to prevent graft rejection in kidney transplant patients who are Epstein-Barr virus (EBV) seropositive. Preliminary data suggested that rates of post-transplant lymphoproliferative disorder (PTLD) were higher in individuals treated with belatacept compared to CNI therapy alone. METHODS The records of 354 adults who underwent kidney only transplantation from January 2015 through September 2021 at one medical center were evaluated. Patients underwent treatment with either low-doses of mycophenolate, tacrolimus and sirolimus (B0, n = 235) or low-doses of mycophenolate, tacrolimus and belatacept (B1, n = 119). All recipients underwent induction with antithymocyte globulin and a rapid glucocorticosteroid taper. Relevant donor and recipient information were analyzed and endpoints of PTLD were assessed. RESULTS There were no cases of PTLD in either cohort within the study period. Recipients in the belatacept cohort experienced lower estimated glomerular filtration rates at 12 months (B0: 67.48 vs. B1: 59.10, p = 0.0014). Graft failure at 12 (B0: 1.28% vs. B1: 0.84%, p = 1.0) and 24 months (B0:2.55% vs. B1: 0.84%, p = 0.431) were similar. There was no difference in rejection rates at 12 (B0: 1.27% vs. B1: 2.52%, p = 0.408) or 24 months (B0: 2.12% vs. B1: 2.52%, p = 1.000). Both groups had similar rates of malignancy, mortality and CMV/BK viremia. CONCLUSION Non-belatacept (MMF, tacrolimus and sirolimus) and belatacept-based (MMF, tacrolimus and belatacept) regimens do not appear to pose any increased risk of early onset PTLD. Both cohorts benefited from low rates of rejection, malignancy, mortality and graft failure. Recipients will continue to be monitored as PTLD can manifest as a long-term complication.
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Affiliation(s)
- A Chiodo Ortiz
- Albany Medical Center, Albany, NY, United States of America.
| | - G Petrossian
- Albany Medical Center, Albany, NY, United States of America
| | - K Addonizio
- Albany Medical Center, Albany, NY, United States of America
| | - A Hsiao
- Albany Medical Center, Albany, NY, United States of America
| | - N Koizumi
- George Mason University, Fairfax, VA, United States of America
| | - Y Yu
- George Mason University, Fairfax, VA, United States of America
| | - R Plews
- Division of Renal and Pancreatic Transplant Services, Albany Medical Center, Albany, NY, United States of America
| | - D Conti
- Division of Renal and Pancreatic Transplant Services, Albany Medical Center, Albany, NY, United States of America
| | - J Ortiz
- Division of Renal and Pancreatic Transplant Services, Albany Medical Center, Albany, NY, United States of America
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11
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Geng Z, Ye C, Zhu X. Malignancies in systemic rheumatic diseases: A mini review. Front Immunol 2023; 14:1095526. [PMID: 36926334 PMCID: PMC10011115 DOI: 10.3389/fimmu.2023.1095526] [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: 11/24/2022] [Accepted: 02/13/2023] [Indexed: 03/08/2023] Open
Abstract
There is an increased risk of malignancies in patients with many systemic rheumatic diseases, which negatively impact on their quality of life. The risk and types of malignancies can differ by the type of rheumatic diseases. Possible mechanisms linking them are dynamic and complicated, including chronic inflammation and damage in rheumatic disease, inability to clear oncogenic infections, shared etiology and some anti-rheumatic therapies. Although certain disease-modifying anti-rheumatic drugs (DMARDs) have been proved to be potentially carcinogenic, the majority of them were not associated with increased risk of most malignancies in patients with systemic rheumatic diseases.
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Affiliation(s)
- Zhe Geng
- Department of Hematology, Central Hospital of Wuhan, Wuhan, China
| | - Cong Ye
- Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaojian Zhu
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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12
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Reyes A, Mohanty A, Pharaon R, Massarelli E. Association between Immunosuppressive Therapy Utilized in the Treatment of Autoimmune Disease or Transplant and Cancer Progression. Biomedicines 2022; 11:biomedicines11010099. [PMID: 36672607 PMCID: PMC9856025 DOI: 10.3390/biomedicines11010099] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 12/28/2022] [Accepted: 12/28/2022] [Indexed: 01/01/2023] Open
Abstract
Autoimmunity and cancer rates have both been on the rise in Western civilization prompting many to investigate the link between the two entities. This review will investigate the complex interactions between the activation and deactivation of the immune system and the development of malignancy. Additional focus will be placed on the main classes of immune inhibitor therapy utilized in transplant patients and in autoimmune disease including TNF-alpha, Calcineurin, mTOR, purine synthesis antagonists and IMPDH inhibitors.
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13
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Zheng YJ, Ho W, Sanlorenzo M, Vujic I, Daud A, Algazi A, Rappersberger K, Ortiz-Urda S. Melanoma risk during immunomodulating treatment. Melanoma Res 2022; 32:411-418. [PMID: 35993892 DOI: 10.1097/cmr.0000000000000838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
Immunosuppressive therapy is standard for the treatment of inflammatory diseases and for minimizing rejection in transplant patients. However, immunosuppressant drugs are associated with an increased risk of certain cancers. In particular, melanoma is an immunogenic tumor and as such, is strongly influenced by the immune system. We performed this literature review to summarize the effects of commonly used immunomodulating agents on melanoma development, recurrence and progression. We outline the mechanism of action of each drug and discuss the available evidence on its influence on melanoma. Based on existing literature, we recommend avoiding the following agents in patients with a history of invasive melanoma: cyclosporine, sirolimus, natalizumab, IL-6 inhibitors, cyclophosphamide, methotrexate and the tumor necrosis factor-alpha inhibitors infliximab and etanercept. If there are no viable alternative agents, we recommend for these patients to see a dermatologist every 6 months for a thorough skin examination.
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Affiliation(s)
- Yixuan James Zheng
- Department of Dermatology, University of California San Francisco
- School of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Wilson Ho
- Department of Dermatology, University of California San Francisco
| | - Martina Sanlorenzo
- Department of Dermatology, University of California San Francisco
- Department of Oncology, University of Turin, Torino, Italy
- Department of Medicine, Institute of Cancer Research, Medical University of Vienna
| | - Igor Vujic
- Department of Dermatology, University of California San Francisco
- Department of Dermatology and Venereology, The Rudolfstiftung Hospital
- School of Medicine, Sigmund Freud University Vienna, Vienna, Austria
| | - Adil Daud
- Department of Dermatology, University of California San Francisco
| | - Alain Algazi
- Department of Dermatology, University of California San Francisco
| | - Klemens Rappersberger
- Department of Dermatology and Venereology, The Rudolfstiftung Hospital
- School of Medicine, Sigmund Freud University Vienna, Vienna, Austria
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14
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Lepri G, Catalano M, Bellando-Randone S, Pillozzi S, Giommoni E, Giorgione R, Botteri C, Matucci-Cerinic M, Antonuzzo L, Guiducci S. Systemic Sclerosis Association with Malignancy. Clin Rev Allergy Immunol 2022; 63:398-416. [PMID: 36121543 DOI: 10.1007/s12016-022-08930-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/10/2022] [Indexed: 12/17/2022]
Abstract
The association of systemic sclerosis (SSc) and cancer is well known from several decades suggesting common genetic and environmental risk factors involved in the development of both diseases. Immunosuppressive drugs widely used in SSc may increase the risk of cancer occurrence and different SSc clinical and serological features identify patients at major risk to develop malignancy. In this context, among serological features, presence of anti-RNA polymerase III and anti-topoisomerase I autoantibodies seems to increase cancer frequency in SSc patients (particularly lung and breast cancers). Lung fibrosis and a long standing SSc pulmonary involvement have been largely proposed as lung cancer risk factors, and the exposure to cyclophosphamide and an upper gastrointestinal involvement have been traditionally linked to bladder and oesophagus cancers, respectively. Furthermore, immune checkpoint inhibitors used for cancer therapy can induce immune-related adverse events, which are more frequent and severe in patients with pre-existing autoimmune diseases such as SSc. The strong association between SSc and cancer occurrence steers clinicians to carefully survey SSc patients performing periodical malignancy screening. In the present review, the most relevant bilateral relationships between SSc and cancer will be addressed.
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Affiliation(s)
- Gemma Lepri
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology, AOUC & Scleroderma Unit, Florence, Italy.
| | - Martina Catalano
- Medical Oncology Unit, Careggi University Hospital, Florence, Italy
| | - Silvia Bellando-Randone
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology, AOUC & Scleroderma Unit, Florence, Italy
| | - Serena Pillozzi
- Medical Oncology Unit, Careggi University Hospital, Florence, Italy
| | - Elisa Giommoni
- Medical Oncology Unit, Careggi University Hospital, Florence, Italy
| | | | - Cristina Botteri
- Medical Oncology Unit, Careggi University Hospital, Florence, Italy
| | - Marco Matucci-Cerinic
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology, AOUC & Scleroderma Unit, Florence, Italy.,Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, Milan, Italy
| | - Lorenzo Antonuzzo
- Medical Oncology, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Serena Guiducci
- Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology, AOUC & Scleroderma Unit, Florence, Italy
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15
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Shao EX, Betz-Stablein B, Marquat L, Campbell S, Isbel N, Green AC, Plasmeijer EI. Higher mycophenolate dosage is associated with an increased risk of squamous cell carcinoma in kidney transplant recipients. Transpl Immunol 2022; 75:101698. [PMID: 35988897 DOI: 10.1016/j.trim.2022.101698] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 08/16/2022] [Accepted: 08/16/2022] [Indexed: 10/15/2022]
Abstract
BACKGROUND Kidney transplant recipients are at increased risk of keratinocyte cancers, namely squamous cell and basal cell carcinomas (SCCs and BCCs). This is primarily due to the high levels of immunosuppression that are required to prevent allograft rejection. Different immunosuppressive medications confer different risks, and the effect of mycophenolate mofetil on SCC and BCC risk is unclear. We explored the relationship between mycophenolate dose prescribed over the entire transplant period and the risk of SCC and BCC. METHODS Kidney transplant recipients from Queensland, Australia, were recruited between 2012 and 2014 and followed until mid-2016. During this time transplant recipients underwent regular skin examinations to diagnose incident SCCs and BCCs. Immunosuppressive medication regimens were obtained from hospital records, and the average mycophenolate dose/day over the entire transplantation period was calculated for each patient. Doses were divided into three ranked groups, and adjusted relative risks (RRadj) of developing SCC and BCC tumours were calculated using negative binomial regression with the lowest dosage group as reference. Recipients who had used azathioprine previously were excluded; further sub-group analysis was performed for other immunosuppressant medications. RESULTS There were 134 kidney transplant recipients included in the study. The average age was 55, 31% were female and 69% were male. At the highest median mycophenolate dose of 1818 mg/day the SCC risk doubled (RRadj 2.22, 95% CI 1.03-4.77) when compared to the reference group of 1038 mg/day. An increased risk persisted after accounting for ever-use of ciclosporin, ever-use of tacrolimus, and when excluding mammalian target of rapamycin users. This increased risk was mainly carried by kidney transplant recipients immunosuppressed for five or more years (RRadj = 11.05 95% CI 2.50-48.81). In contrast, there was no significant association between BCC incidence and therapy with the highest compared with the lowest mycophenolate dosage (RRadj = 1.27 95% CI 0.56-2.87). CONCLUSION Higher mycophenolate dosage is associated with increased SCCs in kidney transplant recipients, particularly those immunosuppressed for more than five years. The increased SCC risk persists after accounting for usage of other immunosuppressant medications.
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Affiliation(s)
- E X Shao
- Cancer and Population Studies, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Australia; Faculty of Medicine, The University of Queensland, St Lucia, QLD 4072, Australia.
| | - B Betz-Stablein
- Cancer and Population Studies, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Australia
| | - L Marquat
- Cancer and Population Studies, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Australia
| | - S Campbell
- Faculty of Medicine, The University of Queensland, St Lucia, QLD 4072, Australia; Department of Renal Medicine, Princess Alexandra Hospital Metro South, 199 Ipswich Rd, Woolloongabba, ALD 4102, Australia
| | - N Isbel
- Faculty of Medicine, The University of Queensland, St Lucia, QLD 4072, Australia; Department of Renal Medicine, Princess Alexandra Hospital Metro South, 199 Ipswich Rd, Woolloongabba, ALD 4102, Australia
| | - A C Green
- Cancer and Population Studies, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Australia; CRUK Manchester Institute and Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom
| | - E I Plasmeijer
- Cancer and Population Studies, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Australia; Netherlands Cancer Institute, Department of Dermatology, Amsterdam, the Netherlands
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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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Quaresma MV, Azevedo LS, Pereira NV, Saldanha MG, David-Neto E, Sotto MN. Lymphocyte subsets and Langerhans cells in the skin of kidney transplant recipients under three different immunosuppressive regimens. J Eur Acad Dermatol Venereol 2022; 36:2466-2472. [PMID: 35841306 DOI: 10.1111/jdv.18430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 06/10/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND Renal transplant recipients (RTRs) are at increased risk of developing skin cancer; however, the role of immunosuppression is not yet fully understood. In this study, we evaluated the immunohistochemical changes in the skin of RTRs under three different immunosuppression regimens: mTOR inhibitors (mTORi), sirolimus or everolimus, mycophenolic acid (MPA) precursors such as mycophenolate sodium or mofetil, or azathioprine (AZA). METHODS We evaluated biopsies of sun-exposed and sun-protected skin for immunohistochemical quantification of B lymphocytes (CD20+), T lymphocytes (CD3+, CD4+, and CD8+), and Langerhans cells (LCs) (CD1a+) in 30 RTRs and 10 healthy controls. The RTRs were divided into three groups: mTORi (n = 10), MPA (n = 10), and AZA (n = 10). RESULTS No differences were observed in the number of B lymphocytes. However, a significant decrease in the number of T lymphocytes and LCs was observed in both sun-protected and sun-exposed skin in the AZA and MPA groups, although to a lesser degree in the latter group. The skin of the mTORi group did not differ from that of the control group in terms of the number of B and T lymphocytes and LCs. CONCLUSIONS Patients treated with mTORi exhibit preserved cellular elements related to cutaneous immune surveillance. The use of AZA induced a greater degree of skin immunosuppression than in the control group, as demonstrated by the decrease in T lymphocytes and LCs.
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Affiliation(s)
- Maria Victória Quaresma
- Department of Dermatology, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil
| | - Luiz S Azevedo
- Renal Transplantation Service, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil
| | - Naiura V Pereira
- Department of Dermatology, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil
| | - Maíra G Saldanha
- Department of Gynecology, Federal University of São Paulo, São Paulo, Brazil
| | - Elias David-Neto
- Renal Transplantation Service, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil
| | - Mírian N Sotto
- Department of Dermatology, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil.,Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil
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18
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Current Knowledge of Immunosuppression as a Risk Factor for Skin Cancer Development. Crit Rev Oncol Hematol 2022; 177:103754. [DOI: 10.1016/j.critrevonc.2022.103754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 06/27/2022] [Accepted: 07/02/2022] [Indexed: 11/23/2022] Open
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19
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Fuhrmann JD, Valkova K, von Moos S, Wüthrich RP, Müller TF, Schachtner T. Cancer among kidney transplant recipients >20 years after transplantation: post-transplant lymphoproliferative disorder remains the most common cancer type in the ultra long-term. Clin Kidney J 2022; 15:1152-1159. [PMID: 35664271 PMCID: PMC9155242 DOI: 10.1093/ckj/sfac013] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Indexed: 11/23/2022] Open
Abstract
Background Cancer risk is increased by 2- to 4-fold in kidney transplant recipients (KTRs) compared with the general population. Little attention, however, has been given to KTRs with ultra long-term survival >20 years. Methods We studied 293 of 1241 KTRs (23.6%), transplanted between 1981 and 1999, who showed kidney allograft survival >20 years. These long-term survivors were analysed for cancer development, cancer type, cancer-associated risk factors and patient and allograft outcomes. Results By 10, 20 and 30 years post-transplantation, these long-term KTRs showed a cancer rate of 4.4%, 14.6% and 33.2%, and a non-melanoma skin cancer (NMSC) rate of 10.3%, 33.5% and 76.8%, respectively. By recipients' ages of 40, 60 and 80 years, KTRs showed a cancer rate of 3.4%, 14.5% 55.2%, and a NMSC rate of 1.7%, 31.6% and 85.2%, respectively. By 30 years post-transplantation, post-transplant lymphoproliferative disorder (PTLD) showed the highest incidence of 8.5%, followed by renal cell carcinoma (RCC) with 5.1%. Risk factors associated with the development of cancer were only recipient age (P = 0.016). Smoking history was associated with the risk of lung cancer (P = 0.018). Risk factors related to the development of NMSC included recipient age (P = 0.001) and thiazide diuretics (P = 0.001). Cancer increased the risk of death by 2.4-fold (P = 0.002), and PTLD increased the risk of kidney allograft loss by 6.5-fold (P = 0.001). No differences were observed concerning the development of donor-specific antibodies (P > 0.05). Conclusions In long-term KTRs, cancer is a leading cause of death. PTLD remains the most common cancer type followed by RCC. These results emphasize the need for focused long-term cancer surveillance protocols.
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Affiliation(s)
- Julia D Fuhrmann
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Kristyna Valkova
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Seraina von Moos
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Rudolf P Wüthrich
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Thomas F Müller
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Thomas Schachtner
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
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20
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Rodríguez‐Perálvarez M, Colmenero J, González A, Gastaca M, Curell A, Caballero‐Marcos A, Sánchez‐Martínez A, Di Maira T, Herrero JI, Almohalla C, Lorente S, Cuadrado‐Lavín A, Pascual S, López‐Garrido MÁ, González‐Grande R, Gómez‐Orellana A, Alejandre R, Zamora‐Olaya J, Bernal‐Bellido C. Cumulative exposure to tacrolimus and incidence of cancer after liver transplantation. Am J Transplant 2022; 22:1671-1682. [PMID: 35286761 PMCID: PMC9315045 DOI: 10.1111/ajt.17021] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 02/10/2022] [Accepted: 03/03/2022] [Indexed: 01/25/2023]
Abstract
Cancer is the leading cause of death after liver transplantation (LT). This multicenter case-control nested study aimed to evaluate the effect of maintenance immunosuppression on post-LT malignancy. The eligible cohort included 2495 LT patients who received tacrolimus-based immunosuppression. After 13 922 person/years follow-up, 425 patients (19.7%) developed malignancy (cases) and were matched with 425 controls by propensity score based on age, gender, smoking habit, etiology of liver disease, and hepatocellular carcinoma (HCC) before LT. The independent predictors of post-LT malignancy were older age (HR = 1.06 [95% CI 1.05-1.07]; p < .001), male sex (HR = 1.50 [95% CI 1.14-1.99]), smoking habit (HR = 1.96 [95% CI 1.42-2.66]), and alcoholic liver disease (HR = 1.53 [95% CI 1.19-1.97]). In selected cases and controls (n = 850), the immunosuppression protocol was similar (p = .51). An increased cumulative exposure to tacrolimus (CET), calculated by the area under curve of trough concentrations, was the only immunosuppression-related predictor of post-LT malignancy after controlling for clinical features and baseline HCC (CET at 3 months p = .001 and CET at 12 months p = .004). This effect was consistent for de novo malignancy (after excluding HCC recurrence) and for internal neoplasms (after excluding non-melanoma skin cancer). Therefore, tacrolimus minimization, as monitored by CET, is the key to modulate immunosuppression in order to prevent cancer after LT.
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Affiliation(s)
- Manuel Rodríguez‐Perálvarez
- Department of Hepatology and Liver TransplantationHospital Universitario Reina SofíaIMIBIC and University of CórdobaCórdobaSpain,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain
| | - Jordi Colmenero
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain,Liver Transplantation UnitHospital ClínicIDIBAPSUniversity of BarcelonaBarcelonaSpain
| | - Antonio González
- Department of HepatologyHospital Universitario Ntra. Sra. de la CandelariaTenerifeSpain
| | - Mikel Gastaca
- Hepatobiliary Surgery and Liver transplantation UnitHospital Universitario CrucesUniversity of the Basque Country and Biocruces Bizkaia Health Research InstituteBilbaoSpain
| | - Anna Curell
- Department of HPB Surgery and TransplantationHospital Universitario Vall d´HebronBarcelonaSpain
| | - Aránzazu Caballero‐Marcos
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain,Department of Hepatology and Liver TransplantationHospital General Universitario Gregorio MarañónMadridSpain
| | - Ana Sánchez‐Martínez
- Liver Transplantation UnitHospital Universitario Virgen de la Arrixaca and IMIBMurciaSpain
| | - Tommaso Di Maira
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain,Liver Transplantation and Hepatology UnitHospital Universitari I Politècnic La FeValenciaSpain
| | - José Ignacio Herrero
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain,Liver UnitClínica Universidad de Navarra and IdiSNAPamplonaSpain
| | - Carolina Almohalla
- Department of Hepatology and Liver TransplantationHospital Universitario Río HortegaValladolidSpain
| | - Sara Lorente
- Department of Hepatology and Liver TransplantationHospital Clínico Lozano BlesaUniversity of Zaragoza and ISS AragónZaragozaSpain
| | - Antonio Cuadrado‐Lavín
- Department of Gastroenterology and HepatologyMarqués de Valdecilla University HospitalUniversity of Cantabria and IDIVALSantanderSpain
| | - Sonia Pascual
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain,Department of Hepatology and Liver TransplantationHospital General Universitario Alicante and ISABIALAlicanteSpain
| | | | - Rocío González‐Grande
- Department of Hepatology and Liver TransplantationHospital Regional Universitario de MálagaMálagaSpain
| | | | - Rafael Alejandre
- Department of Hepatology and Liver TransplantationHospital Universitario Reina SofíaIMIBIC and University of CórdobaCórdobaSpain
| | - Javier Zamora‐Olaya
- Department of Hepatology and Liver TransplantationHospital Universitario Reina SofíaIMIBIC and University of CórdobaCórdobaSpain
| | - Carmen Bernal‐Bellido
- Hepato‐Biliary‐Pancreatic Surgery Unit and TransplantationHospital Universitario Virgen del RocíoSevillaSpain
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21
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Hsieh CH, Huang YW, Tsai TF. Oral Conventional Synthetic Disease-Modifying Antirheumatic Drugs with Antineoplastic Potential: a Review. Dermatol Ther (Heidelb) 2022; 12:835-860. [PMID: 35381976 PMCID: PMC9021342 DOI: 10.1007/s13555-022-00713-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Indexed: 01/17/2023] Open
Abstract
There is an increasing trend of malignancy worldwide. Disease-modifying antirheumatic drugs (DMARDs) are the cornerstones for the treatment of immune-mediated inflammatory diseases (IMIDs), but risk of malignancy is a major concern for patients receiving DMARDs. In addition, many IMIDs already carry higher background risks of neoplasms. Recently, the black box warning of malignancies has been added for Janus kinase inhibitors. Also, the use of biologic DMARDs in patients with established malignancies is usually discouraged owing to exclusion of such patients in pivotal studies and, hence, lack of evidence. In contrast, some conventional synthetic DMARDs (csDMARDs) have been reported to show antineoplastic properties and can be beneficial for patients with cancer. Among the csDMARDs, chloroquine and hydroxychloroquine have been the most extensively studied, and methotrexate is an established chemotherapeutic agent. Even cyclosporine A, a well-known drug associated with cancer risk, can potentiate the effect of some chemotherapeutic agents. We review the possible mechanisms behind and clinical evidence of the antineoplastic activities of csDMARDs, including chloroquine and hydroxychloroquine, cyclosporine, leflunomide, mycophenolate mofetil, mycophenolic acid, methotrexate, sulfasalazine, and thiopurines. This knowledge may guide physicians in the choice of csDMARDs for patients with concurrent IMIDs and malignancies.
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Affiliation(s)
- Cho-Hsun Hsieh
- Department of Medical Education, National Taiwan University Hospital, Taipei, Taiwan
| | - Yi-Wei Huang
- Department of Dermatology, National Taiwan University Hospital, 7 Chung Shan S Rd, Taipei, 10048, Taiwan
| | - Tsen-Fang Tsai
- Department of Dermatology, National Taiwan University Hospital, 7 Chung Shan S Rd, Taipei, 10048, Taiwan. .,Department of Dermatology, National Taiwan University Hospital & National Taiwan University College of Medicine, Taipei, Taiwan.
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22
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Murakami N, Webber AB, Nair V. Transplant Onconephrology in Patients With Kidney Transplants. Adv Chronic Kidney Dis 2022; 29:188-200.e1. [PMID: 35817526 PMCID: PMC9326185 DOI: 10.1053/j.ackd.2021.09.002] [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: 05/24/2021] [Revised: 08/10/2021] [Accepted: 09/01/2021] [Indexed: 11/11/2022]
Abstract
Cancer is a leading cause of death in patients with kidney transplantation. Patients with kidney transplants are 10- to 200-times more likely to develop cancers after transplant than the general population, depending on the cancer type. Recent advances in cancer therapies have dramatically improved survival outcomes; however, patients with kidney transplants face unique challenges of immunosuppression management, cancer screening, and recurrence of cancer after transplant. Patients with a history of cancer tend to be excluded from transplant candidacy or are required to have long cancer-free wait time before wait-listing. The strategy of pretransplant wait time management may need to be revisited as cancer therapies improve, which is most applicable to patients with a history of multiple myeloma. In this review, we discuss several important topics in transplant onconephrology: the current recommendations for pretransplant wait times for transplant candidates with cancer histories, cancer screening post-transplant, post-transplant lymphoproliferative disorder, strategies for transplant patients with a history of multiple myeloma, and novel therapies for patients with post-transplant malignancies. With emerging novel cancer treatments, it is critical to have multidisciplinary discussions involving patients, caregivers, transplant nephrologists, and oncologists to achieve patient-oriented goals.
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Affiliation(s)
- Naoka Murakami
- Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
| | - Allison B. Webber
- Divisino of Nephrology, Kidney Transplant Service, University of California San Francisco, San Francisco, CA
| | - Vinay Nair
- Division of Kidney Disease and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY
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23
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Domínguez-Gil B, Moench K, Watson C, Serrano MT, Hibi T, Asencio JM, Van Rosmalen M, Detry O, Heimbach J, Durand F. Prevention and Management of Donor-transmitted Cancer After Liver Transplantation: Guidelines From the ILTS-SETH Consensus Conference. Transplantation 2022; 106:e12-e29. [PMID: 34905759 DOI: 10.1097/tp.0000000000003995] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
As with any other intervention in health, liver transplantation (LT) entails a variety of risks, including donor-transmitted cancers (DTCs). At present, 2%-4% of used deceased organ donors are known to have a current or past history of malignancy. The frequency of DTCs is consistently reported at 3-6 cases per 10 000 solid organ transplants, with a similar frequency in the LT setting. A majority of DTCs are occult cancers unknown in the donor at the time of transplantation. Most DTCs are diagnosed within 2 y after LT and are associated with a 51% probability of survival at 2 y following diagnosis. The probability of death is greatest for DTCs that have already metastasized at the time of diagnosis. The International Liver Transplantation Society-Sociedad Española de Trasplante Hepático working group on DTC has provided guidance on how to minimize the occurrence of DTCs while avoiding the unnecessary loss of livers for transplantation both in deceased and living donor LT. The group endorses the Council of Europe classification of risk of transmission of cancer from donor to recipient (minimal, low to intermediate, high, and unacceptable), classifies a range of malignancies in the liver donor into these 4 categories, and recommends when to consider LT, mindful of the risk of DTCs, and the clinical condition of patients on the waiting list. We further provide recommendations to professionals who identify DTC events, stressing the need to immediately alert all stakeholders concerned, so a coordinated investigation and management can be initiated; decisions on retransplantation should be made on a case-by-case basis with a multidisciplinary approach.
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Affiliation(s)
| | - Kerstin Moench
- Donor Transplant Coordination Unit, Westpfalz-Klinikum, Kaiserslautern, Germany
| | - Christopher Watson
- The Roy Calne Transplant Unit and Department of Surgery, University of Cambridge, Cambridge, United Kingdom
| | - M Trinidad Serrano
- Hepatology Section, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
| | - Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - José M Asencio
- Liver Transplant Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | | | - Olivier Detry
- Department of Abdominal Surgery and Transplantation, Centre Hospitalier Universitaire de Liege, University of Liege, Liege, Belgium
| | | | - François Durand
- Hepatology Department, Liver Intensive Care Unit, Hospital Beaujon, Clichy, France
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24
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De Novo Malignancy After Liver Transplantation: Risk Assessment, Prevention, and Management-Guidelines From the ILTS-SETH Consensus Conference. Transplantation 2022; 106:e30-e45. [PMID: 34905760 DOI: 10.1097/tp.0000000000003998] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
De novo malignancies (DNMs) following liver transplantation (LT) have been reported as 1 of the major causes of late mortality, being the most common cause of death in the second decade after LT. The overall incidence of DNMs is reported to be in the range of 3.1% to 14.4%, and the incidence is 2- to 3-fold higher in transplant recipients than in age- and sex-matched healthy controls. Long-term immunosuppressive therapy, which is the key in maintaining host tolerance and achieving good long-term outcomes, is known to contribute to a higher risk of DNMs. However, the incidence and type of DNM also depends on different risk factors, including patient demographics, cause of the underlying chronic liver disease, behavior (smoking and alcohol abuse), and pre-existing premalignant conditions. The estimated standardized incidence ratio for different DNMs is also variable. The International Liver Transplantation Society-Spanish Society of Liver Transplantation Consensus Conference working group on DNM has summarized and discussed the current available literature on epidemiology, risk factors, management, and survival after DNMs. Recommendations for screening and surveillance for specific tumors, as well as immunosuppression and cancer-specific management in patients with DNM, are summarized.
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25
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Urological Cancers and Kidney Transplantation: a Literature Review. Curr Urol Rep 2021; 22:62. [PMID: 34913107 DOI: 10.1007/s11934-021-01078-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/24/2021] [Indexed: 12/24/2022]
Abstract
PURPOSE OF REVIEW The aim of this review is to provide an overview of epidemiology, risk factors, and treatment of urological malignancies in renal transplant recipients (RTR). RECENT FINDINGS Although optimal immunosuppressive therapy and cancer management in these patients remain controversial, adherence to general guidelines is recommended. Kidney transplantation is recognized as the standard of care for the treatment of end-stage renal disease (ESRD) as it offers prolonged survival and better quality of life. In the last decades, survival of RTRs has increased as a result of improved immunosuppressive therapy; nonetheless, the risk of developing cancer is higher among RTRs compared to the general population. Urological malignancies are the second most common after hematological cancer and often have more aggressive behavior and poor prognosis.
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26
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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: 3] [Impact Index Per Article: 0.8] [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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27
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Thet Z, Lam AK, Ranganathan D, Aung SY, Han T, Khoo TK. Reducing non-melanoma skin cancer risk in renal transplant recipients. Nephrology (Carlton) 2021; 26:907-919. [PMID: 34240786 DOI: 10.1111/nep.13939] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 06/11/2021] [Accepted: 07/05/2021] [Indexed: 12/19/2022]
Abstract
With an increasing number of renal transplant recipients (RTRs) and improving patient survival, a higher incidence of non-melanoma skin cancer (NMSC) has been observed. NMSC in RTRs are often more numerous and biologically more aggressive than the general population, thus contributing towards an increase in morbidity and to a lesser degree, mortality. The resultant cumulative health and financial burden is a recognized concern. Proposed strategies in mitigating risks of developing NMSC and early therapeutic options thereof include tailored modification of immunosuppressants in conjunction with sun protection in all transplant patients. This review highlights the clinical and financial burden of transplant-associated skin cancers, carcinogenic mechanisms in association with immunosuppression, importance of skin cancer awareness campaign and integrated transplant skin clinic, and the potential role of chemoprotective agents. A scheme is proposed for primary and secondary prevention of NMSC based on the available evidence.
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Affiliation(s)
- Zaw Thet
- School of Medicine & Dentistry, Griffith University, Gold Coast, Queensland, Australia.,Department of Nephrology, Central Queensland Hospital and Health Service, Rockhampton, Queensland, Australia
| | - Alfred K Lam
- School of Medicine & Dentistry, Griffith University, Gold Coast, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Pathology Queensland, Gold Coast University Hospital, Southport, Queensland, Australia
| | - Dwarakanathan Ranganathan
- School of Medicine & Dentistry, Griffith University, Gold Coast, Queensland, Australia.,Department of Nephrology, Metro North Hospital and Health Service, Herston, Queensland, Australia
| | - Soe Yu Aung
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Department of Oncology, Central Queensland Hospital and Health Service, Rockhampton, Queensland, Australia
| | - Thin Han
- Department of Nephrology, Central Queensland Hospital and Health Service, Rockhampton, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Tien K Khoo
- School of Medicine & Dentistry, Griffith University, Gold Coast, Queensland, Australia.,School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia
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28
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Hirunsatitpron P, Hanprasertpong N, Noppakun K, Pruksakorn D, Teekachunhatean S, Koonrungsesomboon N. Mycophenolic acid and cancer risk in solid organ transplant recipients: Systematic review and meta-analysis. Br J Clin Pharmacol 2021; 88:476-489. [PMID: 34240462 DOI: 10.1111/bcp.14979] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 06/21/2021] [Accepted: 06/30/2021] [Indexed: 12/26/2022] Open
Abstract
AIM Mycophenolic acid (MPA) is an immunosuppressive drug commonly used for prophylaxis of graft rejection in solid organ transplant recipients. The main concern with the prolonged use of immunosuppressive drugs is the risk of developing cancer. However, it remains unclear whether the immunosuppressive regimens containing MPA confer an increased degree of cancer risk. The present study aimed to determine the association between MPA exposure and the incidence of cancer in solid organ transplant recipients. METHODS A systematic search was performed on the PubMed, EMBASE and Cochrane Library databases. Relevant articles that had findings on the incidence (or event) of cancer in cohorts with and without MPA exposure were retrieved for data extraction. A meta-analysis was conducted by means of the random-effects model, and the relative risk (RR) and its 95% confidence interval (95% CI) were used as a summary effect measure. RESULTS A total of 39 studies were eligible for inclusion, with 32 studies that enabled meta-analysis. MPA exposure was significantly associated with a lower risk of cancer when compared to azathioprine exposure (RR = 0.66, 95% CI = 0.53-0.81, P < .001) or no exposure to any additional treatments (RR = 0.85, 95% CI = 0.73-0.99, P = .04). There was no significant difference in cancer risk for the comparison between MPA exposure and mammalian target of rapamycin (mTOR) inhibitor exposure (RR = 1.54, 95% CI = 0.96-2.46, P = .07). CONCLUSIONS MPA exposure was not associated with an increased risk of cancer and may even be associated with a lower risk of cancer when compared to azathioprine or no treatment.
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Affiliation(s)
- Pannaphak Hirunsatitpron
- Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Thailand.,Master's Degree Program in Pharmacology, Faculty of Medicine, Chiang Mai University, Thailand
| | | | - Kajohnsak Noppakun
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Thailand.,Pharmacoepidemiology and Statistics Research Center, Faculty of Pharmacy, Chiang Mai University, Thailand
| | - Dumnoensun Pruksakorn
- Musculoskeletal Science and Translational Research Center, Faculty of Medicine, Chiang Mai University, Thailand.,Omics Center for Health Science, Faculty of Medicine, Chiang Mai University, Thailand.,Biomedical Engineering Institute, Chiang Mai University, Thailand
| | | | - Nut Koonrungsesomboon
- Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Thailand.,Musculoskeletal Science and Translational Research Center, Faculty of Medicine, Chiang Mai University, Thailand
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29
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Review of Outcomes after Diagnosis of Malignancy in Kidney Transplant Patients: UNOS Database. TRANSPLANTOLOGY 2021. [DOI: 10.3390/transplantology2030024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Malignancy is the third major cause of death among transplant recipients. Patient and kidney transplant outcomes after the diagnosis of malignancy are not well described. We reviewed incidences and outcomes of colorectal, lung, PTLD, and renal malignancy after transplant among patients who received a transplant from January 2000 to December 2018 using the UNOS/OPTN database. Incidence of each malignancy was measured at 5 years and 10 years of transplant. The Kaplan–Meier curve was used for time-to-event analysis (graft and patient outcomes). Additionally, we sought to identify the causes of graft failure among these recipients. We found that 12,764 (5.5%) patients suffered malignancy, excluding squamous and basal cell skin carcinoma after transplant. During the first 5 years of transplant, incidence of colorectal, lung, PTLD, and renal malignancies was 2.99, 9.21, 15.61, and 8.55 per 10,000 person-years, respectively. Rates of graft failure were 10.3%, 7.6%, 19.9%, and 18.8%, respectively, among these patients at 5 years. Mortality rate was highest among patients who suffered lung malignancy (84%), followed by colorectal (61.5%), PTLD (49.1%), and renal (35.5%) at 5 years after diagnosis of malignancy. In conclusion, kidney transplant recipients diagnosed with lung malignancy have the lowest graft survival, compared to PTLD, colorectal, and renal malignancy. PTLD has the highest incidence rate in the first 5 years of transplant.
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30
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Hellemans R, Pengel L, Choquet S, Maggiore U. Managing immunosuppressive therapy in potentially cured post-kidney transplant cancer (excluding non-melanoma skin cancer): overview of the available evidence and guidance for shared decision making. Transpl Int 2021; 34:1789-1800. [PMID: 34146426 PMCID: PMC8518116 DOI: 10.1111/tri.13952] [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: 04/30/2021] [Revised: 06/12/2021] [Accepted: 06/16/2021] [Indexed: 11/29/2022]
Abstract
Kidney transplant recipients (KTRs) have increased incidence of de novo cancers. After having undergone treatment for cancer with curative intent, reducing the overall immunosuppressive load and/or switching to an alternative drug regimen may potentially be of great benefit to avoid cancer recurrence, but should be balanced against the risks of rejection and/or severe adverse events. The TLJ (Transplant Learning Journey) project is an initiative from the European Society for Organ Transplantation (ESOT). This article reports a systematic literature search undertaken by TLJ Workstream 3 to answer the questions: (1) Should we decrease the overall anti‐rejection therapy in potentially cured post‐kidney transplant cancer (excluding non‐melanoma skin cancer)? (2) Should we switch to mammalian target of rapamycin inhibitors (mTORi) in potentially cured post‐kidney transplant cancer (excluding non‐melanoma skin cancer)? The literature search revealed insufficient solid data on which to base recommendations, so this review additionally presents an extensive overview of the indirect evidence on the benefits versus risks of alterations in immunosuppressive medication. We hope this summary will help transplant physicians advise KTRs on how best to continue with anti‐rejection therapy after receiving cancer treatment with curative intent, and aid shared decision‐making, ensuring that patient preferences are taken into account.
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Affiliation(s)
- Rachel Hellemans
- Department of Nephrology, Antwerp University Hospital, Edegem, Belgium.,Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Belgium
| | - Liset Pengel
- Centre of Evidence for Transplantation, Nuffield Department of Surgical Sciences, Oxford, UK
| | - Sylvain Choquet
- Service d'Hématologie, Hôpital Pitié Salpêtrière, Paris, France
| | - Umberto Maggiore
- Nephrology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy
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31
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An Unusual Cause of Acute Pancreatitis in a Liver Transplant Recipient. Transplant Direct 2021; 7:e694. [PMID: 33937519 PMCID: PMC8081465 DOI: 10.1097/txd.0000000000001129] [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: 12/01/2020] [Revised: 01/05/2021] [Accepted: 01/08/2021] [Indexed: 11/26/2022] Open
Abstract
Posttransplant lymphoproliferative disorder (PTLD) in liver transplant recipients is relatively uncommon, with an estimated incidence of 1%–3%. Retrospective reviews of liver transplant recipients have mainly reported posttransplant lymphoproliferative disorder affecting the liver, gastrointestinal tract, or lymph nodes. In this case report, we describe a 45-y-old female with a history of deceased donor liver transplantation for autoimmune hepatitis who had recurrent hospital admissions for acute pancreatitis. Ultimately, imaging revealed numerous complex pancreatic and peripancreatic masses, appearing to originate from pancreatic lymphoid tissue. Tissue biopsy later confirmed monomorphic Epstein-Barr virus-negative large B-cell lymphoma. Overall, PTLD involving the pancreas after liver transplantation is incredibly rare. The patient’s cumulative immunosuppression drug dose and time posttransplant were suspected to be her main risk factors, given that she had been exposed to several years of treatment with tacrolimus, azathioprine, mycophenolate mofetil, and prednisone. She was treated with rituximab monotherapy and later escalated to chemoimmunotherapy due to lack of response. PTLD involving the pancreas is an unusual cause of pancreatitis and should be considered in cases of recurrent pancreatitis in transplant recipients.
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32
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Sprangers B, Riella LV, Dierickx D. Posttransplant Lymphoproliferative Disorder Following Kidney Transplantation: A Review. Am J Kidney Dis 2021; 78:272-281. [PMID: 33774079 DOI: 10.1053/j.ajkd.2021.01.015] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 01/02/2021] [Indexed: 12/13/2022]
Abstract
Posttransplant lymphoproliferative disorder (PTLD) is one of the most feared complications following kidney transplantation. Over a 10-year period, the risk of PTLD in kidney transplant recipients (KTRs) is 12-fold higher than in a matched nontransplanted population. Given the number of kidney transplants performed, KTRs who experience PTLD outnumber other organ transplant recipients who experience PTLD. Epstein-Barr virus infection is one of the most important risk factors for PTLD, even though 40% of PTLD cases in contemporary series are not Epstein-Barr virus-associated. The overall level of immunosuppression seems to be the most important driver of the increased occurrence of PTLD in solid organ transplant recipients. Reduction in immunosuppression is commonly accepted to prevent and treat PTLD. Although the cornerstone of PTLD treatment had been chemotherapy (typically cyclophosphamide-doxorubicin-vincristinr-prednisone), the availability of rituximab has changed the treatment landscape in the past 2 decades. The outcome of PTLD in KTRs has clearly improved as a result of the introduction of more uniform treatment protocols, improved supportive care, and increased awareness and use of positron emission tomography combined with computed tomography in staging and response monitoring. In this review, we will focus on the most recent data on epidemiology, presentation, risk factors, and management of PTLD in KTRs.
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Affiliation(s)
- Ben Sprangers
- Department of Microbiology, Immunology and Transplantation, Laboratory of Molecular Immunology (Rega Institute for Medical Research), KU Leuven; Division of Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - Leonardo V Riella
- Division of Nephrology and Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Daan Dierickx
- Laboratory of Experimental Hematology, Department of Oncology, KU Leuven; Department of Hematology, University Hospitals Leuven, Leuven, Belgium.
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33
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Post-transplant lymphoproliferative disorder in adult renal transplant recipients: case series and review of literature. Cent Eur J Immunol 2021; 45:498-506. [PMID: 33658896 PMCID: PMC7882407 DOI: 10.5114/ceji.2020.103427] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Accepted: 10/28/2019] [Indexed: 01/24/2023] Open
Abstract
Post-transplant lymphoproliferative disorder (PTLD) is serious life-threating complication of transplantation. The clinical picture differs from lymphomas observed in the general population, with different manifestation, histopathology, higher aggressiveness with involvement of sites beyond the primary lymph node, and poorer outcome. The objective of the study was to present nine cases of PTLD observed in our centre among the kidney transplant recipient population and discuss the results with up-to-date literature. We performed a retrospective single-centre assessment of PTLD incidence in the cohorts of kidney transplant recipients followed by our centre. We found nine cases of PTLD, five men and four woman, aged from 26 to 67 years at the time of diagnosis (mean [SD] 48 [5] years), transplanted between 1997 and 2013. The disease was diagnosed between 2002 and 2017, from 6 to 440 months after transplantation (mean [SD] 96 [137] months). A diffuse large B-cell lymphoma was found in seven cases early as well as late after transplantation, and two patients presented T-cell lymphoma. Five patients achieved complete remission with no relapses after 6 to 13 months of treatment. In three cases the remission was achieved by switching to mammalian target of rapamycin inhibitors (mTORi) only. Four recipients died from 2 weeks to 15 months after PTLD was diagnosed. Although the diagnostic criteria of different forms of PTLD are commonly known, rapid and correct diagnosis is not easy. PTLD is a relatively a rare disease, so there are too few studies and little consensus on the optimal treatment.
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34
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Songwisit S, Kosiyakul P, Jitprapaikulsan J, Prayoonwiwat N, Ungprasert P, Siritho S. Efficacy and safety of mycophenolate mofetil therapy in neuromyelitis optica spectrum disorders: a systematic review and meta-analysis. Sci Rep 2020; 10:16727. [PMID: 33028926 PMCID: PMC7541495 DOI: 10.1038/s41598-020-73882-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 09/21/2020] [Indexed: 01/11/2023] Open
Abstract
Mycophenolate mofetil (MMF) is an immunosuppressive agent (IS) which is widely prescribed in neuromyelitis optica spectrum disorder (NMOSD) patients. We aim to assess the efficacy and safety of MMF in controlling relapse and disease severity. Eligible studies obtained from the EMBASE and Ovid MEDLINE databases were studies of NMOSD patients treated with MMF, which reported treatment outcomes as Annualized Relapse Rate (ARR) or Expanded Disability Status Scale (EDSS) before and after treatment. Fifteen studies included 1047 patients, of whom 915 (87.4%) were aquaporin-4 immunoglobulin seropositive. The total number of patients that received MMF was 799. A meta-analysis on ARR was conducted in 200 patients from 4 studies and on EDSS in 158 patients from 3 studies. The result showed a significant improvement with a mean reduction of 1.13 [95% confidence interval (CI) 0.60-1.65] in ARR, and a mean reduction of 0.85 (95% CI 0.36-1.34) in EDSS after MMF therapy. Adverse events occurred in 106 (17.8%) of 594 patients during MMF therapy. This systematic review and meta-analysis showed that using MMF as a preventive therapy in NMOSD patients can significantly reduce relapse rates and improve disease severity with acceptable tolerability.
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Affiliation(s)
- Sakdipat Songwisit
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Punchika Kosiyakul
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Jiraporn Jitprapaikulsan
- Division of Neurology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok Noi, Bangkok, 10700, Thailand
- Siriraj Neuroimmunology Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Naraporn Prayoonwiwat
- Division of Neurology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok Noi, Bangkok, 10700, Thailand
- Siriraj Neuroimmunology Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Patompong Ungprasert
- Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, OH, USA
| | - Sasitorn Siritho
- Division of Neurology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok Noi, Bangkok, 10700, Thailand.
- Siriraj Neuroimmunology Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
- Bumrungrad International Hospital, Bangkok, Thailand.
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Benjanuwattra J, Chaiyawat P, Pruksakorn D, Koonrungsesomboon N. Therapeutic potential and molecular mechanisms of mycophenolic acid as an anticancer agent. Eur J Pharmacol 2020; 887:173580. [PMID: 32949604 DOI: 10.1016/j.ejphar.2020.173580] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 09/14/2020] [Accepted: 09/15/2020] [Indexed: 12/14/2022]
Abstract
Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil (MMF), an immunosuppressive drug approved for the prophylaxis of allograft rejection in transplant recipients. Recent advances in the role of the type II isoform of inosine-5'-monophosphate dehydrogenase (IMPDH2) in the tumorigenesis of various types of cancer have called for a second look of MPA, the first IMPDH2 inhibitor discovered a hundred years ago, to be repurposed as an anticancer agent. Over a half century, a number of in vitro and in vivo experiments have consistently shown anticancer activity of MPA against several cell lines obtained from different malignancies and murine models. However, a few clinical trials have been conducted to investigate its anticancer activity in humans, and most of which have shown unsatisfactory results. Understanding of available evidence and underlying mechanism of action is a key step to be done so as to facilitate further investigations of MPA to reach its full therapeutic potential as an anticancer agent. This article provides a comprehensive review of non-clinical and clinical evidence available to date, with the emphasis on the molecular mechanism of action in which MPA exerts its anticancer activities: induction of apoptosis, induction of cell cycle arrest, and alteration of tumor microenvironment. Future perspective for further development of MPA to be an anticancer agent is extensively discussed, with the aim of translating the anticancer property of MPA from bench to bedside.
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Affiliation(s)
| | - Parunya Chaiyawat
- Musculoskeletal Science and Translational Research Center (MSTR), Faculty of Medicine, Chiang Mai University, Thailand; Omics Center for Health Sciences (OCHS), Faculty of Medicine, Chiang Mai University, Thailand
| | - Dumnoensun Pruksakorn
- Musculoskeletal Science and Translational Research Center (MSTR), Faculty of Medicine, Chiang Mai University, Thailand; Omics Center for Health Sciences (OCHS), Faculty of Medicine, Chiang Mai University, Thailand; Biomedical Engineering Institute, Chiang Mai University, Thailand
| | - Nut Koonrungsesomboon
- Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Thailand; Musculoskeletal Science and Translational Research Center (MSTR), Faculty of Medicine, Chiang Mai University, Thailand.
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Motta G, Ferraresso M, Lamperti L, Di Paolo D, Raison N, Perego M, Favi E. Treatment options for localised renal cell carcinoma of the transplanted kidney. World J Transplant 2020; 10:147-161. [PMID: 32742948 PMCID: PMC7360528 DOI: 10.5500/wjt.v10.i6.147] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Revised: 04/07/2020] [Accepted: 05/26/2020] [Indexed: 02/06/2023] Open
Abstract
Currently, there is no consensus among the transplant community about the treatment of renal cell carcinoma (RCC) of the transplanted kidney. Until recently, graftectomy was universally considered the golden standard, regardless of the characteristics of the neoplasm. Due to the encouraging results observed in native kidneys, conservative options such as nephron-sparing surgery (NSS) (enucleation and partial nephrectomy) and ablative therapy (radiofrequency ablation, cryoablation, microwave ablation, high-intensity focused ultrasound, and irreversible electroporation) have been progressively used in carefully selected recipients with early-stage allograft RCC. Available reports show excellent patient survival, optimal oncological outcome, and preserved renal function with acceptable complication rates. Nevertheless, the rarity and the heterogeneity of the disease, the number of options available, and the lack of long-term follow-up data do not allow to adequately define treatment-specific advantages and limitations. The role of active surveillance and immunosuppression management remain also debated. In order to offer a better insight into this difficult topic and to help clinicians choose the best therapy for their patients, we performed and extensive review of the literature. We focused on epidemiology, clinical presentation, diagnostic work up, staging strategies, tumour characteristics, treatment modalities, and follow-up protocols. Our research confirms that both NSS and focal ablation represent a valuable alternative to graftectomy for kidney transplant recipients with American Joint Committee on Cancer stage T1aN0M0 RCC. Data on T1bN0M0 lesions are scarce but suggest extra caution. Properly designed multi-centre prospective clinical trials are warranted.
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Affiliation(s)
- Gloria Motta
- Urology, IRCCS Policlinico San Donato, San Donato Milanese 27288, Italy
| | - Mariano Ferraresso
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan 20122, Italy
| | - Luca Lamperti
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy
| | - Dhanai Di Paolo
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy
| | - Nicholas Raison
- MRC Centre for Transplantation, King’s College London, London WC2R 2LS, United Kingdom
| | - Marta Perego
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy
| | - Evaldo Favi
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan 20122, Italy
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Chen LN, Spivack J, Cao T, Saqi A, Benvenuto LJ, Bulman WA, Mathew M, Stoopler MB, Arcasoy SM, Stanifer BP, Rizvi NA, Shu CA. Characteristics and outcomes of lung cancer in solid organ transplant recipients. Lung Cancer 2020; 146:297-302. [PMID: 32619780 DOI: 10.1016/j.lungcan.2020.06.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 06/11/2020] [Accepted: 06/13/2020] [Indexed: 12/20/2022]
Abstract
OBJECTIVES Lung cancer is the third most common malignancy that develops in patients following solid organ transplantation and is the leading cause of cancer deaths in the general population. The aims of this study are to examine the characteristics of patients who developed lung cancer following solid organ transplantation at our institution and to compare their outcomes to those of lung cancer patients without a history of transplant. MATERIALS AND METHODS We performed a single-institution retrospective study of 44 solid organ transplant recipients who developed lung cancer and compared their characteristics to a cohort of 74 lung cancer patients without a history of transplant. We performed propensity score weighted analyses to compare outcomes between the two groups, including a cox proportional hazards model of overall survival. RESULTS 52 % of post-transplant patients who developed lung cancer were diagnosed with stage III or IV disease. In the propensity score weighted analysis that accounted for age at diagnosis, sex, lung cancer stage at diagnosis, Charlson comorbidity index score, and ECOG performance score, post-transplant patients were more likely to have squamous cell histology (p < 0.01) and had worse overall survival compared to the non-transplant cohort (HR = 1.88, 95 % CI 1.13-3.12, p = 0.02). The difference in survival remained significant after accounting for differences in lung cancer histology and treatment (HR = 2.40, 95 % CI 1.27-3.78, p < 0.01). CONCLUSIONS When compared to non-transplant patients with lung cancer, post-transplant patients have worse overall survival after accounting for differences in age, sex, lung cancer stage, comorbidities, and performance status. This survival difference is not solely attributable to differences in tumor histology and treatments received. This may suggest that post-transplant malignancies are more aggressive and difficult to treat.
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Affiliation(s)
- Lanyi Nora Chen
- Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, New York, NY 10032, United States; Department of Medicine, Columbia University Medical Center, United States.
| | - John Spivack
- Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, New York, NY 10032, United States; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, United States.
| | - Thu Cao
- Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, New York, NY 10032, United States; Department of Surgery, Columbia University Medical Center, United States.
| | - Anjali Saqi
- Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, New York, NY 10032, United States; Department of Pathology, Columbia University Medical Center, United States.
| | - Luke J Benvenuto
- Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, New York, NY 10032, United States; Department of Medicine, Columbia University Medical Center, United States.
| | - William A Bulman
- Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, New York, NY 10032, United States; Department of Medicine, Columbia University Medical Center, United States.
| | - Matthen Mathew
- Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, New York, NY 10032, United States; Department of Medicine, Columbia University Medical Center, United States.
| | - Mark B Stoopler
- Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, New York, NY 10032, United States; Department of Medicine, Columbia University Medical Center, United States.
| | - Selim M Arcasoy
- Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, New York, NY 10032, United States; Department of Medicine, Columbia University Medical Center, United States.
| | - Bryan P Stanifer
- Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, New York, NY 10032, United States; Department of Surgery, Columbia University Medical Center, United States.
| | - Naiyer A Rizvi
- Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, New York, NY 10032, United States; Department of Medicine, Columbia University Medical Center, United States.
| | - Catherine A Shu
- Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, New York, NY 10032, United States; Department of Medicine, Columbia University Medical Center, United States.
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Cheung CY, Tang SCW. An update on cancer after kidney transplantation. Nephrol Dial Transplant 2020; 34:914-920. [PMID: 30260424 DOI: 10.1093/ndt/gfy262] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2018] [Indexed: 12/31/2022] Open
Abstract
The emergence of onconephrology in recent years highlights the importance of the interaction between kidney disease and cancer. Chronic kidney disease (CKD) and cancer are linked with each other in different ways bidirectionally: cancer can cause CKD, whereas CKD itself may be a risk factor for cancer. Kidney transplant recipients (KTRs) have a 2- to 3-fold increased cancer risk when compared with the general population. The elevated risk covers a wide range of cancers. Some are related to CKD, including cancers of the kidney, urinary tract and thyroid, whereas others are related to oncogenic viruses that include non-Hodgkin lymphoma, cervical cancer, nonmelanoma skin cancer and Kaposi's sarcoma. There is no standard protocol regarding how immunosuppressive drugs should be adjusted in patients who develop posttransplant cancers. However, any modification of immunosuppressive regimens should be balanced against the risk of allograft rejection or deterioration in kidney function. Cancer surveillance can be used as a strategy to improve the clinical outcome in KTRs. Although guidelines adopted in the general population have been used as the reference, a personalized approach based on individual cancer risk, life expectancy and concurrent comorbidities has to be adopted.
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Affiliation(s)
- Chi Yuen Cheung
- Renal Unit, Department of Medicine, Queen Elizabeth Hospital, Hong Kong SAR
| | - Sydney Chi Wai Tang
- Division of Nephrology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong SAR
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Yeh CC, Khan A, Muo CH, Yang HR, Li PC, Chang CH, Chen TL, Jeng LB, Liao CC. De Novo Malignancy After Heart, Kidney, and Liver Transplant: A Nationwide Study in Taiwan. EXP CLIN TRANSPLANT 2020; 18:224-233. [PMID: 32133940 DOI: 10.6002/ect.2019.0210] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES In the Asian population, patterns and risk factors for de novo malignancies after solid-organ transplant are not well understood. MATERIALS AND METHODS Insurance claims from Taiwan's National Health Institute Research Database from 1997 to 2011 revealed 687 deceased-donor heart transplant recipients, 5038 kidney transplant recipients (50% living related-donor, 50% deceased-donor transplants), and 2127 liver transplant recipients (mainly living related-donor transplants, 30% deceased-donor transplants). During the follow-up period, rates of malignancy incidence were calculated with standardization based on national age, sex, and year-specific incidence. We used multivariate regression analyses to determine risk factors of posttransplant de novo malignancies. RESULTS Compared with the general population, several de novo cancers were more common posttransplant (P < .05): lung cancer (2.6-fold), non-melanoma skin cancer (5.8-fold), and non-Hodgkin lymphoma (5.4-fold) in heart recipients; transitional cell carcinoma (31.4-fold), renal cell carcinoma (37.3-fold), and non-Hodgkin lymphoma (3.6-fold) in kidney recipients; and gastric cancer (3.0-fold) and lymphatic-hematopoietic malignancy (4.5-fold) in liver recipients. Independent risk factors for posttransplant malignancy in kidney transplant recipients were increased age, female, hepatitis B virus, and mycophenolate use (adjusted hazard ratio 1.5; 95% confidence interval, 1.2-1.8; P < .001). In liver transplant recipients, old age was an independent risk factor. Kidney transplant recipients without diabetes or hypertension had higher risk of transitional cell carcinoma (adjusted hazard ratio 3.0; 95% confidence interval, 2.1-4.4; P < .001) and renal cell carcinoma (adjusted hazard ratio 1.9; 95% confidence interval, 1.1-3.3; P < .05). CONCLUSIONS Regional endemic epidemiologic factors play significant roles in the development of de novo cancers, particularly in kidney transplant recipients due to causes of renal failure other than diabetes and hypertension. Each regional organ transplant program should tailor and establish its surveillance protocol based on epidemiologic data. However, the type and intensity of surveillance require further and long-term investigations in this patient cohort.
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Affiliation(s)
- Chun-Chieh Yeh
- From the School of Medicine, China Medical University, Taichung, Taiwan
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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: 51] [Impact Index Per Article: 10.2] [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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Abstract
Links between autoimmune rheumatic diseases and cancer continue to be elucidated. In this review, we explore this complex, bidirectional relationship. First, the increased risk of cancer across the breadth of the autoimmune rheumatic diseases is described. The magnitude of risk and types of tumors seen can differ by the type of autoimmune disease, timing of disease course, and even clinical and laboratory features within a particular autoimmune disease, suggesting that targeted cancer screening strategies can be considered. Multiple mechanisms linking autoimmune rheumatic diseases and cancer are discussed, including the development of autoimmunity in the context of naturally occurring anti-tumor immune responses and malignancy arising in the context of inflammation and damage from autoimmunity. Immunosuppression for rheumatic disease can increase risk for certain types of cancers. Finally, immune checkpoint inhibitors, a type of cancer immunotherapy, which cause a variety of inflammatory syndromes of importance to rheumatologists, are reviewed.
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Affiliation(s)
- Laura C Cappelli
- Division of Rheumatology, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Arthritis Center, Baltimore, MD, 21224, USA.
| | - Ami A Shah
- Division of Rheumatology, Johns Hopkins University School of Medicine, 5200 Eastern Avenue, Mason F. Lord Center Tower, Suite 4100, Baltimore, MD, 21224, USA.
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Suppression of Hepatocellular Carcinoma by Mycophenolic Acid in Experimental Models and in Patients. Transplantation 2019; 103:929-937. [PMID: 30747839 DOI: 10.1097/tp.0000000000002647] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Tumor recurrence is a major complication following liver transplantation (LT) as treatment for hepatocellular carcinoma (HCC). Immunosuppression is an important risk factor for HCC recurrence, but conceivably may depend on the type of immunosuppressive medication. Mycophenolic acid (MPA) is a currently widely used immunosuppressant. This study investigated the effects of MPA on HCC. METHODS Three human HCC cell lines and organoids from mouse primary liver tumor were used as experimental models. MTT, Alamar Blue assay, cell cycle analysis, colony formation, and [3H]-thymidine assays were performed. An LT database was used for retrospective analysis of the effect of mycophenolate mofetil, the prodrug of MPA, on HCC recurrence. RESULTS With clinically achievable concentrations, MPA effectively inhibited HCC cell proliferation and single-cell colony-forming unit. In short-term experiments, MPA effectively elicited S phase arrest in HCC cell lines. In addition, the initiation and growth of liver tumor organoids were effectively inhibited by MPA. Most importantly, the use of mycophenolate mofetil in patients with HCC-related LT was significantly associated with less tumor recurrence and improved patient survival. CONCLUSIONS MPA can specifically counteract HCC growth in vitro and tumor recurrence in LT patients. These results warrant prospective clinical trials into the role of MPA-mediated immunosuppression following LT of patients with HCC.
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Anti-Tumor Potential of IMP Dehydrogenase Inhibitors: A Century-Long Story. Cancers (Basel) 2019; 11:cancers11091346. [PMID: 31514446 PMCID: PMC6770829 DOI: 10.3390/cancers11091346] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 09/01/2019] [Accepted: 09/02/2019] [Indexed: 01/15/2023] Open
Abstract
The purine nucleotides ATP and GTP are essential precursors to DNA and RNA synthesis and fundamental for energy metabolism. Although de novo purine nucleotide biosynthesis is increased in highly proliferating cells, such as malignant tumors, it is not clear if this is merely a secondary manifestation of increased cell proliferation. Suggestive of a direct causative effect includes evidence that, in some cancer types, the rate-limiting enzyme in de novo GTP biosynthesis, inosine monophosphate dehydrogenase (IMPDH), is upregulated and that the IMPDH inhibitor, mycophenolic acid (MPA), possesses anti-tumor activity. However, historically, enthusiasm for employing IMPDH inhibitors in cancer treatment has been mitigated by their adverse effects at high treatment doses and variable response. Recent advances in our understanding of the mechanistic role of IMPDH in tumorigenesis and cancer progression, as well as the development of IMPDH inhibitors with selective actions on GTP synthesis, have prompted a reappraisal of targeting this enzyme for anti-cancer treatment. In this review, we summarize the history of IMPDH inhibitors, the development of new inhibitors as anti-cancer drugs, and future directions and strategies to overcome existing challenges.
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Tavakolpour S, Darvishi M, Ghasemiadl M. Pharmacogenetics: A strategy for personalized medicine for autoimmune diseases. Clin Genet 2019; 93:481-497. [PMID: 29194620 DOI: 10.1111/cge.13186] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2017] [Revised: 11/24/2017] [Accepted: 11/24/2017] [Indexed: 12/12/2022]
Abstract
For many years, a considerable number of patients with autoimmune diseases (ADs) have suffered from a lack of drug response and drug-related toxicity. Despite the emergence of new therapeutic options such as biological agents, patients continue to struggle with these problems. Unfortunately, new challenges, including the paradoxical effects of biological drugs, have complicated the situation. In recent decades, efforts have been made to predict drug response as well as drug-related side effects. Thanks to the many advances in genetics, evaluation of markers to predict drug response/toxicity before the initiation of treatment may be an avenue toward personalizing treatments. Implementing pharmacogenetics and pharmacogenomics in the clinic could improve clinical care; however, obstacles remain to effective personalized medicine for ADs. The present study attempted to clarify the concept of pharmacogenetics/pharmacogenomics for ADs. After an overview on the pathogenesis of the most common types of treatments, this paper focuses on pharmacogenetic studies related to the selected ADs. Bridging the gap between pharmacogenetics and personalized medicine is also discussed. Moreover, the advantages, disadvantages and recommendations related to making personalized medicine practical for ADs have been addressed.
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Affiliation(s)
- S Tavakolpour
- Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran
| | - M Darvishi
- Infectious Diseases and Tropical Medicine Research Center (IDTMRC), Department of Aerospace and Subaquatic Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - M Ghasemiadl
- Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran
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Abstract
Posttransplant malignancy is a leading cause of death after solid organ transplantation (SOT). Recipients of SOT are at significantly higher risk of multiple cancers compared with the general population, most notably nonmelanoma skin cancer and posttransplant lymphoproliferative disorders. Risk factors for posttransplant malignancy include history of malignancy, immunosuppression, oncogenic viral infections, sun exposure, and disease-specific associations. Early detection and treatment of malignancies can improve survival.
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Chatron E, Dégot T, Salvaterra E, Dumazet A, Porzio M, Hirschi S, Schuller A, Massard G, Renaud-Picard B, Kessler R. Lung cancer after lung transplantation: An analysis of 25 years of experience in a single institution. Clin Transplant 2018; 33:e13446. [DOI: 10.1111/ctr.13446] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 10/26/2018] [Accepted: 11/04/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Eva Chatron
- Groupe de transplantation pulmonaire; Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil; Strasbourg Cedex France
| | - Tristan Dégot
- Groupe de transplantation pulmonaire; Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil; Strasbourg Cedex France
| | - Elena Salvaterra
- Groupe de transplantation pulmonaire; Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil; Strasbourg Cedex France
| | - Antoine Dumazet
- Groupe de transplantation pulmonaire; Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil; Strasbourg Cedex France
| | - Michele Porzio
- Groupe de transplantation pulmonaire; Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil; Strasbourg Cedex France
| | - Sandrine Hirschi
- Groupe de transplantation pulmonaire; Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil; Strasbourg Cedex France
| | - Armelle Schuller
- Groupe de transplantation pulmonaire; Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil; Strasbourg Cedex France
| | - Gilbert Massard
- Groupe de transplantation pulmonaire; Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil; Strasbourg Cedex France
| | - Benjamin Renaud-Picard
- Groupe de transplantation pulmonaire; Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil; Strasbourg Cedex France
| | - Romain Kessler
- Groupe de transplantation pulmonaire; Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil; Strasbourg Cedex France
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Åberg F, Isoniemi H, Pukkala E, Jalanko H, Rasmussen A, Storm HH, Schultz N, Bennet W, Ekvall N, Ericzon BG, Malenicka S, Tretli S, Line PD, Boberg KM, Østensen A, Karlsen TH, Nordin A. Cancer After Liver Transplantation in Children and Young Adults: A Population-Based Study From 4 Nordic Countries. Liver Transpl 2018; 24:1252-1259. [PMID: 30120902 DOI: 10.1002/lt.25305] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2018] [Accepted: 06/19/2018] [Indexed: 02/07/2023]
Abstract
Cancer after liver transplantation (LT) constitutes a threat also for young recipients, but cancer risk factors are usually absent in children and large studies on the cancer risk profile in young LT recipients are scarce. Data of patients younger than 30 years who underwent LT during the period 1982-2013 in the Nordic countries were linked with respective national cancer registries to calculate standardized incidence ratios (SIRs). A total of 37 cancer cases were observed in 923 patients with 7846 person-years of follow-up. The SIR for all cancer types, compared with the matched general population, was 9.8 (12.4 for males and 7.8 for females). Cumulative incidence of cancer adjusted for the competing risk of death was 2% at 10 years, 6% at 20 years, and 22% at 25 years after LT. Non-Hodgkin lymphoma was the most common cancer type (n = 14) followed by colorectal (n = 4) and hepatocellular cancer (n = 4). Age was a significant risk factor for cancer, and the absolute risk of most cancers (except for lymphoma) increased considerably in young adults older than 20 years. The cancer risk pattern is different in pediatric and young LT patients compared with adult recipients. The striking increase in cancer incidence in young adulthood after the second decade of life deserves further consideration in transition programs.
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Affiliation(s)
- Fredrik Åberg
- Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland
| | - Helena Isoniemi
- Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland
| | - Eero Pukkala
- Institute for Statistical and Epidemiological Cancer Research, Finnish Cancer Registry, Helsinki, Finland.,Faculty of Social Sciences, University of Tampere, Tampere, Finland
| | - Hannu Jalanko
- Department of Pediatric Nephrology and Transplantation, Children's Hospital, Helsinki University Hospital, Helsinki, Finland
| | - Allan Rasmussen
- Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | | | - Nicolai Schultz
- Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - William Bennet
- Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Nils Ekvall
- Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg and Queen Silvia Children's Hospital, Gothenburg, Sweden
| | - Bo-Göran Ericzon
- Division of Transplantation Surgery, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Silvia Malenicka
- Department of Pediatrics, Astrid Lindgren's Children's Hospital Huddinge, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | | | - Pål-Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Kirsten Muri Boberg
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
| | - Anniken Østensen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway
| | - Tom Hemming Karlsen
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.,Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Arno Nordin
- Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland
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48
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Zeng J, Christiansen A, Pooli A, Qiu F, LaGrange CA. Safety and Clinical Outcomes of Robot-Assisted Radical Prostatectomy in Kidney Transplant Patients: A Systematic Review. J Endourol 2018; 32:935-943. [PMID: 30039723 DOI: 10.1089/end.2018.0394] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE To evaluate the safety and outcomes of robot-assisted radical prostatectomy (RARP) in renal transplant recipients (RTRs) based on available literature. MATERIALS AND METHODS A literature search was performed using PubMed, Embase, and Web of Science through "robot" AND "prostatectomy" AND "transplant." Three authors separately reviewed the records to select the relevant articles with any discrepancies solved by open discussion. Patient age, prostate-specific antigen, Gleason score, and tumor stage were recorded as well as intraoperative and postoperative complications, length of stay, surgical margin status, and disease recurrence, if provided. The operative techniques and modification/adjustments to standard port placements were also reviewed. We also include our case report in this review. RESULTS We retrieved 10 articles reporting clinical data on RARP for kidney transplant patients, including 5 case series (level 4) and 5 case reports (level 4). A total of 35 kidney transplant recipients undergoing RARP were analyzed in this systematic review, one case in our institution included. None of the cases had major technical difficulties precluding the operation. Technical modifications to the standard technique were described in 10 of the 11 articles specifically including modifications to port placement (54% of patients), development of the space of Retzius (60% of patients), and performance of lymphadenectomy. Mean operative time was 220 minutes. Perioperative complication rate was 17.1% (6 of 35 patients), with only one Clavien III or greater complication. The rate of positive surgical margins was found to be 31.4%. Data on biochemical recurrence revealed a combined rate of 18.1%. CONCLUSIONS RARP is technically feasible for treating localized prostate cancer in RTRs. Graft function did not deteriorate in any patient. Modifications to the standard technique should be considered specifically for port placement, development of the space of Retzius, and performance of lymphadenectomy. Oncologic outcomes remain difficult to interpret given the small number of reported cases.
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Affiliation(s)
- Jiping Zeng
- 1 College of Medicine, University of Nebraska Medical Center , Omaha, Nebraska
| | - Andrew Christiansen
- 2 Division of Urology, University of Nebraska Medical Center , Omaha, Nebraska
| | - Aydin Pooli
- 3 Department of Urology, David Geffen School of Medicine at University of California , Los Angeles, California
| | - Fang Qiu
- 4 Department of Biostatistics, College of Public Health, University of Nebraska Medical Center , Omaha, Nebraska
| | - Chad A LaGrange
- 2 Division of Urology, University of Nebraska Medical Center , Omaha, Nebraska
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49
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Acuna SA. Etiology of increased cancer incidence after solid organ transplantation. Transplant Rev (Orlando) 2018; 32:218-224. [PMID: 30017342 DOI: 10.1016/j.trre.2018.07.001] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 06/28/2018] [Accepted: 07/05/2018] [Indexed: 01/15/2023]
Abstract
Over the past decades, there has been an encouraging increase in survival after solid organ transplantation. However, with longer life spans, more transplant recipients are at risk of dying with functioning grafts from illnesses such as cancer and cardiovascular conditions. Malignancy has emerged as an important cause of death in transplant recipients and is expected to become the leading cause of death in transplanted patients within the next decade. While it is known that solid organ transplant recipients have a three to five-fold increased risk of developing cancer compared with the general population, the mechanisms that lead to the observed excess risk in transplant recipients are less clear. This review explores the etiology of the increased cancer incidence in solid organ transplant including the effect of immunosuppressants on immunosurveillance and activation of oncogenic viruses, and carcinogenic effects of these medications; the role of chronic stimulation of the immune system on the development of cancer; and the impact of pre-existing cancer risk factors and factors related to end-stage organ disease on the cancer excess incidence in solid organ transplant recipients.
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Affiliation(s)
- Sergio A Acuna
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada; Department of Surgery, St. Michael's Hospital, Toronto, Canada; Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Canada.
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50
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Sprangers B, Nair V, Launay-Vacher V, Riella LV, Jhaveri KD. Risk factors associated with post-kidney transplant malignancies: an article from the Cancer-Kidney International Network. Clin Kidney J 2018; 11:315-329. [PMID: 29942495 PMCID: PMC6007332 DOI: 10.1093/ckj/sfx122] [Citation(s) in RCA: 96] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Accepted: 09/15/2017] [Indexed: 12/13/2022] Open
Abstract
In kidney transplant recipients, cancer is one of the leading causes of death with a functioning graft beyond the first year of kidney transplantation, and malignancies account for 8-10% of all deaths in the USA (2.6 deaths/1000 patient-years) and exceed 30% of deaths in Australia (5/1000 patient-years) in kidney transplant recipients. Patient-, transplant- and medication-related factors contribute to the increased cancer risk following kidney transplantation. While it is well established that the overall immunosuppressive dose is associated with an increased risk for cancer following transplantation, the contributive effect of different immunosuppressive agents is not well established. In this review we will discuss the different risk factors for malignancies after kidney transplantation.
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Affiliation(s)
- Ben Sprangers
- Department of Microbiology and Immunology, KU Leuven and Division of Nephrology, University Hospitals Leuven, Leuven, Belgium
- Department of Microbiology and Immunology, KU Leuven and Laboratory of Experimental Transplantation, University Hospitals Leuven, Leuven, Belgium
- Cancer-Kidney International Network, Brussels, Belgium
| | - Vinay Nair
- Department of Medicine, Division of Kidney Diseases and Hypertension, Hofstra Northwell School of Medicine, Hempstead, NY, USA
| | - Vincent Launay-Vacher
- Cancer-Kidney International Network, Brussels, Belgium
- Service ICAR and Department of Nephrology, Pitié-Salpêtrière University Hospital, Paris, France
| | - Leonardo V Riella
- Department of Medicine, Schuster Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Boston, MA, USA
| | - Kenar D Jhaveri
- Cancer-Kidney International Network, Brussels, Belgium
- Department of Medicine, Division of Kidney Diseases and Hypertension, Hofstra Northwell School of Medicine, Hempstead, NY, USA
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