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      Risk of lymphoma subtypes after solid organ transplantation in the United States

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          Abstract

          Background:

          Solid organ transplant recipients have high risk of lymphomas, including non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). A gap in our understanding of post-transplant lymphomas involves the spectrum and associated risks of their many histologic subtypes.

          Methods:

          We linked nationwide data on solid organ transplants from the US Scientific Registry of Transplant Recipients (1987–2008) to 14 state and regional cancer registries, yielding 791 281 person-years of follow-up for 19 distinct NHL subtypes and HL. We calculated standardised incidence ratios (SIRs) and used Poisson regression to compare SIRs by recipient age, transplanted organ, and time since transplantation.

          Results:

          The risk varied widely across subtypes, with strong elevations (SIRs 10–100) for hepatosplenic T-cell lymphoma, Burkitt's lymphoma, NK/T-cell lymphoma, diffuse large B-cell lymphoma, and anaplastic large-cell lymphoma (both systemic and primary cutaneous forms). Moderate elevations (SIRs 2–4) were observed for HL and lymphoplasmacytic, peripheral T-cell, and marginal zone lymphomas, but SIRs for indolent lymphoma subtypes were not elevated. Generally, SIRs were highest for younger recipients (<20 years) and those receiving organs other than kidneys.

          Conclusion:

          Transplant recipients experience markedly elevated risk of a distinct spectrum of lymphoma subtypes. These findings support the aetiologic relevance of immunosuppression for certain subtypes and underscore the importance of detailed haematopathologic workup for transplant recipients with suspected lymphoma.

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          Most cited references36

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          Cancer incidence before and after kidney transplantation.

          Immune suppression after organ transplantation is associated with a markedly increased risk of nonmelanoma skin cancer and a few virus-associated cancers. Although it is generally accepted that other cancers do not occur at increased rates, there have been few long-term population-based cohort studies performed. To compare the incidence of cancer in patients receiving immune suppression after kidney transplantation with incidence in the same population in 2 periods before receipt of immune suppression: during dialysis and during end-stage kidney disease before renal replacement therapy (RRT). A population-based cohort study of 28,855 patients with end-stage kidney disease who received RRT, with 273,407 person-years of follow-up. Incident cancers (1982-2003) were ascertained by record linkage between the Australia and New Zealand Dialysis and Transplant Registry and the Australian National Cancer Statistics Clearing House. Standardized incidence ratios (SIRs) of cancer, using age-specific, sex-specific, calendar year-specific, and state/territory-specific population cancer incidence rates. The overall incidence of cancer, excluding nonmelanoma skin cancer and those cancers known to frequently cause end-stage kidney disease, was markedly increased after transplantation (n = 1236; SIR, 3.27; 95% confidence interval [CI], 3.09-3.46). In contrast, cancer incidence was only slightly increased during dialysis (n = 870; SIR, 1.35; 95% CI, 1.27-1.45) and before RRT (n = 689; SIR, 1.16; 95% CI, 1.08-1.25). After transplantation, cancer occurred at significantly increased incidence at 25 sites, and risk exceeded 3-fold at 18 of these sites. Most of these cancers were of known or suspected viral etiology. Kidney transplantation is associated with a marked increase in cancer risk at a wide variety of sites. Because SIRs for most types of cancer were not increased before transplantation, immune suppression may be responsible for the increased risk. These data suggest a broader than previously appreciated role of the interaction between the immune system and common viral infections in the etiology of cancer.
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            Cancer after kidney transplantation in the United States.

            Previous reports of cancer after kidney transplantation have been limited by small numbers of patients in single-center studies and incomplete ascertainment of cases in large registries. We examined rates of malignancies among first-time recipients of deceased or living donor kidney transplantations in 1995-2001 (n = 35 765) using Medicare billing claims. For most common tumors, e.g. colon, lung, prostate, stomach, esophagus, pancreas, ovary and breast, cancer rates were roughly twofold higher after kidney transplantation compared with the general population. Melanoma, leukemia, hepatobiliary tumors, cervical and vulvovaginal tumors were each approximately fivefold more common. Testicular and bladder cancers were increased approximately threefold, while kidney cancer was approximately 15-fold more common. Kaposi's sarcoma, non-Hodgkin's lymphomas, and nonmelanoma skin cancers were more than 20-fold increased than in the general population. Compared with patients on the waiting list, several tumors were more common after transplantation (p < 0.01): nonmelanoma skin cancers (2.6-fold), melanoma (2.2-fold), Kaposi's sarcoma (9.0-fold), non-Hodgkin's lymphoma (3.3-fold), cancer of the mouth (2.2-fold), and cancer of the kidney (39% higher). The rates for most malignancies are higher after kidney transplantation compared with the general population. Cancer should continue to be a major focus of prevention in kidney transplantation.
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              Lymphomas after solid organ transplantation: a collaborative transplant study report.

              We used the Collaborative Transplant Study database to analyze the incidence, risk, and impact of malignant lymphomas in approximately 200,000 organ transplant recipients. Over a 10-year period, the risk in renal transplant recipients was 11.8-fold higher than that in a matched nontransplanted population (p<0.0001). The majority of lymphomas were diagnosed after the first post-transplant year. Heart-lung transplants showed the highest relative risk (RR 239.5) among different types of organ transplants. In kidney recipients, immunosuppression with cyclosporine did not confer added risk compared with azathioprine/steroid treatment, whereas treatment with FK506 increased the risk approximately twofold. Induction therapy with OKT3 or ATG, but not with anti-IL2 receptor antibodies, increased the risk of lymphoma during the first year. Antirejection therapy with OKT3 or ATG also increased the risk. First-year mortality in renal and heart transplant patients with lymphoma was approximately 40% and 50%, respectively, and showed no improvement in recent years. A pattern of preferential localization to the vicinity of the transplant was noted, and the prognosis of the patient was related to localization. This study highlights the continuing risk for lymphoma with time post-transplantation, the contribution of immunosuppression to increased risk, and continuing poor outcomes in patients with post-transplant lymphoma.
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                Author and article information

                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                09 July 2013
                11 June 2013
                : 109
                : 1
                : 280-288
                Affiliations
                [1 ]Cancer Prevention Institute of California , 2201 Walnut Avenue, Suite 300, Fremont, CA 94538-2334, USA
                [2 ]Division of Epidemiology, Department of Health Research and Policy and Medicine, Stanford University School of Medicine , Stanford, CA, USA
                [3 ]Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Rockville, MD, USA
                [4 ]Department of Epidemiology, University of Iowa , Iowa City, IA, USA
                [5 ]Department of Pathology, City of Hope National Medical Center , Duarte, CA, USA
                [6 ]Department of Epidemiology, University of California , Los Angeles, CA, USA
                Author notes
                Article
                bjc2013294
                10.1038/bjc.2013.294
                3708563
                23756857
                505ab00c-d5ac-45eb-a650-36d86639ba6d
                Copyright © 2013 Cancer Research UK

                From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

                History
                : 13 March 2013
                : 30 April 2013
                : 20 May 2013
                Categories
                Epidemiology

                Oncology & Radiotherapy
                non-hodgkin's lymphoma,hodgkin's lymphoma,transplantation,immunosuppression,burkitt's lymphoma,t-cell lymphoma

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