Molecular Insights in Transmission of Cancer From an Organ Donor to Four Transplant Recipients

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  • 1 Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco;
  • 2 UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco;
  • 3 Division of Nephrology, Department of Medicine,
  • 4 Division of Surgical Pathology,
  • 5 Department of Pathology and Laboratory Medicine,
  • 6 Department of Radiology,
  • 7 School of Medicine, and
  • 8 Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, California;
  • 9 Gene Upshaw Memorial Tahoe Forest Cancer Center, Truckee, California; and
  • 10 Clinical Cancer Genomics Laboratory, and
  • 11 Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, California.
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Organ donors are systematically screened for infection, whereas screening for malignancy is less rigorous. The true incidence of donor-transmitted malignancies is unknown due to a lack of universal tumor testing in the posttransplant setting. Donor-transmitted malignancy may occur even when not suspected based on donor or recipient factors, including age and time to cancer diagnosis. We describe the detection of a gastrointestinal adenocarcinoma transmitted from a young donor to 4 transplant recipients. Multidimensional histopathologic and genomic profiling showed a CDH1 mutation and MET amplification, consistent with gastric origin. At the time of writing, one patient in this series remains alive and without evidence of cancer after prompt organ explant after cancer was reported in other recipients. Because identification of a donor-derived malignancy changes management, our recommendation is to routinely perform short tandem repeat testing (or a comparable assay) immediately upon diagnosis of cancer in any organ transplant recipient. Routine testing for a donor-origin cancer and centralized reporting of outcomes are necessary to establish a robust evidence base for the future development of clinical practice guidelines.

Submitted February 25, 2020; accepted for publication July 15, 2020.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Disclaimer: This study used data from the Organ Procurement and Transplantation Network (OPTN). The OPTN data system includes data on all donor, waitlisted candidates, and transplant recipients in the United States, submitted by OPTN members. The Health Resources & Services Administration of the US Department of Health & Human Services provides oversight to the activities of the OPTN contractor.

Correspondence: Chloe E. Atreya, MD, PhD, UCSF Helen Diller Family Comprehensive Cancer Center, 550 16th Street, 6th Floor, Box 3211, San Francisco, CA 94158. Email: chloe.atreya@ucsf.edu

Supplementary Materials

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  • 1.

    Ison MG, Llata E, Conover CS, . Transmission of human immunodeficiency virus and hepatitis C virus from an organ donor to four transplant recipients. Am J Transplant 2011;11:12181225.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Rogers MF, Simonds RJ, Lawton KE, . Guidelines for preventing transmission of human immunodeficiency virus through transplantation of human tissue and organs. MMWR Recomm Rep 1994;43:117.

    • Search Google Scholar
    • Export Citation
  • 3.

    Martin DC, Rubini M, Rosen VJ. Cadaveric renal homotransplantation with inadvertent transplantation of carcinoma. JAMA 1965;192:752754.

  • 4.

    McIntosh DA, McPhaul JJ, Peterson EW, . Homotransplantation of a cadaver neoplasm and a renal homograft. JAMA 1965;192:11711173.

  • 5.

    Penn I. Transmission of cancer from organ donors. Ann Transplant 1997;2:712.

  • 6.

    Buell JF, Beebe TM, Trofe J, . Donor transmitted malignancies. Ann Transplant 2004;9:5356.

  • 7.

    Morath C, Schwenger V, Schmidt J, . Transmission of malignancy with solid organ transplants. Transplantation 2005;80(1 Suppl):S164166.

  • 8.

    Kauffman HM, McBride MA, Cherikh WS, . Transplant tumor registry: donors with central nervous system tumors. Transplantation 2002;73:579582.

  • 9.

    Desai R, Collett D, Watson CJ, . Cancer transmission from organ donors—unavoidable but low risk. Transplantation 2012;94:12001207.

  • 10.

    Green M, Covington S, Taranto S, . Donor-derived transmission events in 2013: a report of the Organ Procurement Transplant Network Ad Hoc Disease Transmission Advisory Committee. Transplantation 2015;99:282287.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Wolfe C, Tlusty S, Vece G, . Donor derived transmissions in 2016-2017: analysis of the OPTN Ad Hoc Disease Transmission Advisory Committee (DTAC) [abstract]. Am J Transplant 2017;17(Suppl 3):Abstract 565.

    • Search Google Scholar
    • Export Citation
  • 12.

    Stephens JK, Everson GT, Elliott CL, . Fatal transfer of malignant melanoma from multiorgan donor to four allograft recipients. Transplantation 2000;70:232236.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Matser YAH, Terpstra ML, Nadalin S, . Transmission of breast cancer by a single multiorgan donor to 4 transplant recipients. Am J Transplant 2018;18:18101814.

  • 14.

    Strauss DC, Thomas JM. Transmission of donor melanoma by organ transplantation. Lancet Oncol 2010;11:790796.

  • 15.

    Schmitt C, Ciré K, Schattenkirchner S, . Highly sensitive DNA typing for detecting tumors transmitted by transplantation. Transpl Int 1998;11:382386.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Zhou S, Xu B, Qi L, . Next-generation sequencing reveals mutational accordance between cell-free DNA from plasma, malignant pleural effusion and ascites and directs targeted therapy in a gastric cancer patient. Cancer Biol Ther 2019;20:1520.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Kato S, Okamura R, Baumgartner JM, . Analysis of circulating tumor DNA and clinical correlates in patients with esophageal, gastroesophageal junction, and gastric adenocarcinoma. Clin Cancer Res 2018;24:62486256.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Wilson RE, Hager EB, Hampers CL, . Immunologic rejection of human cancer transplanted with a renal allograft. N Engl J Med 1968;278:479483.

  • 19.

    Elder GJ, Hersey P, Branley P. Remission of transplanted melanoma—clinical course and tumour cell characterisation. Clin Transplant 1997;11:565568.

  • 20.

    Lipson EJ, Bagnasco SM, Moore J Jr, . Tumor regression and allograft rejection after administration of anti-PD-1. N Engl J Med 2016;374:896898.

  • 21.

    Spain L, Higgins R, Gopalakrishnan K, . Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma. Ann Oncol 2016;27:11351137.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Hassan N, Abudayyeh A, Shah M, . The outcome of checkpoint inhibitor therapy in patients with cancer and solid organ transplant: a systematic review of the literature [abstract]. J Clin Oncol 2018;36(Suppl):Abstract 41.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Kittai AS, Oldham H, Cetnar J, . Immune checkpoint inhibitors in organ transplant patients. J Immunother 2017;40:277281.

  • 24.

    Maggiore U, Pascual J. The bad and the good news on cancer immunotherapy: implications for organ transplant recipients. Adv Chronic Kidney Dis 2016;23:312316.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Boyle SM, Ali N, Olszanski AJ, . Donor-derived metastatic melanoma and checkpoint inhibition. Transplant Proc 2017;49:15511554.

  • 26.

    Gielis EM, Ledeganck KJ, De Winter BY, . Cell-free DNA: an upcoming biomarker in transplantation. Am J Transplant 2015;15:25412551.

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