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Impact of Cytomegalovirus on Long-term Mortality and Cancer Risk After Organ Transplantation

Desai, Rajeev1; Collett, Dave1; Watson, Christopher J. E.2; Johnson, Philip J.3,4; Moss, Paul5,6; Neuberger, James1

doi: 10.1097/TP.0000000000000641
Original Clinical Science-General

Background: There is conflicting evidence of the effect of cytomegalovirus (CMV) infection on survival and the risk of cancer after transplantation.

Methods: All recipients of kidney, liver, heart, and lung transplants in the United Kingdom between 1987 and 2007 with known CMV immunoglobulin G status were identified from the U.K. Transplant Registry. Based on the donor-recipient CMV status, recipients were grouped into: donor (D) negative recipient (R) negative (D− R−), D−R+, D + R+ and D + R−. Cancer data were obtained from the Office for National Statistics. The impact of CMV infection on survival and cancer incidence was assessed.

Results: The 10-year posttransplant survival in D−R− recipients (73.6% [95%CI, 72.3, 74.9]) was significantly higher (P < 0.0001) than in other recipients (66.1% [65.3, 66.9]). Compared with the D− R− group, the risk-adjusted hazard of death within 10 years of transplantation for D+ R− group was 14% higher for kidney recipients (P = 0.0495), 13% higher for liver recipients (P = 0.16), 34% higher for heart recipients (P = 0.01), and 35% higher for lung recipients (P = 0.006). The proportion of recipients with a cardiovascular cause of death was higher (P = 0.03) among the recipients exposed to CMV (18%) as compared to the D− R− recipients (16%). The CMV status was not associated with an increased risk of cancer.

Conclusions: The results from this large study demonstrate that CMV is associated with a significantly increased long-term mortality in kidney and cardiothoracic transplant recipients and an increased risk of cardiovascular death but not of posttransplant cancer.

A large registry study from the United Kingdom covering all kidney, liver, heart and lung recipients over a 20-year period shows the highly significant contribution of CMV status to recipient survival, with the high risk groups having substantial increases in overall and cardiovascular but not cancer-related mortality.

1 National Health Service Blood and Transplant, Stoke Gifford, Bristol, United Kingdom.

2 University Department of Surgery, Addenbrooke's Hospital, Hills Road, Cambridge, United Kingdom.

3 Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, Merseyside, United Kingdom.

4 Clatterbridge Cancer Centre, Wirral, Merseyside, United Kingdom.

5 School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.

6 University Hospitals Birmingham, Edgbaston, Birmingham, United Kingdom.

Received 3 February 2014. Revision requested 3 March 2014.

Accepted 26 November 2014.

Funding provided by NHS Blood and Transplant.

The authors declare no conflicts of interest.

The NHS Blood and Transplant played no role in the conduct of this study, manuscript preparation, or the decision to submit for publication.

The Science, Technology, Engineering and Mathematics Ethical Review Committee at the University of Birmingham, UK has granted full ethical approval for this project.

R.D. designed the study, conducted literature search, data collection, data analysis, interpreted the results and drafted the manuscript. D.C. participated in data collection, data analysis and interpretation of results. C.J.E.W. participated in data collection and literature search. P.J.J. and P.M. participated in data analysis and interpretation. J.N. designed the study and contributed to data collection and interpretation. All authors contributed to the writing of the manuscript.

Correspondence: Rajeev Desai, MRCP, NHS Blood and Transplant, Fox Den Road, Stoke Gifford, Bristol BS34 8RR, United Kingdom. (rajeev.desai@nhs.net).

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