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  3. Effect of reduced immunosuppression after kidney transplant failure on risk of cancer: population based retrospective cohort study
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Research

Effect of reduced immunosuppression after kidney transplant failure on risk of cancer: population based retrospective cohort study

BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c570 (Published 11 February 2010) Cite this as: BMJ 2010;340:c570
  1. Marina T van Leeuwen, lecturer, epidemiologist12,
  2. Angela C Webster, senior lecturer, medical epidemiologist, and nephrologist345,
  3. Margaret R E McCredie, associate professor, epidemiologist6,
  4. John H Stewart, nephrologist6,
  5. Stephen P McDonald, associate professor, nephrologist37,
  6. Janaki Amin, senior lecturer, statistician1,
  7. John M Kaldor, professor, epidemiologist1,
  8. Jeremy R Chapman, professor, nephrologist5,
  9. Claire M Vajdic, senior lecturer, epidemiologist8,
  10. Andrew E Grulich, professor, medical epidemiologist1
  1. 1National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, 376 Victoria St, Sydney, NSW, 2010, Australia
  2. 2School of Public Health and Community Medicine, University of New South Wales, Sydney, NSW, 2052, Australia
  3. 3Australia and New Zealand Dialysis and Transplant Registry, Queen Elizabeth Hospital, Woodville South, SA, 5011, Australia
  4. 4School of Public Health, University of Sydney, Sydney, NSW, 2006, Australia
  5. 5Centre for Transplant and Renal Research, Westmead Millennium Institute, University of Sydney, Westmead Hospital, Westmead, NSW, 2145, Australia
  6. 6Department of Preventive and Social Medicine, University of Otago, Dunedin, 9054, New Zealand
  7. 7Disciplines of Medicine and Public Health, University of Adelaide, Adelaide, SA, 5005, Australia
  8. 8University of New South Wales Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, 2052, Australia
  1. Correspondence to: A E Grulich agrulich{at}nchecr.unsw.edu.au
  • Accepted 23 October 2009

Abstract

Objective To compare cancer incidence in kidney transplant recipients during periods of transplant function (and immunosuppression) and after transplant failure (when immunosuppression is ceased or reduced).

Design, setting, and participants Nationwide, population based retrospective cohort study of 8173 Australian kidney transplant recipients registered on the Australia and New Zealand Dialysis and Transplant Registry who first received a transplant during 1982-2003. Incident cancers were ascertained using linkage with national cancer registry records.

Main outcome measures Cancer-specific standardised incidence ratios for periods of transplant function and for dialysis after transplant failure. Incidence was compared between periods using multivariate incidence rate ratios adjusted for current age, sex, and duration of transplantation.

Results All cases of Kaposi’s sarcoma occurred during transplant function. Standardised incidence ratios were significantly elevated during transplant function, but not during dialysis after transplant failure, for non-Hodgkin’s lymphoma, lip cancer, and melanoma. For each of these cancers, incidence was significantly lower during dialysis after transplant failure in multivariate analysis (incidence rate ratios 0.20 (95% CI 0.06 to 0.65) for non-Hodgkin’s lymphoma, 0.04 (0.01 to 0.31) for lip cancer, and 0.16 (0.04 to 0.64) for melanoma). In contrast, standardised incidence ratios during dialysis after transplant failure remained significantly elevated for leukaemia and lung cancer, and cancers related to end stage kidney disease (kidney, urinary tract, and thyroid cancers), with thyroid cancer incidence significantly higher during dialysis after transplant failure (incidence rate ratio 6.77 (2.64 to 17.39)). There was no significant difference in incidence by transplant function for other cancers.

Conclusions The effect of immunosuppression on cancer risk is rapidly reversible for some, but not all, cancer types. Risk reversal was mainly observed for cancers with a confirmed infectious cause. Risk of other cancers, especially those related to end stage kidney disease, remained significantly increased after reduction of immunosuppression.

Footnotes

  • We acknowledge the dedication and care with which dialysis and transplantation units throughout Australia have regularly submitted the information on which this analysis has been performed, and the ANZDATA Registry staff who have created and maintained the database so accurately. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the Australia and New Zealand Dialysis and Transplant Registry. We thank the staff of the state and territory cancer registries for the use of their data. We also acknowledge assistance by the Australian Institute of Health and Welfare, and the Cancer Council Victoria, in the conduct of this study.

  • Author contribution: All authors contributed to the research design. Data were collected by the ANZDATA Registry and the Australian Association of Cancer Registries. Statistical analysis was performed by MTvL and JA. All authors contributed to the analysis and interpretation of data. MTvL, CMV, and AEG were responsible for drafting the manuscript. All authors have contributed to revisions and reviewed the final manuscript.

  • Funding and disclosures: This work was supported by the Cancer Council New South Wales (RG 47/03); the National Health and Medical Research Council (ID 510346 to CMV, ID 401131 to MTvL); and the Cancer Institute New South Wales (07/CDF/1-38 to CMV, 06/RSA/1/28 to MTvL). The ANZDATA Registry administrative office is supported by funding from the Australian Government Department of Health and Ageing, the New Zealand Ministry of Health, and Kidney Health Australia; data collection costs were borne by contributing renal units. The National Centre in HIV Epidemiology and Clinical Research is funded by the Australian Government Department of Health and Ageing and is affiliated with the Faculty of Medicine, University of New South Wales. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.

  • Competing interests: JRC is on advisory boards and speaker panels for pharmaceutical companies Astellas, Novartis, Wyeth, and Hoffmann la Roche, and he has received research support from the Juvenile Diabetes Foundation International, Novartis, Wyeth, Jannsen-Cilag, and Hoffmann la Roche. AEG is on the advisory board for the Gardasil human papillomavirus vaccine for the Commonwealth Serum Laboratories. No other authors reported financial disclosures.

  • Ethical approval: Approval was granted by all relevant institutional ethics committees. The requirement for informed consent from patients was waived because the researchers received only de-identified data.

  • Data sharing: No additional data available.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

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