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

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.

Cancer-specific standardised incidence ratios (SIR) by transplant function and multivariate incidence rate ratios (IRR). *ICDO-3 and ICD-10 codes for cancers: Kaposi’s sarcoma (C46); non-Hodgkin’s lymphoma (ICDO-3 9591, 9670-9729, 9820-9837, 9940, 9948, and 9590 if ICD-10 C82-C85); anogenital (C21 anus, C51-53 vulva, vagina, cervix uteri, C60 penis); oropharyngeal and oral cavity (C01-C02 tongue, C03-C06 mouth, C09 tonsil, C10 oropharynx); stomach (C16); lip (C00); melanoma (C43); leukaemia (ICDO-3 9800-9989 excluding 9820-9837, 9940, and 9948); lung (C33-34); colon (C18); breast (C50); prostate (C61); kidney (C64); urinary tract (C65-C68); thyroid (C73). †Upper confidence interval presented when zero cases observed. ‡Median unbiased estimate.