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Long-term cancer risk of immunosuppressive regimens after kidney transplantation.

ABSTRACT: Cancer is a widely recognized complication of transplantation, and the effects of various immunosuppressive drugs on cancer risk remains controversial. This randomized trial allocated 489 recipients of first cadaveric renal transplants to one of three groups: Azathioprine and prednisolone, cyclosporine monotherapy, or cyclosporine monotherapy followed by a switch to azathioprine and prednisolone after 3 months. Here, we report cancer outcomes by non-skin cancer (including melanoma) and skin cancer (excluding melanoma) for 481 patients during a median follow-up of 20.6 years. A total of 226 patients developed at least one cancer: 95 with non-skin cancer and 171 with skin cancer. In the intention-to-treat analysis, mean times to first non-skin cancer (16.0, 15.3, and 15.7 years for groups 1 through 3, respectively) and first skin cancer (13.6, 14.3, and 15.2 years, respectively) were not different among the three groups or between any subgroup. In multivariate analyses, non-skin cancer associated with increasing age and previous smoking history, whereas skin cancer associated with increasing age, nonbrown eye color, fairer skin, and a functioning transplant. Treatment allocation did not associate with development of either form of cancer in multivariate analyses. In conclusion, these immunosuppressive regimens, widely used in recent decades, carry similar risks for carcinogenicity after kidney transplantation.

SUBMITTER: Gallagher MP

PROVIDER: S-EPMC2865745 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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Long-term cancer risk of immunosuppressive regimens after kidney transplantation.

Gallagher Martin P MP Kelly Patrick J PJ Jardine Meg M Perkovic Vlado V Cass Alan A Craig Jonathan C JC Eris Josette J Webster Angela C AC

Journal of the American Society of Nephrology : JASN 20100429 5

Cancer is a widely recognized complication of transplantation, and the effects of various immunosuppressive drugs on cancer risk remains controversial. This randomized trial allocated 489 recipients of first cadaveric renal transplants to one of three groups: Azathioprine and prednisolone, cyclosporine monotherapy, or cyclosporine monotherapy followed by a switch to azathioprine and prednisolone after 3 months. Here, we report cancer outcomes by non-skin cancer (including melanoma) and skin canc ...[more]

PMID: 20431040

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Project description:BackgroundThe cancer incidence, types, and risk factors after pediatric kidney transplantation (KT) have been reported in the United States, Canada, Europe, Australia, and New Zealand. However, no information is available about cancer in pediatric KT recipients in Asian countries.MethodsChildren aged <20 y who underwent initial KT from 1983 to 2016 were analyzed. We compared the cancer incidence with that in the general Japanese population using standardized incidence ratio and examined posttransplant cancer risk using Cox proportional hazards models.ResultsA total of 356 children (median age, 11.7 y; interquartile range, 5.0-17.6) received KT with a follow-up period of 4466 person-years. The median age of cancer onset was 18.5 y (interquartile range, 8.0-32.3), and 13 cancers occurred in 12 patients (3.4%). Two patients died from cancer. The most common cancers were posttransplant lymphoproliferative disorders (PTLDs) (38.5%). The median time to PTLD and non-PTLD diagnosis after KT was 0.6 and 16.4 y, respectively. There was no occurrence of skin cancer. The posttransplant cancer incidence was 9.9 times higher than that in the general age-matched population (standardized incidence ratio = 9.9; 95% confidence interval, 4.80-18.39). The cumulative cancer incidence was 5.3% in 20 y after KT, which is lower than that reported in previous studies. We could not identify any risk factors for all cancer after KT in all patients, whereas subgroup analysis in 264 patients with available data of recipient Epstein-Barr virus serological status showed that recipient Epstein-Barr virus-negative serology was an independent risk factor for cancer development.ConclusionsThe incidence of cancer is higher in Japanese pediatric KT recipients than in the general population. The cumulative incidence of cancer after KT was lower in our population than that previously reported. This may be because there was no skin cancer observed in the Japanese pediatric KT recipients in our study.

Project description:Background & aimsThe long-term immunogenicity of anti-SARS-CoV-2 vaccines in liver transplant (LT) recipients is unknown. We aimed to assess the long-term antibody response of the Pfizer-BioNTech® BNT162b2 vaccine in LT recipients compared to controls.MethodsLT recipients underwent anti-SARS-CoV-2 anti-receptor-binding domain protein IgG (anti-RBD) and anti-nucleocapsid protein IgG antibody (anti-N) measurements at the first and 1, 4 and 6 months after the second vaccination dose.ResultsOne hundred forty-three LT recipients and 58 controls were enrolled. At baseline, 131/143 (91.6%) LT recipients tested anti-N negative (COVID-19 naïve), and 12/143 (8.4%) tested positive (COVID-19 recovered) compared to negative controls. Among COVID-19 naïve, 22.1% were anti-RBD positives 1 month after the first vaccine dose, while 66.4%, 77%, and 78.8% were 1, 4 and 6 months following the second vaccine dose. In contrast, 100% of controls were positive at 4 months (p <0.001). The median anti-RBD titer 4 months after the second vaccine dose was significantly lower (32 U/ml) in COVID-19 naïve than in controls (852 U/ml, p <0.0001). A higher daily dose of mycophenolate mofetil (MMF) (p <0.001), higher frequency of ascites (p = 0.012), and lower serum leukocyte count (p = 0.016) were independent predictors of anti-RBD negativity at 6 months. All COVID-19 recovered patients tested positive for anti-RBD at each time point. The median antibody titer was similar in those taking MMF (9,400 U/ml, 11,925 U/ml, 13,305 U/ml, and 10,095 U/ml) or not taking MMF (13,950 U/ml, 9,575 U/ml, 3,500 U/ml, 2,835 U/ml, p = NS) 3 weeks after the first and 1, 4 and 6 months after the second vaccine dose, respectively.ConclusionsIn COVID-19-naïve LT recipients, the immunogenicity of anti-SARS-CoV-2 vaccination was significantly lower than that in controls. MMF was the main determinant of vaccination failure in SARS-CoV-2-naïve patients.Lay summaryThe immunogenicity of anti-SARS-CoV-2 vaccination in liver transplant recipients is currently unknown. Herein, we show that liver transplant recipients who have not previously had COVID-19 are less likely to mount effective antibody responses to vaccination than a control population. The main determinant of vaccination failure was the use of the immunosuppressive drug mycophenolate mofetil.

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Long-term cancer risk of immunosuppressive regimens after kidney transplantation.

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Long-term cancer risk of immunosuppressive regimens after kidney transplantation.

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