Increased incidence of early de novo cancer in liver graft recipients treated with cyclosporine: An association with C₂ monitoring and recipient age

Abstract

The goal of this study was to determine the risk factors for de novo cancer after liver transplantation (LTx). Retrospective analyses were performed in 385 LTx patients who underwent transplantation between 1986 and 2007. In total, 50 (13.0%) recipients developed de novo malignancy. The cumulative incidence of de novo cancer at 1, 5, 10, and 15 years after LTx was 2.9% 6 0.9%, 10.5% 6 1.8%, 19.4% 6 3.0%, and 33.6% 6 6.8%, respectively. The standardized incidence ratio of malignancy in LTx patients compared to the general population was 2.2 (95% confidence interval: 1.6-2.8). After excluding posttransplant lymphoproliferative disorder and skin cancer, patients with de novo cancer had a significantly lower survival rate compared to recipients who remained cancer-free. The identified univariate risk factors for de novo cancer were cyclosporine A (CsA) treatment, time period of LTx, and recipient age. In multivariate analysis, only CsA treatment emerged as an independent risk factor for de novo cancer, which was attributed to more aggressive cancer types. A surprising finding was that CsA treatment specifically enhanced cancer risk in patients who underwent transplantation after 2004, when C 2 monitoring (blood concentration at 2 hours postdose) was introduced. In addition, these patients showed a significantly lower acute rejection rate, which might reflect a more robust immunosuppressive status caused by the CsA-C 2 regimen. When age was considered, only patients 50 years had a higher cancer rate when treated with CsA compared to treatment with tacrolimus. Our data suggest that, compared to tacrolimus treatment, CsA treatment with C 2 monitoring or in younger patients of 50 years is associated with a higher early de novo cancer risk after LTx. Liver Transpl 16:837-846, 2010.

Progression of Incidental Intraductal Papillary Mucinous Neoplasms of the Pancreas in Liver Transplant Recipients

“…Although immunosuppressive therapy after LT is associated with a standardized incidence ratio of malignancy of 2.2 as compared with the general population, 31 we demonstrated that immunosuppression does not correspond to increased development of features associated with malignant transformation of IPMN. Specifically, cyclosporine therapy and duration of an immunosuppressed state have been shown to be independent determinants of cancer development in post-LT patients.…”

“…Specifically, cyclosporine therapy and duration of an immunosuppressed state have been shown to be independent determinants of cancer development in post-LT patients. 31 Tacrolimus has been reported to be superior to cyclosporine in reducing mortality, graft loss, and acute rejection and improving renal function, lipid profiles, and blood pressure. 32,33 As our study did not demonstrate a preference for either calcineurin inhibitor, it does not appear that the choice of immunosuppression should be based on the presence of 34 Because of our limited sample size of patients on multiple immunosuppressants, we could not evaluate the effects of this regimen compared with single-agent therapy.…”

Liver transplantation

“…To our knowledge, only one single-centre study has described an increased risk of malignancy in liver transplant patients treated with cyclosporine compared with tacrolimus [28]. However, the authors admit that a different monitoring was used for cyclosporine, and lower rejection rates were detected in this group, suggesting higher immunosuppressive potency with cyclosporine than with tacrolimus in this series.…”

Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients

“…240 Challenges still remain, however, in determining the type and dose of immunosuppressive therapy posttransplant to further reduce HCC recurrence and improve its prognosis. CNIs in general are reported as having direct prooncogenic activity 241 ; high levels of cyclosporine (>300 ng/mL) and tacrolimus (>10 ng/mL) have been associated with an increased risk of HCC recurrence. 242 mTORi have antiangiogenic and antiproliferative properties.…”