Emma Taylor1, Mark Jones2, Matthew J Hourigan1, David W Johnson3, Devinder S Gill4, Nicole Isbel5, Carmel M Hawley5, Paula Marlton4, Maher K Gandhi6, Scott B Campbell5, Peter Mollee4. 1. Department of Haematology, Pathology Queensland and Cancer Services, Princess Alexandra Hospital, Brisbane, Australia. 2. School of Population Health, University of Queensland, Brisbane, Australia. 3. Department of Renal Medicine, Princess Alexandra Hospital, Brisbane, Australia School of Medicine, University of Queensland, Brisbane, Australia Translational Research Institute, University of Queensland, Brisbane, Australia. 4. Department of Haematology, Pathology Queensland and Cancer Services, Princess Alexandra Hospital, Brisbane, Australia School of Medicine, University of Queensland, Brisbane, Australia. 5. Department of Renal Medicine, Princess Alexandra Hospital, Brisbane, Australia School of Medicine, University of Queensland, Brisbane, Australia. 6. Department of Haematology, Pathology Queensland and Cancer Services, Princess Alexandra Hospital, Brisbane, Australia Diamantina Institute, University of Queensland, Brisbane, Australia.
Abstract
BACKGROUND: The optimal reduction of immunosuppressive therapy (IST) in renal transplant patients with post-transplant lymphoproliferative disorders (PTLDs) is uncertain. As chemotherapy is immunosuppressive, IST may be stopped during this time without compromising graft function. Subsequent long-term reduction of IST reduces relapse risk, but may increase risk of graft rejection. METHODS: We performed a retrospective, matched cohort study of adult renal transplant patients in whom IST was ceased during chemotherapy and resumed at lower dose (calcineurin inhibitor at 50%, prednisolone ≤10 mg daily, no third agent) approximately 6 weeks after chemotherapy. Outcomes were compared with those of renal transplant patients without PTLD, matched for creatinine at equivalent time post-transplant that PTLD was diagnosed in cases, as well as for age, gender and year of transplant. RESULTS: Twenty-four cases of PTLD occurring at a median of 9.2 years post-transplant were compared with 83 matched controls. PTLD cases were followed for a median of 11.9 years. Using competing risks analysis, time to 25% increase in serum creatinine was not significantly different between the two groups [adjusted hazard ratio (HR) 1.8, 95% confidence interval (CI) 0.89-3.6]. Similar results were obtained using multivariable Cox regression analysis (HR 1.19, 95% CI 0.44-3.23). Only one PTLD case experienced a ≥25% increase in creatinine <6 months after IST cessation in the setting of progressive PTLD and death. Three cases recommenced dialysis, compared with three controls (HR 2.5, 95% CI 0.47-13.00). Five-year patient survival rates for cases and controls were 70 and 94%, respectively (P = 0.01). CONCLUSIONS: IST can be safely ceased during chemotherapy for PTLD in renal transplant patients. Furthermore, long-term reduction in IST is not associated with a significant difference in renal function deterioration. Prospective trials are needed to address the optimal reduction of IST in PTLDs.
BACKGROUND: The optimal reduction of immunosuppressive therapy (IST) in renal transplant patients with post-transplant lymphoproliferative disorders (PTLDs) is uncertain. As chemotherapy is immunosuppressive, IST may be stopped during this time without compromising graft function. Subsequent long-term reduction of IST reduces relapse risk, but may increase risk of graft rejection. METHODS: We performed a retrospective, matched cohort study of adult renal transplant patients in whom IST was ceased during chemotherapy and resumed at lower dose (calcineurin inhibitor at 50%, prednisolone ≤10 mg daily, no third agent) approximately 6 weeks after chemotherapy. Outcomes were compared with those of renal transplant patients without PTLD, matched for creatinine at equivalent time post-transplant that PTLD was diagnosed in cases, as well as for age, gender and year of transplant. RESULTS: Twenty-four cases of PTLD occurring at a median of 9.2 years post-transplant were compared with 83 matched controls. PTLD cases were followed for a median of 11.9 years. Using competing risks analysis, time to 25% increase in serum creatinine was not significantly different between the two groups [adjusted hazard ratio (HR) 1.8, 95% confidence interval (CI) 0.89-3.6]. Similar results were obtained using multivariable Cox regression analysis (HR 1.19, 95% CI 0.44-3.23). Only one PTLD case experienced a ≥25% increase in creatinine <6 months after IST cessation in the setting of progressive PTLD and death. Three cases recommenced dialysis, compared with three controls (HR 2.5, 95% CI 0.47-13.00). Five-year patient survival rates for cases and controls were 70 and 94%, respectively (P = 0.01). CONCLUSIONS: IST can be safely ceased during chemotherapy for PTLD in renal transplant patients. Furthermore, long-term reduction in IST is not associated with a significant difference in renal function deterioration. Prospective trials are needed to address the optimal reduction of IST in PTLDs.