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Initial benefit of mycophenolate mofetil (MMF) in heart transplant recipients with renal impairment is maintained at two-year follow up
S140
Abstracts
The Journal of Heart and Lung Transplantation February 2004
Slopes of FEV1 and BOS stages were compared before and after ATG using two-tailed paired Student t tests. Clinical predictors of a therapeutic response were examined using a multivariate linear regression model with BOS stage after ATG as the dependent variable. The mean FEV1 slope was less steep after ATG than before ATG (⫺1.4 ⫾ 3.5 vs ⫺5.6 ⫾ 4.3 ml/d; p ⬍ 0.005) and the mean BOS stages before and after ATG were not significantly different (1.8 ⫾ 0.9 vs 1.9 ⫾ 1.2; p ⫽ 0.3). The results of the multivariate linear regression model are shown in Table 1. In conclusion, treatment with ATG is associated with a reduction in the rate of decline in FEV1 and a delay in the progression to more advanced stages of BOS. Male gender, high FEV1 slopes before and after ATG, a lower BOS stage before ATG, and the magnitude of reduction in the absolute lymphocyte count after ATG are associated with a favorable response. Independent variable
Regression coefficient
95% CI
p
Constant FEV1 slope (ml/d) after ATG FEV1 slope (ml/d) before ATG Male gender ALC before ATG BOS stage before ATG ALC 3 months after ATG
1 ⫺0.17 ⫺0.07 ⫺1 ⫺0.0006 0.47 0.0009
0.3 to 1.7 ⫺0.23 to ⫺0.1 ⫺0.12 to ⫺0.01 ⫺1.5 to ⫺0.6 ⫺0.001 to ⫺0.0001 0.26 to 0.69 0.0001 to 0.001
0.007 ⬍0.0005 0.015 ⬍0.0005 0.007 ⬍0.0005 ⬍0.0005
Model R2 ⫽ 0.78, p ⬍ 0.0005. ALC, absolute lymphocyte count.
290 INITIAL BENEFIT OF MYCOPHENOLATE MOFETIL (MMF) IN HEART TRANSPLANT RECIPIENTS WITH RENAL IMPAIRMENT IS MAINTAINED AT TWO-YEAR FOLLOW UP M.J. Matuszewski,1 T.J. Locke,1 D.N. Hopkinson,1 P.C. Braidley,1 1 Heart and Lung Transplant Unit, Northern General Hospital, Sheffield, South Yorkshire, United Kingdom Aim: to assess the safety of MMF therapy and potential benefit to heart transplant recipients with deteriorating renal function. Method: Forty patients with deteriorating renal function on standard immunosuppression therapy were commenced on MMF (1 gram twice daily). Cyclosporine or Tacrolimus doses were subsequently reduced. Mean age was 55.3 years (20-71yrs); mean time post transplant 5.2 years (0-10.5yrs). Patients were followed for two years. 29 heart transplant recipients with deteriorating renal function were used as retrospective controls. Creatinine clearance was estimated using the Cockcroft-Gault formula. Results: Creatinine clearance in the study group was significantly higher at 6-24 months than when MMF was started (25.1-26.9 vs. 21.1 ml/min, p ⬍ 0.01, compare Figure 1). Cyclosporine levels were significantly lower at two years than those at onset of treatment (91 vs. 153.8, p ⬍ 0.001), although no correlation with creatinine clearance was found. Multivariate analysis of the MMF group and the control group identified time post transplant (p ⬍ 0.01), creatinine clearance when treatment was started (p ⬍ 0.01), and MMF administration (p ⫽ 0.02) as significant predictors of creatinine clearance two years later. Three patients of MMF group died: one of lung cancer, one of complete heart block, and one of heart failure. One patient developed lymphoma (MMF was discontinued). Five patients, in whom MMF was started 7.8 years post transplant, with the mean creatinine clearance of 15.4 ml/min, required dialysis. No increased incidence of rejection was seen. Conclusion: renal function improves following conversion to MMF and this improvement is maintained at two years. This regimen appears to be generally well tolerated and effective if introduced early.
291 RENAL FUNCTION IS PRESERVED FOLLOWING HEART TRANSPLANTATION USING IL-2 RECEPTOR BLOCKADE G. Wheatley,1 C.W. Yancy,2 M.A. Wait,1 D.M. Meyer,1 M.E. Jessen,1 M.C. Paul,1 P. Kaiser,1 R.A. Bhojani,1 M. Drazner,2 W.S. Ring,1 J.M. DiMaio,1 1Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX; 2Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX The search to preserve renal function following heart transplantation has led us to establish a protocol utilizing an IL-2 receptor monoclonal antibody (basiliximab) in our post-transplant population. Methods: We compared the results of our last 50 consecutive heart transplant recipients who each received basiliximab as induction therapy, and late cyclosporine, to a control group (n ⫽ 30) who received early cyclosporine. Both groups received mycophenolate mofetil and steroids in similar dosing regimens. The basiliximab was given on the day of transplant and POD #5 in 20 mg dosage. Cyclosporine was held until renal function normalized after surgery (creatinine ⬍2.0 mg/dL). Both groups were treated to cyclosporine levels of 300-400 mg/mL). Results: There were no differences between the two groups in pre-operative measures of age, sex, UNOS status, or etiology of heart failure. There were also no differences in post-operative measurements of mortality, acute rejection, number of rejections/patient, time to rejection, or vascular rejection. There was not a significant difference in mean creatinine clearance before transplant as compared to 12 month levels in the basiliximab group that received early cyclosporine (70 vs 59 mL/min cleared). There was a significant difference mean creatinine clearance in the control group receiving no basiliximab and early cyclosporine dosing (92 vs 71 mL/min cleared, p ⫽ 0.006). Conclusions: We show that an induction protocol utilizing IL-2 recptor blockade with basiliximab followed by late initiation of cyclosporine preserves renal function as compared to a group where cyclosporine is begun immediately after transplantation. This induction protocol did not result in significant differences in regard to rejection or mortality.
292 IMPACT OF SIROLIMUS ON GONADAL FUNCTION IN HEART TRANSPLANT RECIPIENTS
Abstracts
The Journal of Heart and Lung Transplantation February 2004
Slopes of FEV1 and BOS stages were compared before and after ATG using two-tailed paired Student t tests. Clinical predictors of a therapeutic response were examined using a multivariate linear regression model with BOS stage after ATG as the dependent variable. The mean FEV1 slope was less steep after ATG than before ATG (⫺1.4 ⫾ 3.5 vs ⫺5.6 ⫾ 4.3 ml/d; p ⬍ 0.005) and the mean BOS stages before and after ATG were not significantly different (1.8 ⫾ 0.9 vs 1.9 ⫾ 1.2; p ⫽ 0.3). The results of the multivariate linear regression model are shown in Table 1. In conclusion, treatment with ATG is associated with a reduction in the rate of decline in FEV1 and a delay in the progression to more advanced stages of BOS. Male gender, high FEV1 slopes before and after ATG, a lower BOS stage before ATG, and the magnitude of reduction in the absolute lymphocyte count after ATG are associated with a favorable response. Independent variable
Regression coefficient
95% CI
p
Constant FEV1 slope (ml/d) after ATG FEV1 slope (ml/d) before ATG Male gender ALC before ATG BOS stage before ATG ALC 3 months after ATG
1 ⫺0.17 ⫺0.07 ⫺1 ⫺0.0006 0.47 0.0009
0.3 to 1.7 ⫺0.23 to ⫺0.1 ⫺0.12 to ⫺0.01 ⫺1.5 to ⫺0.6 ⫺0.001 to ⫺0.0001 0.26 to 0.69 0.0001 to 0.001
0.007 ⬍0.0005 0.015 ⬍0.0005 0.007 ⬍0.0005 ⬍0.0005
Model R2 ⫽ 0.78, p ⬍ 0.0005. ALC, absolute lymphocyte count.
290 INITIAL BENEFIT OF MYCOPHENOLATE MOFETIL (MMF) IN HEART TRANSPLANT RECIPIENTS WITH RENAL IMPAIRMENT IS MAINTAINED AT TWO-YEAR FOLLOW UP M.J. Matuszewski,1 T.J. Locke,1 D.N. Hopkinson,1 P.C. Braidley,1 1 Heart and Lung Transplant Unit, Northern General Hospital, Sheffield, South Yorkshire, United Kingdom Aim: to assess the safety of MMF therapy and potential benefit to heart transplant recipients with deteriorating renal function. Method: Forty patients with deteriorating renal function on standard immunosuppression therapy were commenced on MMF (1 gram twice daily). Cyclosporine or Tacrolimus doses were subsequently reduced. Mean age was 55.3 years (20-71yrs); mean time post transplant 5.2 years (0-10.5yrs). Patients were followed for two years. 29 heart transplant recipients with deteriorating renal function were used as retrospective controls. Creatinine clearance was estimated using the Cockcroft-Gault formula. Results: Creatinine clearance in the study group was significantly higher at 6-24 months than when MMF was started (25.1-26.9 vs. 21.1 ml/min, p ⬍ 0.01, compare Figure 1). Cyclosporine levels were significantly lower at two years than those at onset of treatment (91 vs. 153.8, p ⬍ 0.001), although no correlation with creatinine clearance was found. Multivariate analysis of the MMF group and the control group identified time post transplant (p ⬍ 0.01), creatinine clearance when treatment was started (p ⬍ 0.01), and MMF administration (p ⫽ 0.02) as significant predictors of creatinine clearance two years later. Three patients of MMF group died: one of lung cancer, one of complete heart block, and one of heart failure. One patient developed lymphoma (MMF was discontinued). Five patients, in whom MMF was started 7.8 years post transplant, with the mean creatinine clearance of 15.4 ml/min, required dialysis. No increased incidence of rejection was seen. Conclusion: renal function improves following conversion to MMF and this improvement is maintained at two years. This regimen appears to be generally well tolerated and effective if introduced early.
291 RENAL FUNCTION IS PRESERVED FOLLOWING HEART TRANSPLANTATION USING IL-2 RECEPTOR BLOCKADE G. Wheatley,1 C.W. Yancy,2 M.A. Wait,1 D.M. Meyer,1 M.E. Jessen,1 M.C. Paul,1 P. Kaiser,1 R.A. Bhojani,1 M. Drazner,2 W.S. Ring,1 J.M. DiMaio,1 1Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX; 2Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX The search to preserve renal function following heart transplantation has led us to establish a protocol utilizing an IL-2 receptor monoclonal antibody (basiliximab) in our post-transplant population. Methods: We compared the results of our last 50 consecutive heart transplant recipients who each received basiliximab as induction therapy, and late cyclosporine, to a control group (n ⫽ 30) who received early cyclosporine. Both groups received mycophenolate mofetil and steroids in similar dosing regimens. The basiliximab was given on the day of transplant and POD #5 in 20 mg dosage. Cyclosporine was held until renal function normalized after surgery (creatinine ⬍2.0 mg/dL). Both groups were treated to cyclosporine levels of 300-400 mg/mL). Results: There were no differences between the two groups in pre-operative measures of age, sex, UNOS status, or etiology of heart failure. There were also no differences in post-operative measurements of mortality, acute rejection, number of rejections/patient, time to rejection, or vascular rejection. There was not a significant difference in mean creatinine clearance before transplant as compared to 12 month levels in the basiliximab group that received early cyclosporine (70 vs 59 mL/min cleared). There was a significant difference mean creatinine clearance in the control group receiving no basiliximab and early cyclosporine dosing (92 vs 71 mL/min cleared, p ⫽ 0.006). Conclusions: We show that an induction protocol utilizing IL-2 recptor blockade with basiliximab followed by late initiation of cyclosporine preserves renal function as compared to a group where cyclosporine is begun immediately after transplantation. This induction protocol did not result in significant differences in regard to rejection or mortality.
292 IMPACT OF SIROLIMUS ON GONADAL FUNCTION IN HEART TRANSPLANT RECIPIENTS