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Sirolimus + Tacrolimus Maintenance with No Induction Therapy May Maximize Survival in Lung Transplant Recipients
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The Journal of Heart and Lung Transplantation, Vol 38, No 4S, April 2019
276 Ten-Year-Experience with Alemtuzumab as Induction Therapy: A Single-Center Analysis of More Than 500 Patients A. Benazzo,1 S. Schwarz,1 D. Weber,2 G. Murakozy,1 C. Lambers,2 B. Moser,1 J. Matilla,1 G. Lang,2 S. Taghavi,1 W. Klepetko,1 K. Hoetzenecker,1 and P. Jaksch.1 1Thoracic Surgery, Medical University of Vienna, Vienna, Austria; and the 2Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria. Purpose: According to ISHLT increasing number of lung recipients receive induction therapy. Long-term data on the use of alemtuzumab are scarce, therefore, we aimed to review our experience and analyzed the impact of alemtuzumab. Methods: Patients transplanted between 2007 and 2017, who received alemtuzumab were included in this retrospective single-center analysis. The following parameters were evaluated: survival, ACR, CLAD, malignancies and kidney function, infections incidence. Results: Within the study period 525 patients received alemtuzumab as induction therapy. An episode of infection within the first year after LTx was reported in 358 patients (68%), however, only 216 of them (22%) needed hospitalization. In the same period 39 recipients (7.4%) died from infection complications. As one of the main advantages of induction therapy is the reduction of CNI, we analyzed rates of kidney insufficiency. During follow-up 94 patients (17.9%) developed kidney insufficiency (eGFR> 60 ml/min). Only two patients required chronic dialysis and one a kidney transplantation. At 1- and 5-years 98% and 97% patients were free from ACR. Three- and 5-years freedom rates from CLAD were 78.7% and 71.8%. Overall survival rates at 3- and 5-years were 79% and 74%, respectively. Conclusion: This study shows that alemtuzumab is an effective induction agent with low incidence of severe infections and good survival rates. The associated reduction of CNI doses led to low incidence of kidney insufficiency and long freedom rates from severe CLAD.
Dermatology, Medical University of Vienna, Vienna, Austria; and the Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria. 3
Purpose: Extracorporeal photopheresis (ECP) is used at the Medical University of Vienna as an empiric treatment option for lung transplant recipients suffering from bronchiolitis obliterans syndrome (BOS). The objective of the present retrospective investigation was to evaluate hospital-related costs and the clinical value of ECP when applied as an adjunct to the local standard therapy of BOS compared to standard treatment alone. Methods: The patient population consisted of 32 double-lung transplant recipients who had been diagnosed with BOS. Sixteen matched pairs, each pair comprising of one ECP-treated patient and one control patient was built (matched population). Preselect pair-match criteria were weighted. The primary matching criterion was the BOS grade at diagnosis. Secondary matching factors were the year of transplantation, age at transplantation, and gender. Results: Study groups were identical in demographic characteristics and clinical parameters at baseline. Over the observation period of up to 15.5 years, survival probability was improved by approximately 30% in the ECP treated patients as compared to matched controls (see Figure A; p<0.05). The mean number of total re-admissions to the hospital was only 5 § 3 (mean § standard deviation) for the ECP group vs 27 § 16 for the control group (p<0.05). Consequently, the total inpatient days of care were only 67 § 58 days in ECP patients and 133 § 94 days in control patients (p<0.05). Relevant parameters of lung function were not significantly affected. Conclusion: Compared to standard BOS-directed therapies, ECP improves significantly survival probability in double-lung transplant patients diagnosed with BOS. ECP exerts a significant impact on the number of total re-admissions to the hospital, the total days of care, and the total patient days. Thus, ECP has proved highly effective and cost saving in the treatment of lung transplant patients presenting with BOS.
278 Sirolimus + Tacrolimus Maintenance with No Induction Therapy May Maximize Survival in Lung Transplant Recipients M. Wijesinha, J. Hirshon, M. Terrin, L. Magder, C. Brown, K. Stafford and A. Iacono. University of Maryland School of Medicine, Baltimore, MD.
277 Extracorporeal Photopheresis Improves Survival Probability and Lowers Hospital-Related Expenses In Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome C. Joukhadar,1 R. Knobler,2 A. Cho,2 U. Just,2 G. Muraközy,3 and P. Jaksch.3 1J&P Medical Research Ltd, Vienna, Austria; 2Department of
Purpose: Sirolimus has purported advantages in lung transplant maintenance therapy, such as anti-fibrotic, anti-proliferative, and anti-aging effects, which may help improve survival. Methods: Among U.S. lung transplant recipients from 2003-2016 in the United Network for Organ Sharing (UNOS) dataset, we compared sirolimus [SIR] (n=219) to mycophenolate mofetil [MMF] (n=5482), within a tacrolimus-based regimen. The SIR group consisted of patients on SIR within 1 year post-transplant, since prophylactic SIR initiation is usually delayed by up to 1 year to avoid the risk of bronchial anastomotic dehiscence and other complications. Due to the delayed initiation of SIR, this study was restricted to patients alive at 1 year in both groups, to prevent immortal time bias. All patients in both groups were free of bronchiolitis
Abstracts
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obliterans syndrome and malignancy at 1 year, to exclude these common rescue uses of SIR. We also assessed survival for SIR and MMF after subdividing by whether or not patients received induction therapy (with basiliximab, daclizumab, antithymocyte globulin, or alemtuzumab). Survival comparisons were based on Kaplan-Meier estimates and Cox multivariable regression utilizing multiple imputation to handle missing data. Results: SIR had better survival than MMF: median (MS) 8.9 vs 7.1 yr.; adjusted Hazard Ratio (HR)=0.71, p=0.003. When subdividing by whether patients received induction, SIR with no induction had the best survival (MS=10.7 yr.; HR=0.48, p=0.002), followed by SIR with induction (MS=7.9 yr.; HR=0.90, p=0.45), MMF with induction (MS=7.4 yr.; reference group), and MMF with no induction (MS=6.8 yr.; HR=1.15, p=0.01). Conclusion: Sirolimus, initiated within 1 year after lung transplantation in a tacrolimus-based regimen, may improve survival compared to MMF. National data representing the U.S. lung transplant population suggest that sirolimus + tacrolimus maintenance with no induction therapy is associated with a median survival of approximately 10 years.
279 End Stage Renal Disease after Lung Transplantation: An 11-Year National Cohort Study M. Kosztowski, X. Luo, J. Garonzik-Wang, R. Higgins, D.L. Segev and E. Bush. Department of Surgery, Johns Hopkins, Baltimore, MD. Purpose: End stage renal disease (ESRD) is a dreaded complication after lung transplantation and is associated with inferior post-transplant survival. In this study, we sought to identify the incidence and risk factors for the development of ESRD in lung transplant recipients. Methods: We studied lung transplant recipients in the US between 01/01/ 2006-12/31/2016 using data from the Scientific Registry of Transplant Recipients (SRTR). We included recipients greater or equal to 12 years old. We excluded patients with ESRD prior to transplant. For ascertainment of our outcome of interest (ESRD), we linked our cohort data to the United States Renal Data System (USRDS). ESRD was defined as the initiation of dialysis, waitlisting, or kidney transplantation, whichever was identified first. We used Kaplan-Meier methods to estimate the cumulative incidence of ESRD and used multivariate Cox regression to determine risk factors associated with ESRD. Results: Among 17,054 lung transplant recipients, 514 developed ESRD at a mean of 3.57§2.45 years. Median follow up time was 2.9 years. The risk of ESRD increased over time. The cumulative incidence at 1, 3, and 5 years was 0.6% (95% CI, 0.5-0.7), 1.9% (1.7-2.2), and 4.1% (3.6-4.5). Pre-transplant risk factors associated with ESRD are shown in Table 1. Conclusion: This is the largest study to date looking at ESRD after lung transplantation, and we found a five-year risk of 4.1%. Closely monitoring modifiable risk factors that we identified might reduce the long-term risk of ESRD.
280 Hemodynamic and ECHO Measurements during VA ECMO Weaning Suggest Acceptable LV Unloading A.M. El Banayosy, C. Gordon, M.M. Koerner, M.D. Harper, D. Horstmanshof, D. Vanhooser, J.W. Long and A. El Banayosy INTEGRIS Baptist Medical Center, Oklahoma City, OK. Purpose: One major concern of utilizing veno-arterial (VA) ECMO in advanced cardiogenic shock (ACS) patients is its inability to completely unload the left ventricle (LV). However, the clinically significant degree of LV unloading required for recovery is not well described. We hypothesized that measuring hemodynamics during VA ECMO weaning would elucidate the impact of VA ECMO on LV unloading. Methods: From January 2017 to September 2018, 67 ACS patients required VA ECMO support longer than 24 hours. Acute or chronic heart failure patients were excluded. A weaning protocol using hemodynamic
The Journal of Heart and Lung Transplantation, Vol 38, No 4S, April 2019
276 Ten-Year-Experience with Alemtuzumab as Induction Therapy: A Single-Center Analysis of More Than 500 Patients A. Benazzo,1 S. Schwarz,1 D. Weber,2 G. Murakozy,1 C. Lambers,2 B. Moser,1 J. Matilla,1 G. Lang,2 S. Taghavi,1 W. Klepetko,1 K. Hoetzenecker,1 and P. Jaksch.1 1Thoracic Surgery, Medical University of Vienna, Vienna, Austria; and the 2Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria. Purpose: According to ISHLT increasing number of lung recipients receive induction therapy. Long-term data on the use of alemtuzumab are scarce, therefore, we aimed to review our experience and analyzed the impact of alemtuzumab. Methods: Patients transplanted between 2007 and 2017, who received alemtuzumab were included in this retrospective single-center analysis. The following parameters were evaluated: survival, ACR, CLAD, malignancies and kidney function, infections incidence. Results: Within the study period 525 patients received alemtuzumab as induction therapy. An episode of infection within the first year after LTx was reported in 358 patients (68%), however, only 216 of them (22%) needed hospitalization. In the same period 39 recipients (7.4%) died from infection complications. As one of the main advantages of induction therapy is the reduction of CNI, we analyzed rates of kidney insufficiency. During follow-up 94 patients (17.9%) developed kidney insufficiency (eGFR> 60 ml/min). Only two patients required chronic dialysis and one a kidney transplantation. At 1- and 5-years 98% and 97% patients were free from ACR. Three- and 5-years freedom rates from CLAD were 78.7% and 71.8%. Overall survival rates at 3- and 5-years were 79% and 74%, respectively. Conclusion: This study shows that alemtuzumab is an effective induction agent with low incidence of severe infections and good survival rates. The associated reduction of CNI doses led to low incidence of kidney insufficiency and long freedom rates from severe CLAD.
Dermatology, Medical University of Vienna, Vienna, Austria; and the Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria. 3
Purpose: Extracorporeal photopheresis (ECP) is used at the Medical University of Vienna as an empiric treatment option for lung transplant recipients suffering from bronchiolitis obliterans syndrome (BOS). The objective of the present retrospective investigation was to evaluate hospital-related costs and the clinical value of ECP when applied as an adjunct to the local standard therapy of BOS compared to standard treatment alone. Methods: The patient population consisted of 32 double-lung transplant recipients who had been diagnosed with BOS. Sixteen matched pairs, each pair comprising of one ECP-treated patient and one control patient was built (matched population). Preselect pair-match criteria were weighted. The primary matching criterion was the BOS grade at diagnosis. Secondary matching factors were the year of transplantation, age at transplantation, and gender. Results: Study groups were identical in demographic characteristics and clinical parameters at baseline. Over the observation period of up to 15.5 years, survival probability was improved by approximately 30% in the ECP treated patients as compared to matched controls (see Figure A; p<0.05). The mean number of total re-admissions to the hospital was only 5 § 3 (mean § standard deviation) for the ECP group vs 27 § 16 for the control group (p<0.05). Consequently, the total inpatient days of care were only 67 § 58 days in ECP patients and 133 § 94 days in control patients (p<0.05). Relevant parameters of lung function were not significantly affected. Conclusion: Compared to standard BOS-directed therapies, ECP improves significantly survival probability in double-lung transplant patients diagnosed with BOS. ECP exerts a significant impact on the number of total re-admissions to the hospital, the total days of care, and the total patient days. Thus, ECP has proved highly effective and cost saving in the treatment of lung transplant patients presenting with BOS.
278 Sirolimus + Tacrolimus Maintenance with No Induction Therapy May Maximize Survival in Lung Transplant Recipients M. Wijesinha, J. Hirshon, M. Terrin, L. Magder, C. Brown, K. Stafford and A. Iacono. University of Maryland School of Medicine, Baltimore, MD.
277 Extracorporeal Photopheresis Improves Survival Probability and Lowers Hospital-Related Expenses In Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome C. Joukhadar,1 R. Knobler,2 A. Cho,2 U. Just,2 G. Muraközy,3 and P. Jaksch.3 1J&P Medical Research Ltd, Vienna, Austria; 2Department of
Purpose: Sirolimus has purported advantages in lung transplant maintenance therapy, such as anti-fibrotic, anti-proliferative, and anti-aging effects, which may help improve survival. Methods: Among U.S. lung transplant recipients from 2003-2016 in the United Network for Organ Sharing (UNOS) dataset, we compared sirolimus [SIR] (n=219) to mycophenolate mofetil [MMF] (n=5482), within a tacrolimus-based regimen. The SIR group consisted of patients on SIR within 1 year post-transplant, since prophylactic SIR initiation is usually delayed by up to 1 year to avoid the risk of bronchial anastomotic dehiscence and other complications. Due to the delayed initiation of SIR, this study was restricted to patients alive at 1 year in both groups, to prevent immortal time bias. All patients in both groups were free of bronchiolitis
Abstracts
S123
obliterans syndrome and malignancy at 1 year, to exclude these common rescue uses of SIR. We also assessed survival for SIR and MMF after subdividing by whether or not patients received induction therapy (with basiliximab, daclizumab, antithymocyte globulin, or alemtuzumab). Survival comparisons were based on Kaplan-Meier estimates and Cox multivariable regression utilizing multiple imputation to handle missing data. Results: SIR had better survival than MMF: median (MS) 8.9 vs 7.1 yr.; adjusted Hazard Ratio (HR)=0.71, p=0.003. When subdividing by whether patients received induction, SIR with no induction had the best survival (MS=10.7 yr.; HR=0.48, p=0.002), followed by SIR with induction (MS=7.9 yr.; HR=0.90, p=0.45), MMF with induction (MS=7.4 yr.; reference group), and MMF with no induction (MS=6.8 yr.; HR=1.15, p=0.01). Conclusion: Sirolimus, initiated within 1 year after lung transplantation in a tacrolimus-based regimen, may improve survival compared to MMF. National data representing the U.S. lung transplant population suggest that sirolimus + tacrolimus maintenance with no induction therapy is associated with a median survival of approximately 10 years.
279 End Stage Renal Disease after Lung Transplantation: An 11-Year National Cohort Study M. Kosztowski, X. Luo, J. Garonzik-Wang, R. Higgins, D.L. Segev and E. Bush. Department of Surgery, Johns Hopkins, Baltimore, MD. Purpose: End stage renal disease (ESRD) is a dreaded complication after lung transplantation and is associated with inferior post-transplant survival. In this study, we sought to identify the incidence and risk factors for the development of ESRD in lung transplant recipients. Methods: We studied lung transplant recipients in the US between 01/01/ 2006-12/31/2016 using data from the Scientific Registry of Transplant Recipients (SRTR). We included recipients greater or equal to 12 years old. We excluded patients with ESRD prior to transplant. For ascertainment of our outcome of interest (ESRD), we linked our cohort data to the United States Renal Data System (USRDS). ESRD was defined as the initiation of dialysis, waitlisting, or kidney transplantation, whichever was identified first. We used Kaplan-Meier methods to estimate the cumulative incidence of ESRD and used multivariate Cox regression to determine risk factors associated with ESRD. Results: Among 17,054 lung transplant recipients, 514 developed ESRD at a mean of 3.57§2.45 years. Median follow up time was 2.9 years. The risk of ESRD increased over time. The cumulative incidence at 1, 3, and 5 years was 0.6% (95% CI, 0.5-0.7), 1.9% (1.7-2.2), and 4.1% (3.6-4.5). Pre-transplant risk factors associated with ESRD are shown in Table 1. Conclusion: This is the largest study to date looking at ESRD after lung transplantation, and we found a five-year risk of 4.1%. Closely monitoring modifiable risk factors that we identified might reduce the long-term risk of ESRD.
280 Hemodynamic and ECHO Measurements during VA ECMO Weaning Suggest Acceptable LV Unloading A.M. El Banayosy, C. Gordon, M.M. Koerner, M.D. Harper, D. Horstmanshof, D. Vanhooser, J.W. Long and A. El Banayosy INTEGRIS Baptist Medical Center, Oklahoma City, OK. Purpose: One major concern of utilizing veno-arterial (VA) ECMO in advanced cardiogenic shock (ACS) patients is its inability to completely unload the left ventricle (LV). However, the clinically significant degree of LV unloading required for recovery is not well described. We hypothesized that measuring hemodynamics during VA ECMO weaning would elucidate the impact of VA ECMO on LV unloading. Methods: From January 2017 to September 2018, 67 ACS patients required VA ECMO support longer than 24 hours. Acute or chronic heart failure patients were excluded. A weaning protocol using hemodynamic