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Rabbit antithymocyte globulin induction therapy for lung transplantation does not affect long-term allograft function or survival
The Journal of Heart and Lung Transplantation Volume 24, Number 2S
Abstracts
Conclusions: Multiple cytokine analysis of the donor lungs with quantitative multiplex rapid RT-PCR correlates well with the conventional RT-PCR analysis of donor lungs, showing significant promise as a strategy to biologically evaluate donor lungs prior to implantation. 118 RANDOMISED TRIAL OF CYCLOSPORIN C0 VS. C2 MONITORING IN DE NOVO LUNG TRANSPLANT RECIPIENTS: INTERIM RESULTS J. Cornelissen,1 A. Wood,2 S. Pasupathy-Rajah,3 A. Trull,1 J. Wallwork,3 1Clinical Pharmacology, Papworth Hospital NHS Trust, Cambridge, United Kingdom; 2MRC Biostatistics Unit, Cambridge, United Kingdom; 3Transplant Unit, Papworth Hospital NHS Trust, Cambridge, United Kingdom Introduction: Cyclosporin blood concentrations (CYAbc) at 2 hours post-dose (C2) should better control CYA exposure compared to pre-dose (C0) monitoring. Lung transplant recipients receive high doses of CYA and were chosen for a clinical trial to compare C0 vs. C2 monitoring. Methods: 50 de novo lung transplant recipients have so far been randomised for CYA dose adjustment to either C0, Low C2 (LC2) or High C2 (HC2) (see table). Results: Mean CYA dose (mg/kg/day) declined faster in the C2 arms vs. the C0 group (p⬍0.001) and in the LC2 vs. the HC2 group (p⫽0.001). CYA doses (mean, 95%CI) at 3– 6 months were: 5.0, 4.9 –5.1(C0); 3.3, 3.2–3.4(LC2); 3.9, 3.8 – 4.1(HC2). There were no significant between-group differences in serum creatinine or creatinine clearance (CC) levels, although CC levels (mean, 95%CI) appeared higher at 3 months in the C2 arms: 56.4, 36.8 –75.9(C0); 60.3, 40.8 –79.9(LC2); 71.5, 54.0 – 89.0(HC2). There was a higher time trend for MAP in the C0 vs. the HC2 group (p⫽0.03), while no significant differences were found in FEV1, Chol and Trig levels. Interestingly biopsy-proven treated rejection episodes were reduced in both the C2 arms vs. the C0 group (p⫽0.2): 10(C0); 5(LC2); 1(HC2). Conclusion: Lung transplant recipients can be successfully managed using C2 levels, though optimum target ranges and the long-term benefits of C2 monitoring remain to be determined. [Funded by Novartis Pharmaceuticals UK Ltd]
Group
C0 Low C2 High C2
No.
19 15 16
Follow-up (median days, IQR) (p ⴝ 0.2)
0–3 month target CYAbc
0–3 month CYAbc (mean, 95%CI)
3–6 month target CYAbc
3–6 month CYAbc (mean, 95%CI)
118, 57–182 99, 34–175 42, 23–179
250–300 800–1000 1000–1200
268, 259–309 929, 885–974 1040, 984–1095
200–250 600–800 800–1000
234, 217–252 915, 843–987 877, 796–957
119 A RANDOMIZED CONTROL TRIAL OF DACLIZUMAB VS. ANTI-THYMOCYTE GLOBULIN INDUCTION FOR LUNG TRANSPLANTATION J.C. Mullen,1 A. Dueck,1 M.J. Bentley,1 D.L. Modry,1 K. Stewart,1 D.C. Lien,1 P.F. Halloran,1 1University of Alberta, Edmonton, AB Purpose: To test the efficacy and safety of Daclizumab (DZM) vs. Anti-thymocyte Globulin (ATG) as a component of induction therapy in lung transplantation. Methods: 50 adults undergoing lung transplantation were randomized to receive either ATG or DZM during induction therapy. Patients in the DZM group received an initial dose of 2mg/kg iv at the time of transplant and 1mg/kg iv on post-op day 4. Patients were followed for 1 year.
S81
Results: Absolute lymphocyte and platelet counts were significantly higher in the DZM group. CMV mismatch was significantly higher in the DZM group. Other donor characteristics and intra-op variables did not differ significantly between groups. Total ICU, drug and hospital costs did not differ. One patient in the ATG group developed thrombocytopenia and lymphopenia as an adverse reaction. There was no significant difference in number of rejections, malignancy or steroid-induced diabetes (DM). The DZM group had a higher number of infections, however number of CMV infections was also significantly greater, corresponding to the higher incidence of CMV mismatch. Both incidences of malignancy were PTLD. Two patients in the ATG group were re-transplanted, one 6 days post-op due to graft failure and the other after 2 months due to anastomosis dehiscence. One year survival was excellent in both groups.
Absolute Lymphocytes Platelets CMV Mismatch Rejections Rejections/Patient Infections CMV Infections Malignancy Steroid-induced DM Re-transplant 1 Year Survival
ATG (n ⴝ 25)
DZM (n ⴝ 25)
p
0.6 ⫾ 0.3 151 ⫾ 50 1 25 1.0 45 4 1 2 2 92%
0.9 ⫾ 0.5 212 ⫾ 93 8 18 0.7 81 16 1 6 0 96%
0.05 0.03 0.02 0.3 0.3 0.01 0.02 1.0 0.3 0.5 1.0
Conclusion: Daclizumab is a safe component of induction therapy in lung transplantation. Significant infections were more frequent in the DZM group however this was likely due to a higher incidence of CMV mismatch. Both methods of induction therapy worked well with excellent 1 year survival. 120 RABBIT ANTITHYMOCYTE GLOBULIN INDUCTION THERAPY FOR LUNG TRANSPLANTATION DOES NOT AFFECT LONGTERM ALLOGRAFT FUNCTION OR SURVIVAL M.G. Hartwig,1 L.D. Snyder,2 J.Z. Appel,1 S. Simsir,1 S.S. Lin,1 S.M. Palmer,2 R.D. Davis,1 1Deparment of Surgery, Duke University, Durham, NC; 2Department of Medicine, Duke University, Durham, NC Background: Lung transplant survival is limited by the development of chronic allograft dysfunction, manifest as bronchiolitis obliterans syndrome (BOS). The severity and frequency of acute rejection episodes are linked to BOS development. Previously, we demonstrated that rabbit antithymocyte globulin (RATG) induction therapy is associated with a decrease in the incidence of early acute rejection.
S82
Abstracts
This analysis seeks to determine the long-term effects of RATG induction in lung transplantation. Methods: The initial randomized, prospective study included fortyfour lung recipients assigned to receive either RATG induction (locally developed preparation dosed at 1.5 mg/kg/d for 3 days) with conventional immunosuppression or conventional immunosuppression alone. These 2 groups were retrospectively analyzed for episodes of biopsy-proven acute rejection, BOS development, and survival. Results: Patients receiving RATG suffered fewer early rejections (⬍ 6 months posttransplant) Grade 2 or higher (5%), compared to those with conventional therapy alone (41%; Fisher’s Test, p⫽0.01). With a mean follow-up of 4.4 years, the overall incidence of acute rejection between groups did not differ (RATG⫽62%, Conventional⫽68%; p⫽0.52). Median time to rejection was 614 days for the RATG group and 206 days for recipients without induction therapy (p⫽0.52). Freedom from BOS and survival at five years was 62% and 41% for the RATG group, compared to 34% and 46% for recipients treated conventionally (log-rank, p⫽0.14 and 0.48, respectively). Conclusion: Although RATG delays the onset of acute rejection and is associated with a trend towards delayed onset of BOS, significant differences were not observed in long-term allograft survival.
121 ONE YEAR COMPLETE FOLLOW-UP OF A PORSPECTIVE RANDOMIZED INTERNATIONAL INVESTIGATOR DRIVEN STUDY COMPARING Tac AND CsA (ⴙMMF/STEROIDS) AFTER LUNG TRANSPLANTATION IN 274 PATIENTS H. Reichenspurner,1 A. Glanville,2 W. Klepetko,3 R. Lama,4 G.M. Verleden,5 C. Bravo,6 M. Estenne,7 S. Hirt,8 F.Z. Goni,9 J. Aubert,10 J.M. Borro,11 P. Usetti,12 T. Wahlers,13 C. Aboyoun,2 H. Treede,1 1Department of Cardiovascular Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany; 2Alfreds Hospital, University of Sydney, Sydney, Australia; 3University of Vienna, Vienna, Austria; 4University of Cordoba, Cordoba, Spain; 5 University of Leuven, Leuven, Belgium; 6University of Barcelona, Barcelona, Spain; 7University of Bruxelles, Bruxelles, Belgium; 8 University of Kiel, Kiel, Germany; 9University of Santander, Santander, Spain; 10University of Lausanne, Lausanne, Switzerland; 11University of La Coruna, La Coruna, Spain; 12 University of Madrid, Madrid, Spain; 13University of Jena, Jena, Germany A total of 274 patients have finally been included in this prospective randomized international multi-center investigator driven study comparing Tac and CsA, both in combination with MMF and steroids after lung transplantation. One year data of all included patients will be revealed in October 2004 and will be prepared for presentation at the ISHLT annual meeting in 2005. Primary objective of the study was to assess the efficacy and safety of both immunosuppressive regimens for the prevention of bronchiolitis obliterans after transplantation. Secondary objectives were number of acute rejections per patient and per hundred patient days and the time to first rejection. Number of courses of high dose steroids per patient for treatment of AR. Patient and graft survival as well as adverse events. Patients were centrally computer randomized either to treatment group A: Tac (0.01– 0.03 mg/kg/d iv 3 0.05– 0.3 mg/kg/d po) or group B: CsA (1–3 mg/kg/d iv 3 4 –18 mg/kg/d po) (Stratification for cystic fibrosis). MMF (1– 4 g/d) was given according to trough levels. (No induction therapy). For this interim analysis data of all included patients will be available at a 1 year follow-up. Results will be discussed at the ISHLT conference.
The Journal of Heart and Lung Transplantation February 2005
122 SAFETY OF EBV DNA GUIDED REDUCTION OF IMMUNOSUPPRESSION AFTER LUNG TRANSPLANTATION E. Verschuuren,1 A. de Haan,2 B. Hepkema,2 M. Erasmus,3 J. Prop,2 W. Timens,2 G. Koeter,1 W. van der Bij,1 1Pulmonology, Univ. Hosp., Groningen, Netherlands; 2Pathology and Medical Biology, Univ. Hosp., Groningen, Netherlands; 3Cardiothoracic Surgery, Univ. Hosp., Groningen, Netherlands Introduction: Reduction of immunosuppression (IS) after lung transplantation (Ltx) is not a usually routine and mostly done in the context of relapsing infections or treatment for PTLD. Since 3 years we reduce immunosuppression, pre-emptively, based on EBV-DNA load, to prevent PTLD, in our lung transplant patients. To assess the safety of this approach we evaluated all patients for acute rejection, current BOS status, PTLD and conversion of IS because of recurrent rejection. Methods: Since June 2001, 73 primary transplants were performed. After exclusion of 13 perioperative deaths, 60 pts were included in the study. IS consisted of Basiliximab, Tacrolimus(T), Azathioprine(A) and prednisolone(P). Recurrently rejecting pts were converted from A to MMF. Whole blood EBV DNA load was measured weekly during admissions and at all outpatient’s visits during the first year or until negative values were measured, and every half year thereafter. A rising titer of EBV DNA was followed by a stepwise reduction in immunosuppression (first Azathioprine then Tacrolimus). Results: Of the 60 patients, 54 were EBV-seropositive (EBV⫹) before Tx and 6 were EBV-seronegative. (Tables).
EBV seropos recipients
No pts
IS reduction
IS conversion
Acute rejection*
BOS %
PTLD
Survival %
EBV DNA pos EBV DNA neg
17 36
8 0
1 7
0 10
0 3
0 0
79 100
EBV seroneg recipients
No pts
IS reduction
IS conversion
Acute rej*
BOS %
PTLD
Survival %
EBV DNA pos EBV DNA neg
5 1
5 0
0 0
2 0
0 0
1 0
100 100
*EBV DNA pos pts: Acute rejections after reduction of immunosuppression, EBV DNA neg: acute rejection later than one month after Ltx.
Conclusion: EBV DNA guided reduction of the immunosuppression seems effective with regard to PTLD and is safe without jeopardizing transplant function. The routine measurement of EBV DNA load might be a useful tool to individualize immunosuppression after lung transplantation. 123 LONG-TERM FOLLOW UP OF A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF CYCLOSPORINE INHALATION SOLUTION (CyIS) IN LUNG TRANSPLANT RECIPIENTS A.T. Iacono,1 W.B. Capra, S.B. Shrewsbury, B.A. Johnson, W.F. Grgurich, T.E. Corcoran,1 J.G. Youssef, D.A. Smith-Seiler, G.C. Smaldone, A. Zeevi, S.A. Yousem, J.J. Fung, J.H. Dauber,1 G.J. Burckart, B. Griffith,2 K.R. McCurry,3 1Pulmonary Transplantation/Pulmonary Critical Care, University of Pittsburgh, Pittsburgh, PA; 2Cardiothoracic Surgery, University of Maryland, Baltimore, MD; 3Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA Despite best efforts, survival following lung transplant has not improved in the last decade. Following early positive results in open-label studies, a randomized, double-blind, placebo-controlled
Abstracts
Conclusions: Multiple cytokine analysis of the donor lungs with quantitative multiplex rapid RT-PCR correlates well with the conventional RT-PCR analysis of donor lungs, showing significant promise as a strategy to biologically evaluate donor lungs prior to implantation. 118 RANDOMISED TRIAL OF CYCLOSPORIN C0 VS. C2 MONITORING IN DE NOVO LUNG TRANSPLANT RECIPIENTS: INTERIM RESULTS J. Cornelissen,1 A. Wood,2 S. Pasupathy-Rajah,3 A. Trull,1 J. Wallwork,3 1Clinical Pharmacology, Papworth Hospital NHS Trust, Cambridge, United Kingdom; 2MRC Biostatistics Unit, Cambridge, United Kingdom; 3Transplant Unit, Papworth Hospital NHS Trust, Cambridge, United Kingdom Introduction: Cyclosporin blood concentrations (CYAbc) at 2 hours post-dose (C2) should better control CYA exposure compared to pre-dose (C0) monitoring. Lung transplant recipients receive high doses of CYA and were chosen for a clinical trial to compare C0 vs. C2 monitoring. Methods: 50 de novo lung transplant recipients have so far been randomised for CYA dose adjustment to either C0, Low C2 (LC2) or High C2 (HC2) (see table). Results: Mean CYA dose (mg/kg/day) declined faster in the C2 arms vs. the C0 group (p⬍0.001) and in the LC2 vs. the HC2 group (p⫽0.001). CYA doses (mean, 95%CI) at 3– 6 months were: 5.0, 4.9 –5.1(C0); 3.3, 3.2–3.4(LC2); 3.9, 3.8 – 4.1(HC2). There were no significant between-group differences in serum creatinine or creatinine clearance (CC) levels, although CC levels (mean, 95%CI) appeared higher at 3 months in the C2 arms: 56.4, 36.8 –75.9(C0); 60.3, 40.8 –79.9(LC2); 71.5, 54.0 – 89.0(HC2). There was a higher time trend for MAP in the C0 vs. the HC2 group (p⫽0.03), while no significant differences were found in FEV1, Chol and Trig levels. Interestingly biopsy-proven treated rejection episodes were reduced in both the C2 arms vs. the C0 group (p⫽0.2): 10(C0); 5(LC2); 1(HC2). Conclusion: Lung transplant recipients can be successfully managed using C2 levels, though optimum target ranges and the long-term benefits of C2 monitoring remain to be determined. [Funded by Novartis Pharmaceuticals UK Ltd]
Group
C0 Low C2 High C2
No.
19 15 16
Follow-up (median days, IQR) (p ⴝ 0.2)
0–3 month target CYAbc
0–3 month CYAbc (mean, 95%CI)
3–6 month target CYAbc
3–6 month CYAbc (mean, 95%CI)
118, 57–182 99, 34–175 42, 23–179
250–300 800–1000 1000–1200
268, 259–309 929, 885–974 1040, 984–1095
200–250 600–800 800–1000
234, 217–252 915, 843–987 877, 796–957
119 A RANDOMIZED CONTROL TRIAL OF DACLIZUMAB VS. ANTI-THYMOCYTE GLOBULIN INDUCTION FOR LUNG TRANSPLANTATION J.C. Mullen,1 A. Dueck,1 M.J. Bentley,1 D.L. Modry,1 K. Stewart,1 D.C. Lien,1 P.F. Halloran,1 1University of Alberta, Edmonton, AB Purpose: To test the efficacy and safety of Daclizumab (DZM) vs. Anti-thymocyte Globulin (ATG) as a component of induction therapy in lung transplantation. Methods: 50 adults undergoing lung transplantation were randomized to receive either ATG or DZM during induction therapy. Patients in the DZM group received an initial dose of 2mg/kg iv at the time of transplant and 1mg/kg iv on post-op day 4. Patients were followed for 1 year.
S81
Results: Absolute lymphocyte and platelet counts were significantly higher in the DZM group. CMV mismatch was significantly higher in the DZM group. Other donor characteristics and intra-op variables did not differ significantly between groups. Total ICU, drug and hospital costs did not differ. One patient in the ATG group developed thrombocytopenia and lymphopenia as an adverse reaction. There was no significant difference in number of rejections, malignancy or steroid-induced diabetes (DM). The DZM group had a higher number of infections, however number of CMV infections was also significantly greater, corresponding to the higher incidence of CMV mismatch. Both incidences of malignancy were PTLD. Two patients in the ATG group were re-transplanted, one 6 days post-op due to graft failure and the other after 2 months due to anastomosis dehiscence. One year survival was excellent in both groups.
Absolute Lymphocytes Platelets CMV Mismatch Rejections Rejections/Patient Infections CMV Infections Malignancy Steroid-induced DM Re-transplant 1 Year Survival
ATG (n ⴝ 25)
DZM (n ⴝ 25)
p
0.6 ⫾ 0.3 151 ⫾ 50 1 25 1.0 45 4 1 2 2 92%
0.9 ⫾ 0.5 212 ⫾ 93 8 18 0.7 81 16 1 6 0 96%
0.05 0.03 0.02 0.3 0.3 0.01 0.02 1.0 0.3 0.5 1.0
Conclusion: Daclizumab is a safe component of induction therapy in lung transplantation. Significant infections were more frequent in the DZM group however this was likely due to a higher incidence of CMV mismatch. Both methods of induction therapy worked well with excellent 1 year survival. 120 RABBIT ANTITHYMOCYTE GLOBULIN INDUCTION THERAPY FOR LUNG TRANSPLANTATION DOES NOT AFFECT LONGTERM ALLOGRAFT FUNCTION OR SURVIVAL M.G. Hartwig,1 L.D. Snyder,2 J.Z. Appel,1 S. Simsir,1 S.S. Lin,1 S.M. Palmer,2 R.D. Davis,1 1Deparment of Surgery, Duke University, Durham, NC; 2Department of Medicine, Duke University, Durham, NC Background: Lung transplant survival is limited by the development of chronic allograft dysfunction, manifest as bronchiolitis obliterans syndrome (BOS). The severity and frequency of acute rejection episodes are linked to BOS development. Previously, we demonstrated that rabbit antithymocyte globulin (RATG) induction therapy is associated with a decrease in the incidence of early acute rejection.
S82
Abstracts
This analysis seeks to determine the long-term effects of RATG induction in lung transplantation. Methods: The initial randomized, prospective study included fortyfour lung recipients assigned to receive either RATG induction (locally developed preparation dosed at 1.5 mg/kg/d for 3 days) with conventional immunosuppression or conventional immunosuppression alone. These 2 groups were retrospectively analyzed for episodes of biopsy-proven acute rejection, BOS development, and survival. Results: Patients receiving RATG suffered fewer early rejections (⬍ 6 months posttransplant) Grade 2 or higher (5%), compared to those with conventional therapy alone (41%; Fisher’s Test, p⫽0.01). With a mean follow-up of 4.4 years, the overall incidence of acute rejection between groups did not differ (RATG⫽62%, Conventional⫽68%; p⫽0.52). Median time to rejection was 614 days for the RATG group and 206 days for recipients without induction therapy (p⫽0.52). Freedom from BOS and survival at five years was 62% and 41% for the RATG group, compared to 34% and 46% for recipients treated conventionally (log-rank, p⫽0.14 and 0.48, respectively). Conclusion: Although RATG delays the onset of acute rejection and is associated with a trend towards delayed onset of BOS, significant differences were not observed in long-term allograft survival.
121 ONE YEAR COMPLETE FOLLOW-UP OF A PORSPECTIVE RANDOMIZED INTERNATIONAL INVESTIGATOR DRIVEN STUDY COMPARING Tac AND CsA (ⴙMMF/STEROIDS) AFTER LUNG TRANSPLANTATION IN 274 PATIENTS H. Reichenspurner,1 A. Glanville,2 W. Klepetko,3 R. Lama,4 G.M. Verleden,5 C. Bravo,6 M. Estenne,7 S. Hirt,8 F.Z. Goni,9 J. Aubert,10 J.M. Borro,11 P. Usetti,12 T. Wahlers,13 C. Aboyoun,2 H. Treede,1 1Department of Cardiovascular Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany; 2Alfreds Hospital, University of Sydney, Sydney, Australia; 3University of Vienna, Vienna, Austria; 4University of Cordoba, Cordoba, Spain; 5 University of Leuven, Leuven, Belgium; 6University of Barcelona, Barcelona, Spain; 7University of Bruxelles, Bruxelles, Belgium; 8 University of Kiel, Kiel, Germany; 9University of Santander, Santander, Spain; 10University of Lausanne, Lausanne, Switzerland; 11University of La Coruna, La Coruna, Spain; 12 University of Madrid, Madrid, Spain; 13University of Jena, Jena, Germany A total of 274 patients have finally been included in this prospective randomized international multi-center investigator driven study comparing Tac and CsA, both in combination with MMF and steroids after lung transplantation. One year data of all included patients will be revealed in October 2004 and will be prepared for presentation at the ISHLT annual meeting in 2005. Primary objective of the study was to assess the efficacy and safety of both immunosuppressive regimens for the prevention of bronchiolitis obliterans after transplantation. Secondary objectives were number of acute rejections per patient and per hundred patient days and the time to first rejection. Number of courses of high dose steroids per patient for treatment of AR. Patient and graft survival as well as adverse events. Patients were centrally computer randomized either to treatment group A: Tac (0.01– 0.03 mg/kg/d iv 3 0.05– 0.3 mg/kg/d po) or group B: CsA (1–3 mg/kg/d iv 3 4 –18 mg/kg/d po) (Stratification for cystic fibrosis). MMF (1– 4 g/d) was given according to trough levels. (No induction therapy). For this interim analysis data of all included patients will be available at a 1 year follow-up. Results will be discussed at the ISHLT conference.
The Journal of Heart and Lung Transplantation February 2005
122 SAFETY OF EBV DNA GUIDED REDUCTION OF IMMUNOSUPPRESSION AFTER LUNG TRANSPLANTATION E. Verschuuren,1 A. de Haan,2 B. Hepkema,2 M. Erasmus,3 J. Prop,2 W. Timens,2 G. Koeter,1 W. van der Bij,1 1Pulmonology, Univ. Hosp., Groningen, Netherlands; 2Pathology and Medical Biology, Univ. Hosp., Groningen, Netherlands; 3Cardiothoracic Surgery, Univ. Hosp., Groningen, Netherlands Introduction: Reduction of immunosuppression (IS) after lung transplantation (Ltx) is not a usually routine and mostly done in the context of relapsing infections or treatment for PTLD. Since 3 years we reduce immunosuppression, pre-emptively, based on EBV-DNA load, to prevent PTLD, in our lung transplant patients. To assess the safety of this approach we evaluated all patients for acute rejection, current BOS status, PTLD and conversion of IS because of recurrent rejection. Methods: Since June 2001, 73 primary transplants were performed. After exclusion of 13 perioperative deaths, 60 pts were included in the study. IS consisted of Basiliximab, Tacrolimus(T), Azathioprine(A) and prednisolone(P). Recurrently rejecting pts were converted from A to MMF. Whole blood EBV DNA load was measured weekly during admissions and at all outpatient’s visits during the first year or until negative values were measured, and every half year thereafter. A rising titer of EBV DNA was followed by a stepwise reduction in immunosuppression (first Azathioprine then Tacrolimus). Results: Of the 60 patients, 54 were EBV-seropositive (EBV⫹) before Tx and 6 were EBV-seronegative. (Tables).
EBV seropos recipients
No pts
IS reduction
IS conversion
Acute rejection*
BOS %
PTLD
Survival %
EBV DNA pos EBV DNA neg
17 36
8 0
1 7
0 10
0 3
0 0
79 100
EBV seroneg recipients
No pts
IS reduction
IS conversion
Acute rej*
BOS %
PTLD
Survival %
EBV DNA pos EBV DNA neg
5 1
5 0
0 0
2 0
0 0
1 0
100 100
*EBV DNA pos pts: Acute rejections after reduction of immunosuppression, EBV DNA neg: acute rejection later than one month after Ltx.
Conclusion: EBV DNA guided reduction of the immunosuppression seems effective with regard to PTLD and is safe without jeopardizing transplant function. The routine measurement of EBV DNA load might be a useful tool to individualize immunosuppression after lung transplantation. 123 LONG-TERM FOLLOW UP OF A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF CYCLOSPORINE INHALATION SOLUTION (CyIS) IN LUNG TRANSPLANT RECIPIENTS A.T. Iacono,1 W.B. Capra, S.B. Shrewsbury, B.A. Johnson, W.F. Grgurich, T.E. Corcoran,1 J.G. Youssef, D.A. Smith-Seiler, G.C. Smaldone, A. Zeevi, S.A. Yousem, J.J. Fung, J.H. Dauber,1 G.J. Burckart, B. Griffith,2 K.R. McCurry,3 1Pulmonary Transplantation/Pulmonary Critical Care, University of Pittsburgh, Pittsburgh, PA; 2Cardiothoracic Surgery, University of Maryland, Baltimore, MD; 3Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA Despite best efforts, survival following lung transplant has not improved in the last decade. Following early positive results in open-label studies, a randomized, double-blind, placebo-controlled