LUNG TRANSPLANTATION Pediatric Recipients ISHLT 2012 J Heart

LUNG TRANSPLANTATION Pediatric Recipients ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095

RECIPIENT AGE DISTRIBUTION FOR PEDIATRIC LUNG RECIPIENTS - NUMBER (Transplants: January 1986 - June 2011) Number of Transplants 1, 400 1, 200 <1 1 -5 6 -11 12 -17 1, 000 800 600 400 200 0 1986 -1998 (N=602) ISHLT 1999 -6/2011 (N=1, 168) 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Analysis includes living donor transplants

RECIPIENT AGE DISTRIBUTION FOR PEDIATRIC LUNG RECIPIENTS – PERCENTAGE (Transplants: January 1986 - June 2011) 100% % of Transplants 90% 80% 70% 12 -17 60% 50% 6 -11 40% 1 -5 30% <1 20% 10% 0% 1986 -1998 (N=602) ISHLT 1999 -6/2011 (N=1, 168) 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Analysis includes living donor transplants

DONOR TYPE DISTRIBUTION BY YEAR OF TRANSPLANT FOR PEDIATRIC LUNG RECIPIENTS (Transplants: 1986 -2010) Living 120 Deceased 100 80 60 40 20 8 19 6 8 19 7 8 19 8 8 19 9 9 19 0 9 19 1 9 19 2 9 19 3 9 19 4 9 19 5 9 19 6 9 19 7 9 19 8 9 20 9 0 20 0 0 20 1 0 20 2 0 20 3 0 20 4 0 20 5 0 20 6 0 20 7 0 20 8 0 20 9 10 0 19 Number of Transplants 140 ISHLT 2012 NOTE: This figure includes only the lung transplants that are reported to the ISHLT Transplant Registry. As such, the presented data may not mirror the changes in the number of lung transplants performed worldwide. J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Analysis includes living donor transplants

DONOR TYPE DISTRIBUTION BY RECIPIENT AGE GROUP WITHIN ERA FOR PEDIATRIC LUNG RECIPIENTS (Transplants: January 1986 – June 2011) Number of Transplants 900 800 700 Living Deceased 600 500 400 300 200 100 0 0 -5 years 6 -11 years 12 -17 years 1999 -6/2011 1986 -1998 Recipient Age (Years) ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Analysis includes living donor transplants

AGE DISTRIBUTION FOR DONORS OF PEDIATRIC LUNG RECIPIENTS (Transplants: January 1986 - June 2011) 100% 10 % of Transplants 90% 86 211 80% 60+ 281 70% 60% 50 -59 35 -49 347 50% 18 -34 40% 12 -17 30% 0 -11 689 20% 10% 0% ISHLT Donor Age (Years) 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095

140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 12 -17 Years 1 -11 Years 96 <1 Year 95 96 82 89 73 73 72 74 97 125126 114 108 103 78 49 52 48 45 23 3 5 7 8 19 6 8 19 7 8 19 8 8 19 9 9 19 0 9 19 1 9 19 2 9 19 3 9 19 4 9 19 5 9 19 6 9 19 7 9 19 8 9 20 9 0 20 0 0 20 1 0 20 2 0 20 3 0 20 4 0 20 5 0 20 6 0 20 7 0 20 8 0 20 9 10 1 19 Number of Transplants AGE DISTRIBUTION OF PEDIATRIC LUNG RECIPIENTS BY YEAR OF TRANSPLANT ISHLT NOTE: This figure includes only the pediatric lung transplants that are reported to the ISHLT Transplant Registry. Therefore, these numbers should not be interpreted as the rate of change in pediatric lung procedures performed worldwide. 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Analysis includes living donor transplants

NUMBER OF CENTERS REPORTING PEDIATRIC LUNG TRANSPLANTS 55 50 40 35 30 25 20 15 10 5 8 19 6 8 19 7 8 19 8 8 19 9 9 19 0 9 19 1 9 19 2 9 19 3 9 19 4 9 19 5 9 19 6 9 19 7 9 19 8 9 20 9 0 20 0 0 20 1 0 20 2 0 20 3 0 20 4 0 20 5 0 20 6 0 20 7 0 20 8 0 20 9 10 0 19 Number of Centers 45 Transplant Year ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Analysis includes living donor transplants

NUMBER OF CENTERS REPORTING PEDIATRIC LUNG TRANSPLANTS BY CENTER VOLUME 55 20+ transplants 10 -19 transplants 45 5 -9 transplants 40 1 -4 transplants 35 30 25 20 15 10 5 8 19 6 8 19 7 8 19 8 8 19 9 9 19 0 9 19 1 9 19 2 9 19 3 9 19 4 9 19 5 9 19 6 97 19 9 19 8 9 20 9 0 20 0 0 20 1 0 20 2 0 20 3 0 20 4 0 20 5 0 20 6 0 20 7 0 20 8 0 20 9 10 0 19 Number of Centers 50 Transplant Year ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Analysis includes living donor transplants

130 120 110 100 90 80 70 60 50 40 30 20 10 0 20+ transplants 10 -19 transplants 5 -9 transplants 8 19 6 8 19 7 8 19 8 8 19 9 9 19 0 9 19 1 9 19 2 9 19 3 9 19 4 9 19 5 9 19 6 97 19 9 19 8 9 20 9 0 20 0 0 20 1 0 20 2 0 20 3 0 20 4 0 20 5 0 20 6 0 20 7 0 20 8 0 20 9 10 1 -4 transplants 19 Number of Transplants NUMBER OF PEDIATRIC LUNG TRANSPLANTS BY CENTER VOLUME Transplant Year ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Analysis includes living donor transplants

PEDIATRIC LUNG TRANSPLANTS: Indications (Transplants: January 1990 - June 2011) Diagnosis AGE: < 1 Year AGE: 1 -5 Years AGE: 6 -11 Years AGE: 12 -17 Years Cystic Fibrosis 1 1. 1% 6 5. 0% 171 53. 8% 826 71. 5% Idiopathic Pulmonary Arterial Hypertension 12 13. 2% 27 22. 5% 31 9. 7% 83 7. 2% 7 5. 8% 9 2. 8% 35 3. 0% Congenital Heart Disease 14 15. 4% 9 7. 5% 4 1. 3% 10 0. 9% Idiopathic Pulmonary Fibrosis 9 9. 9% 21 17. 5% 15 4. 7% 39 3. 4% Obliterative Bronchiolitis (Not Re-TX) 10 8. 3% 23 7. 2% 49 4. 2% Re-Transplant: Not OB 3 3. 3% 4 3. 3% 9 2. 8% 30 2. 6% Interstitial Pneumonitis 1 1. 1% 2 1. 7% 3 0. 9% Pulmonary Vascular Disease 8 8. 8% 7 5. 8% 4 1. 3% 1 0. 1% Eisenmenger’s Syndrome 1 1. 1% 5 4. 2% 5 1. 6% 7 0. 6% Pulmonary Fibrosis, Other 6 6. 6% 8 6. 7% 16 5. 0% 24 2. 1% Surfactant Protein B Deficiency 16 17. 6% 3 2. 5% COPD/Emphysema 4 4. 4% 2 1. 7% 3 0. 9% 9 0. 8% Bronchopulmonary Dysplasia 3 3. 3% 3 2. 5% 7 2. 2% 2 0. 2% Bronchiectasis 1 1. 1% 6 1. 9% 14 1. 2% Other 12 13. 2% 6 5. 0% 12 3. 8% 27 2. 3% Re-Transplant: Obliterative Bronchiolitis ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Analysis includes living donor transplants

DIAGNOSIS IN PEDIATRIC LUNG RECIPIENTS BY YEAR OF TRANSPLANT Age: 12 -17 Years 100 Cystic Fibrosis 75 50 25 10 20 09 20 08 20 07 20 06 20 05 20 04 20 03 20 02 20 01 20 00 20 99 19 98 19 97 19 96 19 95 19 94 19 93 19 92 19 91 19 90 0 19 % of Transplants IPAH Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Analysis includes living donor transplants

PEDIATRIC LUNG TRANSPLANTS Age Distribution by Location (Transplants: January 2000 – June 2011) 0 -5 years 6 -11 years 12 -17 years 100% % of Transplants 80% 60% 40% 20% 0% Europe (N=410) ISHLT North America (N=619) 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Other (N=66) Analysis includes living donor transplants

PEDIATRIC LUNG TRANSPLANTS Diagnosis Distribution by Location (Transplants: January 2000 – June 2011) Cystic Fibrosis IPAH IPF OB Other Congenital heart disease Re-TX 100% % of Transplants 80% 60% 40% 20% 0% Europe (N=387) ISHLT North America (N=619) Other (N=57) NOTE: Unknown diagnoses were excluded from this tabulation Total number of transplants reported: Europe = 410 North America = 619 Other = 66 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Analysis includes living donor transplants

PEDIATRIC LUNG TRANSPLANTS Donor Age Distribution by Location (Transplants: January 2000 – June 2011) 0 -5 6 -11 12 -17 18 -34 35 -49 50 -59 60+ 100% % of Donors 80% 60% 40% 20% 0% Europe (N=405) North America (N=583) Other (N=58) NOTE: Transplants with unknown donor age and living donor transplants were excluded from this tabulation. Total number of transplants reported: Europe = 410 North America = 619 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Other = 66 ISHLT 2012

LUNG TRANSPLANTS Kaplan-Meier Survival by Recipient Age Group (Transplants: January 1990 - June 2010) 100 Adult (N=36, 015) Pediatric (N=1, 543) Survival (%) 75 p = 0. 4368 50 25 HALF-LIFE Adult = 5. 3 Years; Pediatric = 4. 7 Years 0 0 1 2 3 4 5 6 7 8 9 10 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 11 12 13 14 15 16 17

PEDIATRIC LUNG TRANSPLANTS Kaplan-Meier Survival by Procedure Type (Transplants: January 1990 - June 2010) 100 Single Lung (N=92) Bilateral/Double Lung (N=1, 449) Survival (%) 75 p < 0. 0001 50 25 HALF-LIFE Single Lung: 1. 9 Years; Bilateral/Double Lung: 5. 3 Years 0 0 1 2 3 4 5 6 7 8 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 9 10 11 12 13 14

PEDIATRIC LUNG TRANSPLANTS Kaplan-Meier Survival for Congenital Diagnoses (Transplants: January 1990 - June 2010) 100 Eisenmenger’s vs. Other: p = 0. 5078 Survival (%) 75 N at risk = 11 N at risk = 10 50 N at risk = 15 25 Eisenmenger's Syndrome (N=16) Other Congenital Heart Disease (N=34) Eisenmenger's + Other Congenital Heart Disease (N=50) 0 0 1 2 3 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 4 5

PEDIATRIC LUNG TRANSPLANTS Kaplan-Meier Survival by Recipient Age Group (Transplants: January 1990 - June 2010) 100 <1 year vs. 1 -11 years: p = 0. 2101 <1 year vs. 12 -17 years: p = 0. 9694 1 -11 years vs. 12 -17 years: p = 0. 0106 Survival (%) 75 <1 Year (N=89) 1 -11 Years (N=411) 12 -17 Years (N=1, 043) 50 N at risk = 17 HALF-LIFE <1 Year: 6. 4 Years 1 -11 Years: 6. 2 Years 12 -17 Years: 4. 3 Years 25 N at risk = 10 N at risk = 26 0 0 1 2 3 4 5 6 7 8 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 9 10 11 12 13 14

PEDIATRIC LUNG TRANSPLANTS Conditional Kaplan-Meier Survival by Recipient Age Group (Transplants: January 1990 - June 2010) 100 <1 year vs. 1 -11 years: p = 0. 7629 <1 year vs. 12 -17 years: p = 0. 1241 1 -11 years vs. 12 -17 years: p = 0. 0083 Survival (%) 75 N at risk = 17 CONDITIONAL HALF-LIFE <1 Year: 8. 8 Years 1 -11 Years: 10. 5 Years 12 -17 Years: 6. 4 Years 50 N at risk = 10 N at risk = 26 25 <1 Year (N=55) 1 -11 Years (N=297) 12 -17 Years (N=737) 0 0 1 2 3 4 5 6 7 8 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 9 10 11 12 13 14

PEDIATRIC LUNG TRANSPLANTS Kaplan-Meier Survival by Era (Transplants: January 1988 - June 2010) 100 HALF-LIFE (Years) Unconditional 1988 -1994: 2. 5; 1995 -2001: 4. 0; 2002 -6/2010: 5. 8 Conditional 1988 -1994: 10. 4; 1995 -2001: 7. 3; 2002 -6/2010: 8. 9 Survival (%) 75 1988 -1994 vs. 1995 -2001: p = 0. 0556 1988 -1994 vs. 2002 -6/2010: p < 0. 0001 1995 -2001 vs. 2002 -6/2010: p = 0. 0033 N at risk = 27 50 N at risk = 10 1988 -1994 (N=216) 25 1995 -2001 (N=511) N at risk = 22 2002 -6/2010 (N=828) 0 0 1 2 3 4 5 6 7 8 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 9 10 11 12 13 14 15

PEDIATRIC LUNG TRANSPLANTS Kaplan-Meier Survival by Donor Type for Recipients Age 12 -17 Years (Transplants: January 1990 - June 2010) 100 HALF-LIFE Deceased: 4. 3 Years Living: 3. 8 Years p = 0. 2897 Survival (%) 75 50 N at risk = 23 25 Deceased Donor (N = 1, 043) Living Donor (N = 80) 0 0 1 2 3 4 5 6 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 7 8 9 10 11

PEDIATRIC LUNG RE-TRANSPLANTS Between January 1994 and June 2011 Number of Re-Transplants 35 30 25 20 15 10 5 0 0 -<1 month 1 -<12 months 12 -<36 months 36+ months Not reported Time Between Previous and Current Transplant ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Analysis includes living donor transplants

PEDIATRIC LUNG RE-TRANSPLANTS Survival for Transplants Performed Between January 1994 and June 2010 100 Survival (%) 80 60 N at risk at 5 years = 18 40 20 0 0 1 2 3 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 4 5

PEDIATRIC LUNG RE-TRANSPLANTS Survival for Transplants Performed Between January 1988 and June 2010 Stratified by Inter-Transplant Interval 100 p = 0. 1097 Survival (%) 80 60 N at risk = 12 40 N at risk = 13 20 <1 Year (N = 32) 1+ Year (N = 64) 0 0 1 2 3 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 4 5 Analysis includes living donor transplants. Only patients who were less than 18 years old at the time of retransplant are included.

PEDIATRIC LUNG RE-TRANSPLANTS Survival for Transplants Performed Between January 1988 and June 2010 Stratified by Diagnosis 100 p = 0. 6119 Survival (%) 80 60 N at risk = 12 40 N at risk = 11 20 Obliterative Bronchiolitis (N = 55) Non Obliterative Bronchiolitis (N = 64) 0 0 1 2 3 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 4 5 Analysis includes living donor transplants. Only patients who were less than 18 years old at the time of retransplant are included.

PEDIATRIC LUNG RECIPIENTS Cross-Sectional Analysis Functional Status of Surviving Recipients (Follow-ups: April 1994 – June 2011) 100% 80% 60% 40% 20% No Activity Limitations Performs with Assistance Total Assistance 3 Years (N = 206) 5 Years (N = 128) 0% 1 Year (N = 330) ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095

PEDIATRIC LUNG RECIPIENTS Functional Status of Surviving Recipients US Recipients Only (Follow-ups: March 2005 – June 2011) 100% 10% 20% 80% 30% 40% 60% 50% 60% 40% 70% 80% 20% 90% 100% 0% 1 Year (N = 298) ISHLT 2 Years (N = 229) 3 Years (N = 180) 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095

PEDIATRIC LUNG RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients (Follow-ups: April 1994 – June 2011) 100% 80% 60% 40% 20% No Hospitalization Hospitalized, Rejection + Infection Hospitalized, Not Rejection/Not Infection Hospitalized, Infection Only 0% Up to 1 Year (N=690) ISHLT Between 2 and 3 Years (N=406) 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Between 4 and 5 Years (N=251)

PEDIATRIC LUNG RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients (Follow-ups: April 1994 – June 2011) 100% 80% 60% 40% 20% No Hospitalization Hospitalized, Rejection + Infection Hospitalized, Not Rejection/Not Infection Hospitalized, Infection Only 0% Up to 1 Year (N=690) ISHLT Between 1 and 3 Years (N=371) 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Between 3 and 5 Years (N=231)

PEDIATRIC LUNG RECIPIENTS Induction Immunosuppression (Transplants: January 2001 – June 2011) 70 % of patients 60 50 40 30 20 10 0 Any Induction (N = 318) ISHLT Polyclonal ALG/ATG (N = 70) IL-2 R Antagonist (N = 245) 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Analysis is limited to patients who were alive at the time of the discharge

PEDIATRIC LUNG RECIPIENTS Induction Immunosuppression (Transplants: January 2001 – June 30, 2011) 90 80 % of patients 70 60 50 40 30 20 10 0 01 02 03 04 05 06 07 08 09 10 11 001 002 003 004 005 006 007 008 009 0106/11 20 20 201 -6/ 2 2 2 2 2 12 2 2 2 2 11 1 / / 1 1 1/1 Any Induction ISHLT Polyclonal ALG/ATG 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 IL-2 R Antagonist Analysis is limited to patients who were alive at the time of the discharge

PEDIATRIC LUNG TRANSPLANTS Kaplan-Meier Survival Stratified by Induction Use (Transplants: January 2001 - June 2010) 100 p = 0. 8790 Survival (%) 75 50 HALF-LIFE Induction: 6. 5 Years No Induction: 6. 0 Years 25 Induction (N = 282) No Induction (N = 177) 0 0 1 2 3 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 4 5 6

PEDIATRIC LUNG RECIPIENTS Maintenance Immunosuppression at Time of Follow-up (Follow-ups: January 2001 – June 2011) 100 Year 1 (N = 407) Year 5 (N = 178) % of patients 80 60 40 20 0 Cyclosporine Tacrolimus Sirolimus/ Everolimus MMF/MPA Azathioprine Prednisone NOTE: Different patients are analyzed in Year 1 and Year 5 ISHLT 2012 Analysis is limited to patients who were alive at the time of the follow-up J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095

PEDIATRIC LUNG RECIPIENTS Maintenance Immunosuppression at Time of Follow-up (Follow-ups: January 2001 – June 2011) 100 % of Patients 80 60 Tac MMF/ MPA Cy. A AZA 40 20 0 Calcineurin Cell. Cycle Prednisone Inhibitor 1 Year Follow-up (N = 407) NOTE: Different patients are analyzed in Year 1 and Year 5 ISHLT 5 Year Follow-up (N = 178) NOTE: 0. 2% of patients were on both calcineurin inhibitors at different point during the 1 -year; these patients are not counted in either group. And 0. 5% (2 patients) was on neither drug during the 1 -year. In the 5 -year tabulations, 0. 6% were reported to be on both drugs during the year and 1. 7% (3 patients) was reported to be on neither drugs. 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Analysis is limited to patients who were alive at the time of the follow-up

PEDIATRIC LUNG RECIPIENTS Maintenance Immunosuppression Drug Combinations at Time of Follow-up (Follow-ups: January 2001 – June 2011) 100% Other % of Patients 80% Tacrolimus + Sirolimus/Everolimus Tacrolimus 60% Tacrolimus + MMF/MPA 40% Tacrolimus + AZA Cyclosporine + MMF/MPA 20% Cyclosporine + AZA 0% Year 1 (N = 407) Year 5 (N = 178) NOTE: Different patients are analyzed in Year 1 and Year 5 ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 Analysis is limited to patients who were alive at the time of the follow-up

POST-LUNG TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Morbidity Rates in Survivors within 1 Year Post. Transplant (Follow-ups: April 1994 - June 2011) Within 1 Year Total number with known response Hypertension 41. 7% (N = 664) Renal Dysfunction 10. 0% (N = 683) Outcome Abnormal Creatinine < 2. 5 mg/dl 6. 9% Creatinine > 2. 5 mg/dl 2. 0% Chronic Dialysis 0. 7% Renal Transplant 0. 3% Hyperlipidemia 5. 1% (N = 683) Diabetes 23. 5% (N = 684) Bronchiolitis Obliterans Syndrome 13. 2% (N = 638) ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095

POST-LUNG TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Morbidity Rates in Survivors within 5 Years Post. Transplant (Follow-ups: April 1994 - June 2011) Within 5 Years Total number with known response Hypertension 69. 8% (N = 179) Renal Dysfunction 32. 8% (N = 189) Outcome Abnormal Creatinine < 2. 5 mg/dl 24. 3% Creatinine > 2. 5 mg/dl 5. 3% Chronic Dialysis 1. 6% Renal Transplant 1. 6% Hyperlipidemia 15. 8% (N = 184) Diabetes 36. 8% (N = 190) Bronchiolitis Obliterans Syndrome 35. 9% (N = 145) ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095

POST-LUNG TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Morbidity Rates in Survivors within 7 Years Post. Transplant (Follow-ups: April 1994 - June 2011) Outcome Renal Dysfunction Abnormal Creatinine < 2. 5 mg/dl Within 7 Years Total number with known response 41. 3% (N = 92) 29. 3% Creatinine > 2. 5 mg/dl 7. 6% Chronic Dialysis 0. 0% Renal Transplant 4. 3% Diabetes 33. 9% (N = 62) Bronchiolitis Obliterans Syndrome 44. 6% (N = 56) ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095

Freedom from Bronchiolitis Obliterans Syndrome % Free from Bronchiolitis Obliterans Syndrome For Pediatric Lung Recipients (Follow-ups: April 1994 -June 2011) 100 90 80 70 60 50 40 30 20 10 0 0 1 2 3 4 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 5 6 7 8

Freedom from Bronchiolitis Obliterans Syndrome For Pediatric Lung Recipients by Age Group % Free from Bronchiolitis Obliterans Syndrome (Follow-ups: April 1994 -June 2011) 100 90 p = 0. 0308 80 70 60 50 40 30 <1 Year (N=53) 20 1 -11 Years (N=204) 10 12 -17 Years (N=385) 0 0 1 2 3 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 4 5 6

Freedom from Bronchiolitis Obliterans Syndrome % Free from Bronchiolitis Obliterans Syndrome For Pediatric Lung Recipients by Diagnosis (Follow-ups: April 1994 -June 2011) 100 90 p = 0. 0606 80 70 60 50 40 30 Cystic Fibrosis (N=341) 20 IPAH (N=61) 10 0 0 1 2 3 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 4 5 6

Freedom from Bronchiolitis Obliterans Syndrome For Pediatric Lung Recipients by Induction Use % Free from Bronchiolitis Obliterans Syndrome (Follow-ups: April 1994 -June 2011) 100 90 p = 0. 9867 80 70 60 50 40 30 Induction (N = 274) 20 No Induction (N = 339) 10 0 0 1 2 3 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 4 5 6

Freedom from Severe Renal Dysfunction* % Free from Severe Renal Dysfunction For Pediatric Lung Recipients (Follow-ups: April 1994 -June 2011) 100 90 80 70 *Severe renal dysfunction = Creatinine > 2. 5 mg/dl (221 μmol/L), dialysis or renal transplant 60 50 0 1 2 3 4 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 5 6 7 8

MALIGNANCY POST-LUNG TRANSPLANT FOR PEDIATRICS Cumulative Morbidity Rates in Survivors (Follow-ups: April 1994 -June 2011) Malignancy/Type No Malignancy (all types combined) 1 -Year Survivors 5 -Year Survivors 7 -Year Survivors 657 (94. 4%) 175 (88. 8%) 87 (90. 6%) 39 (5. 6%) 22 (11. 2%) 9 (9. 4%) Malignancy Lymphoma Type* Other Type Not Reported 36 22 9 2 1 0 0 ”Other” includes Liver and primitive neuroectodermal tumor. * Recipients may have experienced more than one type of malignancy so sum of individual malignancy types may be greater than total number with malignancy. ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095

Freedom from Malignancy For Pediatric Lung Recipients (Follow-ups: April 1994 - June 2011) % Free from Malignancy 100 90 80 All malignancy Lymphoma 70 Skin Other 60 50 0 1 2 3 4 5 Years ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 6 7 8 9 10

PEDIATRIC LUNG TRANSPLANT RECIPIENTS Cause of Death (Deaths: January 1992 - June 2011) CAUSE OF DEATH BRONCHIOLITIS 0 -30 Days (N 31 Days - 1 Year >1 Year - 3 Years >3 Years - 5 Years >5 Years =114) (N = 159) (N = 209) (N = 92) (N = 84) 16 (10. 1%) 80 (38. 3%) 36 (39. 1%) 38 (45. 2%) 3 (2. 6%) 3 (1. 9%) 2 (1. 0%) 2 (2. 2%) LYMPHOMA 8 (5. 0%) 7 (3. 3%) 4 (4. 3%) 5 (6. 0%) MALIGNANCY, NON-LYMPHOMA 1 (0. 6%) 1 (0. 5%) 3 (3. 6%) CMV 5 (3. 1%) INFECTION, NON-CMV 15 (13. 2%) 53 (33. 3%) 32 (15. 3%) 18 (19. 6%) 9 (10. 7%) GRAFT FAILURE 35 (30. 7%) 31 (19. 5%) 49 (23. 4%) 20 (21. 7%) 17 (20. 2%) CARDIOVASCULAR 18 (15. 8%) 6 (3. 8%) 3 (1. 4%) 1 (1. 1%) TECHNICAL 13 (11. 4%) 5 (3. 1%) 6 (2. 9%) 3 (3. 3%) 1 (1. 2%) MULTIPLE ORGAN FAILURE 11 (9. 6%) 19 (11. 9%) 10 (4. 8%) 3 (3. 3%) 6 (7. 1%) OTHER 19 (16. 7%) 12 (7. 5%) 19 (9. 1%) 5 (5. 4%) 5 (6. 0%) ACUTE REJECTION ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095

PEDIATRIC LUNG TRANSPLANT RECIPIENTS Relative Incidence of Leading Causes of Death (Deaths: January 1992 - June 2011) 50 Bronchiolitis Graft Failure Multiple Organ Failure Infection (non-CMV) Cardiovascular % of Deaths 40 30 20 10 0 0 -30 Days 31 Days – 1 >1 Year – 3 (N = 114) Year (N = 159) Years (N =209) ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 >3 Years – 5 Years (N = 92) >5 Years (N = 84 )

PEDIATRIC LUNG TRANSPLANT RECIPIENTS (1/1993 -6/2010) Risk Factors For 1 Year Mortality/Graft Failure VARIABLE N Relative Risk Single lung transplant 11 3. 92 0. 002 1. 63 - 9. 41 On ventilator 133 3. 17 <. 0001 2. 10 - 4. 77 Year of transplant: 1993 -2000 vs. 2001 -6/2010 337 1. 67 0. 002 1. 21 - 2. 31 Donor CMV+/Recipient CMV- 262 1. 40 0. 034 1. 03 - 1. 91 Chronic steroid use 299 1. 33 0. 085 0. 96 - 1. 84 N = 826 ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 P-value 95% Confidence Interval

PEDIATRIC LUNG TRANSPLANT RECIPIENTS (1/1993 -6/2010) Risk Factors For 1 Year Mortality/Graft Failure Continuous Factors (see figures) Pediatric transplant center volume (borderline) ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095

PEDIATRIC LUNG TRANSPLANT RECIPIENTS (1/1993 -6/2010) Risk Factors For 1 Year Mortality/Graft Failure Center Volume Pediatric Transplants Relative Risk of 1 Year Mortality 2. 0 p = 0. 0870 1. 5 1. 0 0. 5 0. 0 0 1 2 3 4 5 6 7 Center Volume (cases per year) ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 8 9 10

PEDIATRIC LUNG TRANSPLANT RECIPIENTS (1/1993 -6/2006) Risk Factors For 5 Year Mortality/Graft Failure VARIABLE N Relative Risk Single lung transplant 9 4. 37 0. 0001 2. 07 - 9. 21 On ventilator 91 1. 98 0. 0004 1. 36 - 2. 89 Chronic steroid use 214 1. 32 0. 0208 1. 04 - 1. 66 Year of transplant: 1993 -2000 vs. 2001 -6/2006 337 1. 30 0. 0304 1. 02 - 1. 64 N = 609 ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 P-value 95% Confidence Interval

PEDIATRIC LUNG TRANSPLANT RECIPIENTS (1/1993 -6/2006) Risk Factors For 5 Year Mortality/Graft Failure Continuous Factors (see figures) Recipient age Pediatric transplant center volume ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095

PEDIATRIC LUNG TRANSPLANT RECIPIENTS (1/1993 -6/2006) Risk Factors For 5 Year Mortality/Graft Failure Recipient Age Relative Risk of 5 Year Mortality 2. 0 p = 0. 0424 1. 5 1. 0 0. 5 0. 0 0 1 2 3 4 5 6 7 8 9 10 Recipient Age ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 11 12 13 14 15 16 17

PEDIATRIC LUNG TRANSPLANT RECIPIENTS (1/1993 -6/2006) Risk Factors For 5 Year Mortality/Graft Failure Center Volume Pediatric Transplants Relative Risk of 5 Year Mortality 2. 0 p = 0. 0075 1. 0 0. 5 0. 0 0 1 2 3 4 5 6 7 Center Volume (cases per year) ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 8 9 10

PEDIATRIC LUNG TRANSPLANT RECIPIENTS (1/1991 -6/2001) Risk Factors For 10 Year Mortality/Graft Failure VARIABLE N Relative Risk On ventilator 65 2. 17 <. 0001 1. 49 - 3. 15 Single lung transplant 24 2. 11 0. 0122 1. 18 - 3. 78 Donor cause of death = anoxia 36 1. 45 0. 0740 0. 96 - 2. 17 N = 369 ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 P-value 95% Confidence Interval

PEDIATRIC LUNG TRANSPLANT RECIPIENTS (1/1991 -6/2001) Risk Factors For 10 Year Mortality/Graft Failure Continuous Factors (see figures) Recipient age Pediatric transplant center volume (borderline) ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095

Relative Risk of 10 Year Mortality PEDIATRIC LUNG TRANSPLANT RECIPIENTS (1/1991 -6/2001) Risk Factors For 10 Year Mortality/Graft Failure Recipient Age 2. 0 p = 0. 0195 1. 0 0. 5 0. 0 0 1 2 3 4 5 6 7 8 9 10 Recipient Age ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 11 12 13 14 15 16 17

Relative Risk of 10 Year Mortality PEDIATRIC LUNG TRANSPLANT RECIPIENTS (1/1991 -6/2001) Risk Factors For 10 Year Mortality/Graft Failure Center Volume Pediatric Transplants 2. 0 p = 0. 0896 1. 5 1. 0 0. 5 0. 0 0 1 2 3 4 5 6 7 Center Volume (cases per year) ISHLT 2012 J Heart Lung Transplant. 2012 Oct; 31(10): 1045 -1095 8 9 10