HEARTLUNG TRANSPLANTATION Pediatric Recipients 2019 JHLT 2019 Oct

HEART-LUNG TRANSPLANTATION Pediatric Recipients 2019 JHLT. 2019 Oct; 38(10): 1015 -1066

Table of Contents < Donor, recipient and center characteristics: slides 3 -13 < Post-transplant – survival and other outcomes: slides 15 -22 < Focus theme – slides 23 -32 2019 JHLT. 2019 Oct; 38(10): 1015 -1066

Donor, Recipient and Center Characteristics 2019 JHLT. 2019 Oct; 38(10): 1015 -1066

Pediatric Heart-Lung Transplants Recipient Age Distribution (Transplants: January 1988 – June 2018) 500 429 Number of Transplants 450 400 350 300 250 200 150 96 100 50 119 19 0 <1 1 -5 6 -10 Recipient Age (Years) 2019 JHLT. 2019 Oct; 38(10): 1015 -1066 11 -17

Pediatric Heart-Lung Transplants Donor Age Distribution (Transplants: January 1988 – June 2018) 400 Number of Transplants 350 322 300 250 200 158 150 100 66 50 43 10 1 50 -59 60+ 0 0 -10 11 -17 18 -34 35 -49 Donor Age (Years) 2019 JHLT. 2019 Oct; 38(10): 1015 -1066

Pediatric Heart-Lung Transplants Age Distribution by Year 60 11 -17 55 6 -10 50 1 -5 45 <1 40 35 30 25 20 15 10 5 0 19 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 2099 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 17 Number of Transplants 65 2019 JHLT. 2019 Oct; 38(10): 1015 -1066 NOTE: This figure includes only the heart-lung transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as evidence that the number of pediatric heart-lung transplants worldwide has declined in recent years.

Pediatric Heart-Lung Transplants Age Distribution by Era of Transplant Age (Years) <1 1 -5 6 -10 11 -17 100% 90% % of Transplants 80% 70% 60% 50% 40% 30% 20% 10% 0% 1992 -2001 (N=283) 2002 -2009 (N=108) 2019 JHLT. 2015 2019 Oct; 34(10): 38(10): 1255 -1263 1015 -1066 2010 -6/2018 (N=63)

Pediatric Heart-Lung Transplants Number of Centers Reporting Transplants by Location 30 Other 25 North America Europe 20 15 10 5 0 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 1 20 0 1 20 1 1 20 2 1 20 3 1 20 4 1 20 5 1 20 6 17 No. of Pediatric Transplant Centers (Transplants: January 1988 – December 2017) Transplant Year 2019 JHLT. 2019 Oct; 38(10): 1015 -1066

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 1 20 0 1 20 1 1 20 2 1 20 3 1 20 4 1 20 5 1 20 6 17 No. of Pediatric Transplant Centers Pediatric Heart-Lung Transplants Number of Centers Reporting Transplants by Center Volume 30 25 Transplant Year 2019 JHLT. 2019 Oct; 38(10): 1015 -1066 1 -4/yr 5 -9/yr 10 -19/yr 20 -29/yr 20 15 10 5 0

Pediatric Heart-Lung Transplants Diagnosis Distribution (Transplants: January 1988 – December 2017) 34% “Other” includes A 1 ATD, Non CF-bronchiectasis, and LAM/tuberous sclerosis CF 3% 3% 1% IIP ILD-not IIP IPAH OB PH-not IPAH 29% 27% 2% 75 CF Other 1% IPAH PH-not IPAH 50 25 0 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 1 20 0 1 20 1 1 20 2 1 20 3 1 20 4 1 20 5 1 20 6 17 % of Cases 100 Retransplant NOTE: Unknown diagnoses were excluded from this tabulation. 2019 JHLT. 2019 Oct; 38(10): 1015 -1066

Pediatric Heart-Lung Transplants Age Distribution by Location (Transplants: January 2000 – June 2018) <1 1 -5 6 -10 11 -17 100% % of Transplants 80% 60% 40% 20% 0% Europe North America 2019 JHLT. 2019 Oct; 38(10): 1015 -1066 Other

Pediatric Heart-Lung Transplants Diagnosis Distribution by Location (Transplants: January 2000 – June 2018) CF IPAH PH-not IPAH Other 100% % of Transplants 80% 60% 40% 20% 0% Europe (N=78) North America (N=65) 2019 JHLT. 2019 Oct; 38(10): 1015 -1066 Other (N=19)

Pediatric Heart-Lung Transplants Donor Age Distribution by Location (Transplants: January 2000 – June 2018) 0 -10 11 -17 18 -34 35 -49 50 -59 60+ 100% % of Donors 80% 60% 40% 20% 0% Europe North America 2019 JHLT. 2019 38(10): 1015 -1066 JHLT. 2015 2014 Oct; 34(10): 33(10): 1255 -1263 1025 -1033 Other

Post-Transplant: Survival and Other Outcomes 2019 JHLT. 2019 Oct; 38(10): 1015 -1066

Pediatric Heart-Lung Transplants Kaplan-Meier Survival by Major Diagnosis (Transplants: January 1992 – June 2017) 100 CF (N=96) IPAH (N=117) PH-not IPAH (N=132) Survival (%) 75 Median survival (years): CF=4. 0; IPAH=6. 0; PH-not IPAH=2. 5 50 25 No pairwise comparisons were significant at p<0. 05. 0 0 1 2 3 4 5 6 7 8 Years 2019 JHLT. 2019 Oct; 38(10): 1015 -1066 9 10 11 12 13 14 15

Pediatric Heart-Lung Transplants Kaplan-Meier Survival Conditional on Survival to 1 Year by Major Diagnosis (Transplants: January 1992 – June 2017) 100 CF (N=70) IPAH (N=93) PH-not IPAH (N=78) Survival (%) 75 Median survival (years): CF=6. 1; IPAH=9. 3; PH-not IPAH=7. 8 50 25 No pairwise comparisons were significant at p<0. 05. 0 0 1 2 3 4 5 6 7 8 Years 2019 JHLT. 2019 Oct; 38(10): 1015 -1066 9 10 11 12 13 14 15

Pediatric Heart-Lung Transplants Kaplan-Meier Survival by Age Group (Years) (Transplants: January 1992 – June 2017) 100 0 -5 (N = 81) 6 -10 (N = 69) Survival (%) 75 No pairwise comparisons were significant at p<0. 05. 11 -17 (N = 297) 50 25 Median survival (years): 0 -5=1. 6; 6 -10=5. 9; 11 -17=3. 8 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Years 2019 JHLT. 2019 Oct; 38(10): 1015 -1066

Pediatric Heart-Lung Transplants Kaplan-Meier Survival Conditional on Survival to 1 Year by Age Group (Transplants: January 1992 – June 2017) 100 No pairwise comparisons were significant at p<0. 05. 6 -10 (N = 50) 75 Survival (%) 0 -5 (N = 49) 11 -17 (N = 208) 50 25 Median survival (years): 0 -5=8. 2; 6 -10=13. 8; 11 -17=7. 8 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Years 2019 JHLT. 2019 Oct; 38(10): 1015 -1066

Pediatric Heart-Lung Transplants Kaplan-Meier Survival by Era (Transplants: January 1992 – June 2017) 100 1992 -2001 (N=281) 2002 -2009 (N=108) 2010 -6/2017 Survival (%) 75 No pairwise comparisons were significant at p<0. 05. 50 25 Median survival (years): 1992 -2001=3. 2; 2002 -2009=5. 3; 2010 -6/2017=NA 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Years 2019 JHLT. 2019 Oct; 38(10): 1015 -1066

Pediatric Heart-Lung Transplants Kaplan-Meier Survival Conditional on Survival to 1 Year by Era (Transplants: January 1992 – June 2017) 100 1992 -2001 (N=185) 2002 -2009 (N=77) 2010 -6/2017 (N=45) Survival (%) 75 No pairwise comparisons were significant at p<0. 05. 50 25 Median survival (years): 1992 -2001=6. 3; 2002 -2009=11. 4; 2010 -6/2017=NA 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Years 2019 JHLT. 2019 Oct; 38(10): 1015 -1066

Pediatric Heart-Lung Transplants Cause of Death (Deaths: January 2000 – June 2018) CAUSE OF DEATH OB/BOS 0 -30 Days (N = 26) 31 Days - 1 Year >1 Year - 3 Years >3 Years - 5 Years (N = 18) (N = 31) (N = 15) >5 Years (N = 64) 0 1 (5. 6%) 12 (38. 7%) 5 (33. 3%) 13 (20. 3%) 2 (7. 7%) 0 0 1 (6. 7%) 1 (1. 6%) Lymphoma 0 1 (5. 6%) 0 0 1 (1. 6%) Malignancy, Other 0 1 (5. 6%) 1 (3. 2%) 0 2 (3. 1%) Infection, Non-CMV 2 (7. 7%) 4 (22. 2%) 2 (6. 5%) 2 (13. 3%) 10 (15. 6%) Graft Failure 7 (26. 9%) 2 (11. 1%) 11 (35. 5%) 3 (20. 0%) 15 (23. 4%) Cardiovascular 2 (7. 7%) 1 (5. 6%) 2 (6. 5%) 1 (6. 7%) 10 (15. 6%) Technical 5 (19. 2%) 0 0 1 (6. 7%) 0 Multiple Organ Failure 4 (15. 4%) 2 (11. 1%) 1 (3. 2%) 0 7 (10. 9%) Other 4 (15. 4%) 6 (33. 3%) 2 (6. 5%) 2 (13. 3%) 5 (7. 8%) Acute Rejection 2019 JHLT. 2019 Oct; 38(10): 1015 -1066

Pediatric Heart-Lung Transplants Relative Incidence of Leading Causes of Death (Deaths: January 2000 – June 2018) 60 OB/BOS Infection (Non-CMV) Graft Failure Cardiovascular 50 % of Deaths 40 30 20 10 0 0 -30 Days (N = 26) 31 Days - 1 Year (N = 18) >1 Year - 3 Years (N = 31) 2019 JHLT. 2019 Oct; 38(10): 1015 -1066 >3 Years - 5 Years (N = 15) >5 Years (N = 64)

Focus Theme: Size Match (Donor-Recipient Height Difference) 2019 JHLT. 2019 Oct; 38(10): 1015 -1066

Pediatric Heart-Lung Transplants Distribution of Donor-Recipient Height Difference by Recipient Age (Transplants : January 1992 – June 2018) <-15 cm - <-5 cm - 5 cm >5 cm - 15 cm >15 cm 100% % of Transplants 80% 60% 40% 20% 0% 0 -5 years (N=53) 6 -10 years (N=39) 11 -17 years (N=173) Recipient Age 2019 JHLT. 2019 Oct; 38(10): 1015 -1066 All (N=265)

Pediatric Heart-Lung Transplants Distribution of Donor-Recipient Height Difference by Donor-Recipient Sex Combination (Transplants : January 1992 – June 2018) <-15 cm - <-5 cm - 5 cm >5 cm - 15 cm >15 cm 100% % of Transplants 80% 60% 40% 20% 0% Female-to-Female (N=74) Female-to-Male (N=49) 2019 JHLT. 2019 Oct; 38(10): 1015 -1066 Male-to-Female (N=65) Male-to-Male (N=77)

Pediatric Heart-Lung Transplants Distribution of Donor-Recipient Height Difference by Donor Age (Transplants : January 1992 – June 2018) <-15 cm - <-5 cm - 5 cm >5 cm - 15 cm >15 cm 100% % of Transplants 80% 60% 40% 20% 0% 0 -10 Years (N=122) 11 -17 Years (N=80) Donor Age 2019 JHLT. 2019 Oct; 38(10): 1015 -1066 18 -34 Years (N=35) 35+ Years (N=28)

Pediatric Heart-Lung Transplants Distribution of Donor-Recipient Height Difference by Ischemic Time (Transplants : January 1992 – June 2018) <-15 cm - <-5 cm - 5 cm >5 cm - 15 cm >15 cm 100% % of Transplants 80% 60% 40% 20% 0% <2 hours (N=4) 2 -4 hours (N=70) Ischemic Time 2019 JHLT. 2019 Oct; 38(10): 1015 -1066 4+ hours (N=70)

Pediatric Heart-Lung Transplants Distribution of Donor-Recipient Height Difference by Geographic Location (Transplants : January 1992 – June 2018) <-15 cm - <-5 cm - 5 cm >5 cm - 15 cm >15 cm 100% % of Transplants 80% 60% 40% 20% 0% Europe (N=123) North America (N=127) 2019 JHLT. 2019 Oct; 38(10): 1015 -1066 Other (N=15)

Pediatric Heart-Lung Transplants Kaplan-Meier Survival Within 1 Year by Donor-Recipient Height Difference (Transplants: January 1992 – June 2017) 100 Survival (%) 75 50 No pairwise comparisons were significant at p < 0. 05. 25 <-15 cm (N=23) -15 cm - <-5 cm (N=52) >5 cm - 15 cm (N=68) >15 cm (N=25) -5 cm - 5 cm (N=93) 0 0 1 2 3 4 5 6 Months 2019 JHLT. 2019 Oct; 38(10): 1015 -1066 7 8 9 10 11 12

Pediatric Heart-Lung Transplants Kaplan-Meier Survival Within 1 Year by Donor-Recipient Weight Difference (Transplants: January 1992 – June 2017) No pairwise comparisons were significant at p < 0. 05. 2019 JHLT. 2019 Oct; 38(10): 1015 -1066

Pediatric Heart-Lung Transplants Kaplan-Meier Survival Within 5 Years by Donor-Recipient Height Difference (Transplants: January 1992 – June 2013) 100 No pairwise comparisons were significant at p < 0. 05. Survival (%) 75 50 25 <-15 cm (N=21) -15 cm - <-5 cm (N=47) >5 cm - 15 cm (N=65) >15 cm (N=22) -5 cm - 5 cm (N=89) 0 0 1 2 2019 3 Years JHLT. 2019 Oct; 38(10): 1015 -1066 4 5

Pediatric Heart-Lung Transplants Kaplan-Meier Survival Within 5 Years by Donor-Recipient Weight Difference (Transplants: January 1992 – June 2013) No pairwise comparisons were significant at p < 0. 05. 2019 JHLT. 2019 Oct; 38(10): 1015 -1066