Optimizing lung transplant outcomes in the adult and pediatric patient. Cynthia S. Herrington, MD Associate Professor of Surgery Keck School of Medicine University of Southern California
Feb 24, 2016
Optimizing lung transplant outcomes in the adult and pediatric
patient.
Cynthia S. Herrington, MDAssociate Professor of Surgery
Keck School of MedicineUniversity of Southern California
Optimizing Lung Transplant Outcomes
Holy SRTR
International practices and outcomes and where the pitfalls exist --ISHLT
How to asses a program when the wheels fall off the bus
The Adults
Optimizing Lung Transplant Outcomes
AGE DISTRIBUTION OF ADULT LUNG TRANSPLANT RECIPIENTS BY ERA
0
5
10
15
20
25
18-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-65 66+
% o
f tra
nspl
ants
.
1985-1994 (N=4,426)1995-1999 (N=6,691)2000-6/2009 (N=20,099)
p < 0.0001Mean age by era1985-1994 = 44.6 years1995-1999 = 47.3 years2000-6/2009 = 50.1 years
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival (Transplants: January 1994 - June 2008)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13Years
Bilateral/Double Lung (N=14,055)Single Lung (N=10,869)All Lungs (N= 24,936)
Double lung: 1/2-life = 6.6 Years; Conditional 1/2-life = 9.1 YearsSingle lung: 1/2-life = 4.6 Years; Conditional 1/2-life = 6.4 YearsAll lungs: 1/2-life = 5.3 Years; Conditional 1/2-life = 7.5 Years
P < 0.0001
Surv
ival
(%)
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTATIONProcedure Type within Indication, by Year
0
10
20
30
40
50
60
70
80
90
100
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
% o
f tra
nspl
ants
Bilateral/Double Lung Transplant Single Lung Transplant
AT Def COPD IPF IPAH
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Era (Transplants: January 1988 – June 2008)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12Years
Surv
ival
(%)
1988-1994 (N=4,318)1995-1999 (N=6,558)2000-6/2008 (N=17,227)
1988-1994: 1/2-life = 4.0 Years; Conditional 1/2-life = 7.0 Years1995-1999: 1/2-life = 4.6 Years; Conditional 1/2-life = 7.3 Years2000-6/2008: 1/2-life = 5.7 Years; Conditional 1/2-life = 7.9 Years
N at risk = 129
N at risk = 406
N at risk = 577
Survival comparisons by era1988-94 vs. 1995-99: p = 0.00021988-94: vs. 2000-6/08: p <0.0001 1995-99 vs. 2000-6/08: p <0.0001
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Age Group (Transplants: January 1990 – June 2008)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12
Years
18-34 (N = 4,819)35-49 (N = 7,127)50-59 (N = 10,069)60-65 (N = 4,929)66+ (N = 907)
Survival comparisonsAll p-values significant at p < 0.0001 except 18-34 vs. 35-49: p =0.4955; 60-65 vs. 66+: p = 0.0001
HALF-LIFE 18-34: 5.9 Years; 35-49: 6.3 Years; 50-59: 5.1 Years; 60-65: 4.3 Years; 66+: 3.3 Years
Surv
ival
(%)
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Gender (Transplants: January 1990 – June 2008)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Years
Surv
ival
(%)
Male (N=14,799)
Female (N=13,050)
HALF-LIFE Male: 5.0 years; Female: 5.4 Years
p = 0.0003 N at risk at 10 years=928
N at risk = 154N at risk at 10 years=910
N at risk = 127
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2008)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13Years
Surv
ival
(%)
Alpha-1 (N=2,187) CF (N=4,144) COPD (N=9,616)IPF (N=5,459) IPAH (N=1,123) Sarcoidosis (N=660)
HALF-LIFE Alpha-1: 6.1 Years; CF: 7.1 Years; COPD: 5.2 Years; IPF: 4.3 Years; IPAH: 4.9 Years; Sarcoidosis: 5.1 Years
Survival comparisonsAll comparisons with Alpha-1 and CF are statistically significant at 0.01
IPAH vs. IPF: p = 0.0210COPD vs. IPF: p < 0.0001
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis Conditional on Survival to 1 Year
(Transplants: January 1990 – June 2008)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13Years
Surv
ival
(%)
Alpha-1 (N=1,630) CF (N=3,085)COPD (N=7,214) IPF (N=3,618)IPAH (N=720) Sarcoidosis (N=439)
HALF-LIFE Alpha-1: 8.5 Years; CF: 9.4 Years; COPD: 6.6 Years;IPF: 6.7 Years; IPAH: 9.3 Years; Sarcoidosis: 8.5 Years
Survival comparisonsAll comparisons with Alpha-1 and COPD are statistically significant at 0.01 except Alpha-1 vs. Sarcoidosis p = 0.6576 and COPD vs. IPF p = 0.7539
CF vs. IPF: p < 0.0001IPAH vs. IPF: p < 0.0001IPF vs. Sarcoidosis: p = 0.0028
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTS (1996-6/2008) Risk Factors for 1 Year Mortality
DIAGNOSIS Procedure type N
Relative Risk P-value
95% conf. Interval
IPAH All 406 2.19 <0.0001 1.63 - 2.95
Retransplant All 424 2.01 <0.0001 1.62 - 2.49
Other* All 724 1.82 <0.0001 1.50 - 2.20
Sarcoidosis Double 264 1.78 <0.0001 1.34 - 2.37
Alpha-1 antitrypsin deficiency Single 356 1.77 <0.0001 1.40 - 2.22
Pulmonary Fibrosis (not IPF) All 149 1.75 0.0018 1.23 - 2.49
Alpha-1 antitrypsin deficiency Double 448 1.47 0.0022 1.15 - 1.88
IPF Double 1,219 1.47 0.0002 1.20 - 1.80
IPF Single 1,890 1.35 0.0011 1.13 - 1.62
Cystic fibrosis All 1,783 1.32 0.0197 1.04 - 1.66
COPD/Emphysema Double 1,765 1.19 0.0250 1.02 - 1.39
(N=13,079) *Other = All diagnoses other than COPD, IPAH, IPF, cystic fibrosis, pulmonary fibrosis, bronchiectasis, alpha-1 antitrypsin deficiency, retransplant and LAM.
Reference group = COPD/Emphysema, Single lung
2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTS (1996-6/2008) Risk Factors for 1 Year Mortality
TRANSPLANT CHARACTERISTICS N Relative Risk P-value
95% Confidence
Interval
Transplant year = 1996/1997 vs. 2007/2008 1,546 1.86 <0.0001 1.59 - 2.18
Transplant year = 1998/1999 vs. 2007/2008 1,589 1.82 <0.0001 1.56 - 2.13
Transplant year = 2000/2001 vs. 2007/2008 1,862 1.56 <0.0001 1.33 - 1.81
Donor CMV +/ Recipient CMV - 2,643 1.21 <0.0001 1.10 - 1.33
Transplant year = 2002/2003 vs. 2007/2008 2,053 1.17 0.0468 1.00 - 1.37
(N=13,079)
2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTS (1996-6/2008) Risk Factors for 1 Year Mortality
DONOR CHARACTERISTICS N Relative Risk P-value
95% Confidence
Interval
Donor history of diabetes 479 1.45 <0.0001 1.20 - 1.75
RECIPIENT CHARACTERISTICS
Recipient on dialysis 49 1.81 0.0097 1.16 - 2.85
IV inotropes 54 1.73 0.0051 1.18 - 2.54
Hospitalized (including ICU) 1,316 1.65 <0.0001 1.44 - 1.88
Ventilator 390 1.54 <0.0001 1.26 - 1.88
Chronic steroid use 6,170 1.11 0.013 1.02 - 1.21
(N=13,079)
2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTS (1996-6/2008) Borderline Significant Risk Factors for 1 Year Mortality
RECIPIENT CHARACTERISTICS N Relative Risk P-value
95% Confidence
Interval
Diagnosis = sarcoidosis, single lung 135 1.41 0.0752 0.97 - 2.07
Prior pulmonary embolism 126 1.33 0.0812 0.96 - 1.84
Recipient prior malignancy 515 1.20 0.0584 0.99 - 1.44
Anoxia 901 0.87 0.0983 0.73 - 1.03
(N=13,079)
2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTS (1/1996-6/2008) Risk Factors for 1 Year Mortality
Recipient Age
0
0.5
1
1.5
2
25 30 35 40 45 50 55 60 65
Recipient Age
p < 0.0001
Rel
ativ
e R
isk
of 1
Yea
r Mor
talit
y
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTS (1996-6/2004) Risk Factors for 5 Year Mortality
TRANSPLANT CHARACTERISTICS N Relative Risk P-value
95% Confidence
Interval
Transplant year = 1998/1999 vs. 2002-2004 1,589 1.44 <0.0001 1.31 - 1.58
Transplant year = 1996/1997 vs. 2002-2004 1,546 1.42 <0.0001 1.29 - 1.56
Transplant year = 2000/2001 vs. 2002-2004 1,862 1.26 <0.0001 1.15 - 1.37
Donor CMV +/ Recipient CMV - 1,435 1.14 0.0014 1.05 - 1.24
0-3 HLA mismatches vs. 4-6 mismatches 1,033 0.90 0.0430 0.82 - 1.00
(N=7,609)
2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTS (1996-6/2004) Risk Factors for 5 Year Mortality
DIAGNOSIS Procedure type N
Relative Risk P-value
95% conf. Interval
Alpha-1 antitrypsin deficiency Single 303 1.34 0.0008 1.13 - 1.59
Retransplant All 182 1.31 0.0154 1.05 - 1.62
Cystic fibrosis All 1,091 0.79 0.0140 0.65 - 0.95
LAM All 71 0.52 0.0069 0.32 - 0.84
(N=7,609)
Reference group = COPD/Emphysema, Single lung
2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTS (1996-6/2004) Risk Factors for 5 Year Mortality
DONOR CHARACTERISTICS N Relative Risk P-value 95% Confidence
Interval
Donor history of diabetes 214 1.32 0.0037 1.09 - 1.58
Donor cause of death = anoxia 406 0.77 0.0015 0.65 - 0.90
RECIPIENT CHARACTERISTICS
IV inotropes 54 2.02 <0.0001 1.45 - 2.83
Recipient on dialysis 22 1.81 0.0166 1.11 - 2.93
Prior sternotomy 348 1.27 0.0013 1.10 - 1.47
Hospitalized (including ICU) 548 1.25 0.0018 1.09 - 1.44
Recipient history of diabetes 605 1.21 0.0023 1.07 - 1.37
Chronic steroid use 3,548 1.10 0.0091 1.02 - 1.18
(N=7,609)
2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTS (1996-6/2004) Borderline Significant Risk Factors for 5 Year Mortality
RECIPIENT CHARACTERISTICS N Relative Risk
P-value
95% Confidence
Interval
Diagnosis = IPAH 292 1.40 0.0866 0.95 - 2.06
Prior pulmonary embolism 72 1.32 0.0693 0.98 - 1.79
Ventilator 156 1.27 0.0548 1.00 - 1.62
Diagnosis = other* 343 1.17 0.0686 0.99 - 1.40
Female recipient/female donor vs. male recipient/male donor 2,143 0.88 0.0953 0.76 - 1.02
(N=7,609)*Other = All diagnoses other than COPD, IPAH, IPF, cystic fibrosis, pulmonary fibrosis, bronchiectasis, alpha-1 antitrypsin deficiency, retransplant and LAM.
Reference diagnosis group = COPD/Emphysema, Single lung
2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTS (1/1996-6/2004) Risk Factors for 5 Year Mortality
Recipient Age
0
0.5
1
1.5
2
20 25 30 35 40 45 50 55 60 65
Recipient Age
Rel
ativ
e R
isk
of 5
Yea
r Mor
talit
y
p < 0.0001
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG RECIPIENTSLongitudinal Analysis
Functional Status of Surviving Recipients(Follow-ups: April 1994 – June 2009)
For the Same Patients
0%
20%
40%
60%
80%
100%
1 Year (N = 1,632) 3 Year (N = 1,632) 5 Year (N = 1,632)
No Activity Limitations Performs with Some Assistance Requires Total Assistance
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG RECIPIENTSEmployment Status of Surviving Recipients
(Follow-ups: April 1994 – June 2009)
0%
20%
40%
60%
80%
100%
1 Year (N=9,787) 3 Year (N=6,090) 5 Year (N=3,777) 10 year (N=702)
Working (FT/PTStatus unknown)Working Part Time
Working Full Time
Retired
Not Working
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG RECIPIENTS: Rehospitalization Post-transplant of Surviving Recipients
(Follow-ups: April 1994 - June 2009)
0%
20%
40%
60%
80%
100%
1 Year (N = 12,933) 3 Year ( N = 8,059) 5 Year (N = 4,988) 10 Year (N=894)
No Hospitalization Hosp: No Rej/No Inf Hosp: RejectionHosp: Infection Hosp: Rej/Inf
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
POST-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 1 Year Post-Transplant
(Follow-ups: April 1994 - June 2009)
Follow-ups: April 1994 – June 2000
Follow-ups: July 2000 – June 2009
Outcome Within 1 Year Total number with known response
Within 1 Year Total number with known response
Hypertension 49.1% (N = 3,757) 54.10% (N = 8,040)
Renal Dysfunction 23.20% (N = 3,675) 24.80% (N = 9,057)
Abnormal Creatinine < 2.5 mg/dl 12.9% 18.40%
Creatinine > 2.5 mg/dl 8.6% 4.80%
Chronic Dialysis 1.8% 1.50%
Renal Transplant 0.0% 0.10%
Hyperlipidemia 13.1% (N = 3,897) 29.20% (N = 8,624)
Diabetes 16.8% (N = 3,718) 30.30% (N = 8,976)
Bronchiolitis Obliterans Syndrome 10.7% (N = 3,450) 9.10% (N = 8,547)
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
POST-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 1 and 5 Years
Post-Transplant (Follow-ups: April 1994 - June 2009)
Outcome Within 1 Year Total number with known response
Within 5 Years Total number with known response
Hypertension 52.5% (N = 11,797) 84.4% (N = 3,271)
Renal Dysfunction 24.40% (N = 12,732) 34.7% (N = 3,834)
Abnormal Creatinine < 2.5 mg/dl 16.8% 23.1%
Creatinine > 2.5 mg/dl 5.9% 8.3%
Chronic Dialysis 1.6% 2.8%
Renal Transplant 0.1%
0.5%
Hyperlipidemia 24.2% (N = 12,521) 56.5% (N = 3,600)
Diabetes 26.3% (N = 12,694) 38.0% (N = 3,551)
Bronchiolitis Obliterans Syndrome 9.6% (N = 11,997) 36.9% (N = 2,965)
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
POST-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 10 Years Post-Transplant
(Follow-ups: April 1994 - June 2009)
Outcome Within 10 Years Total number with known response
Hypertension 97.3% (N = 337)
Renal Dysfunction 41.5% (N = 612)
Abnormal Creatinine < 2.5 mg/dl 26.5% Creatinine > 2.5 mg/dl 5.9% Chronic Dialysis 6.9% Renal Transplant 2.3%
Hyperlipidemia 68.5% (N = 410)
Diabetes 37.4% (N = 374)
Bronchiolitis Obliterans Syndrome 54.1% (N = 379)
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
FREEDOM FROM BRONCHIOLITIS OBLITERANS SYNDROME For Adult Lung Recipients (Follow-ups: April 1994-June 2009)
Conditional on Survival to 14 days
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11Years
Freedom from Bronchiolitis ObliteransSyndrome (N = 12,058)
N at risk at 5 years = 1,575
N at risk = 90
% F
reed
om fr
om B
ronc
hiol
itis
Obl
itera
ns S
yndr
ome
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
FREEDOM FROM BRONCHIOLITIS OBLITERANS SYNDROME STRATIFIED BY INDUCTION USE
For Adult Lung Recipients (Follow-ups: April 1994-June 2009)Conditional on Survival to 14 days
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11Years
No induction (N=6,189)Induction (N=4,978)
p = 0.0019
N at risk at 5 years = 583
N at risk at 5 years = 891
N at risk = 48
N at risk = 25
% F
reed
om fr
om B
ronc
hiol
itis
Obl
itera
ns S
yndr
ome
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
FREEDOM FROM MALIGNANCYFor Adult Lung Recipients (Follow-ups: April 1994-June 2009)
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13Years
% F
ree
from
Mal
igna
ncy
All malignancy Lymph Skin Other
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANT RECIPIENTS: Cause Of Death (Deaths: January 1992- June 2009)
CAUSE OF DEATH0-30 Days (N = 1,966)
31 Days – 1 Year
(N = 3,387)
>1 Year – 3 Years
(N = 3,073)
>3 Years – 5 Years
(N = 1,737 )
>5 Years – 10 Years
(N = 2,014)
>10 Years (N = 483)
BRONCHIOLITIS 6 (0.3%) 159 (4.7%) 781 (25.4%) 508 (29.2%) 507 (25.2%) 95 (19.7%)
ACUTE REJECTION 74 (3.8%) 61 (1.8%) 48 (1.6%) 10 (0.6%) 15 (0.7%) 1 (0.2%)
LYMPHOMA 1 (0.1%) 86 (2.5%) 63 (2.1%) 28 (1.6%) 46 (2.3%) 23 (4.8%)
MALIGNANCY, OTHER 4 (0.2%) 100 (3.0%) 202 (6.6%) 151 (8.7%) 219 (10.9%) 47 (9.7%)
CMV 0 96 (2.8%) 29 (0.9%) 5 (0.3%) 4 (0.2%) 0
INFECTION, NON-CMV 396 (20.1%) 1,205 (35.6%) 710 (23.1%) 329 (18.9%) 363 (18.0%) 81 (16.8%)
GRAFT FAILURE 557 (28.3%) 589 (17.4%) 591 (19.2%) 327 (18.8%) 379 (18.8%) 87 (18.0%)
CARDIOVASCULAR 213 (10.8%) 144 (4.3%) 118 (3.8%) 82 (4.7%) 99 (4.9%) 36 (7.5%)
TECHNICAL 162 (8.2%) 76 (2.2%) 18 (0.6%) 8 (0.5%) 12 (0.6%) 6 (1.2%)
OTHER 553 (28.1%) 871 (25.7%) 513 (16.7%) 289 (16.6%) 370 (18.4%) 107 (22.2%)
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
Children
Optimizing Lung Transplant Outcomes
AGE DISTRIBUTION OF PEDIATRIC LUNG RECIPIENTS
By Year of Transplant
1 3 4 6
20
48 51 48
8274
87 89
68 6863
71 75 7887 87
95102
43
0102030405060708090
100110
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
12-17 Years1-11 Years<1 Year
Num
ber o
f Tra
nspl
ants
Analysis includes living donor transplants
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.
2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
NUMBER OF CENTERS REPORTING PEDIATRIC LUNG TRANSPLANTS BY CENTER VOLUME
0
10
20
30
40
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
Transplant Year
Num
ber o
f Cen
ters
Rep
ortin
g Pe
diat
ric T
rans
plan
ts
20+ transplants10-19 transplants5-9 transplants1-4 transplants
Analysis includes living donor transplants 2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
0%
20%
40%
60%
80%
100%
Europe (N=211) North America (N=498) Other (N=37)
% o
f Tra
nspl
ants
-
Cystic Fibrosis IPAH IPF OB Other Congenital heart disease Re-TX
PEDIATRIC LUNG TRANSPLANTS:DIAGNOSIS DISTRIBUTION BY LOCATION
Transplants between January 2000 and June 2009
NOTE: Unknown diagnoses were excluded from this tabulation.
Total number of transplants reported:Europe = 237North America = 498Other = 41
Analysis includes living donor transplants
2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
LUNG TRANSPLANTATIONKaplan-Meier Survival by Age Group
(Transplants: January 1990 - June 2008)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15Years
Surv
ival
(%)
Adult (N=27,851)
Pediatric (N=1,174)
HALF-LIFE Adult = 5.2 Years; Pediatric = 4.6 Years
P = 0.9423
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type
(Transplants: January 1990 - June 2008)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14Years
Surv
ival
(%)
Single Lung (N=73)
Bilateral/Double Lung (N=1,101)
HALF-LIFE Single Lung: 2.2 Years; Bilateral/double Lung: 4.9 Years
P < .0001
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Age Group
(Transplants: January 1990 - June 2008)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12
Years
Surv
ival
(%)
<1 Year (N=84)1-11 Years (N=334)12-17 Years (N=756)
<1 year vs. 1-11 years: p = 0.3124<1 year vs. 12-17 years: p = 0.83871-11 years vs. 12-17 years: p = 0.0395
HALF-LIFE<1 Year: 6.4 Years1-11 Years: 6.0 Years12-17 Years: 4.3 Years
N at risk = 10N at risk = 17
N at risk = 20
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC LUNG TRANSPLANTATIONConditional Kaplan-Meier Survival by Age Group
(Transplants: January 1990 - June 2008)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12
Years
Surv
ival
(%)
<1 Year (N=50)1-11 Years (N=231)12-17 Years (N=524)
<1 year vs. 1-11 year: p = 0.6485<1 year vs. 12-17 years: p = 0.13861-11 years vs. 12-17 years: p =0.0696
N at risk = 10
N at risk = 17
N at risk = 20
CONDITIONAL HALF-LIFE<1 Year: 8.8 Years1-11 Years: 8.7 Years12-17 Years: 6.1 Years
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Donor Type for Recipients Age 12-17 Years
(Transplants: January 1990 - June 2008)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10Years
Surv
ival
(%)
Deceased Donor (N = 756)
Living Donor (N = 77)
p = 0.3570
N at risk = 7
N at risk = 35
HALF-LIFEDeceased: 4.3 YearsLiving: 3.7 Years
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
0
5
10
15
20
25
0-<1 month 1-<12 months 12-<36 months 36+ months Not reported
Num
ber o
f R
e-Tr
ansp
lant
s
Time Between Previous and Current Transplant
PEDIATRIC LUNG RE-TRANSPLANTS Between January 1994 and June 2009
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5
Years
Surv
ival
(%)
N at risk at 5 years = 8
PEDIATRIC LUNG RETRANSPLANTSSurvival for Transplants Performed Between January 1994 and June 2008
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC LUNG RECIPIENTSLongitudinal Analysis
Functional Status of Surviving RecipientsFor the Same Patients
(Follow-ups: April 1994-June 2009)
0%
20%
40%
60%
80%
100%
1 Year (N = 82) 3 Years (N = 82) 5 Years (N = 82)
No Activity Limitations Performs with Assistance Total Assistance
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
PEDIATRIC LUNG RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients
(Follow-ups: April 1994 - June 2009)
0%
20%
40%
60%
80%
100%
Up to 1 Year (N =578)
Between 2 and 3Years (N = 346)
Between 4 and 5Years (N = 203)
Between 6 and 7Years (N = 102)
No Hospitalization Hospitalized, Not Rejection/Not InfectionHospitalized, Rejection Hospitalized, Infection OnlyHospitalized, Rejection + Infection
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
POST-LUNG TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Prevalence in Survivors within 1 Year Post-Transplant
(Follow-ups: April 1994 - June 2009)
Outcome Within 1 Year
Total number with known response
Hypertension 43.0% (N = 561)
Renal Dysfunction 10.7% (N = 571) Abnormal Creatinine < 2.5 mg/dl 7.5% Creatinine > 2.5 mg/dl 2.1% Chronic Dialysis 0.7% Renal Transplant 0.4%
Hyperlipidemia 5.0% (N = 579)
Diabetes 25.7% (N = 571)
Bronchiolitis Obliterans Syndrome 13.6% (N = 536)
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
Optimizing the outcomes…..evaluate program vulnerabilities by doing root cause analysis on each death
Take risks proportional to the stability of the program
Optimizing Lung Transplant Outcomes
ADULT LUNG TRANSPLANT RECIPIENTS: Cause Of Death (Deaths: January 1992- June 2009)
CAUSE OF DEATH0-30 Days (N = 1,966)
31 Days – 1 Year
(N = 3,387)
>1 Year – 3 Years
(N = 3,073)
>3 Years – 5 Years
(N = 1,737 )
>5 Years – 10 Years
(N = 2,014)
>10 Years (N = 483)
BRONCHIOLITIS 6 (0.3%) 159 (4.7%) 781 (25.4%) 508 (29.2%) 507 (25.2%) 95 (19.7%)
ACUTE REJECTION 74 (3.8%) 61 (1.8%) 48 (1.6%) 10 (0.6%) 15 (0.7%) 1 (0.2%)
LYMPHOMA 1 (0.1%) 86 (2.5%) 63 (2.1%) 28 (1.6%) 46 (2.3%) 23 (4.8%)
MALIGNANCY, OTHER 4 (0.2%) 100 (3.0%) 202 (6.6%) 151 (8.7%) 219 (10.9%) 47 (9.7%)
CMV 0 96 (2.8%) 29 (0.9%) 5 (0.3%) 4 (0.2%) 0
INFECTION, NON-CMV 396 (20.1%) 1,205 (35.6%) 710 (23.1%) 329 (18.9%) 363 (18.0%) 81 (16.8%)
GRAFT FAILURE 557 (28.3%) 589 (17.4%) 591 (19.2%) 327 (18.8%) 379 (18.8%) 87 (18.0%)
CARDIOVASCULAR 213 (10.8%) 144 (4.3%) 118 (3.8%) 82 (4.7%) 99 (4.9%) 36 (7.5%)
TECHNICAL 162 (8.2%) 76 (2.2%) 18 (0.6%) 8 (0.5%) 12 (0.6%) 6 (1.2%)
OTHER 553 (28.1%) 871 (25.7%) 513 (16.7%) 289 (16.6%) 370 (18.4%) 107 (22.2%)
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
0
20
40
60
80
100
CyA TAC Rapamycin MMF AZA CyA TAC Rapamycin MMF AZA
% o
f Pat
ient
s
1-Year Follow-Up 5-Year Follow-Up
Consecutive bars within each drug type represent follow-ups in 2002, 2003, 2004, 2005, 2006, 2007, 2008 & 2009.
ADULT LUNG RECIPIENTSMaintenance Immunosuppression at Time of Follow-up
For follow-ups between January 2002 through June 2009 Analysis limited to patients receiving prednisone
NOTE: Different patients are analyzed in Year 1 and Year 5
Analysis is limited to patients who were alive at the time of the follow-up
2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG RECIPIENTSKaplan-Meier Survival by Maintenance Immunosuppression
Combinations Conditional on Survival to 1 Year (Transplants: January 2000-June 2008)
Analysis limited to patients receiving prednisone
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8
Years
Surv
ival
(%)
Tacrolimus + MMF use at discharge and 1 year (N=1,986)Tacrolimus + AZA use at discharge and 1 year (N=1,068)Cyclosporine + MMF use at discharge and 1 year (N=415)Cyclosporine + AZA use at discharge and 1 year (N=474)
p = 0.0046
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTATION: Indications for Single Lung Transplants (Transplants: January 1995 - June 2009)
*Other includes:Sarcoidosis: 2.0%Bronchiectasis: 0.4%Congenital Heart Disease: 0.3%LAM: 0.9%OB (non-ReTx): 0.5%Miscellaneous: 5.3%
48%
31%
9%
6%
2%
1%3%
Alpha-1 COPD CF IPF IPAH Re-Tx Other*
2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTATION: Indications for Bilateral/Double Lung Transplants (Transplants: January 1995 - June 2009)
26%
16% 2%5%
26%
7%
17%
Alpha-1 COPD CF IPF IPAH Re-Tx Other*
*Other includes:Sarcoidosis: 3.0%Bronchiectasis: 4.4%Congenital Heart Disease: 1.3%LAM: 1.2%OB (non-ReTx): 1.2%Miscellaneous: 5.8%
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTS (1/1996-6/2008) Risk Factors for 1 Year Mortality
Continuous Factors (see figures) Recipient age
Transplant center volume
Cardiac output
Recipient FVC % predicted (borderline)
Bilirubin
Recipient oxygen required at rest
Height difference
Recipient FEV1 % predicted (borderline)
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTS (1/1996-6/2008) Risk Factors for 1 Year Mortality
Center Volume
0
0.5
1
1.5
2
5 10 15 20 25 30 35 40 45 50
Center Volume (cases per year)
p < 0.0001
Rel
ativ
e R
isk
of 1
Yea
r Mor
talit
y
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTS (1/1996-6/2004) Risk Factors for 5 Year Mortality
Continuous Factors (see figures) Recipient age
Transplant center volume
Cardiac output
Bilirubin
Recipient oxygen required at rest
Donor age
Recipient FEV1 % predicted
Recipient height (borderline)
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTS (1/1996-6/2004) Risk Factors for 5 Year Mortality
Donor Age
0
0.5
1
1.5
2
15 20 25 30 35 40 45 50 55
Donor Age
Rel
ativ
e R
isk
of 5
Yea
r Mor
talit
y
p = 0.0063
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
ADULT LUNG TRANSPLANTS (1/1996-6/2004) Risk Factors for 5 Year Mortality
Center Volume
0
0.5
1
1.5
2
5 10 15 20 25 30 35 40 45 50
Center Volume (cases per year)
Rel
ativ
e R
isk
of 5
Yea
r Mor
talit
y
p < 0.0001
2010ISHLT
J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141