LUNG TRANSPLANTATION

LUNG TRANSPLANTATION

Overall

2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141

NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND PROCEDURE TYPE

5 7 36 78190

419

704

921

10881223

1336145214621490

16291693

188219322071

23842448

2769

1357

2716

0

250

500

750

1000

1250

1500

1750

2000

2250

2500

2750

3000

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

Nu

mb

er

of

Tra

ns

pla

nts

Bilateral/Double LungSingle Lung

NOTE: This figure includes only the lung transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as representing changes in the number of lung transplants performed worldwide.


AVERAGE CENTER VOLUMELung Transplants: January 1, 2000 - June 30, 2009

49

3225

147

26

50

10

20

30

40

50

60

1-4 5-9 10-19 20-29 30-39 40-49 50+

Average number of lung transplants per year

Nu

mb

er

of

ce

nte

rs

0

5

10

15

20

25

30

Number of centers Percentage of transplants

Per

cen

tag

e o

f tr

ansp

lan

ts


DISTRIBUTION OF TRANSPLANTS BY CENTER VOLUME

Lung Transplants: January 1, 2000 - June 30, 2009

6.4

17.9

25.221.2 21

5.7

2.70

5

10

15

20

25

30

35

1-4/yr 5-9/yr 10-19/yr 20-29/yr 30-39/yr 40-49/yr 50+/yr

Average number of lung transplants per year

Per

cen

tag

e o

f tr

ansp

lan

ts


LUNG TRANSPLANTS: Transplant Recipient Age by Year of Transplant

Transplants: January 1, 1987 – June 30, 2009

0%

20%

40%

60%

80%

100%

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

0

10

20

30

40

50

60

0-11 12-17 18-34 35-49 50-59 60-65 66+ Mean Age

Mea

n r

ecip

ien

t ag

e (y

ears

)

% o

f T

ran

sp

lan

tsrs

Year of Transplant


AGE DISTRIBUTION OF LUNG TRANSPLANT RECIPIENTS (1/1985-6/2009)

0

5

10

15

20

25

30

35

0-11 12-17 18-29 30-39 40-49 50-59 60-65 66+

Recipient Age

% o

f tr

an

sp

lan

ts


AGE DISTRIBUTION OF LUNG TRANSPLANT RECIPIENTS BY ERA

0

5

10

15

20

25

30

35

40

0-11 12-17 18-29 30-39 40-49 50-59 60-65 66+

% o

f tr

ansp

lan

ts

1985-1994 (N = 4,650)

1995-1999 (N = 7,091)

2000-6/2009 (N = 20,875)

p < 0.0001

Transplants with unknown recipient age were excluded from this tabulation.2010ISHLT

J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141

LUNG TRANSPLANTS: Donor Age by Year of Transplant

Transplants: January 1, 1987 – June 30, 2009

0%

20%

40%

60%

80%

100%

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

Year of Transplant

0

5

10

15

20

25

30

35

40

0-11 12-17 18-34 35-49 50-59 60+ Mean Donor Age

% o

f T

ran

spla

nts

Mea

n d

on

or

age

(yea

rs)


DONOR AGE DISTRIBUTION FOR LUNG TRANSPLANTS (1/1985-6/2009)

0

5

10

15

20

25

30

35

0-11 12-17 18-29 30-39 40-49 50-59 60-65 66+

Donor Age

% o

f tr

an

sp

lan

ts


DONOR AGE DISTRIBUTION FOR LUNG TRANSPLANTS BY ERA

0

5

10

15

20

25

30

35

40

0-11 12-17 18-29 30-39 40-49 50-59 60-65 66+

% o

f tr

ansp

lan

ts

1985-1994 (N = 4,547)

1995-1999 (N = 6,936)

2000-6/2009 (N = 20,688)

p < 0.0001

Transplants with unknown donor age were excluded from this tabulation.2010ISHLT


LUNG TRANSPLANTATION

Adult Recipients


AGE DISTRIBUTION OF ADULT LUNG TRANSPLANT RECIPIENTS (1/1985-6/2009)

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+

Recipient Age

% o

f tr

an

sp

lan

ts


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 tr

ansp

lan

ts

.

1985-1995 (N = 5,701)

1996-6/2009 (N = 25,515 )

p < 0.0001

Mean age by era1985-1995 = 44.9 years1996-6/2009 = 49.6 years


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 tr

ansp

lan

ts

.

1985-1994 (N=4,426)1995-1999 (N=6,691)2000-6/2009 (N=20,099)

p < 0.0001

Mean age by era1985-1994 = 44.6 years1995-1999 = 47.3 years2000-6/2009 = 50.1 years


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 13

Years

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

Su

rviv

al (

%)


ADULT LUNG TRANSPLANTATION: Indications (1/1995-6/2009)

DIAGNOSIS SLT (N = 10,925) BLT (N = 15,013) TOTAL (N = 25,938)

COPD/Emphysema 5,249 ( 48.0% ) 3,967 ( 26.4% ) 9,216 ( 35.5% )

Idiopathic Pulmonary Fibrosis 3,371 ( 30.9% ) 2,369 ( 15.8% ) 5,740 ( 22.1% )

Cystic Fibrosis 197 ( 1.8% ) 3,964 ( 26.4% ) 4,161 ( 16.0% )

Alpha-1 678 ( 6.2% ) 1,104 ( 7.4% ) 1,782 ( 6.9% )

Idiopathic Pulmonary Arterial Hypertension 75 ( 0.7% ) 768 ( 5.1% ) 843 ( 3.3% )

Sarcoidosis 221 ( 2.0% ) 448 ( 3.0% ) 669 ( 2.6% )

Bronchiectasis 46 ( 0.4% ) 662 ( 4.4% ) 708 ( 2.7% )

LAM 96 ( 0.9% ) 178 ( 1.2% ) 274 ( 1.1% )

Congenital Heart Disease 34 ( 0.3% ) 195 ( 1.3% ) 229 ( 0.9% )

Re-Transplant: Obliterative Bronchiolitis 209 ( 1.9% ) 173 ( 1.2% ) 382 ( 1.5% )

Obliterative Bronchiolitis

(Not Re-Transplant)

57 ( 0.5% ) 174 ( 1.2% ) 231 ( 0.9% )

Re-Transplant: Not Obliterative Bronchiolitis 114 ( 1.0% ) 140 ( 0.9% ) 254 ( 1.0% )

Connective Tissue Disease 73 ( 0.7% ) 144 ( 1.0% ) 217 ( 0.8% )

Cancer 5 ( 0.0% ) 19 ( 0.1% ) 24 ( 0.1% )

Other 500 ( 4.6% ) 708 ( 4.7% ) 1,208 ( 4.7% )


ADULT LUNG TRANSPLANTATION: Distribution of Procedure Type for Major Indications (1993-2008)

Year of TX

Alpha-1 COPD Cystic Fibrosis IPF IPAH

Double Single Double Single Double Single Double Single Double Single

1993 38.7 61.3 16.0 84.0 94.9 5.1 16.5 83.5 53.8 46.2

1994 43.0 57.0 18.9 81.1 86.1 13.9 14.0 86.0 63.5 36.5

1995 45.9 54.1 21.4 78.6 90.1 9.9 28.0 72.0 89.3 10.7

1996 47.3 52.7 26.9 72.9 87.0 13.0 27.4 72.6 82.0 18.0

1997 46.4 53.6 26.3 73.7 92.5 7.5 21.8 78.2 90.0 10.0

1998 48.5 51.5 29.0 71.0 92.7 7.3 20.0 80.0 86.8 13.2

1999 47.0 53.0 28.1 71.7 90.8 9.2 22.9 76.7 86.2 13.8

2000 57.7 42.3 29.2 70.8 94.7 5.3 31.7 68.3 92.7 7.3

2001 60.1 39.9 28.5 71.5 94.0 6.0 30.7 69.3 90.0 10.0

2002 56.6 43.4 38.6 61.4 96.2 3.8 35.2 64.8 89.9 10.1

2003 65.4 34.6 42.6 57.4 95.2 4.8 41.9 58.1 95.5 4.5

2004 73.9 25.4 45.4 54.6 96.2 3.8 44.6 55.4 94.5 5.5

2005 78.0 22.0 49.8 50.1 97.7 2.3 46.4 53.6 90.6 9.4

2006 76.3 23.7 58.5 41.3 99.2 0.8 49.4 50.6 100.0 0.0

2007 86.9 13.1 64.8 35.2 97.1 2.9 48.9 51.1 94.0 6.0

2008 80.6 19.4 65.8 34.2 97.8 2.2 52.0 48.0 94.7 5.3


ADULT LUNG TRANSPLANTATIONProcedure Type within Indication, by Year

0

10

20

30

40

50

60

70

80

90

100

19

95

19

96

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

20

07

20

08

19

95

19

96

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

20

07

20

08

19

95

19

96

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

20

07

20

08

19

95

19

96

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

20

07

20

08

% o

f tr

an

spla

nts

Bilateral/Double Lung Transplant Single Lung Transplant

AT Def COPD IPF IPAH


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*


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%


ADULT LUNG TRANSPLANTATIONMajor Indications By Year (%)

0

20

40

60

80

100

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

Transplant Year

% o

f T

ran

sp

lan

ts

CF IPF COPD Alpha-1 IPAH Re-Tx


ADULT LUNG TRANSPLANTATIONMajor Indications By Year (Number)

0

250

500

750

1000

1250

1500

1750

2000

2250

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

Transplant Year

Nu

mb

er

of

Tra

ns

pla

nts

CF IPF COPD Alpha-1 IPAH Re-Tx


0%

20%

40%

60%

80%

100%

Europe North America Other

% o

f T

ran

sp

lan

ts

18-34 years 35-49 years 50-59 years 60-65 years 66+ years

ADULT LUNG TRANSPLANTS:AGE DISTRIBUTION BY LOCATION Transplants between January 2000 and June 2009


0%

20%

40%

60%

80%

100%


Sarcoidosis

Re-TX

IPAH

Other

IPF

CF

COPD

Bronchiectasis

Alpha-1

Nu

mb

er

of

Tra

ns

pla

nts

ADULT LUNG TRANSPLANTS:DIAGNOSIS DISTRIBUTION BY LOCATION

Transplants between January 2000 and June 2009


0%

20%

40%

60%

80%

100%


1-5 6-10 11-17 18-34 35-49 50-59 60-65 66+

% o

f D

on

ors

ADULT LUNG TRANSPLANTS:DONOR AGE DISTRIBUTION BY LOCATION

Transplants between January 2000 and June 2009


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 12

Years

Su

rviv

al (

%)

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


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

Su

rviv

al (

%)


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

Su

rviv

al (

%)

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


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

Su

rviv

al (

%)

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


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis Conditional on

Survival to 3 Months (Transplants: January 1990 – June 2008)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13

Years

Su

rviv

al (

%)

Alpha-1 (N=1,860) CF (N= 3,547)COPD (N=8,334) IPF (N=4,460)IPAH (N=815) Sarcoidosis (N=533)

HALF-LIFE Alpha-1: 7.5 Years; CF: 8.3 Years; COPD: 5.8 Years;IPF: 5.4 Years; IPAH: 8.6 Years; Sarcoidosis: 7.0 Years

Survival comparisonsAll comparisons with Alpha-1, CF and IPAH are statistically significant at 0.01 except Alpha-1 vs. Sarcoidosis p = 0.1099 and CF vs. IPAH p = 0.8588

COPD vs. IPF: p = 0.0087IPF vs. Sarcoidosis: p = 0.0162


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 13

Years

Su

rviv

al (

%)

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


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival for Eisenmenger’s Syndrome


0

25

50

75

100

0 1 2 3 4 5

Years

Su

rviv

al (

%)

ASD (N=126) VSD (N= 56)

HALF-LIFE ASD: 3.3 Years; VSD: 1.1 Years

p = 0.3361

N at risk= 42

N at risk = 15


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Procedure Type

(Transplants: January 1990 – June 2008) Diagnosis: Alpha-1 Antitrypsin Deficiency

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13

Years

Su

rviv

al (

%)

Alpha-1/Single lung (N=1,003)

Alpha-1/Double lung (N=1,183)p < 0.0001

N at risk at 5 years = 431

N at risk at 5 years = 424N at risk = 55

N at risk = 61


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Procedure Type and Age

(Transplants: January 1990 – June 2008) Diagnosis: Alpha-1 Antitrypsin Deficiency

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12

Years

Su

rviv

al (

%)

Single Lung, < 50 (N = 450) Double Lung, <50 (N =629)Single Lung, 50+ (N = 553) Double Lung, 50+ (N = 554)

p =0.0029

N at risk at 12 years:Single Lung, <50 = 55; Double Lung, <50 = 63; Single Lung, 50+ = 27; Double Lung, 50+ = 15


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type

(Transplants: January 1990 – June 2008) Diagnosis: Emphysema/COPD

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13

Years

Su

rviv

al (

%)

COPD/Single lung (N=5,959)

COPD/Double lung (N=3,653) N=115

N=51

P < 0.0001


N at risk at 5 years = 1,970


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type and Age


Diagnosis: Emphysema/COPD

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13

Years

Su

rviv

al (

%)

<50/Single lung (N=724) <50/Double lung (N=823)

50+/Single lung (N=5,235) 50+/Double lung (N=2,830) N=34N=81

N=22N=29

P < 0.0001




Diagnosis: Idiopathic Pulmonary Fibrosis

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12

Years

Su

rviv

al (

%)

IPF/Single lung (N=3,418)

IPF/Double lung (N=2,040)N=55

N=24

p < 0.0001





(Transplants: January 1990 – June 2008)Diagnosis: Idiopathic Arterial Pulmonary Hypertension

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13

Years

Su

rviv

al (

%)

IPAH/Single lung (N=266)

IPAH/Double lung (N=857)N=28

N=33N at risk at 5 years = 89


p = 0.0036


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type and Era


Diagnosis: Emphysema/COPD, Single Lung

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11

Years

Su

rviv

al (

%)

COPD/Single lung/1990-1994 (N=1,000)

COPD/Single lung/1995-1999 (N=1,775)

COPD/Single lung/2000-6/2008 (N=3,184)

Survival comparisons1990-1994 vs. 1995-1999: p = 0.32481990-1994 vs. 2000-6/2008: p < 0.00011995-1999 vs. 2000-6/2008: p = 0.0007

N=100

N=112

N=114




Diagnosis: Emphysema/COPD, Double Lung

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11

Years

Su

rviv

al (

%)

COPD/Double lung/1990-1994 (N=208)

COPD/Double lung/1995-1999 (N=642)

COPD/Double lung/2000-6/2008 (N=2,803)

Survival comparisons1990-1994 vs. 1995-1999: p = 0.23711990-1994 vs. 2000-6/2008: p = 0.49671995-1999 vs. 2000-6/2008: p = 0.0145

N=17

N=50

N=70




Diagnosis: Idiopathic Pulmonary Fibrosis, Single Lung

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11

Years

Su

rviv

al (

%)

IPF/Single lung/1990-1994 (N=456)

IPF/Single lung/1995-1999 (N=827)

IPF/Single lung/2000-6/2008 (N=2,135)

Survival comparisons1990-1994 vs. 1995-1999: p = 0.49311990-1994 vs. 2000-6/2008: p = 0.00411995-1999 vs. 2000-6/2008: p = 0.0087

N=27 N=47

N=41




Diagnosis: Idiopathic Pulmonary Fibrosis, Double Lung

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (

%)

IPF/Double lung/1990-1994 (N=67)

IPF/Double lung/1995-1999 (N=263)

IPF/Double lung/2000-6/2008 (N=1,710)

Survival comparisons1990-1994 vs. 1995-1999: p = 0.44361990-1994 vs. 2000-6/2008: p = 0.00641995-1999 vs. 2000-6/2008: p < 0.0001

N=33

N=44

N=12


ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Donor CMV status/Recipient CMV status

(Transplants: October 1999 – June 2008)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

Years

Su

rviv

al (

%)

D(-)/R(-) (N=1,653)D(-)/R(+) (N=2,161)D(+)/R(-) (N=2,149)D(+)/R(+) (N=3,521)

Survival comparisonsD(-)/R(-) vs. D(+)/R(-): p < 0.0001D(-)/R(-) vs. D(+)/R(+): p < 0.0001D(-)/R(+) vs. D(+)/R(-): p < 0.0001D(-)/R(+) vs. D(+)/R(+): p = 0.0007


PERCENTAGE OF ADULT LUNG TRANSPLANT RECIPIENTS Experiencing Rejection between Transplant Discharge and 1-Year Follow-UpStratified by Donor/Recipient CMV status (Follow-ups: July 2004 - June 2009)

0

10

20

30

40

50

60

% e

xper

ien

cin

g r

ejec

tio

n w

ith

in 1

yea

r

D(-)/R(-), Treatment D(-)/R(-), No Treatment D(-)/R(+), Treatment D(-)/R(+), No Treatment

D(+)/R(-), Treatment D(+)/R(-), No Treatment D(+)/R(+), Treatment D(+)/R(+), No Treatment

D(-)/R(-): N = 866D(-)/R(+): N = 1,106D(+)/R(-): N = 1,218D(+)/R(+): N = 1,987

No comparisons were statistically significant at 0.05

Analysis is limited to patients who were alive at the time of the follow-up

Treated rejection = Recipient was reported to (1) have at least one acute rejection episode that was treated with an anti-rejection agent; or (2) have been hospitalized for rejection.

No rejection = Recipient had (i) no acute rejection episodes and (ii) was reported either as not hospitalized for rejection or did not receive anti-rejection agents.2010ISHLT


PERCENTAGE OF ADULT LUNG TRANSPLANT RECIPIENTS Experiencing Rejection between Transplant Discharge and 1-Year Follow-Up Stratified by Donor/Recipient CMV status (Follow-ups: July 2004 - June 2009)

0

10

20

30

40

50

60

% e

xp

eri

en

cin

g r

eje

cti

on

wit

hin

1 y

ea

r

D(-)/R(-), Treatment D(-)/R(-), No TreatmentD(-)/R(+), Treatment D(-)/R(+), No TreatmentD(+)/R(-), Treatment D(+)/R(-), No TreatmentD(+)/R(+), Treatment D(+)/R(+), No Treatment

18-34 35-49 50-59 60-65 66+ Female Male

No comparisons were statistically significant at 0.05 except 50-59: D(+)/R(-) vs. D(+)/R(+) (p=0.0385)



No rejection = Recipient had (i) no acute rejection episodes and (ii) was reported either as not hospitalized for rejection or did not receive anti-rejection agents.


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



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



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)



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)


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)


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)



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 Y

ear

Mo

rtal

ity



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 Y

ear

Mo

rtal

ity



Recipient Pre-Transplant Bilirubin

0

0.5

1

1.5

2

2.5

0 0.5 1 1.5 2

Recipient Bilirubin (mg/dl)

p = 0.0026

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity



Recipient Oxygen Required at Rest

0

0.5

1

1.5

2

0 1 2 3 4 5 6

Oxygen Required at Rest (L/min)

p < 0.0001

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity



Recipient Pre-Transplant Cardiac Output

0

0.5

1

1.5

2

3 4 5 6 7 8

Cardiac output

p = 0.0011

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity



Height Difference

0

0.5

1

1.5

2

-15 -10 -5 0 5 10 15 20

Donor Height - Recipient Height (cm)

p = 0.0161

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity



Recipient FEV1 (% predicted)

0

0.5

1

1.5

2

25 30 35 40 45 50 55 60 65 70 75 80


p = 0.0532

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity



Recipient FVC (% predicted)

0

0.5

1

1.5

2

25 30 35 40 45 50 55 60 65 70 75 80

Recipient FVC (% predicted)

p = 0.0518

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity


ADULT LUNG TRANSPLANTS (1/1996-6/2008) Diagnosis = COPD/EmphysemaRisk Factors for 1 Year Mortality

RECIPIENT CHARACTERISTICS N


95% Confidence Interval

Ventilator 47 2.33 0.0005 1.44 - 3.76

Hospitalized (including ICU) 242 1.73 0.0002 1.30 - 2.32


TRANSPLANT CHARACTERISTICS

Transplant Year: 1996/1997 vs. 2007/2008 600 1.48 0.0091 1.10 - 2.00


Donor CMV +/ Recipient CMV - 804 1.3 0.0035 1.09 - 1.56

Female recipient/female donor vs. male recipient/male donor

1,391 0.7 0.0253 0.51 - 0.96

DONOR CHARACTERISTICS

Donor history of diabetes 178 1.43 0.0362 1.02 - 1.99

(N=4,918)


ADULT LUNG TRANSPLANTS (1/1996-6/2008) Diagnosis = COPD/Emphysema

Borderline Significant Risk Factors for 1 Year Mortality

TRANSPLANT CHARACTERISTICS N




Double lung 1,768 1.16 0.0775 0.98 - 1.38

Female recipient/male donor vs. male recipient/male donor

1,178 0.78 0.0741 0.60 - 1.02

DONOR CHARACTERISTICS

Donor history of malignancy 67 0.50 0.0940 0.22 - 1.12

(N=4,918)


ADULT LUNG TRANSPLANTS (1/1996-6/2008)Diagnosis = COPD/Emphysema

Risk Factors for 1 Year Mortality


Recipient age

Oxygen required at rest


Cardiac output



Risk Factors for 1 Year MortalityRecipient Age

0

0.5

1

1.5

2

45 50 55 60 65

Recipient Age

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity

p < 0.0001



Risk Factors for 1 Year MortalityCenter Volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50


Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity

p < 0.0001



Risk Factors for 1 Year MortalityRecipient Oxygen Required at Rest

0

0.5

1

1.5

2

0 1 2 3 4


Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity

p = 0.0074


ADULT LUNG TRANSPLANTS (1/1996-6/2008)Diagnosis = COPD/Emphysema

Risk Factors for 1 Year Mortality Recipient Pre-Transplant Cardiac Output

0

0.5

1

1.5

2

3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8Cardiac output

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity

p = 0.0266


ADULT LUNG TRANSPLANTS (1/1996-6/2008)

Diagnosis = IPFRisk Factors for 1 Year Mortality


Risk P-value

95% Confidence

Interval

Ventilator 103 1.82 0.0014 1.26 - 2.63

Hospitalized (including ICU) 330 1.82 <0.0001 1.42 - 2.33

Previous pregnancy 660 1.43 0.0009 1.16 - 1.76

TRANSPLANT CHARACTERISTICS

Transplant Year: 1998/1999 vs. 2007/2008 276 2.52 <0.0001 1.89 - 3.35



Donor CMV+ / Recipient CMV- 616 1.52 <0.0001 1.28 - 1.81


BORDERLINE SIGNIFICANT CHARACTERISTICS

Donor cause of death = anoxia 232 0.74 0.0810 0.52 - 1.04

(N=3,124)


ADULT LUNG TRANSPLANTS (1/1996-6/2008)

Diagnosis = IPFRisk Factors for 1 Year Mortality


Recipient age

Donor weight

Bilirubin

Cardiac output (borderline)

Height difference (borderline)

Center volume

Oxygen required at rest

FVC (% predicted)

Ischemia time

Creatinine (borderline)


ADULT LUNG TRANSPLANTS (1/1996-6/2008) Diagnosis = IPF

Risk Factors for 1 Year MortalityRecipient Age

0

0.5

1

1.5

2

35 40 45 50 55 60 65

Recipient Age

p < 0.0001

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity



Risk Factors for 1 Year MortalityDonor Weight

0

0.5

1

1.5

2

50 60 70 80 90 100

Donor Weight (kg)

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity

p = 0.0099


ADULT LUNG TRANSPLANTS (1/1996-6/2008)Diagnosis = IPF

Risk Factors for 1 Year MortalityRecipient O2 Required at Rest

0

0.5

1

1.5

2

0 1 2 3 4 5 6

O2 Required at Rest (L/min)

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity

p = 0.0098



Risk Factors for 1 Year MortalityCenter volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50


Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity

p < 0.0001



Risk Factors for 1 Year MortalityIschemia Time

0

0.5

1

1.5

2

2 3 4 5 6 7

Ischemia time (hours)

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity

p = 0.0417



Risk Factors for 1 Year MortalityRecipient Bilirubin

0

0.5

1

1.5

2

0 0.5 1 1.5

Bilirubin (mg/dl)

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity

p = 0.0001



Risk Factors for 1 Year MortalityRecipient FVC (% predicted)

0

0.5

1

1.5

2

25 30 35 40 45 50 55 60 65 70

FVC (% predicted)

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity

p = 0.0471



Risk Factors for 1 Year Mortality Recipient Pre-Transplant Cardiac Output

0

0.5

1

1.5

2

3 4 5 6 7 8

Cardiac output

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity

p = 0.0616



Risk Factors for 1 Year Mortality Recipient Creatinine at Transplant

0

0.5

1

1.5

2

0.5 1 1.5

Creatinine

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity

p = 0.0540



Risk Factors for 1 Year Mortality Height Difference

0

0.5

1

1.5

2

-15 -10 -5 0 5 10 15 20

Donor Height - Recipient Height (cm)

p = 0.0862

Rel

ativ

e R

isk

of

1 Y

ear

Mo

rtal

ity




Risk P-value

95% Confidence

Interval

Transplant year = 1998/1999 vs. 2002-2004 1,589 1.44 <0.0001 1.31 - 1.58



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)





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)





Risk P-value


Donor history of diabetes 214 1.32 0.0037 1.09 - 1.58



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


Recipient history of diabetes 605 1.21 0.0023 1.07 - 1.37


(N=7,609)




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




Recipient age


Cardiac output

Bilirubin

Recipient oxygen required at rest

Donor age

Recipient FEV1 % predicted

Recipient height (borderline)



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 Y

ear

Mo

rtal

ity

p < 0.0001



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 Y

ear

Mo

rtal

ity

p = 0.0063



Center Volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50


Rel

ativ

e R

isk

of

5 Y

ear

Mo

rtal

ity

p < 0.0001



Recipient Pre-Transplant Bilirubin

0

0.5

1

1.5

2

2.5

0 0.5 1 1.5 2

Recipient Bilirubin (mg/dl)

Rel

ativ

e R

isk

of

5 Y

ear

Mo

rtal

ity

p = 0.0244



Recipient Oxygen Required at Rest

0

0.5

1

1.5

2

0 1 2 3 4 5 6


Rel

ativ

e R

isk

of

5 Y

ear

Mo

rtal

ity

p = 0.0008




0

0.5

1

1.5

2

25 30 35 40 45 50 55 60 65 70 75 80


p = 0.0331

Rel

ativ

e R

isk

of

5 Y

ear

Mo

rtal

ity




0

0.5

1

1.5

2

3 4 5 6 7

Cardiac output

Rel

ativ

e R

isk

of

5 Y

ear

Mo

rtal

ity

p = 0.0050



Recipient Height

0

0.5

1

1.5

2

155 160 165 170 175 180 185

Recipient Height (cm)

Rel

ativ

e R

isk

of

5 Y

ear

Mo

rtal

ity

p = 0.0625


ADULT LUNG TRANSPLANTS (1996-6/2004) Risk Factors for 5 Year MortalityConditional on Survival to 1 Year



95% conf. Interval

Alpha-1 antitrypsin deficiency

Double 236 0.67 0.0063 0.50 - 0.89

IPF Double 276 0.62 0.0009 0.47 - 0.82

Cystic fibrosis All 877 0.56 <0.0001 0.43 - 0.73

IPAH All 200 0.51 0.0032 0.33 - 0.80

LAM All 62 0.47 0.0110 0.26 - 0.84

(N=5,769)





Risk P-value




Prior sternotomy 248 1.35 0.0028 1.11 - 1.65

Recipient history of diabetes 462 1.33 0.0006 1.13 - 1.56

(N=5,769)




Risk P-value

95% Confidence

Interval


Transplant year = 1998/1999 vs. 2002-2004 1,174 1.18 0.0109 1.04 - 1.34

Donor CMV +/ Recipient CMV - 1,060 1.14 0.0268 1.01 - 1.27

Mismatches at HLA A locus, per mismatch 0 A MM (N=366)

1 A MM (N=3,067) 2 A MM (N=2,336)

1.10 0.0093 1.02 - 1.19

Female donor/female recipient vs. male donor/male recipient

1,652 0.83 0.0425 0.69 - 0.99

POST-TRANSPLANT FACTORS

OB within 1 year post-transplant 372 2.35 <0.0001 2.03 - 2.73

Treated for infection by discharge 2,294 1.13 0.0081 1.03 - 1.24

Rejection within 1 year post-transplant 2,778 1.13 0.0080 1.03 - 1.24

(N=5,769)



Conditional on Survival to 1 Year

CHARACTERISTICS N Relative

Risk P-value

95% Confidence

Interval

Post-transplant dialysis prior to discharge 136 1.28 0.0823 0.97 - 1.69



Donor cause of death = cerebrovascular/stroke

2,061 1.10 0.0972 0.98 - 1.23

Recipient pre-transplant chronic steroid use 2,667 1.08 0.0856 0.99 - 1.19

Induction with IL2R-antagonist 1,218 0.89 0.0815 0.79 - 1.01

Diagnosis = Other* 233 0.79 0.0755 0.61 - 1.02

Diagnosis = Sarcoidosis, single lung 63 0.67 0.0869 0.42 - 1.06

(N=5,769)

*Other = All diagnoses other than COPD, IPAH, IPF, cystic fibrosis, pulmonary fibrosis, bronchiectasis, alpha-1 antitrypsin deficiency, retransplant and LAM.



ADULT LUNG TRANSPLANTS (1/1996-6/2004) Risk Factors for 5 Year MortalityConditional on Survival to 1 Year


Recipient age


Cardiac output (borderline)

Recipient FEV1 % predicted (borderline)

Height difference

Donor age (borderline)

Recipient Height (borderline)


ADULT LUNG TRANSPLANTS (1/1996-6/2004) Risk Factors for 5 Year Mortality Conditional on 1 Year Survival

Recipient Age

0

0.5

1

1.5

2

2.5

3

20 25 30 35 40 45 50 55 60 65

Recipient Age

Rel

ativ

e R

isk

of

5 Y

ear

Mo

rtal

ity

p < 0.0001


ADULT LUNG TRANSPLANTS (1/1996-6/2004)Risk Factors for 5 Year Mortality Conditional on 1 Year Survival

Center Volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50


Rel

ativ

e R

isk

of

5 Y

ear

Mo

rtal

ity

p = 0.0016



Height Difference

0

0.5

1

1.5

2

-10 -5 0 5 10 15 20

Donor height - recipient height (cm)

Rel

ativ

e R

isk

of

5 Y

ear

Mo

rtal

ity

p = 0.0216



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 Y

ear

Mo

rtal

ity

p = 0.0966



Recipient Height

0

0.5

1

1.5

2

155 160 165 170 175 180 185

Recipient Height (cm)

Rel

ativ

e R

isk

of

5 Y

ear

Mo

rtal

ity

p = 0.0772




0

0.5

1

1.5

2

3 4 5 6 7 8

Cardiac output

Rel

ativ

e R

isk

of

5 Y

ear

Mo

rtal

ity

p = 0.0718




0

0.5

1

1.5

2

25 30 35 40 45 50 55 60 65 70 75


p = 0.0507

Rel

ativ

e R

isk

of

5 Y

ear

Mo

rtal

ity


ADULT LUNG RECIPIENTSCross-Sectional Analysis

Functional Status of Surviving Recipients(Follow-ups: April 1994 – June 2009)

0%

20%

40%

60%

80%

100%

1 Year (N = 6,845) 3 Year (N = 4,381) 5 Year (N = 2,516) 10 Years (N = 430)

No Activity Limitations Performs with Some Assistance Requires Total Assistance


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


ADULT LUNG RECIPIENTSFunctional Status of Surviving Recipients

(Follow-ups: March 2005 - June 2009)US Recipients Only

0%

20%

40%

60%

80%

100%

1 Year (N = 4,893) 2 Years (N = 3,835) 3 Years (N = 3,189)

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%


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


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: Rejection

Hosp: Infection Hosp: Rej/Inf


0

5

10

15

20

25

30

35

40

45

50

55

Any Induction (N =4,902)

Polyclonal ALG/ATG (N= 1,089)

IL2R-antagonist (N =3,315)

Campath (N = 481)

% o

f p

ati

en

tsADULT LUNG RECIPIENTS

Induction Immunosuppression (Transplants: January 2002 - June 2009)Analysis limited to patients receiving prednisone



0

10

20

30

40

50

60

70

Any Induction PolyclonalALG/ATG

IL2R-antagonist Campath

% o

f p

ati

en

ts

1997 2002 1/2009-6/2009

ADULT LUNG RECIPIENTS Induction Immunosuppression

(Transplants: 1997, 2002 and 1/2009-6/2009) Analysis limited to patients receiving prednisone

Analysis is limited to patients who were alive at the time of the follow-up2010ISHLT


0

10

20

30

40

50

60

70

2000

2001

2002

2003

2004

2005

2006

2007

2008

2000

2001

2002

2003

2004

2005

2006

2007

2008

2000

2001

2002

2003

2004

2005

2006

2007

2008

2000

2001

2002

2003

2004

2005

2006

2007

2008

% o

f p

ati

en

ts

ADULT LUNG RECIPIENTSInduction Immunosuppression (Transplants: January 2000 - December 2008)

Analysis limited to patients receiving prednisone

Any Induction Polyclonal ALG/ATG IL2R-antagonist Campath



SURVIVAL BY INDUCTION USAGE For Adult Lung Recipients (Transplants: April 1994-June 2008)

Conditional on survival to 14 days

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13

Years

Su

rviv

al (

%)

No induction (N = 7,766)

Induction (N = 6,029)

p = 0.0024

N at risk = 63

N at risk = 137




SURVIVAL BY INDUCTION USAGE For Adult Lung Recipients (Transplants: January 2000-June 2008)

Conditional on survival to 14 days

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8

Years

Su

rviv

al (

%)

No induction (N = 4,774)

Induction (N = 4,802)

p = 0.0001

N at risk = 231

N at risk = 208


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine

% o

f P

ati

en

ts

Year 1 (N=7,234) Year 5 (N=3,021)

ADULT LUNG RECIPIENTSMaintenance Immunosuppression at Time of Follow-up

For follow-ups between January 2002 through June 2009Analysis limited to patients receiving prednisone

NOTE: Different patients are analyzed in Year 1 and Year 5



0

20

40

60

80

100

CyA TAC Rapamycin MMF AZA CyA TAC Rapamycin MMF AZA

% o

f P

ati

en

ts

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




0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine

% o

f P

ati

en

ts

2000 (N = 589) 2003 (N =825) July 2008 - June 2009 (N = 1,160)

ADULT LUNG RECIPIENTSMaintenance Immunosuppression at Time of 1 Year Follow-up

(Follow-ups: 2000, 2003, 7/2008 – 6/2009) Analysis limited to patients receiving prednisone

NOTE: Different patients are analyzed in each time frame.



0

20

40

60

80

100

CalcineurinInhibitor

CellCycle Rapamycin CalcineurinInhibitor

CellCycle Rapamycin

% o

f P

ati

en

ts

CyA

Tac Tac

CyA

Rapa Rapa

MMF MMF

AZA AZA

ADULT LUNG RECIPIENTS Maintenance Immunosuppression at Time of Follow-up

For follow-ups between January 2002 through June 2009Analysis limited to patients receiving prednisone

1 Year Follow-up (N =7,234) 5 Year Follow-up (N = 3,021)




0

20

40

60

80

100

Year 1 (N = 7,234) Year 5 (N = 3,021)

% o

f P

atie

nts

Other

Rapa + Calcineurin + Cellcycle

Rapa + Cellcycle

Rapa + Calcineurin

Tacrolimus

Tacrolimus + MMF

Tacrolimus + AZA

Cyclosporine + MMF

Cyclosporine + AZA

ADULT LUNG RECIPIENTS Maintenance Immunosuppression Drug Combinations at Time of Follow-up

For follow-ups between January 2002 through June 2009 Analysis limited to patients receiving prednisone



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

Su

rviv

al (

%)

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




Analysis limited to patients receiving prednisone Diagnosis: COPD/Emphysema

0

20

40

60

80

100

0 1 2 3 4 5 6 7

Years

Su

rviv

al (

%)

Tacrolimus + MMF use at discharge and 1 year (N=687)

Tacrolimus + AZA use at discharge and 1 year (N=388)



p = 0.0289




Analysis limited to patients receiving prednisone Diagnosis: Idiopathic Pulmonary Fibrosis

0

20

40

60

80

100

0 1 2 3 4 5 6

Years

Su

rviv

al (

%)





p = 0.0841




Analysis limited to patients receiving prednisone Diagnosis: Cystic Fibrosis

0

20

40

60

80

100

0 1 2 3 4 5 6

Years

Su

rviv

al (

%)





p = 0.8486


PERCENTAGE OF ADULT LUNG TRANSPLANT RECIPIENTS Experiencing Rejection between Transplant Discharge and 1-Year Follow-Up

(Follow-ups: July 1, 2004 - June 30, 2009)

0

10

20

30

40

50

60

% e

xp

eri

en

cin

g r

eje

cti

on

wit

hin

1 y

ea

r

No induction, Treatment No induction, No Treatment

Overall 18-34 35-49 50-59 60-65 66+ Female Male

18-34 vs. 35-49 p = 0.012918-34 vs. 60-65 p = 0.0270


Overall: N = 5,67218-34: N = 78735-49: N = 1,00550-59: N = 1,93760-65: N = 1,51466+: N = 429Female: N = 2,540 Male: N = 3,132





Stratified by Type of Induction (Follow-ups: July 1, 2004 - June 30, 2009)

0

10

20

30

40

50

60

% e

xp

eri

en

cin

g r

eje

cti

on

wit

hin

1 y

ea

r

No induction, Treatment No induction, No TreatmentPolyclonal, Treatment Polyclonal, No TreatmentIL2R-antagonist, Treatment IL2R-antagonist, No TreatmentCampath, Treatment Campath, No Treatment

No induction vs. IL2R (p < 0.0001) No induction vs. Campath (p = 0.0442) Polyclonal vs. IL2R (p = 0.0002)

No induction: N = 2,624Polyclonal: N = 502IL2R- antagonist: N = 2,142Campath: N = 358







0

10

20

30

40

50

60

70

% e

xp

eri

en

cin

g r

eje

cti

on

wit

hin

1 y

ea

r


18-34 (N=783) 35-49 (N=999) 50-59 (N=1,918) 60-65 (N=1,502) 66+ (N=424)

18-34: no induct vs. IL2 (p=0.0164); poly vs. IL2R (p=0.007); IL2R vs. Campath (p=0.0084)35-49: no induct vs. Campath (p=0.0310); IL2R vs. Campath (p=0.0112; 50-59: no induct vs. IL2R (p=0.0005); 60-65: no induct vs. IL2R (p=0.0018); no induct vs. Campath (p=0.0100) 66+: no induct vs. poly (p=0.0014); poly vs. IL2 (p<0.0001); poly vs. Campath (p<0.0001)







0

10

20

30

40

50

60

70

% e

xp

eri

en

cin

g r

eje

cti

on

wit

hin

1 y

ea

r


Female (N = 2,524) Male (N =3,102)

Female: no induct vs. IL2R (p=0.0032); IL2R vs. Campath (p=0.0152)Male: no induct vs.IL2R (p<0.0001); poly vs. IL2R (p = 0.0011)





PERCENTAGE OF ADULT LUNG TRANSPLANT RECIPIENTSExperiencing Rejection between Transplant Discharge and 1-Year Follow-UpStratified by Maintenance Immunosuppression (Follow-ups: July 1, 2004 - June 30, 2009)

0

10

20

30

40

50

60

70

CyA + MMF, Treatment CyA + MMF, No Treatment CyA + AZA, Treatment CyA + AZA, No Treatment

TAC + MMF, Treatment TAC + MMF, No Treatment TAC + AZA, Treatment TAC + AZA, No Treatment

% e

xper

ien

cin

g r

ejec

tio

n w

ith

in 1

yea

r

All comparisons are statistically significant at 0.05

Cyclosporine + MMF: N = 371 Cyclosporine + AZA: N = 555Tacrolimus + MMF: N = 2,476Tacrolimus + AZA: N = 1,448






Stratified by Maintenance Immunosuppression (Follow-ups: July 1, 2004 - June 30, 2009)

0

10

20

30

40

50

60

70

80

90 CyA + MMF, Treatment CyA + MMF, No Treatment

CyA + AZA, Treatment CyA + AZA, No Treatment

TAC + MMF, Treatment TAC + MMF, No Treatment

TAC + AZA, Treatment TAC + AZA, No Treatment

% e

xper

ien

cin

g r

ejec

tio

n w

ith

in 1

yea

r

18-34 (N=667) 35-49 (N=858) 50-59 (N=1,657) 60-65 (N=1,299) 66+ (N=369)

All age groups: all comparisons with CyA + AZA are significant at 0.02 except 35-49:CyA + AZA vs. CyA+ MMF (p=0.1033) and 66+: CyA + AZA vs. CyA + MMF (p=0.0850)35-49: CyA + MMF vs. TAC + MMF( p=0.0260); CyA + MMF vs. TAC + AZA (p=0.0253) 50-59: CyA + MMF vs. TAC + MMF (p=0.0076) 60-65: CyA + MMF vs. TAC + MMF (p=0.0078); TAC + MMF vs. TAC + AZA (p=0.0022)66+: TAC + MMF vs. TAC + AZA (p=0.0301)







0

10

20

30

40

50

60

70

80

90 CyA + MMF, Treatment CyA + MMF, No Treatment

CyA + AZA, Treatment CyA + AZA, No Treatment

TAC + MMF, Treatment TAC + MMF, No Treatment

TAC + AZA, Treatment TAC + AZA, No Treatment

% e

xper

ien

cin

g r

ejec

tio

n w

ith

in 1

yea

r

Female (N = 2,174) Male (N = 2,676)

Females: all comparisons are statistically significant at 0.01 except CyA + MMF vs. TAC + AZA (p=0.2562) Males: all comparisons were statistically significant at 0.01 except CyA +MMF vs. TAC + AZA (p=0.0590) and TAC + MMF vs. TAC + AZA (p=0.0922)





PERCENTAGE OF ADULT LUNG TRANSPLANT RECIPIENTS Experiencing Rejection between Transplant Discharge and 3-Year Follow-Up Stratified by Maintenance Immunosuppression (Follow-ups: July 1, 2004 - June 30, 2009)

0

10

20

30

40

50

60

70

80

CyA + MMF, Treatment CyA + MMF, No Treatment CyA + AZA, Treatment CyA + AZA, No Treatment

TAC + MMF, Treatment TAC + MMF, No Treatment TAC + AZA, Treatment TAC + AZA, No Treatment

% e

xper

ien

cin

g r

ejec

tio

n w

ith

in 3

yea

rs all comparisons with CyA + AZA are significant at p < 0.0001

Cyclosporine + MMF: N = 188 Cyclosporine + AZA: N = 289Tacrolimus + MMF: N = 909Tacrolimus + AZA: N = 678

Analysis is limited to patients with rejection or no rejection reported on all three annual follow-ups through 3 years






0

10

2030

40

50

6070

80

90CyA + MMF, Treatment CyA + MMF, No TreatmentCyA + AZA, Treatment CyA + AZA, No TreatmentTAC + MMF, Treatment TAC + MMF, No TreatmentTAC + AZA, Treatment TAC + AZA, No Treatment

% e

xp

eri

en

cin

g r

eje

cti

on

wit

hin

3 y

ea

rs

18-34 35-49 50-59 60-65 66+ MaleFemale

All age groups and genders: all comparisons with CyA + AZA are significant at 0.02 except 35-49:CyA + AZA vs. CyA+ MMF (p=0.6121) and 66+: CyA + AZA vs. CyA + MMF (p=0.1044)35-49: CyA + MMF vs. TAC + MMF (p=0.0515); CyA + MMF vs. TAC + AZA (p=0.0368);

Analysis is limited to patients with rejection or no rejection reported on all three annual follow-ups through 3 years




POST-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 1 Year Post-Transplant


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)


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)


POST-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 10 Years Post-Transplant


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)


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 11

Years

Freedom from Bronchiolitis ObliteransSyndrome (N = 12,058)


N at risk = 90

% F

ree

do

m f

rom

Bro

nc

hio

litis

O

blit

era

ns

Sy

nd

rom

e


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 = 48

N at risk = 25

% F

ree

do

m f

rom

Bro

nc

hio

litis

O

blit

era

ns

Sy

nd

rom

e


FREEDOM FROM BRONCHIOLITIS OBLITERANS SYNDROME

Stratified by Donor CMV Status/Recipient CMV StatusFor 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

Years

D(-)/R(-) (N=1,895)D(-)/R(+) (N=2,616)D(+)/R(-) (N=2,309)D(+)/R(+) (N=4,069)

N at risk = 20

N at risk = 27

N at risk = 36

N at risk = 48

No p-values are significant at p = 0.05 except D(-)/R(-) vs. D(+)/R(-): p = 0.0150D(-)/R(+) vs. D(+)/R(+): p = 0.0261D(+)/R(-) vs. D(+)/R(+): p = 0.0035

% F

ree

do

m f

rom

Bro

nc

hio

litis

O

blit

era

ns

Sy

nd

rom

e


FREEDOM FROM SEVERE RENAL DYSFUNCTION*For Adult Lung Recipients (Follow-ups: April 1994-June 2009)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12

Years

% F

ree

do

m f

rom

Se

ve

re R

en

al

Dy

sfu

nc

tio

n

Freedom from Severe RenalDysfunction (N=12,751)


N at risk = 62

* Severe renal dysfunction = Creatinine > 2.5 mg/dl (221 μmol/L), dialysis or renal transplant


MALIGNANCY POST-LUNG TRANSPLANTATION FOR ADULTSCumulative Prevalence in Survivors (Follow-ups: April 1994 - June 2009)

Malignancy/Type 1-Year Survivors 5-Year Survivors 10-Year Survivors

No Malignancy 12,669 (96.4%) 3,406 (87.0%) 451 (71.8%)

Malignancy (all types combined) 470 (3.6%) 510 (13.0%) 177 (28.2%)

Malignancy Type*

Skin 127 306 114

Lymph 195 72 31

Other 129 158 52

Type Not Reported

19 8 0

* Recipients may have experienced more than one type of malignancy so sum of individual malignancy types may be greater than total number with malignancy.

Other malignancies reported include: adenocarcinoma (2; 2; 1), bladder (2; 1; 0), lung (2; 4; 0), breast (1; 5; 2); prostate (0; 5; 1), cervical (1; 1; 0); liver (1; 1; 1); colon (1; 1; 0). Numbers in parentheses represent the number of reported cases within each time period.


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 13

Years

% F

ree

fro

m M

alig

na

nc

y

All malignancy Lymph Skin Other


ADULT LUNG TRANSPLANT RECIPIENTS: Cause Of Death (Deaths: January 1992- June 2009)

CAUSE OF DEATH

0-30 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%)


ADULT LUNG TRANSPLANT RECIPIENTS: Relative Incidence of Leading Causes of Death

(Deaths: January 1992 - June 2009)

0

10

20

30

40

50

0-30 Days (N=1,966)

31 Days – 1Year

(N=3,387)

>1 Year – 3Years

(N=3,073)

>3 Years – 5Years

(N=1,737)

>5 Years – 10Years

(N=2,014)

>10 Years (N=483)

Bronchiolitis Malignancy (non-Lymph/PTLD)

Infection (non-CMV) Graft Failure

Cardiovascular

Pe

rce

nta

ge

of

De

ath

s


ADULT LUNG TRANSPLANT RECIPIENTS: Cause Of Death Stratified by Donor CMV Status/Recipient CMV Status

(Deaths: January 1992- June 2009)

Donor CMV Status/

Recipient CMV Status

Cause of Death 0-30 Days31 Days –

1 Year

>1 Year –

3 Years

>3 Years –

5 Years>5 Years – 10 Years

>10 Years

D(-)/R(-)

(N=1,421)

BRONCHIOLITIS 1 (0.5%) 22 (6.3%) 88 (24.6%) 68 (32.4%) 61 (24.0%) 14 (21.5%)

INFECTION, NON-CMV 31 (16.9%) 123 (35.0%) 86 (24.0%) 39 (18.6%) 35 (13.8%) 12 (18.5%)

GRAFT FAILURE 56 (30.6%) 70 (19.9%) 73 (20.4%) 44 (21.0%) 50 (19.7%) 10 (15.4%)

D(-)/R(+)

(N=2,106)

BRONCHIOLITIS 3 (1.1%) 26 (5.5%) 126 (25.2%) 89 (25.7%) 111 (26.7%) 20 (19.2%)


GRAFT FAILURE 81 (30.1%) 78 (16.5%) 94 (18.8%) 58 (16.8%) 86 (20.7%) 20 (19.2%)

D(+)/R(-)

(N=1,741)

BRONCHIOLITIS 0 14 (2.6%) 108 (24.0%) 60 (25.6%) 60 (24.8%) 3 (5.8%)


GRAFT FAILURE 66 (28.8%) 109 (20.4%) 101 (22.4%) 54 (23.1%) 56 (23.1%) 9 (17.3%)

D(+)/R(+)

(N=3,130)

BRONCHIOLITIS 1 (0.2%) 40 (5.2%) 196 (24.1%) 129 (26.9%) 118 (21.9%) 22 (18.0%)


GRAFT FAILURE 128 (31.3%) 164 (21.3%) 153 (18.8%) 98 (20.5%) 112 (20.8%) 28 (23.0%)


LUNG TRANSPLANTATION

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