LUNG TRANSPLANTATION Overall ISHLT 2007 J Heart Lung Transplant 2007;26: 782-795.

LUNG TRANSPLANTATION

Overall

ISHLT 2007 J Heart Lung Transplant 2007;26: 782-795

NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND PROCEDURE TYPE

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

Nu

mb

er o

f T

ran

spla

nts

Bilateral/Double LungSingle Lung

ISHLT 2007

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.

14 15 46 83189

418

707

9221088

12311369

13701462

14581479

15791591

17881915

2169

1791

J Heart Lung Transplant 2007;26: 782-795

AVERAGE CENTER VOLUMELung Transplants: January 1, 1998 - June 30, 2006

52

27 29

15 16

2 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


DISTRIBUTION OF TRANSPLANTS BY CENTER VOLUME

Lung Transplants: January 1, 2000 - June 30, 2006

3.47.7

21.718.5

28.1

4.9

15.8

0

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

Pe

rce

nta

ge

of

tra

ns

pla

nts

.


AGE DISTRIBUTION OF LUNG TRANSPLANT RECIPIENTS (1/1985-6/2006)

0

5

10

15

20

25

30

35

0-11 12-17 18-29 30-39 40-49 50-59 60-64 65+

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 60-64 65+

% o

f tr

ansp

lan

ts

1985-1994 (N = 4,658)

1995-1999 (N=7,116)

2000-6/2006 (N=11,851)

p < 0.0001


LUNG TRANSPLANTS: Donor Age by Year of Transplant

0%

20%

40%

60%

80%

100%

Year of Transplant

% o

f T

ran

sp

lan

ts

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

0

5

10

15

20

25

30

35

40

Me

an

do

no

r a

ge

(y

ea

rs)

Mean Age


DONOR AGE DISTRIBUTION FOR LUNG TRANSPLANTS (1/1985-6/2006)

0

5

10

15

20

25

30

35

0-11 12-17 18-29 30-39 40-49 50-59 60-64 65+

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 60-64 65+

% o

f tr

ansp

lan

ts

1985-1994 (N = 4,658)

1995-1999 (N=7,116)

2000-6/2006 (N=11,851)

p < 0.0001


LUNG TRANSPLANTATION

Adult Recipients


AGE DISTRIBUTION OF ADULT LUNG TRANSPLANT RECIPIENTS (1/1985-6/2006)

0

5

10

15

20

25

18-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65+

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 60-64 65+

% o

f tr

ansp

lan

ts .

1985-1995 (N = 5,722)

1996-6/2006 (N =16,856 )

p < 0.0001

ISHLT 2007

Mean age by era1985-1995 = 45.0 years1996-6/2006 = 48.9 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 60-64 65+

% o

f tr

ansp

lan

ts

.

1985-1994 (N=4,437)1995-1999 (N=6,726)2000-6/2006 (N=11,415)

p < 0.0001

ISHLT 2007

Mean age by era1985-1994 = 44.7 years1995-1999 = 47.3 years2000-6/2006 = 49.5 years


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival (Transplants: January 1994 - June 2005)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (%

) .

Bilateral/Double Lung (N=8,658)

Single Lung (N=8,369)

All Lungs (N=17,027)

Double lung: 1/2-life = 5.9 Years; Conditional 1/2-life = 8.6 YearsSingle lung: 1/2-life = 4.4 Years; Conditional 1/2-life = 6.3 YearsAll lungs: 1/2-life = 5.0 Years; Conditional 1/2-life = 7.1 Years

P < 0.0001


ADULT LUNG TRANSPLANTATION: Indications (1/1995-6/2006)

DIAGNOSIS SLT (N = 8,316) BLT (N = 9,300) TOTAL (N = 17,616)

COPD/Emphysema 4,305 (52%) 2,225 (24%) 6,530 (37%)

Idiopathic Pulmonary Fibrosis 2,193 (26%) 1,217 (13%) 3,410 (19%)

Cystic Fibrosis 167 (2.0%) 2,722 (29%) 2,889 (16%)

Alpha-1 626 (7.5%) 795 (8.5%) 1,421 (8.1%)

Primary Pulmonary Hypertension 65 (0.8%) 575 (6.2%) 640 (3.6%)

Sarcoidosis 178 (2.1%) 260 (2.8%) 438 (2.5%)

Bronchiectasis 30 (0.4%) 473 (5.1%) 503 (2.9%)

LAM 59 (0.7%) 116 (1.2%) 175 (1.0%)

Congenital Heart Disease 16 (0.2%) 132 (1.4%) 148 (0.8%)

Re-Transplant: Obliterative Bronchiolitis

111 (1.3%) 85 (0.9%) 196 (1.1%)

Obliterative Bronchiolitis

(Not Re-Transplant)

46 (0.6%) 103 (1.1%) 149 (0.8%)

Re-Transplant: Not Obliterative Bronchiolitis

76 (0.9%) 70 (0.8%) 146 (0.8%)

Connective Tissue Disease 51 (0.6%) 65 (0.7%) 116 (0.7%)

Interstitial Pneumonitis 24 (0.3%) 13 (0.1%) 37 (0.2%)

Cancer 7 (0.1%) 12 (0.1%) 19 (0.1%)

Other 362 (4.4%) 437 (4.7%) 799 (4.5%)


ADULT LUNG TRANSPLANTATION: Distribution of Procedure Type for Major Indications (1991-2005)

ISHLT 2007

Year of TX

Alpha-1 COPD Cystic Fibrosis IPF PPH

Double Single Double Single Double Single Double Single Double Single

1991 19.0 81.0 14.2 85.8 95.7 4.3 15.1 84.9 23.4 76.6

1992 28.1 71.9 16.1 83.9 97.0 3.0 9.2 90.8 26.6 73.4

1993 38.7 61.3 16.0 84.0 94.9 5.1 16.5 83.5 53.8 46.2

1994 42.6 57.4 18.7 81.3 85.5 14.5 14.0 86.0 64.3 35.7

1995 45.8 54.2 21.5 78.5 89.6 10.4 27.6 72.4 90.4 9.6

1996 46.4 53.6 26.9 73.1 86.8 13.2 27.5 72.5 82.0 18.0

1997 45.7 54.3 26.8 73.2 92.8 7.2 22.2 77.8 90.0 10.0

1998 46.6 53.4 28.9 71.1 92.6 7.4 20.2 79.8 86.8 13.2

1999 46.8 53.2 27.3 72.7 90.5 9.5 23.1 76.9 85.7 14.3

2000 56.8 43.2 28.5 71.5 95.0 5.0 32.9 67.1 92.0 8.0

2001 59.4 40.6 27.7 72.3 94.1 8.9 28.7 71.3 90.6 9.4

2002 53.2 46.8 37.3 62.7 96.4 3.6 35.0 65.0 88.3 11.7

2003 65.1 34.9 39.8 60.2 96.1 3.9 40.7 59.3 94.3 5.7

2004 71.7 28.3 43.0 57.0 96.2 3.8 43.2 56.8 95.8 4.2

2005 75.7 24.3 48.0 52.0 97.8 2.2 45.9 54.1 89.5 10.5


ADULT LUNG TRANSPLANTATIONProcedure Type within Indication, by Year

0

10

20

30

40

50

60

70

80

90

100

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

% o

f tr

ansp

lan

ts

Bilateral/Double Lung Transplant Single Lung Transplant

AT Def COPD IPF PPH

2007

ISHLTJ Heart Lung Transplant 2007;26: 782-795

ADULT LUNG TRANSPLANTATION: Indications for Single Lung Transplants (Transplants: January 1996 - June 2006)

52%

26%

9%

8%

2%1%

2%

Alpha-1 COPD CF IPF PPH Re-TX Other*

ISHLT 2007

*Other includes:

Sarcoidosis: 2.1%

Bronchiectasis: 0.4%

Congenital Heart Disease: 0.2%

LAM: 0.7%

OB (non-ReTx): 0.6%

Miscellaneous: 5.4%


ADULT LUNG TRANSPLANTATION: Indications for Bilateral/Double Lung Transplants (Transplants: January 1996 - June 2006)

24%

13%

17%

9%

29%

6% 2%

Alpha-1 COPD CF IPF PPH Re-Tx Other*

ISHLT 2007

*Other includes:

Sarcoidosis: 2.8%

Bronchiectasis: 5.1%

Congenital Heart Disease: 1.4%

LAM: 1.2%

OB (non-ReTx): 1.1%

Miscellaneous: 5.6%


ADULT LUNG TRANSPLANTATIONIndications By Year (%)

0

20

40

60

80

100

Transplant Year

% o

f T

ran

spla

nts

CF IPF COPD Alpha-1 PPH


ADULT LUNG TRANSPLANTATIONIndications By Year (Number)

0

250

500

750

1000

1250

1500

1750

Transplant Year

Nu

mb

er o

f T

ran

spla

nts

CF IPF COPD Alpha-1 PPH


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 60-64 years 65+ years

ADULT LUNG TRANSPLANTS:AGE DISTRIBUTION BY LOCATION Transplants between January 2000 and June 2006


0%

20%

40%

60%

80%

100%


Nu

mb

er

of T

ran

sp

lan

ts-

Sarcoidosis

Re-TX

PPH

Other

IPF

CF

COPD

Bronchiectasis

Alpha-1

ADULT LUNG TRANSPLANTS:DIAGNOSIS DISTRIBUTION BY LOCATION

Transplants between January 2000 and June 2006


0%

20%

40%

60%

80%

100%


% o

f Do

nors

1-5 6-10 11-17 18-34 35-49 50-59 60-64 65+

ADULT LUNG TRANSPLANTS:DONOR AGE DISTRIBUTION BY LOCATION

Transplants between January 2000 and June 2006


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Era (Transplants: January 1988 – June 2005)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (

%)

1988-1994 (N=4,392)1995-1999 (N=6,726)2000-6/2005 (N=9,419)

1988-1994: 1/2-life = 3.9 Years; Conditional 1/2-life = 7.0 Years1995-1999: 1/2-life = 4.5 Years; Conditional 1/2-life = 7.1 Years2000-6/2005: 1/2-life = 5.3 Years; Conditional 1/2-life = 6.4 Years

Survival comparisons by era1988-94 vs. 1995-99: p = 0.00571988-94: vs. 2000-6/05: p <0.0001 1995-99 vs. 2000-6/05: p <0.0001


ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Age Group (Transplants: January 1990 – June 2005)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (%

) .

18-34 (N= 3,718)35-49 (N= 5,687)50-59 (N= 7,402)60-64 (N= 2,764)65+ (N= 710)

Survival comparisons18-34 vs. 50-59: p <0.000118-34 vs. 60-64 and vs. 65+ : p < 0.000135-49 vs. 50-59, 60-64 and 65+: p < 0.000150-59 vs. 60-64 and vs. 65+: p < 0.000160-64 vs. 65+: p =.0548

HALF-LIFE 18-34: 5.2 Years; 35-49: 5.6 Years; 50-59: 4.7 Years; 60-64: 3.9 Years; 65+: 3.4 Years


ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Gender (Transplants: January 1990 – June 2005)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (%

) Male (N=8,997)

Female (N=8,319)

HALF-LIFE Male: 4.8 years; Female: 5.2 Years

p = 0.0135


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2005)

YearALPHA-1 (N=1,844)

CF

(N=2,947)COPD

(N=7,113)IPF

(N=3,362)PPH

(N=926)SARCOIDOSIS

(N=429)

1 77.4 81.0 81.5 71.6 66.6 68.2

3 63.2 65.2 64.0 56.4 56.4 54.9

5 53.2 54.8 49.0 44.0 47.7 49.0

7 43.3 47.0 36.2 33.3 40.4 42.9

10 31.0 36.6 20.5 19.7 28.8 33.4

Survival comparisonsAlpha-1 vs. CF: p = 0.0031 CF vs. COPD: p < 0.0001Alpha-1 vs. COPD: p = 0.0005 CF vs. IPF: p < 0.0001Alpha-1 vs. IPF: p <0.0001 CF vs. PPH: p = 0.0001Alpha-1 vs. PPH: p = 0.0007 CF vs. Sarcoidosis: p = 0.0002Alpha-1 vs. Sarcoidosis p = .0492 COPD vs. IPF: p <0.0001

Note: Other comparisons are not statistically different. ISHLT 2007 J Heart Lung Transplant 2007;26: 782-795

ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis Conditional on

Survival to 3 Months (Transplants: January 1990 – June 2005)


CF

(N= 2,508)COPD

(N= 6,220)IPF

(N= 2,685)PPH

(N= 656)SARCOIDOSIS

(N=341)

1 89.1 90.7 89.9 86.0 90.1 82.6

3 72.8 72.9 70.6 67.7 76.3 66.4

5 61.2 61.3 54.1 52.8 64.5 59.3

7 49.8 52.6 39.9 40.0 54.6 51.9

10 35.7 40.9 22.6 23.6 39.0 40.4

Survival comparisonsAlpha-1 vs. CF: p =.0472 PPH vs. COPD: p < 0.0001Alpha-1 vs. COPD: p < 0.0001 PPH vs. IPF: p < 0.0001Alpha-1 vs. IPF: p < 0.0001 IPF vs. Sarcoidosis: p = 0.0209 CF vs. COPD: p < 0.0001CF vs. IPF: p < 0.0001

Note: Other comparisons are not statistically different.ISHLT 2007 J Heart Lung Transplant 2007;26: 782-795

ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis Conditional on Survival to 1 Year (Transplants: January 1990 – June 2005)


CF

(N=2,178)COPD

(N=5,378)IPF

(N=2,178)PPH

(N= 573)SARCOIDOSIS

(273)

1 100.0 99.9 100.0 100.0 99.8 100.0

3 81.7 80.3 78.5 78.7 84.5 80.4

5 68.7 67.5 60.1 61.4 71.5 71.8

7 55.9 57.9 44.4 46.6 60.5 62.9

10 40.1 45.0 25.2 27.4 43.2 48.9

Survival comparisonsAlpha-1 vs. IPF: p < 0.0001 Alpha-1 vs. COPD: p < 0.0001CF vs. COPD: p < 0.0001 CF vs. IPF: p < 0.0001PPH vs. COPD: p < 0.0001 PPH vs. IPF: p < 0.0001COPD vs. Sarcoidosis: p < 0.0001 IPF vs. Sarcoidosis: p = 0.0002

Note: Other comparisons are not statistically different.


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2005)

0

25

50

75

100

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

Su

rviv

al (

%)

Alpha-1 (N=1,844) CF (N= 2,947) COPD (N= 7,113)

IPF (N= 3,362) PPH (N= 926) Sarcoidosis (N=429)

HALF-LIFE Alpha-1: 5.7 Years; CF: 6.2 Years; COPD: 4.8 Years; IPF: 3.9 Years; PPH: 4.5 Years; Sarcoidosis: 4.8 Years

ISHLT 2007

Survival comparisonsAlpha-1 vs. CF: p = 0.0031Alpha-1 vs. COPD p = 0.0005Alpha-1 vs. IPF p < 0.0001Alpha-1 vs. PPH: p = 0.0007 Alpha-1 vs. Sarcoidosis: p = 0.0492CF vs. COPD: p < 0.0001CF vs. IPF: p < 0.0001CF vs. PPH: p < 0.0001CF vs. Sarcoidosis: p = 0.0002COPD vs. IPF: p <0.0001


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis Conditional on

Survival to 3 Months (Transplants: January 1990 – June 2005)

0

25

50

75

100

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

Su

rviv

al (

%)

Alpha-1 (N=1,547) CF (N= 2,508)COPD (N= 6,220) IPF (N= 2,685)PPH (N= 656) Sarcoidosis (N=341)


Survival comparisonsAlpha-1 vs. CF: p = 0.0472Alpha-1 vs. IPF: p < 0.0001 Alpha-1 vs. COPD: p < 0.0001CF vs. COPD: p < 0.0001 CF vs. IPF: p < 0.0001PPH vs. COPD: p < 0.0001 PPH vs. IPF: p < 0.0001IPF vs. Sarcoidosis: p = 0.0209


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis Conditional on Survival to 1 Year

(Transplants: January 1990 – June 2005)

0

25

50

75

100

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

Su

rviv

al (

%)

Alpha-1 (N=1,343) CF (N= 2,178)COPD (N= 5,378) IPF (N= 2,178)PPH (N= 573) Sarcoidosis (N=273)


Survival comparisonsAlpha-1 vs. IPF: p < 0.0001 Alpha-1 vs. COPD: p < 0.0001CF vs. COPD: p < 0.0001 CF vs. IPF: p < 0.0001PPH vs. COPD: p < 0.0001 PPH vs. IPF: p < 0.0001COPD vs. Sarcoidosis: p < 0.0001 IPF vs. Sarcoidosis: p = 0.0002


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival for Eisenmenger’s Syndrome


0

25

50

75

100

0 1 2 3 4 5Years

Su

rviv

al (%

)

ASD (N= 123) VSD (N= 57)

HALF-LIFE ASD: 2.9 Years; VSD: 1.0 Years

ISHLT 2007

p = 0.2632

N= 38

N= 15


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Procedure Type

(Transplants: January 1990 – June 2005) Diagnosis: Alpha-1 Antitrypsin Deficiency

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (%

)

Alpha-1/Single lung (N=944)

Alpha-1/Double lung (N=900)P = 0.0001

ISHLT 2007

N at risk at 10 years is 87 for Single Lung and 74 for Double Lung.


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Procedure Type and Age

(Transplants: January 1990 – June 2005) Diagnosis: Alpha-1 Antitrypsin Deficiency

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (

%)

Single Lung, < 50 (N=438) Double Lung, <50 (N =516)

Single Lung, 50+ (N = 506) Double Lung, 50+ (N = 384)

ISHLT 2007

N at risk at 10 years:

Single Lung, <50 = 57; Double Lung, <50 = 62; Single Lung, 50+ = 30; Double Lung, 50+ = 12

p = 0.0724


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type (Transplants: January 1990 – June 2005)

Diagnosis: Emphysema/COPD

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (

%)

COPD/Single lung (N=4,990)

COPD/Double lung (N=2,123) N=182

N=75

P < 0.0001


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

Years

Su

rviv

al (

%)

<50/Single lung (N=683) <50/Double lung (N=606)

50+/Single lung (N=4,307) 50+/Double lung (N=1,517)N=51N=131

N=33N=42

P < 0.0001


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type


Diagnosis: Idiopathic Pulmonary Fibrosis

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (

%)

IPF/Single lung (N=2,350)

IPF/Double lung (N=1,012)

N=64

N=18

P = 0.0301


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type

(Transplants: January 1990 – June 2005)Diagnosis: Primary Pulmonary Hypertension

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (

%)

PPH/Single lung (N=264)

PPH/Double lung (N=662)

N=35 at 10 years

N=43 at 10 years

P = 0.0532


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

Years

Su

rviv

al (

%)

COPD/Single lung/1990-1994 (N=1000)

COPD/Single lung/1995-1999 (N=1,761)

COPD/Single lung/2000-6/2005 (N=2,229)

Survival comparisons1990-1994 vs. 1995-1999: p = 0.51291990-1994 vs. 2000-6/2005: p = 0.00131995-1999 vs. 2000-6/2005: p = 0.0761




Diagnosis: Emphysema/COPD, Double Lung

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (

%)

COPD/Double lung/1990-1994 (N=204)

COPD/Double lung/1995-1999 (N=633)

COPD/Double lung/2000-6/2005 (N=1,286)





Diagnosis: Idiopathic Pulmonary Fibrosis, Single Lung

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (

%)

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

IPF/Single lung/1995-1999 (N=810)

IPF/Single lung/2000-6/2005 (N=1,084)





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=66)

IPF/Double lung/1995-1999 (N=259)

IPF/Double lung/2000-6/2005 (N=687)

Survival comparisons1990-1994 vs. 1995-1999: p = 0.95261990-1994 vs. 2000-6/2005: p = 0.00261995-1999 vs. 2000-6/2005: p < 0.0001


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

(Transplants: October 1999 – June 2005)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5

Years

Su

rviv

al (

%)

D(-)/R(-) (N=954)D(-)/R(+) (N=1,215)D(+)/R(-) (N=1,113)D(+)/R(+) (N=1,827)

Survival comparisonsD(-)/R(-) vs. D(+)/R(-): p = 0.0119D(-)/R(-) vs. D(+)/R(+): p = 0.0093D(-)/R(+) vs. D(+)/R(-): p = 0.0127D(-)/R(+) vs. D(+)/R(+): p = 0.0111


ADULT LUNG TRANSPLANTS (1995-6/2005) Risk Factors for 1 Year Mortality

DIAGNOSIS N

Relative Risk P-value

95% confidence

Interval

PPH 389 2.35 <.0001 1.74 -3.19

Pulmonary fibrosis (not IPF) 90 2.31 <.0001 1.60 -3.32

Sarcoidosis 276 1.82 <.0001 1.42 -2.34

Other diagnoses* 772 1.72 <.0001 1.42 -2.08

IPF 1961 1.53 <.0001 1.30 -1.80

Alpha-1 antitrypsin deficiency 826 1.48 <.0001 1.25 -1.75

Cystic fibrosis 1507 1.42 0.0029 1.13 -1.79

(N=10,415)

ISHLT 2007

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



DONOR CHARACTERISTICS N


95% Confidence

Interval

Donor history of diabetes 290 1.48 0.0008 1.18 -1.85

RECIPIENT CHARACTERISTICS

IV inotropes 72 1.78 0.0007 1.27 -2.49

Ventilator 234 1.75 <.0001 1.36 -2.24

Hospitalized (including ICU) 798 1.42 <.0001 1.21 -1.68

Prior sternotomy 384 1.24 0.0363 1.01 -1.51

Chronic steroid use 4801 1.10 0.0382 1.01 -1.20

Prior thoracotomy 854 0.81 0.0334 0.67 -0.98

ISHLT 2007

(N=10,415)



TRANSPLANT CHARACTERISTICS N Relative

Risk P-value

95% Confidence

Interval

Repeat transplant 248 1.53 0.0104 1.10 -2.11

Transplant year = 1995/1996 vs. 1999/2000

1716 1.23 0.0027 1.08 -1.41

Donor CMV +/ Recipient CMV - 1895 1.22 0.0002 1.10 -1.36

4, 5 or 6 HLA mismatches (vs. 0-3 mismatches)

9106 with 4, 5 or 6 HLA MM 1.18 0.0136 1.04 -1.34


2207 0.81 0.0028 0.71 -0.93


3087 0.68 <.0001 0.60 -0.78

ISHLT 2007

(N=10,415)


ADULT LUNG TRANSPLANTS (1/1995-6/2005) Risk Factors for 1 Year Mortality

Continuous Factors (see figures)

Recipient age

Donor age (borderline)

Recipient weight

Donor weight

PVR

Transplant center volume

Bilirubin

Recipient oxygen required at rest

Recipient FEV1 % predicted

Cardiac output



Recipient Age

0

0.5

1

1.5

2

25 30 35 40 45 50 55 60 65

Recipient Age

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p < 0.0001



Donor Age

0

0.5

1

1.5

2

15 20 25 30 35 40 45 50 55

Donor Age

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.083



Donor Weight

0

0.5

1

1.5

2

50 55 60 65 70 75 80 85 90 95

Donor Weight (kg)

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.012



Pre-Transplant Recipient Weight

0

0.5

1

1.5

2

45 55 65 75 85 95

Recipient weight (kg)

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.0078



Center volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50

Center Volume (cases per year)

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p < 0.0001



Recipient FEV1 (% predicted)

0

0.5

1

1.5

2

25 30 35 40 45 50 55 60 65 70Recipient FEV1 (% predicted)

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

P = 0.024



Recipient Pre-Transplant Bilirubin

0

0.5

1

1.5

2

2.5

0 0.5 1 1.5 2 2.5 3

Recipient Bilirubin (mg/dl)

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.0033



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)

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p < 0.0001



Recipient Pre-Transplant Cardiac Output

0

0.5

1

1.5

2

3 4 5 6 7

Cardiac output

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.009



Recipient PVR

0

0.5

1

1.5

2

1 2 3 4 5 6 7 8 9

PVR (Wood units)

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.022


ADULT LUNG TRANSPLANTS (1995-6/2005) Factors Not Significant for 1 Year Mortality

Recipient factors:Transfusions, recent infection requiring IV drug therapy, diabetes, sternotomy, dialysis, FVC, creatinine, PRA, chronic steroid use, height, gender, history of cancer

Donor factors:History of hypertension, history of cancer, cause of death, height, clinical infection, gender

Transplant factors:Ischemia time



Model including BMI

DIAGNOSIS N


95% confidence

Interval

PPH 389 2.40 <.0001 1.77 -3.25

Pulmonary fibrosis (not IPF) 90 2.35 <.0001 1.63 -3.38

Sarcoidosis 276 1.85 <.0001 1.44 -2.37

Other diagnoses* 772 1.73 <.0001 1.43 -2.09

IPF 1961 1.57 <.0001 1.33 -1.84

Alpha-1 antitrypsin deficiency 826 1.50 <.0001 1.27 -1.78

Cystic fibrosis 1507 1.38 0.0062 1.10 -1.74

(N=10,415)

ISHLT 2007




Model including BMI

DONOR CHARACTERISTICS N


95% Confidence

Interval

Donor history of diabetes 290 1.48 0.0008 1.17 -1.85


IV inotropes 72 1.81 0.0005 1.29 -2.53

Ventilator 234 1.74 <.0001 1.36 -2.23

Hospitalized (including ICU) 798 1.42 <.0001 1.20 -1.67


Chronic steroid use 4801 1.10 0.0416 1.00 -1.20


ISHLT 2007

(N=10,415)



Model including BMI

TRANSPLANT CHARACTERISTICS N Relative Risk

P-value 95%

Confidence Interval

Repeat transplant 248 1.51 0.0129 1.09 -2.09


1716 1.23 0.0030 1.07 -1.41

Donor CMV +/ Recipient CMV - 1895 1.22 0.0002 1.10 -1.36

4, 5 or 6 HLA mismatches (vs. 0-3 mismatches)

9106 with 4, 5 or 6 HLA MM

1.18 0.0143 1.03 -1.35


2207 0.81 0.0027 0.71 -0.93


3087 0.68 <.0001 0.60 -0.78

ISHLT 2007

(N=10,415)



Model including BMI


Recipient age

Recipient BMI (borderline)

Donor weight (borderline)

PVR


Bilirubin

Recipient oxygen required at rest


Cardiac output


ADULT LUNG TRANSPLANTS (1/1995-6/2005) Risk Factors for 1 Year Mortality (Model including BMI)

Recipient Age

0

0.5

1

1.5

2

25 30 35 40 45 50 55 60 65

Recipient Age

p < 0.0001

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



Donor Weight

0

0.5

1

1.5

2

50 55 60 65 70 75 80 85 90 95

Donor Weight (kg)

p = 0.058

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



Pre-Transplant Recipient BMI

0

0.5

1

1.5

2

17 20 23 26 29 32

Recipient BMI (kg/m2)

p = 0.092

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



Center volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50


p < 0.0001

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



Recipient FEV1 (% predicted)

0

0.5

1

1.5

2

25 30 35 40 45 50 55 60 65 70Recipient FEV1 (% predicted)

p = 0.0320

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



Recipient Pre-Transplant Bilirubin

0

0.5

1

1.5

2

2.5

0 0.5 1 1.5 2 2.5 3

Recipient Bilirubin (mg/dl)

p = 0.0013

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



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

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



Recipient Pre-Transplant Cardiac Output

0

0.5

1

1.5

2

3 4 5 6 7

Cardiac output

p = 0.0254

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



Recipient PVR

0

0.5

1

1.5

2

1 2 3 4 5 6 7 8 9

PVR (Wood units)

p = 0.018

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality


ADULT LUNG TRANSPLANTS (1995-6/2005) Diagnosis = COPD/EmphysemaRisk Factors for 1 Year Mortality

RECIPIENT CHARACTERISTICS N


95% Confidence Interval

Ventilator 44 2.66 .0002 1.60 -4.42

Hospitalized (including ICU) 160 1.61 .0090 1.13 -2.31

Chronic steroid use 2001 1.34 .0001 1.15 -1.55

TRANSPLANT CHARACTERISTICS

Transplant Year: 2001/2002 vs. 1999/2000 952 0.78 .0396 0.62 -0.99

Transplant Year: 2003/2005 vs. 1999/2000 1159 0.77 .0221 0.61 -0.96

Donor CMV +/ Recipient CMV - 617 1.32 .0045 1.09 -1.60

DONOR CHARACTERISTICS

Donor history of diabetes 119 1.53 .0301 1.04 -2.26

(N=4,235)ISHLT 2007 J Heart Lung Transplant 2007;26: 782-795

ADULT LUNG TRANSPLANTS (1/1995-6/2005)Diagnosis = COPD/Emphysema

Risk Factors for 1 Year Mortality


Recipient age

Oxygen required at rest

Cardiac output



PCO2 (borderline)


ADULT LUNG TRANSPLANTS (1/1995-6/2005) Diagnosis = COPD/Emphysema

Risk Factors for 1 Year MortalityRecipient Age

0

0.5

1

1.5

2

40 45 50 55 60 65

Recipient Age

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

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


Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.024



Risk Factors for 1 Year MortalityCardiac Output

0

0.5

1

1.5

2

3 4 5 6 7

Cardiac Output

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.029



Risk Factors for 1 Year Mortality Recipient Oxygen Required at Rest

0

0.5

1

1.5

2

0 1 2 3 4 5 6Recipient Oxygen Required at Rest (L/min)

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.008



Risk Factors for 1 Year Mortality Ischemia Time

0

0.5

1

1.5

2

0 1 2 3 4 5 6Ischemia time (hours)

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.029



Risk Factors for 1 Year Mortality Recipient PCO2 at Transplant

0

0.5

1

1.5

2

25 30 35 40 45 50 55 60 65 70Recipient PCO2 (mm/Hg)

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.064


ADULT LUNG TRANSPLANTS (1995-6/2005) Diagnosis = IPF

Risk Factors for 1 Year Mortality

RECIPIENT CHARACTERISTICS N Relative

Risk P-value

95% Confidence

Interval

Ventilator 43 2.54 0.0001 1.61 -3.99




Donor CMV+ / Recipient CMV- 350 1.51 0.0001 1.23 -1.87

Transplant Year: 2001/02 vs. 1999/2000 400 0.72 0.0223 0.54 -0.95

Transplant Year: 2003/05 vs. 1999/2000 741 0.60 0.0001 0.46 -0.78

(N=1,961)


ADULT LUNG TRANSPLANTS (1/1995-6/2005)

Diagnosis = IPFRisk Factors for 1 Year Mortality


Recipient age

Donor age


Donor weight

Bilirubin

Center volume (borderline)

PA diastolic pressure

Wedge pressure (borderline)

Oxygen required at rest

Cardiac output (borderline)


ADULT LUNG TRANSPLANTS (1/1995-6/2005) 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 = 0.048

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality



Risk Factors for 1 Year MortalityDonor Age

0

0.5

1

1.5

2

15 20 25 30 35 40 45 50 55

Donor Age

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.039



Risk Factors for 1 Year MortalityRecipient PA Diastolic Pressure

0

0.5

1

1.5

2

10 15 20 25 30

PA Diastolic Pressure

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.011



Risk Factors for 1 Year MortalityDonor Weight

0

0.5

1

1.5

2

50 60 70 80 90 100

Donor Weight (kg)

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.022


ADULT LUNG TRANSPLANTS (1/1995-6/2005)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)

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

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


Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.058



Risk Factors for 1 Year MortalityRecipient BMI

0

0.5

1

1.5

2

20 22 24 26 28 30 32

Recipient BMI (kg/m2)

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.078



Risk Factors for 1 Year MortalityRecipient Bilirubin

0

0.5

1

1.5

2

0 0.5 1 1.5 2

Bilirubin (mg/dl)

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.026



Risk Factors for 1 Year MortalityRecipient Cardiac Output

0

0.5

1

1.5

2

3 4 5 6 7

Cardiac Output

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.0505



Risk Factors for 1 Year MortalityRecipient Wedge Pressure

0

0.5

1

1.5

2

4 7 10 13 16 19

Pulmonary Capillary Wedge Pressure (mm/Hg)

Rela

tive R

isk o

f 1 Y

ear

Mo

rtality

.

p = 0.0682



DIAGNOSIS N Relative

Risk P-value 95% Confidence

Interval

PPH 238 1.60 .0089 1.13 -2.28

Other diagnoses* 401 1.25 .0118 1.05 -1.49

Alpha-1 antitrypsin deficiency 511 1.25 .0019 1.08 -1.44

LAM 59 0.53 .0155 0.32 -0.89


Recipient on IV inotropes 53 1.94 .0001 1.40 -2.69

Recipient on ventilator 135 1.43 .0060 1.11 -1.84

Recipient with prior sternotomy 199 1.31 .0035 1.09 -1.57

Recipient history of diabetes 335 1.24 .0048 1.07 -1.45

Hospitalized (including ICU) 454 1.23 .0090 1.05 -1.44

(N=5,640)

ISHLT 2007




DONOR CHARACTERISTICS N Relative

Risk P-value

95% Confidence Interval

Donor history of diabetes 125 1.40 .0030 1.12 -1.76

Donor cause of death = Anoxia 254 0.72 .0012 0.59 -0.88


4-6 total HLA mismatches 4907 1.23 .0005 1.09 -1.37

Transplant year: 1995/1996 vs. 1999/2000 1581 1.21 <.0001 1.11 -1.32

Donor CMV +/ Recipient CMV - 980 1.17 .0011 1.07 -1.29

(N=5,640)ISHLT 2007 J Heart Lung Transplant 2007;26: 782-795

ADULT LUNG TRANSPLANTS (1995-6/2001) Borderline Significant Risk Factors for 5 Year Mortality

VARIABLE N Relative

Risk P-value

95% Confidence

Interval

Repeat transplant 122 1.28 .0792 0.97 -1.68

DIagnosis: IPF 903 1.15 .0562 1.00 -1.34

Female donor/female recipient 1550 0.91 .0659 0.82 -1.01

Diagnosis: Cystic fibrosis 826 0.84 .0816 0.69 -1.02

(N=5,640)




Recipient age

Donor age

Donor height

Recipient BSA

Center volume

Oxygen at rest

FEV1 % predicted (borderline)

PA diastolic



Recipient Age

0

0.5

1

1.5

2

25 30 35 40 45 50 55 60 65

Recipient Age

Rela

tive R

isk o

f 5 Y

ear

Mo

rtalit

y

p < 0.0001



Donor Age

0

0.5

1

1.5

2

15 25 35 45 55Donor Age

Rela

tive R

isk o

f 5 Y

ear

Mo

rtalit

y

p = 0.008



Donor Height

0

0.5

1

1.5

2

155 160 165 170 175 180 185

Donor height (cm)

Rel

ativ

e R

isk

of

5 Y

ear

Mo

rtal

ity

p = 0.0013



Pre-Transplant Recipient Body Surface Area

0

0.5

1

1.5

2

1.5 1.6 1.7 1.8 1.9 2

Recipient BSA (m2)

Rel

ativ

e R

isk

of

5 Y

ear

Mo

rtal

ity

p = 0.0028



Pre-Transplant Recipient PA Diastolic Pressure

0

0.5

1

1.5

2

10 15 20 25 30 35 40

PA Diastolic (mm/Hg)

Rela

tive R

isk o

f 5 Y

ear

Mo

rtality

p = 0.029



Center Volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50

Center Volume (Cases per year)

Rela

tive R

isk o

f 5 Y

ear

Mo

rtality

p < 0.0001



Pre-Transplant Recipient FEV1 (% predicted)

0

0.5

1

1.5

2

10 20 30 40 50 60 70

Recipent FEV1 (% predicted)

Rela

tive R

isk o

f 5 Y

ear

Mo

rtalit

y

p = 0.08



Oxygen Required at Rest

0

0.5

1

1.5

2

0 1 2 3 4 5 6

Oxygen required at rest (L/min)

Rela

tive R

isk o

f 5 Y

ear

Mo

rtalit

y

p = 0.012


ADULT LUNG TRANSPLANTS (1995-6/2000) Factors Not Significant for 5 Year Mortality

Recipient factors:Transfusions, history of malignancy, cardiac output, PRA, FVC, PCO2, dialysis, recent infection requiring IV

drug therapy, PRA, bilirubin, creatinine

Donor factors:Clinical infection, history of hypertension, history of cancer, weight

Transplant factors:Ischemia time


ADULT LUNG TRANSPLANTS (1995-6/2001) Risk Factors for 5 Year MortalityConditional on Survival to 1 Year

DIAGNOSIS N Relative

Risk P-value

95% Confidence

Interval

PPH vs. COPD 148 0.71 0.0321 0.52 -0.97

Cystic Fibrosis vs. COPD 652 0.61 0.0002 0.47 -0.79

LAM vs. COPD 48 0.42 0.0151 0.21 -0.84

Pulmonary Fibrosis (not IPF) vs. COPD

28 0.37 0.0268 0.15 -0.89

(N=4,205)



DONOR, RECIPIENT AND TRANSPLANT CHARACTERISTICS N


95% Confidence

Interval

Donor cause of death = anoxia vs. head trauma

201 0.62 0.0006 0.47 -0.81

Recipient sternotomy prior to transplant

132 1.52 0.001 1.18 -1.95

Recipient diabetes 238 1.37 0.0034 1.11 -1.69

Transplant year: 1995/1996 vs. 1999-6/2001

1126 1.16 0.0192 1.02 -1.31

Transplant year: 1997/1998 vs. 1999-6/2001

1290 1.14 0.0308 1.01 -1.29

Number of mismatches at HLA A locus

2244 1 A MM; 1692 2 A MM

1.12 per MM

0.0112 1.03 -1.22

(N=4,205)ISHLT 2007



POST-TRANSPLANT FACTORS N Relative

Risk P-value

95% Confidence

Interval

Bronchiolitis obliterans within 1st year 302 2.26 <.0001 1.92 -2.66

Dialysis prior to discharge 82 1.39 .0467 1.00 -1.93

Rejection between discharge and 1 year 1403 1.29 <.0001 1.16 -1.43

Drug-treated infection prior to discharge 1630 1.24 <.0001 1.12 -1.38

(N=4,205)


ADULT LUNG TRANSPLANTS (1995-6/2001) Borderline Significant Risk Factors for 5 Year Mortality

Conditional on Survival to 1 Year

CHARACTERISTICS N Relative

Risk P-value

95% Confidence

Interval

Diagnosis = Sarcoidosis vs. COPD 96 0.7 0.0708 0.47 -1.03

(N=4,205)


ADULT LUNG TRANSPLANTS (1/1995-6/2001) Risk Factors for 5 Year Mortality Conditional on Survival to 1 Year


Recipient Age

Donor Age

Center Volume



ADULT LUNG TRANSPLANTS (1/1995-6/2001) Risk Factors for 5 Year Mortality Conditional on 1 Year Survival

Recipient Age

0

0.5

1

1.5

2

2.5

25 30 35 40 45 50 55 60 65

Recipient Age

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p < 0.0001



Donor Age

0

0.5

1

1.5

2

15 25 35 45 55Donor Age

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.026



Recipient BMI

0

0.5

1

1.5

2

18 20 22 24 26 28 30Recipient BMI (kg/m2)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.09



Center Volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50Center volume (cases per year)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.004


ADULT LUNG TRANSPLANTS (1995-6/2000) Factors Not Significant for Conditional 5 Year Mortality

Recipient factors:Ventilator, inotropes, hospitalized at transplant, pCO2, gender,

chronic steroid use, transfusions, history of malignancy, PRA, repeat transplant, FEV1, FVC, PA pressures, O2 required,

bilirubin, creatinine, recent infection requiring use of IV drug therapy, thoracotomy, cardiac output

Donor factors:Gender, clinical infection, history of hypertension, history of cancer, history of diabetes, weight


ADULT LUNG TRANSPLANTS (1995-6/2000) Factors Not Significant for Conditional 5 Year Mortality

Transplant factors:ABO compatibility, CMV mismatch

Post-transplant factors:Induction, stroke prior to discharge, prolonged graft dysfunction prior to discharge, treated for rejection prior to discharge


ADULT LUNG RECIPIENTSFunctional Status of Surviving Recipients

(Follow-ups: April 1994 – June 2006)

0%

20%

40%

60%

80%

100%

1 Year (N=6,596) 3 Year (N=4,176) 5 Year (N=2,402) 10 Year (N=398)

No Activity Limitations Performs with Some Assistance Requires Total Assistance


ADULT LUNG RECIPIENTSEmployment Status of Surviving Recipients

(Follow-ups: April 1994 – June 2006)

0%

20%

40%

60%

80%

100%

1 Year (N=7,327) 3 Year (N=4,443) 5 Year (N=2,648) 10 Year (N= 507)

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 2006)

0%

20%

40%

60%

80%

100%

1 Year (N=9,129) 3 Year (N=5,589) 5 Year (N=3,338) 10 Year (N=592)

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

Any Induction (N =2,482)

Polyclonal ALG/ATG (N= 565)

IL2R-antagonist (N =1,752)

Campath (N = 148)

% o

f p

atien

tsADULT LUNG RECIPIENTS

Induction Immunosuppression (Transplants: January 2002 - June 2006)Analysis limited to patients receiving prednisone


0

10

20

30

40

50

% o

f p

ati

en

ts

ADULT LUNG RECIPIENTSInduction Immunosuppression (Transplants: January 2000 - December 2005)

Analysis limited to patients receiving prednisone

ISHLT 2007

Any Induction Polyclonal ALG/ATG IL2R-antagonist Campath


SURVIVAL BY INDUCTION USAGE For Adult Lung Recipients (Transplants: April 1994-June 2005)

Conditional on survival to 14 days

0

20

40

60

80

100

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

Su

rviv

al (

%)

No induction (N=6,589)

Induction (N=3,994)

p = 0.0001

ISHLT 2007

At 10 years there were 105 patients at risk in the induction group and 219 in the no induction group.


SURVIVAL BY INDUCTION USAGE For Adult Lung Recipients (Transplants: January 2000-June 2005)

Conditional on survival to 14 days

0

20

40

60

80

100

0 1 2 3 4 5

Years

Su

rviv

al (

%)


Induction (N=2,605)

p =0.0004

ISHLT 2007

At 5 years there were 279 patients at risk in the induction group and 382 in the no induction group.


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine

% o

f P

ati

en

ts

Year 1 (N=4,488) Year 5 (N=1,973)

ADULT LUNG RECIPIENTSMaintenance Immunosuppression at Time of Follow-up

For follow-ups between January 2002 through June 2006 Analysis 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

atie

nts

1-Year Follow-Up 5-Year Follow-Up

Consecutive bars within each drug type represent follow-ups in 2002, 2003, 2004, 2005, & 2006.

ADULT LUNG RECIPIENTSMaintenance Immunosuppression at Time of Follow-up

For follow-ups between January 2002 through June 2006 Analysis limited to patients receiving prednisone



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 2006Analysis limited to patients receiving prednisone

1 Year Follow-up (N = 4,488) 5 Year Follow-up (N = 1,973)



0

20

40

60

80

100

Year 1 (N = 4,488) Year 5 (N = 1,973)

% o

f P

atie

nts

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 2006Conventional Combinations



0

10

20

30

40

50

Year 1 (N = 4,488) Year 5 (N = 1,973)

% o

f P

atie

nts

Other

Rapa + Cellcycle

Rapa + Calcineurin

Tacrolimus

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

For follow-ups between January 2002 through June 2006Other Combinations



PERCENTAGE OF ADULT LUNG TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR

Stratified by Type of Induction (Transplants: January 1, 2000 - June 30, 2005)

0

10

20

30

40

50

60

Overall

% tre

ate

d fo

r re

jectio

n w

ith

in 1

year

No induction (N=3,329) Polyclonal (N=862) IL2R-antagonist (N=1,700)

No induction vs. polyclonal (p < 0.0001); polyclonal vs. IL2R (p = 0.002); no induction vs. IL2R (p = 0.12)




0

10

20

30

40

50

60

70

18-34(N=866)

35-49(N=1,361)

50-59(N=2,254)

60-64(N=1,200)

65+(N=345)

F(N=2,927)

M(N=3,099)

% tre

ate

d fo

r re

jectio

n w

ith

in 1

year

No induction Polyclonal IL2R-antagonist

For female: no induction vs. polyclonal (p = 0.0017) ; polyclonal vs. IL2R (p = 0.067)For male: no induction vs. polyclonal (p = 0.0006); polyclonal vs. IL2R (p = 0.011)

35-49: no induct vs. poly (p=0.065); poly vs. IL2 (p = 0.046); 50-59: no induct vs. poly (p=0.015); no induct vs. IL2 (p = 0.091)60-64: no induct vs. poly (p = 0.0004); poly vs. IL2R (p=0.018); 65+: no induct vs. poly (p=0.077); poly vs IL2 (p = 0.027)


NUMBER OF REJECTION EPISODES FOR ADULT LUNG TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR


00.20.40.60.8

11.21.41.61.8

2

Overall

Avera

ge n

um

ber

of re

jectio

n e

pis

od

es


No induction vs. polyclonal (p < 0.0001); no induction vs. IL2R (p = 0.008); polyclonal vs. IL2R (p = 0.034).


NUMBER OF REJECTION EPISODES FOR ADULT LUNG TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR Stratified by Type of Induction (Transplants: January 1, 2000 - June 30, 2005)

0

0.5

1

1.5

2

2.5

18-34 35-49 50-59 60-64 65+ F M

Avera

ge n

um

ber

of re

jectio

n e

pis

od

es


18-34: no induct vs. poly (p=0.002); poly vs. IL2R (p=0.019); 35-49: no induct vs. IL2R (p=0.055)

50-59: no induct vs. poly (p=0.0007); poly vs. IL2R (p=0.028); 65+: no induct vs. poly (p=0.07); poly vs. IL2R (p=0.062)

Females: no induction vs. polyclonal (p = 0.030); no induction vs. IL2R (p = 0.025);

Males: no induction vs. polyclonal (p = 0.0003); polyclonal vs. IL2R (p = 0.0096)



Stratified by Maintenance Immunosuppression (Transplants: January 1, 2000 - June 30, 2005)

0

10

20

30

40

50

60

OverallCyclosporine + MMF (N=956) Cyclosporine + AZA (N=1,392) Tacrolimus + MMF (N=1,491) Tacrolimus + AZA (N=1,249)

% tre

ate

d fo

r re

jectio

n w

ith

in 1

year

CyA + MMF vs. TAC + AZA (p = 0.068); CyA + AZA vs. TAC + MMF (p = 0.0065); CyA + AZA vs. TAC + AZA (p = 0.0004)




0

10

20

30

40

50

60

70

80

18-34 35-49 50-59 60-64 65+ F M

Cyclosporine + MMF Cyclosporine + AZATacrolimus + MMF Tacrolimus + AZA

% tre

ate

d fo

r re

jectio

n w

ith

in 1

year

35-49: CyA + AZA vs. TAC + AZA (p = 0.0202)

50-59: CyA + MMF vs. TAC + MMF (p = 0.077); CyA + MMF vs. TAC + AZA (p = 0.0043); CyA + AZA vs. TAC + MMF (p = 0.056);

CyA + AZA vs. TAC + AZA (p = 0.0019)

60-64: CyA + MMF vs. CyA + AZA (p = 0.0103)

60+: CyA + AZA vs. TAC + MMF (p = 0.0466)

Females: CyA + AZA vs. TAC + AZA (p = 0.0214)

Males: CyA + MMF vs. TAC + MMF (p = 0.0037); CyA + AZA vs. TAC + AZA (p = 0.0081)


NUMBER OF REJECTION EPISODES FOR ADULT LUNG TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR Stratified by Maintenance Immunosuppression (Transplants: January 1, 2000 - June 30, 2005)

0

0.5

1

1.5

2

2.5

Overall

Avera

ge n

um

ber

of re

jectio

n e

pis

od

es

Cyclosporine + MMF Cyclosporine + AZA Tacrolimus + MMF Tacrolimus + AZA

CyA + MMF vs. CyA + AZA (p = 0.002); CyA + AZA vs. TAC + MMF (p < 0.0001); TAC + MMF vs. TAC + AZA (p = 0.026) ; CyA + AZA vs. TAC + AZA (p = 0.0682)


NUMBER OF REJECTION EPISODES FOR ADULT LUNG TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR


0

0.5

1

1.5

2

2.5

3

18-34 35-49 50-59 60-64 65+ F M

Avera

ge n

um

ber

of re

jectio

n e

pis

od

es

Cyclosporine + MMF Cyclosporine + AZATacrolimus + MMF Tacrolimus + AZA

18-34: CyA + AZA vs. TAC + MMF (p = 0.0119); TAC + MMF vs. TAC + AZA (p = 0.099) 50-59: CyA + AZA vs. TAC + MMF (p = 0.0644)60-64: CyA + MMF vs. CyA + AZA (p = 0.0232); CyA + AZA vs. TAC + MMF (p = 0.0103); CyA + TAC + AZA (p = 0.0944)65+: CyA + MMF vs. CyA + AZA (p = 0.0232)Female: CyA + MMF vs. TAC + MMF (p = 0.0633); CyA + AZA vs. TAC + MMF (p = 0.0003); CyA + AZA vs. TAC + AZA (p = 0.085); TAC + MMF vs. TAC + AZA (p = 0.0610)Male: CyA + MMF vs. CyA + AZA (p = 0.0072); CyA + AZA vs. TAC + MMF (p = 0.0391)


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 2006

Outcome Within 1

Year

Total number with known response

Within 1 Year


Hypertension 48.9% (N = 3,805) 54.0% (N = 5,131)

Renal Dysfunction 23.2% (N = 3,722) 27.1% (N = 5,329)

Abnormal Creatinine < 2.5 mg/dl 12.9% 19.8%

Creatinine > 2.5 mg/dl 8.5% 5.5%

Chronic Dialysis 1.7% 1.7%

Renal Transplant 0.0% 0.1%

Hyperlipidemia 13.1% (N = 3,952) 26.0% (N = 5,514)

Diabetes 17.0% (N = 3,764) 29.6% (N = 5,254)

Bronchiolitis Obliterans 10.6% (N = 3,424) 7.3% (N = 4,872)


POST-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 1 and 5 Years

Post-Transplant (Follow-ups: April 1994 - June 2006)

Outcome Within 1

Year


Within 5 Years


Hypertension 51.9% (N = 8,936) 85.6% (N = 2,177)

Renal Dysfunction 25.5% (N = 9,051) 37.8% (N = 2,344)

Abnormal Creatinine < 2.5 mg/dl 17.0% 23.0%

Creatinine > 2.5 mg/dl 6.8% 11.0%

Chronic Dialysis 1.7% 3.2%

Renal Transplant 0.0% 0.6%

Hyperlipidemia 20.6% (N = 9,466) 52.2% (N = 2,413)

Diabetes 24.3% (N = 9,018) 33.5% (N = 2,160)

Bronchiolitis Obliterans 8.7% (N = 8,296) 33.3% (N = 1,771)


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


Outcome Within 10

Years


Hypertension 98.2% (N = 227)

Renal Dysfunction 40.5% (N = 262)

Abnormal Creatinine < 2.5 mg/dl 21.4% Creatinine > 2.5 mg/dl 9.2% Chronic Dialysis 7.3% Renal Transplant 2.7%

Hyperlipidemia 65.1% (N = 272)

Diabetes 33.2% (N = 229)

Bronchiolitis Obliterans 42.7% (N = 150)


FREEDOM FROM BRONCHIOLITIS OBLITERANSFor Adult Lung Recipients (Follow-ups: April 1994-June 2006)

Conditional on Survival to 14 days

0

20

40

60

80

100

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

% F

reed

om

fro

m O

B

Freedom from Bronch Oblit (N=10,173)


FREEDOM FROM BRONCHIOLITIS OBLITERANS STRATIFIED BY INDUCTION USE

For Adult Lung Recipients Follow-ups: April 1994-June 2006)Conditional on Survival to 14 days

0

20

40

60

80

100

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

% F

reed

om

fro

m O

B


Induction (N=3,057)

p = 0.9244


FREEDOM FROM SEVERE RENAL DYSFUNCTION*For Adult Lung Recipients (Follow-ups: April 1994-June 2006)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10

Years

% F

reed

om

fro

m S

ever

e R

enal

D

ysfu

nct

ion

* 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 2006)

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

No Malignancy 9064 (96.3%) 2108 (87.6%) 204 (75.0%)

Malignancy (all types combined) 346 (3.7%) 299 (12.4%) 68 (25.0%)

Malignancy Type*

Skin 82 160 45

Lymph 161 59 16

Other 83 91 15

Type Not Reported

20 11 1

* 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; 0), 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 2006)

50

60

70

80

90

100

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

% F

ree

fro

m M

alig

nan

cy

All malignancy Lymph Skin Other


ADULT LUNG TRANSPLANT RECIPIENTS: Cause Of Death (Deaths: January 1992- June 2006)

CAUSE OF DEATH0-30 Days

(N = 1,427)

31 Days –

1 Year

(N = 2,128)

>1 Year –

3 Years

(N = 1,827)

>3 Years –

5 Years

(N = 1063)

>5 Years – 10 Years

(N = 1,097)

>10 Years

(N = 148)

BRONCHIOLITIS 6 (0.4%) 103 (4.8%) 505 (27.6%) 319 (30.0%) 295 (26.9%) 35 (23.6%)

ACUTE REJECTION 67 (4.7%) 43 (2.0%) 34 (1.9%) 9 (0.8%) 8 (0.7%) 0

LYMPHOMA 1 (0.1%) 55 (2.6%) 39 (2.1%) 17 (1.6%) 31 (2.8%) 7 (4.7%)

MALIGNANCY, OTHER 1 (0.1%) 55 (2.6%) 104 (5.7%) 83 (7.8%) 94 (8.6%) 11 (7.4%)

CMV 0 72 (3.4%) 22 (1.2%) 4 (0.4%) 3 (0.3%) 0

INFECTION, NON-CMV 290 (20.3%) 775 (36.4%) 439 (24.0%) 195 (18.3%) 198 (18.0%) 24 (16.2%)

GRAFT FAILURE 404 (28.3%) 409 (19.2%) 335 (18.3%) 200 (18.8%) 197 (18.0%) 34 (23.0%)

CARDIOVASCULAR 154 (10.8%) 89 (4.2%) 57 (3.1%) 51 (4.8%) 57 (5.2%) 9 (6.1%)

TECHNICAL 117 (8.2%) 58 (2.7%) 13 (0.7%) 3 (0.3%) 3 (0.3%) 1 (0.7%)

OTHER 387 (27.1%) 469 (22.0%) 279 (15.3%) 185 (17.1%) 211 (19.2%) 27 (18.2%)


LUNG TRANSPLANTATION Overall ISHLT 2007 J Heart Lung Transplant 2007;26: 782-795.

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Transcript of LUNG TRANSPLANTATION Overall ISHLT 2007 J Heart Lung Transplant 2007;26: 782-795.