LUNG TRANSPLANTATION Overall ISHLT 2008 J Heart Lung Transplant 2008;27: 937-983.

LUNG TRANSPLANTATION

Overall

ISHLT 2008 J Heart Lung Transplant 2008;27: 937-983

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 2008

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 45 83189

418

707

923

1087

122913661375

146114571481

15741615

1788

21962168

1789

1924

J Heart Lung Transplant 2008;27: 937-983

AVERAGE CENTER VOLUMELung Transplants: January 1, 2000 - June 30, 2007

50

28 2818 16

610

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, 2007

3.27.9

18.821.5

27.5

19

2.10

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

.


LUNG TRANSPLANTS: Transplant Recipient Age by Year of Transplant

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

Year of Transplant

% o

f T

ran

sp

lan

ts

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

0

10

20

30

40

50

60

Me

an

do

no

r a

ge

(y

ea

rs)

Mean Age

ISHLT 2008

Transplants between January 1987 and June 2007


AGE DISTRIBUTION OF LUNG TRANSPLANT RECIPIENTS (1/1985-6/2007)

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 = 4,659)

1995-1999 (N = 7,126)

2000-6/2007 (N = 14,096)

p < 0.0001

ISHLT 2008

Transplants with unknown recipient age were excluded from this tabulation.


LUNG TRANSPLANTS: Donor Age by Year of Transplant

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

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

ISHLT 2008



DONOR AGE DISTRIBUTION FOR LUNG TRANSPLANTS (1/1985-6/2007)

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 = 4,565)

1995-1999 (N = 6,989)

2000-6/2007 (N = 14,002)

p < 0.0001

ISHLT 2008

Transplants with unknown donor age were excluded from this tabulation.


LUNG TRANSPLANTATION

Adult Recipients


AGE DISTRIBUTION OF ADULT LUNG TRANSPLANT RECIPIENTS (1/1985-6/2007)

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 = 5,716)

1996-6/2007 (N = 19,010 )

p < 0.0001

ISHLT 2008

Mean age by era1985-1995 = 45.0 years1996-6/2006 = 49.1 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=4,434)1995-1999 (N=6,728)2000-6/2007 (N=13,564)

p < 0.0001

ISHLT 2008

Mean age by era1985-1994 = 44.7 years1995-1999 = 47.3 years2000-6/2007 = 49.8 years


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival (Transplants: January 1994 - June 2006)

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=10,064)

Single Lung (N=9,384)

All Lungs (N=19,448)

Double lung: 1/2-life = 6.2 Years; Conditional 1/2-life = 8.8 YearsSingle lung: 1/2-life = 4.5 Years; Conditional 1/2-life = 6.4 YearsAll lungs: 1/2-life = 5.2 Years; Conditional 1/2-life = 7.3 Years

P < 0.0001


ADULT LUNG TRANSPLANTATION: Indications (1/1995-6/2007)

DIAGNOSIS SLT (N = 9,017) BLT (N = 10,775) TOTAL (N = 19,792)

COPD/Emphysema 4,549 ( 50% ) 2,637 ( 24% ) 7,186 ( 36% )

Idiopathic Pulmonary Fibrosis 2,497 ( 28% ) 1,472 ( 14% ) 3,969 ( 20% )

Cystic Fibrosis 169 ( 1.9% ) 3,049 ( 28% ) 3,218 ( 16% )

Alpha-1 644 ( 7.1% ) 865 ( 8.0% ) 1,509 ( 7.6% )

Primary Pulmonary Hypertension 67 ( 0.7% ) 622 ( 5.8% ) 689 ( 3.5% )

Sarcoidosis 191 ( 2.1% ) 324 ( 3.0% ) 515 ( 2.6% )

Bronchiectasis 35 ( 0.4% ) 519 ( 4.8% ) 554 ( 2.8% )

LAM 64 ( 0.7% ) 130 ( 1.2% ) 194 ( 1.0% )

Congenital Heart Disease 17 ( 0.2% ) 138 ( 1.3% ) 155 ( 0.8% )

Re-Transplant: Obliterative Bronchiolitis

124 ( 1.4% ) 109 ( 1.0% ) 233 ( 1.2% )

Obliterative Bronchiolitis

(Not Re-Transplant)

48 ( 0.5% ) 114 ( 1.1% ) 162 ( 0.8% )

Re-Transplant: Not Obliterative Bronchiolitis

93 ( 1.0% ) 81 ( 0.8% ) 174 ( 0.9% )

Connective Tissue Disease 61 ( 0.7% ) 92 ( 0.9% ) 153 ( 0.8% )

Interstitial Pneumonitis 29 ( 0.3% ) 16 ( 0.1% ) 45 ( 0.2% )

Cancer 6 ( 0.1% ) 13 ( 0.1% ) 19 ( 0.1% )

Other 423 ( 4.7% ) 594 ( 5.5% ) 1,017 ( 5.1% )


ADULT LUNG TRANSPLANTATION: Distribution of Procedure Type for Major Indications (1992-2006)

ISHLT 2008

Year of TX

Alpha-1 COPD Cystic Fibrosis IPF PPH

Double Single Double Single Double Single Double Single Double Single

1992 27.0 73.0 15.7 84.3 97.0 3.0 10.3 89.7 26.3 73.7

1993 38.1 61.9 15.5 84.5 94.8 5.2 16.5 83.5 53.8 46.2

1994 41.7 58.3 17.9 82.1 85.8 14.2 14.0 86.0 64.6 35.4

1995 43.7 56.3 20.9 79.1 89.5 10.5 27.9 72.1 90.5 9.5

1996 44.3 55.7 26.6 73.4 87.0 13.0 26.6 73.4 82.0 18.0

1997 45.7 54.3 26.7 73.3 92.8 7.2 22.2 77.8 90.0 10.0

1998 47.3 52.7 28.9 71.1 92.5 7.5 20.1 79.9 86.8 13.2

1999 47.3 52.7 27.1 72.9 90.5 9.5 23.1 76.9 86.0 14.0

2000 57.1 42.9 28.4 71.6 95.0 5.0 32.6 67.4 92.0 8.0

2001 58.9 41.1 27.6 72.4 94.5 5.5 28.7 71.3 90.7 9.3

2002 53.5 46.5 37.2 62.8 96.4 3.6 35.1 64.9 88.3 11.7

2003 65.1 34.9 39.9 60.1 96.1 3.9 40.9 59.1 94.5 5.5

2004 72.1 27.9 43.5 56.5 96.2 3.8 43.4 56.6 93.9 6.1

2005 75.5 24.5 48.0 52.0 97.8 2.2 45.6 54.4 88.1 11.9

2006 76.4 23.6 57.4 42.6 99.1 0.9 49.2 50.8 100.0 0.0


ADULT LUNG TRANSPLANTATIONProcedure Type within Indication, by Year

0

10

20

30

40

50

60

70

80

90

100

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

% o

f tr

ansp

lan

ts

Bilateral/Double Lung Transplant Single Lung Transplant

AT Def COPD IPF PPH

2008

ISHLTJ Heart Lung Transplant 2008;27: 937-983

ADULT LUNG TRANSPLANTATION: Indications for Single Lung Transplants (Transplants: January 1995 - June 2007)

50%

28%

2%1%

2%

7%

10%

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

ISHLT 2008

*Other includes:

Sarcoidosis: 2.1%

Bronchiectasis: 0.4%

Congenital Heart Disease: 0.2%

LAM: 0.7%

OB (non-ReTx): 0.5%

Miscellaneous: 5.8%


ADULT LUNG TRANSPLANTATION: Indications for Bilateral/Double Lung Transplants (Transplants: January 1995 - June 2007)

24%

14%

18%

8%

28%

6% 2%

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

ISHLT 2008

*Other includes:

Sarcoidosis: 3.0%

Bronchiectasis: 4.8%

Congenital Heart Disease: 1.3%

LAM: 1.2%

OB (non-ReTx): 1.1%

Miscellaneous: 6.6%


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 60-65 years 66+ years

ADULT LUNG TRANSPLANTS:AGE DISTRIBUTION BY LOCATION Transplants between January 2000 and June 2007


0%

20%

40%

60%

80%

100%


Nu

mb

er

of

Tra

ns

pla

nts

-

Sarcoidosis

Re-TX

PPH

Other

IPF

CF

COPD

Bronchiectasis

Alpha-1

ADULT LUNG TRANSPLANTS:DIAGNOSIS DISTRIBUTION BY LOCATION



0%

20%

40%

60%

80%

100%


% o

f Don

ors

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

ADULT LUNG TRANSPLANTS:DONOR AGE DISTRIBUTION BY LOCATION



ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Era (Transplants: January 1988 – June 2006)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (

%)

1988-1994 (N=4,390)1995-1999 (N=6,728)2000-6/2006 (N=11,537)

1988-1994: 1/2-life = 3.9 Years; Conditional 1/2-life = 6.9 Years1995-1999: 1/2-life = 4.5 Years; Conditional 1/2-life = 7.2 Years2000-6/2006: 1/2-life = 5.5 Years; Conditional 1/2-life = 7.1 Years

N at risk = 159

N at risk = 523

N at risk = 762

Survival comparisons by era1988-94 vs. 1995-99: p = 0.00091988-94: vs. 2000-6/06: p <0.0001 1995-99 vs. 2000-6/06: p <0.0001


ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Age Group (Transplants: January 1990 – June 2006)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al

(%)

.

18-34 (N= 4,033)35-49 (N= 6,051)50-59 (N= 8,209)60-65 (N= 3,579)66+ (N= 527)

Survival comparisons18-34 vs. 35-49: p=0.4384; 18-34 vs. 50-59, 60-65 and 66+ : p < 0.000135-49 vs. 50-59, 60-65 and 66+: p < 0.000150-59 vs. 60-65 and vs. 66+: p < 0.000160-65 vs. 66+: p =0.0011

HALF-LIFE 18-34: 5.5 Years; 35-49: 6.0 Years; 50-59: 4.9 Years; 60-65: 4.1 Years; 66+: 3.0 Years


ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Gender (Transplants: January 1990 – June 2006)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al

(%)

Male (N=11,671)

Female (N=10,724)

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

p = 0.0013

N at risk at 5 years=3,053

N at risk =633

N at risk at 5 years=2,867

N at risk =622


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2006)

YearALPHA-1 (N=1,925)

CF

(N=3,275)COPD

(N=7,760)IPF

(N=3,931)PPH

(N=970)SARCOIDOSIS

(N=506)

1 77.9 81.8 82.1 72.5 67.2 69.9

3 63.9 66.2 65 57.1 57 56.5

5 54.1 56 50 44.6 48.5 50.8

7 44 48.3 37.4 33.8 41.5 42.7

10 31.2 38.6 21.8 21.1 30 31

Survival comparisonsAlpha-1 vs. CF: p = 0.0003 CF vs. COPD: p < 0.0001Alpha-1 vs. COPD: p = 0.0009 CF vs. IPF: p < 0.0001Alpha-1 vs. IPF: p < 0.0001 CF vs. PPH: p < 0.0001Alpha-1 vs. PPH: p = 0.0027 CF vs. Sarcoidosis: p < 0.0001Alpha-1 vs. Sarcoidosis p = 0.0263 COPD vs. IPF: p <0.0001

Note: Other comparisons are not statistically different. ISHLT 2008 J Heart Lung Transplant 2008;27: 937-983

ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis Conditional on

Survival to 3 Months (Transplants: January 1990 – June 2006)


CF

(N=2,851)COPD

(N=6,892)IPF

(N=3,197)PPH

(N=697)SARCOIDOSIS

(N=410)

1 89.3 91.1 90.2 86.4 90.8 84.2

3 73.2 73.8 71.4 68 76.9 68

5 62 62.4 54.9 53.2 65.4 61.1

7 50.5 53.8 41.1 40.3 56.1 51.4

10 35.8 43 23.9 25.1 40.5 37.3

Survival comparisonsAlpha-1 vs. CF: p = 0.0081 CF vs. Sarcoidosis : p = 0.0137 Alpha-1 vs. COPD: p < 0.0001 PPH vs. COPD: p < 0.0001Alpha-1 vs. IPF: p < 0.0001 PPH vs. IPF: p < 0.0001Alpha-1 vs. PPH: p = 0.0094 PPH vs. Sarcoidosis: p = 0.0105CF vs. COPD: p < 0.0001 COPD vs. IPF: p = 0.0319CF vs. IPF: p < 0.0001 IPF vs. Sarcoidosis: p = 0.0252

Note: Other comparisons are not statistically different.ISHLT 2008


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis Conditional on Survival to 1 Year (Transplants: January 1990 – June 2006)


CF

(N=2,475)COPD

(N=5,983)IPF

(N=2,595)PPH

(N=616)SARCOIDOSIS

(N=319)

1 100 99.8 100 99.9 99.8 100

3 82 80.9 79.1 78.6 84.6 80.8

5 69.4 68.4 60.8 61.5 72 72.6

7 56.5 58.9 45.5 46.6 61.7 61.1

10 40.1 47.2 26.5 29 44.6 44.3

Survival comparisonsAlpha-1 vs. IPF: p < 0.0001 Alpha-1 vs. COPD: p < 0.0001Alpha-1 vs. PPH: p = 0.0200 CF vs. COPD: p < 0.0001CF vs. IPF: p < 0.0001 PPH vs. COPD: p < 0.0001PPH vs. IPF: p < 0.0001 COPD vs. Sarcoidosis: p = 0.0001IPF vs. Sarcoidosis: p = 0.0006

Note: Other comparisons are not statistically different.


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2006)

0

25

50

75

100

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

Su

rviv

al (

%)

Alpha-1 (N=1,925) CF (N=3,275) COPD (N=7,760)

IPF (N=3,931) PPH (N=970) Sarcoidosis (N=506)

HALF-LIFE Alpha-1: 5.9 Years; CF: 6.4 Years; COPD: 5.0 Years; IPF: 4.1 Years; PPH: 4.6 Years; Sarcoidosis: 5.1 Years

ISHLT 2008

Survival comparisonsAlpha-1 vs. CF: p = 0.0003Alpha-1 vs. COPD p = 0.0009Alpha-1 vs. IPF p < 0.0001Alpha-1 vs. PPH: p = 0.0027Alpha-1 vs. Sarcoidosis: p = 0.0263CF vs. COPD: p < 0.0001CF vs. IPF: p < 0.0001CF vs. PPH: p < 0.0001CF vs. Sarcoidosis: p < 0.0001COPD vs. IPF: p <0.0001


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis Conditional on

Survival to 3 Months (Transplants: January 1990 – June 2006)

0

25

50

75

100

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

Su

rviv

al

(%)

Alpha-1 (N=1,655) CF (N= 2,851)COPD (N=6,892) IPF (N=3,197)PPH (N=697) Sarcoidosis (N=410)


ISHLT 2008

Survival comparisonsAlpha-1 vs. CF: p = 0.0081Alpha-1 vs. IPF: p < 0.0001 Alpha-1 vs. COPD: p < 0.0001Alpha-1 vs. PPH: p = 0.0094CF vs. COPD: p < 0.0001 CF vs. IPF: p < 0.0001CF vs. Sarcoidosis: p = 0.0137PPH vs. COPD: p < 0.0001 PPH vs. IPF: p < 0.0001PPH vs. Sarcoidosis: p = 0.0105COPD vs. IPF: p = 0.0319IPF vs. Sarcoidosis: p = 0.0252


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

(Transplants: January 1990 – June 2006)

0

25

50

75

100

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

Su

rviv

al

(%)

Alpha-1 (N=1,442) CF (N=2,475)COPD (N=5,983) IPF (N=2,595)PPH (N=616) Sarcoidosis (N=319)


ISHLT 2008

Survival comparisonsAlpha-1 vs. IPF: p < 0.0001 Alpha-1 vs. COPD: p < 0.0001Alpha-1 vs. PPH: p=0.0200CF 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 = 0.0001IPF vs. Sarcoidosis: p = 0.0006


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=100) VSD (N= 56)

HALF-LIFE ASD: 3.9 Years; VSD: 1.1 Years

ISHLT 2008

p = 0.0860

N at risk= 35

N at risk = 14


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Procedure Type

(Transplants: January 1990 – June 2006) 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=969)

Alpha-1/Double lung (N=956)P = 0.0012

ISHLT 2008

N at risk = 80

N at risk = 106

N at risk at 5 years = 354



ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Procedure Type and Age

(Transplants: January 1990 – June 2006) 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 = 443) Double Lung, <50 (N = 529)

Single Lung, 50+ (N = 526) Double Lung, 50+ (N = 427)

ISHLT 2008

N at risk at 10 years:

Single Lung, <50 = 67; Double Lung, <50 = 65; Single Lung, 50+ = 39; Double Lung, 50+ = 15

p = 0.0654


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type (Transplants: January 1990 – June 2006)

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=5,316)

COPD/Double lung (N=2,444)N=231

N=90

P < 0.0001

ISHLT 2008


N at risk at 5 years = 1,571


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=689) <50/Double lung (N=631)

50+/Single lung (N=4,627) 50+/Double lung (N=1,813)N=60N=171

N=38N=52

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=2,641)

IPF/Double lung (N=1,290) N=87

N=27

P = 0.0133

ISHLT 2008




ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type

(Transplants: January 1990 – June 2006)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=260)

PPH/Double lung (N=710)N=35

N=56N at risk at 5 years = 80


P = 0.0051


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=1,002)

COPD/Single lung/1995-1999 (N=1,764)

COPD/Single lung/2000-6/2006 (N=2,550)

Survival comparisons1990-1994 vs. 1995-1999: p = 0.28291990-1994 vs. 2000-6/2006: p = 0.00021995-1999 vs. 2000-6/2006: p = 0.0203

N=43

N=87

N=144




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=197)

COPD/Double lung/1995-1999 (N=628)

COPD/Double lung/2000-6/2006 (N=1,619)


N=20

N=48

N=42




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/2000-6/2006 (N=1,375)


N=16

N=37

N=50




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=257)

IPF/Double lung/2000-6/2006 (N=966)

Survival comparisons1990-1994 vs. 1995-1999: p = 0.73311990-1994 vs. 2000-6/2006: p = 0.00631995-1999 vs. 2000-6/2006: p < 0.0001

N=40

N=20

N=10


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

(Transplants: October 1999 – June 2006)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5

Years

Su

rviv

al (

%)

D(-)/R(-) (N=1,175)D(-)/R(+) (N=1,560)D(+)/R(-) (N=1,396)D(+)/R(+) (N=2,438)

Survival comparisonsD(-)/R(-) vs. D(+)/R(-): p = 0.0003D(-)/R(-) vs. D(+)/R(+): p < 0.0001D(-)/R(+) vs. D(+)/R(-): p = 0.0019D(-)/R(+) vs. D(+)/R(+): p = 0.0004


ADULT LUNG TRANSPLANTS (1995-6/2006) Risk Factors for 1 Year Mortality

DIAGNOSIS Procedure type N

Relative Risk P-value

95% conf. Interval

PPH All 398 2.53 <0.0001 1.87 -3.42

Pulmonary Fibrosis (not IPF)

All 111 2.3 <0.0001 1.63 -3.25

Sarcoidosis Double 194 2.02 <0.0001 1.50 -2.72

Other* All 852 1.89 <0.0001 1.59 -2.24

Alpha-1 antitrypsin deficiency

Single 387 1.68 <0.0001 1.35 -2.10

IPF Double 775 1.64 <0.0001 1.33 -2.02

Sarcoidosis Single 129 1.62 0.009 1.13 -2.33

IPF Single 1495 1.4 0.0002 1.17 -1.67

Alpha-1 antitrypsin deficiency

Double 424 1.37 0.0134 1.07 -1.76

Cystic fibrosis All 1569 1.31 0.0257 1.03 -1.66

(N=11,079)

ISHLT 2008

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



DONOR CHARACTERISTICS N Relative

Risk P-value

95% Confidence

Interval

Donor history of diabetes 327 1.40 0.0032 1.12 -1.74

RECIPIENT CHARACTERISTICS

IV inotropes 70 1.75 0.0014 1.24 -2.45

Ventilator 274 1.60 0.0001 1.27 -2.02

Hospitalized (including ICU) 934 1.51 <0.0001 1.29 -1.76

Prior sternotomy 367 1.20 0.0813 0.98 -1.47

Chronic steroid use 5224 1.15 0.0015 1.06 -1.26

ISHLT 2008

(N=11,079)



TRANSPLANT CHARACTERISTICS N Relative

Risk P-value

95% Confidence

Interval

Transplant year = 1995/1996 vs. 2005/2006

1473 1.93 <0.0001 1.66 -2.25


1632 1.58 <0.0001 1.35 -1.84


1656 1.56 <0.0001 1.34 -1.81

Donor CMV +/ Recipient CMV - 2070 1.22 0.0002 1.10 -1.35

Male donor/female recipient 5317 0.88 0.0487 0.78 -1.00

ISHLT 2008

(N=11,079)


ADULT LUNG TRANSPLANTS (1995-6/2006) Borderline Significant Risk Factors for 1 Year Mortality

TRANSPLANT CHARACTERISTICS N Relative

Risk P-value

95% Confidence

Interval

0-3 HLA mismatches vs. 4-6 mismatches

1470 0.89 0.065 0.78 -1.01

ISHLT 2008

(N=11,079)


ADULT LUNG TRANSPLANTS (1/1995-6/2006) Risk Factors for 1 Year Mortality

Continuous Factors (see figures)

Recipient age

Transplant center volume

Cardiac output

PVR (borderline)

Bilirubin

Recipient oxygen required at rest

Recipient FEV1 % predicted (borderline)



Recipient Age

0

0.5

1

1.5

2

25 30 35 40 45 50 55 60 65

Recipient Age

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p < 0.0001



Center Volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50

Center Volume (cases per year)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

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)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0133



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)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p < 0.0001



Recipient Pre-Transplant Cardiac Output

0

0.5

1

1.5

2

3 4 5 6 7

Cardiac output

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.018



Recipient FEV1 (% predicted)

0

0.5

1

1.5

2

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

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.069



Recipient PVR

0

0.5

1

1.5

2

1 2 3 4 5 6 7 8 9

PVR (Wood units)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.083


ADULT LUNG TRANSPLANTS (1995-6/2006) Diagnosis = COPD/EmphysemaRisk Factors for 1 Year Mortality

RECIPIENT CHARACTERISTICS N


95% Confidence Interval

Ventilator 44 3.20 .0000 1.97 -5.20

Hospitalized (including ICU) 181 1.69 .0023 1.21 -2.37

Chronic steroid use 2073 1.39 .0000 1.20 -1.62

TRANSPLANT CHARACTERISTICS

Transplant Year: 1995/1996 vs. 2005/2006 581 1.58 .0016 1.19 -2.10


Donor CMV +/ Recipient CMV - 665 1.31 .0050 1.09 -1.58

DONOR CHARACTERISTICS

Donor history of diabetes 132 1.64 .0084 1.14 -2.37

(N=4,384)ISHLT 2008 J Heart Lung Transplant 2008;27: 937-983

ADULT LUNG TRANSPLANTS (1995-6/2006) Diagnosis = COPD/Emphysema

Borderline Significant Risk Factors for 1 Year Mortality

TRANSPLANT CHARACTERISTICS N




DONOR CHARACTERISTICS

Donor history of malignancy 61 0.47 .0968 0.20 -1.14


ADULT LUNG TRANSPLANTS (1/1995-6/2006)Diagnosis = COPD/Emphysema

Risk Factors for 1 Year Mortality


Recipient age

Oxygen required at rest

Bilirubin (borderline)

Transplant center volume

PCO2 (borderline)


ADULT LUNG TRANSPLANTS (1/1995-6/2006) 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

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p < 0.0001


ADULT LUNG TRANSPLANTS (1/1995-6/2006) Diagnosis = COPD/Emphysema

Risk Factors for 1 Year MortalityCenter volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50


Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p < 0.0001



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)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.028



Risk Factors for 1 Year Mortality Recipient Pre-Transplant Bilirubin

0

0.5

1

1.5

2

2.5

0 0.5 1 1.5 2Recipient bilirubin (mg/dl)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.072



Risk Factors for 1 Year Mortality Recipient PCO2 at Transplant

0

0.5

1

1.5

2

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

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.10


ADULT LUNG TRANSPLANTS (1995-6/2006)

Diagnosis = IPFRisk Factors for 1 Year Mortality

RECIPIENT CHARACTERISTICS N Relative

Risk P-value

95% Confidence

Interval

Ventilator 58 1.77 0.0217 1.09 -2.89

Previous pregnancy 510 1.47 0.0008 1.17 -1.84


Transplant Year: 1995/96 vs. 2005/06 229 2.01 <0.0001 1.48 -2.75

Transplant Year: 1999/2000 vs. 2005/06 277 2.01 <0.0001 1.50 -2.68

Transplant Year: 1997/1998 vs. 2005/06 259 1.84 0.0001 1.35 -2.49

Donor CMV+ / Recipient CMV- 407 1.55 <0.0001 1.27 -1.90

(N=2,270)


ADULT LUNG TRANSPLANTS (1995-6/2006)

Diagnosis = IPFBorderline Significant Risk Factors for 1 Year Mortality


Risk P-value

95% Confidence

Interval

Hospitalized (including ICU) 185 1.37 0.068 0.98 -1.91


Transplant Year: 2001/02 vs. 2005/06 368 1.32 0.058 0.99 -1.77

(N=2,270)


ADULT LUNG TRANSPLANTS (1/1995-6/2006)

Diagnosis = IPFRisk Factors for 1 Year Mortality


Recipient age

Recipient weight

Donor weight

Bilirubin

Center volume

Oxygen required at rest

FEV1 (% predicted)

Ischemia time


ADULT LUNG TRANSPLANTS (1/1995-6/2006) 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

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity



Risk Factors for 1 Year MortalityRecipient Weight

0

0.5

1

1.5

2

50 60 70 80 90 100

Recipient Weight (kg)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0099



Risk Factors for 1 Year MortalityDonor Weight

0

0.5

1

1.5

2

50 60 70 80 90 100

Donor Weight (kg)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.026


ADULT LUNG TRANSPLANTS (1/1995-6/2006)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)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0012



Risk Factors for 1 Year MortalityCenter volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50


Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p < 0.0001



Risk Factors for 1 Year MortalityIschemia Time

0

0.5

1

1.5

2

2 4 6 8

Ischemia time (hours)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0067



Risk Factors for 1 Year MortalityRecipient Bilirubin

0

0.5

1

1.5

2

0 0.5 1 1.5 2

Bilirubin (mg/dl)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.0086



Risk Factors for 1 Year MortalityRecipient FEV1 (% predicted)

0

0.5

1

1.5

2

25 30 35 40 45 50 55 60 65 70

FEV1 (% predicted)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.013



DIAGNOSIS Procedure Type N

Relative Risk

P-value

95% Confidence

Interval

PPH All 261 1.84 0.0008 1.29 2.63

Alpha-1 antitrypsin deficiency Single 305 1.39 0.0001 1.17 1.64

Other diagnoses* Double 237 1.31 0.011 1.06 1.61

IPF Single 780 1.17 0.0092 1.04 1.31

COPD Double 612 0.87 0.0457 0.76 1.00

LAM All 64 0.62 0.044 0.39 0.99

(N=6,273)

ISHLT 2008


NOTE: COPD/Single lung is the reference group




Risk P-value

95% Confidence

Interval

Recipient on dialysis 15 2.06 0.0154 1.15 -3.68

Recipient on IV inotropes 61 1.88 0.0001 1.37 -2.56

Recipient on ventilator 145 1.37 0.0144 1.06 -1.76

Recipient with prior sternotomy 241 1.29 0.0031 1.09 -1.53

Hospitalized (including ICU) 498 1.22 0.0096 1.05 -1.42

Recipient history of diabetes 421 1.15 0.0489 1.00 -1.33

Chronic steroid use 2932 1.09 0.0313 1.01 1.17

(N=6,273)

ISHLT 2008




DONOR CHARACTERISTICS N Relative

Risk P-value


Donor history of diabetes 151 1.4 0.0017 1.13 -1.72

Donor cause of death = Anoxia 288 0.74 0.0022 0.62 -0.90


Transplant year: 1995/1996 vs. 2001/2002 1473 1.39 <0.0001 1.25 -1.54

Transplant year: 1997/1998 vs. 2001/2002 1632 1.24 <0.0001 1.12 -1.38

Donor CMV +/ Recipient CMV - 1129 1.21 <0.0001 1.10 -1.32

Transplant year: 1999/2000 vs. 2001/2002 1656 1.17 0.0022 1.06 -1.30

Number of HLA mismatches (A+B+DR) per mismatch

853 0-3 MM 1.06 0.0016 1.02 -1.10



VARIABLE N Relative

Risk P-value

95% Confidence

Interval

Female donor/female recipient 1732 0.88 0.0982 0.75 -1.02

(N=6,273)




Recipient age

Donor age

Donor height

Recipient BSA

Center volume

Oxygen at rest

Height ratio (borderline)

PA mean (borderline)



Recipient Age

0

0.5

1

1.5

2

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 = 0.0008



Oxygen Required at Rest

0

0.5

1

1.5

2

0 1 2 3 4 5 6

Oxygen required at rest (L/min)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.0055



Center Volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50

Center Volume (Cases per year)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p < 0.0001



Pre-Transplant Recipient Body Surface Area

0

0.5

1

1.5

2

1.3 1.4 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 = 0.0005



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 < 0.0001

ISHLT 2008

NOTE: Results should be considered in the context of height ratio (next slide)J Heart Lung Transplant 2008;27: 937-983


Donor/Recipient Height Ratio

0

0.5

1

1.5

2

0.8 0.9 1 1.1 1.2

Donor height (cm)

Rel

ativ

e R

isk

of

5 Y

ear

Mo

rtal

ity

p = 0.0667

ISHLT 2008

NOTE: Results should be considered in the context of donor height (previous slide)J Heart Lung Transplant 2008;27: 937-983

ADULT LUNG TRANSPLANTS (1995-6/2002) Risk Factors for 5 Year MortalityConditional on Survival to 1 Year

DIAGNOSIS Procedure

Type N Relative

Risk P-value

95% Confidence

Interval

Alpha-1 antitrypsin deficiency Double 193 0.69 0.0158 0.50 -0.93

PPH All 166 0.65 0.0346 0.44 -0.97

IPF Double 161 0.63 0.009 0.44 -0.89

Cystic Fibrosis All 712 0.58 0.0003 0.43 -0.78

LAM All 52 0.51 0.0317 0.28 -0.94

Pulmonary Fibrosis (not IPF) All 30 0.38 0.0201 0.17 -0.86

(N=4,735)

ISHLT 2008

NOTE: COPD/single lung is the reference group.



DONOR, RECIPIENT AND TRANSPLANT CHARACTERISTICS N


95% Confidence

Interval Donor cause of death = anoxia vs. head trauma

231 0.68 0.0046 0.53 -0.89

Recipient sternotomy prior to transplant

165 1.54 0.0002 1.23 -1.94

Recipient diabetes 309 1.24 0.0299 1.02 -1.51

Transplant year: 1997/1998 vs. 2001/2002

1230 1.19 0.0186 1.03 -1.37

Transplant year: 1995/1996 vs. 2001/2002

1040 1.18 0.0307 1.02 -1.37

# of mismatches at HLA A locus 2515 1 A MM; 1922 2 A MM 1.13 0.0047 1.04 -1.22

Female donor/female recipient 1333 0.80 0.0421 0.65 -0.99

(N=4,735)ISHLT 2008



POST-TRANSPLANT FACTORS N Relative

Risk P-value

95% Confidence

Interval

Bronchiolitis obliterans within 1st year 337 2.49 <0.0001 2.13 2.91

Rejection prior to discharge and rejection between discharge and 1 year

469 1.31 0.0007 1.12 1.54

Drug-treated infection prior to discharge 1871 1.19 0.0008 1.07 1.31

Rejection between discharge and 1 year but no rejection prior to discharge

1212 1.15 0.0221 1.02 1.3

(N=4,735)



Conditional on Survival to 1 Year

CHARACTERISTICS N Relative

Risk P-value

95% Confidence

Interval

Stroke prior to discharge 78 1.4 0.0529 1.00 -1.98

Donor cause of death = cerebrovascular/stroke vs. head trauma

1665 1.12 0.0621 0.99 -1.27

(N=4,735)


ADULT LUNG TRANSPLANTS (1/1995-6/2002) Risk Factors for 5 Year Mortality Conditional on Survival to 1 Year


Recipient Age Donor Height Weight Ratio

Bilirubin

Center Volume Recipient BSA (borderline)

FEV1 (borderline) Ischemia time (borderline)


ADULT LUNG TRANSPLANTS (1/1995-6/2002) 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/Recipient Weight Ratio

0

0.5

1

1.5

2

0.7 0.8 0.9 1 1.1 1.2 1.3 1.4 1.5 1.6 1.7

Donor/Recipient Weight Ratio

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.046


ADULT LUNG TRANSPLANTS (1/1995-6/2002)Risk Factors for 5 Year Mortality Conditional on 1 Year Survival

Donor Height

0

0.5

1

1.5

2

150 160 170 180 190Donor Height (cm)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.0141



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 = 0.044


ADULT LUNG TRANSPLANTS (1/1995-6/2002)Risk Factors for 5 Year Mortality Conditional on 1 Year Survival

Recipient BSA

0

0.5

1

1.5

2

1.3 1.4 1.5 1.6 1.7 1.8 1.9 2Recipient BSA (m2)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.053



Recipient Pre-Transplant FEV1

0

0.5

1

1.5

2

10 15 20 25 30 35 40 45 50 55 60 65 70 75

Pre-Transplant FEV1 (% predicted)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.08


ADULT LUNG RECIPIENTSFunctional Status of Surviving Recipients

(Follow-ups: April 1994 – June 2007)

0%

20%

40%

60%

80%

100%

1 Year (N =6,863) 3 Year (N=4,355) 5 Year (N=2,503) 10 Years (N=419)

No Activity Limitations Performs with Some Assistance Requires Total Assistance


ADULT LUNG RECIPIENTSEmployment Status of Surviving Recipients

(Follow-ups: April 1994 – June 2007)

0%

20%

40%

60%

80%

100%

1 Year (N=8,204) 3 Year (N=4,952) 5 Year (N=3,029) 10 year (N=635)

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 2007)

0%

20%

40%

60%

80%

100%

1 Year (N = 10,471) 3 Year ( N=6,330) 5 Year (N=3,888) 10 Year (N=770)

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 =3,219)

Polyclonal ALG/ATG (N= 757)

IL2R-antagonist (N =2,183)

Campath (N = 252)

% o

f p

ati

en

tsADULT LUNG RECIPIENTS

Induction Immunosuppression (Transplants: January 2002 - June 2007)Analysis limited to patients receiving prednisone

ISHLT 2008

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


0

10

20

30

40

50

20002001

20022003

20042005

20062000

20012002

20032004

20052006

20002001

20022003

20042005

20062000

20012002

20032004

20052006

% o

f p

ati

en

ts

ADULT LUNG RECIPIENTSInduction Immunosuppression (Transplants: January 2000 - December 2006)

Analysis limited to patients receiving prednisone

ISHLT 2008

Any Induction Polyclonal ALG/ATG IL2R-antagonist Campath



SURVIVAL BY INDUCTION USAGE For Adult Lung Recipients (Transplants: 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 10

Years

Su

rviv

al (

%)

No induction (N = 6,879)

Induction (N = 4,466)

p = 0.0075

N at risk = 161

N at risk = 328




SURVIVAL BY INDUCTION USAGE For Adult Lung Recipients (Transplants: January 2000-June 2006)

Conditional on survival to 14 days

0

20

40

60

80

100

0 1 2 3 4 5

Years

Su

rviv

al (

%)

No induction (N = 3,826)

Induction (N = 3,232)

p =0.0003

N at risk = 669

N at risk = 506


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine

% o

f P

ati

en

ts

Year 1 (N=5,001) Year 5 (N=2,178)

ADULT LUNG RECIPIENTSMaintenance Immunosuppression at Time of Follow-up

For follow-ups between January 2002 through June 2007 Analysis limited to patients receiving prednisone

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

ISHLT 2008



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, & 2007.

ADULT LUNG RECIPIENTSMaintenance Immunosuppression at Time of Follow-up

For follow-ups between January 2002 through June 2007 Analysis limited to patients receiving prednisone

NOTE: Different patients are analyzed in Year 1 and Year 5ISHLT 2008

Analysis is limited to patients who were alive at the time of the follow-upJ Heart Lung Transplant 2008;27: 937-983

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 2007Analysis limited to patients receiving prednisone

1 Year Follow-up (N = 5,001) 5 Year Follow-up (N = 2,178)

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

ISHLT 2008



0

20

40

60

80

100

Year 1 (N = 5,001) Year 5 (N = 2,178)

% 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 2007Conventional Combinations


ISHLT 2008



0

10

20

30

40

50

Year 1 (N = 5,001) Year 5 (N =2,178)

% 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 2007Other Combinations


ISHLT 2008



PERCENTAGE OF ADULT LUNG TRANSPLANT RECIPIENTS EXPERIENCING REJECTION IN 1ST YEAR

Stratified by Type of Induction (Follow-ups: July 1, 2004 - June 30, 2007)

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 Treatment

No induction vs. polyclonal (p = 0.8004); polyclonal vs. IL2R (p < 0.0001); no induction vs. IL2R (p = 0.0006)

ISHLT 2008

No induction: N = 1,897Polyclonal: N = 358IL2R- antagonist: N = 1,186



Stratified by Type of Induction (Follow-ups: July 1, 2004 - June 30, 2007)

0

10

20

30

40

50

60

70

% 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 Treatment

ISHLT 2008

18-34: N = 52835-49: N = 67650-59: N = 1,35660-65: N = 87766+: N = 177Female: N = 1,684 Male: N = 1,930

18-34 35-49 50-59 60-65 66+ Female Male18-34: no induct vs. IL2 (p=0.041); poly vs. IL2R (p=0.009); 35-49: poly vs. IL2R (p =0.020);50-59: no induct vs. IL2R (p<0.0001); 60-65: no induct vs. poly (p=0.044); no induct vs. IL2R (p=0.016); 66+: no induct vs. IL2R (p=0.004).For female: no induct vs. IL2R (p<0.0001)For male: no induct vs.IL2R (p<0.0001); poly vs. IL2R (p = 0.002)



Stratified by Maintenance Immunosuppression (Follow-ups: July 1, 2004 - June 30, 2007)

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 were statistically significant at 0.05 except TAC + MMF vs. TAC+ AZA

ISHLT 2008

Cyclosporine + MMF: N = 330 Cyclosporine + AZA: N = 551Tacrolimus + MMF: N = 1,297Tacrolimus + AZA: N = 898



Stratified by Maintenance Immunosuppression (Follow-ups: July 1, 2004 - June 30, 2007)

0

10

20

30

40

50

60

70

80

CyA + 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

1 y

ea

r

18-34: CyA + MMF vs. Cya + AZA (p=0.039); CyA + AZA vs. TAC + MMF (p=0.0001); CyA + AZA vs. TAC + AZA (p=0.002)35-49: all comparisons are statistically significant at 0.05 except CyA + MMF vs. Cya + AZA and TAC + MMF vs. TAC + AZA 50-59: all comparisons were statistically significant at 0.01 except TAC + MMF vs. TAC + AZA 60-65: all comparisons are statistically significant at 0.05 except CyA + MMF vs. TAC + AZA and TAC + MMF vs. TAC + AZA 66+: CyA + AZA vs. TAC + MMF (p <0.0001); CyA + AZA vs. TAC + AZA (p=0.011) Females: all comparisons were statistically significant at 0,05 except TAC + MMF vs. TAC + AZA Males: all comparisons were statistically significant at 0.01 except TAC + MMF vs. TAC + AZA

ISHLT 2008

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


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 2007

Outcome Within 1

Year

Total number with known response

Within 1 Year


Hypertension 48.90% (N = 3,802) 54.00% (N = 6,180)

Renal Dysfunction 23.1% (N = 3,719) 26.6% (N = 6,586)

Abnormal Creatinine < 2.5 mg/dl 12.90% 19.60%

Creatinine > 2.5 mg/dl 8.50% 5.20%

Chronic Dialysis 1.70% 1.70%

Renal Transplant 0.00% 0.10%

Hyperlipidemia 13.10% (N = 3,949) 27.50% (N = 6,690)

Diabetes 17.10% (N = 3,761) 30.60% (N = 6,508)

Bronchiolitis Obliterans 10.60% (N = 3,496) 8.20% (N = 6,203)


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

Post-Transplant (Follow-ups: April 1994 - June 2007)

Outcome Within 1

Year


Within 5 Years


Hypertension 52.10% (N = 9,982) 85.30% (N = 2,538)

Renal Dysfunction 25.3% (N = 10,305) 37.0% (N = 2,798)

Abnormal Creatinine < 2.5 mg/dl 17.20% 23.40%

Creatinine > 2.5 mg/dl 6.40% 10.00%

Chronic Dialysis 1.70% 3.10%

Renal Transplant 0.00% 0.50%

Hyperlipidemia 22.20% (N = 10,639) 53.60% (N = 2,829)

Diabetes 25.70% (N = 10,269) 35.50% (N = 2,582)

Bronchiolitis Obliterans 9.10% (N = 9,699) 33.70% (N = 2,128)


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


Outcome Within 10

Years


Hypertension 97.70% (N = 298)

Renal Dysfunction 41.1% (N = 358)

Abnormal Creatinine < 2.5 mg/dl 21.80% Creatinine > 2.5 mg/dl 8.40% Chronic Dialysis 7.30% Renal Transplant 3.60%

Hyperlipidemia 67.10% (N = 359)

Diabetes 37.80% (N = 315)

Bronchiolitis Obliterans 46.30% (N = 214)


FREEDOM FROM BRONCHIOLITIS OBLITERANSFor Adult Lung Recipients (Follow-ups: April 1994-June 2007)

Conditional on Survival to 14 days

0

20

40

60

80

100

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

% F

ree

do

m f

rom

OB

Freedom from Bronch Oblit (N = 17,443)


N at risk = 49


FREEDOM FROM BRONCHIOLITIS OBLITERANS STRATIFIED BY INDUCTION USE

For Adult Lung Recipients Follow-ups: April 1994-June 2007)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

No induction (N=6,913)

Induction (N=4,357)

p = 0.4056



N at risk = 30

N at risk = 11


FREEDOM FROM SEVERE RENAL DYSFUNCTION*For Adult Lung Recipients (Follow-ups: April 1994-June 2007)

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

Freedom from Severe RenalDysfunction (N=17,452)


N at risk = 81

* 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 2007)

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

No Malignancy 10,279 (96.4%) 2,514 (87.7%) 268 (72.2%)

Malignancy (all types combined) 386 (3.6%) 351 (12.3%) 103 (27.8%)

Malignancy Type*

Skin 94 194 65

Lymph 173 63 21

Other 99 110 29

Type Not Reported

20 11 2

* 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 2007)

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 2007)

CAUSE OF DEATH0-30 Days

(N = 1,622)

31 Days –

1 Year

(N = 2,781)

>1 Year –

3 Years

(N = 2,481)

>3 Years –

5 Years

(N = 1,445)

>5 Years – 10 Years

(N = 1,592)

>10 Years

(N = 310)

BRONCHIOLITIS 8 (0.5%) 129 (4.6%) 648 (26.1%) 412 (28.5%) 394 (24.7%) 62 (20.0%)

ACUTE REJECTION 70 (4.3%) 50 (1.8%) 40 (1.6%) 10 (0.7%) 11 (0.7%) 0

LYMPHOMA 1 (0.1%) 74 (2.7%) 56 (2.3%) 26 (1.8%) 41 (2.6%) 15 (4.8%)

MALIGNANCY, OTHER 2 (0.1%) 71 (2.6%) 145 (5.8%) 114 (7.9%) 151 (9.5%) 22 (7.1%)

CMV 0 86 (3.1%) 25 (1.0%) 5 (0.3%) 3 (0.2%) 0

INFECTION, NON-CMV 330 (20.3%) 1,011 (36.4%) 578 (23.3%) 278 (19.2%) 292 (18.3%) 59 (19.0%)

GRAFT FAILURE 458 (28.2%) 504 (18.1%) 462 (18.6%) 274 (19.0%) 286 (18.0%) 61 (19.7%)

CARDIOVASCULAR 180 (11.1%) 109 (3.9%) 77 (3.1%) 63 (4.4%) 76 (4.8%) 17 (5.5%)

TECHNICAL 134 (8.3%) 63 (2.3%) 16 (0.6%) 4 (0.3%) 11 (0.7%) 4 (1.3%)

OTHER 439 (27.1%) 684 (24.6%) 434 (17.5%) 259 (17.9%) 327 (20.5%) 70 (22.6%)


LUNG TRANSPLANTATION Overall ISHLT 2008 J Heart Lung Transplant 2008;27: 937-983.

Documents

Transcript of LUNG TRANSPLANTATION Overall ISHLT 2008 J Heart Lung Transplant 2008;27: 937-983.