lung transplantation

LUNG TRANSPLANTATION

Pediatric Recipients

ISHLT 2005J Heart Lung Transplant 2005;24: 945-982

AGE DISTRIBUTION OF PEDIATRIC LUNG RECIPIENTS (Transplants: January 1986 - June 2004)

0102030405060708090

100110120130

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Recipient Age (Years)

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AGE DISTRIBUTION OF PEDIATRIC LUNG RECIPIENTS (Transplants: January 1996 - June 2004)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17


Nu

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AGE DISTRIBUTION BY DONOR TYPE FOR PEDIATRIC LUNG RECIPIENTS (Transplants: January 1986 - June 2004)

0102030405060708090

100110120130

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17


Nu

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spla

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LivingDeceased


AGE DISTRIBUTION BY DONOR TYPE FOR PEDIATRIC LUNG RECIPIENTS (Transplants: January 1996 - June 2004)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17


Nu

mb

er

of

Tra

nsp

lan

ts .

LivingDeceased


AGE DISTRIBUTION FOR DONORS OF PEDIATRIC

LUNG RECIPIENTS (Transplants: January 1986 - June 2004)

0

25

50

75

100

125

150

175

200

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18-25

26-30

31+

Donor Age (Years)

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.


AGE DISTRIBUTION FOR DONORS OF PEDIATRIC

LUNG RECIPIENTS (Transplants: January 1996 - June 2004)

0

25

50

75

100

125

150

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18-25

26-30

31+

Donor Age (Years)

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AGE DISTRIBUTION OF PEDIATRIC LUNG RECIPIENTS

By Year of Transplant

0

20

40

60

80

100

11-17 Years1-10 Years

<1 Year

Nu

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spla

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1 3 4 6

20

4751

45 43

84

72

84 84

67 66

5765 63


NUMBER OF CENTERS REPORTING PEDIATRIC LUNG TRANSPLANTS

0

10

20

30

40

1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Transplant Year

Nu

mb

er o

f P

edia

tric

Cen

ters

R

epo

rtin

g


PEDIATRIC LUNG TRANSPLANTATION: Indications (Transplants: January 1991 - June 2004)

DIAGNOSIS AGE: < 1 Year AGE: 1-10 Years

Cystic Fibrosis 72 36.5%

Primary Pulmonary Hypertension 7 13.7% 26 13.2%

Congenital Heart Disease 24 47.1% 21 10.7%

Idiopathic Pulmonary Fibrosis 12 6.1%

Pulmonary Vascular Disease 7 13.7% 6 3.0%

Re-Transplant: Non-Obliterative bronchiolitis

3 5.9% 8 4.1%

Re-Transplant: Obliterative bronchiolitis 11 5.6%

Interstitial Pneumonitis 3 5.9% 7 3.6%

Obliterative Bronchiolitis

(Not Re-Transplant)

9 4.6%

Bronchiectasis 2 1.0%

COPD/Emphysema 2 1.0%

Other 7 13.7% 21 10.7%


2%

72%

3%

4%

10%

6%

3%

Congenital Heart Disease

Cystic Fibrosis

IPF

Other

PPH

ReTX

OB (Non-ReTX)

DIAGNOSIS IN PEDIATRIC LUNG RECIPIENTSAge: 11-17 Years

0

25

50

75

100

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

% o

f Cas

es

PPH Cystic Fibrosis


PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type

(Transplants: January 1990 - June 2003)

0

25

50

75

100

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

Su

rviv

al (

%)

Single Lung (N=76)

Bilateral/Double Lung (N=654)

HALF-LIFE Single Lung: 2.2 Years; Bilateral/double Lung: 4.3 Years

P = 0.0003


PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival for Congenital Diagnosis (Transplants: January 1990 – June 2003)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9Years

Su

rviv

al (

%)

Eisenmenger's Syndrome (N=14)

Other Congenital (N=40)

Eisenmenger's + Other Congenital (N=54)


PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type

Diagnosis: Primary Pulmonary Hypertension (Transplants: January 1990 - June 2003)

0

25

50

75

100

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

Years Post-Transplantation

Su

rviv

al (

%)

.

Single Lung (N = 17) Double Lung (N=59)

P = 0.003


PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Age Group


0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Years

Su

rviv

al (

%)

<1 Year (N=51)

1-10 Years (N=194)

11-17 Years (N=485)

No comparisons are statistically significant

HALF-LIFE<1 Year: 3.5 Years1-10 Years: 5.4 Years11-17 Years: 3.7 Years


PEDIATRIC LUNG TRANSPLANTATIONConditional Kaplan-Meier Survival by Age Group


0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Years

Su

rviv

al (

%)

<1 Year (N=30)1-10 Years (N=125)

11-17 Years (N=458)


HALF-LIFE<1 Year: 7.1 Years1-10 Years: 10.5 Years11-17 Years: 6.1 Years


PEDIATRIC LUNG TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: January 1988 - June 2003)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Years

Su

rviv

al (

%)

1988-1992 (N=128)

1993-1997 (N=328)

1998-6/2003 (N=374)

HALF-LIFEUnconditional 1988-1992: 2.6 Years; 1993-1997: 3.8 Years; 1998-2003: 4.7 YearsConditional 1988-1992: 8.2 Years; 1993-1997: 6.1 Years; 1998-2003: 6.0 Years



PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Donor Type for Age 11-17 years


0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Years

Su

rviv

al (

%)

Deceased Donor (N = 485)

Living Donor (N = 71)

p = 0.7

HALF-LIFEDeceased: 3.7 YearsLiving: 3.8 Years


PEDIATRIC LUNG RECIPIENTS Functional Status of Surviving Recipients

(Follow-ups: April 1994-June 2004)

0%

20%

40%

60%

80%

100%

1 Year (N = 351) 3 Years (N = 233) 5 Years (N = 133)

No Activity Limitations Performs with Assistance Total Assistance


PEDIATRIC LUNG RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients

(Follow-ups: April 1994 - June 2004)

0%

20%

40%

60%

80%

100%

Up to 1 Year (N = 411) Between 2 and 3 Years (N = 250)

Between 4 and 5 Years (N = 142)

No Hospitalization Hospitalized, Not Rejection/Not InfectionHospitalized, Rejection Hospitalized, Infection OnlyHospitalized, Rejection + Infection


0

10

20

30

40

50

Any Induction (N = 77) Polyclonal ALG/ATG (N = 24) IL2R-antagonist (N = 55)

% o

f p

atien

tsPEDIATRIC LUNG RECIPIENTS

Induction ImmunosuppressionFor follow-ups between January 2001 and June 2004


0

10

20

30

40

50

60

Any Induction Polyclonal ALG/ATG IL2R-antagonist

% o

f p

atie

nts

2001 2002

2003 1/2004-6/2004

PEDIATRIC LUNG RECIPIENTSInduction Immunosuppression (Follow-ups: January 2001 - June 2004)


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

% o

f P

atie

nts

.

Year 1 (N = 118) Year 5 (N = 66)

PEDIATRIC LUNG RECIPIENTS Maintenance Immunosuppression at Time of Follow-up

(Follow-ups: January 2001 and June 2004)

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


PEDIATRIC LUNG TRANSPLANTATION

Kaplan-Meier Survival Stratified by Induction Use (Transplants: January 2001 - June 2004)

0

25

50

75

100

0 1 2 3

Years

Su

rviv

al (

%)

.

Induction (N = 77)

No Induction (N = 86)

p = 0.7


0

20

40

60

80

100

CalcineurinInhibitor

CellCycle Prednisone CalcineurinInhibitor

CellCycle Prednisone

% o

f P

ati

en

ts .

CyA

TacTac

CyA

AZA AZA

MMFMMF

PEDIATRIC LUNG RECIPIENTS Maintenance Immunosuppression at Time of Follow-up


1 Year Follow-up (N = 118) 5 Year Follow-up (N = 66)NOTE: Different patients are analyzed in Year 1 and Year 5


0%

20%

40%

60%

80%

100%

Year 1 (N = 117) Year 5 (N = 65)

% o

f P

ati

en

ts .

Other

Tacrolimus + MMF

Tacrolimus + AZA

Cyclosporine + MMF

Cyclosporine + AZA

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


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


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


Outcome Within 1

Year Total number with known response

Hypertension 37.3% (N = 400)

Renal Dysfunction 7.8% (N = 402)

Abnormal Creatinine < 2.5 mg/dl 4.7% Creatinine > 2.5 mg/dl 2.2% Chronic Dialysis 0.7% Renal Transplant 0.2%

Hyperlipidemia 1.9% (N = 413)

Diabetes 23.6% (N = 403)

Bronchiolitis Obliterans 14.2% (N = 366)


POST-LUNG TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Prevalence in Survivors within 5 Years Post-Transplant


Outcome Within 5

Years Total number with known response

Hypertension 71.8% (N = 85)

Renal Dysfunction 22.1% (N = 86) Abnormal Creatinine < 2.5 mg/dl 12.8% Creatinine > 2.5 mg/dl 5.8% Chronic Dialysis 2.3% Renal Transplant 1.2%

Hyperlipidemia 4.5% (N = 88)

Diabetes 30.2% (N = 86)

Bronchiolitis Obliterans 30.6% (N = 62)


Freedom from Bronchiolitis Obliterans For Pediatric Lung Recipients (Follow-ups: April 1994 - June 2004)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

% F

ree f

rom

Bro

nch

ioliti

s O

blite

ran

s .


Freedom from Severe Renal Dysfunction*For Pediatric Lung Recipients (Follow-ups: April 1994 - June 2004)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6Years

% F

ree f

rom

Severe

Ren

al

Dysfu

ncti

on

* Severe renal dysfunction = Creatinine > 2.5 mg/dl, dialysis or renal transplant


FREEDOM FROM BRONCHIOLITIS OBLITERANS

For Pediatric Lung Recipients by Induction Use (Transplants: April 1994 - June 2004)

0

25

50

75

100

0 1 2 3 4

Years

Su

rviv

al (

%)

Induction (N = 95)

No Induction (N = 299)

p = 0.7


MALIGNANCY POST-LUNG TRANSPLANTATION FOR PEDIATRICSCumulative Incidence for Survivors (Follow-ups: April 1994 - June 2004)

Malignancy/Type 1-Year Survivors 5-Year Survivors

No Malignancy 354 (94.4%) 80 (90.9%)

Malignancy (all types combined) 23 (5.6%) 8 (9.1%)

Malignancy Type

Lymph 20 7

Other 2 1

”Other” includes Liver and primitive neuroectodermal tumor.


Freedom from MalignancyFor Pediatric Lung Recipients (Follow-ups: April 1994 - June 2004)

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

% F

ree

fro

m M

alig

nan

cy

.

All malignancy Lymph Skin Other


PEDIATRIC LUNG TRANSPLANT RECIPIENTS: Cause Of Death(Deaths: January 1992- June 2004)

CAUSE OF DEATH0-30 Days

(N = 60)31 Days - 1 Year

(N = 89)

>1 Year - 3 Years

(N = 99)

>3 Years - 5 Years

(N = 46)

>5 Years

(N = 26)

BRONCHIOLITIS 6 (6.7%) 34 (34.3%) 20 (43.5%) 12 (46.2%)

ACUTE REJECTION 1 (1.7%) 3 (3.4%) 1 (2.2%)

LYMPHOMA 3 (3.4%) 4 (4.0%) 1 (2.2%) 3 (11.5%)

CMV 7 (7.9%)

INFECTION, NON-CMV 7 (11.7%) 34 (38.2%) 20 (20.2%) 12 (26.1%) 2 (7.7%)

GRAFT FAILURE 22 (36.7%) 16 (18.0%) 17 (17.2%) 4 (8.7%) 4 (15.4%)

CARDIOVASCULAR 8 (13.3%) 2 (2.2%) 2 (2.0%)

TECHNICAL 9 (15.0%) 1 (1.1%)

MULTIPLE ORGAN FAILURE

2 (3.3%) 9 (10.1%) 9 (9.1%) 3 (6.5%) 2 (7.7%)

OTHER 11 (18.3%) 8 (9.0%) 13 (13.1%) 4 (8.7%) 3 (11.5%)


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