2004 ISHLT J Heart Lung Transplant 2004; 23: 933-947 LUNG TRANSPLANTATION Pediatric Recipients.

2004ISHLTJ Heart Lung Transplant 2004; 23: 933-947

LUNG TRANSPLANTATION

Pediatric Recipients


AGE DISTRIBUTION OF PEDIATRIC LUNG RECIPIENTS (Transplants: January 1986 - June 2003)

0

10

20

30

40

50

60

70

80

90

100

110

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

Recipient Age (Years)

Nu

mb

er o

f T

ran

spla

nts


AGE DISTRIBUTION OF PEDIATRIC LUNG RECIPIENTS (Transplants: January 1996 - June 2003)

0

10

20

30

40

50

60

70

80

90

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

Recipient Age (Years)

Nu

mb

er o

f T

ran

spla

nts


AGE DISTRIBUTION FOR DONORS OF PEDIATRIC

LUNG RECIPIENTS (Transplants: January 1986 - June 2003)

0

25

50

75

100

125

150

175

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)

Nu

mb

er

of

Tra

ns

pla

nts


AGE DISTRIBUTION FOR DONORS OF PEDIATRIC

LUNG RECIPIENTS (Transplants: January 1996 - June 2003)

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)

Nu

mb

er

of

Tra

ns

pla

nts


AGE DISTRIBUTION OF PEDIATRIC LUNG RECIPIENTS

By Year of Transplant

0

20

40

60

80

100

11-17 Years1-10 Years

<1 Year

Nu

mb

er o

f T

ran

spla

nts

1 3 4 6

20

4751

4543

8473

84 84

67 66

5660


NUMBER OF CENTERS REPORTING PEDIATRIC LUNG TRANSPLANTS

0

10

20

30

4019

86

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

Transplant Year

Num

ber

of P

edia

tric

Cen

ters

R

epor

ting


PEDIATRIC LUNG TRANSPLANTATION: Indications (Transplants: January 1991 - June 2003)

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

Cystic Fibrosis 66 35.9%

PPH 7 14.3% 25 13.6%

Congenital Heart Disease 23 46.9% 20 10.9%

IPF 13 7.1%

Pulmonary Vascular Disease 6 12.2% 6 3.0%

Re-TX: Non-OB 3 6.1% 8 4.3%

Re-TX: OB 11 6.0%

OB (Non-ReTX) 7 3.8%

Bronchiectasis 2 1.1%

COPD/Emphysema 2 1.1%

Other 10 20.0% 24 13.0%


2%

68%

4%

6%

10%

6%

4%

Congenital Heat 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

% o

f Cas

es

PPH Cystic Fibrosis


PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival for Congenital Diagnosis (Transplants: January 1990 – June 2002)

0

25

50

75

100

0 1 2 3 4 5 6 7 8Years

Su

rviv

al (

%)

Eisenmenger's Syndrome (N=14)

Other Congenital (N=36)

Eisenmenger's + Other Congenital (N=50)


PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type

(Transplants: January 1990 - June 2002)

0

25

50

75

100

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

Su

rviv

al

(%)

Single Lung (N=71)

Bilateral/Double Lung (N=587)

HALF-LIFE Single Lung: 2.2 Years; Bilateral/double Lung: 4.0 Years

P = 0.0001



Diagnosis: PPH (Transplants: January 1990 - June 2002)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years Post-Transplantation

Sur

viva

l (%

)

Single Lung (N = 17) Double Lung (N=52)

P = 0.0013



Diagnosis: PPH (Transplants: January 1994 - June 2002)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years Post-Transplantation

Sur

viva

l (%

)

Single Lung (N = 4) Double Lung (N=38)

P = 0.0013


PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Age Group

(Transplants: January 1990 - June 2002)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (

%)

<1 Year (N=47)

1-10 Years (N=184)

11-17 Years (N=440)

No comparisons are statistically significant

HALF-LIFE<1 Year: ½-life = 3.5 Years1-10 Years: ½-life = 3.9 Years11-17 Years: ½-life = 3.7 Years


PEDIATRIC LUNG TRANSPLANTATION

Conditional Kaplan-Meier Survival by Age Group (Transplants: January 1990 - June 2002)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (

%)

<1 Year (N=28)

1-10 Years (N=114)

11-17 Years (N=285)


HALF-LIFE<1 Year: ½-life = 7.1 Years1-10 Years: ½-life = 6.7 Years11-17 Years: ½-life = 6.1 Years


PEDIATRIC LUNG TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: January 1988 - June 2002)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (

%)

1988-1992 (N=128)

1993-1997 (N=329)

1998-6/2002 (N=301)

HALF-LIFEUnconditional 1988-1992: 2.6 Years; 1993-1997: 3.8 Years; 1998-2002: 3.8 YearsConditional 1988-1992: 8.2 Years; 1993-1997: 6.1 Years



PEDIATRIC LUNG RECIPIENTS Functional Status (Follow-ups: April 1994-June 2003)

0%

20%

40%

60%

80%

100%

1 Year (N = 310) 3 Years (N = 200) 5 Years (N = 111)

No Activity Limitations Performs with Assistance Total Assistance


PEDIATRIC LUNG RECIPIENTS Rehospitalization Post-transplant (Follow-ups: April 1994 - June 2003)

0%

20%

40%

60%

80%

100%

Up to 1 Year (N = 363) Between 2 and 3 Years (N = 216)

Between 4 and 5 Years (N = 117)

No Hospitalization Hospitalized, Not Rejection/Not Infection

Hospitalized, Rejection Hospitalized, Infection Only

Hospitalized, Rejection + Infection


0

10

20

30

40

50

Any Induction (N = 55) Polyclonal ALG/ATG (N = 18) IL2R-antagonist (N = 38)

% o

f p

ati

en

tsPEDIATRIC LUNG RECIPIENTS

Induction ImmunosuppressionFor follow-ups between January 2001 and June 2003


0

10

20

30

40

50

60

% o

f p

ati

en

ts

2001 2002 2003 (6 months)

PEDIATRIC LUNG RECIPIENTSInduction Immunosuppression (Follow-ups: January 2001 - June 2003)


0

10

20

30

40

50

60

Any Induction Polyclonal ALG/ATG IL2R-antagonist

% o

f p

atie

nts

2001 2002 2003

PEDIATRIC LUNG RECIPIENTSInduction Immunosuppression (Follow-ups: January 2001 - June 2003)


0

20

40

60

80

100

Cyclosporine Tacrolimus MMF Azathioprine Prednisone

% o

f P

atie

nts

Year 1 (N = 78) Year 5 (N = 45)

PEDIATRIC LUNG RECIPIENTS Maintenance Immunosuppression at Time of Follow-up

For follow-ups between January 2001 and June 2003

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


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 = 78) 5 Year Follow-up (N = 45)NOTE: Different patients are analyzed in Year 1 and Year 5


0%

20%

40%

60%

80%

100%

Year 1 (N = 80) Year 5 (N = 46)

% o

f P

atie

nts

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

(Follow-ups: April 1994 - June 2003)

Outcome Within 1

Year Total number with known response

Hypertension 37.8% (N = 352)

Renal Dysfunction 6.8% (N = 354)

Abnormal Creatinine < 2.5 mg/dl 4.0% Creatinine > 2.5 mg/dl 1.7% Chronic Dialysis 0.8% Renal Transplant 0.3%

Hyperlipidemia 1.4% (N = 365)

Diabetes 22.5% (N = 355)

Bronchiolitis Obliterans 14.6% (N = 329)


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

(Follow-ups: April 1994 - June 2003)

Outcome Within 5

Years Total number with known response

Hypertension 71.6% (N = 67)

Renal Dysfunction 22.1% (N = 68) Abnormal Creatinine < 2.5 mg/dl 10.3% Creatinine > 2.5 mg/dl 7.4% Chronic Dialysis 2.9% Renal Transplant 1.5%

Hyperlipidemia 2.9% (N = 69)

Diabetes 27.9% (N = 68)

Bronchiolitis Obliterans 26.5% (N = 49)


Freedom from Bronchiolitis Obliterans For Pediatric Lung Recipients (Follow-ups: April 1994 - June 2003)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

% F

ree

fro

m B

ron

ch

ioli

tis

O

bli

tera

ns


Freedom from Severe Renal Dysfunction*For Pediatric Lung Recipients (Follow-ups: April 1994 - June 2003)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6Years

% F

ree

fro

m S

ev

ere

Re

na

l D

ys

fun

cti

on

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


MALIGNANCY POST-LUNG TRANSPLANTATION FOR PEDIATRICSCumulative Incidence for Survivors (Follow-ups: April 1994 - June 2003)

Malignancy/Type 1-Year Survivors 5-Year Survivors

No Malignancy 345 (94.3%) 63 (91.3%)

Malignancy (all types combined) 21 (5.7%) 6 (8.7%)

Malignancy Type

Lymph 19 6

Other 2


Freedom from MalignancyFor Pediatric Lung Recipients (Follow-ups: April 1994 - June 2003)

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 2003)

CAUSE OF DEATH0-30 Days (N = 45)

31 Days - 1 Year

(N = 75)

>1 Year - 3 Years

(N = 81)

>3 Years - 5 Years

(N = 35)

>5 Years

(N = 11)

BRONCHIOLITIS 5 (6.7%) 30 (37.0%) 16 (45.7%) 5 (45.5%)

ACUTE REJECTION 3 (4.0%) 1 (2.9%)

LYMPHOMA 3 (4.0%) 4 (4.9%) 1 (2.9%) 2 (18.2%)

CMV 5 (6.7%)

INFECTION, NON-CMV

6 (13.3%) 31 (41.3%) 17 (21.0%) 8 (22.9%) 1 (9.1%)

GRAFT FAILURE 20 (44.4%) 14 (18.7%) 16 (19.8%) 3 (8.6%) 2 (18.2%)

CARDIOVASCULAR 6 (13.3%) 2 (2.7%) 2 (2.5%)

TECHNICAL 6 (13.3%) 1 (1.3%)

OTHER 7 (15.6%) 11 (14.7%) 12 (14.8%) 6 (17.1%) 1 (9.1%)

2004 ISHLT J Heart Lung Transplant 2004; 23: 933-947 LUNG TRANSPLANTATION Pediatric Recipients.

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Transcript of 2004 ISHLT J Heart Lung Transplant 2004; 23: 933-947 LUNG TRANSPLANTATION Pediatric Recipients.