LUNG TRANSPLANTATION Pediatric Recipients ISHLT 2006 J Heart Lung Transplant 2006;25:904-911.

LUNG TRANSPLANTATION

Pediatric Recipients

ISHLT 2006J Heart Lung Transplant 2006;25:904-911

RECIPIENT AGE DISTRIBUTION FOR PEDIATRIC LUNG RECIPIENTS - NUMBER

(Transplants: January 1986 - June 2005)

050

100150200250300350400450500550600650700

1986-1995 1996-6/2005

Nu

mb

er

of

Tra

ns

pla

nts

<1 1-5 6-11 12-17


RECIPIENT AGE DISTRIBUTION FOR PEDIATRIC LUNG RECIPIENTS - PERCENTAGE


0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1986-1995 1996-6/2005

% o

f T

ran

sp

lan

ts

12-17

6-11

1-5

<1


DONOR TYPE DISTRIBUTION BY YEAR OF TRANSPLANT FOR PEDIATRIC LUNG RECIPIENTS

(Transplants: 1986-2004)

0

10

20

30

40

50

60

70

80

90

1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

Transplant Year

Nu

mb

er

of

Tra

ns

pla

nts

LivingDeceased

ISHLT 2006NOTE: This figure includes only the lung transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as evidence that the number of lung transplants worldwide has declined in recent years.J Heart Lung Transplant 2006;25:904-911

DONOR TYPE DISTRIBUTION BY RECIPIENT AGE GROUP WITHIN ERA FOR PEDIATRIC LUNG RECIPIENTS (Transplants: January 1986 - June 2005)

0

50

100

150

200

250

300

350

400

450

500

0-5 years 6-11 years 12-17 years 0-5 years 6-11 years 12-17 years

Recipient Age (Years)

Nu

mb

er

of

Tra

ns

pla

nts

LivingDeceased

1986-1995 1996-6/2005


AGE DISTRIBUTION FOR DONORS OF PEDIATRIC

LUNG RECIPIENTS (Transplants: January 1986 - June 2005)

453

155

165

138

38

2

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Donor Age (Years)

Nu

mb

er o

f T

ran

spla

nts

60+

50-59

35-49

18-34

12-17

0-11


AGE DISTRIBUTION OF PEDIATRIC LUNG RECIPIENTS

By Year of Transplant

0

20

40

60

80

10012-17 Years1-11 Years

<1 Year

Nu

mb

er o

f T

ran

spla

nts

1 4 4 6

20

4855

4943

84

75

89 86

69 6965 67

62

ISHLT 2006

67

J Heart Lung Transplant 2006;25:904-911

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 2004

Transplant Year

Nu

mb

er o

f C

ente

rs R

epo

rtin

g

Ped

iatr

ic T

ran

spla

nts


PEDIATRIC LUNG TRANSPLANTATION: Indications (Transplants: January 1991 - June 2005)

DIAGNOSIS AGE: < 1 Year

AGE: 1-5 Years

AGE: 6-11 Years

AGE: 12-17 Years

Cystic Fibrosis 2 2.80% 98 54.40% 366 69.80%

Primary Pulmonary Hypertension 9 16.10% 15 20.80% 22 12.20% 43 8.20%

Re-Transplant: Obliterative Bronchiolitis 6 8.30% 8 4.40% 19 3.60%

Congenital Heart Disease 18 32.10% 7 9.70% 2 1.10% 5 1.00%

Idiopathic Pulmonary Fibrosis 7 9.70% 6 3.30% 17 3.20%

Obliterative Bronchiolitis (Not Re-TX) 4 5.60% 7 3.90% 16 3.10%

Re-Transplant: Not OB 3 5.40% 1 1.40% 7 3.90% 15 2.90%

Interstitial Pneumonitis 6 10.70% 10 13.90% 4 0.80%

Pulmonary Vascular Disease 7 12.50% 4 5.60% 6 3.30%

Eisenmenger’s Syndrome 1 1.80% 5 6.90% 5 2.80% 5 1.00%

Pulmonary Fibrosis, Other 1 1.80% 1 1.40% 3 1.70% 9 1.70%

Surfactant Protein B Deficiency 7 12.50% 1 1.40%

COPD/Emphysema 1 1.40% 2 1.10% 4 0.80%

Bronchopulmonary Dysplasia 1 1.80% 1 1.40% 5 2.80%

Bronchiectasis 3 1.70% 3 0.60%

Other 3 5.40% 7 9.70% 6 3.30% 18 3.40%


DIAGNOSIS IN PEDIATRIC LUNG RECIPIENTSBY YEAR OF TRANSPLANT

Age: 12-17 Years

0

25

50

75

100

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

% o

f T

ran

spla

nts

PPH Cystic Fibrosis


0

2

4

6

8

10

12

14

16

0-<1 month 1-<12 months 12-<36 months 36+ months Not reported

Nu

mb

er

of R

e-T

ran

sp

lan

ts-

PEDIATRIC LUNG RE-TRANSPLANTS Between January 1994 and June 2005

ISHLT 2006

Time Between Previous and Current Transplant

J Heart Lung Transplant 2006;25:904-911

0

10

20

30

40

50

60

70

80

90

100

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

Years

Su

rviv

al (

%)

0-<1 month (N=5) 1-<12 months (N=9)

12-<36 months (N=10) 36+ months (N=12)

PEDIATRIC LUNG RE-TRANSPLANTS Between January 1994 and June 2004

Stratified by Time Between Previous and Current Transplant


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 13Years

Su

rviv

al (

%)

Adult (N=18,145)

Pediatric (N=926)

HALF-LIFE Adult = 4.8 Years; Pediatric = 4.4 Years

P = 0.72


PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type


0

25

50

75

100

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

Su

rviv

al (

%)

Single Lung (N=102)

Bilateral/Double Lung (N=720)

HALF-LIFE Single Lung: 3.5 Years; Bilateral/double Lung: 4.7 Years

P = 0.006


PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival for Congenital Diagnosis (Transplants: January 1990 – June 2004)

0

25

50

75

100

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

Su

rviv

al (

%)

Eisenmenger's Syndrome (N=14)

Other Congenital Heart Disease (N=31)

Eisenmenger's + Other Congenital Heart Disease (N=45)


PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type

Diagnosis: Primary Pulmonary Hypertension (Transplants: January 1990 - June 2004)

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=63)

P = 0.0025


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 15

Years

Su

rviv

al

(%)

<1 Year (N=58)

1-11 Years (N=267)

12-17 Years (N=497)

<1 year vs. 12-17 years: p = 0.031 No other comparisons were statistically significant.

HALF-LIFE<1 Year: 6.5 Years1-11 Years: 5.5 Years12-17 Years: 4.0 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 15

Years

Su

rviv

al (

%)

<1 Year (N=38)1-11 Years (N=175)

12-17 Years (N=321)

No comparisons were statistically significant at p<0.05

HALF-LIFE<1 Year: 8.8 Years1-11 Years: n.c.12-17 Years: 6.1 Years


PEDIATRIC LUNG TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: January 1988 - June 2004)

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 (

%)

1988-1994 (N=225)

1995-1999 (N=403)

2000-6/2004 (N=295)

HALF-LIFEUnconditional 1988-1994: 2.8 Years; 1995-1999: 4.0 Years; 2000-6/2004: n.c.Conditional 1988-1994: 7.6 Years; 1995-1999: 7.3 Years; 2000-6/2004: n.c.

P-value for 88-94 vs. 00-6/04: 0.0016


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


0

25

50

75

100

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

Years

Su

rviv

al (

%)

Deceased Donor (N = 538)

Living Donor (N = 73)

p = 0.80

HALF-LIFEDeceased: 4.0 YearsLiving: 3.8 Years


PEDIATRIC LUNG RECIPIENTS Functional Status of Surviving Recipients

(Follow-ups: April 1994-June 2005)

0%

20%

40%

60%

80%

100%

1 Year (N = 362) 3 Years (N = 238) 5 Years (N = 142) 7 Years (N=65)

No Activity Limitations Performs with Assistance Total Assistance


PEDIATRIC LUNG RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients

(Follow-ups: April 1994 - June 2005)

0%

20%

40%

60%

80%

100%

Up to 1 Year (N =450)

Between 2 and 3Years (N = 271)



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


PEDIATRIC LUNG RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients


0%

20%

40%

60%

80%

100%

Up to 1 Year (N =450)

Between 1 and 3Years (N =238)



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


0

10

20

30

40

50

60

Any Induction (N = 110) Polyclonal ALG/ATG (N = 36) IL2R-antagonist (N = 76)

% o

f p

atien

tsPEDIATRIC LUNG RECIPIENTS

Induction ImmunosuppressionFor transplants between January 2001 and June 2005


0

10

20

30

40

50

60

Any Induction Polyclonal ALG/ATG IL2R-antagonist

% o

f p

atie

nts

2001 20022003 20041/2005-6/2005

PEDIATRIC LUNG RECIPIENTSInduction Immunosuppression (Transplants: January 2001 - June 2005)


PEDIATRIC LUNG TRANSPLANTATION

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

0

25

50

75

100

0 1 2 3 4

Years

Su

rviv

al (

%)

Induction (N = 79)

No Induction (N = 81)

p = 0.5


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

% o

f P

atie

nts

Year 1 (N = 154) Year 5 (N = 83)

PEDIATRIC LUNG RECIPIENTS Maintenance Immunosuppression at Time of Follow-up

(Follow-ups: January 2001 and June 2005)

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

CyAAZA AZA

MMFMMF

PEDIATRIC LUNG RECIPIENTS Maintenance Immunosuppression at Time of Follow-up


1 Year Follow-up (N = 154) 5 Year Follow-up (N = 83)NOTE: Different patients are analyzed in Year 1 and Year 5


0%

20%

40%

60%

80%

100%

Year 1 (N = 154) Year 5 (N = 83)

% 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 38.5% (N = 439)

Renal Dysfunction 8.4% (N=441)

Abnormal Creatinine < 2.5 mg/dl 5.4% Creatinine > 2.5 mg/dl 2.0% Chronic Dialysis 0.7% Renal Transplant 0.2%

Hyperlipidemia 3.1% (N = 453)

Diabetes 25.8% (N = 442)

Bronchiolitis Obliterans 14.1% (N = 405)


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


Outcome Within 5

Years Total number with known response


Renal Dysfunction 22.0% (N = 100) Abnormal Creatinine < 2.5 mg/dl 15.0% Creatinine > 2.5 mg/dl 5.0% Chronic Dialysis 1.0% Renal Transplant 1.0%


Diabetes 32.0% (N = 100)



POST-LUNG TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Prevalence in Survivors within 7 Years Post-Transplant


Outcome Within 7

Years Total number with known response


Renal Dysfunction 34.8% (N = 46) Abnormal Creatinine < 2.5 mg/dl 21.7% Creatinine > 2.5 mg/dl 4.3% Chronic Dialysis 0.0% Renal Transplant 8.7%


Diabetes 24.4% (N = 45)



Freedom from Bronchiolitis Obliterans For Pediatric Lung Recipients (Follow-ups: April 1994 - June 2005)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

% F

ree

fro

m B

ron

ch

ioli

tis

Ob

lite

ran

s


FREEDOM FROM BRONCHIOLITIS OBLITERANS

For Pediatric Lung Recipients by Induction Use (Transplants: April 1994 - June 2005)

0

25

50

75

100

0 1 2 3 4 5

Years

Su

rviv

al (

%)

Induction (N = 105)

No Induction (N = 287)

p = 0.64


Freedom from Severe Renal Dysfunction*For Pediatric Lung Recipients (Follow-ups: April 1994 - June 2005)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7Years

% 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 2005)

Malignancy/Type 1-Year Survivors

5-Year Survivors

7-Year Survivors

No Malignancy 429 (94.5%) 91 (89.2%) 42 (91.3%)

Malignancy (all types combined)

25 (5.5%) 11 (10.8%) 4 (8.7%)

Malignancy Type

Lymph 22 10 4

Other 3 1 0

”Other” includes Liver and primitive neuroectodermal tumor.


Freedom from MalignancyFor Pediatric Lung Recipients (Follow-ups: April 1994 - June 2005)

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 2005)

CAUSE OF DEATH0-30 Days

(N =70 )31 Days - 1 Year

(N = 102)

>1 Year - 3 Years

(N = 103)

>3 Years - 5 Years

(N = 48)

>5 Years

(N = 30)

BRONCHIOLITIS 9 (8.8%) 39 (37.9%) 21 (43.8%) 12 (40.0%)

ACUTE REJECTION 3 (4.3%) 4 (3.9%) 1 (2.1%)

LYMPHOMA 3 (2.9%) 4 (3.9%) 1 (2.1%) 3 (10.0%)

MALIGNANCY, NON-LYMPHOMA

1 (2.1%)

CMV 7 (6.9%)

INFECTION, NON-CMV 9 (12.9%) 38 (37.3%) 23 (22.3%) 13 (27.1%) 2 (6.7%)

GRAFT FAILURE 23 (32.9%) 19 (18.6%) 17 (16.5%) 4 (8.3%) 6 (20.0%)

CARDIOVASCULAR 9 (12.9%) 3 (2.9%) 2 (1.9%)

TECHNICAL 9 (12.9%) 1 (1.0%)

MULTIPLE ORGAN FAILURE

4 (5.7%) 10 (9.8%) 9 (8.7%) 3 (6.3%) 3 (10.0%)

OTHER 13 (18.6%) 8 (7.8%) 9 (8.7%) 4 (8.3%) 4 (13.3%)


LUNG TRANSPLANTATION Pediatric Recipients ISHLT 2006 J Heart Lung Transplant 2006;25:904-911.

Documents

number of lung transplants

pediatric lung retransplants

renal transplant ishlt

current transplant ishlt

year of transplant age

ishlt transplant registry

years ishlt

age group transplants