lung transplantation pediatric recipients ishlt 2007 j heart lung transplant 2007;26

LUNG TRANSPLANTATION

Pediatric Recipients

ISHLT 2007J Heart Lung Transplant 2007;26

RECIPIENT AGE DISTRIBUTION FOR PEDIATRIC LUNG RECIPIENTS - NUMBER

(Transplants: January 1986 - June 2006)

050

100150200250300350400450500550600650700750

1986-1995 (N=303) 1996-6/2006 (N=752)

Nu

mb

er

of

Tra

nsp

lan

ts

<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 (N=303) 1996-6/2006 (N=752)

% 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: 1986-2005)

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 2005

Transplant Year

Nu

mb

er

of

Tra

nsp

lan

ts

LivingDeceased

ISHLT 2007NOTE: 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 2007;26

DONOR TYPE DISTRIBUTION BY RECIPIENT AGE GROUP WITHIN ERA FOR PEDIATRIC LUNG RECIPIENTS (Transplants: January 1986 - June 2006)

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 T

ran

sp

lan

ts

LivingDeceased

1986-1995 1996-6/2006


AGE DISTRIBUTION FOR DONORS OF PEDIATRIC

LUNG RECIPIENTS (Transplants: January 1986 - June 2006)

485

178

168

146

39

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 3 4 6

20

4751

4643

8272

84 85

67 6659

6671

ISHLT 2007

70

77

J Heart Lung Transplant 2007;26

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 2005

Transplant Year

Nu

mb

er o

f C

ente

rs R

epo

rtin

g

Ped

iatr

ic T

ran

spla

nts

ISHLT 2007 J Heart Lung Transplant 2007;26

NUMBER OF CENTERS REPORTING PEDIATRIC LUNG TRANSPLANTS BY CENTER VOLUME

0

10

20

30

40

1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Transplant Year

Nu

mb

er o

f C

ente

rs R

epo

rtin

g

Ped

iatr

ic T

ran

spla

nts

20+ transplants

10-19 transplants

5-9 transplants

1-4 transplants


PEDIATRIC LUNG TRANSPLANTATION: Indications (Transplants: January 1991 – June 2006)

DIAGNOSIS AGE: < 1 Year

AGE: 1-5 Years

AGE: 6-11 Years

AGE: 12-17 Years

Cystic Fibrosis 3 3.7% 107 54.9% 441 69.%

Primary Pulmonary Hypertension 10 16.1% 18 22.2% 23 11.8% 53 8.3%

Re-Transplant: Obliterative Bronchiolitis 6 7.4% 8 4.1% 22 3.4%

Congenital Heart Disease 19 30.6% 8 9.9% 2 1.0% 5 0.8%

Idiopathic Pulmonary Fibrosis 7 8.6% 6 3.1% 23 3.6%

Obliterative Bronchiolitis (Not Re-TX) 5 6.2% 9 4.6% 21 3.3%

Re-Transplant: Not OB 3 4.8% 1 1.2% 7 3.6% 16 2.5%

Interstitial Pneumonitis 6 9.7% 11 13.6% 1 0.5% 5 0.8%

Pulmonary Vascular Disease 7 11.3% 4 4.9% 6 3.1% 1 0.2%

Eisenmenger’s Syndrome 1 1.6% 5 6.2% 5 2.6% 6 0.9%

Pulmonary Fibrosis, Other 1 1.6% 1 1.2% 4 2.1% 11 1.7%

Surfactant Protein B Deficiency 9 14.5% 2 2.5%

COPD/Emphysema 1 1.2% 2 1.0% 5 0.8%

Bronchopulmonary Dysplasia 1 1.6% 2 2.5% 6 3.1%

Bronchiectasis 3 1.5% 4 0.6%

Other 5 8.1% 7 8.6% 6 3.1% 26 4.1%


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%

20%

40%

60%

80%

100%

Europe (N=82) North America (N=338) Other (N=24)

% o

f T

ran

sp

lan

ts

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

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


0%

20%

40%

60%

80%

100%


% o

f T

ran

sp

lan

ts-

Cystic Fibrosis PPH IPF OB Other Congenital heart disease Re-TX

PEDIATRIC LUNG TRANSPLANTS:DIAGNOSIS DISTRIBUTION BY LOCATION

Transplants between January 2000 and June 2006

ISHLT 2007

NOTE: Unknown diagnoses were excluded from this tabulation.

Total number of transplants reported:Europe = 82North America = 338Other = 24J Heart Lung Transplant 2007;26

0%

20%

40%

60%

80%

100%


% o

f Do

no

rs

0-5 6-11 12-17 18-34 35-49 50-59 60+

PEDIATRIC LUNG TRANSPLANTS:DONOR AGE DISTRIBUTION BY LOCATION

Transplants between January 2000 and June 2006

ISHLT 2007

NOTE: Transplants with unknown donor age were excluded from this tabulation.

Total number of transplants reported:Europe = 82North America = 338Other = 24J Heart Lung Transplant 2007;26

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=20,275)

Pediatric (N=965)

HALF-LIFE Adult = 4.8 Years; Pediatric = 4.3 Years

P = 0.7878


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=80)

Bilateral/Double Lung (N=792)

HALF-LIFE Single Lung: 2.2 Years; Bilateral/double Lung: 4.6 Years

P < .0001


PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival for Congenital Diagnoses (Transplants: January 1990 – June 2005)

0

25

50

75

100

0 1 2 3 4 5Years

Su

rviv

al (

%)

Eisenmenger's Syndrome (N=15)

Other Congenital Heart Disease (N=34)

Eisenmenger's + Other Congenital Heart Disease (N=49)

N at risk = 8

N at risk = 9

N at risk = 11

ISHLT 2007

Eisenmenger’s vs. Other: p = 0.19


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

Years

Su

rviv

al (

%)

<1 Year (N=58)

1-11 Years (N=268)

12-17 Years (N=546)

<1 year vs. 1-11 years: p = .6597<1 year vs. 12-17 years: p = 0.11751-11 years vs. 12-17 years: p = .0122

HALF-LIFE<1 Year: 6.4 Years1-11 Years: 5.7 Years12-17 Years: 4.0 Years

N at risk = 5

N at risk = 9

N at risk = 8


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

Years

Su

rviv

al (%

)

<1 Year (N=37)1-11 Years (N=183)

12-17 Years (N=353)

<1 year vs. 1-11 year: p = .5737<1 year vs. 12-17 years: p = .06861-11 years vs. 12-17 years: p = .0279

N at risk = 5

N at risk = 9

N at risk = 8

CONDITIONAL HALF-LIFE<1 Year: 8.8 Years1-11 Years: 10.5 Years12-17 Years: 5.8 Years


PEDIATRIC LUNG TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: January 1988 - June 2005)

0

20

40

60

80

100

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

Years

Su

rviv

al (

%)

1988-1994 (N=217)

1995-6/2005 (N=758)

HALF-LIFEUnconditional 1988-1994: 2.6 Years; 1995-6/2005: 4.5 YearsConditional 1988-1994: 7.1 Years; 1995-6/2005: 7.2 Years

P-value for 88-94 vs. 95-6/05: 0.0563

N at risk = 18

N at risk = 11


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

Years

Su

rviv

al (

%)

Deceased Donor (N = 546)

Living Donor (N = 72)

p = 0.9149

N at risk = 8

N at risk = 19

HALF-LIFEDeceased: 4.0 YearsLiving: 3.8 Years


0

2

4

6

8

10

12

14

16

18

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

Nu

mb

er o

f R

e-T

ran

spla

nts

PEDIATRIC LUNG RE-TRANSPLANTS Between January 1994 and June 2006

ISHLT 2007

Time Between Previous and Current Transplant


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 (

%)

N=5 at risk at 5 years

PEDIATRIC LUNG RETRANSPLANTSSurvival for Transplants Performed Between January 1994 and June 2005


PEDIATRIC LUNG RECIPIENTS Functional Status of Surviving Recipients

(Follow-ups: April 1994-June 2006)

0%

20%

40%

60%

80%

100%

1 Year (N = 361) 3 Years (N = 239) 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 2006)

0%

20%

40%

60%

80%

100%

Up to 1 Year (N =491)

Between 2 and 3Years (N = 303)



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 =491)

Between 1 and 3Years (N =270)



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


0

10

20

30

40

50

60

Any Induction (N = 155) Polyclonal ALG/ATG (N = 46) IL2R-antagonist (N = 108)

% o

f p

atien

tsPEDIATRIC LUNG RECIPIENTS

Induction ImmunosuppressionFor transplants between January 2001 and June 2006


0

10

20

30

40

50

60

70

Any Induction Polyclonal ALG/ATG IL2R-antagonist

% o

f p

ati

en

ts

2001 2002

2003 2004

2005 1/2006-6/2006

PEDIATRIC LUNG RECIPIENTSInduction Immunosuppression (Transplants: January 2001 - June 2006)


PEDIATRIC LUNG TRANSPLANTATION

Kaplan-Meier Survival Stratified by Induction Use (Transplants: January 2001 - June 2005)

0

25

50

75

100

0 1 2 3 4

Years

Su

rviv

al (

%)

Induction (N = 114)

No Induction (N = 104)

p = 0.9324


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

% o

f P

atie

nts

Year 1 (N = 210) Year 5 (N = 112)

PEDIATRIC LUNG RECIPIENTS Maintenance Immunosuppression at Time of Follow-up

(Follow-ups: January 2001 and June 2006)

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 = 210) 5 Year Follow-up (N = 112)NOTE: Different patients are analyzed in Year 1 and Year 5

ISHLT 2007

NOTE: 5% of patients were on both calcineurin inhibitors at different point during the year; these patients are not counted in either group. In the 5-year tabulations, 14% were reported to be on both drugs during the year.J Heart Lung Transplant 2007;26

0%

20%

40%

60%

80%

100%

Year 1 (N = 210) Year 5 (N = 112)

% 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 39.4% (N = 480)

Renal Dysfunction 8.7% (N=483)

Abnormal Creatinine < 2.5 mg/dl 5.6% Creatinine > 2.5 mg/dl 2.3% Chronic Dialysis 0.6% Renal Transplant 0.2%

Hyperlipidemia 3.6% (N = 496)

Diabetes 25.8% (N = 484)

Bronchiolitis Obliterans 13.5% (N = 446)


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 22.6% (N = 124) Abnormal Creatinine < 2.5 mg/dl 15.3% Creatinine > 2.5 mg/dl 4.0% Chronic Dialysis 1.6% Renal Transplant 1.6%


Diabetes 35.5% (N = 124)



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 36.2% (N = 58) Abnormal Creatinine < 2.5 mg/dl 24.1% Creatinine > 2.5 mg/dl 5.2% Chronic Dialysis 0.0% Renal Transplant 6.9%


Diabetes 31.6% (N = 57)



Freedom from Bronchiolitis Obliterans For Pediatric Lung Recipients (Follow-ups: April 1994 - June 2006)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

% F

ree f

rom

Bro

nch

ioliti

s O

blite

ran

s


FREEDOM FROM BRONCHIOLITIS OBLITERANSFor Pediatric Lung Recipients by Induction Use

(Transplants: April 1994 - June 2006)

0

25

50

75

100

0 1 2 3 4 5 6 7

Years

Induction (N = 129)

No Induction (N = 306)

p = 0.2297

% F

ree fro

m B

ron

ch

iolit

is O

blit

era

ns


Freedom from Severe Renal Dysfunction*For Pediatric Lung Recipients (Follow-ups: April 1994 - June 2006)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7Years

% F

ree f

rom

Severe

Ren

al

Dysfu

ncti

on

* Severe renal dysfunction = Creatinine > 2.5 mg/dl (221 μmol/L), dialysis or renal transplant


MALIGNANCY POST-LUNG TRANSPLANTATION FOR PEDIATRICSCumulative Incidence for Survivors (Follow-ups: April 1994 - June 2006)

Malignancy/Type 1-Year Survivors

5-Year Survivors

7-Year Survivors

No Malignancy 469 (94.6%) 111 (88.1%) 51 (87.9%)

Malignancy (all types combined)

27 (5.4%) 15 (11.9%) 7 (12.1%)

Malignancy Type

Lymph 24 14 6

Other 3 1 1

”Other” includes Liver and primitive neuroectodermal tumor.


Freedom from MalignancyFor Pediatric Lung Recipients (Follow-ups: April 1994 - June 2006)

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

% F

ree

from

Mal

igna

ncy

All malignancy Lymph Skin Other


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

CAUSE OF DEATH0-30 Days

(N =72 )31 Days - 1 Year

(N = 107)

>1 Year - 3 Years

(N = 111)

>3 Years - 5 Years

(N = 56)

>5 Years

(N = 38)

BRONCHIOLITIS 9 (8.4%) 43 (38.7%) 24 (42.9%) 16 (42.1%)

ACUTE REJECTION 1 (1.4%) 3 (2.8%) 1 (1.8%)

LYMPHOMA 3 (2.8%) 4 (3.6%) 2 (3.6%) 4 (10.5%)

MALIGNANCY, NON-LYMPHOMA

1 (1.8%)

CMV 6 (5.6%)

INFECTION, NON-CMV 9 (12.5%) 44 (41.1%) 23 (20.7%) 13 (23.2%) 3 (7.9%)

GRAFT FAILURE 24 (33.3%) 20 (18.7%) 21 (18.9%) 7 (12.5%) 8 (21.1%)

CARDIOVASCULAR 9 (12.5%) 4 (3.7%) 2 (1.8%)

TECHNICAL 10 (13.9%) 1 (0.9%)

MULTIPLE ORGAN FAILURE

6 (8.3%) 9 (8.4%) 9 (8.1%) 3 (5.4%) 3 (7.9%)

OTHER 13 (18.1%) 8 (7.5%) 9 (8.1%) 5 (8.9%) 4 (10.5%)


PEDIATRIC LUNG TRANSPLANT RECIPIENTS: Cause Of Death(Deaths: April 1994- June 2006)

CAUSE OF DEATH0-30 Days

(N =60 )31 Days - 1 Year

(N = 91)

>1 Year - 3 Years

(N = 103)

>3 Years - 5 Years

(N = 55)

>5 Years

(N = 38)

BRONCHIOLITIS 9 (9.9%) 40 (38.8%) 24 (43.6%) 16 (42.1%)

ACUTE REJECTION 1 (1.7%) 1 (1.1%) 1 (1.8%)

LYMPHOMA 1 (1.1%) 3 (2.9%) 2 (3.6%) 4 (10.5%)

MALIGNANCY, NON-LYMPHOMA

1 (1.8%)

CMV 5 (5.5%)

INFECTION, NON-CMV 8 (13.3%) 37 (40.7%) 21 (20.4%) 13 (23.6%) 3 (7.9%)

GRAFT FAILURE 17 (28.3%) 19 (20.9%) 21 (20.4%) 7 (12.7%) 8 (21.1%)

CARDIOVASCULAR 7 (11.7%) 3 (3.3%) 1 (1.%)

TECHNICAL 9 (15.%)

MULTIPLE ORGAN FAILURE

6 (10.%) 9 (9.9%) 9 (8.7%) 3 (5.5%) 3 (7.9%)

OTHER 12 (20.%) 7 (7.7%) 8 (7.8%) 4 (7.3%) 4 (10.5%)


lung transplantation pediatric recipients ishlt 2007 j heart lung transplant 2007;26

Documents

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