HEART TRANSPLANTATION

HEART TRANSPLANTATION

Pediatric Recipients

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

AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS (Transplants: January 1996 - June 2007)

0100200

300400500600

700800900

10001100

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 HEART RECIPIENTS

(Transplants: January 1996 - June 2007)

Nu

mb

er o

f T

ran

spla

nts

ISHLT 2008

0

100

200

300

400

500

600

700

800

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)

J Heart Lung Transplant 2008;27: 937-983

AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS

By Year of Transplant

0

50

100

150

200

250

300

350

400

450

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

11-17 Years

1-10 Years

<1 Year

Nu

mb

er o

f T

ran

spla

nts

ISHLT 2008

NOTE: This figure includes only the heart transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as evidence that the number of hearts transplanted worldwide has increased and/or decreased in recent years.


NUMBER OF CENTERS REPORTING PEDIATRIC HEART TRANSPLANTS

0102030405060708090

100110

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006N

um

ber

of

Ped

iatr

ic C

ases

Rep

ort

ing


AVERAGE CENTER VOLUMEPediatric Heart Transplants: January 1, 1997 - June 30, 2007

125

17

110

17 1590102030405060708090

100110120130

1-4/yr 5-9/yr 10-19/yr

Average number of heart transplants per year

Nu

mb

er

of

ce

nte

rs

.

1997-2000

2001-June 2007

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

DISTRIBUTION OF TRANSPLANTS BY CENTER VOLUME

Pediatric Heart Transplants: January 1, 1997 - June 30, 2007

35.728.4 30.627.7 24.5

47.8

0

10

20

30

40

50

1-4 5-9 10-19

Average number of heart transplants per year

% o

f tr

ansp

lan

ts .

1997-2000 2001-June 2007

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

PEDIATRIC HEART RE-TRANSPLANTSBy Transplant Year

Retransplants: January 1994 – December 2006

0

5

10

15

20

25

30

35

40

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

Nu

mb

er

of

tra

ns

pla

nts

Year of transplantISHLT 2008J Heart Lung Transplant 2008;27: 937-983

0

10

20

30

40

50

<1 month 1-<12 months 12-<36 months 36-<60 months 60+ months Not reported

% o

f R

e-T

ran

spla

nts

PEDIATRIC HEART RE-TRANSPLANTSBy Intertransplant Interval

Retransplants: January 1994 - June 2007

ISHLT 2008

Time Between Previous and Current Transplant


40

50

60

70

80

90

100

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

Su

rrv

iva

l (%

)

<1 Year (N=40) 1-<3 Years (N=30) 3-<5 Years (N=38)

5+ Years (N=114) Primary TX (N=4,593)

Comparison of survival for re-transplant groups: p = 0.0053

KAPLAN-MEIER SURVIVAL RATES FOR PEDIATRIC HEART RETRANSPLANTS STRATIFIED BY INTER-TRANSPLANT INTERVAL

Retransplants: January 1994 - June 2006

ISHLT 2008

Time (years) since most recent transplant


DIAGNOSIS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS (Age: < 1 Year)

02550

75100

Myopathy Congenital

30%

63%

6%

1%

17%

78%4%

1%

Myopathy

Congenital

Other

ReTX

1988-1995 1/1996-6/2007

% o

f C

ases


DIAGNOSIS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS (Age: 1-10 Years)

025

5075

100Myopathy Congenital

52%

37%

6%

5%52%

40%

4%

4%Myopathy

Congenital

Other

ReTX

1988-1995 1/1996-6/2007

% o

f C

ases


DIAGNOSIS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS (Age: 11-17 Years)

025

5075

100Myopathy Congenital

61%

7%

25%

7%67%

3%

26%

4%

Myopathy

Congenital

Other

ReTX1988-1995 1/1996-6/2007

% o

f C

ases


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival (Transplants: 1/1982-6/2006)

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 18 19 20

Years

<1 Year (N = 1,862) 1-10 Years (N = 2,598)11-17 Years (N = 2,742) Overall (N = 7,202)

0-<1 vs. 1-10: p = 0.0005; 0-<1 vs. 11-17: p=0.1835; 1-10 vs. 11-17: p=0.0099.

Half-life <1: 15.8 Years; 1-10: 15.0 Years; 11-17: 11.3 Years

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONConditional Kaplan-Meier Survival

(Transplants: 1/1982-6/2006)

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 18 19 20

Years

<1 Year (N = 1,267) 1-10 Years (N = 1,985)11-17 Years (N = 2,130) Overall (N = 5,382)

0-<1 vs. 1-10: p = 0.0096; 0-<1 vs. 11-17: p < 0.0001;1-10 vs. 11-17: p < 0.0001.

Half-life: <1: n.c.; 1-10: 18.7 Years; 11-17: 15.2 Years

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONConditional Kaplan-Meier Survival for Recent Era

(Transplants: 1/1999-6/2006)

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

<1 Year (N = 519) 1-10 Years (N = 873)11-17 Years (N = 910) Overall (N = 2,302)

0-<1 vs. 1-10: p = 0.3648;0-<1 vs. 11-17: p = 0.0032; 1-10 vs. 11-17: p < 0.0001

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Era

(Transplants: 1/1982-6/2006)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Years

1982-1989 (N=869) 1990-1994 (N=1,863)

1995-1999 (N=1,902) 2000-6/2006 (N=2,568)

All p-values significant at p< 0.0001 except comparison of 1995-1999 vs. 2000-6/2006

Half-life 1982-1989: 9.9 years; 1990-1994: 12.4 years; 1995-1999: n.c.; 2000-6/2006: n.c.

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: 1/1982-6/2005)

Age: < 1 Year

0

20

40

60

80

100

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

1982-1989 (N=167) 1990-1994 (N=562)

1995-1999 (N=480) 2000-6/2005 (N =473)

P-values for era comparisons82-89 vs. 90-94: 0.3879; 82-89 vs. 95-99: <.0001; 82_90 vs. 00-6/05: <.000190-94 vs. 95-99: <.0001; 90-94 vs. 00-6/05: <.0001; 95-99 vs. 00-6/05: 0.7892

Half-life 1982-1989: 10.8 years; 1990-1994: 10.6 years; 1995-1999: n.c. ; 2000-6/2005: n.c.S

urv

ival

(%

)

ISHLT 2008 Last updated based on data as of December 2006 J Heart Lung Transplant 2008;27: 937-983

PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Era (Transplants: 1/1982-6/2005)

Age: 1-10 Years

0

20

40

60

80

100

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

Years

1982-1989 (N = 266) 1990-1994 (N=652)

1995-1999 (N=724) 2000-6/2005 (N=790)

P-values for era comparisons82-89 vs. 90-94: 0.0270; 82-89 vs. 95-99: <.0001; 82-89 vs. 00-6/05: <.0001 90-94 vs. 95-99: 0.0021;89-94 vs. 00-6/05: <.0001; 95-99 vs. 00-6/05: 0.2005

Half-life 1982-1989: 10.9; 1990-1994: 12.5; 1995-1999: . ; 2000-6/2005: n.a.

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Era (Transplants: 1/1982-6/2005)

Age: 11-17 Years

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

Years

1982-1989 (N=427) 1990-1994 (N=628)

1995-1999 (N=673) 2000-6/2005 (N=833)

P-values for era comparisons82-89 vs. 90-94: 0.0465; 82-89 vs. 95-99: 0.0860; 82_90 vs. 88-6/05: <.0001; 90-94 vs. 95-99: 0.6394; 90-94 vs. 00-6/05: 0.0577; 95-99 vs. 00-6/05: 0.2086

Half-life 1982-1989: 9.9; 1990-1994: 11.5; 1995-1999: 10.1; 2000-6/2005: n.a.

Su

rviv

al (

%)


0%

20%

40%

60%

80%

100%

Europe North America Other

% o

f T

ran

spla

nts

1-4/yr 5-9/yr 10-19/yr

PEDIATRIC HEART TRANSPLANTS: AVERAGE CENTER VOLUME DISTRIBUTION BY LOCATION

Transplants between January 2000 and June 2007


0%

20%

40%

60%

80%

100%


% o

f T

ran

spla

nts

<1 years 1-10 years 11-17 years

PEDIATRIC HEART TRANSPLANTS:AGE DISTRIBUTION BY LOCATION



0%

20%

40%

60%

80%

100%


% o

f T

ran

sp

lan

ts

Other

Re-TX/GraftFailure

Malignancy

Coronary ArteryDisease

Congenital

Cardiomyopathy

PEDIATRIC HEART TRANSPLANTS:DIAGNOSIS DISTRIBUTION BY LOCATION



0%

20%

40%

60%

80%

100%


% o

f D

ono

rs

<1 1-10 11-17 18-34 35-49 50-64

PEDIATRIC HEART TRANSPLANTS:DONOR AGE DISTRIBUTION BY LOCATION



PEDIATRIC HEART TRANSPLANTS (1/1995-6/2006)

Risk Factors For 1 Year Mortality

N=3,395

VARIABLE N

Relative Risk

P-value 95% Confidence Interval

Congenital diagnosis, age > 0, on ECMO 56 4.80 <0.0001 2.94 -7.83

Congenital diagnosis, age = 0, on ECMO 63 4.74 <0.0001 2.99 -7.53

Congenital diagnosis, age > 0, no ECMO 735 2.32 <0.0001 1.76 -3.06

Retransplant 201 2.26 0.0001 1.52 -3.36

Congenital diagnosis, age=0, on PGE 209 1.93 0.0021 1.27 -2.93

Congenital diagnosis, age = 0, no PGE or ECMO 352 1.7 0.0039 1.19 -2.45

Year of Transplant: 1995-96 vs. 1999-2000 505 1.54 0.0057 1.13 -2.08

On ventilator 636 1.51 0.0008 1.19 -1.92

Female recipient 1488 1.23 0.0321 1.02 -1.48

Not ABO identical 759 0.77 0.0231 0.61 -0.96

ISHLT 2008

Reference diagnosis = cardiomyopathyJ Heart Lung Transplant 2008;27: 937-983


Borderline Significant Risk Factors For 1 Year Mortality

N=3,395

VARIABLE N Relative

Risk P-value

95% Confidence Interval

VAD (diagnosis other than congenital) 217 1.44 0.0769 0.96 -2.14

Infection requiring IV drug therapy (with 2wk/TX)

511 1.23 0.0952 0.96 -1.56

Donor cause of death = anoxia 764 0.82 0.0893 0.66 -1.03


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2006) Risk Factors for 1 Year Mortality

Continuous Factors (see figures)

Recipient Age (borderline) Creatinine

Donor Age Donor BSA (borderline)

Pediatric transplant volume

ISHLT 2008

N=3,395



Recipient Age

0

0.5

1

1.5

2

2.5

0 3 6 9 12 15 18

Recipient Age (Years)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.081

ISHLT 2008 N=3,395J Heart Lung Transplant 2008;27: 937-983


Donor Age

0

0.5

1

1.5

2

0 10 20 30 40

Donor Age (Years)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.006



Pre-Transplant Creatinine

0

0.5

1

1.5

2

0 0.5 1 1.5 2 2.5

Recipient serum creatinine (mg/dl)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p < 0.0001



Center Volume for Pediatric Transplants

0

0.5

1

1.5

2

2.5

0 2 4 6 8 10 12 14 16 18 20

Center Volume (cases per year)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.012



Donor BSA

0

0.5

1

1.5

2

0 0.5 1 1.5 2

Donor body surface area (m2)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.074


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2006) Factors Not Significant for 1 Year Mortality

Recipient Factors:IV inotropes, sternotomy, history of malignancy, hospitalized, diabetes

Donor Factors:Gender, clinical infection, history of diabetes

Transplant Factors:CMV mismatch, ischemia time, HLA mismatch



Risk Factors For 10 Year Mortality

N=697

VARIABLE N Relative

Risk P-

value 95% Confidence

Interval

Congenital diagnosis, ECMO 15 3.31 .0078 1.37 -7.99

Ventilator 107 1.60 .0339 1.04 -2.48

Female donor 299 1.56 .0141 1.09 -2.24



Continuous Factors (see figures)

Creatinine BSA ratio (borderline)

Pediatric transplant volume Donor weight

ISHLT 2008

N=697J Heart Lung Transplant 2008;27: 937-983


Pre-Transplant Creatinine

0

0.5

1

1.5

2

2.5

0 0.5 1 1.5 2

Creatinine (mg/dl)

Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

ali

ty

p = 0.0029

ISHLT 2008



Donor Weight

0

0.5

1

1.5

2

2.5

0 10 20 30 40 50 60 70 80

Donor weight (kg)

Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

ali

ty

p = 0.0008

ISHLT 2008 N=697J Heart Lung Transplant 2008;27: 937-983


Center Volume for Pediatric Transplants

0

0.5

1

1.5

2

0 2 4 6 8 10 12 14 16 18 20

Center Volume (cases per year)

Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

ali

ty

p = 0.0017

ISHLT 2008



BSA Ratio (Donor BSA/Recipient BSA)

0

0.5

1

1.5

2

2.5

0.8 1 1.2 1.4 1.6 1.8 2

BSA ratio

Re

lati

ve

Ris

k o

f 1

0 Y

ea

r M

ort

ali

ty

p = 0.052

ISHLT 2008


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2000) Factors Not Significant for 10 Year Mortality

Recipient Factors:PRA, diabetes, repeat transplant, transfusions, hospitalized, gender, PGE, VAD, bilirubin

Donor Factors:Cause of death, age, clinical infection

Transplant Factors:Ischemia time, HLA mismatch, CMV mismatch


PEDIATRIC HEART RECIPIENTS Functional Status of Surviving Recipients

(Follow-ups: April 1994 - June 2007)

0%

20%

40%

60%

80%

100%

1 Year (N = 2,134) 5 Year (N = 1,415) 10 Year (N = 554)

No Activity Limitations Performs with Some Assistance Requires Total Assistance


PEDIATRIC HEART RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients

(Follow-ups: April 1994 - June 2007)

0%

20%

40%

60%

80%

100%

1 Year (N = 3,110) 5 Years (N = 1,965) 10 Years (N = 883)

No Hospitalization Hospitalized, Not Rejection/Not Infection

Hospitalized, Rejection Hospitalized, Infection Only

Hospitalized, Rejection + Infection


0

10

20

30

40

50

Any Induction (N =1,033)

Polyclonal ALG/ATG (N= 685)

OKT3 (N = 44) IL2R-antagonist (N =332)

PEDIATRIC HEART RECIPIENTS Induction Immunosuppression

(Transplants: January 2001 - June 2007)

% o

f P

atie

nts

ISHLT 2008

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


0

10

20

30

40

50

60

70

Any Induction Polyclonal ALG/ATG IL2R-antagonist

% o

f P

ati

en

ts

2001200220032004200520062007

PEDIATRIC HEART RECIPIENTSInduction Immunosuppression (Transplants: January 2001 - June 2007)

ISHLT 2008

Test of increasing trend over time:Any induction p < 0.0001Polyclonal p < 0.0001IL2 p = 0.0029Analysis is limited to patients who were alive at the time of the follow-upJ Heart Lung Transplant 2008;27: 937-983

PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Group

(Transplants: January 2000 – June 2005) Conditional on Survival to 14 Days

50

60

70

80

90

100

0 1 2 3 4

Years

No induction (N =891)

Polyclonal induction (N = 509)

IL2R-antagonist (N =185)

Su

rviv

al (

%)

No comparisons were statistically significant.


PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Group and Rejection Between Transplant

Discharge and 1-Year Follow-up (1-Year Follow-ups: July 2004 - June 2006) Conditional on Survival to 1 Year

50

60

70

80

90

100

0 1 2

Years

No induction/No rejection (N = 180)

Polyclonal induction/No rejection (N = 95)

IL2R-antagonist/No rejection (N = 33)

No induction/Rejection (N = 68)

Polyclonal induction/Rejection (N = 61)

IL2R-antagonist/Rejection (N = 41)

Su

rviv

al (

%)

No pair-wise comparisons of survival by induction were statistically significant within either rejection grouping except No induction/Rejection vs. Polyclonal/Rejection (p=0.0329).


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2005)

Conditional on Survival to 14 DaysAge: < 1 Year

50

60

70

80

90

100

0 1 2 3 4

Years

No induction (N = 185)Polyclonal induction (N = 191)IL2R-antagonist (N = 23)


Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2005)

Conditional on Survival to 14 DaysAge: 1-10 Years

50

60

70

80

90

100

0 1 2 3 4

Years

No induction (N = 358)Polyclonal induction (N = 177)IL2R-antagonist (N = 66)

Su

rviv

al (

%)

ISHLT 2008


Last updated based on data as of December 2006 J Heart Lung Transplant 2008;27: 937-983

PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2005)

Conditional on Survival to 14 DaysAge: 11-17 Years

50

60

70

80

90

100

0 1 2 3 4

Years

No induction (N = 348)

Polyclonal induction (N = 141)

IL2R-antagonist (N = 96)


Su

rviv

al (

%)


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

Year 1 (N = 1,647) Year 5 (N = 1,114)

PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up

(Follow-ups: January 2001 - June 2007)

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

% o

f P

atie

nts

ISHLT 2008



PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up

for Same Patients at Each Time Point(Follow-ups: January 2001 - June 2007)

% o

f P

atie

nts

ISHLT 2008

0%

20%

40%

60%

80%

100%

Year 1 (N = 432) Year 5 (N = 432)

None

Other

Tacrolimus

Tacrolimus + MMF

Tacrolimus + AZA

Cyclosporine

Cyclosporine + MMF

Cyclosporine + AZA



0%

20%

40%

60%

80%

100%

Year 1 (N = 1,647) Year 5 (N = 1,114)

None

Other

Tacrolimus

Tacrolimus + MMF

Tacrolimus + AZA

Cyclosporine

Cyclosporine + MMF

Cyclosporine + AZA

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

(Follow-ups: January 2001 - June 2007)

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

% o

f P

atie

nts

ISHLT 2008



PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Prednisone Use

Conditional on Survival to 1 Year (Transplants: April 1994 - June 2006)

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9

Years

Prednisone use at discharge and 1 year (N = 1,684)

No Prednisone at discharge or at 1 year (N = 344)

Prednisone at discharge/not at 1 year (N = 319)

p < 0.0001

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Prednisone Use for a Recent Era

Conditional on Survival to 1 Year (Transplants: January 1998 – June 2006)

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

Prednisone use at discharge and 1 year (N = 1,352)

No Prednisone at discharge or at 1 year (N = 254)

Prednisone at discharge/not at 1 year (N = 259)

p = 0.0050

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Stratified by Tacrolimus vs. Cyclosporine Use at Discharge

(Transplants: January 1998 - June 2006) Conditional on Survival to 14 Days

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

Tacrolimus use at discharge (N = 987)

Cyclosporine use at discharge (N = 1,330)

Su

rviv

al (

%)

ISHLT 2008

p = 0.1706


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Rejection within 1st Year

(1-Year Follow-ups: July 2004 - June 2006)

50

60

70

80

90

100

0 1 2

Years

Free from Rejection during 1 year (N = 191)Rejection within 1st Year (N = 130)

p = 0.0346

Su

rviv

al (

%)



Stratified by Calcineurin Use at Discharge (1-Year Follow-ups: July 2004 - June 2006)

50

60

70

80

90

100

0 1 2

Years

CyA: Free from Rejection during 1 year (N = 68)

CyA: Rejection within 1st Year (N = 58)

TAC: Free from Rejection during 1 year (N = 106)

TAC: Rejection within 1st Year (N = 58)

Free from Rejection: CyA vs. TAC p = 0.9104Rejection: CyA vs. TAC p = 0.8471 CyA: Rejection vs. no rejection p = 0.3447TAC: Rejection vs. no rejection p = 0.1567

Su

rviv

al (

%)



Stratified by Calcineurin Use at Discharge: Age = 0-10 Years (1-Year Follow-ups: July 2004 - June 2006)

50

60

70

80

90

100

0 1 2

Years


CyA: Rejection within 1st Year (N = 44)



Free from Rejection: CyA vs. TAC p = 0.1832Rejection: CyA vs. TAC p = 0.5836 CyA: Rejection vs. no rejection p = 0.3782TAC: Rejection vs. no rejection p = 0.1706

Su

rviv

al (

%)



Stratified by Calcineurin Use at Discharge: Age = 11-17 Years (1-Year Follow-ups: July 2004 - June 2006)

50

60

70

80

90

100

0 1 2

Years


CyA: Rejection within 1st Year (N =14)



Free from Rejection: CyA vs. TAC p = 0.1772Rejection: CyA vs. TAC p = 0.2053 CyA: Rejection vs. no rejection naTAC: Rejection vs. no rejection p = 0.5540

Su

rviv

al (

%)


PERCENTAGE OF PEDIATRIC HEART TRANSPLANT RECIPIENTS EXPERIENCING ACUTE REJECTION IN 1ST YEAR

Stratified by Induction (Follow-ups: July 2004 - June 2007)

0

10

20

30

40

50

60

70No induction Used, Treatment No induction Used, No Treatment

Induction Used (no OKT3), Treatment Induction Used (no OKT3), No Treatment

% e

xper

ien

cin

g a

cute

rej

ecti

on

wit

hin

1 y

ear

Overall: p = 0.042

ISHLT 2008

Overall < 1 1-10 10-17 Female Male




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

0

10

20

30

40

50

60

70 No induction, Treatment No induction, No TreatmentPolyclonal, Treatment Polyclonal, No TreatmentIL2R-antagonist, Treatment IL2R-antagonist, No Treatment

% e

xper

ien

cin

g a

cute

rej

ecti

on

wit

hin

1 y

ear

Overall: No induct vs. IL2R (p=0.001); Polyclonal vs. IL2R (p = 0.006) 1-10: No induct vs. IL2R (p=0.019) 11-17: No induction vs. IL2R (p=0.037)Female: No induction vs. IL2R (p = 0.006); Polyclonal vs. IL2R (p =0.026)Male: No induction vs. IL2R (p = 0.034)

ISHLT 2008

Overall < 1 1-10 10-17 Female Male




Stratified by Maintenance Immunosuppression and Induction (Follow-ups: July 2004 - June 2007)

0

10

20

30

40

50

60

70CyA + No induction, Treatment CyA + No induction, No TreatmentCyA + Induction (no OKT3), Treatment CyA + Induction (no OKT3), No TreatmentTAC + No induction, Treatment TAC + No induction, No TreatmentTAC + Induction (no OKT3), Treatment TAC + Induction (no OKT3), No Treatment

% e

xper

ien

cin

g a

cute

rej

ecti

on

wit

hin

1 y

ear

Overall: all comparisons were statistically significant at 0.05 except CyA + no induction vs. CyA + induction and TAC + no induction vs. TAC + induction<1 year: CyA + no induction vs. TAC + no induction: p=0.001; CyA + no induction vs. TAC + induction: p=0.001; CyA + induction vs. TAC + no induction: p=0.032; CyA + induction vs. TAC + induction: p= 0.026

1-10 years: CyA + induction vs. TAC + induction: p =0.006; CyA + induction vs. TAC + no induction: p = 0.0001

11-17 years: CyA + no induction vs. TAC + no induction: p = 0.001; CyA + induction vs. TAC + no induction: p < 0.0001; CyA + induction vs. TAC + induction: p =0.008

ISHLT 2008

Overall < 1 1-10 10-17




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

0

10

20

30

40

50

60

70

Cyclosporine + MMF, Treatment Cyclosporine + MMF, No TreatmentCyclosporine + AZA, Treatment Cyclosporine + AZA, No TreatmentTacrolimus + MMF, Treatment Tacrolimus + MMF, No TreatmentTacrolimus + AZA, Treatment Tacrolimus + AZA, No Treatment

% e

xper

ien

cin

g a

cute

rej

ecti

on

wit

hin

1 y

ear

Overall: CyA +MMF vs. TAC + MMF (p < 0.0001); CyA + MMF vs. TAC + AZA (p =0.001); <1: CyA + MMF vs. TAC + MMF (p =0.0004); CyA + MMF vs. TAC + AZA )p=0.016).1-10: CyA + MMF vs. TAC + MMF (p = 0.010).11-17: CyA + MMF vs. TAC + MMF (p =0.0002).

ISHLT 2008

Overall < 1 1-10 10-17




Stratified by Calcineurin Inhibitor Use at Discharge (Follow-ups: July 2004 - June 2007)

0

10

20

30

40

50

60Cyclosporine, Treatment Cyclosporine, No TreatmentTacrolimus, Treatment Tacrolimus, No Treatment

% e

xper

ien

cin

g a

cute

rej

ect

ion

wit

hin

1 y

ear

Overall: CyA vs. TAC (p < 0.0001)<1: CyA vs. TAC (p=0.0005) 1-10: CyA vs. TAC (p < 0.0008)11-17: CyA vs. TAC (p < 0.0001)

ISHLT 2008

Overall < 1 1-10 10-17



FREEDOM FROM CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2007)

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

Years

% F

reed

om

fro

m C

AV


FREEDOM FROM CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2007)

Stratified by Induction

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

Years

Induction (N = 1,084)

No Induction (N = 1,673)% F

ree

do

m f

rom

CA

V

p = 0.7992


FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2007)

Stratified by Age Group

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

Years

<1 Year (N =732)

1-10 Years (N = 1,024)

11-17 Years (N = 1,013)

p < 0.0001

% F

ree

do

m f

rom

CA

V


FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: January 1999-June 2007)

Stratified by Age Group

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

<1 Year (N = 484)

1-10 Years (N = 724)

11-17 Years (N = 732)

p < 0.0001

% F

ree

do

m f

rom

CA

V



Stratified by Ischemia Time

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

0-<2 hours (N=296)

2-<4 hours (N=1,407)

4+ hours (N=874)

p = 0.0204

% F

ree

do

m f

rom

CA

V


FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: January 1999 - June 2007)

Stratified by Ischemia Time for Recent Era

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

0-<2 hours (N=183)

2-<4 hours (N=972)

4+ hours (N=614)

p = 0.0476

% F

ree

do

m f

rom

CA

V



Stratified by Ischemia Time and Recipient Age

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9

Years

0-<2 hours/0-10 years (N=165)

2+ hours/0-10 years (N=1,469)

0-<2 hours/11-17 years (N=115)

2+ hours/11-17 years (N=718)

0-10 years: p = 0.0106;11-17 years: p = 0.4709

% F

ree

do

m f

rom

CA

V


GRAFT SURVIVAL FOLLOWING REPORT OF CORONARY ARTERY VASCULOPATHY

For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2007)Stratified by Age Group

0

10

20

30

40

50

60

70

80

90

100

0 0.5 1 1.5 2 2.5 3 3.5

Time since Report of CAV (Years)

<1 Year (N = 70)

1-10 Years (N = 117)

11-17 Years (N = 162)

p = 0.2006

Su

rviv

al s

ince

Rep

ort

of

CA

V (

%)


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

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9

Years

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

% F

reed

om

fro

m S

ever

e

Ren

al D

ysfu

nct

ion


MALIGNANCY POST-HEART TRANSPLANTATION FOR PEDIATRICSCumulative Prevalence in Survivors (Follow-ups: April 1994 - June 2007)

Malignancy/Type 1-Year Survivors

5-Year Survivors

10-Year Survivors

No Malignancy 3,065 (98.1%) 1,177 (95%) 253 (91.7%)

Malignancy (all types combined) 58 (1.9%) 62 (5%) 23 (8.3%)

Malignancy Type

Lymph 54 57 22

Other 3 6

Skin 1

Type Not Reported 1 1

ISHLT 2008

NOTE: Multiple types may be reported; sum of types may be greater than total number with malignancy.


FREEDOM FROM MALIGNANCYFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2007)

80

85

90

95

100

0 1 2 3 4 5 6 7 8 9 10

Years

All malignancy Lymph Skin Other

% F

reed

om

fro

m M

alig

nan

cy


PEDIATRIC HEART RECIPIENTS Incidence of Hypertension between 1 and 3 Years

(Transplants: April 1993 - June 2004)

Maintenance Immunosuppression at discharge and 1 year

% HTN reported between 1 and 3 years

P-valueFor Patients

on drugFor Patients not on drug

Azathioprine 22.2 25.7 0.2649

Cyclosporine 20.8 27.1 0.0569

MMF 22.1 22.8 0.8454

Prednisone 29.7 8.4 <.0001

Rapamycin 50.0 22.1 -

Tacrolimus 30.8 19.6 0.0007


PEDIATRIC HEART RECIPIENTS Incidence of Hypertension between 3 and 8 Years

(Transplants: April 1993 - June 1999)

Maintenance Immunosuppression at discharge and 1 year

% HTN reported between 3 and 8 years

P-valueFor Patients

on drugFor Patients not on drug

Azathioprine 37.5 44.7 0.4159

Cyclosporine 36.7 42.9 0.5334

MMF 38.1 37.6 0.9627

Prednisone 47.7 21.5 0.0003

Rapamycin . 37.3 -

Tacrolimus 40.9 34.5 0.5515


PEDIATRIC HEART RECIPIENTSRelationship of Rejection and Coronary Artery Vasculopathy

(Follow-ups: July 2004 – June 2007)

Rejection During 1st

Year

Reported CAV between 1st and 3rd years

post-transplant

Yes No All

Yes 1

5.5%

17

94.4%

18

100%

No 1

3.4%

28

96.6%

29

100%p = 0.7279


PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2007)

CAUSE OF DEATH 0-30 Days (N = 444)

31 Days - 1 Year (N = 392)

>1 Year - 3 Years (N = 294)

>3 Years - 5 Years (N = 216)

>5 Years - 10 Years (N = 323)

>10 Years (N = 144)

CORONARY ARTERY VASCULOPATHY

5 (1.1%) 31 (7.9%) 59 (20.1%) 65 (30.1%) 92 (28.5%) 44 (30.6%)

ACUTE REJECTION 42 (9.5%) 94 (24.0%) 69 (23.5%) 29 (13.4%) 36 (11.1%) 8 (5.6%)

LYMPHOMA 10 (2.6%) 11 (3.7%) 5 (2.3%) 32 (9.9%) 9 (6.3%)

MALIGNANCY, OTHER 4 (1.0%) 2 (0.7%) 1 (0.5%) 4 (1.2%) 10 (6.9%)

CMV 1 (0.2%) 8 (2.0%) 1 (0.3%)

INFECTION, NON-CMV 53 (11.9%) 64 (16.3%) 20 (6.8%) 8 (3.7%) 14 (4.3%) 10 (6.9%)

PRIMARY FAILURE 101 (22.7%)

21 (5.4%) 10 (3.4%) 15 (6.9%) 17 (5.3%) 4 (2.8%)

GRAFT FAILURE 95 (21.4%) 41 (10.5%) 53 (18.0%) 49 (22.7%) 68 (21.1%) 32 (22.2%)

TECHNICAL 24 (5.4%) 3 (0.8%) 2 (0.7%) 2 (0.9%) 4 (1.2%)

OTHER 26 (5.9%) 30 (7.7%) 33 (11.2%) 25 (11.6%) 35 (10.8%) 12 (8.3%)

MULTIPLE ORGAN FAILURE

41 (9.2%) 47 (12.0%) 10 (3.4%) 6 (2.8%) 9 (2.8%) 7 (4.9%)

RENAL FAILURE 1 (0.2%) 3 (0.8%) 1 (0.5%) 2 (1.4%)

PULMONARY 29 (6.5%) 23 (5.9%) 15 (5.1%) 8 (3.7%) 6 (1.9%) 5 (3.5%)

CEREBROVASCULAR 26 (5.9%) 13 (3.3%) 9 (3.1%) 2 (0.9%) 6 (1.9%) 1 (0.7%)


PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1998 - June 2007)

CAUSE OF DEATH 0-30 Days (N = 189)

31 Days - 1 Year (N = 208)

>1 Year - 3 Years (N = 179)

>3 Years - 5 Years (N = 142)

>5 Years - 10 Years (N = 257)

>10 Years (N =137)

CAV 2 (1.1%) 13 (6.3%) 30 (16.8%) 39 (27.5%) 71 (27.6%) 42 (30.7%)

ACUTE REJECTION 20 (10.6%) 39 (18.8%) 34 (19.0%) 20 (14.1%) 27 (10.5%) 8 (5.8%)

LYMPHOMA 6 (2.9%) 6 (3.4%) 3 (2.1%) 27 (10.5%) 9 (6.6%)

MALIGNANCY, OTHER

1 (0.5%) 1 (0.6%) 3 (1.2%) 9 (6.6%)

CMV 4 (1.9%) 1 (0.6%)

INFECTION, NON-CMV

23 (12.2%) 30 (14.4%) 11 (6.1%) 3 (2.1%) 10 (3.9%) 8 (5.8%)

PRIMARY FAILURE 39 (20.6%) 7 (3.4%) 4 (2.2%) 6 (4.2%) 9 (3.5%) 4 (2.9%)

GRAFT FAILURE 29 (15.3%) 21 (10.1%) 39 (21.8%) 40 (28.2%) 59 (23.0%) 30 (21.9%)

TECHNICAL 11 (5.8%) 2 (1.1%) 4 (1.6%)

OTHER 19 (10.1%) 22 (10.6%) 28 (15.6%) 18 (12.7%) 30 (11.7%) 12 (8.8%)

MULTIPLE ORGAN FAILURE

22 (11.6%) 33 (15.9%) 9 (5.0%) 5 (3.5%) 7 (2.7%) 7 (5.1%)

RENAL FAILURE 3 (1.4%) 1 (0.7%) 1 (0.7%) 2 (1.5%)

PULMONARY 11 (5.8%) 20 (9.6%) 10 (5.6%) 6 (4.2%) 5 (1.9%) 5 (3.6%)

CEREBROVASCULAR 13 (6.9%) 9 (4.3%) 4 (2.2%) 1 (0.7%) 5 (1.9%) 1 (0.7%)


HEART TRANSPLANTATION

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