HEART TRANSPLANTATION Pediatric Recipients ISHLT 2006 J Heart Lung Transplant 2006;25:893-903.

HEART TRANSPLANTATION

Pediatric Recipients

ISHLT 2006 J Heart Lung Transplant 2006;25:893-903

AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS (Transplants: January 1996 - June 2005)

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

Recipient Age (Years)

Nu

mb

er o

f T

ran

spla

nts


AGE DISTRIBUTION FOR DONORS OF PEDIATRIC HEART RECIPIENTS

(Transplants: January 1996 - June 2005)

Nu

mb

er o

f T

ran

spla

nts

ISHLT 2006

0

100

200

300

400

500

600

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 2006;25:893-903

AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS

By Year of Transplant

0

100

200

300

400 11-17 Years

1-10 Years

<1 Year

11 945

77122

142

195

257

326

368366

384370

381355

386374

358362

346360

354 343

Nu

mb

er o

f T

ran

spla

nts

ISHLT 2006

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 declined in recent years.


NUMBER OF CENTERS REPORTING PEDIATRIC HEART TRANSPLANTS

0

20

40

60

80

100

Nu

mb

er o

f P

edia

tric

Cas

es R

epo

rtin

g


AVERAGE CENTER VOLUMEPediatric Heart Transplants: January 1, 1997 - June 30, 2005

114

19 1

96

22 1180

10

20

30

40

50

60

70

80

90

100

110

120

1-4 5-9 10-19 20-29

Average number of heart transplants per year

Nu

mb

er

of

cen

ters

. 1997-2000

2001-6/2005

ISHLT 2006J Heart Lung Transplant 2006;25:893-903

DISTRIBUTION OF TRANSPLANTS BY CENTER VOLUME

Pediatric Heart Transplants: January 1, 1997 - June 30, 2005

33.3 32.928.4

5.4

25.9

35.139.0

0

5

10

15

20

25

30

35

40

1-4 5-9 10-19 20-29

Average number of heart transplants per year

% o

f tr

ansp

lan

ts .

1997-2000

2001-6/2005


PEDIATRIC HEART RE-TRANSPLANTSBy Transplant Year

Retransplants: January 1990 – December 2003

0

5

10

15

20

25

30

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

Nu

mb

er

of

tra

ns

pla

nts

Year of transplant


ISHLT

0

10

20

30

40

50

60

70

80

90

100

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

Nu

mb

er

of

Re

-Tra

ns

pla

nts

PEDIATRIC HEART RE-TRANSPLANTSBy Intertransplant Interval

Retransplants: January 1994 - June 2005

ISHLT 2006

Time Between Previous and Current Transplant


50

60

70

80

90

100

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

Su

rrviv

al (

%)

<1 month (N=21) 1-<12 months (N=13) 12-<36 months (N=26)

36+ months (N=104) Primary TX (N=3560)

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

Retransplants: January 1994 - June 2004

ISHLT 2006

Time (years) since most recent transplant


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

025

5075

100

MyopathyCongenital

31%

66%

2%

1%

16%

81%1%

2%

Myopathy

Congenital

Other

ReTX

1988-1995 1/1996-6/2005

% o

f C

ases


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

025

5075

100Myopathy Congenital

53%

1%

0%

37%

2%

7%53%

1%

0%

40%

2%

4% Myopathy

CoronaryArtery DiseaseMalignancy

CongenitalHeart DiseaseOther

ReTX

1988-1995 1/1996-6/2005

% o

f C

ases


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

025

5075

100Myopathy Congenital

63%

27%

2%

7%

1% 0%

67%

26%

2%

3%

2%0%

Myopathy

Coronary ArteryDiseaseMalignancy

Congenital

Other

ReTX

1

1988-1995 1/1996-6/2005

% o

f C

ases


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival (1/1982-6/2004)

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 18 19 20

Years

<1 Year (N = 1,503) 1-10 Years (N = 2,213)11-17 Years (N = 2,308) Overall (N = 6,024)

<1 year vs. 1-10 years: p = 0.0027

HALF-LIFE <1: 14.9 years; 1-10: 13.4 years; 11-17: 11.5 years

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONConditional Kaplan-Meier Survival (1/1982-6/2004)

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 = 1,014) 1-10 Years (N = 1,666)11-17 Years (N = 1,780) Overall (N = 4,460)

0-1 vs. 1-10: p=0.0092Both comparisons with 11-17 years significant at p < 0.0001

HALF-LIFE <1: 18.4 years;1-10: 17.5 years; 11-17: 15.2 years

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONConditional 5-year Kaplan-Meier Survival (1/1982-6/2004)

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 = 598) 1-10 Years (N = 936)11-17 Years (N = 945) Overall (N = 2,479)

0-1 vs. 1-10: p=0.00030-1 vs. 11-17: p<0.00011-10 vs. 11-17: p=0.0025

HALF-LIFE 1-10: 19.8 years

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONConditional Kaplan-Meier Survival for Recent Era

(1/1999-6/2004)

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

<1 Year (N = 333) 1-10 Years (N = 582)11-17 Years (N = 585) Overall (N = 1,500)

0-1 vs. 11-17: p<0.039

Half-life not computable for any age group.

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Era (1/1982-6/2004)

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 = 850) 1990-1994 (N=1,775)

1995-1999 (N=1,820) 2000-6/2004 (N=1,579)

All p-values significant at p< 0.0001 except comparison of 1995-1999 vs. 2000-6/2004

HALF-LIFE 1982-1989: 10.0 years; 1990-1994: 11.9 years; 1995-1999: n.c.; 2000-6/2004: n.c.

Su

rviv

al (

%)



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=164) 1990-1994 (N=521)

1995-1999 (N=451) 2000-6/2004 (N =367)

P-values for era comparisons1982-89 vs. 1990-94: p=0.39; 1982-89 vs. 1995-1999: p < 0.0001;1982-89 vs. 2000-6/04: p < 0.0001; 1990-94 vs. 1995-99: p < 0.0001;1990-94 vs. 2000-6/04: p < 0.0001; 1995-99 vs. 2000-6/04: p = 0.41

HALF-LIFE 1982-1989: 10.8 years; 1990-1994: 10.6 years;1995-1999: n.c.; 2000-6/2004: n.c.S

urv

ival

(%

)



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 = 264) 1990-1994 (N=641)

1995-1999 (N=709) 2000-6/2004 (N=599)

P-values for era comparisons1982-89 vs. 1990-94: p = 0.028; 1982-89 vs. 1995-99: p < 0.0001; 1982-89 vs. 2000-6/04: p < 0.0001; 1990-94 vs. 1995-99: p = 0.0009; 1989-94 vs. 2000-6/04: p < 0.0001; 1995-99 vs. 2000-6/04: p = 0.71

HALF-LIFE 1982-1989: 10.9 years; 1990-1994: 12.6 years; 1995-1999: n.c.; 2000-6/2004: n.c.

Su

rviv

al (

%)



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=422) 1990-1994 (N=613)

1995-1999 (N=660) 2000-6/2004 (N=613)

P-values for era comparisons1982-89 vs. 1990-94: p=0.08; 1982-89 vs. 1995-99: p = 0.0101; 1982-89 vs. 2000-6/04: p < 0.0001; 1990-94 vs. 1995-99: p = 0.77; 1990-94 vs. 2000-6/04: p = 0.75; 1995-99 vs. 2000-6/04: p = 0.31

HALF-LIFE 1982-1989: 9.9 years; 1990-1994: 11.3 years; 1995-1999: 10.1 years; 2000-6/2004: n.c.

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2004)

Risk Factors For 1 Year Mortality

N=3,341

VARIABLE N

Relative Risk

P-value 95% Confidence

Interval

Congenital diagnosis, on ECMO 81 4.57 <0.0001 3.03 -6.89

Congenital diagnosis, no ECMO 1025 2.11 <0.0001 1.68 -2.65

Other diagnosis (not congenital, cardiomyopathy or retransplant)

122 1.92 0.0072 1.19 -3.10

Retransplant 160 1.85 0.0043 1.21 -2.83

Year of Transplant: 1995 vs. 1998 361 1.84 0.0016 1.26 -2.68

Congenital diagnosis, age=0, on PGE 189 1.73 0.0074 1.16 -2.58


Hospitalized (including ICU) 2384 1.38 0.0097 1.08 -1.75

On ventilator 513 1.37 0.0132 1.07 -1.75



Borderline Significant Risk Factors For 1 Year Mortality

N=3,341

VARIABLE N Relative

Risk P-value

95% Confidence Interval

ECMO, diagnosis other than congenital 80 1.66 0.0649 0.97 -2.83

VAD 165 1.47 0.0535 0.99 -2.17


Female recipient 1451 1.2 0.0554 1 -1.44

Donor cause of death: anoxia 607 0.82 0.0977 0.64 1.04


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2004) Risk Factors for 1 Year Mortality

Continuous Factors (see figures) Donor Age

Bilirubin

Creatinine

Weight ratio



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 = 0.0005



Pre-Transplant Bilirubin

0

0.5

1

1.5

2

0 1 2 3 4 5 6 7 8 9 10

Recipient Bilirubin (mg/dl)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.03



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 = 0.001



Weight Ratio

0

0.5

1

1.5

2

2.5

0.5 1 1.5 2 2.5 3 3.5

Weight ratio (donor weight/recipient weight)

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p = 0.004


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2004) Factors Not Significant for 1 Year Mortality

Recipient Factors:IV inotropes, sternotomy, thoracotomy, history of malignancy, height, recent infection, age, PA pressure, cardiac output, pulmonary vascular resistance, PRA



Donor Factors:Gender, history of hypertension, height, clinical infection, history of diabetes

Transplant Factors:CMV mismatch, ABO identical/compatible, ischemia time, HLA mismatch, transplant center volume


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2004) 1-Year Predicted Survival

50%

60%

70%

80%

90%

100%

0 0.2 0.4 0.6 0.8 1

Time (years)

Pre

dic

ted

Su

rviv

all

Recipient: 12 year old female, 30 kg, creatinine=1.4;

Donor: 16 year old female, COD = MVA, 45 kg, ischemia time = 3 hours.

Retransplant, on home milrinone

Primary transplant, ECMO, ventilator



Risk Factors For 5 Year Mortality

N=1,953

VARIABLE N Relative

Risk P-

value 95% Confidence

Interval

Re-transplant 79 2.22 .0000 1.51 -3.25

Recipient on dialysis 21 2.02 .0292 1.07 -3.79

ECMO 63 1.88 .0040 1.22 -2.90

Congenital diagnosis, no ECMO 595 1.55 .0001 1.25 -1.93

Congenital diagnosis, age=0, PGE 144 1.53 .0294 1.04 -2.24

Year of Transplant: 1995 vs. 1998 361 1.40 .0277 1.04 -1.89

Year of Transplant: 1996 vs. 1998 341 1.36 .0463 1.01 -1.85

Hospitalized (including ICU) 1388 1.26 .0400 1.01 -1.56

Female donor 836 1.25 .0142 1.05 -1.49

A locus HLA mismatches (0,1 or 2 – RR per mismatch)

1 MM – 752 2 MM - 1096 1.21 .0157 1.04 -1.42



Borderline Significant Risk Factors For 5 Year Mortality

N=1,953

VARIABLE N Relative

Risk P-

value 95% Confidence

Interval Other diagnosis (not congenital, cardiomyopathy or retransplant)

66 1.53 .0828 0.95 -2.49

Female recipient 817 1.19 .0575 0.99 -1.43



Continuous Factors (see figure)

Recipient weight


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2000) Risk Factors for 5 Year Mortality Pre-Transplant Recipient Weight

0

1

2

3

0 15 30 45 60 75

Recipient Weight (kg)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity

p = 0.004



Recipient Factors:History of malignancy, recent infection, bilirubin, age, PRA, pulmonary vascular resistance, PA pressures, cardiac output, sternotomy, height



Donor Factors:Cause of death, history of hypertension, weight, height, age

Transplant Factors:Donor/recipient weight ratio, CMV mismatch, ischemia time, HLA mismatch, transplant center volume


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2000)Risk Factors For 5 Year Mortality Conditional on 1 Year Survival

N=1,571

VARIABLE N Relative Risk

P-value 95% Confidence Interval

ECMO, diagnosis other than congenital

23 2.71 0.018 1.19 -6.2

Re-transplant 61 2.51 0.0004 1.51 -4.17

Treated for rejection (after transplant hospitalization)

424 1.96 <.0001 1.47 -2.62

Female recipient 654 1.39 0.0261 1.04 -1.85


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2000)Borderline Significant Risk Factors

For 5 Year Mortality Conditional on 1 Year Survival

N=1,571

VARIABLE N Relative Risk

P-value 95% Confidence Interval

Congenital diagnosis, age=0, PGE 106 1.78 0.0728 0.95 3.35


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2000) Risk Factors For 5 Year Mortality Conditional on 1 Year Survival

Continuous Factors (see figures)

Recipient weight


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2000) Risk Factors For 5 Year Mortality Conditional on 1 Year Survival

Recipient Weight

0

0.5

1

1.5

2

0 15 30 45 60 75

Recipient Weight (kg)

Re

lati

ve

Ris

k o

f 5

Ye

ar

Mo

rta

lity p = 0.0034


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2000) Factors Not Significant for Conditional 5 Year Mortality

Recipient Factors:History of malignancy, recent infection, hospitalized at time of transplant, bilirubin, creatinine, cardiac output, pulmonary vascular resistance, PRA, sternotomy, ventilator, VAD, age, PA pressures


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2000) Factors Not Significant for Conditional 5 Year Mortality

Donor Factors:Cause of death, history of hypertension, weight, height, age, gender, clinical infection at donation

Transplant Factors:Donor/recipient weight ratio, year of transplant, CMV mismatch, transplant center volume, induction use, treated for infection prior to discharge, dialysis prior to discharge


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2000) 5-Year Predicted Survival Conditional on Survival to 1 Year

50%

60%

70%

80%

90%

100%

1 2 3 4 5

Time (years)

Pre

dic

ted

Su

rviv

all

Treated for rejection

Not treated for rejection

Recipient: male with dilated cardiomyopathy, 1 year old, 8 kg, creatinine=0.8, not hospitalized at time of transplant;

Donor: male, 2 years old, 13 kg, COD = asphyxia, ischemia time = 3 hours.


PEDIATRIC HEART RECIPIENTS Functional Status of Surviving Recipients

(Follow-ups: April 1994 - June 2005)

0%

20%

40%

60%

80%

100%

1 Year (N = 2,072) 3 Years (N = 1,715) 5 Years (N = 1,386) 8 Years (N = 861)

No Activity Limitations Performs with Some Assistance Requires Total Assistance


PEDIATRIC HEART RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients


0%

20%

40%

60%

80%

100%

Up to 1 Year (N = 2,503)

Between 2 and 3Years (N = 1,975)



No Hospitalization Hospitalized, Not Rejection/Not Infection

Hospitalized, Rejection Hospitalized, Infection Only

Hospitalized, Rejection + Infection


0

10

20

30

40

50

Any Induction (N = 626) Polyclonal ALG/ATG (N= 413)

OKT3 (N = 34) IL2R-antagonist (N =208)

PEDIATRIC HEART RECIPIENTS Induction Immunosuppression (Transplants: January 2001 - June 2005)

% o

f P

atie

nts


0

10

20

30

40

50

60

Any Induction Polyclonal ALG/ATG OKT3 IL2R-antagonist

% o

f P

atien

ts

2001

2002

2003

2004

1/2005-6/2005

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


PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Group

(Transplants: January 2000 – June 2004) Conditional on Survival to 14 Days

50

60

70

80

90

100

0 1 2 3

Years

No induction (N = 704)

Polyclonal induction (N = 386)

IL2R-antagonist (N = 148)

Su

rviv

al (

%)

No comparisons were statistically significant.


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2004)

Conditional on Survival to 14 DaysAge: < 1 Year

50

60

70

80

90

100

0 1 2 3

Years

No induction (N = 149)Polyclonal induction (N = 148)IL2R-antagonist (N = 18)


Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2004)

Conditional on Survival to 14 DaysAge: 1-10 Years

50

60

70

80

90

100

0 1 2 3

Years

No induction (N = 287)Polyclonal induction (N = 139)IL2R-antagonist (N = 49)

Su

rviv

al (

%)

ISHLT 2006



PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier Survival by Induction Group (Transplants: January 2000 – June 2004)

Conditional on Survival to 14 DaysAge: 11-17 Years

50

60

70

80

90

100

0 1 2 3

Years

No induction (N = 268)

Polyclonal induction (N = 99)

IL2R-antagonist (N = 81)


Su

rviv

al (

%)


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

Year 1 (N = 1,105) Year 5 (N = 756)

PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up

(Follow-ups: January 2001 - June 2005)

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

% o

f P

atie

nts


PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier Survival Based on Prednisone Use

Conditional on Survival to 1 Year (Transplants: April 1994 - June 2004)

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 = 1,349)

No Prednisone at discharge or at 1 year (N = 241)

Prednisone at discharge/not at 1 year (N = 270)

p = 0.0017

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 2004)

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

Prednisone use at discharge and 1 year (N = 1,017)

No Prednisone at discharge or at 1 year (N = 160)

Prednisone at discharge/not at 1 year (N = 207)

p = 0.023

Su

rviv

al (

%)


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

(Transplants: January 1998 - June 2004) 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 = 600)

Cyclosporine use at discharge (N = 1,128)

Su

rviv

al (

%)

ISHLT 2006

p = 0.56


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

(Transplants: April 1994 - June 2003)

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

Years

Free from Rejection during 1 year (N = 888)Rejection within 1st Year (N =1,000)

p = 0.0005

Su

rviv

al (

%)



for Recent Transplants

(Transplants: January 2000 – June 2003)

50

60

70

80

90

100

0 1 2 3 4 5

Years

Free from Rejection during 1st Year (N = 405)Rejection within 1st Year (N = 319)

p = 0.038

Su

rviv

al (

%)



Stratified by Calcineurin Use at Discharge (Transplants: April 1994 - June 2003)

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

Years

CyA: Free from Rejection during 1 year (N = 633)

CyA: Rejection within 1st Year (N = 728)

TAC: Free from Rejection during 1 year (N = 224)

TAC: Rejection within 1st Year (N = 232)

Free from Rejection: CyA vs. TAC p = 0.7508Rejection: CyA vs. TAC p = 0.2764 CyA: Rejection vs. no rejection p = 0.0014TAC: Rejection vs. no rejection p = 0.3098

Su

rviv

al (

%)



for Recent TransplantsStratified by Calcineurin Use at Discharge (Transplants: January 2000 - June 2003)

50

60

70

80

90

100

0 1 2 3 4 5

Years

CyA: Free from Rejection during 1 year (N = 237)

CyA: Rejection within 1st Year (N = 254)

TAC: Free from Rejection during 1 year (N =162)

TAC: Rejection within 1st Year (N = 128)

Free from Rejection: CyA vs. TAC p = 0.8565Rejection: CyA vs. TAC p = 0.1541 CyA: Rejection vs. no rejection p = 0.0593TAC: Rejection vs. no rejection p = 0.4562

Su

rviv

al (

%)


0%

20%

40%

60%

80%

100%

Year 1 (N = 1,105) Year 5 (N = 756)

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 2005)

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

% o

f P

atie

nts


PERCENTAGE OF PEDIATRIC HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEARStratified by Induction (Transplants: January 2000 - June 2004)

0

10

20

30

40

50

60

70

Overall <1 1-10 11-17 F M

No induction Used Induction Used (no OKT3)

Age group Gender

% t

reat

ed f

or

reje

ctio

n w

ith

in 1

yea

r

No within age group or gender comparisons were significant except 1-10 years (p=0.005).


NUMBER OF REJECTION EPISODES FOR PEDIATRIC HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR

Stratified by Induction (Transplants: January 2000 - June 2004)

0

0.5

1

1.5

2

2.5

Overall <1 1-10 11-17 F M

No induction Used Induction Used (no OKT3)

No within age group or gender comparisons were significant.

Age group Gender

Ave

rag

e n

um

ber

of

reje

ctio

n e

pis

od

es


PERCENTAGE OF PEDIATRIC HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR

Stratified by Type of Induction (Transplants: January 2000 - June 2004)

0

10

20

30

40

50

60

70

80

90

Overall <1 1-10 11-17 F M

No induction PolyclonalIL2R-antagonist OKT3

% t

reat

ed f

or

reje

ctio

n w

ith

in 1

yea

r

Overall: No induction vs. OKT3 (p = 0.0007); polyclonal vs. OKT3 (p = 0.009); IL2 vs. OKT3 (p = 0.009). 1-10: No induction vs. polyclonal (p = 0.022); 11-17: No induction vs. OKT3 (p = 0.004); polyclonal vs. OKT3 (p = 0.019); IL2R vs. OKT3 (p = 0.005)Female: No induction vs. OKT3 (p = 0.007); polyclonal vs. OKT3 (p = 0.021)Male: No induction vs. OKT3 (p=0.034); IL2R vs. OKT3 (p = 0.035)



Stratified by Type of Induction (Transplants: January 2000 - June 2004)

0

0.5

1

1.5

2

2.5

Overall <1 1-10 11-17 F M

No induction Polyclonal IL2R-antagonist OKT3

11-17 years: No induction vs. OKT3 (p = 0.04). No other comparisons were significant.

Ave

rag

e n

um

ber

of

reje

ctio

n e

pis

od

es



Stratified by Maintenance Immunosuppression and Induction (Transplants: January 2000 - June 2004)

0

10

20

30

40

50

60

70

Overall <1 1-10 11-17 F M

CyA + No induction Used CyA + Induction Used (no OKT3)TAC + No induction Used TAC + Induction Used (no OKT3)

Age group Gender% t

reat

ed f

or

reje

ctio

n w

ith

in 1

yea

r

Overall: CyA + no induction vs. TAC + no induction: p = 0.0076; CyA + induction vs. TAC + induction: p = 0.012; CyA + induction vs. TAC + no induction: p = 0.0025; CyA + no induction vs. TAC + induction: p = 0.024; <1: CyA + no induction vs. TAC + no induction: p = 0.0471-10 years: CyA + no induction vs. TAC + no induction: p = 0.047; CyA + induction vs. TAC + induction: p = 0.036; CyA + induction vs. TAC + no induction: p < 0.0001; CyA + no induction vs. CyA + induction: 0.0143.Female: CyA + no induction vs. TAC + no induction: p=0.028; CyA + induction vs. TAC + induction: p = 0.0049; CyA + induction vs. TAC + no induction: p = 0.0097; CyA + no induction vs. TAC + induction: p = 0.011.No other age group or gender differences were significant.



Stratified by Maintenance Immunosuppression and Induction (Transplants: January 2000 - June 2004)

0

0.5

1

1.5

2

2.5

Overall <1 1-10 11-17 F M

CyA + No induction Used CyA + Induction Used (no OKT3)TAC + No induction Used TAC + Induction Used (no OKT3)

<1 years: CyA + no induction vs. TAC + no induction: p = 0.048.No other age group or gender comparisons were significant.

Age group Gender

Ave

rag

e n

um

ber

of

reje

ctio

n e

pis

od

es



Stratified by Maintenance Immunosuppression (Transplants: January 2000 - June 2004)

0

10

20

30

40

50

60

70

Overall <1 1-10 11-17 F M

Cyclosporine + MMF Cyclosporine + AZATacrolimus + MMF Tacrolimus + AZA

% t

reat

ed f

or

reje

ctio

n w

ith

in 1

yea

r

Overall: CyA+MMF vs. TAC+MMF (p = 0.0011); CyA +MMF vs. TAC + AZA (p = 0.0011); CyA + AZA vs. TAC + MMF (p = 0.009); CyA + AZA vs. TAC + AZA (p = 0.009).<1: CyA + MMF vs. TAC + MMF ( p = 0.004); CyA + AZA vs. TAC + MMF (p = 0.01). 1-10: CyA + MMF vs. TAC + MMF (p = 0.4); Cya + MMF vs. TAC + AZA (p = 0.004); CyA + AZA vs. TAC + AZA (p = 0.019).11-17: CyA + AZA vs. TAC + MMF (p = 0.012). Female: CyA + MMF vs. TAC + AZA (p = 0.002); CyA + AZA vs. TAC + MMF (p = 0.045); CyA + AZA vs. TAC + AZA (p=0.001); TAC + MMF vs. TAC + AZA (p = 0.038). Male: CyA + MMF vs. TAC + MMF (p = 0.007)


NUMBER OF REJECTION EPISODES FOR PEDIATRIC HEART TRANSPLANT RECIPIENTS TREATED FOR REJECTION IN 1ST YEAR Stratified by Maintenance Immunosuppression (Transplants: January 2000 - June 2004)

0

0.5

1

1.5

2

2.5

3

Overall <1 1-10 11-17 F M

Cyclosporine + MMF Cyclosporine + AZATacrolimus + MMF Tacrolimus + AZA

Ave

rag

e n

um

ber

of

reje

ctio

n e

pis

od

es

<1 years: CyA + AZA vs. TAC + MMF (p=0.004). No other age group or gender comparisons were significant.



Stratified by Calcineurin Inhibitor Use at Discharge (Transplants: January 2000 - June 2004)

0

10

20

30

40

50

60

Overall <1 1-10 11-17 F M

Cyclosporine Tacrolimus

Age group Gender

% t

reat

ed f

or

reje

ctio

n w

ith

in 1

yea

r

Overall: CyA vs. TAC (p < 0.0001) <1: CyA vs. TAC (p = 0.032) 1-10: CyA vs. TAC (p = 0.0004)Females: CyA vs. TAC (p = 0.0002) Male: CyA vs. TAC (p = 0.



Stratified by Calcineurin Inhibitor Use at Discharge (Transplants: January 2000 - June 2004)

0

0.5

1

1.5

2

2.5

Overall <1 1-10 11-17 F M

Cyclosporine Tacrolimus

No within age group or gender comparisons were significant other than <1 (p = 0.035).

Age group Gender

Ave

rag

e n

um

ber

of

reje

ctio

n e

pis

od

es


POST-HEART TRANSPLANT MORBIDITY FOR PEDIATRICS

Cumulative Prevalence in Survivors within 1 Year Post-Transplant (Follow-ups: April 1994 - June 2005)

Outcome Within 1

Year Total number with known response

Hypertension 47.2% (N = 2,428)

Renal Dysfunction 5.8% (N = 2,431)

Abnormal Creatinine < 2.5 mg/dl 3.9% Creatinine > 2.5 mg/dl 1.2% Chronic Dialysis 0.7% Renal Transplant 0.0%

Hyperlipidemia 10.8% (N = 2,555)

Diabetes 3.4% (N = 2,436)

Coronary Artery Vasculopathy 2.6% (N = 2,235)


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


Outcome Within 5 Years

Total number with known response

Hypertension 62.7% (N = 836)

Renal Dysfunction 9.9% (N = 862)

Abnormal Creatinine < 2.5 mg/dl 8.2% Creatinine > 2.5 mg/dl 0.8% Chronic Dialysis 0.6% Renal Transplant 0.2%

Hyperlipidemia 25.1% (N = 902)

Diabetes 5.2% (N = 833)

Coronary Artery Vasculopathy 10.9% (N = 605)


POST-HEART TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Prevalence in Survivors within 8 Years Post-Transplant


Outcome Within 8 Years

Total number with known response

Hypertension 68.3% (N = 325)

Renal Dysfunction 10.3% (N = 339) Abnormal Creatinine < 2.5 mg/dl 7.7% Creatinine > 2.5 mg/dl 0.6% Chronic Dialysis 1.5% Renal Transplant 0.6%

Hyperlipidemia 28.1% (N = 356)

Diabetes 4.0% (N = 323)

Coronary Artery Vasculopathy 12.8% (N = 188)


FREEDOM FROM CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2005)

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

Years

% F

reed

om

fro

m C

AV



Stratified by Induction

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

Years

Induction (N =859)

No Induction (N = 1,440)% F

ree

do

m f

rom

CA

V

p = 0.78



Stratified by Age Group

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

Years

<1 Year (N =618)

1-10 Years (N = 952)

11-17 Years (N = 923)

p < 0.0001

% F

ree

do

m f

rom

CA

V


FREEDOM FROM CORONARY ARTERY VASCULOPATHY For Pediatric Heart Recipients (Follow-ups: January 1999-June 2005)

Stratified by Age Group

50

60

70

80

90

100

0 1 2 3 4 5 6

Years

<1 Year (N = 401)

1-10 Years (N = 649)

11-17 Years (N = 670)

p = 0.0005

% F

ree

do

m f

rom

CA

V


FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2005)

Stratified by Ischemia Time

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

0-<2 hours (N=254)

2-<4 hours (N=1,174)

4+ hours (N=741)

p = 0.0109

% F

ree

do

m f

rom

CA

V


FREEDOM FROM CORONARY ARTERY VASCULOPATHYFor Pediatric Heart Recipients (Follow-ups: April 1994 - June 2005)

Stratified by Ischemia Time and Recipient Age

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

0-<2 hours/0-10 years (N=136)2-<4 hours/0-10 years (N=699)4+ hours/0-10 years (N=741)0-<2 hours/11-17 years (N=102)2-<4 hours/11-17 years (N=424)4+ hours/11-17 years (N=159)

0-10 years: p = 0.1483;11-17 years: p = 0.2163

% 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 2005)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 = 44)

1-10 Years (N = 86)

11-17 Years (N = 110)

p = 0.014

Su

rviv

al s

ince

Rep

ort

of

CA

V (

%)


FREEDOM FROM SEVERE RENAL DYSFUNCTION*For Pediatric Heart Recipients (Follow-ups: April 1994 - June 2005)

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, 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 2005)

Malignancy/Type 1-Year Survivors

5-Year Survivors

8-Year Survivors

No Malignancy 2493 (98.0%) 864 (95.7%) 330 (92.4%)

Malignancy (all types combined) 52 (2.0%) 39 (4.3%) 27 (7.6%)

Malignancy Type

Lymph 48 35 27

Other 3 5 1

Skin 1

Type Not Reported 1

ISHLT 2006

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 2005)

80

85

90

95

100

0 1 2 3 4 5 6 7 8

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 2002)

Maintenance Immunosuppression at discharge and 1 year

% HTN reported between 1 and 3 years

P-valueFor Patients

on drugFor Patients not on drug

Azathioprine 22.3% 23.2% 0.8

Cyclosporine 20.6% 24.3% 0.34

MMF 20.8% 21.9% 0.8

Prednisone 29.2% 7.2% <0.0001

Rapamycin . 21.0%

Tacrolimus 28.1% 19.2% 0.022


PEDIATRIC HEART RECIPIENTSRelationship of Rejection and Coronary Artery Vasculopathy

(Follow-ups: April 1994 – June 2005)

Rejection During 1st Year

Reported CAV between 1st and 3rd years

post-transplant

Reported CAV between 3rd

and 5th years

post-transplant

Yes No All Yes No All

Yes 40

7.8%

473

92.2%

513

100%

19

7.5%

235

92.5%

254

100%

No 15

2.9%

504

97.1%

519

100%

10

4.1%

234

95.9%

244

100%p = 0.0004 p = 0.1072

NOTE: Only those recipients without CAV prior to 3 years were included in the last set of columnsISHLT 2006


PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2005)

CAUSE OF DEATH 0-30 Days (N = 358)

31 Days - 1 Year (N = 303)

>1 Year - 3 Years (N = 220)

>3 Years - 5 Years (N = 150)

>5 Years (N = 281)

CORONARY ARTERY VASCULOPATHY

4 (1.1%) 26 (8.6%) 42 (19.1%) 55 (36.7%) 79 (28.1%)

ACUTE REJECTION 33 (9.2%) 80 (26.4%) 59 (26.8%) 19 (12.7%) 37 (13.2%)

LYMPHOMA 6 (2.0%) 10 (4.5%) 3 (2.0%) 24 (8.5%)

MALIGNANCY, OTHER 4 (1.3%) 2 (0.9%) 1 (0.7%) 10 (3.6%)

CMV 1 (0.3%) 7 (2.3%) 1 (0.5%)

INFECTION, NON-CMV 49 (13.7%) 49 (16.2%) 17 (7.7%) 7 (4.7%) 21 (7.5%)

PRIMARY FAILURE 62 (17.3%) 12 (4.0%) 7 (3.2%) 8 (5.3%) 12 (4.3%)

GRAFT FAILURE 85 (23.7%) 35 (11.6%) 40 (18.2%) 34 (22.7%) 55 (19.6%)

TECHNICAL 22 (6.1%) 2 (0.7%) 2 (0.9%) 1 (0.7%) 1 (0.4%)

OTHER 18 (5.0%) 17 (5.6%) 18 (8.2%) 12 (8.0%) 19 (6.8%)

MULTIPLE ORGAN FAILURE

35 (9.8%) 36 (11.9%) 4 (1.8%) 3 (2.0%) 10 (3.6%)

RENAL FAILURE 1 (0.3%) 4 (1.3%) 1 (0.5%)

PULMONARY 24 (6.7%) 18 (5.9%) 10 (4.5%) 6 (4.0%) 9 (3.2%)

CEREBROVASCULAR 24 (6.7%) 7 (2.3%) 7 (3.2%) 1 (0.7%) 4 (1.4%)


HEART TRANSPLANTATION Pediatric Recipients ISHLT 2006 J Heart Lung Transplant 2006;25:893-903.

Documents

Transcript of HEART TRANSPLANTATION Pediatric Recipients ISHLT 2006 J Heart Lung Transplant 2006;25:893-903.