2003 ishlt j heart lung transplant 2003; 22: 610-72. heart transplantation pediatric recipients

2003ISHLTJ Heart Lung Transplant 2003; 22: 610-72.

HEART TRANSPLANTATION

Pediatric Recipients


AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS (Transplants: January 1982 - June 2002)

0

200

400

600

800

1000

1200

1400

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 1982 - June 2002)

0

200

400

600

800

1000

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 o

f T

ran

spla

nts


AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS

By Year of Transplant

0

100

200

300

40011-17 Years1-10 Years

<1 Year

11 942

74108

128

190

249

307357 360

383354 371

342363

343334

351328

Nu

mb

er o

f T

ran

spla

nts


NUMBER OF CENTERS REPORTING PEDIATRIC HEART TRANSPLANTS

0

20

40

60

80

100

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

Nu

mb

er o

f P

edia

tric

Cen

ters

Rep

ort

ing


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

0

25

50

75

100

1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

% o

f Cas

es

MyopathyCongenital

20%

1%

76%3%

Myopathy

Congenital

Other

ReTX


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

0

25

50

75

100

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

% o

f Cas

es

MyopathyCongenital

51% 37%

5% 7%

Myopathy

Congenital

Other

ReTX


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

0

25

50

75

100

1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

% o

f Cas

es

Myopathy Congenital

63%

24%

4% 9%

Myopathy

Congenital

Other

ReTX


PEDIATRIC HEART TRANSPLANTATIONActuarial Survival (1/1982-6/2001)

30

40

50

60

70

80

90

100

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

Years

Su

rviv

al (

%)

<1 Year (N=1,124) 1-10 Years (N=1,773)11-17 Years (N=1,865) Overall (N=4,762)

<1 year vs. 1-10 years: p = 0.0004<1 year vs. 11-17 years: p = 0.003

HALF-LIFE <1: not computable; 1-10: 12.4 years; 11-17: 11.0 years


PEDIATRIC HEART TRANSPLANTATIONConditional Actuarial Survival (1/1982-6/2001)

30

40

50

60

70

80

90

100

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

Years

Su

rviv

al

(%)

<1 Year (N=714) 1-10 Years (N=1,212)11-17 Years (N=1,302) Overall (N=3,228)

Both comparisons with 11-17 years significant at p < 0.0001

HALF-LIFE <1: not computable; 1-10: not computable; 11-17: 13.5 years


PEDIATRIC HEART TRANSPLANTATIONConditional Actuarial Survival for Recent Era (1/1998-6/2001)

50

60

70

80

90

100

0 1 2 3 4

Years

Su

rviv

al (

%)

<1 Year (N=168) 1-10 Years (N=312)11-17 Years (N=281) Overall (N=761)

No comparison were statistically significant


PEDIATRIC HEART TRANSPLANTATION

Actuarial Survival by Era (1/1982-6/2001)

0

20

40

60

80

100

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

Years

1982-1987 (N=372) 1988-1992 (N=1,463)

1993-1997 (N=1,813) 1/1998-6/2001 (N=1,197)

All comparisons with 1998-2001 are significant at p < 0.0001Comparison of 1982-1987 vs. 1988-1992 was significant at p = 0.002Comparison of 1982-1987 vs. 1993-1997 was significant at p < 0.0001

HALF-LIFE 1982-1987: 6.6 years; 1988-1992: 11.7 yearsSu

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATION Actuarial Survival by Age Group

For Diagnosis = Cardiomyopathy (Transplants: January 1998 - June 2001)

0

20

40

60

80

100

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

Years

<1 (N=219)

1-10 (N=894)

11-17 (N=1,172)

HALF-LIFE 1-10: 12.4 Years; 11-17: 10.2 Years

No comparisons were statistically significant.

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTATION Actuarial Survival By Age Group

For Diagnosis = Congenital Disease (Transplants: January 1988 - June 2001)

0

20

40

60

80

100

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

Years

<1 (N=857)

1-10 (N=668)

11-17 (N=445)

Comparison of <1 vs. 11-17 was significant at p < 0.05

HALF-LIFE <1: 12.2 Years 1-10: 12.9 Years; 11-17: 11.7 Years

Su

rviv

al (

%)


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2001)

Risk Factors For 1 Year Mortality

N=2,055

VARIABLE

Odds Ratio

P-value 95%

Confidence Interval

Congenital heart disease 2.00 <.0001 1.53 - 2.62

Other diagnosis (excluding cardiomyopathy and retransplant)

1.97 0.04 1.02 - 3.82

Hospitalized (including ICU) 1.56 0.004 1.16 - 2.10

Ventilator 1.76 0.0008 1.26 - 2.44


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2001) Risk Factors for 1 Year Mortality

Continuous Factors (see figures) Recipient age

Donor weight

Bilirubin

Serum creatinine



Recipient Age

0

1

2

3

4

0 3 6 9 12 15 18


Od

ds

of

1 Y

ear

Mo

rtal

ity

p = 0.008



Donor Weight

0

0.5

1

1.5

2

0 10 20 30 40 50 60 70 80 90 100

Donor Weight (kg)

Od

ds

of

1 Y

ear

Mo

rtal

ity

p = 0.01



Bilirubin

0

0.5

1

1.5

2

0 1 2 3 4 5 6 7 8

Bilirubin (mg/dl)

Od

ds

of

1 Y

ear

Mo

rtal

ity

p = 0.046



Recipient creatinine

0

0.5

1

1.5

2

2.5

3

0 0.5 1 1.5 2 2.5 3 3.5 4

Creatinine (mg/dl)

Od

ds

of

1 Y

ear

Mo

rtal

ity

p = 0.047


PEDIATRIC HEART TRANSPLANTS (1/1995-6/2001) Factors Not Significant for 1 Year Mortality

Recipient Factors:IV inotropes, PGE, ECMO, sternotomy, history of malignancy, weight, height, dialysis, recent infection, gender



Donor Factors:Gender, clinical infection, history of diabetes, height, age, COD

Transplant Factors:Donor/recipient weight ratio, CMV mismatch, ABO identical/compatible, year of transplant, repeat transplant, ischemia time, HLA mismatch, transplant center volume



Risk Factors For 5 Year Mortality

N=828

VARIABLE

Odds Ratio

P-value 95%

Confidence Interval

Ventilator 1.75 0.02 1.09 - 2.81

Prior sternotomy 1.42 0.07 0.98 - 2.07



Continuous Factors (see figures)

Recipient age Serum creatinine



Recipient Age

0

1

2

3

4

0 3 6 9 12 15 18


Od

ds

of

5 Y

ear

Mo

rtal

ity

p = 0.045



Recipient creatinine

0

0.5

1

1.5

2

2.5

3

0 0.5 1 1.5 2 2.5 3 3.5 4

Creatinine (mg/dl)

Od

ds

of

5 Y

ear

Mo

rtal

ity

p = 0.02



Recipient Factors:IV inotropes, PGE, ECMO, history of malignancy, weight, height, dialysis, recent infection, gender, diagnosis, hospitalized at time of transplant, bilirubin



Donor Factors:Gender, clinical infection, history of diabetes, height, weight, age, COD

Transplant Factors:Donor/recipient weight ratio, CMV mismatch, ABO identical/compatible, year of transplant, repeat transplant, ischemia time, HLA mismatch, transplant center volume



Risk Factors For 5 Year Mortality Conditional on 1 Year Survival

N=630

VARIABLE

Odds Ratio

P-value 95%

Confidence Interval

Repeat transplant 4.68 0.003 1.68 - 3.01

IV inotropes 2.06 0.01 1.19 - 3.56

PGE 4.05 0.03 1.15 - 14.25

Hospitalized for rejection or treated with anti-rejection medications between discharge and 1 Year

2.39 0.003 1.36 - 4.19


PEDIATRIC HEART RECIPIENTS Functional Status (Follow-ups: April 1994-June 2002)

0%

20%

40%

60%

80%

100%

1 Year (N = 1,475) 3 Years (N = 1,227) 5 Years (N = 995)

No Activity Limitations Performs with Some Assistance Requires Total Assistance


PEDIATRIC HEART RECIPIENTS Rehospitalization Post-transplant (Follow-ups: April 1994 - June 2002)

0%

20%

40%

60%

80%

100%

Up to 1 Year (N = 15,905) Between 2 and 3 Years (N= 13,416)

Between 4 and 5 Years (N= 11,271)

No Hospitalization Hospitalized, Not Rejection/Not Infection

Hospitalized, Rejection Hospitalized, Infection Only

Hospitalized, Rejection + Infection


0

10

20

30

40

Any Induction (N = 274) Polyclonal ALG/ATG (N= 183)

OKT3 (N = 40) IL2R-antagonist (N = 69)

% o

f p

ati

en

ts

PEDIATRIC HEART RECIPIENTS Induction Immunosuppression (Follow-ups: January 2000 - June 2002)


0

10

20

30

40

50

Any Induction (N = 107)

Polyclonal ALG/ATG (N = 86)

OKT3 (N = 21)

IL2R-antagonist (N = 10)



OKT3 (N = 13)




OKT3 (N = 6)


% o

f p

ati

en

ts

2000 2001 2002(6 months)

PEDIATRIC HEART RECIPIENTSInduction Immunosuppression (Follow-ups: January 2000 - June 2002)


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

% o

f Pa

tien

ts

Year 1 (N = 533)

Year 5 (N = 383)

PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Any Time During Follow-up Period

For follow-ups between January 2000 through June 2002

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


0

20

40

60

80

100

Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone

% o

f P

ati

en

ts

Year 1 (N = 522) Year 5 (N = 370)

PEDIATRIC HEART RECIPIENTS Maintenance Immunosuppression at Time of Follow-up




0%

20%

40%

60%

80%

100%

Year 1 (N = 522) Year 5 (N = 370)

% o

f P

ati

en

ts

Other

Tacrolimus + MMF

Tacrolimus + AZA

Cyclosporine + MMF

Cyclosporine + AZA

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




POST-HEART TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Prevalence in Survivors within 1 Year Post-Transplant

(Follow-ups: April 1994-June 2002)

Outcome Within 1 Year

Hypertension 44.2% (N=1,507)

Renal Dysfunction 5.1% (N=1,516) Abnormal Creatinine < 2.5 mg/dl 3.2% Creatinine > 2.5 mg/dl 1.4% Chronic Dialysis 0.5% Renal Transplant 0.0%

Hyperlipidemia

8.6% (N=1,578)

Diabetes 3.2% (N=1,509)

CAV 2.5% (N=1,363)


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

(Follow-ups: April 1994-June 2002)

Outcome Within 5 Years

Hypertension 60.0% (N=365)

Renal Dysfunction 7.5% (N=389) Abnormal Creatinine < 2.5 mg/dl 5.9% Creatinine > 2.5 mg/dl 0.8% Chronic Dialysis 0.8% Renal Transplant 0.0%

Hyperlipidemia

17.1% (N=398)

Diabetes 4.9% (N=366)

CAV 11.4% (N=228)


Freedom from CAV For Pediatric Heart Recipients (Follow-ups: April 1994-June 2002)

0

20

40

60

80

100

0 1 2 3 4 5 6 7

Years

% F

ree

do

m f

rom

CA

V


Freedom from CAV For Pediatric Heart Recipients (Follow-ups: April 1994-June 2002)

Stratified by Age Group

0

20

40

60

80

100

0 1 2 3 4 5 6 7

Years

% F

ree

do

m f

rom

CA

V

<1 Year

1-10 Years

11-17 Years

<1 year vs. 1-10 years: p = 0.14<1 year vs. 11-17 years: p = 0.0021-10 years vs. 11-17 years: p = 0.06


SURVIVAL FOLLOWING REPORT OF CAV For Pediatric Heart Recipients (Follow-ups: April 1994-June 2002)

Stratified by Age Group

0

20

40

60

80

100

0 1 2 3 4

Time since Report of CAV (Years)

Su

rviv

al s

ince

Rep

ort

of

CA

V (

%)

<1 Year

1-10 Years

11-17 Years

No comparisons were statistically significant


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

2002)

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Years

% F

reed

om fr

om S

ever

e R

enal

Dys

func

tion

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


MALIGNANCY POST-HEART TRANSPLANTATION FOR PEDIATRICSCumulative Prevalence in Survivors (Follow-ups: April 1994-June 2002)

Malignancy/Type 1-Year Survivors 5-Year Survivors

No Malignancy 1674 (98.1%) 434 (95.4%)

Malignancy (all types combined) 32 (1.9%) 21 (4.6%)

Malignancy Type

Lymph 28 19

Other 3 2

Type Not Reported 1


Freedom from MalignancyFor Pediatric Heart Recipients (Follow-ups: April 1994-June

2002)

50

60

70

80

90

100

0 1 2 3 4 5 6 7

Months

% F

reed

om fr

om M

alig

nanc

y

All malignancy Lymph Skin Other


PEDIATRIC HEART TRANSPLANTATIONActuarial Survival Based on Prednisone Use

(Transplants: April 1994 - June 2001)

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9

Years

Su

rviv

al (

%)

Prednisone use at discharge and 1 year (N=1025)

No Prednisone at discharge or at 1 year (N=238)

Prednisone at discharge/not at 1 year (N = 159)

p = 0.002


PEDIATRIC HEART TRANSPLANTATIONActuarial Survival Based on Rejection within 1st Year


50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

Years

Su

rviv

al (

%)

Free from Rejection during 1st Year (N = 576)Rejection within 1st Year (N = 744)

P = 0.01


PEDIATRIC HEART RECIPIENTSRelationship of Prednisone Use and CAV

(Follow-ups: April 1994 – June 2002)

Prednisone Use at

Discharge and at 1

Year

Reported CAV between 1st and 2nd years post-

transplant

Reported CAV between 1st and 3rd years post-

transplant

Yes No Yes No

Yes 34

5.2%

617

94.7%

30

7.0%

397

93.0%

No 4

2.5%

154

97.5%

3

2.7%

110

97.3%p = 0.15 p = 0.08


PEDIATRIC HEART RECIPIENTSRelationship of Rejection and CAV

(Follow-ups: April 1994 – June 2002)

Rejection During 1st

Year

Reported CAV between 1st and 2nd years post-

transplant

Reported CAV between 1st and 3rd years post-

transplant

Yes No Yes No

Yes 24

5.8%

390

94.2%

19

6.9%

258

93.1%

No 6

1.6%

361

98.4%

8

3.2%

242

96.8%p = 0.003 p = 0.06


PEDIATRIC HEART RECIPIENTS Incidence of Hypertension between 1 and 3 Years


Maintenance Immunosuppression at discharge and 1 year

% HTN reported between 1 and 3 years

P-valueFor Patients on

drugFor Patients not on

drug

Cyclosporine 19.4% 14.0% 0.3

Tacrolimus 17.3% 18.6% 0.8

Azathioprine 22.2% 14.1% 0.1

MMF 15.9% 20.9% 0.4

Rapamycin - 19.4% -

Prednisone 28.5% 6.4% <0.0001


PEDIATRIC HEART RECIPIENTS Growth Following Transplantation: Height

Stratified by Prednisone Use at Discharge and at 1 Year

-1.25

-1

-0.75

-0.5

-0.25

0

Immediately Pre-Transplant

1 Year Follow-up 2 Year Follow-up 3 Year Follow-up

Time of Measurement

Z-S

core

11-17 Years/No Prednisone 11-17 Years/Prednisone



PEDIATRIC HEART RECIPIENTS Growth Following Transplantation: Weight

Stratified by Prednisone Use at Discharge and at 1 Year

-1.25

-1

-0.75

-0.5

-0.25

0

0.25

0.5

Immediately Pre-Transplant

1 Year Follow-up 2 Year Follow-up 3 Year Follow-up

Time of Measurement

Z-S

core





Risk Factors For Developing CAV between 1 and 5 Years

N=363

VARIABLE

Odds Ratio

P-value 95%

Confidence Interval

Repeat transplant 5.75 0.03 1.15 - 28.65

Hospitalized for rejection or treated with anti-rejection medications between discharge and 1 Year

2.38 0.03 1.08 - 5.25


PEDIATRIC HEART TRANSPLANTS (1/1995-6/1997) Risk Factors for Developing CAV between 1 and 5 Years

Recipient Age

0

1

2

3

0 3 6 9 12 15 18


Od

ds

of

Dev

elo

pin

g C

AV

b

etw

een

1 a

nd

5 Y

ears p = 0.01


PEDIATRIC HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2002)

CAUSE OF DEATH 0-30 Days (N = 276)

31 Days - 1 Year (N = 231)

>1 Year - 3 Years (N = 147)

>3 Years - 5 Years (N = 93)

>5 Years (N = 156)

CAV 2 (0.7%) 21 (9.1%) 32 (21.8%) 35 (37.6%) 54 (34.6%)

ACUTE REJECTION 25 (9.1%) 66 (28.6%) 39 (26.5%) 15 (16.1%) 20 (12.8%)

LYMPHOMA 5 (2.2%) 8 (5.4%) 2 (2.2%) 14 (9.0%)

MALIGNANCY, OTHER 4 (1.7%) 1 (0.7%) 1 (1.1%) 6 (3.8%)

CMV 1 (0.4%) 5 (2.2%)

INFECTION, NON-CMV 38 (13.8%) 37 (16.0%) 11 (7.5%) 5 (5.4%) 5 (3.2%)

PRIMARY FAILURE 44 (15.9%) 12 (5.2%) 5 (3.4%) 6 (6.5%) 10 (6.4%)

GRAFT FAILURE 76 (27.5%) 28 (12.1%) 25 (17.0%) 17 (18.3%) 30 (19.2%)

TECHNICAL 17 (6.2%) 3 (1.3%) 2 (1.4%) 1 (1.1%) 2 (1.3%)

OTHER 7 (2.5%) 7 (3.0%) 8 (5.4%) 4 (4.3%) 8 (5.1%)

MULTIPLE ORGAN FAILURE

24 (8.7%) 23 (10.0%) 3 (2.0%) 1 (1.1%) 1 (0.6%)

RENAL FAILURE 1 (0.4%) 1 (0.4%)

PULMONARY 22 (8.0%) 12 (5.2%) 7 (4.8%) 5 (5.4%) 4 (2.6%)

CEREBROVASCULAR 19 (6.9%) 7 (3.0%) 6 (4.1%) 1 (1.1%) 2 (1.3%)

2003 ishlt j heart lung transplant 2003; 22: 610-72. heart transplantation pediatric recipients

Documents

ishlt j heart lung transplant

pediatric heart transplants

year slide

time of transplant

cod transplant factors

year mortality slide

transplant center volume

gender slide