lung transplantation pediatric recipients ishlt 2006 j heart lung transplant 2006;25:904-911
TRANSCRIPT
LUNG TRANSPLANTATION
Pediatric Recipients
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
RECIPIENT AGE DISTRIBUTION FOR PEDIATRIC LUNG RECIPIENTS - NUMBER
(Transplants: January 1986 - June 2005)
050
100150200250300350400450500550600650700
1986-1995 1996-6/2005
Nu
mb
er
of
Tra
ns
pla
nts
<1 1-5 6-11 12-17
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
RECIPIENT AGE DISTRIBUTION FOR PEDIATRIC LUNG RECIPIENTS - PERCENTAGE
(Transplants: January 1986 - June 2005)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1986-1995 1996-6/2005
% o
f T
ran
sp
lan
ts
12-17
6-11
1-5
<1
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
DONOR TYPE DISTRIBUTION BY YEAR OF TRANSPLANT FOR PEDIATRIC LUNG RECIPIENTS
(Transplants: 1986-2004)
0
10
20
30
40
50
60
70
80
90
1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004
Transplant Year
Nu
mb
er
of
Tra
ns
pla
nts
LivingDeceased
ISHLT 2006NOTE: This figure includes only the lung transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as evidence that the number of lung transplants worldwide has declined in recent years.J Heart Lung Transplant 2006;25:904-911
DONOR TYPE DISTRIBUTION BY RECIPIENT AGE GROUP WITHIN ERA FOR PEDIATRIC LUNG RECIPIENTS (Transplants: January 1986 - June 2005)
0
50
100
150
200
250
300
350
400
450
500
0-5 years 6-11 years 12-17 years 0-5 years 6-11 years 12-17 years
Recipient Age (Years)
Nu
mb
er
of
Tra
ns
pla
nts
LivingDeceased
1986-1995 1996-6/2005
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
AGE DISTRIBUTION FOR DONORS OF PEDIATRIC
LUNG RECIPIENTS (Transplants: January 1986 - June 2005)
453
155
165
138
38
2
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Donor Age (Years)
Nu
mb
er o
f T
ran
spla
nts
60+
50-59
35-49
18-34
12-17
0-11
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
AGE DISTRIBUTION OF PEDIATRIC LUNG RECIPIENTS
By Year of Transplant
0
20
40
60
80
10012-17 Years1-11 Years
<1 Year
Nu
mb
er o
f T
ran
spla
nts
1 4 4 6
20
4855
4943
84
75
89 86
69 6965 67
62
ISHLT 2006
67
J Heart Lung Transplant 2006;25:904-911
NUMBER OF CENTERS REPORTING PEDIATRIC LUNG TRANSPLANTS
0
10
20
30
40
1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004
Transplant Year
Nu
mb
er o
f C
ente
rs R
epo
rtin
g
Ped
iatr
ic T
ran
spla
nts
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
PEDIATRIC LUNG TRANSPLANTATION: Indications (Transplants: January 1991 - June 2005)
DIAGNOSIS AGE: < 1 Year
AGE: 1-5 Years
AGE: 6-11 Years
AGE: 12-17 Years
Cystic Fibrosis 2 2.80% 98 54.40% 366 69.80%
Primary Pulmonary Hypertension 9 16.10% 15 20.80% 22 12.20% 43 8.20%
Re-Transplant: Obliterative Bronchiolitis 6 8.30% 8 4.40% 19 3.60%
Congenital Heart Disease 18 32.10% 7 9.70% 2 1.10% 5 1.00%
Idiopathic Pulmonary Fibrosis 7 9.70% 6 3.30% 17 3.20%
Obliterative Bronchiolitis (Not Re-TX) 4 5.60% 7 3.90% 16 3.10%
Re-Transplant: Not OB 3 5.40% 1 1.40% 7 3.90% 15 2.90%
Interstitial Pneumonitis 6 10.70% 10 13.90% 4 0.80%
Pulmonary Vascular Disease 7 12.50% 4 5.60% 6 3.30%
Eisenmenger’s Syndrome 1 1.80% 5 6.90% 5 2.80% 5 1.00%
Pulmonary Fibrosis, Other 1 1.80% 1 1.40% 3 1.70% 9 1.70%
Surfactant Protein B Deficiency 7 12.50% 1 1.40%
COPD/Emphysema 1 1.40% 2 1.10% 4 0.80%
Bronchopulmonary Dysplasia 1 1.80% 1 1.40% 5 2.80%
Bronchiectasis 3 1.70% 3 0.60%
Other 3 5.40% 7 9.70% 6 3.30% 18 3.40%
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
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
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
0
2
4
6
8
10
12
14
16
0-<1 month 1-<12 months 12-<36 months 36+ months Not reported
Nu
mb
er
of R
e-T
ran
sp
lan
ts-
PEDIATRIC LUNG RE-TRANSPLANTS Between January 1994 and June 2005
ISHLT 2006
Time Between Previous and Current Transplant
J Heart Lung Transplant 2006;25:904-911
0
10
20
30
40
50
60
70
80
90
100
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5
Years
Su
rviv
al (
%)
0-<1 month (N=5) 1-<12 months (N=9)
12-<36 months (N=10) 36+ months (N=12)
PEDIATRIC LUNG RE-TRANSPLANTS Between January 1994 and June 2004
Stratified by Time Between Previous and Current Transplant
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
LUNG TRANSPLANTATIONKaplan-Meier Survival by Age Group
(Transplants: January 1990 - June 2004)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13Years
Su
rviv
al (
%)
Adult (N=18,145)
Pediatric (N=926)
HALF-LIFE Adult = 4.8 Years; Pediatric = 4.4 Years
P = 0.72
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type
(Transplants: January 1990 - June 2004)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11Years
Su
rviv
al (
%)
Single Lung (N=102)
Bilateral/Double Lung (N=720)
HALF-LIFE Single Lung: 3.5 Years; Bilateral/double Lung: 4.7 Years
P = 0.006
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival for Congenital Diagnosis (Transplants: January 1990 – June 2004)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11Years
Su
rviv
al (
%)
Eisenmenger's Syndrome (N=14)
Other Congenital Heart Disease (N=31)
Eisenmenger's + Other Congenital Heart Disease (N=45)
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type
Diagnosis: Primary Pulmonary Hypertension (Transplants: January 1990 - June 2004)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12
Years Post-Transplantation
Su
rviv
al (
%)
.
Single Lung (N = 17) Double Lung (N=63)
P = 0.0025
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Age Group
(Transplants: January 1990 - June 2004)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Years
Su
rviv
al
(%)
<1 Year (N=58)
1-11 Years (N=267)
12-17 Years (N=497)
<1 year vs. 12-17 years: p = 0.031 No other comparisons were statistically significant.
HALF-LIFE<1 Year: 6.5 Years1-11 Years: 5.5 Years12-17 Years: 4.0 Years
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
PEDIATRIC LUNG TRANSPLANTATIONConditional Kaplan-Meier Survival by Age Group
(Transplants: January 1990 - June 2004)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Years
Su
rviv
al (
%)
<1 Year (N=38)1-11 Years (N=175)
12-17 Years (N=321)
No comparisons were statistically significant at p<0.05
HALF-LIFE<1 Year: 8.8 Years1-11 Years: n.c.12-17 Years: 6.1 Years
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
PEDIATRIC LUNG TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: January 1988 - June 2004)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Years
Su
rviv
al (
%)
1988-1994 (N=225)
1995-1999 (N=403)
2000-6/2004 (N=295)
HALF-LIFEUnconditional 1988-1994: 2.8 Years; 1995-1999: 4.0 Years; 2000-6/2004: n.c.Conditional 1988-1994: 7.6 Years; 1995-1999: 7.3 Years; 2000-6/2004: n.c.
P-value for 88-94 vs. 00-6/04: 0.0016
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Donor Type for Recipients Age 11-17 Years
(Transplants: January 1990 - June 2004)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Years
Su
rviv
al (
%)
Deceased Donor (N = 538)
Living Donor (N = 73)
p = 0.80
HALF-LIFEDeceased: 4.0 YearsLiving: 3.8 Years
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
PEDIATRIC LUNG RECIPIENTS Functional Status of Surviving Recipients
(Follow-ups: April 1994-June 2005)
0%
20%
40%
60%
80%
100%
1 Year (N = 362) 3 Years (N = 238) 5 Years (N = 142) 7 Years (N=65)
No Activity Limitations Performs with Assistance Total Assistance
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
PEDIATRIC LUNG RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients
(Follow-ups: April 1994 - June 2005)
0%
20%
40%
60%
80%
100%
Up to 1 Year (N =450)
Between 2 and 3Years (N = 271)
Between 4 and 5Years (N = 159)
Between 6 and 7Years (N = 79)
No Hospitalization Hospitalized, Not Rejection/Not InfectionHospitalized, Rejection Hospitalized, Infection OnlyHospitalized, Rejection + Infection
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
PEDIATRIC LUNG RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients
(Follow-ups: April 1994 - June 2005)
0%
20%
40%
60%
80%
100%
Up to 1 Year (N =450)
Between 1 and 3Years (N =238)
Between 3 and 5Years (N = 141)
Between 5 and 7Years (N = 71)
No Hospitalization Hospitalized, Not Rejection/Not InfectionHospitalized, Rejection Hospitalized, Infection OnlyHospitalized, Rejection + Infection
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
0
10
20
30
40
50
60
Any Induction (N = 110) Polyclonal ALG/ATG (N = 36) IL2R-antagonist (N = 76)
% o
f p
atien
tsPEDIATRIC LUNG RECIPIENTS
Induction ImmunosuppressionFor transplants between January 2001 and June 2005
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
0
10
20
30
40
50
60
Any Induction Polyclonal ALG/ATG IL2R-antagonist
% o
f p
atie
nts
2001 20022003 20041/2005-6/2005
PEDIATRIC LUNG RECIPIENTSInduction Immunosuppression (Transplants: January 2001 - June 2005)
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
PEDIATRIC LUNG TRANSPLANTATION
Kaplan-Meier Survival Stratified by Induction Use (Transplants: January 2001 - June 2004)
0
25
50
75
100
0 1 2 3 4
Years
Su
rviv
al (
%)
Induction (N = 79)
No Induction (N = 81)
p = 0.5
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
0
20
40
60
80
100
Cyclosporine Tacrolimus Rapamycin MMF Azathioprine Prednisone
% o
f P
atie
nts
Year 1 (N = 154) Year 5 (N = 83)
PEDIATRIC LUNG RECIPIENTS Maintenance Immunosuppression at Time of Follow-up
(Follow-ups: January 2001 and June 2005)
NOTE: Different patients are analyzed in Year 1 and Year 5
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
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
(Follow-ups: January 2001 and June 2005)
1 Year Follow-up (N = 154) 5 Year Follow-up (N = 83)NOTE: Different patients are analyzed in Year 1 and Year 5
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
0%
20%
40%
60%
80%
100%
Year 1 (N = 154) Year 5 (N = 83)
% o
f P
ati
en
ts
Other
Tacrolimus + MMF
Tacrolimus + AZA
Cyclosporine + MMF
Cyclosporine + AZA
PEDIATRIC LUNG RECIPIENTS Maintenance Immunosuppression Drug Combinations at Time of Follow-up Report
(Follow-ups: January 2001 and June 2005)
NOTE: Different patients are analyzed in Year 1 and Year 5
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
POST-LUNG 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 38.5% (N = 439)
Renal Dysfunction 8.4% (N=441)
Abnormal Creatinine < 2.5 mg/dl 5.4% Creatinine > 2.5 mg/dl 2.0% Chronic Dialysis 0.7% Renal Transplant 0.2%
Hyperlipidemia 3.1% (N = 453)
Diabetes 25.8% (N = 442)
Bronchiolitis Obliterans 14.1% (N = 405)
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
POST-LUNG TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Prevalence in Survivors within 5 Years Post-Transplant
(Follow-ups: April 1994 - June 2005)
Outcome Within 5
Years Total number with known response
Hypertension 68.7% (N = 99)
Renal Dysfunction 22.0% (N = 100) Abnormal Creatinine < 2.5 mg/dl 15.0% Creatinine > 2.5 mg/dl 5.0% Chronic Dialysis 1.0% Renal Transplant 1.0%
Hyperlipidemia 4.9% (N = 102)
Diabetes 32.0% (N = 100)
Bronchiolitis Obliterans 30.7% (N = 75)
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
POST-LUNG TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Prevalence in Survivors within 7 Years Post-Transplant
(Follow-ups: April 1994 - June 2005)
Outcome Within 7
Years Total number with known response
Hypertension 72.7% (N = 44)
Renal Dysfunction 34.8% (N = 46) Abnormal Creatinine < 2.5 mg/dl 21.7% Creatinine > 2.5 mg/dl 4.3% Chronic Dialysis 0.0% Renal Transplant 8.7%
Hyperlipidemia 2.2% (N = 46)
Diabetes 24.4% (N = 45)
Bronchiolitis Obliterans 32.1% (N = 28)
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
Freedom from Bronchiolitis Obliterans For Pediatric Lung Recipients (Follow-ups: April 1994 - June 2005)
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7
Years
% F
ree
fro
m B
ron
ch
ioli
tis
Ob
lite
ran
s
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
FREEDOM FROM BRONCHIOLITIS OBLITERANS
For Pediatric Lung Recipients by Induction Use (Transplants: April 1994 - June 2005)
0
25
50
75
100
0 1 2 3 4 5
Years
Su
rviv
al (
%)
Induction (N = 105)
No Induction (N = 287)
p = 0.64
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
Freedom from Severe Renal Dysfunction*For Pediatric Lung Recipients (Follow-ups: April 1994 - June 2005)
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7Years
% F
ree
fro
m S
ev
ere
Re
na
l D
ys
fun
cti
on
* Severe renal dysfunction = Creatinine > 2.5 mg/dl, dialysis or renal transplant
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
MALIGNANCY POST-LUNG TRANSPLANTATION FOR PEDIATRICSCumulative Incidence for Survivors (Follow-ups: April 1994 - June 2005)
Malignancy/Type 1-Year Survivors
5-Year Survivors
7-Year Survivors
No Malignancy 429 (94.5%) 91 (89.2%) 42 (91.3%)
Malignancy (all types combined)
25 (5.5%) 11 (10.8%) 4 (8.7%)
Malignancy Type
Lymph 22 10 4
Other 3 1 0
”Other” includes Liver and primitive neuroectodermal tumor.
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
Freedom from MalignancyFor Pediatric Lung Recipients (Follow-ups: April 1994 - June 2005)
50
60
70
80
90
100
0 1 2 3 4 5 6 7
Years
% F
ree
fro
m M
alig
nan
cy
All malignancy Lymph Skin Other
ISHLT 2006J Heart Lung Transplant 2006;25:904-911
PEDIATRIC LUNG TRANSPLANT RECIPIENTS: Cause Of Death(Deaths: January 1992- June 2005)
CAUSE OF DEATH0-30 Days
(N =70 )31 Days - 1 Year
(N = 102)
>1 Year - 3 Years
(N = 103)
>3 Years - 5 Years
(N = 48)
>5 Years
(N = 30)
BRONCHIOLITIS 9 (8.8%) 39 (37.9%) 21 (43.8%) 12 (40.0%)
ACUTE REJECTION 3 (4.3%) 4 (3.9%) 1 (2.1%)
LYMPHOMA 3 (2.9%) 4 (3.9%) 1 (2.1%) 3 (10.0%)
MALIGNANCY, NON-LYMPHOMA
1 (2.1%)
CMV 7 (6.9%)
INFECTION, NON-CMV 9 (12.9%) 38 (37.3%) 23 (22.3%) 13 (27.1%) 2 (6.7%)
GRAFT FAILURE 23 (32.9%) 19 (18.6%) 17 (16.5%) 4 (8.3%) 6 (20.0%)
CARDIOVASCULAR 9 (12.9%) 3 (2.9%) 2 (1.9%)
TECHNICAL 9 (12.9%) 1 (1.0%)
MULTIPLE ORGAN FAILURE
4 (5.7%) 10 (9.8%) 9 (8.7%) 3 (6.3%) 3 (10.0%)
OTHER 13 (18.6%) 8 (7.8%) 9 (8.7%) 4 (8.3%) 4 (13.3%)
ISHLT 2006J Heart Lung Transplant 2006;25:904-911