Predictive factors for long-term survival Predictive factors for long-term survival after lung transplantation; a review in a after lung transplantation; a review in a single large-volume centersingle large-volume center
University Hospital GasthuisbergLeuvenBelgium
A. Demir, G.M. Verleden, L. Dupont, G. Van Helleputte, A. Demir, G.M. Verleden, L. Dupont, G. Van Helleputte, W. Coosemans, H. Decaluwé, P. De Leyn, Ph. Nafteux, W. Coosemans, H. Decaluwé, P. De Leyn, Ph. Nafteux, T.Lerut , D. Van RaemdonckT.Lerut , D. Van Raemdonck
AVERAGE CENTER VOLUMEAVERAGE CENTER VOLUMELung Transplants: January 1, 2000 - June 30, 2008Lung Transplants: January 1, 2000 - June 30, 2008
46
2533
2217
730
10
20
30
40
50
60
1-4 5-9 10-19 20-29 30-39 40-49 50+
Average number of lung transplants per year
Nu
mb
er o
f ce
nte
rs
0
5
10
15
20
25
30
Number of centers Percentage of transplants
Pe
rce
nta
ge
of
tra
ns
pla
nts
ISHLT
2009
NUMBER OF LUNG TRANSPLANTS REPORTED NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND PROCEDURE TYPEBY YEAR AND PROCEDURE TYPE
5 7 36 78190
419
704
922
10871223
13581338145014601491
16281690
187919302071
23862448
2708
0
250
500
750
1000
1250
1500
1750
2000
2250
2500
2750
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Nu
mb
er
of
Tra
ns
pla
nts
Bilateral/Double LungSingle Lung
ISHLTNOTE: This figure includes only the lung transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as representing changes in the number of lung transplants performed worldwide.
2009
AGE DISTRIBUTION OF LUNG TRANSPLANT AGE DISTRIBUTION OF LUNG TRANSPLANT RECIPIENTSRECIPIENTS (1/1985-6/2008)(1/1985-6/2008)
0
5
10
15
20
25
30
35
0-11 12-17 18-29 30-39 40-49 50-59 60-65 66+
Recipient Age
% o
f tr
an
sp
lan
ts
ISHLT
2009
DONOR AGE DISTRIBUTION FOR LUNG DONOR AGE DISTRIBUTION FOR LUNG TRANSPLANTS TRANSPLANTS (1/1985-6/2008)(1/1985-6/2008)
0
5
10
15
20
25
30
35
0-11 12-17 18-29 30-39 40-49 50-59 60-65 66+
Donor Age
% o
f tr
an
sp
lan
ts
ISHLT
2009
AimAim
Long- Long- term survival after lung term survival after lung transplantation (LTx) may vary between transplantation (LTx) may vary between patients as a result of increased risk patients as a result of increased risk factors both in the donor and in the factors both in the donor and in the recipient. recipient. The objective of this retrospective study The objective of this retrospective study was to analyze factors from a prospective was to analyze factors from a prospective database that are predictive fordatabase that are predictive for long-term long-term survival in our lung transplant cohort.survival in our lung transplant cohort.
Patients and MethodsPatients and Methods
Donor variablesDonor variables (age, gender, smoking, cytomegalovirus, (age, gender, smoking, cytomegalovirus, PaO2/FiO2, mechanical ventilation time, PaO2/FiO2, mechanical ventilation time, cause of death and cold ischemic time) cause of death and cold ischemic time)
RRecipient variablesecipient variables (age, gender, cytomegalovirus(age, gender, cytomegalovirus, , underlying underlying lung disorderlung disorder and LTx type) and LTx type)
AAnalysed for long-term survival in a univariate nalysed for long-term survival in a univariate and multivariate analysisand multivariate analysis
Patients and MethodsPatients and Methods
Between July 1991 and December 2009Between July 1991 and December 2009
258 females and 203 males258 females and 203 males
Mean age:48 years [13-69 years]. Mean age:48 years [13-69 years].
461 consecutive LTx 461 consecutive LTx – Single (n=149) Single (n=149) – Bilateral (n=312) Bilateral (n=312)
Patients and MethodsPatients and Methods
Indications for LTx Indications for LTx – emphysema (n=193)emphysema (n=193)– pulmonary fıbrosis (n=85)pulmonary fıbrosis (n=85)– cystic fibrosis (n=68)cystic fibrosis (n=68)– alfa-1-antitrypsin deficiency (n=33)alfa-1-antitrypsin deficiency (n=33)– pulmonary hypertension (n=16)pulmonary hypertension (n=16)– others (n=66)others (n=66)
ADULT LUNG TRANSPLANTATIONADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By DiagnosisKaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2007)(Transplants: January 1990 – June 2007)
YearYear ALPHA-1 ALPHA-1 (N=2,085)(N=2,085)
CF CF (N=3,746)(N=3,746)
COPD COPD (N=8,812)(N=8,812)
IPF IPF (N=4,695)(N=4,695)
IPAH IPAH (N=1,065)(N=1,065)
SARCOIDOSIS SARCOIDOSIS (N=597)(N=597)
11 78.778.7 82.682.6 82.482.4 74.174.1 71.171.1 72.272.2
33 64.864.8 67.567.5 65.365.3 58.558.5 60.360.3 57.857.8
55 55.755.7 57.457.4 50.850.8 45.945.9 51.751.7 51.951.9
77 45.945.9 5050 38.538.5 35.435.4 44.544.5 43.543.5
1010 32.632.6 39.639.6 22.922.9 22.322.3 32.432.4 31.931.9
Survival comparisonsAlpha-1 vs. CF: p < 0.0001 Alpha-1 vs. COPD: p < 0.0001 Alpha-1 vs. IPF: p < 0.0001 Alpha-1 vs. Sarcoidosis: p = 0.0380CF vs. COPD: p < 0.0001 CF vs. IPF: p < 0.0001CF vs. IPAH: p < 0.0001 CF vs. Sarcoidosis: p < 0.0001IPAH vs. IPF: p = 0.0046 COPD vs. IPF: p < 0.0001
Note: Other comparisons are not statistically different.
ISHLT
2009
ADULT LUNG TRANSPLANTATIONADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By DiagnosisKaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2007)(Transplants: January 1990 – June 2007)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12
Years
Su
rviv
al (
%)
Alpha-1 (N=2,085) CF (N=3,746) COPD (N=8,812)
IPF (N=4,695) IPAH (N=1,065) Sarcoidosis (N=597)
HALF-LIFE Alpha-1: 6.1 Years; CF: 7.0 Years; COPD: 5.1 Years; IPF: 4.3 Years; IPAH: 5.6 Years; Sarcoidosis: 5.3 Years
ISHLT
Survival comparisonsAlpha-1 vs. CF: p < 0.0001Alpha-1 vs. COPD: p < 0.0001 Alpha-1 vs. IPF: p < 0.0001Alpha-1 vs. Sarcoidosis: p = 0.0380CF vs. COPD: p < 0.0001CF vs. IPF: p < 0.0001CF vs. IPAH: p < 0.0001CF vs. Sarcoidosis: p < 0.0001IPAH vs. IPF: p = 0.0046COPD vs. IPF: p < 0.0001
2009
ADULT LUNG TRANSPLANTATIONADULT LUNG TRANSPLANTATIONKaplan-Meier Survival Kaplan-Meier Survival (Transplants: January 1994 - June 2007)(Transplants: January 1994 - June 2007)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10
Years
Su
rviv
al (
%)
.
Bilateral/Double Lung (N=12,246)
Single Lung (N=10,081)
All Lungs (N=22,328)
Double lung: 1/2-life = 6.6 Years; Conditional 1/2-life = 9.0 YearsSingle lung: 1/2-life = 4.6 Years; Conditional 1/2-life = 6.4 YearsAll lungs: 1/2-life = 5.4 Years; Conditional 1/2-life = 7.4 Years
P < 0.0001
ISHLT
2009
ADULT LUNG TRANSPLANTATIONADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Age GroupKaplan-Meier Survival by Age Group (Transplants: January 1990 – June 2007)(Transplants: January 1990 – June 2007)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10
Years
Su
rviv
al (
%)
.
18-34 (N = 4,420)35-49 (N = 6,629)50-59 (N = 9,229)60-65 (N = 4,262)66+ (N = 694)
Survival comparisonsAll p-values significant at p < 0.0001 except 18-34 vs. 35-49: p = 0.7127; 60-65 vs. 66+: p = 0.0007
HALF-LIFE 18-34: 5.9 Years; 35-49: 6.3 Years; 50-59: 5.1 Years; 60-65: 4.2 Years; 66+: 3.2 Years
ISHLT
2009
ADULT LUNG TRANSPLANTATIONADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by GenderKaplan-Meier Survival by Gender (Transplants: January 1990 – June 2007)(Transplants: January 1990 – June 2007)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10
Years
Su
rviv
al (
%)
Male (N=13,251)
Female (N=11,981)
HALF-LIFE Male: 5.0 years; Female: 5.4 Years
p = 0.0006
N at risk at 5 years=3,456
N at risk = 783N at risk at 5 years=3,311
N at risk = 762
ISHLT
2009
ADULT LUNG TRANSPLANTSADULT LUNG TRANSPLANTS (1/1995-6/2007)(1/1995-6/2007)Diagnosis = IPFDiagnosis = IPF
Risk Factors for 1 Year MortalityRisk Factors for 1 Year MortalityIschemia TimeIschemia Time
0
0,5
1
1,5
2
2 3 4 5 6 7
Ischemia time (hours)
Rel
ativ
e R
isk
of
1 Y
ear
Mo
rtal
ity
p = 0.084
ISHLT
2009
In a univariate analysisIn a univariate analysis
DDonoronor – Gender Gender ((pp<0.05<0.05))– CCold ischemic time old ischemic time ((pp<0.0001<0.0001))
RRecipientecipient – Age Age ((pp<0.05<0.05))– GGender ender ((p<0.001p<0.001))– Underlying lung disorder (Underlying lung disorder (pp<0.01<0.01))– LTx type LTx type ((pp<0.000<0.000))
In a multivariate analysisIn a multivariate analysis
TThe following he following recipient variablesrecipient variables remained remained independent negative prognostic factors of independent negative prognostic factors of survival: survival: – AAge <20 years ge <20 years ((pp<0.05<0.05))– MMale gender ale gender ((pp<0.05<0.05))– PPulmonary hypertension ulmonary hypertension ((pp<0.05<0.05))– SSingle LTx ( ingle LTx ( pp<0.01). <0.01).
ConclusionConclusion
PatientsPatients younger than 20 years (H.R 0.3) younger than 20 years (H.R 0.3) andand those with those with pulmonary hypertensive pulmonary hypertensive diseasedisease (H.R 2.7)(H.R 2.7) have an increased risk have an increased risk of inferior survival after LTx .of inferior survival after LTx .
Female recipients (H.R 0.5) and bilateral Female recipients (H.R 0.5) and bilateral lung recipients (H.R 2.5) experience better lung recipients (H.R 2.5) experience better long-term survivallong-term survival