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

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of

Tra

ns

pla

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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

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60

80

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

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%)

.

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)

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0 1 2 3 4 5 6 7 8 9 10

Years

Su

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%)

.

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)

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Years

Su

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%)

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

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0,5

1

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Ischemia time (hours)

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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