prof geert m. verleden uz gasthuisberg leuven · uz leuven . 2 14 . 7 13 12 . 12 ... increasing...
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Prof Geert M. Verleden UZ Gasthuisberg
Leuven
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Patients with chronic end-stage lung disease, such as COPD, CF, PAH, Pulmonary fibrosis ◦ Max 50-55 y for HLTx ◦ 60-65 y for LTx
Failing medical treatment Or no medical treatment exists Need for ◦ Information ◦ Demonstration of adequate health behavior ◦ Willingness to adhere to guidelines
Aim of LTx: survival benefit and increase in QOL
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Malignancy in the last 2 years, except cutaneous squamous and basal cell tumors ◦ Remains questionnable regarding for instance
breast cancer, renal cancer. How long tumor free?
Untreatable advanced dysfunction of other organs (kidney, liver, …) ◦ Unless combined transplantation
Untreatable coronary artery disease ◦ What is nowadays untreatable?
Non-curable chronic extrapulmonary infections (hep B, hep C, HIV) ◦ Also questionnable
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Significant chest wall/spinal deformity ◦ To be discussed with surgeons
Documented non-adherence ◦ Specific problem in young CF patients
Untreatable psychiatric or psychologic condition with inability to comply with medical therapy
Absence of social support ◦ Difficulties to adhere to strict follow up
protocols Substance addiction: tobacco, alcohol,
narcotics, drug abuse that is active or within the last 6 months ◦ Is six months enough delay?
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Age > 65 y Critical or unstable clinical condition
(invasive ventilation, ECMO) BMI > 30 Colonization with highly resistant or
virulent bacteria, fungi or mycobacteria ◦ CF patients specifically ◦ Mycobacterial colonization/infection remains
problematic arterial hypertension peptic ulcer GER (50% or more preTx) Severe or symptomatic osteoporosis Diabetes
Should be adequately treated before Tx
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J Heart Lung Transplant 2010;29: 1083-1141.
5 7 36 78190
419
704
9211088
12231336
14521462149016291693
188219322071
23842448
2769
1357
2716
0250500750
100012501500175020002250250027503000
1985
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Num
ber o
f Tra
nspl
ants
Bilateral/Double LungSingle Lung
UZ Leuven
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2
14
7
13 12 12 13 13 12
20
0
5
10
15
20
25
Num
ber
Lung Transplantations per year in UZ Leuven
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Increasing number of referrals Increasing number of accepted donors ◦ Increasing number of transplant procedures ◦ Decreasing waiting list mortality
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20
32 33
43 39 39
57 53
49 47
58 62
81
56
0
10
20
30
40
50
60
70
80
90
Num
ber
Lung Transplantations per year in UZ Leuven
> 50/y
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J Heart Lung Transplant 2010;29: 1083-1141
49
3225
147
2650
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
Num
ber o
f cen
ters
0
5
10
15
20
25
30
Number of centers Percentage of transplants
Perc
enta
ge o
f tra
nspl
ants
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(HEART)-LUNG Tx IN LEUVEN BY DISEASE (n = 766)
4%
42% 14% 6%
3% 5% 23%
2% 2%
alpha1 ATD emphysema cystic fibrosis PH Eisenmenger ReTx Fibrosis Bronchiectasis miscellaneous
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0
50
100
150
200
250
300
350
< 20 20-30 31-40 41-50 51-60 >60 age distribution
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0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10
Surv
ival
(%)
Years
1988-1994 (N=4,392) 1995-1999 (N=6,726) 2000-6/2005 (N=9,419)
ISHLT 2007
J Heart Lung Transplant 2007;26: 782-795
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0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10
Surv
ival
(%)
Years
1988-1994 (N=4,392) 1995-1999 (N=6,726) 2000-6/2005 (N=9,419) Leuven
ISHLT 2007
J Heart Lung Transplant 2007;26: 782-795 Verleden et al; Clinical Transplants 2007.
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75%
60%
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Survival evolution in Leuven
5-y survival
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P=0.0021
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13Years
Su
rv
iva
l (%
)
Alpha-1 (N=2,187) CF (N=4,144) COPD (N=9,616)IPF (N=5,459) IPAH (N=1,123) Sarcoidosis (N=660)
HALF-LIFE Alpha-1: 6.1 Years; CF: 7.1 Years; COPD: 5.2 Years; IPF: 4.3 Years; IPAH: 4.9 Years; Sarcoidosis: 5.1 Years
Survival comparisonsAll comparisons with Alpha-1 and CF are statistically significant at 0.01
IPAH vs. IPF: p = 0.0210COPD vs. IPF: p < 0.0001
Leuven ISHLT
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Increasing experience Increase in number of transplantations per year
Use of marginal donors Use of non-heart beating donors (DCD donors) Use of euthanasia donors
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Age > 45-50 j Smokers (> 10 py) PaO2 < 400 mm Hg Chest X-ray with infiltrates Purulent secretions
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Meers et al. Transpl Int. 2010;23: 628-35
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De Vleeschauwer et al. JHLT 2011( n=21) Van de Wauwer et al. Eur J CardioThorac Surg. 2011; (n=27)
• NHBD
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Increasing experience Increase in number of transplantations per year
Use of marginal donors Use of non-heart beating donors (DCD donors)
Shift from single to double lung
transplantation
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0
5
10
15
20
25
30
35
40
45
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
HLTx SLtx SSLTx
91%
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Increasing experience Increase in number of transplantations per year
Use of marginal donors Use of non-heart beating donors (DCD donors)
Shift from single to double lung
transplantation
Specific follow up in Leuven
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Outpatient clinic run by specialized nurses, supervised by staff members of transplant unit
Every year global check up during short admission
All complications treated in own transplant unit in Leuven (role of experience!!)
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Increasing experience Increase in number of transplantations per year
Use of marginal donors Use of non-heart beating donors (DCD donors)
Shift from single to double lung transplantation
Specific follow up in Leuven
Cooperation with GP/specialist
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Calcineurin inhibitor ◦ Ciclosporine or tacrolimus
Proliferator inhibitor ◦ Azathioprine or mycophenolate
corticosteroids
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Macrolides ◦ clarithomycin
Antifungal drugs ◦ Itraconazole, voriconazole, fluconazole
NSAID ◦ Ibuprofen and others
Antihistamines Antidepressants
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Increasing experience Increase in number of transplantations per year
Use of marginal donors Use of non-heart beating donors (DCD donors)
Shift from single to double lung
transplantation
Specific follow up in Leuven
Cooperation with GP/specialist
Better treatment options for chronic rejection
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0
0,5
1
1,5
2
2,5
3
3,5
407
/01/
2002
07/0
5/20
02
07/0
9/20
02
07/0
1/20
03
07/0
5/20
03
07/0
9/20
03
07/0
1/20
04
07/0
5/20
04
07/0
9/20
04
07/0
1/20
05
07/0
5/20
05
07/0
9/20
05
07/0
1/20
06
FEV1, L
Postoperative time
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Vos R et al. Eur Respir J 2011; 37:164-72.
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P=0.0025
active
placebo
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ESW
Time after HLTx
FK + MMF rATG
rATG
BOS 2 75% Neutrophils in BAL
Verleden et al. Eur Respir J 2005; 25: 221-224.
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ESW
Time after HLTx
FK + MMF rATG
rATG
FEV1
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Verleden et al. Transpl Int 2011; 24:651-656.
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P=0.028
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0
20
40
60
80
100
120
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96
Free
dom
from
BO
S
Months post transplantation
ISHLT Leuven 69%
53%
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Number of Tx procedures is imperative for good results ◦ More SSLTx ◦ Use of marginal and NHB donors
Results of lung transplantation have significantly increased in recent years
Expertise of a whole team is extremely important
Close follow up is evenly important Chronic rejection remains the major
cause of death ◦ Role of azi in prevention/treatment ofchronic
rejection (35-40% responders) ◦ Trying to stabilize FEV1 decline with MLK
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Medics Tx Nurses Robin Vos Lieven Dupont Kristel Jans Dirk Van Raemdonck Kris Rosseel Marion Delcroix Veronique Schaevers Jonas Yserbyt Mieke Meelberg Leuven pulmonology and Annemieke Schoonis surgical team E 650 paramedics Erik Verbeken (pathology) BOF-ZAP researcher Bart Vanaudenaerde PhD Students Kathleen Blondeau Veerle Mertens Nele Geudens Stéphanie Devleeschauwer Caroline Meers Shana Wouters Stijn Verleden David Ruttens, Elly Vandermeulen