Prof Geert M. Verleden UZ Gasthuisberg

Leuven

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

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

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?

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

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

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

Num

ber o

f Tra

nspl

ants

Bilateral/Double LungSingle Lung

UZ Leuven

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

Increasing number of referrals Increasing number of accepted donors ◦ Increasing number of transplant procedures ◦ Decreasing waiting list mortality

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

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

(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

0

50

100

150

200

250

300

350

< 20 20-30 31-40 41-50 51-60 >60 age distribution

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

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.

75%

60%

Survival evolution in Leuven

5-y survival

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

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

Age > 45-50 j Smokers (> 10 py) PaO2 < 400 mm Hg Chest X-ray with infiltrates Purulent secretions

Meers et al. Transpl Int. 2010;23: 628-35

De Vleeschauwer et al. JHLT 2011( n=21) Van de Wauwer et al. Eur J CardioThorac Surg. 2011; (n=27)

• NHBD

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

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%

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

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!!)

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

Calcineurin inhibitor ◦ Ciclosporine or tacrolimus

Proliferator inhibitor ◦ Azathioprine or mycophenolate

corticosteroids

Macrolides ◦ clarithomycin

Antifungal drugs ◦ Itraconazole, voriconazole, fluconazole

NSAID ◦ Ibuprofen and others

Antihistamines Antidepressants

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

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

Vos R et al. Eur Respir J 2011; 37:164-72.

P=0.0025

active

placebo

ESW

Time after HLTx

FK + MMF rATG

rATG

BOS 2 75% Neutrophils in BAL

Verleden et al. Eur Respir J 2005; 25: 221-224.

ESW

Time after HLTx

FK + MMF rATG

rATG

FEV1

Verleden et al. Transpl Int 2011; 24:651-656.

P=0.028

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%

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

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