WHO AND WHEN TO REFER FOR LUNG

TRANSPLANTATION?

Geert M. VerledenMedical DirectorLung Transplant Programme Leuven, Belgium

Patient selection: indications for LTx 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 guidelinesAim of LTx: survival benefit and increase in QOL

Meaning of failing medical treatment?

COPD Rehabilitation LVRS?? Bullectomy

IPF and ILD Study protocols?

CF What about mulitiresistent Pseudomonas

or Cepacia?

Regarding PAH

Need expertise in treatment with Prostaglandins PDE inhibitors Endothelin receptor blockers …

Absolute contra-indications 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

Absolute contra-indications 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?

Relative contra-indications Age > 60-65 y

Critical or unstable clinical condition (invasive ventilation, ECMO)

Risk Factors for 1 Year Mortality

DONOR CHARACTERISTICS N Relative Risk P-value

95% Confidence

Interval

Donor history of diabetes 327 1.40 0.0032 1.12 -1.74

RECIPIENT CHARACTERISTICS

IV inotropes 70 1.75 0.0014 1.24 -2.45

Ventilator 274 1.60 0.0001 1.27 -2.02

Hospitalized (including ICU) 934 1.51 <0.0001 1.29 -1.76

Prior sternotomy 367 1.20 0.0813 0.98 -1.47

Chronic steroid use 5224 1.15 0.0015 1.06 -1.26

(N=11,079)

J Heart Lung Transplant 2008;27: 937-983

Risk Factors for 1 Year Mortality

Recipient Age

0

0,5

1

1,5

2

25 30 35 40 45 50 55 60 65Recipient Age

Rel

ativ

e R

isk

of 1

Yea

r Mor

talit

y

p < 0.0001

J Heart Lung Transplant 2008;27: 937-983

Risk Factors for 5 Year Mortality

Recipient Age

0

0,5

1

1,5

2

25 30 35 40 45 50 55 60 65Recipient Age

Rel

ativ

e R

isk

of 5

Yea

r Mor

talit

y

p < 0.0001

J Heart Lung Transplant 2008;27: 937-983

Risk Factors for 1 Year Mortality

Center Volume

0

0,5

1

1,5

2

5 10 15 20 25 30 35 40 45 50Center Volume (cases per year)

Rel

ativ

e R

isk

of 1

Yea

r Mor

talit

y

p < 0.0001

J Heart Lung Transplant 2008;27: 937-983

Relative contra-indications Colonization with highly resistant or

virulent bacteria, fungi or mycobacteria CF patients specifically Mycobacterial colonization/infection remains

problematic

ADULT LUNG TRANSPLANTATION Survival By Diagnosis

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10Years

Surv

ival

(%)

Alpha-1 (N=1,925) CF (N=3,275) COPD (N=7,760)IPF (N=3,931) PPH (N=970) Sarcoidosis (N=506)

HALF-LIFE Alpha-1: 5.9 Years; CF: 6.4 Years; COPD: 5.0 Years; IPF: 4.1 Years; PPH: 4.6 Years; Sarcoidosis: 5.1 Years

CF vs. COPD: p < 0.0001CF vs. IPF: p < 0.0001CF vs. PPH: p < 0.0001CF vs. Sarcoidosis: p < 0.0001

J Heart Lung Transplant 2008;27: 937-983

Relative contra-indications BMI > 30 Severe or symptomatic osteoporosis Diabetes arterial hypertension peptic ulcer GER (50% or more preTx) …

Should be adequately treated before Tx

When to refer? Disease-specific criteria:

Orens et al. International guidelines for the selection of lung transplant candidates: 2006 update--a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2006; 25: 745.

Taking into account several centre characteristics: Donor availability Local waiting time

Increasing role of DCD donors

0 365 730 10950

20

40

60

80

100

HBD LTx

NHBD long Tx

Dagen

Act

uarië

le o

verle

ving

N=17N=126

Time window referral - transplantation

Referral

Transplantation

Waiting time

Decline for Tx ? Urgent Tx ?

< expected survival before Tx

If estimated WT > expected survival

Mean waiting time in Leuven

'92 '93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05 '06 '07 '08 090

50

100

150

200

250

300

Jaartal

Dag

en

Waiting time is blood group dependent

050

100150200250300350

O/B A/ABbloedgroep

Days

Blood Group

P<0.001

… and heigth dependent

> 168 cm < 168 cm0

100

200

300days

167

219

p < 0.05

(160 ± 7 cm)(175 ± 6 cm)

Adapted from D. Van Raemdonck, Leuven 2003

How to refer: role of the Tx Team

Director(s) of the programPulmonologist

SurgeonOther MD

Collaboration with other MD disciplines

Transplantation protocolDescribing procedures, local responsabilities,

treatment modalities, …

Collaboration withTransplant coordinators

Collaboration with paramedics, such as

Nurses, physiotherapists,Dieticians,

social workers, Psychologist, …

Establish a Network with

Referring physicians

How to refer? Telephone call

With referring physician To discuss current patient situation

First outpatient visit To see the patient personally and to give furher

information on what to expect If no clear contra-indications so far Pretransplant work-up performed by referring

physician Afterwards team discussion and short

admission to the transplant hospital On waiting listPromote early referral !!

Surgeon Pulmonologist

Pulmonologist Surgeon

Survival results

0 1 3 6 12 24 36 48 60 72 840

20

40

60

80

100

LTx Leuven LTx ISHLTPostoperatieve maanden

Actu

arië

le o

verle

ving

(%

)

Survival Results (2)

0 365 730 1095 1460 1825 2190 2555 2920 3285 36500

20

40

60

80

100

SSLTxSLTx

Postoperatieve dagen

Act

uariël

e ov

erle

ving

(%)

Conclusions General indications and contra-indications provide

guidelines for Tx Specific disease-based criteria will be helpfull No single criteria is enough to predict prognosis Best option:

Contact transplant center and discuss the patient Refer the patient for a first “physical” contact when in doubt Be on time !!!

Do not let the referring physician decide to

transplant or not