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WHO AND WHEN TO REFER FOR LUNG
TRANSPLANTATION?
Geert M. VerledenMedical DirectorLung Transplant Programme Leuven, Belgium
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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
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Meaning of failing medical treatment?
COPD Rehabilitation LVRS?? Bullectomy
IPF and ILD Study protocols?
CF What about mulitiresistent Pseudomonas
or Cepacia?
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Regarding PAH
Need expertise in treatment with Prostaglandins PDE inhibitors Endothelin receptor blockers …
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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
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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?
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Relative contra-indications Age > 60-65 y
Critical or unstable clinical condition (invasive ventilation, ECMO)
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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
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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
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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
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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
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Relative contra-indications Colonization with highly resistant or
virulent bacteria, fungi or mycobacteria CF patients specifically Mycobacterial colonization/infection remains
problematic
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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
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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
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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
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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
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Time window referral - transplantation
Referral
Transplantation
Waiting time
Decline for Tx ? Urgent Tx ?
< expected survival before Tx
If estimated WT > expected survival
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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
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Waiting time is blood group dependent
050
100150200250300350
O/B A/ABbloedgroep
Days
Blood Group
P<0.001
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… 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
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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
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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 !!
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Surgeon Pulmonologist
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Pulmonologist Surgeon
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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
(%
)
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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
(%)
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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