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‫‪LUNG‬‬
‫‪TRANSPLANTATION‬‬
‫‪2012‬‬
‫דר' לקסר אורי‬
‫מכון הראה‬
‫בית החולים האוניברסיטאי הדסה‬
INDICATION
Lung transplantation is indicated for patients with
chronic, end-stage lung disease who are failing maximal
medical therapy, or for whom no effective medical
therapy exists.
•COPD
•IPF
•PPH
•CF
The Journal of Heart and Lung Transplantation
July 2006
.
TIMING
Ideally, listing for transplantation should occur when
life expectancy is greatly reduced but nonetheless
greater than the expected waiting time for a suitable
organ, and transplantation should be performed when
life expectancy after transplantation exceeds life
expectancy without the procedure.
The Journal of Heart and Lung Transplantation
July 2006
AIMS
 Survival benefit

Quality of life
 Palliation
Absolute contraindications
• Malignancy in the last 2 years.
• .Untreatable advanced dysfunction of another
major organ system
• .Non-curable chronic extrapulmonary infection
including HBV HCV HIV
• .Significant chest wall/spinal deformity.
• .Documented nonadherence
• .Untreatable psychiatric or psychologic condition
• .Absence of a consistent or reliable social support
• .Substance addiction (e.g., alcohol, tobacco, or
narcotics)
The Journal of Heart and Lung Transplantation
July 2006
Relative contraindications
•
•
•
•
•
•
•
•
Age >65y
Unstable condition
Limited functional condition
18 >bmi>30
Colonization with resistant organism
Ventilation
Osteoporosis
IHD,D.M.,GERD,HTN….
The Journal of Heart and Lung Transplantation
July 2006
COPD
Guidelines for Referral
• .BODE index exceeding 5
Guidelines for Transplantation
• .Patients with a BODE index* of 7 to 10 or at least 1
of the following:
• .History of hospitalization for exacerbation associated
with acute hypercapnia (PCO2 exceeding 50 mm Hg).
• Pulmonary hypertension or cor pulmonale, or both,
despite oxygen therapy.
• .FEV1 of less than 20% and either DLCO of less than 20%
or homogenous distribution of emphysema.
The Journal of Heart and Lung Transplantation
July 2006
Cystic fibrosis and bronchiectasis
Guidelines for Referral
• .FEV1 below 30% predicted or a rapid decline in FEV1.
• .Exacerbation of pulmonary disease requiring ICU stay.
• .Increasing frequency of exacerbations requiring antibiotic
therapy.
• .Refractory and/or recurrent pneumothorax.
• .Recurrent hemoptysis not controlled by embolization.
Guideline for Transplantation
• .Oxygen-dependent respiratory failure.
• .Hypercapnia.
• .Pulmonary hypertension.
The Journal of Heart and Lung TransplantationJuly 2006
PULMONARY FIBROSIS
Guideline for Referral
early,do not wait to treatment
• .Histologic or radiographic evidence of UIP irrespective of vital capacity.
• .Histologic evidence of fibrotic NSIP.
Guideline for Transplantation
• .Histologic or radiographic evidence of UIP and any of the following:
• .A DLCO of less than 39% predicted.
• .A 10% or greater decrement in FVC during 6 months of follow-up.
• .A decrease in pulse oximetry below 88% during 6-MWT.
• .Honeycombing on HRCT (fibrosis score of 2).
• .Histologic evidence of NSIP and any of the following:
•.
•
A DLCO of less than 35% predicted.
.A 10% or greater decrement in FVC or 15% decrease
in DLCO during 6 months of follow-up.
The Journal of Heart and Lung Transplantation
July 2006
PULMONARY ARTERIAL
HYPERTENSION
Guideline for Referral
• .NYHA functional class III or IV, irrespective of ongoing therapy.
• .Rapidly progressive disease.
Guideline for Transplantation
• .Persistent NYHA class III or IV on maximal medical therapy.
• .Low (350 meter) or declining 6-MWT.
• .Failing therapy with intravenous epoprostenol, or equivalent.
• .Cardiac index of less than 2 liters/min/m2.
• .Right atrial pressure exceeding 15 mm Hg.
The Journal of Heart and Lung Transplantation
July 2006
NUMBER OF LUNG TRANSPLANTS REPORTED
BY YEAR AND PROCEDURE TYPE
2708
2750
Bilateral/Double Lung
Single Lung
2250
2000
2448
2386
2071
18791930
1690
1628
145014601491
13581338
1223
1087
1750
1500
1250
922
1000
704
750
419
500
190
250
5
7
36
78
0
19
85
19
86
19
87
19
88
19
89
19
90
19
91
19
92
19
93
19
94
19
95
19
96
19
97
19
98
19
99
20
00
20
01
20
02
20
03
20
04
20
05
20
06
20
07
Number of Transplants
2500
ISHLT
2009
NOTE: 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.
LUNG TRANSPLANTS:
Transplant Recipient Age by Year of Transplant
Transplants: January 1, 1987 – June 30, 2008
100%
50
40
60%
30
40%
20
20%
10
0%
0
19
87
19
88
19
89
19
90
19
91
19
92
19
93
19
94
19
95
19
96
19
97
19
98
19
99
20
00
20
01
20
02
20
03
20
04
20
05
20
06
20
07
20
08
% of Transplantsrs
80%
Year of Transplant
0-11
12-17
ISHLT
18-34
35-49
2009
50-59
60-65
66+
Mean Age
Mean recipient age (years)
60
AGE DISTRIBUTION OF LUNG TRANSPLANT
RECIPIENTS (1/1985-6/2008)
35
% of transplants
30
25
20
15
10
5
0
0-11
12-17
18-29
30-39
40-49
Recipient Age
ISHLT
2009
50-59
60-65
66+
DONOR AGE DISTRIBUTION FOR LUNG
TRANSPLANTS (1/1985-6/2008)
35
% of transplants
30
25
20
15
10
5
0
0-11
12-17
18-29
30-39
40-49
Donor Age
ISHLT
2009
50-59
60-65
66+
ADULT LUNG TRANSPLANTATION
Kaplan-Meier Survival
(Transplants: January 1994 - June 2007)
Survival (%)
.
100
Double lung: 1/2-life = 6.6 Years; Conditional 1/2-life = 9.0 Years
Single lung: 1/2-life = 4.6 Years; Conditional 1/2-life = 6.4 Years
All lungs: 1/2-life = 5.4 Years; Conditional 1/2-life = 7.4 Years
80
60
P < 0.0001
40
Bilateral/Double Lung (N=12,246)
Single Lung
(N=10,081)
All Lungs
(N=22,328)
20
0
0
1
2
3
4
5
Years
ISHLT
2009
6
7
8
9
10
ADULT LUNG TRANSPLANTATION: Indications for Single Lung Transplants (Transplants: January
1995 - June 2008)
Alpha-1
COPD
CF
IPF
IPAH
Re-Tx
Other*
29%
1%
3%
2%
*Other includes:
10%
6%
49%
ISHLT
2009
Sarcoidosis:
2.1%
Bronchiectasis:
0.4%
Congenital Heart Disease:
0.2%
LAM:
0.8%
OB (non-ReTx):
0.5%
Miscellaneous:
6.3%
ADULT LUNG TRANSPLANTATION
Kaplan-Meier Survival by Procedure Type (Transplants: January 1990 – June 2007)
Diagnosis: Emphysema/COPD
100
P < 0.0001
Survival (%)
75
N at risk at 5 years = 744
50
N=60
N at risk at 5 years = 1,786
25
COPD/Single lung (N=5,683)
N=138
COPD/Double lung (N=3,129)
0
0
1
2
3
4
5
6
Years
ISHLT
2009
7
8
9
10
11
12
ADULT LUNG TRANSPLANTS (1/1995-6/2007)
Risk Factors for 1 Year Mortality
Recipient Age
Relative Risk of 1 Year Mortality
2
1.5
1
0.5
p < 0.0001
0
25
30
35
40
45
50
Recipient Age
ISHLT
2009
55
60
65
ADULT LUNG RECIPIENTS
Functional Status of Surviving Recipients
(Follow-ups: April 1994 – June 2008)
100%
80%
60%
40%
20%
No Activity Limitations
Performs with Some Assistance
Requires Total Assistance
0%
1 Year (N = 6,820)
ISHLT
3 Year (N = 4,333)
2009
5 Year (N = 2,492)
10 Years (N = 422)
ADULT LUNG RECIPIENTS
Employment Status of Surviving Recipients
(Follow-ups: April 1994 – June 2008)
100%
80%
Working (FT/PT
Status unknown)
Working Part Time
60%
Working Full Time
40%
Retired
Not Working
20%
0%
1 Year (N=8,937) 3 Year (N=5,452) 5 Year (N=3,386) 10 year (N=704)
ISHLT
2009
ADULT LUNG RECIPIENTS
Maintenance Immunosuppression Drug Combinations at Time of Follow-up
For follow-ups between January 2002 through June 2008
Analysis limited to patients receiving prednisone
100
Other
Rapa + Cellcycle
% of Patients
80
Rapa + Calcineurin
Tacrolimus
Tacrolimus + MMF
Tacrolimus + AZA
60
40
Cyclosporine + MMF
Cyclosporine + AZA
20
0
Year 1 (N = 6,105)
ISHLT
Year 5 (N = 2,573)
2009
Analysis is limited to patients who were
alive at the time of the follow-up
POST-LUNG TRANSPLANT MORBIDITY FOR ADULTS
Cumulative Prevalence in Survivors within 10 Years Post-Transplant (Follow-ups: April
1994 - June 2008)
Outcome
Hypertension
Renal Dysfunction
Total number
with known
response
97.30%
(N = 337)
42.10%
(N = 484)
24.20%
7.40%
7.60%
2.90%
68.50%
Abnormal Creatinine < 2.5 mg/dl
Creatinine > 2.5 mg/dl
Chronic Dialysis
Renal Transplant
Hyperlipidemia
Diabetes
Bronchiolitis Obliterans Syndrome
ISHLT
Within 10
Years
2009
(N = 410)
37.40%
(N = 374)
50.20%
(N = 297)
FREEDOM FROM BRONCHIOLITIS OBLITERANS SYNDROME
For Adult Lung Recipients (Follow-ups: April 1994-June 2008)
Conditional on Survival to 14 days
% Freedom from Bronchiolitis
Obliterans Syndrome
100
Freedom from Bronchiolitis Obliterans
Syndrome (N = 10,835)
80
N at risk at 5 years = 1,329
60
40
N at risk = 61
20
0
0
1
2
3
4
5
Years
ISHLT
2009
6
7
8
9
10
FREEDOM FROM SEVERE RENAL DYSFUNCTION*
For Adult Lung Recipients (Follow-ups: April 1994-June 2008)
% Freedom from Severe Renal
Dysfunction
100
Freedom from Severe Renal
Dysfunction (N=11,463)
80
N at risk at 5 years = 1,910
60
N at risk = 110
40
* Severe renal dysfunction = Creatinine > 2.5 mg/dl
(221 μmol/L), dialysis or renal transplant
20
0
0
1
2
3
4
5
Years
ISHLT
2009
6
7
8
9
10
FREEDOM FROM MALIGNANCY
For Adult Lung Recipients (Follow-ups: April 1994-June 2008)
% Free from Malignancy
100
90
80
70
60
All malignancy
Lymph
Skin
Other
50
0
1
2
3
4
5
Years
ISHLT
2009
6
7
8
9
10
ADULT LUNG TRANSPLANT RECIPIENTS:
Relative Incidence of Leading Causes of Death
(Deaths: January 1992 - June 2008)
50
Malignancy (non-Lymph/PTLD)
Infection (non-CMV)
Graft Failure
Cardiovascular
40
Percentage of Deaths
Bronchiolitis
30
20
10
0
0-30 Days (N 31 Days – 1
= 1,621 )
Year (N =
3,110)
ISHLT
>1 Year – 3
Years (N
=2,776 )
2009
>3 Years – 5 >5 Years – 10 >10 Years (N
Years (N =
Years (N
= 392)
1,593 )
=1,797 )
‫מה קורה בישראל?‬
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‫רשימה ארצית לפי ‪ : LAS SCORE-‬שקלול‬
‫חומרת המחלה וסכויי הצלחת ההשתלה‬
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‫ראה‪,‬מחלות רקע‪,‬מחלת היסוד‪,‬מצב תפקודי וכ'‬
‫תרומה מתורם עם מוות מוחי מוכרז‬
‫אין תרומה מהחי‬
‫אין ‪STATUS ONE‬‬
‫ריאה מאופיינת בזמן איסכמיה קצר ‪ 4-6‬שעות‬
‫זמן המתנה עד שנה לערך‪ 70-‬חולים על‬
‫הרשימה‬
‫אין שיתוף פעולה אזורי או בינלאומי‬
‫תודה‬