“Lung in a Box” No Disclosures Ex vivo Lung Perfusion (EVLP) · Program & Surgical Director,...
Transcript of “Lung in a Box” No Disclosures Ex vivo Lung Perfusion (EVLP) · Program & Surgical Director,...
5/31/2013
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Jasleen Kukreja, M.D., M.P.H.
Program & Surgical Director, Lung Transplant
University of California
San Francisco
“Lung in a Box” Ex vivo Lung Perfusion (EVLP)
Critical Care Medicine & Trauma Conference 2013
No Disclosures
Lung Transplant Facts
• As of Februrary 8, 2013, 1658 patients waiting for lung transplant in 70 Lung transplant programs in the U.S
• California has the highest number on waitlist
• >50% wait more than 6 months on the list
• 12% to 15% die waiting for suitable organs
Increasing waiting list has not been matched with donation rate
• Only 15-20% offered lungs accepted; 80% rejected due to:
- poor quality
- prolonged ischemia
time
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Supply : Demand
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Optimizing Supply : Demand Ratio
• Recipient selection criteria
– Age
– Diagnosis
– Single vs double lung
transplant
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LUNG TRANSPLANTATION Kaplan-Meier Survival by Age Group (Transplants: January 1990 – June 2009)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Years
18-34 (N = 5,523)
35-49 (N = 7,980)
50-59 (N = 11,389)
60-65 (N = 5,685)
>65 (N = 1,217)
Survival comparisons
All p-values significant at p < 0.0001 except 18-34 vs. 35-49: p =0.1708
HALF-LIFE 18-34: 6.4 Years; 35-49: 6.7 Years; 50-59: 5.3 Years; 60-65: 4.4 Years; >65: 3.5
Years
Su
rviv
al
(%)
ISHLT 2011
J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132
LUNG TRANSPLANTS: Transplant Recipient Age by Year of Transplant
Transplants: January 1, 1987 – June 30, 2010
0%
20%
40%
60%
80%
100%
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
0
12
24
36
48
60
0-11 12-17 18-34 35-4950-59 60-65 66+ Median Age
Me
dia
n r
ec
ipie
nt
ag
e (
ye
ars
)
% o
f tr
an
sp
lan
tsrs
Year of Transplant
ISHLT 2011
J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132
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LUNG TRANSPLANTATION Kaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2009)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Years
Su
rviv
al (%
)
Alpha-1 (N=2,349) CF (N=4,828) COPD (N=10,741)
IPF (N=6,478) IPAH (N=1,189) Sarcoidosis (N=756)
HALF-LIFE Alpha-1: 6.3 Years; CF: 7.4 Years; COPD: 5.3 Years;
IPF: 4.5 Years; IPAH: 4.9 Years; Sarcoidosis: 5.3 Years
Survival comparisons
All comparisons with Alpha-1 and CF are
statistically significant at < 0.01
COPD vs. IPF: p < 0.0001
ISHLT 2011
J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132
Single vs Double Lung Transplant
Single Lung Single Lung
ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival (Transplants: January 1994 - June 2009)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Years
Bilateral/Double Lung (N=16,628)
Single Lung (N=12,085)
All Lungs (N= 28,727)
Double lung: 1/2-life = 6.8 Years;
Single lung: 1/2-life = 4.7 Years
All lungs: 1/2-life = 5.5 Years
P < 0.0001
Su
rviv
al (%
)
ISHLT 2011
J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132
Optimizing Supply : Demand Ratio
• Recipient selection
criteria:
– Age
– Diagnosis
– Single vs double lung
transplant
• Donor selection criteria:
-Age
-Single vs double lung transplant
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LUNG TRANSPLANTS: Donor Age by Year of Transplant
Transplants: January 1, 1987 – June 30, 2010
0%
20%
40%
60%
80%
100%
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
Year of Transplant
0
10
20
30
40
50
0-11 12-17 18-34 35-49 50-59 60+ Median Donor Age
% o
f tr
an
sp
lan
ts
Me
dia
n d
on
or
ag
e (
ye
ars
)
ISHLT 2011
J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132
ADULT LUNG TRANSPLANTS (1/1997-6/2005)
Risk Factors for 5 Year Mortality Donor Age
0
0.5
1
1.5
2
15 20 25 30 35 40 45 50 55
Donor Age
Re
lati
ve
Ris
k o
f 5
Yea
r M
ort
ality
p = 0.0646
ISHLT 2011
J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132
Optimizing Supply : Demand Ratio
• Recipient selection
criteria:
– Age
– Diagnosis
– Single vs double lung
transplant
• Donor selection criteria:
-Age
-Single vs double
-Rehabilitation/ reconditioning
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Standard Lung Procurement
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“Lungs in a Box”
• Bronchoscopy • Antibiotic treatment • Constant Monitoring
– Dynamic compliance – Peak Inspiratory
pressure – Pulmonary vascular
resistance – P/F ratio
Ex Vivo Reconditioning Donor Lungs
Transplantation Proceedings, 42, 440–443 (2010)
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N Engl J Med 2011;364:1431-40.
From the Toronto Lung Transplant Program
Normothermic Ex-vivo Perfusion in Lung Transplant
N Engl J Med 364;15 April 14, 2011
High Risk Donors:
• Inclusion Criteria: • PaO2/FiO2 < 300 mm Hg • Bilateral infiltrates w/o infection • Poor lung deflation or inflation intraoperatively • Blood transfusions exceeding 10 Units • Donation after cardiac death
• Exclusion Criteria: • Established pneumonia • Mechanical lung injury • Gross gastric aspiration
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U.S. NOVEL Lung Trial Marginal Donor Lungs
ADULT LUNG TRANSPLANT RECIPIENTS: Relative Incidence of Leading Causes of Death
(Deaths: January 1992 - June 2010)
ISHLT 2011
J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132
0
10
20
30
40
50
0-30 Days
(N=2,204)
31 Days – 1
Year
(N=3,781)
>1 Year – 3
Years
(N=3,425)
>3 Years – 5
Years
(N=1,962)
>5 Years – 10
Years
(N=2,336)
>10 Years
(N=675)
Bronchiolitis Malignancy (non-Lymph/PTLD)
Infection (non-CMV) Graft Failure
Cardiovascular
Perc
en
tag
e o
f D
ea
ths
OCS INSPIRE Trial International Randomized Trial
Goals: To compare the safety and effectiveness of the OCS Lung compared to cold storage for donor lung preservation
Design: A prospective, international, multi-center, randomized controlled trial comparing preservation of donor lungs using OCS-Lung perfusion device (Treatment Group) to cold flush and storage (Control Group)
Size: Up-to 20 participating sites with up to 264 randomized male and female subjects who are primary lung transplant recipients.
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OCS™ Lung Technology
The ONLY Portable, Integrated and Automated Perfusion & Ventilation System
INSPIRE Endpoints
Primary: A composite of patient and graft survival at day 30 post transplantation, and absence of ISHLT Primary Graft Dysfunction (PGD) Grade 3 at 72 hours post-transplantation.
Secondary: • Incidence of ISHLT PGD Grade 3 at 72 hours post-transplantation • Incidence of ISHLT PGD Grade 2 or 3 at 72 hours post-transplantation • Patient survival at day 30 • Graft survival at day 30
INSPIRE Trial Centers To-Date
Hannover
Berlin
Madrid
Padua
Leuven
Strasbourg
Bichat
Harefield
Leuven
EU Sites
Cleveland Clinic
UCLA
UPMC
The Methodist
UCSF
US Sites
Sydney
Australia
Edmonton
Canada
Early Clinical Experience
• OCS Lung was released in the European market
in Jan 2011
• Between February-July 2011, 13 double lung
transplant procedures on the OCS™-Lung
device
• Non-randomized and were consecutive case
series at Hannover Medical School, Hannover,
Germany and Puerta de Hierro Majdahonda
Hospital, Madrid, Spain
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The INSPIRE International Lung Trial
With The Organ Care System
Technology (OCS™) G. Warnecke, A. Haverich, G. Massard, N. Santelmo, F. Rea, C. Knosalla, R. Hetzer,
G. Leseche, A. Ardehali, A. R. Simon, J. Kukreja, K. McCurrey
Early outcome Post transplant outcomes OCS
(N=9) SOC
(N=10) ICU time (hours) Mean +/- SD 170+/-350 97+/-91
Median 50 65 Range 15 - 1033 16 - 276
Mechanical ventilation time (hours)
Mean +/- SD 14.4+/-5.5 15.5+/-5.6
Median 14.5 15.0 Range 5 - 22 9 - 27 Survival at 30 days Patient [n(%)] 6 (100) 7 (100) Graft [n(%)] 6 (100) 7 (100) Primary Graft Dysfunction (PGD) Grade 3
T 0 [n(%)] 0 (0) 2 (20) T 24 [n(%)] 0 (0) 0 (0) T 48 [n(%)] 0 (0) 1 (11) T 72 [n(%)] 0 (0) 1 (11)
“Lung in a Box” might be the ANSWER!
Improved Survival
Increased Supply
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Thank You !