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Axel Rahmel. Organ Donation and Transplantation in the European Union Challenges and opportunities of international cooperation in organ allocation. Technical Assistance for Alignment in Organ Donation 1 st International Symposium Istanbul – May 29-31, 2014. 135. Eurotransplant. 62.9. - PowerPoint PPT Presentation
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Axel Rahmel
Organ Donation and Transplantation in the European Union
Challenges and opportunities of international cooperation in
organ allocation
Technical Assistance for Alignment in Organ Donation 1st International SymposiumIstanbul – May 29-31, 2014
European Organ Exchange Organizations(million pop.)
.
7.17.21010.311
2124.2
38.243.2
56.961.562.9
135
Baltransplant
SwissTransplant
OPT Portugal
Czech Transplant
Hellas NTO
NTA Romenia
Scandiatransplant
Poltransplant
ONT Spain
CNT Italy
ABM France
UKTransplant
Eurotransplant
Organ Procurement
OrganizationTransplant-
center
National Competent Authorities
Transplantat Law
Organ donation Allocation Transplantatio
n
Distribution of tasks in organ transplantation
WHO GUIDING PRINCIPLES ON HUMAN CELL, TISSUE AND ORGAN TRANSPLANTATIONGuiding Principle 9
Where donation rates do not meet clinical demand, allocation criteria should be defined at national or subregional level by a committee that includes experts in the relevant medical specialties, bioethics and public health…
WHO GUIDING PRINCIPLES ON HUMAN CELL, TISSUE AND ORGAN TRANSPLANTATIONGuiding Principle 9
The allocation of organs, cells and tissues should be guided by clinical criteria and ethical norms, not financial or other considerations. Allocation rules, defined by appropriately constituted committees, should be equitable, externally justified, and transparent.
Aims of organ allocation
• Finding a suitable donor organ for all patients on the waiting list (including special patient groups) …in time
• Optimizing the match between donor and recipient to improve long term outcome of transplantation
• Preventing organ loss
Requirements for an organ allocation system
• Objectivity■ Allocation is independent of subjective factors (procurement
and allocation organization, transplant center)• Reliability
■ With same donor information and same waiting list information an identical matchlist is generated
• Transparency and accountability■ Every step in the allocation process is documented and can
be explained• Validity of allocation criteria
■ Ethically acceptable, medically based
ET o
ffice
ET A
C
Requirements for an organ allocation system
• Objectivity■ Allocation is independent of subjective factors (procurement
and allocation organization, transplant center)• Reliability
■ With same donor information and same waiting list information an identical matchlist is generated
• Transparency and accountability■ Every step in the allocation process is documented and can
be explained• Validity of allocation criteria
■ Ethically acceptable, medically based
ET o
ffice
ET A
C
The allocation center
Donor data Recipient data
Match
Match
Matchlist Allocation
Requirements for an organ allocation system
• Objectivity■ Allocation is independent of subjective factors (procurement
and allocation organization, transplant center)• Reliability
■ With same donor information and same waiting list information an identical matchlist is generated
• Transparency and accountability■ Every step in the allocation process is documented and can
be explained• Validity of allocation criteria
■ Ethically acceptable, medically based
ET o
ffice
ET A
C
Allocation – The key steps
Step 1 - Selection: • Identifying those patients that are
suitable at all for a specific organ among all patients on the waiting list.
Step 2 - Ranking: • Determining the allocation sequence
among all suitable recipients.
Selection of suitable recipients
Selection criteria• Blood group• Age (specific programs)• Organ specific matching factors
• Size, weight, total lung capacity (TLC)• Recipient and center profile
• Donor age• Donor risk factors
• Virology (Hep B, C (maybe in the future HIV)• History of malignancy• Drug abuse• Sepsis• Meningitis
Selecting: recipient and center profile
Determination of the MatchlistSelection and Ranking
A
H JE
I
DF GCB
Waiting listDay 1
Donor A65 yrs, 50kg
X X
X XX X
Matchlist 1Pat. „C“ is number 2 on the matchlist
A
H JE
I
DFCB
Waiting listDay 2 KG
D
Determination of the MatchlistSelection and Ranking
A
H JE
I
DFCB
Waiting list
Donor B40 yrs, 75kg
KXX
Matchlist 2Pat. „C“ is number 5 on the matchlist
Determination of the MatchlistSelection and Ranking
Urgency Outcome
Balancing urgency and outcome
Examples of the consequences of allocation trade-offs
Recipient60 years
with Diabetes
20 years withoutDiabetes
20 years with
DiabetesLifespanwithout transplant*
4 years 16 years 9 years
Lifespanwith transplant* 9 years 22 years 16 years
Incremantal survival 5 years 6 years 7 years
*Median survival for this specific patient group (US data)
Examples of the consequences of allocation trade-offs
Recipient60 years
with Diabetes
20 years withoutDiabetes
20 years with
DiabetesLifespanwithout transplant*
4 years 16 years 9 years
Lifespanwith transplant* 9 years 22 years 16 years
Incremantal survival 5 years 6 years 7 years
*Median survival for this specific patient group (US data)
Allocation to the most urgent patient(maximize waiting list survival)
Examples of the consequences of allocation trade-offs
Recipient60 years
with Diabetes
20 years withoutDiabetes
20 years with
DiabetesLifespanwithout transplant*
4 years 16 years 9 years
Lifespanwith transplant* 9 years 22 years 16 years
Incremantal survival 5 years 6 years 7 years
*Median survival for this specific patient group (US data)
Allocation to the patient with best outcome(maximize post transplant survival)
Examples of the consequences of allocation trade-offs
Recipient60 years
with Diabetes
20 years withoutDiabetes
20 years with
DiabetesLifespanwithout transplant*
4 years 16 years 9 years
Lifespanwith transplant* 9 years 22 years 16 years
Incremantal survival 5 years 6 years 7 years
*Median survival for this specific patient group (US data)
Allocation to the patient largest benefit (maximize incremental survival)
The benefits of international cooperation
Benefits of international cooperation in organ transplantation
• Preventing organ loss• Addressing the needs of special patient
groups• Improving the outcome of organ
transplantation• International harmonization of activities
in organ donation and transplantation
Benefits of international cooperation in organ transplantation
• Preventing organ loss• Addressing the needs of special patient
groups• Improving the outcome of organ
transplantation• International harmonization of activities
in organ donation and transplantation
Transplanted organs per donor in countries with less than 15 Mill inhabitantsET vs. countries without multinational collaboration
ET countries < 15 Mill population
EU countries < 15 Mill populationnot multinational
Deceased donors 813 (19,3 pmp) 1061 (15,6 pmp)Multi-organ donors 78,7% 57,3%Tx kidney p.d. 1,74 1,67Tx liver p.d. 0,76 0,51Tx heart p.d. 0,27 0,20Tx lung p.d. 0,28 0,07Tx pancreas p.d. 0,13 0,07
Newsletter transplant, September 2010
Estimating the increase in donor organs with better use of available donor organs• If the use of donor organs in EU countries with a
population of < 15 Mill (currently without established international collaboration) would be similar to that of the small ET countries, the number of available donor organs would increase by:
■ 88 kidneys■ 265 livers■ 89 hearts■ 222 lungs■ 68 pancreata
• This is a total increase of 732 organs or 2 organs per day
without any increase in the number of utilized donors / donation rates pmp
Benefits of international cooperation in organ transplantation
• Preventing organ loss• Addressing the needs of special
patient groups• Improving the outcome of organ
transplantation• International harmonization of activities
in organ donation and transplantation
General organ allocation sequenceEurotransplant
International HU(Accepted) Combined Organs
Elective
Elective
Elective
Elective
Elective
Other Organ Exchange Organizations
National HU National HU National HU National HU
Euro
tran
spla
nt
General organ allocation sequenceEurotransplant
International HU(Accepted) Combined Organs
Elective
Elective
Elective
Elective
Elective
Other Organ Exchange Organizations
National HU National HU National HU National HU
Euro
tran
spla
nt
n=201 (16%) n=1053 (84%)
Waiting time HU Liver-transplantFirst HU Liver-Tx [n=1254]
Pediatric (<16 yrs) Adult (16+ yrs)
Median waiting time: 2 d (both groups)
819
39
191
4
0-2 d 3-4 d
5-8 d 9-16 d
128
43
27
39
0-2 d 3-4 d 5-8 d
9-16 d 16+ d
Organ allocation - KidneyHighly Immunized -
Acceptable Mismatch (AM) – ABO compatible
ETKAS Point Score System including HU : ABO Identical
A D HB/L
Pediatric donor (< 16yrs) recipients with status pediatricABO identical
NL SLO
0 HLA Mismatches (“full house”)
ESP/ESDP ABO identical
ABO identical
HR
Organ allocation - KidneyHighly Immunized -
Acceptable Mismatch (AM) – ABO compatible
ETKAS Point Score System including HU : ABO Identical
A D HB/L
Pediatric donor (< 16yrs) recipients with status pediatricABO identical
NL SLO
0 HLA Mismatches (“full house”)
ESP/ESDP ABO identical
ABO identical
HR
Procedure AM Program• HLA typing of every potential donor is
introduced in ENIS. • Recipient is selected on the basis of
compatibility of the donor with the patient’s HLA-A,-B and -DR antigens in combination with acceptable mismatches.
• In case of a compatible donor: mandatory shipment of the kidney to recipient center.
Claas et al. Transplantation, 2004
Benefits of international cooperation in organ transplantation
• Preventing organ loss• Addressing the needs of special patient
groups• Improving the outcome of organ
transplantation• International harmonization of activities
in organ donation and transplantation
Probability of dying on the liver waiting list or removal due to clinical deterioration Elective l iver-tx candidates, ET Jan 2002 – Jun 2009
0 1 2 3 4 5 6 7 8 9 10 11 120
5
10
15
20Pts registered Jan 2002 - Jun 2005 (PreMELD) [N=6367]
Pts registered Jan 2007 -Dec 2007 (First year MELD)[N=1991]
Pts on WL 15.12.06 [N=1990]
Months after registration
Prob
abili
ty o
f dea
th /
rem
oval
WL
[%]
Organ allocation - KidneyHighly Immunized -
Acceptable Mismatch (AM) – ABO compatible
ETKAS Point Score System including HU : ABO Identical
A D HB/L
Pediatric donor (< 16yrs) recipients with status pediatricABO identical
NL SLO
0 HLA Mismatches (“full house”)
ESP/ESDP ABO identical
ABO identical
HR
Role of HLA-matching for graft survival after kidney transplantationCTS Newsletter 2004:1
6.2 yrs.difference
100%10073total0,4%4462,4 %2445
10,5 %1055430,2%3043326,6 %26792
832121760
PercentageNo. of transplantations
No. of mismatches
21,6 %8,3 %
HLA-matching in kidney transplantationEurotransplant 2000-2004, non-ESP patients
Impact of kidney organ exchange on selected patient groupsEurotransplant 01.01.2002 -31.12.2006
0%
20%
40%
60%
80%
100%
Outside ET 0 1 0 0 44Other ET country 121 1022 141 87 1422Recipient country 60 1420 336 271 9106
Highly immunized
000- HLA MM Paediatric High
Urgency Other
Impact of kidney organ exchange on selected patient groupsBelgium, 01.01.2001 - 31.12.2005
0%
20%
40%
60%
80%
100%
outside ET 0 1 0 0 5other ET country 11 129 5 37 418own country 3 64 3 22 1176
Highly Immunized
000- HLA MM
High Urgency Children other
The challengesof international cooperation
Challenges of international cooperation in organ transplantation
• International harmonization of allocation rules
• Logistical challenges including limitation of ischemic time
• Balancing of organ exchange
Challenges of international cooperation in organ transplantation
• International harmonization of allocation rules
• Logistical challenges including limitation of ischemic time
• Balancing of organ exchange
Examples of the consequences of allocation trade-offs
Recipient60 years
with Diabetes
20 years withoutDiabetes
20 years with
DiabetesLifespanwithout transplant*
4 years 16 years 9 years
Lifespanwith transplant* 9 years 22 years 16 years
Incremantal survival 5 years 6 years 7 years
*Median survival for this specific patient group (US data)
Allocation to the patient largest benefit (maximize incremental survival)
National Competent Authorities
Allocation development – role of ET
ET-BoardEC ISWG
OPC
ETKAC
ELIAC EThAC
EPAC
FC TTC
ET Council
ET-Office
„Recommendations“
for approval
„Guid
eline
s“
for im
plemen
taion
„Policies“
Cont
rol
SupportData collection and -analysis etc.
Allocation Allocation-Development
General organ allocation sequenceEurotransplant
International HU(Accepted) Combined Organs
Elective
Elective
Elective
Elective
Elective
Other Organ Exchange Organizations
National HU National HU National HU National HU
Euro
tran
spla
nt
Leiden
Eurotransplant liver allocation policyCountries with central MELD-based allocation as of 16.12.2006
Patient-oriented, centralMELD-basedallocation
Center-oriented, local allocation
Challenges of international cooperation in organ transplantation
• International harmonization of allocation rules
• Logistical challenges including limitation of ischemic time
• Balancing of organ exchange
0
120
240
360
480
600
720
840
960
1080
1200
1320
Local/regionalNationalInternationalNon-ET donor
Isch
emic
tim
e [m
in]
Ischemic time kidney transplantationLocal/regional vs. national vs. international allocation
12,4 h
15,8 h18,1 h
19,5 h
Ischemic time kidney transplantationLocal/regional vs national vs international allocationGermany
0
120
240
360
480
600
720
840
960
1080
1200
1320
Local/regionalNationalInternationalNon-ET donor
Isch
emic
tim
e [m
in]
12,4 h
15,8 h18,1 h
19,5 h
Ischemic time kidney transplantation Local/regional vs national vs international allocation
Austria
Belgium
German
y
Netherl
ands
Sloven
ia0
120
240
360
480
600
720
840
960
1080
1200
1320
Local/regionalNationalInternationalNon-ET donor
Isch
emic
tme
[min
]
Challenges of international cooperation in organ transplantation
• International harmonization of allocation rules
• Logistical challenges including limitation of ischemic time
• Balancing of organ exchange
Organ donation – Eurotransplant 2012
ET A B D HR H NL L SLO0
5
10
15
20
25
30
35
15.2
22.6
29.0
12.5
34.3
13.215.1
7.6
22.4
Utili
zed
dono
rs p
mp
-1,6
/ -9
,5%
-0,6
/ -2
,5%
-0,3
/ -1
,0%
-1,9
/ -1
3,2% +0
,7 /
+2,1
%
+1,8
/ +1
3,5%
+7,1
/ +4
8,3%
The concept of self-sufficency and organ balancing • Self-sufficiency in organ transplantation means
the adequate provision of transplantation services and supply of human organs from within a given population, to satisfy the organ transplantation needs of that population
• In practice, populations pursuing self-sufficiency are likely to correspond to the citizens or residents of nation states.
• In the context of multinational organ exchange organizations like Eurotransplant the concept of self-sufficiency therefore typically includes a balancing system between countries
International organ exchange and balancing within EurotransplantBasic principles
Prevent cross-border organ exchange when medically not indicated by giving preference to national (regional/local) allocation
■ Kidney: distance points■ Non-renal organs: National allocation except for
international mandatory exchange and prevention of organ loss
Ethical basis: short ischemic time leads to better transplant outcome
Origin of transplanted donor organs Eurotransplant 01.01.2001 – 31.12.2005
81.6%
16.8%
1.6%
Own countryOther ET countryOutside ET/ other EOEO
International organ exchange Basic principles of balancing
• International organ exchange imbalances (in spite of the preferentially national allocation system) are addressed by organ specific balancing systems
• Different mechanisms for balancing• Aim of the mechanisms used is a
“reasonable balance” between “import” and “export” of donor organs per country
Summary
• An organ allocation system should be transparent, objective and reliable
• The allocation rules should have a solid ethical foundation and should be based on evidence-based medical criteria
• Continuous monitoring of the allocation rules and their impact is essential
• International cooperation helps addressing the needs of special patient groups and is in line with the self-sufficiency principle
• Without access to the waiting list the best allocation cannot help