Eurotransplant - Principles of Organ Allocation Dr. Axel Rahmel Medical Director

1. Eurotransplant - Principles of Organ Allocation Dr. Axel Rahmel Medical Director Eurotransplant International Foundation Meeting with Representatives from the Ministry of Health and the Republic Expert Commissions Belgrade, Serbia – 10.08.2009

2. The key problem in organ transplantation in Europe is organ shortage…

3. Kidney waiting list and transplantsEurotransplant 1969 - 2007 11308 3703 1032

4. Grim facts… Each day, 9 European citizens die whilst waiting for a suitable organ transplant* *3.262 deaths on the waiting list in 2007, Council of Europe data 2008

5. ...and organ donation rates are not equally distributed over Europe

6. Donors pmp > 20 15-20 10-15 < 10 Council of Europe; Newsletter Transplant, Vol .13 No. 1, September 2008

7. Organ donation – Eurotransplant andRepublic of Serbia - 2008 PMP

8. 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…

9. 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.

10. Allocationprinciples

11. Organ allocation principles • Equity: every patient the same chance • Queuing: longest waiting first • Utility: best post-Tx outcome first • Need: sickest patient first • Net benefit: balancing urgency and outcome

12. Organ allocation principles • Equity: every patient the same chance • Sense of fairness or impartiality • Lack of bias or discrimination • Queuing: longest waiting first • Need/urgency: sickest patient first • Utility: best post-Tx outcome first • Net benefit: balancing urgency and outcome Equal/similar patients have to be treated equal/similar Lottery

13. Organ allocation principles • Equity: every patient the same chance • Queuing: longest waiting first • Waiting time is easy to understand • “first come first served” is a fair way to do things • Need/urgency: sickest patient first • Utility: best post-Tx outcome first • Net benefit: balancing urgency and outcome

14. Important factors in allocationPublic opinion No priority High priority Waiting time (87%) Post-tx outcome (79%) Young age (66%) Parental status (56%) • Gender (95%) • Income (97%) • Employment status (95%) • Profession (92%) Social Science and Medicine 2001; 52:853-861

15. Queuing: longest waiting firstEmergency department ?

16. Urgency vs. outcome in allocationThe „net-benefit“-concept • Need/urgency: sickest patient first • Direct organs to those most in need, i.e. most at risk of death without a transplant (medical urgency) • Utility: patient with best outcome first • Transplanting patients who will not survive is a waste of a limited resource • Net benefit-concept: Balancing urgency and outcome in allocation Urgency Outcome

17. Balancing urgency and outcome“Transplant window“-concept “too late” Mortality Med. Therapy Transplantation “Transplantation window” “too early” benefit -> Increasing organ failure ->

18. Organ exchange between the European Organ Exchange Organizations (EOEO)

19. European organ exchange organizations (EOEO) Eurotransplant Balttransplant Poltransplant Czechtransplant Hungarotransplant CNT, Italy HNTO, Greece Scandiatransplant UK Transplant AdB, France Swiss Transplant Lusotransplante ONT, Spain

20. OEOs, by number of deceased donor transplants in 2003 5966

21. Organ allocation Allocation within the own country /Organ Exchange Organization No suitable recipient within own country/OEO Offering to other Organ Exchange Organizations

22. Origin of donor organs transplanted in ET01.01.2001 – 31.12.2005

23. Organ offers from other OEO‘s to ETKidney transplantation 2001-2005(n = 207)

24. Principles of organ exchange between EOEOs • Organ exchange between European OEO‘s is mainly „donor-driven“: • Donor organ exchange only if no suitable recipient for this donor is available in donor country • Difficult to allocate donor • Extended criteria donor (ECD) • Rare blood group, size or age • -> Reduction of loss of donor organs • -> No balancing of exchanged donor organs • Main benefit for countries/EOEOs with • Large waiting list • Liberal organ acceptance policy

25. Principles of organ exchange within ET • Organ exchange within the Eurotransplant area is also „recipient driven“: • Donororgan exchange for special patient groups and medical reasons • High urgent patients • Immunized patients • Pediatric patients etc. • -> Supports special patient groups / improves outcome • -> Optimization of donor organ usage

26. Origin of donor organs transplanted in ET01.01.2001 – 31.12.2005

27. Principles of organ exchange within ET • Solidarity principle between Eurotransplant member countries • Exchange when medically indicated • National, regional or local allocation when possible and/or medically indicated (short ischemic time) • ET Senior program • Extended criteria donor organs • National balancing mechanisms

28. Kidney allocation

29. Kidney waiting list and transplantsEurotransplant 1969 - 2007 11308 3703 1032

30. ET Organ allocation - renal Highly immunized - Acceptable Mismatch (AM) - Program Zero Mismatch (“full house”) Pediatric Donor (< 10 a) to Pediatric Recipient (< 6 a) when HLA-DR-identical ETKAS Point Score System (including HU) Eurotransplant Senior Program (ESP) A B/L D HR NL SLO

31. ET Organ allocation - renal Highly immunized - Acceptable Mismatch (AM) - Program Zero Mismatch (“full house”) Pediatric Donor (< 10 a) to Pediatric Recipient (< 6 a) when HLA-DR-identical ETKAS Point Score System (including HU) Eurotransplant Senior Program (ESP) A B/L D HR NL SLO

32. Chance of every new highly sensitized patient to receive a suitable crossmatch negative organ within 12 months (real life data) Offer [%] AM Standard allocation

33. Claas et al. Transplantation, 2004

34. ET Organ allocation - renal Highly immunized - Acceptable Mismatch (AM) - Program Zero Mismatch (“full house”) Pediatric Donor (< 10 a) to Pediatric Recipient (< 6 a) when HLA-DR-identical ETKAS Point Score System (including HU) Eurotransplant Senior Program (ESP) A B/L D HR NL SLO

35. Role of HLA-matching for graft survivalafter kidney transplantationCTS Newsletter 2004:1 6.2 yrs. difference

36. Influence of HLA-A,B,DR matching for primary transplant on subsequent sensitization (CDC) %

37. HLA-matching in kidney transplantationET 2000-2004, non-ESP patients No. ofmismatches No. of transplantations Percentage 2176 21,6 % 0 1 832 8,3 % 2 2679 26,6 % 3 3043 30,2% 4 1055 10,5 % 5 244 2,4 % 6 44 0,4% total 10073 100%

38. ET Organ allocation - renal Highly immunized - Acceptable Mismatch (AM) - Program Zero Mismatch (“full house”) Pediatric Donor (< 10 a) to Pediatric Recipient (< 6 a) when HLA-DR-identical ETKAS Point Score System (including HU) Eurotransplant Senior Program (ESP) A B/L D HR NL SLO

39. ETKAS - Pediatric allocation factors

40. Probability of receiving a kidney transplantET, Registration WL 01.01.1999 – 31.12.2000 Recipient age Waiting time (yrs)

41. Mortality on the kidney waiting listET, Registration WL 01.01.1999 – 31.12.2000 Recipient age

42. ET Organ allocation - renal Highly immunized Acceptable Mismatch (AM) - Program Zero Mismatch (“full house”) Pediatric Donor (< 10 a) to Pediatric Recipient (< 6 a) when HLA-DR-identical ETKAS Point Score System (including HU) Eurotransplant Senior Program (ESP) A B/L D HR NL SLO

43. Development in organ donation for different donor age groupsReported kidney donors, Eurotransplant, 2000-2006 Donor age groups Number of donors (in relation to 2000)

44. Eurotransplant Senior Program (ESP)Rationale • HLA-matching probably less important in older recipients • Reduced risk of repeated re-transplantation • Older patients might be less prone to rejection after transplantation • Short ischemic time might reduce risk of graft loss from older donors • For older recipients shorter waiting time might be especially important

45. Eurotransplant Senior Program (ESP)Practical implementation • Priority allocation for kidneys from donors over age 65 years to recipients over age 65 years -> “old for old” program • First transplant • No HLA-matching • Regional allocation • Short ischemic time

46. Eurotransplant Kidney discard rate by donor age:US vs. Eurotransplant 60 50 40 US 30 Percent Discarded 20 10 0 3 9 18 50 55 60 65 66+ Donor Age

47. Patient survival for ESP patients vs. controlEurotransplant, 1999-2004 = ETKAS 60-64 y Frei et al.. AJT 2007; 7:1-8

48. ET organ allocation - renal Highly immunized - Acceptable Mismatch (AM) - Program Zero Mismatch (“full house”) Pediatric Donor (< 10 a) to Pediatric Recipient (< 6 a) when HLA-DR-identical ETKAS Point Score System (including HU) Eurotransplant Senior Program (ESP) A B/L D HR NL SLO

49. ETKAS allocation factors

50. International organ exchange in kidney transplantationImpact for selected patient groupsEurotransplant 01.01.2002 -31.12.2006