Paired Donation. Andrew Bradley Rachel Johnson Joanne Allen Susan V Fuggle. Cambridge University NHS Hospitals NHS Foundation trust

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1 Paired Donation Andrew Bradley Rachel Johnson Joanne Allen Susan V Fuggle Cambridge University NHS Hospitals NHS Foundation trust

2 Showing a preference 1860 John Calcott Horsley

3 UK Living Donor kidney transplant Altruistic donor (non-directed) Paired exchange donor Unrelated donor (directed) Related donor Number Year

4 Analysis of UK living donor transplants ( , n= 3142) Graft survival Unrelated Related p 1 year 96% 95% ns 5 year 93% 89% No influence of HLA matching on graft survival

5 UK paired donation scheme Human Tissue Act made paired (and nondirected altruistic) living kidney donation possible from September 2006 BTS & NHSBT developed arrangements for paired donation in the UK

6 UK paired donation scheme Human Tissue Act made paired (and nondirected altruistic) living kidney donation possible from September 2006 BTS & NHSBT developed arrangements for paired donation in the UK NEWS BBC July 2007 : Couples swap kidneys in UK first Peter Horrell, from Cambridgeshire, donated a kidney to a man from Lothian, while the man's wife gave a kidney to Mr Horrell's wife Roma.

7 Arrangements for KPD Donor and patient assessments Registration with ODT Quarterly matching runs' to identify possible transplants and optimise transplants according to scoring scheme (working with experts in matching algorithms from Glasgow University) Crossmatch tests for suitability of transplants Independent Assessor review & HTA panel approvals Operations arranged and carried out simultaneously Anonymity Donor kidney travels

8 Simulations Having identified relevant factors, simulations used to inform decision-making about appropriate weights and other issues Simulations based on real data from 20 centres 400 transplants that could not proceed over 2-year period due to ABO or HLA incompatibility

9 How many couples are needed? Maximum % transplanted No. of couples on list

10 How many points for Local exchange (based on 5 areas of the UK) HLA match (4 levels) Prioritisation factors Sensitisation (% of blood group identical donors having antigens which are declared unacceptable for the recipient pool of 10,000) Age difference between the 2 donors Blood group match consider restricting use of O donors Identify combination of transplants with highest sum of point scores for individual transplants

11 Cold ischaemia time and Allograft Outcomes in Live Donor Renal Transplantation: Is Live Donor Organ Transplantation Feasible? C.E. Simpkins et al John Hopkins University 2007; 7: Analysed LD kidney transplants reported to OPTN in USA Impact of CIT on: delayed graft function acute rejection 1-year creatinine allograft survival

12 CIT 0-2h 2-4h 4-6h 6-8h (32 719) (4 663) (692) (393) DGF 4.7% 4.9% 8.3% 9.2% Simpkins et al AJT 2007; 7:

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14 Matching runs 2-way matching runs quarterly since April way exchanges also considered since April 2008 Donor 1 Recip 1 Donor Recip 3 3 Donor 5 Recip 5 Donor 2 Recip 2 Donor 4 Recip 4 2-way exchange 3-way exchange (paired exchange (pooled exchange)

15 Paired donation - national matching scheme Points score for each possible transplant to prioritise possible exchanges Local exchange (based on 5 areas of UK): 20 points Sensitised patient: 0-50 points for 0-100% sensitised HLA matched transplant: Small donor-donor age difference: max 15 points for 000 mismatch 3 points if <=20 years Blood group O donor kidneys only used in group O recipients HLA match and maximum donor age can be specified at registration

16 Paired donation programme Jan 2007 April 2010 Total of 335 patients (364 pairs) enrolled All 23 UK adult kidney transplant centres involved 53% spouse/partner pairs 40% ABO incompatible, 44% HLA incompatible, 16% ABOi + HLAi 144 transplants identified 64 (19%) of enrolled patients transplanted by end June 2010 max 22% if all remaining possible transplants proceed

17 Paired donation matching run summary Run no. Run date No. of pairs No. of exchanges identified 2-way 3-way No. of transplants possible No. of transplants achieved 1 Apr Jul Oct Jan Apr Jul Oct Jan Apr Jul Oct Jan Apr ? 64 transplants to date including six 3-way exchanges

18 Blood group composition of pool: Jan pairs listed (141 patients); 83 (55%) blood group incompatible Recipient Blood Group O A B AB Total Donor Blood Group O A B AB Total (37%) are A to O incompatible pairs

19 HLA sensitisation of pool:jan 2010 Calculated sensitisation (%)* Total No. of patients % of patients * Calculated based on comparing each patient s unacceptable antigens with HLA types of blood group identical donors in pool of 10,000 actual donors

20 Transplant summary Jan 07 April transplants in total 46 (72%) from two-way, 18 (28%) from three-way exchanges 31 ABOi pairs, 31 HLAi and 2 ABOi & HLAi pairs 45 (70%) spouse/partner pairs Median CIT 5 hrs (range 1-9 hrs) DGF in 8/49 (16%) transplants 3 failed transplants (day 54, 97, 177) 71/144 (49%) identified transplants confirmed as not proceeding 37% +ve XM 23% alternative transplant 20% donor or recipient unfit 21% other reasons

21 Transplant rates by ABO Recipient ABO O A B AB Donor ABO O A 5/74 (7%) 12/116 (10%) 12/24 (50%) 9/40 (23%) 4/11 (36%) 9/24 (38%) 0/0 (0%) 0/3 (0%) B 4/30 (13%) 8/21 (38%) 0/8 (0%) 1/2 (50%) AB 0/5 (0%) 0/2 (0%) 0/4 (0%) 0/0 (0%) Number transplanted / number enrolled (%)

22 HLA sensitisation issue April 2010 pool Calculated sensitisation (%) Total No. of patients % of patients Sensitisation calculated based on comparing each patient s unacceptable antigens with HLA types of blood group identical donors in pool of 10,000 actual donors No. of patients enrolled Transplant rates Tx. rates: 25% 33% 23% 3% No PD tx PD tx Sensitisation level

23 Summary 335 patients enrolled; 144 transplants identified 64 (19%) of enrolled patients transplanted (inc 18 in 3-way exchanges) Most success for A/B, B/A ABOi and moderately sensitised patients (esp A/O combination) 49% identified transplants did not proceed 3.1% of live donor transplants in UK in 2009 Implement domino (chain) paired donation in 2011

24 Improvements made following recent workshop Suspension of patients from DD list immediately they are matched Suspension of patients from paired list after unsuccessful run so they are properly reviewed for next run Review of crossmatching logistics / materials

25 N Engl J Med 2009, 360;11

26 NEAD Chain

27 Domino (chain) paired donation

28 Domino (chain) paired donation

29 Domino (chain) paired donation

30 Altruistic, non-directed donors 32 altruistic donor transplants (July 2007-Dec 2009) Mean donor age 51 years (range 24-69); 15 F, 17 M Mean recipient age 49 years (range years) Average recipient waiting time 4 years Median CIT 6 hrs (range 1-20 hrs) 1 PNF, 3 DGF in 24 transplants with follow-up

31 Further plans (2010) Altruistic donor chains (domino paired donation) agreed in principle Simultaneous transplants and short chains in first instance Prioritise paired donation patients who have had most unsuccessful matching runs

32 Desensitisation vs Paired donation Desensitisation Advantages (1) Donor known to recipient (2) Timing predictable (3) HLA match may be better Disadvantages (1) Complex and expensive (2) May not be available locally (3) Risks of desensitisation procedure (4) Transplant outcome may be inferior

33 Desensitisation vs Paired donation Paired donation Advantages (1) No added risk to recipient (2) Good outcome after transplantation (3) Listing for PD increases effectiveness of pool Disadvantages (1) Unpredictable wait (2-5% annual mortality on dialysis) (2) Donor & recipient not known to each other (3) Likely to be poor HLA match

34 Making the choice Desensitsation Nature of incompatibility: ABOi vs HLAi Ease of desensitisation Likely outcome after desensitisation Paired donation Likelihood of finding a matched pair HLA match Patient s views Number of matching runs

35 Treatment options ABOi and or HLA Abi LD Paired exchange Desensitisation Offering neither is not acceptable

36 Treatment options ABOi and or HLA Abi LD Paired exchange No match Desensitisation No match Match found Remain on DD list LD Transplant

37 Treatment options ABOi and or HLA Abi LD Paired exchange No match Desensitisation Paired exchange plus desensitisation No match Match found Remain on DD list LD Transplant

38 Making the choice ABOi Outcome after Ab depletion equivalent to ABO compatible? Morbidity from antibody depletion protocol Donor Recipient Ab titre Chance of match A B often low 50% B A often low 50% A2 O usually low 10% A or B O often high 10%

39 Bingham AW et al NEJM 2010 San Antonio Tx centre Initiated KPD scheme in March 2008 Enrolled Ab incompatible donors Also enrolled compatible pairs with donor aged >45 yrs All recipients negative Flow XM Matching daily

40 Expansion of Kidney Paired Donation (KPD) San Antonio Bingaman AW et al. N Engl J Med 2010;363:

41 Showing a preference Paired exchange Desensitisation