Predicting Chance of Transplant in Highly Sensitised Patients

Predicting the Chance of Transplant for Highly Sensitised Patients in different European Deceased Donor Populations Lisa Bradbury, Alex Hudson, Linda Shelper, Laura Pankhurst, Frans Claas, Susan Fuggle on behalf of the EUROSTAM partners BSHI 2015

Introduction The level to which a patient is sensitised against the general donor population can play an important role in organ allocation: - 2006 Kidney Allocation Scheme Highly sensitised patients that are zero HLA mismatched receive priority over patients with lower levels or no sensitisation Software is available in the UK that allows the transplant community to calculate a standardised sensitisation percentage

Calculated Reaction Frequency The existing tool estimates the proportion of the UK donor population HLA incompatible with a given patient Sensitisation Calculator (cRF%) Await cRF% result Await cRF% result Await cRF% result Sensitisation (cRF%) 0% 87% 87% Select ABO blood group Select ABO blood group Enter Blood Group O A B B C D A1 A2 B5 B51 B52 B21 B49 B50 CW1 CW2 CW3 CW9 CW10 CW4 CW5 CW6 CW7 CW8 CW12 CW13 CW14 CW15 CW16 CW17 CW18 DR1 DR2 DR15 DR16 DR3 DR17 DR18 DR4 DR5 DR11 DR12 DR6 DR13 DR14 DR1403 DR1404 DR7 DR8 DR9 DR10 DR103 DR51 DR52 DR53 DQ1 DQ5 DQ6 DQ2 DQ3 DQ7 DQ8 DQ9 DQ4 Y Y A203 A210 A3 A9 A23 A24 A2403 A10 A25 A26 A34 A66 A11 A19 A29 A30 A31 A32 A33 A74 A28 A68 A69 A36 A43 A80 B5102 B5103 B4005 B22 B54 B55 B56 B27 B2708 B35 B37 B40 B60 B61 B41 B42 B46 B47 B48 B53 B59 B67 B70 B71 B72 B73 B78 B81 B82 B83 BW4 BW6 Y Y B7 B703 B8 B12 B44 B45 B13 B14 B64 B65 B15 B62 B63 B75 B76 B77 B16 B38 B39 B3901 B3902 B17 B57 B58 B18 Y Y Add unacceptable antigens (antibody defined or otherwise) Y Y Y Y Splits Super Broads Broads with splits Broads no splits

Highly sensitised patients Very highly sensitised patients wait longer for transplant 100 90 80 70 >7 years 60 5-7 years 50 3-5 years 40 1-3 years 30 <1 year 20 10 0 0-9% 10-39% 40-59% 60-84% 85-94% 95-99% 100% Higher chance of transplant in European donor pool? o Differences in HLA specificities in different donor pools

EUROSTAM A EUROpe-wide Strategy to enhance Transplantation of highly sensitised patients on the basis of Acceptable HLA Mismatches WP6: Development of a tool to calculate the chance of transplant for a highly sensitised patient in different donor populations

Creating the database

Database - donors Five donor files received: - Barcelona - Eurotransplant - Greece - UK - Prague: no Cw typing - excluded Files contain: - Donor HLA type A, B, DR, Cw, DQ - Donor blood group Some partners have only recently collected HLA-Cw & DQ - relatively small donor populations

Database - donors Final donor files only contained complete information Number of donors in each country: Barcelona Eurotransplant Greece UK Prague ~300 ~4400 ~750 ~12500 ~280 Some partners only provided broad antigens for certain specificities

Broad antigens Broad Barcelona Eurotransplant Greece UK Prague A9 1 1 A10 3 1 A28 5 49 3 B5 9 2 B14 34 164 4 86 2 B15 26 5 12 3 B16 1 1 B17 12 B22 5 B40 24 7 13 2 B70 11 CW3 36 1140 57 375 DR2 1 10 DR6 1 3 DQ1 1 14 114 DQ3 6 2447 36 163 17

Database - recipients Five recipient files received: - Barcelona - Eurotransplant - Greece - UK - Prague Files contain: - Recipient HLA type A, B, DR, Cw, DQ - Recipient acceptable mismatches - Donor blood group Some partners only report broad antigens for some patients - If B62 & B63 & B75 & B76 & B77 acceptable then B15 acceptable - If B64 & B65 acceptable then B14 acceptable etc.

Patient to donor pool matching

Simulations Blood group identical matches only If donor typed for B64 & B65 then matched on splits, if only typed for B14 then matched on broad Similar approach for B15, B40, Cw3 and DQ3

Results - Barcelona Number of HSP long waiting patients: 133 Patients that benefit from different donor pool: 30 (22%) - 12 patients 1% increase - 9 patients 2% increase - 5 patients 3% increase - 3 patients 4% increase Greece donor pool - 1 patient 5% increase UK donor pool

Results - Eurotransplant Number of HSP long waiting patients: 121 Patients that benefit from different donor pool: 27 (22%) - 19 patients 1% increase - 5 patients 2% increase - 2 patients 4% increase Barcelona donor pool - 1 patient 5% increase UK donor pool

Results - Greece Number of HSP long waiting patients: 113 Patients that benefit from different donor pool: 45 (40%) - 25 patients 1% increase - 7 patients 2% increase - 4 patients 3% increase - 3 patients 4% increase - 3 patients 5% increase - 1 patient 7% increase Barcelona donor pool - 1 patient 10% increase UK donor pool - 1 patient 23% increase UK donor pool

Results - UK Number of HSP long waiting patients: 334 Patients that benefit from different donor pool: 89 (27%) - 58 patients 1% increase - 10 patients 2% increase - 11 patients 3% increase - 4 patients 4% increase - 3 patients 5% increase Barcelona donor pool - 3 patients 9% increase Greece donor pool

Results - Prague Number of HSP long waiting patients: 23 Patients that benefit from different donor pool: 4 (17%) - 1 patient 2% increase - 1 patient 5% increase - 1 patient 9% increase Greece donor pool - 1 patient 27% increase Barcelona donor pool

Summary Already established UK tool to estimate proportion of UK HLA compatible donors Tool can be applied to different European donor populations - Demonstrated potential for very difficult to transplant patients Using these simulations a pilot could be conducted as a proof of principle

Acknowledgements EUROSTAM Partners: Leiden University Medical Centre: Frans Claas Athens: Aliki Iniotaki Barcelona: Jaume Martorell NHSBT: Susan Fuggle Prague: Antonij Slavcev Eurotransplant Geneva: Alicia Sanchez-Mazas Liverpool: Derek Middleton Multiplicom, Belgium Absorber, Sweden This work has received funding from the European Union s Seventh Framework Programme [FP/2007-2014] under grant agreement number HEALTH-F4-2012-305385