Greater Consistency in Candidate and Deceased Donor HLA Typing Requirements Across Organ Types Histocompatibility Committee Spring 2014

 Promote transplant safety by communicating critical information on deceased donors (DD) to be used for determining donor and recipient compatibility and/or post-transplant monitoring  Expedite allocation by improving virtual crossmatching and preventing unexpected positive crossmatches that result in discards or increased cold ischemia time Goals of the Proposal

 Transplant team needs complete DD HLA typing for decisions about organ acceptance and/or post- transplant monitoring  OPTN policy has inconsistent HLA reporting requirements for DD across organ types Solution: Require the following HLA types to be reported when typing is performed on DD: HLA-A, B, Bw4, Bw6, C, DR, DR51, DR52, DR53, DQA, DQB, DPB Problem #1

HLA Typing Requirements for Deceased Donors OrganABBw4Bw6CDRDR51DR52DR53DPBDQADQB Kidney Pancreas Kidney-Pancreas Heart* Lung* Liver Pancreas Islet *For deceased heart and lung donors, if a transplant hospital requires donor HLA typing prior to submitting a final organ acceptance, it must communicate this request to the OPO and the OPO must provide the HLA information required in the table above and document this request. The transplant hospital may request HLA- DPB typing, but the OPO need only provide it if its affiliated laboratory performs related testing.

 Molecular typing currently only required for deceased KI, K-P, and PA donors  Molecular HLA typing provides highest level of accuracy and enhances patient safety  Thoracic and liver candidates (when requested) entitled to same level of accuracy Solution: Must use molecular methods when performing HLA typing on DDs. Problem #2

 Antibodies to HLA-DQA and -DPB are frequently observed in sensitized candidates  No requirement to report this information for DD and no fields exist in DonorNet®  Missing HLA information may contribute to unexpected positive crossmatches for kidneys shared regionally and nationally (CPRA ≥99%) in new Kidney Allocation System Solution: HLA-DQA and -DPB must be reported when typing is performed on DD Problem #3

Supporting Evidence Frequency of DQA/DPB antibodies Total number of candidates: Lab1 N = 2,783 Lab2 N = 846 Lab3 N = 2,625 Antibodies to HLA-DQAAntibodies to HLA-DPB

Supporting Evidence DPB Typed Deceased Donors

Under the proposal,  HLA typing must be reported for deceased thoracic or liver donors only if requested by the candidate’s transplant program  If requested for deceased thoracic donors, HLA typing must be reported before final offer acceptance (no policy change)  If requested for deceased liver donors, HLA typing must be reported within timeframe specified by candidate’s transplant program (new) Important Consideration

 HLA antibodies likely contribute to negative outcomes in pancreas islet transplant, similar to PA transplant  Currently no HLA typing requirements for deceased pancreas islet donors or candidates. Solution: Align policy requirements for deceased pancreas islet donors and candidates with those of deceased pancreas donors and candidates Problem #4

The Committee incorporated feedback from the following:  OPO Committee  Thoracic Transplantation Committee  Pancreas Transplantation Committee  Liver and Intestinal Organ Transplantation Committee  American Society of Histocompatibility and Immunogenetics (ASHI)  OPTN regions Additional Background

 When performing HLA typing on DD, labs must use molecular methods  Before making KI, K-P, or PA offers, OPOs must report information on HLA-DQA and –DPB in DonorNet®  Thoracic and liver transplant programs must communicate and document any HLA information requests to OPO  OPOs must provide complete HLA typing on deceased donors (timeframe still varies based on organ type) What Members will Need to Do

 If your transplant program tests candidates for antibodies to HLA-DQA and/or HLA-DPB, is it sufficient to have these donor HLA types recorded in DonorNet® to use in making donor acceptance decisions?  Or, is it imperative to add unacceptable antigen fields for these types and program the UNOS system to automatically avoid those donors if these unacceptable antigens are listed? Specific Feedback

 Lee Ann Baxter-Lowe, PhD Committee Chair  Name Region # Representative  Gena Boyle, MPA Committee Liaison Questions?

Backup Slides

Supporting Evidence HLA available* prior to match run: thoracic matches run for deceased donors recovered June 1, 2011 – May 31, 2013 * at least one antigen reported at the HLA-A, B, and DR loci

Supporting Evidence Distribution of donor laboratories by the percentage of DPB typed deceased donors and year