Expanding HLA Typing Requirements (Resolution 10) Histocompatibility Committee Dolly Tyan, PhD Chair

#6- Promote the Efficient Management of the OPTN Prevent unexpected positive crossmatches that result in discards or increased cold ischemia time Strategic Plan

 New KAS takes effect in December  Candidates with CPRA greater than 98% will receive regional and national priority before all other kidney candidates  Literature shows a significant number of sensitized candidates have antibodies to HLA-DQA/DPB  There are currently no fields in DonorNet® to report these HLA types on donors or in Waitlist ℠ as unacceptable antigens for candidates  Without this information, there is a high risk for discards and increased CIT in KAS The Problem

Sequence A KDPI <=20% Sequence B KDPI >20% but <35% Sequence C KDPI >=35% but <=85% Sequence D KDPI>85% Highly Sensitized 0-ABDRmm (top 20% EPTS) Prior living donor Local pediatrics Local top 20% EPTS 0-ABDRmm (all) Local (all) Regional pediatrics Regional (top 20%) Regional (all) National pediatrics National (top 20%) National (all) Highly Sensitized 0-ABDRmm Prior living donor Local pediatrics Local adults Regional pediatrics Regional adults National pediatrics National adults Highly Sensitized 0-ABDRmm Prior living donor Local Regional National Highly Sensitized 0-ABDRmm Local + Regional National CPRA greater than 98%

Policy has inconsistent HLA reporting requirements for deceased donors (DD) across organ types Molecular typing only required for deceased KI, K-P, and PA donors No HLA typing requirements for deceased islet donors or candidates Other Problems

 HLA DQA and –DPB reported when typing is performed on DD. Program DQA and DPB fields in DonorNet ® and Waitlist ® as unacceptable antigens  Require consistent and complete list of loci reported on DD  Require molecular methods when performing HLA typing on DD  Align policy requirements for deceased islet donors and candidates with those of pancreas donors and candidates Proposed Changes

Product Policies 2.11.A E, 3.4.D, and 4.2 Target Population Impact: Total IT Implementation Hours 1,500/10,680 Total Overall Implementation Hours 2,160/17,885 Overall Project Impact All deceased donors, candidates, and recipients. Special emphasis for highly sensitized candidates and all kidney candidates.

Frequency of DQA/DPB UAs 10,556 (10%) have 98%+ CPRA 2,351 have 99% and 6,900 have 100% CPRA Kidney WL data Data for 6 labs/10 tx centers 98%+ CPRA candidates (N=593): 63% had DQA/DPB UAs Bray et al, AJT, in press

% of KPD Candidates with HLA-DPB and DQA UAs % of candidates with UAs N=462 CPRA Value Note that for kidney waiting list: 84% have CPRA 0-79%, 4% %, 5% and 6% - 100%

#1 DonorNet® Only #2 DonorNet® and Waitlist ℠ Two Programming Options

Pro: Allows deceased donor HLA info to be reported for these types Slight reduction in IT programming estimate (still in large category) Con: Patient safety concerns Burdensome for transplant programs Inconsistent with programming for all other HLA reporting and the KPD program Committees expressed patient safety concerns

Pro: Eliminates patient safety concerns Less burdensome to transplant programs Consistent with KPD programming Supported by community (based on feedback from regions, Kidney Committee, OPO Committee, Pancreas Committee, Operations and Safety Committee, and ASHI) Con: Higher IT programming cost (very large category)

DonorNet ® and Waitlist ® DonorNet ® Only Cost-Benefit Analysis

Regions Unanimous Support Committees Feedback from 6 Unanimous Support Individual Unanimous Support Professional Societies ASTS, AST, ASHI, CAP Unanimous Support Public Comment/Professional Society Feedback

The Board is asked to approved additions and changes to Policies 2.11.A (Required information for Deceased Kidney Donors); 2.11.B (Required information for Deceased Liver Donors); 2.11.C (Required Information for Deceased Heart Donors); 2.11.D (Required Information for Deceased Lung Donors); 2.11.E (Required Information for Deceased Pancreas Donors); 3.4.D (Candidate Human Leukocyte Antigen (HLA Information); and 4.2 (Requirements for Performing and Reporting HLA Typing) to provide greater consistency in HLA typing requirements across organ types. *Page 74 of Board book RESOLUTION 20

Extra Slides

Committee noticed inconsistencies in HLA typing requirements Fall 2012 BOD did not approve original request to program DQA and DPB Summer 2012 Policy changes recommended Outreach to organ specific committees Dec Approved for public comment Update presented to BOD (June 2014) Spring 2014 Background

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.

Supporting Evidence DPB Typed Deceased Donors