Comments

American Society of Transplantation | 09/12/2024

The American Society of Transplantation (AST) agrees that potentially clinically relevant HLA discrepancies should be reported and offers the following comments for consideration in response to the proposal, “Require Reporting of HLA Critical Discrepancies and Crossmatching Events to the OPTN”:

•The definition of what constitutes a critical HLA discrepancy requires further clarification. The proposal lists error categories for HLA-related events of "verification error, interpretation error, equipment malfunction, typing method error (assay failure), lab IT/ technical issue, etc.," but clear definitions of these categories of error would be beneficial. For example:

-Some antigen splits and some eplet mismatches may have immunologic significance, such as (`A*02:01` vs `A*02:02`). The immunologic significance is dependent upon the recipient’s identified antibodies.

-Reporting of HLA-DP typing is currently limited in the available options for reporting, which could lead to apparent discrepancies, as may be seen with DPB1. What if the true genotype wasn't explicitly enumerated in the attached PDF report, but the report simply states, "This genotype was chosen as the most likely; cannot exclude one or more rare genotypes?" When we transition to P-group level reporting in UNet, the proposal does not indicate if calling the wrong P-group within the same split antigen be considered a critical discrepancy.

-For other HLA loci, there is a nonzero chance that an alternative genotype is the true genotype and some of the alternate genotypes are in a different split antigen category. If the alternative genotypes are listed in the attached PDF as not being ruled out by the assay, is that a critical discrepancy?

-What if the true genotype has a broad antigen assignment of DQ1 and the true allele was in either DQ5 or 6?

•The AST agrees with requiring reporting through the Patient Safety Portal to standardize reporting and a timely review of this information.

Region 9 | 09/10/2024

Sentiment:  4 strongly support, 9 support, 1 neutral/abstain, 0 oppose, 0 strongly oppose 

Overall, the region supports the proposal.  A member expressed support for the proposal and for the 24 hour reporting timeframe.  They requested clarification as to whether the lab who performed the typing or the lab who discovered the discrepancy would be responsible for reporting discrepancies, as they are not always the same.  An attendee commented that the 24 hour timeframe is too rigid and should be expanded to 72 hours to match the transplant reporting requirements.  

Karyn Glover | 09/05/2024

This will benefit recipients greatly. Reporting these issues will give a clearer view of matching donor with recipient making transplant more effective ,accurate, and save. thereby decreasing the potential risks associated with transplant ie, rejection, immunosuppression gvhd, infections, and fevers to name a few. Reporting these issues will hold OPOS to a standard that all will have to adhere to It will benefit transplant recipients donors and transplant centers.

Marcelo Fernandez Vina | 09/05/2024

It is worth defining acceptable discrepancies that cross split antigens when making antigen assignments from molecular typing results. One of the most common discrepancies results when a donor types as B*15:15 and in the IMGT the serologic assignment is HLA-B62 because the initial cell was assigned with limited old serology. Subsequent studies favor B75 instead of B62. Another example is B*48:02 that clearly is not HLA-B48 when tested by serology.
DPB1 typing occasionally results in discrepancies because of limited resolution or ambiguities. A rule for alleles indicating that results including different alleles of the same P group should be considered as non-discrepant.

Rebecca Baranoff | 09/05/2024

Strongly Support

OU Health HLA lab | 09/04/2024

"Require histocompatibility laboratories report an HLA critical discrepancy to the OPTN within 24 hours of discovery"
For time concerned, reporting discrepancy to OPTN with 24 hours is not achievable. Should be the same period of time as TIEDI within 30 days. Or change TIEDI report time limit as well.

Region 6 | 09/03/2024

Sentiment: 2 strongly support, 9 support, 0 neutral/abstain, 0 oppose, 0 strongly oppose

Following the presentation, one attendee commented that the 24-hour time frame for reporting should be 24 business hours. Another attendee commented that from a clinical standpoint, a 24-hour reporting deadline is ideal for ensuring patient care and improving transplant outcomes. They added that this requirement may place a significant burden on HLA labs, so it is essential to consider the impact on their ability to meet this deadline. Overall, there was agreement on the 24-hour reporting rule after the discovery of a discrepancy, though not necessarily requiring a full corrective action plan within that time frame. The 24-hour window allows for re-testing if necessary, which enhances patient safety.

Another attendee commented that one area needing clarification is the last row of Table 18-6, which mentions an "incorrect candidate HLA antibody test analyzed for a virtual crossmatch." They requested more details on the timing requirements, specifically whether reporting is required even if the issue was discovered pre-allocation and didn’t impact allocation timing. Additionally, it is unclear if this reporting is necessary for all virtual crossmatch assessments, including those that didn’t lead to a transplant or were declined for other reasons. One attendee expressed concerns that 24 hours may be too short of a timeframe for reporting.

Anonymous | 08/31/2024

I agree the discovering lab should report critical HLA discrepancies to the OPTN. I think 24 hours is a reasonable reporting time. It appears all the lab has to do is send a report that a discrepancy was discovered. This appears similar to the notification that is sent to the OPO and transplant center when a discrepancy is found. It does not sound like a requirement that would tax resources, require training or be time consuming.

I am a transplant recipient who is always on the watch for signs of rejection. In my view, reporting is a necessary measure to identify where and how critical discrepancy errors were made, and to develop internal controls to avoid future errors and to protect future recipients.

I do not have the expertise to know if a discrepancy entails immunological significance. I will leave that up to the experts, hoping they err on the side of caution if there is any possibility a recipient’s safety might be at risk.

Region 1 | 08/29/2024

Sentiment: 3 strongly support, 6 support, 1 neutral/abstain, 0 oppose, 0 strongly oppose

Overall, the region supports the proposal. A member commented that they were in favor of the proposal overall but wondered if the 24 hour timeframe might be a little too short. An attendee suggested that the committee consider recommending that OPOs designate someone to receive these reports, to help streamline communication. An attendee requested that the committee clarify that the policy is referring to using the wrong patient’s antibody information, not using an older sample versus a newer one. A member commented that the 24 hour timeframe is ample and expressed uncertainty as to why split antigens are excluded if they are immunologically significant. Another attendee stated that patient safety is paramount and there should be no delays in reporting potentially dangerous events. The attendee recommended having one reporting mechanism for all parties to receive this information, to reduce burden. 

Region 8 | 08/27/2024

Sentiment: 4 strongly support, 15 support, 1 neutral/abstain, 0 oppose, 0 strongly oppose

The region agreed on the modified definition of a critical HLA discrepancy and pointed out that errors that don't have a clinically significant impact may be a near-miss (which warrants investigation and consideration in implementation). Another attendee commented that this has long been an area of concern for the community and the new language aligns with the current technological capabilities of our testing methods and will reduce the number of incorrectly assigned "discrepancies".

· In agreeance with the discovering lab being responsible for reporting critical HLA discrepancies to the OPTN, an attendee also added that ideally both the discovering lab and the original testing lab should be involved in reporting discrepancies via the Patient Safety Portal to ensure the most comprehensive information is provided for the occurrence.

· Regarding the time frame questions, an attendee suggested that the effort would be better spent determining the root cause of the error and implementation of corrective actions, with subsequent notification to the OPTN notification within 48 hours.

· Attendees agreed that incorrect donor or recipient samples used for crossmatch should be included in required reports, and that incorrect donor HLA typings or incorrect candidate HLA antibody test should be used for virtual crossmatch in required reports. An attendee commented that this data is critical to determining members’ opportunities as a community for improving patient safety and optimizing organ allocation.

Region 4 | 08/19/2024

Sentiment: 3 strongly support, 9 support, 4 neutral/abstain, 3 oppose, 0 strongly oppose 

During the discussion, attendees raised a concern that 24 hours is too tight of a timeframe for reporting and recommended changing it to at least 72 hours. Another attendee added that if the 24 timeframe is not extended, there should be a change to the timeline in other policies that require retyping and reporting.

Region 2 | 08/16/2024

Sentiment: 7 strongly support, 14 support, 1 neutral/abstain, 1 oppose, 0 strongly oppose 

Members of the region were supportive of the proposal.  Attendees noted the importance of matching organs to the best candidates, as it is believed to improve outcomes and increase the longevity of transplants. There was some uncertainty about whether the 24-hour window is sufficient and whether earlier knowledge of HLA matching could enable more effective interventions, such as reallocation or intensified induction for already transplanted organs.  Several attendees suggested increasing the 24-hour reporting requirement either to 36-48 hours or by the next business day to account for weekends and holidays.  An attendee noted that HLA experts need to provide input on this proposal and that the committee should consider all public comments before finalizing the proposal.  Lastly, one attendee highlighted the importance of prioritizing HLA matching for children in organ transplants, emphasizing that better matching could significantly reduce transplant failures and the development of donor-specific antibodies. It was suggested that children should receive additional priority for HLA matching, similar to practices in Europe, to improve long-term transplant success.