Comments

UC San Diego Health Center for Transplantation | 03/20/2024

UCSD Center for Transplantation (CASD) appreciates the effort the Histocompatibility Committee put into the proposal to Update Post-Transplant Histocompatibility Data Collection as well as the opportunity to provide feedback.
We generally agree that updates to the post-transplant data collection forms will facilitate a means of standardization, specifically in relation to current laboratory practices and test methodology and provide additional insight for discrepant HLA typing entries. While the additional requirements for discrepant results may generate an increase in reporting requirements for some laboratories, this information is critical to evaluating the scope of the matter and allow for future development of related policies. Additionally, as virtual crossmatching becomes more widely accepted, capturing this data will allow for further correlation with organ acceptance offers, recipient treatment, and transplant outcomes.

Region 10 | 03/19/2024

8 strongly support, 13 support, 0 neutral/abstain, 0 oppose, 0 strongly oppose

Region 9 | 03/19/2024

0 strongly support, 7 support, 2 neutral/abstain, 0 oppose, 0 strongly oppose

This proposal was not discussed during the meeting, but attendees were able to submit comments. One member requested that if risk adjusted data were available, that it be added.

Region 6 | 03/19/2024

3 strongly support, 10 support, 1 neutral/abstain, 0 oppose, 0 strongly oppose

This proposal was not discussed during the meeting, but attendees were able to submit comments. One attendee commented that this would significantly impact post-transplant outcomes and morbidity. 

Region 7 | 03/18/2024

5 strongly support, 10 support, 2 neutral/abstain, 0 oppose, 0 strongly oppose 

This was not discussed during the meeting, but attendees were able to submit comments with their sentiment. One attendee noted that this extra data collection is absolutely required.

Region 1 | 03/18/2024

1 strongly support, 9 support, 2 neutral/abstain, 1 oppose, 0 strongly oppose 

This proposal was not discussed during the meeting, but attendees were able to submit comments. A member suggested it would be helpful to review long term outcomes of post-transplant patients with issues related to histocompatibility and that his shared information could better guide the care of patients with negative post-transplant histocompatibility outcomes across the transplant community. Another member indicated support of the policy, but noted it will likely increase the workload on their tissue typing lab as many workflows are manual.

Region 5 | 03/15/2024

10 strongly support, 20 support, 7 neutral/abstain, 0 oppose, 0 strongly oppose 

Region 5 supports this proposal and commented that it eliminates a largely unnecessary clerical task and decreases the workload.

American Society of Transplantation | 03/15/2024

The American Society of Transplantation (AST) generally supports the proposal, “Update Post-Transplant Histocompatibility Data Collection,” and offers the following comments for consideration:

• The ‘cytotoxicity method’ is no longer used to identify HLA antibodies and the AST agrees with its removal from donor recipient histocompatibility forms. However, there are different methods for solid phase antibody testing that should be included. The primary techniques currently used are flow cytometry, Luminex technology, and ELISA. The AST recommends capturing which technique is used to understand any differences that may be attributed to the specific technique used.

• The AST agrees with the decision to separate the virtual crossmatch and physical crossmatch sections and removing the response options “Cytotoxicity no AHG” and “Cytotoxicity AHG” on the donor and recipient histocompatibility forms. The AST strongly recommends that “cytotoxicity crossmatch” remain a response option as both T and B cell cytotoxicity assays have not been abandoned by all programs.

• The AST suggests that the OPTN consider a stated definition in OPTN policy for prospective virtual crossmatch, including upper limits for serum age. The immunological risk in a candidate who, for example, had a one-time historical DSA six months prior to transplant followed by repeated negative testing is different than a patient with positive DSA prior to transplant.

• The AST suggests that another field be added to collect pre-transplant CPRA. In most cases, the most recent CPRA in Waitlist is not the same as the CPRA at time of transplant. The AST suggests adding this field to capture the CPRA value closest to the time of transplant.

• The AST would agree that the proposed data elements, including those recommended in this response, are predominantly collected in discreet fields within a laboratory information system.

• The AST suggests collecting the date of the HLA antibody screen used for virtual crossmatching to inform future optimization of virtual crossmatch strategies.

• The AST suggests collecting the threshold used to designate an antibody (corresponding antigen) an avoid for the calculation of the CPRA.

Donna Lucas | 03/14/2024

Thank you for the opportunity to provide feedback regarding histocompatibility data collection. I am in support of updating the forms. I have a few suggestions/comments regarding the proposed changes.

I believe there is still utility in maintaining the target source in the donor form. The addition of transfusion history would be helpful in deciding whether to request tissue rather than peripheral blood from donors. With the increase in donors and recipients that previously had stem cell transplants, the addition of buccal swab as a source would be useful.

My laboratory uses HistoTac as our Laboratory information system (LIS). I am unaware of the ability for the data for necessary forms to be collected from the LIS. Currently all data entered into UNET is done manually.

In the Discrepant typing report, “original typing confirmed correct” is confusing. What if the original typing is the incorrect typing? What reason would be appropriate in that instance?

I support the removal of historical crossmatch results due to their lack of relevance. I agree with the removal of the CDC responses as they are no longer relevant. I believe the addition of “indeterminate” is an overdue and necessary change.

Although I support the inclusion of virtual crossmatch data as it becomes more widely used, I think the proposal needs clarification. The proposal seems to equate the virtual crossmatch with the prediction of the physical crossmatch results without taking serum date into consideration. A virtual crossmatch might be based on data from an old sample with qualifying statements for the need for a current sample. Also the donor typing resolution could potentially change the virtual crossmatch results. Would these data be captured in the new section? If not, I think the question regarding concordance be omitted.

Association of Organ Procurement Organizations | 03/14/2024

AOPO strongly supports the updates to the Donor Histocompatibility Form, the Recipient Histocompatibility Form, and the Discordant HLA Typing Report. The Donor Histocompatibility Form will be improved and streamlined by removing multiple fields that do not pertain to the molecular typing methods currently required by OPTN policy. AOPO applauds the addition of the data fields related to virtual cross-matching and the resultant ability to evaluate the impact on clinical practice and patient outcomes. AOPO defers to our HLA laboratory colleagues to comment on the comprehensiveness of the proposed modifications to document discrepant HLA typing results. 

Region 3 | 03/11/2024

4 strongly support, 10 support, 2 neutral/abstain, 0 oppose, 0 strongly oppose 

American Society for Histocompatibility and Immunogenetics (ASHI) | 03/09/2024

The American Society for Histocompatibility (ASHI) and its National Clinical Affairs Committee (NCAC) appreciate the opportunity to provide feedback concerning histocompatibility data collection within the OPTN Computer System and support the proposed revisions. Updates to the post-transplant data collection forms will facilitate a means of standardization, specifically in relation to current laboratory practices and test methodology and provide additional insight for discrepant HLA typing entries. While the additional requirements for discrepant results may generate an increase in reporting requirements for some laboratories, this information is critical to evaluating the scope of the matter and allow for future development of related policies. Additionally, as virtual crossmatching becomes more widely accepted, capturing this data will allow for further correlation with organ acceptance offers, recipient treatment, and transplant outcomes.

Region 8 | 03/05/2024

2 strongly support, 9 support, 3 neutral/abstain, 3 oppose, 0 strongly oppose

Region 8 offered several suggestions for this proposal. In support of the proposal an attendee commented that it is an appropriate update that is consistent with current practice. Another opposed this proposal as currently written. A member agreed that laboratories should assess their virtual crossmatch practices as part of their internal quality assurance program. They explained this should be monitored by the laboratory in accordance with their testing and virtual crossmatch processes; it should not become a data mining platform or clinical competency assessment. They suggested that the proposal needs additional clarification regarding intent and may even be counterproductive to recent community advancements towards acceptance of virtual crossmatching by CMS. Several attendees pointed out the need for clear definitions for “virtual crossmatch”. They explained the community has not settled on a single definition for virtual crossmatch because of varying institutional needs. A member asked if a laboratory indicates that the virtual crossmatch and physical crossmatch are not concordant, will the OPTN consider this as a discrepancy requiring further explanation. It is expected that there will be some disagreement between virtual and physical crossmatches as they are not both tests measuring the same analytes. The member inquired if these "discrepancies" require justification of clinical consultations or testing practices. A member suggested that to nationally assess true correlations, not only must virtual crossmatches be performed in the same manner by laboratories, but physical crossmatching and antibody testing must also be standardized across the community. An attendee commented that to require OPTN data collection to correlate a virtual crossmatch (data-based analysis) with a physical T and B crossmatch (lymphocyte-based LDT) suggests that these two are not independent and that the results of each are linked. They commented that this contradicts the communities’ progress and CMS regarding crossmatching. (Notably, CMS has recognized the validity of virtual crossmatch as an independent crossmatch for use by clinical teams.) 

Anonymous | 03/05/2024

Appreciate the opportunity to reply to this proposal and agree that the forms need to be updated. Some feedback regarding the proposed changes include:

In the donor form, addition of donor transfusion history and number of products received would be informative and may help explain reasons for requesting tissue rather than using peripheral blood sample for testing.

In the recipient Histocompatibility form,
1) the proposed responses for the Virtual crossmatch are limited and not clearly defined. Laboratories use different approaches to define a virtual crossmatch. The use of positive and negative suggests that the virtual crossmatch assessment is being compared to the physical crossmatch. The terms should be clearly defined to allow laboratories to categorize appropriately. For example, some centers report a virtual crossmatch as acceptable or unacceptable. An unacceptable virtual crossmatch may not translate into a positive virtual crossmatch but may be indeterminate (unable to assess and requires a physical crossmatch).
2) Under section III: Physical crossmatch. The committee should specify whether this is referring to a prospective or retrospective physical crossmatch.
3) Regarding question: “ if virtual crossmatch was done, was physical crossmatch considered concordant with the virtual…” propose “ Was physical crossmatch concordant with virtual crossmatch”.

In discrepant HLA typing, keep cell source “PBL, LN, spleen.

Region 2 | 02/29/2024

6 strongly support, 16 support, 2 neutral/abstain, 0 oppose, 0 strongly oppose

Region 11 | 02/29/2024

7 strongly support, 10 support, 0 neutral/abstain, 1 oppose, 0 strongly oppose 

This proposal was not discussed during the meeting, but attendees were able to submit comments. The region supports this proposal. A member suggested modifying the proposed “Original Typing Confirmed Correct” to say “This HLA Typing Result was Accepted as Correct” because it could be misleading if the correct results were determined by the receiving center and not the originating OPO laboratory.  

Region 4 | 02/26/2024

2 strongly support, 8 support, 3 neutral/abstain, 0 oppose, 0 strongly oppose 

This proposal was not discussed during the meeting, but attendees were able to submit comments. One attendee commented that virtual crossmatch data collection needs to be better defined to specify what needs to be captured in this field. They added that various labs define a negative/positive virtual crossmatch in different ways.

Anonymous | 02/21/2024

Support

Déboralis Ramos | 01/31/2024

Strongly Support

Neeraj Sinha | 01/29/2024

In the data dictionary of the histocompatibility form, how would the definition of prospective virtual crossmatch be worded? How current should the serum be for the performance of prospective virtual crossmatch?

As the immunological risk in a candidate who, for example, had a one-time historical DSA six months prior to transplant followed by repeated negative testing is different from someone who tests positive for DSA on every test before transplant; I suggest that, on page 15 of the proposal, the questions about current and historical donor specific HLA antibodies are not modified.

If the prospective virtual crossmatch was performed using a low-resolution HLA typing, and subsequently, based on high resolution donor HLA typing, it is revealed that patient did not have a DSA ('retrospective virtual crossmatch based on high resolution typing'), could this clinically relevant data be captured?

Danny Youngs | 01/24/2024

Almost all the proposed changes are good and long overdue, but I have the following concerns and suggestions.
(1) Target Source for donor HLA typing is pointless, and should not be included as a data element. It may have been questionably useful for serological typing, but it has no relevance for typing by molecular methods.
(2) For Virtual Crossmatch, is the definition of Positive, Negative and Indeterminate left up to the lab, or does the OPTN have a specific definition in mind? Some people consider the virtual crossmatch to be a prediction of the physical crossmatch, some consider it to be an evaluation of immunological risk, and some consider it be a determination of the presence/absence of donor-specific HLA antibodies. Although the three definitions greatly overlap, they are not identical. In Section III the new question "Was physical crossmatch considered concordant with virtual crossmatch?" seems to suggest that the virtual crossmatch is meant to predict the physical crossmatch. I recommend that the definition of virtual crossmatch be left up to the lab, and that the "concordant" question be eliminated. There already is an existing data element for physical crossmatch results that is not being eliminated, and any researcher mining OPTN data to establish the relationship between the virtual crossmatch and the physical crossmatch can simply do so by comparing the results for the two entries. In addition, unlike every other data element in the histo forms, the "concordant" question is not something that is likely to be easily retrievable from the lab's LIS, and would thus require onerous manual intervention and interpretation when uploading histo form data to UNet.
(3) Under Discrepant HLA Typings Report the new reason "Original Typing Confirmed Correct" makes it sound as if it applies only to the typing from the lab that first typed the donor. I suggest modifying it to something like "This Typing Confirmed Correct" so that it clearly is meant to be used for the typing from any lab, not just the original lab.