2025 Extramural meeting

Opening

The 2025 extramural meeting was opened by Nils Lachmann (Charité, Berlin).

Following the opening, Gonca Karahan gave an in memoriam talk about the life and work of Frans Claas.

Eurotransplant Desensitization Program

The scientific program began with a presentation by Marissa van der Linden -van Oevelen (ETRL) on the current status of the Acceptable Mismatch (AM) Desensitization program. The AM program is successful for the transplantation of highly immunized patients, but a group of patients still does not receive an organ offer within reasonable time frame. For these patients, rapid desensitization using, for example, the drug Imlifidase may offer a solution. A pilot protocol for such desensitization was introduced in Eurotransplant in September 2023.

In this protocol, patients remain in the AM program while their unacceptable antigens are reviewed for possible delisting. The recipient center makes an initial proposal to ETRL, ETRL assesses and revises the proposal , which is  then audited by the advisory committee. Once the proposal request is approved by all parties involved in assessment, the recipient becomes eligible for the AM desensitization program. Marissa presented preliminary results until 1st of April 2025: 24 of 28 applications have the completed audit process. Of these 13 have been transplanted.  Nine patients via the AM desensitization program, 3 through the regular AM program and 1 with a living identical donor. The patients transplanted via the AM desensitization program are doing well so far.

Noteworthy, the delisting protocol which involves careful assessment  of unacceptable antigens and those in ‘’grey area’’ also improve the chances of transplantation for patients within the AM program.

External proficiency testing

Next, Yvonne Zoet presented the external proficiency testing (EPT) results of the past year (2024). For HLA typing, a discrepancy rate of 2.4%was observed. For cross-matching (all results included) discrepancy rates were 2.7% for donor centers and 2.3% for recipient centers, both within the normal range.

To complete the overview, data from screening detection and screening identification scheme were also shown. In screening detection, discrepancy rates were 0.6% for HLA class I antibodies, and 2.9% for HLA class II antibodies. For screening identification scheme, CDC and SPA Single Antigen techniques were assessed. In CDC, 15 consensus specificities were found and in SPA SA 418 consensus specificities were found. For SPA SA Complement Fixing antibodies 65 consensus specificities were found. Finally, Yvonne showed the changes in the Eurotransplant EPT website for the EPT on detection of HLA antibodies. Both ELISA and flowcytometry now are listed in the category ‘’Other’’. In this category also new techniques can be added. A discussion followed about why the ETRL had chosen for the option to enter ET match determinants in the HLA-typing EPT. This was done because the ETRL would like to retain the interpretation of HLA typing data, and because of current technical possibilities. The ETRL will explore ways to further improve the EPT for HLA-typing.

The next topic on the agenda was the discussion of the three patient-based cases of 2024, also presented by Yvonne Zoet. A summary of the results of each case is published on the EPT website.

The first case was about a male with low MFI donor- specific HLA-DP antibodies, with a negative CDC crossmatch, both without and with DTT. Most participants considered the organ offer acceptable. The relevance of HLA-DP antibodies remains unclear in the literature..

The second case was about a female patient with unexpected positivity in part of the crossmatches both without and with DTT. About two-thirds of the participants considered the donor offer to be suitable, because the crossmatch on recent serum was negative. However, the donor offer was ultimately rejected due to the uncertainty about the cause of the positive crossmatches. After further investigation it turned out the patient had had 4 gifts of Rituximab, influencing the crossmatch results of December 2021 until December 2022.

The last case involved a female patient diagnosed with IgA nephropathy with positive CDC results without DTT, and varying CDC results with DTT.  Options for this patient include virtual crossmatching, which is allowed by both Eurotransplant and Bundesärztekammer when documented properly.

Future directions for HLA typing

The meeting continued with Cynthia Kramer (ETRL) who spoke about future directions for HLA typing of both donors and patients within Eurotransplant. First she showed a brief overview on the HML transmission of donor HLA-typing results since the introduction of the virtual crossmatch in 2023. The system is functioning well: only 1% of the HLA is entered manually and about 10% of the HLA types needs manual adjustment. The adjustments that need to be done can be categorized as follows:

  1. Three match determinants for a locus  
  2. Missing match determinant due to a rare allele in the HML file
  3. A match determinant added because an allele was not included in the HML file

With new fast high resolution HLA-typing methods that become widely available, there is a need to support the submission of high resolution HLA types (by NGS, ONT) through the ET immunology application. This is currently being tested. The following points should be taken into account:

  • High resolution HLA typing is expected to eliminate ambiguities and therefore there is no use of the pre-filter.
  • A test environment of ET immunology application without pre-filter is planned to be developed for further testing.
  • Chances are high that there will be more ’rare’ HLA alleles present in donor HLA typing that are not present in the HLA table.
  • Use of serotypes to convert these alleles to match determinants.
  • Impact of updating HLA table.

Cynthia then discussed the results of a recent survey on recipient HLA-typing which was sent to all 44 tissue typing laboratories in Eurotransplant.  The response rate was 89%. Most centers use at least two typing methods, including one for high resolution typing. More than half of the laboratories already submit their results at second-field level and most centers would like the ability to do so. The tissue typing centers would like to transfer the HLA types electronically. The following suggestions are made:

  • Adopting as similar approach to donor HLA submission using ET Immunology application and HML files
  • Creating a link between laboratory systems and ET ENIS Next (validated results)
  • Enabling batch uploads, as is done for unacceptable antigens
  • Other options, such as uploading a CSV file or submitting a GL string
News from the TTAC

The meeting continued with Gonca Karahan, who presented the topics discussed during the TTAC meeting held on  the 10th of April 2025, in Berlin, Germany.  

Cynthia Kramer will step down as secretary of the TTAC. Her tasks will be taken over temporarily by Rocio Laguna Goya, the deputy secretary.

Current status of policies and recommendations:

  • R-TTAC01.20: AM Program Allocation Extension to HLA-C and DQ; Implemented in July 2024, resulted in an incident which was resolved in October 2024
  • R-TTAC.01.22: AM inclusion criteria change from vPRA to donor frequency; Approved in June 2024-awaiting implementation.
  • ET (AM) Desensitization program update; Started in September 2023 and stopped for Germany in December 2024
  • Current policy in preparation: Possibility to register allele-specific antibodies in acceptable mismatch program

Additional topics discussed:

  • Recipient and donor typing. This was already addressed by Cynthia earlier this day
  • Updating HLA-tables have consequences on both unacceptables and HLA typing
  • Positive decisive recipient center crossmatches. Since the introduction of the virtual crossmatch, the rate of positive recipient center crossmatches remained stable at around 2% of the total number of crossmatches. A discussion followed on the potential shift to retrospective crossmatching on the recipient side. A policy will be drafted to categorically move to retrospective crossmatches in alignment with EFI standards.
  • Virtual crossmatch for  thoracic organs. A project group is currently working on this.

Upcoming meetings: Next Eurotransplant annual meeting will take place 25-26 September this year; The center BBJ (Brussels) volunteers to organize the next year’s extramural meeting

Gonca closed her presentation by thanking Nils Lachmann for organizing the meeting this year!

Scientific lecture

The final speaker of the day was Fabian Halleck from the Charité in Berlin, Germany. He shared the clinician’s perspective on highly immunized patients and desensitization protocols.