Introduction
Both the UK and USA guidelines for cord blood selection recommend three and four mismatches as suitable options for patients with high-risk leukemia and for treatment-resistant types of blood cancer. Some of the WMDA member organisations have implemented standard procedures to run a routine cord search with up to four mismatches as a default. Therefore, WMDA has implemented is implementing this option as well in Search & Match Service as well.
At the moment, the Search & Match Service (with the Hap-E Search matching algorithm) is providing an extensive the full list of potential cord blood units, when a three and/or four mismatch search is performed. For These lists are commonly very long and therefore search coordinators currently find it is difficult to select the best possible most suitable potential stem cell source , in Search & Match when they perform a three and/or four mismatch CBU search in the Search & Match Service today.
The match list presents all possible options. In order to help search coordinators to select the best potential stem cell source, WMDA is implemented an will be implementing additional features to assist search coordinators, you can read the details of these features, below.
How to perform a three and/or four mismatch search for cord blood?
Three and four mismatch searches have been implemented for cord blood searches in Search & Match Service. This is a resource intensive service , therefore you first need to perform a two mismatch cord blood search before you are able start a three mismatch cord blood search:
- Step 1: run a two mismatch cord blood search, before you can start a three mismatch search
- Step 2: run a three mismatch cord blood search before you can start a four mismatch cord blood search
What is important to know about three and/or four mismatch searches?
In the old legacy version of Search & Match Service, no overall match probabilities calculations (P0, P1, P2) for cord blood results were doneavailable. The sorting was performed within the match class (i.e. 5/8. 4/8) based on the Total Nucleated Cell (TNC) or CD34+ cell counts (depending on what a search coordinator prefers). This has been implemented in the same way for in the new updated version of Search & Match Service operating with the Hap-E matching algorithm.
In the new version of Search & Match Service the number of search results can be bigger, as the Hap-E matching algorithm returns more potential matched cord blood units and the service no longer limits a coordinator to only 2 000 search results. If you experience a high number of potential cord blood options, search results you can, for example, filter on the minimum TNC, minimum CD34+ or by selecting certain registries or mismatch locations.
How is sorting done of three and/or four mismatch searches?
Three and/or four mismatch cord blood search results do not have any match probabilities calculated, the results are currently sorted within their match class (e.g. 5/8, 4/8) only by TNC or CD34+. The Hap-E algorithm in the Search & Match Service returns more potential cord blood units than the legacy system. Many of these “extra” Many of cord blood units tend to be low probability cord blood optionsoptions to be selected for a patient in need of a transplant, because these cord blood units have low HLA resolution typing or missing allele typing.
This means that a poorly matched cord blood units with a high cell dose are at the top of the match list and potentially better cord blood units that have a better probability to match the patient with a high enough lower cell dose are lower, appear lower on the list of results. For a search coordinator, it is harder to identify the best possible cord blood unit, because of the increased number of valid potential matches.
In an effort to improve the search coordinator's experience when performing three and/or four mismatch cord blood searches, WMDA is currently developing has developed several features that should improve the efficiency of finding suitable cord blood unitunits. These are:
- Filter A filter for returning only donors/cord blood with typing at HLA-C (and/or DQB1). Available today.
- Filter A filter on match class - a search coordinator can go directly to the 5/8 or 4/8 potential matches. Scheduled for delivery December 2022.
- A "Scorescore" based sorting method for three and/or four mismatch cord blood results (find details below). Scheduled for delivery December 2022.
- Match probability calculation for three and/or four mismatches . Scheduled for delivery Q1 2023.
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- (find details below).
"Score" based sorting for three and/or four mismatch cord blood results (see option 3 in above paragraph)
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- interim solution
It is generally In general it is true that the more highly better HLA-typed a CBU/ donor on a match list stem cell source (donor/cord blood) is, the higher the probability of a potential match it is. As we are WMDA is currently not able to provide match probabilities and it will take a few months to fully develop, we will use a on 3 and 4 mismatched cord blood searches, WMDA will be implementing an interim score based approach. This works in the following wayFind below the explanation:
- WMDA will assign a score to records based on which loci are typed the typing resolution of the cord blood unitAssign a score based on the typed loci and their resolution
- Each locus can have one of the following “resolutions”
- High resolution typing (only one ARD)
- Low or intermediate typing
- No typing
- Each resolution class per locus has a “score”.
- High resolution typing = 20
- Low or intermediate typing = 17
- No typing = 0
- We sort CBUs WMDA will sort cord blood units based on the sum of the score first and only then by TNC/CD34+
- n/6: sum of score at A, B, DRB1
- n/8: sum of score at A, B, C, DRB1
- n/10: sum of score at A, B, C, DRB1 and DQB1
- Sorting for 0, 1 and 2 mismatches remains unchanged
Because of the way the scores are assigned per locus, a CBU cord blood unit with typing at HLA-C when doing an n/8 search will always be ranked higher than a CBU cord blood unit with high resolution typing at 3 loci and no typing at HLA-C.
Below you can find some examples.
Match probabilities
Match probability calculation for three and/or four mismatches (see in paragraph above option 4) - long-term solution
WMDA aims to implement calculation Calculation of actual match probabilities, because this would provide a better way of ranking than score-based ranking. Unfortunately this requires quite search results than by using the above mentioned "scored" ranking. It will however, require a lot of work in to develop this feature, as it will impact core elements of the Hap-E algorithmmatching algorithms. This therefore needs to be done with great care and needs to will be thoroughly tested in order to make sure no part of the Hap-E algorithm algorithms is accidentally broken as a result of the added functionality. It therefore cannot be delivered until Q1 of 2023.