BSHI Guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation

Abstract

List of recommendations• All laboratories performing H&I testing for allogeneic HPC transplantation should follow EFI standards and be accreditated by EFI and UKAS/CPA. (Grade 1A)• HLA typing definitions as described by Nunes et al. 2011 and here should be used (Grade 1A)• HLA typing results should use official WHO HLA Nomenclature (Grade 1A)• The clinical urgency should be made available to the individual performing the related and unrelated donor search (Grade 1B)• HLA high resolution typing should be performed on potential matching; mismatching and haploidentical related donors when familial haplotypes cannot be fully assigned (Grade 1A)• Patients and selected related donors should be typed for HLA-A, -B, -C, -DRB1 and -DQB1 (+/-DPB1) (Grade 1A).• All patients and donors must have their HLA type confirmed on a second sample pre-transplant (Grade 1A).• The patient should be high resolution typed prior to submitting the HLA type for an unrelated donor search (Grade 1A)• A 10/10 high resolution HLA-A, -B, -C, -DRB1 and -DQB1 matched unrelated PBSC or bone marrow donor should be used where possible (Grade 1A).• Where a 10/10 matched PBSC or bone marrow donor is not available a single mismatch at HLA-A, -B, -C, -DRB1 or -DQB1 is acceptable (Grade 1A).• Alternative progenitor cell donors (cord blood or haplo-identical) should be considered early in the donor search when a patient is unlikely to have an HLA matched unrelated donor (Grade 1A).• HLA-DRB3, -DRB4, -DRB5 typing should be performed and, when a choice of otherwise equally matched and appropriate (e.g. CMV status) donors is available, mismatches for these should be minimized (Grade 2A). • For unrelated donor selection, HLA-DPB1 typing should be performed and when a choice of otherwise equally matched and appropriate (e.g. CMV status) donors is available, non-permissive mismatches should be minimised (Grade 2C).• For mismatched related and unrelated donor selection, HVG mismatches are favoured over bi-directional and GVH mismatches (Grade 2C).• UCB units should be HLA typed to high resolution HLA-A, -B, -C, -DRB1, -DQB1 (Grade 1B ).• Selection of UCB units should follow national consensus guidelines published by Hough et al. (Grade 1A).• HLA alloantibody testing of the recipient should be performed at the time of donor search and should be repeated at the time of donor work-up request if an HLA mismatched donor is selected (Grade 1A).• The clinical team must be made aware of any HLA alloantibody incompatibility for a selected donor (Grade 1A).• When a choice of equally well matched donors is available, avoid selection of donors against which the patient has HLA alloantibodies (Grade 1A).• HLA alloantibody testing should be performed in cases of failed engraftment if the donor is HLA mismatched (Grade 1B).• The guideline published by Emery et al., 2013 recommending CMV matching between patient and donor should be followed (Grade 1A).• Major ABO incompatibilities should be avoided when there is a choice of HLA and CMV matched donors (Grade 1A)• Male donors ...

Single molecule real‐time DNA sequencing of HLA genes at ultra‐high resolution from 126 International HLA and Immunogenetics Workshop cell lines

“…One important clinical application of high‐resolution HLA typing is that of matching donors and patients for haematopoietic stem cell transplantation (HSCT). Currently, matching patient and donor ethnicity for HSCT is not a recommendation of the British Society for Histocompatibility and Immunogenetics . However, matching for haplotypes, which are linked to ethnicities, rather than alleles alone could be used to improve clinical outcome after HSCT .…”

“…Currently, matching patient and donor ethnicity for HSCT is not a recommendation of the British Society for Histocompatibility and Immunogenetics. 42 However, matching for haplotypes, which are linked to ethnicities, 43 rather than alleles alone could be used to improve clinical outcome after HSCT. 16,44 These data reinforce the argument for full-length gene sequencing as a method of HLA typing, where intronic polymorphisms can be used to infer haplotypes.…”

The distribution of HLA‐DRB3 alleles among HLA‐DRB1*03:01‐positive haplotypes

“…On the other hand, the so‐called lesser expressed HLA loci (LEL) (HLA‐DRB3/4/5, HLA‐DQB1, and HLA‐DPB1), with the exception of HLA‐DQB1 gene and, in some transplant centers HLA‐DPB1 gene, are not routinely typed and therefore not used for the donor/recipient matching for the HSCT. However, the “Guideline for selection and HLA matching of related, adult unrelated donors and umbilical cord units for haematopoietic progenitor cell transplantation” of the British Society for Histocompatibility and Immunogenetics states that HLA‐DRB3, ‐DRB4, and ‐DRB5 typing should be performed and, that in situations when there is a choice between donors who are otherwise equally matched/appropriate, a donor with a smaller number of mismatches at these loci should be chosen . This guideline was introduced because of the investigation performed by Fernandez‐Vina et al who discovered that there is a higher risk of mortality and TRM for patients who, in addition to one mismatch at HLA‐A, ‐B, ‐C, or ‐DRB1 locus, have three or more LEL mismatches in the graft‐vs‐host direction when compared with those with one or no LEL mismatches.…”

The distribution of the DRB4*01:03:01:02N null allele in HLA‐DRB1~DQB1 haplotypes in the Croatian population

“…The typing of DRB3/4/5 genes in solid organ transplantation is not an obligatory procedure for the allocation program of Eurotransplant, despite the fact that, due to the peculiarity of the DRB genes, the compatibility for DRB1 genes between the recipient and his donor does not mean that the pair will be identical for the second DRB gene, if that gene is present in the DRB haplotype. At the same time, the typing of null alleles for determining the HLA compatibility in solid organ transplantation is still not mandatory and remains questionable . It is well known that in haplotypes carrying DRB1*04 , DRB1*07 or DRB1*09 alleles, the second active DRB gene is DRB4 .…”

“…At the same time, the typing of null alleles for determining the HLA compatibility in solid organ transplantation is still not mandatory and remains questionable. 1 It is well known that in haplotypes carrying DRB1*04, DRB1*07 or DRB1*09 alleles, the second active DRB gene is DRB4. 2 Sutton et al reported about a DRB4 allele of which no protein product could be detected serologically.…”