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

Little, Ann‐Margaret; Akbarzad‐Yousefi, Arash; Anand, Arthi; Burlinson, Natalia Diaz; Dunn, P. P. J.; Evseeva, Irina; Latham, Katy; Poulton, Kay; Railton, Dawn; Vivers, Sharon; Wright, Paul A.

doi:10.1111/iji.12527

Cited by 34 publications

(17 citation statements)

References 229 publications

(385 reference statements)

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“…HLA*LA is the best performing tool on average, across the five HLA alleles but the tool does require an extensive amount of memory and is relatively slow. Mistypings/mismatches at HLA-DQB1 are less critical than mistypings at HLA-A, -B, -C or -DQB1 ( 54 ), hence Optitype is a lighter and faster alternative to HLA*LA for Class I typing and, assuming a DOC of at least 100X, Kourami as an alternative for Class II typing. For the 230 samples in the downsampling study at a DOC of 100X, Optitype had a P group typing accuracy of 98.3% across the three Class I genes (HLA*LA had 96.4%) and Kourami had a P group typing accuracy of 97.8% for HLA-DRB1 (HLA*LA had 98.0%).…”

Section: Discussionmentioning

confidence: 99%

Benchmarking freely available HLA typing algorithms across varying genes, coverages and typing resolutions

Thuesen

Klausen²,

Gopalakrishnan

et al. 2022

Front. Immunol.

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Identifying the specific human leukocyte antigen (HLA) allele combination of an individual is crucial in organ donation, risk assessment of autoimmune and infectious diseases and cancer immunotherapy. However, due to the high genetic polymorphism in this region, HLA typing requires specialized methods. We investigated the performance of five next-generation sequencing (NGS) based HLA typing tools with a non-restricted license namely HLA*LA, Optitype, HISAT-genotype, Kourami and STC-Seq. This evaluation was done for the five HLA loci, HLA-A, -B, -C, -DRB1 and -DQB1 using whole-exome sequencing (WES) samples from 829 individuals. The robustness of the tools to lower depth of coverage (DOC) was evaluated by subsampling and HLA typing 230 WES samples at DOC ranging from 1X to 100X. The HLA typing accuracy was measured across four typing resolutions. Among these, we present two clinically-relevant typing resolutions (P group and pseudo-sequence), which specifically focus on the peptide binding region. On average, across the five HLA loci examined, HLA*LA was found to have the highest typing accuracy. For the individual loci, HLA-A, -B and -C, Optitype’s typing accuracy was the highest and HLA*LA had the highest typing accuracy for HLA-DRB1 and -DQB1. The tools’ robustness to lower DOC data varied widely and further depended on the specific HLA locus. For all Class I loci, Optitype had a typing accuracy above 95% (according to the modification of the amino acids in the functionally relevant portion of the HLA molecule) at 50X, but increasing the DOC beyond even 100X could still improve the typing accuracy of HISAT-genotype, Kourami, and STC-seq across all five HLA loci as well as HLA*LA’s typing accuracy for HLA-DQB1. HLA typing is also used in studies of ancient DNA (aDNA), which is often based on sequencing data with lower quality and DOC. Interestingly, we found that Optitype’s typing accuracy is not notably impaired by short read length or by DNA damage, which is typical of aDNA, as long as the DOC is sufficiently high.

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Section: Discussionmentioning

confidence: 99%

Benchmarking freely available HLA typing algorithms across varying genes, coverages and typing resolutions

Thuesen

Klausen²,

Gopalakrishnan

et al. 2022

Front. Immunol.

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“… Algorithm for the selection of matched CBU donors for malignant and non-malignant ( Little et al, 2021 ). …”

Section: Properties Of Cord Blood As a Donor Cell Source Relevant To ...mentioning

confidence: 99%

“…In mismatched cord blood units, data on non-inherited maternal antigens can be used to select mismatched donors which will be better tolerated post-transplant. This is not an exhaustive list, and the full details of the factors are summarized in the BSHI 2021 guidelines (Little, 2021) ( Little et al, 2021 ).…”

Section: Selection Of Potential Ucb Donorsmentioning

confidence: 99%

Strategies for Success With Umbilical Cord Haematopoietic Stem Cell Transplantation in Children With Malignant and Non-Malignant Disease Indications

Wynn

Nataraj

Nadaf

et al. 2022

Front. Cell Dev. Biol.

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Umbilical Cord blood is an intuitively attractive stem cell source, but its use has declined since it is associated with an increased procedure-related morbidity and transplant related mortality. Some of this reflects that cord blood transplants are more often HLA-mismatched compared to other unrelated donor transplants. The ability to transplant in such a setting, indeed without high rates of chronic Graft versus Host Disease (GVHD), constitutes an advantage compared to other unrelated donor cell sources and there are other advantages specifically associated with cord blood as a donor cell source. These advantages must be weighed against its disadvantage, and we have utilised cord blood preferentially as a donor cell source in certain clinical situations in paediatric medicine. In non-malignant diseases, outcomes in metabolic disease are critically dependent on age at transplant and the enzyme delivered by that transplant, and in cord blood transplantation then the time to transplant can be minimised and the engrafted recipients have higher chimerism that delivers higher enzyme levels. In malignant diseases, studies have described reduced relapse rate and better GVHD-free survival, and so we have prioritised cord as a donor cell source where the risk of relapse is highest, and the effects of higher transplant related mortality is most clearly offset by the reduced relapse rates.

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“…Reducing the time taken from diagnosis to transplant has been recognised as one of the most important factors for success in haematopoietic stem cell transplantatio (HSCT). [2][3][4][5] NHSBT, therefore, has a clinical services key performance indicator (KPI) target that 80% of the IDM screening requests should be reported within 7 days.…”

Section: Problemmentioning

confidence: 99%

Improving the turnaround times of infectious disease markers reporting in an NHS stem cell department

Liu

Proudlove

2022

BMJ Open Qual

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The Stem Cell Donation and Transplantation Department at NHS Blood and Transplant (NHSBT) facilitates unrelated donor haematopoietic stem cell transplantations for patients with life-threatening haematological malignancies or other blood diseases. Donors must be screened for infectious disease markers (IDMs) prior to donation. The purpose of IDM testing is to assess whether the donor currently has, or previously had, an infectious disease that could be transmitted to the recipient. The turnaround time (TaT) from sample collection to the return of IDM results is important to transplant clinicians and their patients. NHSBT has a target TaT of 80% within seven calendar days. Our initial analysis showed us that we failed to meet this in any week in the previous year, and our service was neither efficient nor consistent, so there was considerable improvement potential.This quality improvement (QI) project aimed to improve the TaT of the IDM reporting service. We tested three change ideas through four Plan-Do-Study-Act (PDSA) cycles. We collected data on TaTs from our laboratory information management system (LIMS) and updated our statistical process control charts after each PDSA cycle. Over the course of the project, we reduced the mean TaT from 8.9 days to 5.5 days and increased the proportion of samples reported within the 7-day benchmark from 50% to 89%, reaching the key performance indicator (KPI) target.Conducting this project was a rewarding experience. Although we encountered unanticipated technical issues during PDSA experiments, and we found that some change plans were not as effective in improving the KPIs as we expected, the improvement by the end of the study period was substantial. This QI project enabled us to meet our TaT targets and, ultimately, help ensure that our patients receive timely transplants. It suggests that QI may have wider applications across our part of NHSBT.

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

Cited by 34 publications

References 229 publications

Benchmarking freely available HLA typing algorithms across varying genes, coverages and typing resolutions

Benchmarking freely available HLA typing algorithms across varying genes, coverages and typing resolutions

Strategies for Success With Umbilical Cord Haematopoietic Stem Cell Transplantation in Children With Malignant and Non-Malignant Disease Indications

Improving the turnaround times of infectious disease markers reporting in an NHS stem cell department

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