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Improving cord blood typing with next-generation sequencing: impact of allele-level HLA and NIMA determination on their selection for transplantation

Bone Marrow Transplantation volume 55, pages 1623–1631 (2020)Cite this article

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Abstract

Allele-level HLA compatibility in cord blood transplantation, together with noninherited maternal antigen or NIMA matching, have been associated with better transplant outcomes. The aim of this work is to develop a cost-efficient high-resolution HLA typing strategy based on next-generation sequencing to improve the quality of the Barcelona Cord Blood Bank’s inventory, and to investigate the impact of high-resolution HLA typing and NIMA determination on the preferential selection of cord blood for transplantation. In this line, the developed strategy was validated and the HLA-A, -B, -C, -DRB1, and -DQB1 genes of 5000 cord blood units and 2500 of their associated maternal samples were typed. Subsequently, three study groups of 2012 units each were monitored for up to 2 years: (1) units with high-resolution and maternal HLA typing, (2) units with high-resolution but not maternal typing, and (3) units typed at low-resolution for class I and only high-resolution for HLA-DRB1. Despite a trend toward a greater selection of units with high-resolution typing, no significant impact of these variables was observed. These results highlight the need for evidence-based and globally accepted criteria for cord blood selection, together with the necessity to improve the accessibility of clinicians to donor registry’s data.

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Fig. 1: Schematic representation of the study design.
Fig. 2: Successful validation of the in-house HLA typing strategy based on NGS.
Fig. 3: Evolution of the CBUs inventory at the Barcelona CB bank according to high-resolution and maternal HLA typing.
Fig. 4: Value distribution of the three groups of study according to TNC and CD34 cell counts.
Fig. 5: Evolution of the number of transplants from the Barcelona CB Bank.
Fig. 6: Responses to questionnaires.

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Acknowledgements

We would like to thank all the people who made this study possible, in particular Laura Mongay, Pepi Caro, and Carina Lera for their help with HLA typing, and Iris García-Martínez for her help with interpreting the results of the statistical analysis. Also to Jesus Maroto and Silvia Tuset for his collaboration with CB data, and Alejandro Madrigal for his help in the scientific review. Finally, we would like to thank the donors, the members of the Concordia Program, the technicians from the CB Bank and the transplant centers that answered our questionnaires. No specific funding was obtained to perform this study.

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Authors and Affiliations

  1. Immunogenetics and Histocompatibility Laboratory, Banc de Sang i Teixits, Barcelona, Spain

    Emma Enrich, Eva Campos & Francesc Rudilla

  2. Transfusional Medicine, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona (VHIR-UAB), Barcelona, Spain

    Emma Enrich, Francisco Vidal, Irene Corrales, Nina Borràs, Sergi Querol & Francesc Rudilla

  3. Congenital Coagulopathies, Banc de Sang i Teixits, Barcelona, Spain

    Francisco Vidal, Irene Corrales, Nina Borràs & Lluís Martorell

  4. CIBER de Enfermedades Cardiovasculares (CIBERCV), Barcelona, Spain

    Francisco Vidal

  5. Cell Therapy Service, Banc de Sang i Teixits, Barcelona, Spain

    Lluís Martorell, Mar Sánchez & Sergi Querol

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  1. Emma Enrich
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Correspondence to Sergi Querol or Francesc Rudilla.

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The authors declare that they have no conflict of interest.

Ethical approval

The complete design of the study, together with the use of the CB samples analyzed in this work was approved by the Vall d’Hebron University Hospital’s ethics committee (PR(AG)59/2017). According to “Plan Nacional de Sangre de Cordón Umbilical”, developed in Spain in 2006, all donors signed an informed consent for CBU donation.

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Enrich, E., Vidal, F., Corrales, I. et al. Improving cord blood typing with next-generation sequencing: impact of allele-level HLA and NIMA determination on their selection for transplantation. Bone Marrow Transplant 55, 1623–1631 (2020). https://doi.org/10.1038/s41409-020-0890-9

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