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Observational Study
. 2023 Jun;25(3):e14065.
doi: 10.1111/tid.14065. Epub 2023 Apr 30.

Impact of cytomegalovirus immunodominant HLA-I donor-recipient matching on the incidence and features of virus DNAemia and virus-specific T-cell immune reconstitution in unmanipulated haploidentical hematopoietic stem cell transplantation

Dixie Huntley  1 , Estela Giménez  1 , Lourdes Vázquez  2 , María Jesús Pascual  3 , Paula Amat  4   5 , María José Remigia  4 , Juan Carlos Hernández-Boluda  4   5 , Magdalena García  2 , Beatriz Gago  3 , Ignacio Torres  1 , Carlos Solano de la Asunción  1 , Rafael Hernani  4 , Ariadna Pérez  4 , Eliseo Albert  1 , José Luis Piñana  4 , Carlos Solano  4   5 , David Navarro  1   6
Affiliations
Observational Study

Impact of cytomegalovirus immunodominant HLA-I donor-recipient matching on the incidence and features of virus DNAemia and virus-specific T-cell immune reconstitution in unmanipulated haploidentical hematopoietic stem cell transplantation

Dixie Huntley et al. Transpl Infect Dis. 2023 Jun.

Abstract

Background: We investigated whether donor-recipient mismatch involving one or more cytomegalovirus (CMV) immunodominant (ID) human leukocyte antigen (HLA)-I alleles may impact on the degree of CMV pp65/immediate-early 1 (IE-1) T-cell reconstitution and the incidence of CMV DNAemia in patients undergoing unmanipulated haploidentical hematopoietic stem cell transplantation with high-dose posttransplant cyclophosphamide (PT/Cy-haplo).

Methods: Multicenter observational study including 106 consecutive adult PT/Cy-haplo patients (34 CMV ID HLA-I matched and 72 mismatched). A real-time PCR was used for plasma CMV DNA load monitoring. Enumeration of CMV-specific (pp65/IE-1) interferon (IFN)-γ-producing T cells from several patients was performed by flow cytometry by days +30, +60, +90 and +180 after transplantation.

Results: The cumulative incidence of CMV DNAemia, clinically significant CMV DNAemia episodes (cs-CMVi), and recurrent CMV DNAemia was comparable across CMV ID HLA-I matched and mismatched patients (71.8% vs. 80.9%, p = .95; 40.7% vs. 44.2%, p = .85; 16.4% vs. 28.1%; p = .43, respectively). The percentage of patients exhibiting detectable CMV-specific IFN-γ-producing T-cell responses (either CD8+ or CD4+ ) was similar across groups; nevertheless, significantly higher CMV-specific CD8+ T-cell counts were enumerated in the CMV ID HLA-I matched compared to mismatched patients by day +60 (p = .04) and +180 (p = .016) after transplantation.

Conclusion: CMV ID HLA-I matching may impact on the magnitude of CMV-pp65/IE-1-specific CD8+ T-cell reconstitution; yet, this effect seemed not to have an impact on the incidence of initial, recurrent CMV DNAemia, or cs-CMVi.

Keywords: CMV DNAemia; CMV immunodominant (ID) HLA-I alleles; CMV-specific T-cell reconstitution; PT/Cy-haplo; cytomegalovirus (CMV).

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References

REFERENCES

    1. Luznik L, O'Donnell PV, Symons HJ, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transpl. 2008;14(6):641-650.
    1. McCurdy SR, Luznik L. Immune reconstitution after T-cell replete HLA-haploidentical transplantation. Semin Hematol. 2019;56(3):221-226.
    1. Gagelmann N, Bacigalupo A, Rambaldi A, et al. Haploidentical stem cell transplantation with posttransplant cyclophosphamide therapy vs other donor transplantations in adults with hematologic cancers: a systematic review and meta-analysis. JAMA Oncol. 2019;5 (12):1739-48.
    1. Goldsmith SR, Slade M, DiPersio JF, et al. Cytomegalovirus viremia, disease, and impact on relapse in T-cell replete peripheral blood haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide. Haematologica. 2016;101(11):e465-e468.
    1. Bueno F, Solano C, Vázquez L, et al. Assessment of the association between cytomegalovirus DNAemia and subsequent acute graft-versus-host disease in allogeneic peripheral blood stem cell transplantation: a multicenter study from the Spanish hematopoietic transplantation and cell therapy group. Transpl Infect Dis. 2021;23(4):e13627.

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