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Immune reconstitution after single-unit umbilical cord blood transplantation using anti-thymoglobulin and myeloablative conditioning in adults with hematological malignancies

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Abstract

This study aimed to investigate the kinetics of immune recovery following umbilical cord blood transplantation (UCBT) in adults who received a myeloablative conditioning (MAC) regimen and antithymocyte globulin (ATG). While the immune recovery kinetics has been extensively studied in pediatric UCBT recipients, limited data exist for adults. We conducted a comprehensive analysis of 221 consecutive adult patients who underwent UCBT with MAC and ATG at a single institution. Our objective was to evaluate the influence of patient, disease, and transplant factors, along with acute graft-versus-host disease (aGVHD), on immune reconstitution and overall survival. Our findings confirm a delayed recovery of T cells, while B and NK cell reconstitution exhibited rapid progress, with NK cell counts reaching normal levels within 3 months post-transplantation and B cells within 6 months. Within CD3+ T cells, CD8+ T cells also experienced a delayed recovery (12 months), but to a lesser extent compared to CD4+ T cells (18 months). Delayed immune recovery of T-cell subsets was associated with the development of aGVHD grade II-IV, older age, CMV negativity, and a female donor. Patients with lymphoproliferative diseases showed slower NK cell recovery. Our study demonstrates that adult patients undergoing MAC with ATG and receiving a single unit UCBT for hematologic malignancies experienced rapid reconstitution of NK and B cells. However, T cell recovery, particularly CD4+ T cells, was significantly delayed. To enhance T cell recovery, it may be crucial to consider UCB units with higher cellularity and optimize ATG doses in conditioning.

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Acknowledgements

We would like to acknowledge Ignacio Lorenzo and Federico Moscardó for their guidance and contributions during this work.

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no funding was received.

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Author notes

  1. Lourdes Cordón and Pedro Chorão authors made equal contributions to this work.

Authors and Affiliations

  1. Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia, 46026, Spain

    Lourdes Cordón, Pedro Chorão, Beatriz Martín-Herreros, Aitana Balaguer, Manuel Guerreiro, Marta Villalba, Ana Facal, Marta Santiago, Amparo Sempere, Guillermo F. Sanz, Miguel A. Sanz & Jaime Sanz

  2. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Carlos III, Madrid, Spain

    Lourdes Cordón, Inés Gómez, Amparo Sempere, Guillermo F. Sanz, Miguel A. Sanz & Jaime Sanz

  3. Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain

    Pedro Chorão, Juan Montoro, Aitana Balaguer, Manuel Guerreiro, Marta Villalba, Ana Facal, Pedro Asensi, Pilar Solves, Inés Gómez, Marta Santiago, Brais Lamas, Ana Bataller, Pablo Granados, Amparo Sempere, Guillermo F. Sanz, Miguel A. Sanz & Jaime Sanz

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  1. Lourdes Cordón
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Contributions

L.C. and P. Ch. have made equal contributions to the study. Alongside M.A.S. and J.S., they have collaborated in drafting the manuscript and incorporating all revisions and suggestions provided by B.M.H., J.M., A.B., M.G., M.V., A.F., P.A., P.S., I.G., M.S., B.L., A.Bat., P.G., A.S., G.F.S, who also participated in reviewing the manuscript and contributed to the final draft.

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Correspondence to Lourdes Cordón.

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Cordón, L., Chorão, P., Martín-Herreros, B. et al. Immune reconstitution after single-unit umbilical cord blood transplantation using anti-thymoglobulin and myeloablative conditioning in adults with hematological malignancies. Ann Hematol 103, 2475–2484 (2024). https://doi.org/10.1007/s00277-024-05758-0

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