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Dynamics of recent thymic emigrants in pediatric recipients of allogeneic hematopoetic stem cell transplantation

Bone Marrow Transplantation volume 57, pages 620–626 (2022)Cite this article

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Abstract

After allogeneic hematopoietic stem cell transplantation (allo-HSCT), the recurrence of recent thymic emigrants (RTE) and self-tolerant T cells indicate normalized thymic function. From 2008 to 2019, we retrospectively analyzed the RTE-reconstitution rate and the minimal time to reach normal age-specific first percentiles for CD31+CD45RA+CD4+T cells in 199 pediatric patients after allo-HSCT for various malignant and non-malignant diseases. The impact of clinically significant graft-versus-host disease (GvHD), age at transplantation, underlying disease and cumulative area under the curve of busulfan on RTE-reemergence was assessed in multivariable longitudinal analysis. RTE-reconstitution (coefficient −0.24, 95% CI −0.33 to −0.14, p < 0.001) was slowed down by GvHD and the time to reach P1 was significantly longer (Event Time Ratio 1.49, 95% CI 1.25 to 1.78, p < 0.001). Older age at transplantation was also associated with a slower RTE-reconstitution (coefficient −0.028, 95% CI −0.04 to −0.02, p < 0.001) and time to reach P1 was significantly longer (Event Time Ratio 1.03, 95% CI 1.02 to 1.05, p < 0.001). RTE-reconstitution velocity was not influenced by underlying disease or cumulative busulfan exposure. In summary, duration until thymic reactivation was independent of both conditioning intensity and underlying disease and was negatively influenced by older age and GvHD.

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Fig. 1: Influence of acute graft-versus-host disease (GvHD) on recent thymic emigrants (RTE) re-emergence.
Fig. 2: Influence of underlying disease on recent thymic emigrants (RTE) re-emergence.

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Acknowledgements

The authors thank Maja Rutishauser, senior laboratory technician, who played a major role implementing the flowcytometry analyses and the percentiles for CD4+CD31+ T-cells into the routine laboratory diagnostics at University Children’s Hospital Zürich, Switzerland.

Funding

DD received a grant for this study from the Children’s Research Center, University Children’s Hospital Zürich, University of Zürich, Zürich, Switzerland. MHH is supported by the Prof. Max Cloëtta Foundation.

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Author notes

  1. These authors contributed equally: Daniel Drozdov, Katrin Petermann.

  2. These authors contributed equally: Tayfun Güngör, Mathias Hauri-Hohl.

Authors and Affiliations

  1. Division of Stem Cell Transplantation and Children’s Research Center, University Children’s Hospital Zurich, University of Zürich, Zürich, Switzerland

    Daniel Drozdov, Sibylle Oberholzer, Tayfun Güngör & Mathias Hauri-Hohl

  2. Division of Oncology-Hematology, Department of Pediatrics, Kantonsspital Aarau, Aarau, Switzerland

    Daniel Drozdov

  3. Epidemiology, Biostatistics, and Prevention Institute (EBPI), University of Zürich, Zürich, Switzerland

    Katrin Petermann & Leonhard Held

  4. Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Katrin Petermann

  5. Department of Cardiology, University Hospital Zürich, University of Zürich, Zürich, Switzerland

    Svetlana Dougoud

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  1. Daniel Drozdov
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  2. Katrin Petermann
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  3. Svetlana Dougoud
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  4. Sibylle Oberholzer
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  7. Mathias Hauri-Hohl
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Contributions

DD, TG, MH, SO and SD conceived and designed the study, analyzed the data and wrote the manuscript. KP and LH performed the statistical analysis and reviewed and edited the manuscript.

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Correspondence to Daniel Drozdov.

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The authors declare no competing interests.

Ethics approval and consent to participate

Ethical approval was granted by the Ethics Committee of Canton Zürich, Switzerland (2017-02040). Informed consent was obtained from all study participants transplanted after 01.01.2014. For patients transplanted before 01.01.2014 the informed consent was waived by the Ethics Committee of Canton Zürich, Switzerland.

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Drozdov, D., Petermann, K., Dougoud, S. et al. Dynamics of recent thymic emigrants in pediatric recipients of allogeneic hematopoetic stem cell transplantation. Bone Marrow Transplant 57, 620–626 (2022). https://doi.org/10.1038/s41409-022-01594-w

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