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Improved GVHD-free and relapse-free survival after ex vivo αβTCR and CD19 depleted allogeneic HSCT compared to T cell replete HSCT

Bone Marrow Transplantation volume 60, pages 673–681 (2025)Cite this article

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Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) aims to cure patients without inducing severe graft-versus-host disease (GVHD) or relapse. In prospective studies of mostly pediatric patients with haploidentical donors, ex vivo αβTCR/CD19 depletion has shown to have low incidences of GVHD, but data for adults with matched related (MRD) or unrelated donors (MUD) remain limited. We analyzed the outcomes of recipients who received a myeloablative regimen plus ATG, followed by an αβTCR/CD19-depleted allograft (cohort D+ATG (n = 122)), and compared outcomes to T cell-replete cohorts (cohort R (N = 60)); without ATG; R+ATG = with ATG (N = 129) in a single-center retrospective analysis. In D+ATG, the incidence of aGVHD grade III–IV was 7%, compared to 13% in R and 16% in R+ATG (p = 0.09). Extensive cGVHD was reduced from 23% in R and 10% in R+ATG to 2% in D+ATG (p < 0.001). The reduced incidence of cGVHD led to a superior GVHD-relapse-free survival (GRFS) of 56.7% in D+ATG versus 36.7% in R and 42.8% in R+ATG (p = 0.03) at 2 years. In conclusion, the combination of myeloablative conditioning, ATG, and ex vivo αβTCR/CD19 depletion appears to be a promising approach to enhance GRFS in adult patients up to 75 years of age undergoing allo-HSCT.

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Fig. 1: Cumulative incidence of aGvHD and cGvHD.
Fig. 2: Relapse and NRM by ex vivo αβTCR/CD19 depletion and conditioning with ATG.
Fig. 3: OS, EFS, and GRFS by ex vivo αβTCR/CD19 depletion and conditioning with ATG.

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Data availability

The data that support the findings of this study are available from EBMT the registry, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are, however, available from the authors upon reasonable request and with permission of the corresponding author.

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Author notes

  1. These authors contributed equally: A. H. G. Stuut, C. Nijssen.

  2. These authors jointly supervised this work: J. Kuball, M. A. de Witte.

Authors and Affiliations

  1. Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands

    A. H. G. Stuut, J. Drylewicz, J. Kuball & M. A. de Witte

  2. Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands

    C. Nijssen, L. van der Wagen, A. van Rhenen, L. G. M. Daenen, A. Janssen, F. A. Verheij, I. Brinkman, J. Kuball & M. A. de Witte

  3. Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands

    F. M. Verduyn Lunel

  4. Department of Internal Medicine, Antonius Ziekenhuis, Nieuwegein, The Netherlands

    H. Koene

  5. Department of Internal Medicine, Meander Medisch Centrum, Amersfoort, The Netherlands

    A. Janssen & R. Fijnheer

  6. University Medical Center Utrecht, Utrecht, The Netherlands

    H. J. Prins & K. Westinga

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Contributions

MdW and JK were responsible for the conception and design of the study. MdW and JK were funded for the study. LvdW, AvR, LvH, AJ, HK, RF, JK, and MdW actively managed the patients. AS, CN, FV, IB, FVL, HK, RF, HJP and KW collected the data. AS, CN, IB, and FV had full access to and verified the underlying data. AS, CN, JD, JK, and MdW contributed to data analysis and interpretation. AS, CN, JD, JK, and MdW wrote the original draft of the manuscript. AS and CN prepared the figures. AS and MdW were responsible for the submission of the manuscript. All authors were responsible for the critical revision of the manuscript and approved the final version of the manuscript.

Corresponding author

Correspondence to M. A. de Witte.

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Competing interests

JK is the inventor of multiple patents dealing with gdTCRs, ligands, and isolation strategies of engineered immune cells. JK is cofounder and shareholder of Gadeta (www.gadeta.nl). JK received research, advisor, and clinical study support from Miltenyi Biotech. JK received further research support from Novartis and Gadeta.

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Stuut, A.H.G., Nijssen, C., van der Wagen, L. et al. Improved GVHD-free and relapse-free survival after ex vivo αβTCR and CD19 depleted allogeneic HSCT compared to T cell replete HSCT. Bone Marrow Transplant 60, 673–681 (2025). https://doi.org/10.1038/s41409-025-02538-w

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