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Favorable immune recovery and low rate of GvHD in children transplanted with partially T cell-depleted PBSC grafts

Bone Marrow Transplantation volume 54, pages 53–62 (2019)Cite this article

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Abstract

Transplantation of peripheral blood stem cells (PBSC) from matched unrelated donors (MUD) is still associated with a significant risk for graft vs. host disease (GvHD), especially in pediatric patients receiving grafts from adult donors containing high amounts of T cells. Here, we present long-term follow-up results on 25 pediatric patients, (acute leukemia n = 15, NHL n = 3, CML n = 3, MDS n = 5), transplanted with CD34 or CD133 positively selected PBSC from MUDs supplemented with an add-back of 1 × 107/kg body weight (kgBW) unselected T cells resulting in a median T-cell depletion (TCD) of 1.97 log. A total of 24/25 (96%) patients had primary engraftment. Early T-cell recovery was significantly improved compared to patients receiving CD34-selected grafts without T-cell add-back and similar to patients receiving unmanipulated bone marrow. GvHD incidence was low with 8/4% aGvHD grade II/III, no grade IV and 13% limited cGvHD. In total, 16/25 (64%) patients are alive after a median follow-up of 10 years. Five-year event-free survival (EFS) was 68%, relapse probability 24% and transplantation-related mortality (TRM) 12%. Thus, in PBSC allotransplants from MUD, partial TCD with serotherapy and CSA/MTX prophylaxis, can effectively reduce GvHD without hampering engraftment and immune reconstitution.

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Acknowledgements

This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB 685, TP C3), from the German Cancer Consortium (DKTK), partner site Tuebingen and from the Reinhold-Beitlich Stiftung to P.L. and R.H. We thank Barbara Lang, M.D. for reviewing the manuscript and the Stiftung fuer krebskranke Kinder Tuebingen e.V. for continuous support.

Author contributions

C.M.S., M.E., P.S., and P.L. collected and analyzed data, performed statistical analysis and wrote the paper. M.E., R.H., and P.L., designed the study. M.E., J.G., P.B., T.F., M.P. provided patients, M.S. provided data, C.P.S. critically reviewed the manuscript. All contributors had access to primary trial data, approved the manuscript, and agree with the presented data.

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Authors and Affiliations

  1. Department of General Pediatrics, Hematology/Oncology, University Children’s Hospital, Tuebingen, 72076, Germany

    Christian Martin Seitz, Patrick Schlegel, Martin Ebinger, Carl Philipp Schwarze, Michael Schumm, Rupert Handgretinger & Peter Lang

  2. Department of Hematology, Oncology and Stem Cell- Transplantation, University Children’s Hospital, Wuerzburg, 97080, Germany

    Matthias Eyrich & Paul Gerhardt Schlegel

  3. Department of Hematology/Oncology, University Children’s Hospital, Heidelberg, 69120, Germany

    Johann Greil

  4. Department of Hematology, Oncology and Stem Cell Transplantation, Dr. von Haunersches Kinderspital, Muenchen, 80337, Germany

    Tobias Feuchtinger

  5. Division for Stem Cell Transplantation and Immunology, University Children’s Hospital, Frankfurt, 60590, Germany

    Peter Bader

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Correspondence to Peter Lang.

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Seitz, C.M., Eyrich, M., Greil, J. et al. Favorable immune recovery and low rate of GvHD in children transplanted with partially T cell-depleted PBSC grafts. Bone Marrow Transplant 54, 53–62 (2019). https://doi.org/10.1038/s41409-018-0212-7

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