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Improved immune recovery after transplantation of TCRαβ/CD19-depleted allografts from haploidentical donors in pediatric patients

Bone Marrow Transplantation volume 50, pages S6–S10 (2015)Cite this article

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Abstract

Immune recovery was retrospectively analyzed in a cohort of 41 patients with acute leukemia, myelodysplastic syndrome and nonmalignant diseases, who received αβ T- and B-cell-depleted allografts from haploidentical family donors. Conditioning regimens consisted of fludarabine or clofarabine, thiotepa, melphalan and serotherapy with OKT3 or ATG-Fresenius. Graft manipulation was carried out with anti-TCRαβ and anti-CD19 Abs and immunomagnetic microbeads. The γδ T cells and natural killer cells remained in the grafts. Primary engraftment occurred in 88%, acute GvHD (aGvHD) grades II and III–IV occurred in 10% and 15%, respectively. Immune recovery data were available in 26 patients and comparable after OKT3 (n=7) or ATG-F (n=19). Median time to reach >100 CD3+ cells/μL, >200 CD19+ cells/μL and >200 CD56+ cells/μL for the whole group was 13, 127 and 12.5 days, respectively. Compared with a historical control group of patients with CD34+ selected grafts, significantly higher cell numbers were found for CD3+ at days +30 and +90 (267 vs 27 and 397 vs 163 cells/μL), for CD3+4+ at day +30 (58 vs 11 cells/μL) and for CD56+ at day +14 (622 vs 27 cells/μL). The clinical impact of this accelerated immune recovery will be evaluated in an ongoing prospective multicenter trial.

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Acknowledgements

This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB 685, TP C3), from the BMBF (ivacALL), from the Reinhold–Beitlich Stiftung and from Neovii Biotech (Fresenius) to PL and RH. We thank the Stiftung fuer krebskranke Kinder Tuebingen e.V. for continuous support.

Author Contributions

PL, TF, HMT and RH designed the study, provided patients, analyzed data, performed statistical analysis and wrote the paper. WS, MP, CPS, ME and CU provided patients, collected data and contributed to writing the manuscript; MS provided immune recovery data; PS, BL and AML collected and analyzed data and contributed to writing the manuscript. All contributors had access to primary trial data, approved the manuscript and agree with the presented data.

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Author notes

  1. P Lang and T Feuchtinger: These authors contributed equally to this work.

Authors and Affiliations

  1. Children's University Hospital, University of Tuebingen, Tuebingen, Germany

    P Lang, T Feuchtinger, H-M Teltschik, P Schlegel, M Pfeiffer, M Schumm, A-M Lang, B Lang, C P Schwarze, M Ebinger & R Handgretinger

  2. Children's University Hospital, Medical University of Graz, Graz, Austria

    W Schwinger & C Urban

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  1. P Lang
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Correspondence to P Lang.

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The authors declare no conflict of interest.

Additional information

This article was published as part of a supplement, supported by WIS-CSP Foundation, in collaboration with Gilead, Milteny Biotec, Gamida Cell, Adienne Pharma and Biotech, Medac Hematology, Kiadis Pharma and Almog Diagnostic.

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Lang, P., Feuchtinger, T., Teltschik, HM. et al. Improved immune recovery after transplantation of TCRαβ/CD19-depleted allografts from haploidentical donors in pediatric patients. Bone Marrow Transplant 50 (Suppl 2), S6–S10 (2015). https://doi.org/10.1038/bmt.2015.87

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