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IL-15-stimulated CD3/CD19-depleted stem-cell boosts in relapsed pediatric patients after haploidentical SCT

Leukemia volume 26, pages 2435–2439 (2012)Cite this article

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Natural killer (NK) cells have been shown to participate in graft versus leukemia (GvL) effects after haploidentical transplantation, especially if NK alloreactivity occurs due to incompatibilities between killer immunoglobulin-like receptors on donor NK cells and human leukocyte antigen (HLA) ligands on recipient cells.1, 2, 3 To take advantage of these effects immediately after transplantation, depletion of unwanted T and B cells (CD3/CD19 depletion) is currently used to produce grafts containing not only stem cells but also high numbers of NK cells.4 Moreover, additional NK cell infusions represent an interesting option for further immunotherapy and have been already used to treat or prevent disease relapse.5, 6 As cytokine stimulation strongly increases NK cell-mediated antileukemic activity, we investigated the use of haploidentical, interleukin (IL)-15-stimulated CD3/CD19-depleted grafts in combination with induction and low-dose maintenance chemotherapy for treatment of post-transplant relapse.

Eight patients received IL-15-stimulated stem-cell boosts on a compassionate level of use after providing informed consent. Granulocyte-colony stimulating factor-mobilized peripheral blood stem cells were depleted of CD3+ and CD19+ cells with the ClinicMACS device (Miltenyi Biotec, Bergisch Gladbach, Germany) as published earlier.4 CD3/19− cells (comprising stem cells, NK cells and monocytes) were diluted in RPMI medium containing 10% human AB serum, 2 mM L-glutamine and 10 ng/ml IL-15 under GMP (good manufacturing practice) conditions. Cells were incubated overnight for at least 12 h in tissue culture flasks at a concentration of 10 × 106 cells/ml. Afterwards, cells were washed four times in 0.9% NaCl. Production was performed under the approval of the local authorities according to §4b of the German drug law (AMG).

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Acknowledgements

We thank Anni Babarin-Dorner, Olga Bartuli, Ulrike Junker, Claudia Treuner and Gabi Hochwelker for their excellent technical assistance and Barbara Lang for reviewing this work. This work was supported by grants (SFB 685 and TranSaRNet) from the Deutsche Forschungsgemeinschaft (DFG) and the Bundesministerium für Bildung und Forschung (BMBF) Tuebingen to PL and from the Jung-Stiftung für Wissenschaft und Forschung and the Jose Carreras Leukemia Foundation to MMP.

Author Contributions

The design of this scientific work was done by MMP, MS and PL. MMP did the experimental work; IM, RH and PL took care of the patients and provided selected samples. RH directed the transplantation program and RH, MS and PL supervised the research. Data analysis was done by MMP and PL. The manuscript was written by MMP and PL and critically reviewed by all authors.

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Authors and Affiliations

  1. Department of Pediatric Hematology/Oncology, University Children’s Hospital, Eberhard Karl’s University, Tuebingen, Germany

    M M Pfeiffer, M Schumm, R Handgretinger & P Lang

  2. Department of Pediatric Hematology/Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Ingo Müller

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  1. M M Pfeiffer
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  2. M Schumm
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  3. Ingo Müller
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Correspondence to M M Pfeiffer.

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Pfeiffer, M., Schumm, M., Müller, I. et al. IL-15-stimulated CD3/CD19-depleted stem-cell boosts in relapsed pediatric patients after haploidentical SCT. Leukemia 26, 2435–2439 (2012). https://doi.org/10.1038/leu.2012.167

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