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Favorable NK cell activity after haploidentical hematopoietic stem cell transplantation in stage IV relapsed Ewing’s sarcoma patients

Bone Marrow Transplantation volume 50, pages S72–S76 (2015)Cite this article

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Abstract

Natural killer (NK) cell activity has been shown to have potential activity against Ewing’s sarcoma (EWS) especially in tumors with low HLA I expression and high NKG2D expression. Two patients with metastatic relapsed and primary metastatic stage IV EWS who had received two courses of high dose chemotherapy with autologous stem cell rescue were transplanted from a haploidentical parental stem cell donor. Patients are alive in ongoing CR for 10.2 and 3.4 years now. Post transplant local second and first relapses were treated successfully in both patients. In vivo IL-2 stimulation not only increased the number and activity of effector cells in one patient but was also associated with severe GvHD. In vitro studies demonstrated high NK cell activity against K562 and relevant activity against EWS cell line A673 post transplant. NK activity was enhanced by cytokine prestimulation as well as by EWS targeting anti-GD2 Ab. Haploidentical hematopoietic stem cell transplantation (HSCT) might contribute to long-term survival by NK cell-mediated effect exerted by donor-derived NK cells. Local tumor recurrence was manageable in both high-risk patients indicating systemic immune control preventing subsequent metastasizing. The efficacy of haploidentical HSCT, cytokine application and tumor targeting antibodies for the use of Ab-dependent cellular cytotoxicity needs evaluation in clinical trials.

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Acknowledgements

This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB685), from the BMBF and from the Reinhold Beitlich-Stiftung to PL.

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, University Children's Hospital, Eberhard Karl's University, Tübingen, Germany

    P Schlegel, T Feuchtinger, C Nitschke-Gérard, U J Eva Seidel, A-M Lang, C Kyzirakos, H-M Teltschik, M Ebinger, M Schumm, R Handgretinger & P Lang

  2. Department of Pediatric Hematology and Oncology, Olgahospital Children’s Hospital, Stuttgart, Germany

    E Koscielniak

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Correspondence to P Lang.

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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, Almog Diagnostic.

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Schlegel, P., Feuchtinger, T., Nitschke-Gérard, C. et al. Favorable NK cell activity after haploidentical hematopoietic stem cell transplantation in stage IV relapsed Ewing’s sarcoma patients. Bone Marrow Transplant 50 (Suppl 2), S72–S76 (2015). https://doi.org/10.1038/bmt.2015.100

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