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Post-Transplant Events

Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: a prospective phase II study in two centers

Abstract

Adoptive immunotherapy with allogeneic purified natural killer (NK) cell products might exert graft-versus-tumor alloreactivity with little risk of GVHD. In a prospective phase II study in two centers, we administered purified NK cell products to high-risk patients treated with haploidentical T-cell-depleted SCT. Sixteen patients received a total of 29 NK cell infusions on days +3, +40 and +100 after transplantation. Median doses (and ranges) of infused NK- and T-cells per product were 1.21 (0.3–3.8) × 107/kg and 0.03 (0.004–0.72) × 105/kg, respectively. With a median follow-up of 5.8 years 4/16 patients are alive. Cause of death was relapse in five, GVHD in three, graft failure in three, and transplant related neurotoxicity in one patient. Four patients developed acute GVHDgrade II, all receiving a total of 0.5 × 105 T cells/kg. Compared with historical controls, NK cell infusions had no apparent effect on the rates of graft failure or relapse. Adoptive transfer of allogeneic NK cells is safe and feasible, but further studies are needed to determine the optimal dose and timing of NK cell therapy. Moreover, NK cell activation/expansion may be required to attain clinical benefit, while careful consideration must be given to the number of T cells infused.

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Acknowledgements

This project was supported by ‘Deutsche Forschungsgemeinschaft (DFG, GK-1172)’, by Hilfe für Krebskranke Kinder Frankfurt e.V., ‘Frankfurter Stiftung für Krebskranke Kinder’, ‘Adolf Messer Stiftung’, the ‘Alfred and Angelika Gutermuth-Stiftung’, the ‘Stiftung für hämatologische Forschung’ and the Swiss National Science Foundation (PPOOP3_128461, and 3200B0-118176). We thank patients, nursing staff and data managers involved in this study.

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Correspondence to J R Passweg.

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Stern, M., Passweg, J., Meyer-Monard, S. et al. Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: a prospective phase II study in two centers. Bone Marrow Transplant 48, 433–438 (2013). https://doi.org/10.1038/bmt.2012.162

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