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Bone Marrow Transplantation

Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation

Abstract

This pilot study tested feasibility of natural killer cell purification and infusion (NK-DLI) in patients after haploidentical hematopoietic stem cell transplantation (HSCT). The aim was to obtain 1.0 × 107/kg CD56+/CD3− NK cells and <1.0 × 105/kg CD3+ T cells. Mononuclear cells were collected by 10 l leukapheresis. A two-step ex vivo procedure was used to purify NK cells, using an immunomagnetic T-cell depletion, followed by NK-cell enrichment. Five patients with high-risk myeloid malignancies were included, presenting 3–12 months after a haploidentical HSCT with mixed chimerism (3), impending graft failure (1) or early relapse (1). The purified product contained a median of 1.61 × 107/kg (range 0.21–2.2) NK cells and 0.29 × 105/kg (0.11–1.1) T cells. A purity of NK cells of 97% (78–99), a recovery of 35.5% (13–75), and a T-cell depletion of 3.55 log (2.9–4.5) was achieved. Infusions were well tolerated and none of the patients developed graft-versus-host disease. We observed an increase in donor chimerism in 2/5, stable mixed chimerism, decreasing chimerism and relapse of AML in one patient each. Selection of NK-DLI is technically feasible. NK cells are well tolerated when used as adoptive immunotherapy in recipients of haploidentical HSCT.

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Acknowledgements

We thank Katherine Haupt and the cell collection team, Laura Landi and the cell engineering team, Heike Huxol and the team responsible for chimerism analysis as well as Silvia Mathys and the FACS team for their help. We further thank Miltenyi Biotec for their technical support in NK. This work was supported by a SAKK-Swiss group for Clinical Cancer Research Pilot Project Grant.

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Correspondence to A Tichelli.

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Passweg, J., Tichelli, A., Meyer-Monard, S. et al. Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation. Leukemia 18, 1835–1838 (2004). https://doi.org/10.1038/sj.leu.2403524

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