Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: a prospective phase II study in two centers
- 3 September 2012
- journal article
- research article
- Published by Springer Nature in Bone Marrow Transplantation
- Vol. 48 (3) , 433-438
- https://doi.org/10.1038/bmt.2012.162
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.Keywords
This publication has 37 references indexed in Scilit:
- IL-2 Stimulated but Not Unstimulated NK Cells Induce Selective Disappearance of Peripheral Blood Cells: Concomitant Results to a Phase I/II StudyPLOS ONE, 2011
- Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patientsBlood, 2011
- Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trialThe Lancet Oncology, 2010
- NKG2D ligand expression in AML increases in response to HDAC inhibitor valproic acid and contributes to allorecognition by NK-cell lines with single KIR-HLA class I specificitiesBlood, 2008
- The proinflammatory cytokines IL-2, IL-15 and IL-21 modulate the repertoire of mature human natural killer cell receptorsArthritis Research & Therapy, 2007
- Natural-killer-cell-based treatment in haematopoietic stem-cell transplantationBest Practice & Research Clinical Haematology, 2006
- Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancerBlood, 2005
- Interleukin-15 Enhances Cytotoxicity, Receptor Expression, and Expansion of Neonatal Natural Killer Cells in Long-Term CultureClinical and Vaccine Immunology, 2004
- Effectiveness of Donor Natural Killer Cell Alloreactivity in Mismatched Hematopoietic TransplantsScience, 2002
- European experience of bone-marrow transplantation for severe combined immunodeficiencyThe Lancet, 1990