Abstract
Natural killer (NK) cell based immunotherapy is an emerging strategy in hematologic malignancies because allogeneic NK cells can provide potent antitumor immunity without inducing graft-versus-host disease. Thus, we expanded cord blood-derived NK (CB-NK) cells ex vivo from random (MHC mismatched and KIR mismatched) donors, and investigate the feasibility and efficacy of repeated infusions CB-NK cells as maintenance therapy after autologous hematopoietic stem cell transplantation (ASCT). Thirty-one patients with acute myeloid leukemia and high-risk lymphoma received ASCT and the adoptive CB-NK cell multiple infusions for maintenance therapy. Patients received a median dose of 5.98 × 107/kg (range, 1.87-17.69 × 107/kg) CB-NK cells and 23 patients completed four infusions, 8 patients received three infusions. Only mild infusion reactions occurred in 15.5% of 116 infusions. Compared to a contemporaneous cohort of 90 patients who did not receive NK cell therapy, the adoptive transfer of CB-NK cells as maintenance treatment showed a tendency of difference in decreasing the relapse rate between CB-NK group and control group (9.7% vs 24.4%). The patients who receiving NK cell infusions had a better PFS and OS than controls (4 year PFS, 84.4 ± 8.3% vs 73.5 ± 5.4%; and 4 year OS, 100% vs 78.1 ± 5.4%) . These findings demonstrate safety and validity of maintenance therapy using CB-NK cells multiple infusions after ASCT, and it is worthy of further clinical trial verification.
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The datasets used and/or analyzed during the study are available from the corresponding author on reasonable request.
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Acknowledgements
We would like to thank all of the participants in this study, include patients, nurses, and laboratory technicians for their contributions.
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T.L. designed and guild the clinical research. Q.C. guild the expansion of CB-NK cells products., YL.W., J.J.,Q.C., and T.L. interpreted the data. Y.W., X.L., expand CB-NK cells. P.K., X.C., J.J., Z.L., J.L, and T.D. treated patients. YL.W. and T.L. analyzed the data and wrote the paper. All authors revised and approved the final version of the manuscript.
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The study was reviewed and approved by the Ethics Committees of West China Hospital, Sichuan University, and was registered on the Clinical Trial Registry (clinicaltrials.gov, NCT05250362). Written informed consent was obtained from all patients.
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Wu, Y., Wang, Y., Ji, J. et al. A pilot study of cord blood-derived natural killer cells as maintenance therapy after autologous hematopoietic stem cell transplantation. Ann Hematol 102, 3229–3237 (2023). https://doi.org/10.1007/s00277-023-05471-4
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DOI: https://doi.org/10.1007/s00277-023-05471-4