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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 1998; 339: 1186–1193.
Lacerda JF, Martins C, Carmo JA, Lourenco F, Juncal C, Rodrigues A et al. Haploidentical stem cell transplantation with purified CD34 cells after a chemotherapy-alone conditioning regimen. Biol Blood Marrow Transplant 2003; 9: 633–642.
Rowe JM, Lazarus HM . Genetically haploidentical stem cell transplantation for acute leukemia. Bone Marrow Transplant 2001; 27: 669–676.
Veys P, Amrolia P, Rao K . The role of haploidentical stem cell transplantation in the management of children with haematological disorders. Br J Haematol 2003; 123: 193–206.
Farag SS, Fehniger TA, Ruggeri L, Velardi A, Caligiuri MA . Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect. Blood 2002; 100: 1935–1947.
Giebel S, Locatelli F, Lamparelli T, Velardi A, Davies S, Frumento G et al. Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. Blood 2003; 102: 814–819.
Ruggeri L, Capanni M, Casucci M, Volpi I, Tosti A, Perruccio K et al. Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. Blood 1999; 94: 333–339.
Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002; 295: 2097–2100.
Davies SM, Ruggieri L, DeFor T, Wagner JE, Weisdorf DJ, Miller JS et al. Evaluation of KIR ligand incompatibility in mismatched unrelated donor hematopoietic transplants. Killer immunoglobulin-like receptor. Blood 2002; 100: 3825–3827.
Passweg JR, Meyer-Monard S, Gregor M, Favre G, Heim D, Ebnoether M et al. High stem cell dose will not compensate for T cell depletion in allogeneic non-myeloablative stem cell transplantation. Bone Marrow Transplant 2002; 30: 267–271.
Lang P, Pfeiffer M, Handgretinger R, Schumm M, Demirdelen B, Stanojevic S et al. Clinical scale isolation of T cell-depleted CD56+ donor lymphocytes in children. Bone Marrow Transplant 2002; 29: 497–502.
Iyengar R, Handgretinger R, Babarin-Dorner A, Leimig T, Otto M, Geiger T et al. Purification of human natural killer cells using a clinical-scale immunomagnetic method. Cytotherapy 2003; 5: 479–484.
Sato H, Shiobara S, Yasue S, Chuhjo T, Nakao S . Lymphocyte collection for donor leucocyte infusion from normal donors: estimation of the minimum processed blood volume and safety of the procedure. Vox Sang 2001; 81: 124–127.
Hester J . A clinical role for peripheral blood lymphocyte infusions and perspectives on collection. Therap Apher Dial 2003; 7: 305–311.
Guglielmi C, Arcese W, Dazzi F, Brand R, Bunjes D, Verdonck LF et al. Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose. Blood 2002; 100: 397–405.
Korbling M, Giralt S, Khouri I, Mirza N, Donato M, Anderlini P et al. Donor lymphocyte apheresis for adoptive immunotherapy compared with blood stem cell apheresis. J Clin Apheresis 2001; 16: 82–87.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2403524
Keywords
This article is cited by
-
Generating hematopoietic cells from human pluripotent stem cells: approaches, progress and challenges
Cell Regeneration (2023)
-
Leveraging CD16 fusion receptors to remodel the immune response for enhancing anti-tumor immunotherapy in iPSC-derived NK cells
Journal of Hematology & Oncology (2023)
-
Overview of the pre-clinical and clinical studies about the use of CAR-T cell therapy of cancer combined with oncolytic viruses
World Journal of Surgical Oncology (2022)
-
Pilot study to determine the safety and feasibility of deceased donor liver natural killer cell infusion to liver transplant recipients with hepatocellular carcinoma
Cancer Immunology, Immunotherapy (2022)
-
Natural killer cell therapy for hematologic malignancies: successes, challenges, and the future
Stem Cell Research & Therapy (2021)