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Identifying candidate allogeneic NK-cell donors for hematopoietic stem-cell transplantation based on functional phenotype

Leukemia volume 24, pages 1059–1062 (2010)Cite this article

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Allogeneic hematopoietic stem-cell transplantation (HSCT) in general, and haploidentical HSCT in particular, is a therapeutic approach for leukemias and especially acute myeloid leukemia (AML). Residual malignant disease is mitigated, in part, after transplantation by graft-versus-leukemia activity of donor-derived T cells expressing αβ T-cell receptors that recognize major and minor histocompatibility antigens on malignant cells. In situations of human leukocyte antigen (HLA)-mismatched HSCT, the extensive T-cell depletion of the allograft undertaken to prevent graft-versus-host disease results in delayed T-cell engraftment, increases the probability of infection by opportunistic pathogens and the possibility of relapse. However, the infused and engrafted allogeneic natural killer (NK) cells also contribute to controlling infections and the graft-versus-leukemia effect,1 although using a different activation mechanism.

Donor-derived NK cells engrafting after haploidentical HSCT and adoptive transfer of haploidentical NK cells have shown therapeutic effects. NK-cell alloreactivity resulting from appropriate killer cell Ig-like receptor (KIR)-ligand disparity in HLA haplotype-mismatched HSCT has resulted in improved engraftment, decreased incidence of leukemia relapse and increased survival rates in patients with AML2 and possibly also in children with acute lymphoblastic leukemia.3 Pre-transplant infusion of alloreactive NK cells has been shown to eliminate AML blasts and kill recipient T cells which may allow a reduction in the toxicity of the conditioning regimen. Furthermore, NK cell-mediated eradication of recipient dendritic cells may offer protection against graft-versus-host disease and support an increased T-cell content in the allograft.1 Infusion of haploidentical NK cells after lymphodepleting chemotherapy has also been used to treat subsets of patients with relapsed AML,2 and this observation has formed the basis of clinical trials infusing haploidentical NK cells for patients with relapsed/recurrent neuroblastoma4 and pediatric acute lymphoblastic leukemia.5

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Acknowledgements

The project described was supported in part by Award Number TL1RR024147 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional support is from CCSG Grant (CA16672), RO1 (CA124782, CA120956), R21 (CA129390, CA116127), DOD (PR064229), The Alex Lemonade Stand Foundation, The Burroughs Welcome Fund, The Department of Veterans Affairs Career Development Award, The Gillson Longenbaugh Foundation, The Leukemia and Lymphoma Society, The Lymphoma Research Foundation, The Miller Foundation, The National Foundation for Cancer Research, The Pediatric Cancer Research Foundation, The William Lawrence and Blanche Hughes Foundation.

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Authors and Affiliations

  1. Division of Pediatrics, Children's Cancer Hospital, The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    L V Hurton, R I Siddik, H Singh, S Olivares, D A Lee, S S Kelly & L J N Cooper

  2. Division of Experimental Diagnostic Imaging, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    B A Rabinovich

  3. Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    R Tian, D Mojsilovic & W Hildebrand

  4. Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    R Champlin & E J Shpall

  5. Laboratory Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    M Fernandez-Viña

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  1. L V Hurton
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  14. L J N Cooper
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Correspondence to L J N Cooper.

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Hurton, L., Siddik, R., Singh, H. et al. Identifying candidate allogeneic NK-cell donors for hematopoietic stem-cell transplantation based on functional phenotype. Leukemia 24, 1059–1062 (2010). https://doi.org/10.1038/leu.2010.19

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