Natural Killer Cell Homing and Persistence in the Bone Marrow after Adoptive Immunotherapy Correlates with Better Leukemia Control

Bartosz J Grzywacz, Laura Moench, David H McKenna, Katelyn M Tessier, Veronika Bachanova, Sarah A Cooley, Jeffrey S Miller, Elizabeth L Courville

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Cellular immunotherapy using allogeneic natural killer (NK) cells may overcome chemotherapy-refractory acute myeloid leukemia. Our goal was to document NK cell homing/persistence in the bone marrow following adoptive immunotherapy. Our cohort included 109 patients who received NK cell therapy for refractory acute myeloid leukemia following lymphodepleting conditioning +/-denileukin diftitox, +/-low-dose total body irradiation. We evaluated the NK cell density in bone marrow core biopsies performed an average of 14 days after NK cell transfer using a CD56 immunohistochemical stain. The NK cell density in core biopsies showed only moderate correlation with NK cell percentage in bone marrow aspirates evaluated by flow cytometry (r s =0.48) suggesting that distribution of CD56 + cells in the bone marrow niche offers unique insight into NK cell homing. Better leukemia control was associated with increased NK cell density, such that patients with <5% blasts had a higher NK cell density (P=0.01). As well, NK cell density above the median of reference group was significantly associated with morphologic remission of leukemia (P=0.01). Moreover, the NK cell density varied significantly between conditioning protocols. Our findings suggest that the use of low-dose irradiation or CD25-targeting immunocytokine (denileukin diftitox, IL2DT) as part of conditioning results in increased NK cell homing/persistence in the bone marrow. These novel results will help guide future immunotherapy with NK cells.

Original languageEnglish (US)
Pages (from-to)65-72
Number of pages8
JournalJournal of Immunotherapy
Issue number2
StatePublished - Feb 1 2019

Bibliographical note

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© 2018 Wolters Kluwer Health, Inc. All rights reserved.


  • CD56
  • NK cells
  • acute myeloid leukemia
  • bone marrow
  • immunotherapy


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