Clinical StudiesNatural Killer Cell Homing and Persistence in the Bone Marrow After Adoptive Immunotherapy Correlates With Better Leukemia ControlGrzywacz, Bartosz*; Moench, Laura*; McKenna, David Jr*; Tessier, Katelyn M.†; Bachanova, Veronika‡; Cooley, Sarah‡; Miller, Jeffrey S.‡; Courville, Elizabeth L.*Author Information *Department of Laboratory Medicine and Pathology †Masonic Cancer Center Biostatistics Core ‡Adult Blood and Marrow Transplant Program, Department of Medicine, University of Minnesota, Minneapolis, MN E.L.C. and B.G.: designed the study, performed the research, analyzed the data, and wrote the manuscript. L.M.: contributed to study design, performed research, analyzed data, and edited the manuscript. K.M.T.: provided statistical support and edited the manuscript. D.M., V.B., S.C., and J.S.M.: contributed to study design and edited the manuscript. Reprints: Bartosz Grzywacz, Department of Laboratory Medicine and Pathology, 420 Delaware St. SE, MMC 609, Minneapolis, MN 55455 (e-mail: email@example.com). Journal of Immunotherapy: February/March 2019 - Volume 42 - Issue 2 - p 65-72 doi: 10.1097/CJI.0000000000000250 Buy Metrics Abstract 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 (rs=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. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.