title: Tracking in vivo dynamics of NK cells transferred in patients undergoing stem cell transplantation.
abstract: Haploidentical stem cell transplantation (haploSCT) offers an alternative treatment option for advanced leukemia patients lacking a HLA-compatible donor. Transfer of NK cells represents a promising therapeutic option in combination with SCT, as NK cells can promote graft versus leukemia with low risk of GVH disease. In this study, we show results from a phase I/II trial in which 24 acute myeloid leukemia patients underwent haploSCT in combination with early transfer of unmodified NK cells and observed a promising 2-year overall survival rate of 37%. By performing immunomonitoring and subsequent principal component analysis, we tracked donor NK-cell dynamics in the patients and distinguished between NK cells reconstituting from CD34(+) precursors, giving rise over time to a continuum of multiple differentiation stages, and adoptively transferred NK cells. Transferred NK cells displayed a mature phenotype and proliferated in vivo during the early days after haploSCT even in the absence of exogenous IL-2 administration. Moreover, we identified the NK-cell phenotype associated with in vivo expansion. Thus, our study indicates a promising path for adoptive transfer of unmodified NK cells in the treatment of high-risk acute myeloid leukemia.
authors.affiliation: Innate Immunity, Deutsches Rheuma Forschungszentrum, Berlin, Germany.
authors.forename: Monica
authors.initials: M
authors.lastname: Killig
authors.forename: Birte
authors.initials: B
authors.lastname: Friedrichs
authors.forename: Johannes
authors.initials: J
authors.lastname: Meisig
authors.forename: Chiara
authors.initials: C
authors.lastname: Gentilini
authors.forename: Nils
authors.initials: N
authors.lastname: Blüthgen
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.forename: Nadezda
authors.initials: N
authors.lastname: Basara
authors.forename: Christian
authors.initials: C
authors.lastname: Pfrepper
authors.forename: Dietger W
authors.initials: DW
authors.lastname: Niederwieser
authors.forename: Lutz
authors.initials: L
authors.lastname: Uharek
authors.forename: Chiara
authors.initials: C
authors.lastname: Romagnani
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D033581:Stem Cell Transplantation; D015996:Survival Rate; D061349:Unrelated Donors
chemical_list: D000970:Antineoplastic Agents; C508594:IL2 protein, human; D007376:Interleukin-2
keywords: Acute myeloid leukemia; Hematopoietic stem cell transplantation; NK cells; Principal component analysis