title: Natural killer cell-enriched donor lymphocyte infusions from A 3-6/6 HLA matched family member following nonmyeloablative allogeneic stem cell transplantation.
abstract: Infusing natural killer (NK) cells following transplantation may allow less infections and relapse with little risk of acute graft-versus-host disease (aGVHD). We delivered 51 total NK cell-enriched donor lymphocyte infusions (DLIs) to 30 patients following a 3-6/6 HLA matched T cell-depleted nonmyeloablative allogeneic transplant. The primary endpoint of this study was feasibility and safety. Eight weeks following transplantation, donor NK cell-enriched DLIs were processed using a CD56(+) selecting column with up to 3 fresh infusions allowed. Toxicity, relapse, and survival were monitored. T cell phenotype, NK cell functional recovery, and KIR typing were assessed for association with outcomes. Fourteen matched and 16 mismatched transplanted patients received a total of 51 NK cell-enriched DLIs. Selection resulted in 96% (standard deviation [SD] 8%) purity and 83% (SD 21%) yield in the matched setting and 97% (SD 3%) purity and 77% (SD 24%) yield in the mismatched setting. The median number of CD3(-) CD56(+) NK cells infused was 10.6 (SD 7.91) x 10(6) cells/kg and 9.21 (SD 5.6) x 10(6) cells/kg, respectively. The median number of contaminating CD3(+)CD56(-) T cells infused was .53 (1.1) x 10(6) and .27 (.78) x 10(6) in the matched and mismatched setting, respectively. Only 1 patient each in the matched (n = 14) or mismatched (n = 16) setting experienced severe aGVHD with little other toxicity attributable to the infusions. Long-term responders with multiple NK cell-enriched infusions and improved T cell phenotypic recovery had improved duration of responses (p = .0045) and overall survival (OS) (P = .0058). A 1-step, high-yield process is feasible, and results in high doses of NK cells infused with little toxicity. NK cell-enriched DLIs result in improved immune recovery and outcomes for some. Future studies must assess whether the improved outcomes are the direct result of the high doses and improved NK cell function or other aspects of immune recovery.
authors.affiliation: Duke University Medical Center, Department of Medicine, Division of Cellular Therapy, Durham, North Carloina, 27705, USA. rizzi003@mc.duke.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Rizzieri
authors.forename: Robert
authors.initials: R
authors.lastname: Storms
authors.forename: Dong-Feng
authors.initials: DF
authors.lastname: Chen
authors.forename: Gwynn
authors.initials: G
authors.lastname: Long
authors.forename: Yiping
authors.initials: Y
authors.lastname: Yang
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nikcevich
authors.forename: Cristina
authors.initials: C
authors.lastname: Gasparetto
authors.forename: Mitchell
authors.initials: M
authors.lastname: Horwitz
authors.forename: John
authors.initials: J
authors.lastname: Chute
authors.forename: Keith
authors.initials: K
authors.lastname: Sullivan
authors.forename: Therese
authors.initials: T
authors.lastname: Hennig
authors.forename: Debashish
authors.initials: D
authors.lastname: Misra
authors.forename: Christine
authors.initials: C
authors.lastname: Apple
authors.forename: Megan
authors.initials: M
authors.lastname: Baker
authors.forename: Ashley
authors.initials: A
authors.lastname: Morris
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Green
authors.forename: Vic
authors.initials: V
authors.lastname: Hasselblad
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Chao
mesh_terms: D000328:Adult; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation*; D017710:Lymphocyte Transfusion / Q000379:methods; D008214:Lymphocytes / Q000276:immunology; D033581:Stem Cell Transplantation / Q000379:methods*; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous
chemical_list: D006680:HLA Antigens