title: Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: a prospective phase II study in two centers.
abstract: Adoptive immunotherapy with allogeneic purified natural killer (NK) cell products might exert graft-versus-tumor alloreactivity with little risk of GVHD. In a prospective phase II study in two centers, we administered purified NK cell products to high-risk patients treated with haploidentical T-cell-depleted SCT. Sixteen patients received a total of 29 NK cell infusions on days +3, +40 and +100 after transplantation. Median doses (and ranges) of infused NK- and T-cells per product were 1.21 (0.3-3.8) × 10(7)/kg and 0.03 (0.004-0.72) × 10(5)/kg, respectively. With a median follow-up of 5.8 years 4/16 patients are alive. Cause of death was relapse in five, GVHD in three, graft failure in three, and transplant related neurotoxicity in one patient. Four patients developed acute GVHDgrade II, all receiving a total of 0.5 × 10(5) T cells/kg. Compared with historical controls, NK cell infusions had no apparent effect on the rates of graft failure or relapse. Adoptive transfer of allogeneic NK cells is safe and feasible, but further studies are needed to determine the optimal dose and timing of NK cell therapy. Moreover, NK cell activation/expansion may be required to attain clinical benefit, while careful consideration must be given to the number of T cells infused.
authors.affiliation: Stem Cell Transplant Team, Division of Hematology, University Hospital Basel, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Stern
authors.forename: J R
authors.initials: JR
authors.lastname: Passweg
authors.forename: S
authors.initials: S
authors.lastname: Meyer-Monard
authors.forename: R
authors.initials: R
authors.lastname: Esser
authors.forename: T
authors.initials: T
authors.lastname: Tonn
authors.forename: J
authors.initials: J
authors.lastname: Soerensen
authors.forename: M
authors.initials: M
authors.lastname: Paulussen
authors.forename: A
authors.initials: A
authors.lastname: Gratwohl
authors.forename: T
authors.initials: T
authors.lastname: Klingebiel
authors.forename: P
authors.initials: P
authors.lastname: Bader
authors.forename: A
authors.initials: A
authors.lastname: Tichelli
authors.forename: D
authors.initials: D
authors.lastname: Schwabe
authors.forename: U
authors.initials: U
authors.lastname: Koehl
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D006238:Haploidy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology*; D007938:Leukemia / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D009369:Neoplasms / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D011446:Prospective Studies; D019172:Transplantation Conditioning; D055815:Young Adult