title: Natural killer cell activity influences outcome after T cell depleted stem cell transplantation from matched unrelated and haploidentical donors.
abstract: Lytic activity and recovery of natural killer (NK) cells was monitored in pediatric patients with leukemias (ALL, AML, CML, JMML) and myelodysplastic syndromes after transplantation of T cell depleted stem cells from matched unrelated (n = 18) and mismatched related (haploidentical, n = 29) donors. CD34 + selection with magnetic microbeads resulted in 8 × 10(3)/kg residual T cells. No post-transplant immune suppression was given. NK cells recovered rapidly after transplantation (300 CD56+/μL at day 30, median), whereas T cell recovery was delayed (median: 12 CD3+/μL at day 90). NK activity was measured as specific lysis of K 562 targets several times (mean: 3 assays per patient). Four temporal patterns of lytic activity could be differentiated: consistently low, consistently high, decreasing and increasing activity. Patients with consistently high or increasing activity had significantly lower relapse probability than patients with consistently low or decreasing levels (0.18 vs 0.73 at 2 years, p < 0.05). The subgroup of patients with ALL showed similar results (0.75 vs 0.14 at 2 years, p < 0.05). Speed of T cell recovery had no influence. These data suggest that both achieving and maintaining a high level of NK activity may contribute to prevent relapse. Since NK activity could be markedly increased by in vitro stimulation with Interleukin 2 (IL-2), in vivo administration should be considered.
authors.affiliation: Department of Pediatric Oncology, University Children's Hospital, Eberhard Karl's University Tübingen, Hoppe Seyler Strasse 1, Tübingen, Germany. peter.lang@med.uni-tuebingen.de
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.forename: Matthias
authors.initials: M
authors.lastname: Pfeiffer
authors.forename: Heiko-Manuel
authors.initials: HM
authors.lastname: Teltschik
authors.forename: Patrick
authors.initials: P
authors.lastname: Schlegel
authors.forename: Tobias
authors.initials: T
authors.lastname: Feuchtinger
authors.forename: Martin
authors.initials: M
authors.lastname: Ebinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.forename: Paul-Gerhard
authors.initials: PG
authors.lastname: Schlegel
authors.forename: James
authors.initials: J
authors.lastname: Beck
authors.forename: Johann
authors.initials: J
authors.lastname: Greil
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
mesh_terms: D000293:Adolescent; D018952:Antigens, CD34 / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D036102:Peripheral Blood Stem Cell Transplantation; D012008:Recurrence; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34