title: Immunologic effects of intermediate-dose IL-2 i.v. after autologous hematopoietic cell transplantation in pediatric solid tumors.
abstract: Adoptive immunotherapy with interleukin-2 (IL-2) may control minimal residual disease (MRD) and prevent relapse after autologous hematopoietic cell transplantation (AHCT). The objective of this study was to determine the immunologic effects of intermediate doses of intravenous (i.v.) IL-2 after AHCT in children with poor-prognosis solid tumors. Eleven patients received a median five cycles consisting of escalating doses of IL-2 i.v. for 5 days after a median time interval of 94 days post-AHCT. The phenotype of lymphocyte subsets was investigated before and after each cycle, and parallel determination of natural killer (NK) cell activity was performed. Immunotherapy induced a significant increase in total lymphocyte count (TLC), T, NK, and, to some extent, B cells. Among NK cells, CD56+ bright cells expanded more than CD56+ dim cells. High expansion of CD56+ cells with CD94 inhibitory receptor was observed, whereas no difference was recorded in the number of CD3+ CD56+ and CD8+ CD57+ cells. NK activity stabilized after the first cycle of IL-2 and remained elevated during the study period. Cycles of IL-2 immunotherapy induced repeated significant expansion of T cells and NK cells, mostly of the immature CD56+ bright phenotype. Despite enhanced NK activity, relapses occurred frequently, which might have been due to increased CD94 activation and a poor response from the cytotoxic NK T cells and CD8+ CD57+ T cells.
authors.affiliation: Department of Pediatric Hematology/Oncology, University School of Medicine, Wroclaw, 50-345 Wroclaw, Poland. kk@pedhemat.am.wroc.pl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kalwak
authors.forename: Marek
authors.initials: M
authors.lastname: Ussowicz
authors.forename: Ewa
authors.initials: E
authors.lastname: Gorczyńska
authors.forename: Dominik
authors.initials: D
authors.lastname: Turkiewicz
authors.forename: Jacek
authors.initials: J
authors.lastname: Toporski
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Dobaczewski
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Latos-Grazyńska
authors.forename: Renata
authors.initials: R
authors.lastname: Ryczan
authors.forename: Dorota
authors.initials: D
authors.lastname: Noworolska-Sauren
authors.forename: Alicja
authors.initials: A
authors.lastname: Chybicka
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D005260:Female; D006684:HLA-DR Antigens / Q000097:blood; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000379:methods; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008297:Male; D009369:Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D011379:Prognosis; D033581:Stem Cell Transplantation / Q000401:mortality; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; D006684:HLA-DR Antigens; D007376:Interleukin-2