title: A phase-II study of adoptive immunotherapy with continuous infusion of interleukin-2 in children with advanced neuroblastoma. A report on 11 cases.
abstract: Nine children with poor prognosis neuroblastoma have been treated by continuous infusion of IL-2 and autologous LAK cells, as described previously by West et al. in adult patients. Six patients were in relapse after high-dose chemotherapy and autologous BMT and three presented with primary refractory disease after conventional therapy. Although patients were very young (median age 6 years; average weight 17 kg), infusion of IL-2, cytapheresis and reinjection of LAK cells appeared feasible with the usual and transient complications observed with IL-2. Haematological toxicity, although reversible, was more important than usually described and due to the presence of bone-marrow metastases in 8 of the 9 patients. Life-threatening toxicity was observed in only one of the admission centres and was probably due to the rapid reinjection of a very large number of activated cells. Two patients presenting with very active disease after high-dose chemotherapy and autologous or allogeneic BMT received IL-2 alone, at 120 days and at 90 days after the graft. The reactivation of grade-II GVHD was the major complication in the patient treated after an allograft, whereas no BMT-related toxicity was observed in the patient treated after the autologous BMT. Immunological modifications induced by IL-2 were very different between these patients. As expected, a preferential outgrowth of NK cells with both NK and LAK activity was observed in the patient treated just after the autograft. In contrast, in the patient treated after an allograft and in the 9 patients in relapse, T lymphocytes remained the major mononuclear cell population with a very large excess of CD8+ T cells. All patients progressed after the first induction cycle with the exception of the only patient treated after autologous BMT who reached a very good partial remission with disappearance of the local tumor and bone metastases. Although very preliminary, these data clearly show that the efficacy of IL-2 largely depends on the patient's immunological status with the optimal effect being observed when IL-2 is given in the first few months following an autograft.
authors.affiliation: Pediatric and Bone Marrow Transplant Department, Centre Léon Bérard, Lyon, France.
authors.forename: M
authors.initials: M
authors.lastname: Favrot
authors.forename: D
authors.initials: D
authors.lastname: Floret
authors.forename: J
authors.initials: J
authors.lastname: Michon
authors.forename: S
authors.initials: S
authors.lastname: Negrier
authors.forename: E
authors.initials: E
authors.lastname: Bouffet
authors.forename: C
authors.initials: C
authors.lastname: Coze
authors.forename: M
authors.initials: M
authors.lastname: Gaspard
authors.forename: P
authors.initials: P
authors.lastname: Cochat
authors.forename: P
authors.initials: P
authors.lastname: Thiesse
authors.forename: G
authors.initials: G
authors.lastname: Andreu
mesh_terms: D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D007694:Killer Cells, Natural / Q000276:immunology; D007937:Leukapheresis; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008297:Male; D008991:Monitoring, Physiologic; D009447:Neuroblastoma / Q000276:immunology / Q000628:therapy*; D011379:Prognosis
chemical_list: D007376:Interleukin-2