Interleukin-2 and lymphokine-activated killer cells in 15 children with advanced metastatic neuroblastoma.
A phase II trial using interleukin-2 (IL2) and lymphokine-activated killer (LAK) cells was carried out in an attempt to treat children with end-stage neuroblastoma. Fifteen patients (median age, 7 years) were enrolled in the study. Twelve were in relapse after massive chemotherapy and autologous bone marrow transplantation (ABMT), and three had a primary refractory disease after conventional chemotherapy. IL2 was administered as an 18 x 10(6) IU/m2/d continuous infusion. One course consisted of a double 5-day treatment period separated by a 6-day break. Cytapheresis to harvest LAK progenitor cells was performed during the rest period. After a 4-day in vitro culture, LAK cells were reinjected during the second cycle of therapy. A phenotypic and functional analysis of immunologic parameters was conducted along with the therapeutic protocol. Toxicity was significant with two toxic deaths (cardiotoxicity and respiratory distress). The reinfusion of large amounts of LAK cells was clearly involved in one case, but this particularly severe toxicity has to be related to the patient's status (ie, heavy pretreatment). No significant clinical response was seen. The immunologic monitoring showed phenotypic and functional modifications in these patients before initiation of treatment and an unexpected absence of evolution of these parameters during IL2 therapy. Although the origin of these immune dysfunctions is not clear, they could be involved in the failure of IL2 therapy. Future studies of IL2 therapy in neuroblastoma should be undertaken earlier in the course of the disease.
Negrier
S
S
Department of Pediatrics, Centre Léon Bérard, Lyon, France.
Michon
J
J
Floret
D
D
Bouffet
E
E
Gentet
J C
JC
Philip
I
I
Cochat
P
P
Stamm
D
D
Costil
J
J
Gaspard
M
M
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated; D009447:Neuroblastoma / Q000276:immunology / Q000556:secondary* / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000911:Antibodies, Monoclonal; D007376:Interleukin-2