Amplification of immunological functions by subcutaneous injection of intermediate-high dose interleukin-2 for 2 years after autologous stem cell transplantation in children with stage IV neuroblastoma.
BACKGROUND
Immunotherapy given post-autologous stem cell transplantation may eliminate residual tumor cells escaping the conditioning protocol.


METHODS
Five children suffering from stage IV neuroblastoma were treated by recombinant interleukin-2 (IL-2) post-autologous peripheral blood stem cell transplantation. The patients' peripheral mononuclear cells were monitored for CD3+ and CD56+ levels, their proliferative response and killing of various cell lines targets.


RESULTS
An increase in the level of total lymphocytes, mainly due to expansion of T cells, and enhanced proliferative response to phytohemaglutinin were observed. Elevated cytotoxicity against K562 and neuroblastoma target cells was detected in four patients and against K562 targets in one patient. Toxicity included mild thrombocytopenia, and fever in four patients and mild to moderate encephalopathy which necessitated withdrawing one patient from the protocol. Three of five patients studied are alive today, one of them whose IL-2 was stopped, is in relapse. Two patients have died.


CONCLUSIONS
Immunotherapy with s.c. intermediate-high dose IL-2 is feasible and results in expansion of T cells and in stimulation of killing activity against several targets including in some cases, neuroblastoma tumor cells.
Toren
A
A
Pediatric Hemato-Oncology and the Institute of Hematology, The Chaim Sheba Medical Center, Tel Hashomer, Israel.
Nagler
A
A
Rozenfeld-Granot
G
G
Levanon
M
M
Davidson
J
J
Bielorai
B
B
Kaplinsky
C
C
Meitar
D
D
Mandel
M
M
Ackerstein
A
A
Ballin
A
A
Attias
D
D
Biniaminov
M
M
Rosenthal
E
E
Brok-Simoni
F
F
Rechavi
G
G
Kaufmann
Y
Y
D002675:Child, Preschool; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007167:Immunotherapy; D007223:Infant; D007376:Interleukin-2 / Q000276:immunology* / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000473:pathology* / Q000601:surgery*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014182:Transplantation, Autologous
D007376:Interleukin-2