A novel intensive induction therapy for high-risk neuroblastoma utilizing sequential peripheral blood stem cell collection and infusion as hematopoietic support.
OBJECTIVE
To determine the feasibility, toxicities, and the response rate (RR) of a dose intensive, submyeloablative, induction chemotherapy protocol termed EPiC (etoposide, carboplatin, and intensive cyclophosphamide) utilizing sequential peripheral blood stem cell (PBSC) collection and infusion as hematopoietic support in children with newly diagnosed Stage 4 neuroblastoma.


METHODS
Twenty-five children (age >1 year) with Stage 4 neuroblastoma were enrolled. First and third cycles consisted of cyclophosphamide (4 gm/m2) and carboplatin (400 mg/m2). Second and fourth cycles consisted of carboplatin (1 gm/m2), and etoposide (450 mg/m2). PBSC were collected following Cycles 1, 2, and 3 and reinfused in each subsequent cycle. Following EPiC and surgical resection of the primary tumor, patients proceeded to various consolidation therapies. RR was scored using the International Neuroblastoma Response Criteria.


RESULTS
Using PBSC infusion following EPiC chemotherapy resulted in a dose intensity averaging 85% of intended dose intensity; and in early neutrophil but not platelet recovery. PBSC were adequately collected in all, but one patient. The protocol had minimal non-hematological toxicities. There was one toxic death. The overall RR was 78%, which included PR (partial response) and VGPR (very good partial response). The 5-year event-free survival and overall survival were 44% and 54%, respectively at a median follow-up of 58.6 months.


CONCLUSIONS
EPiC is a feasible, well-tolerated, sub-myeloablative, induction chemotherapy protocol for children with high-risk neuroblastoma. RR is equivalent to prior published studies, however, with minimal toxicities. Sequential PBSC collection and infusion is feasible even in very young children.
Pradhan
Kamnesh R
KR
Indiana University, School of Medicine, Dept. of Pediatrics, USA.
Johnson
Cynthia S
CS
Vik
Terry A
TA
Sender
Leonard S
LS
Kreissman
Susan G
SG
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007223:Infant; D016014:Linear Models; D008297:Male; D009447:Neuroblastoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D010865:Pilot Projects; D012074:Remission Induction; D016019:Survival Analysis
D005047:Etoposide; D016190:Carboplatin