A novel intensive induction therapy for high-risk neuroblastoma utilizing sequential peripheral blood stem cell collection and infusion as hematopoietic support

Kamnesh Pradhan, Cynthia S. Johnson, Terry Vik, Leonard S. Sender, Susan G. Kreissman

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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. Patients and Methods. Twenty-five children (age >1 year) with Stage 4 neuroblastoma were enrolled. First and third cycles consisted of cyclophosphamide (4 gm/m 2) and carboplatin (400 mg/m 2). Second and fourth cycles consisted of carboplatin (1 gm/m 2), and etoposide (450 mg/m 2). 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 close 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 VCPR (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. Conclusion. 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.

Original languageEnglish
Pages (from-to)793-802
Number of pages10
JournalPediatric Blood and Cancer
Volume46
Issue number7
DOIs
StatePublished - Jun 2006

Fingerprint

Carboplatin
Neuroblastoma
Etoposide
Cyclophosphamide
Induction Chemotherapy
Therapeutics
Poisons
Disease-Free Survival
Peripheral Blood Stem Cells
Neutrophils
Blood Platelets
Drug Therapy
Survival
Neoplasms

Keywords

  • High-risk neuroblastoma
  • Induction chemotherapy
  • Peripheral blood stem cells

ASJC Scopus subject areas

  • Cancer Research
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

A novel intensive induction therapy for high-risk neuroblastoma utilizing sequential peripheral blood stem cell collection and infusion as hematopoietic support. / Pradhan, Kamnesh; Johnson, Cynthia S.; Vik, Terry; Sender, Leonard S.; Kreissman, Susan G.

In: Pediatric Blood and Cancer, Vol. 46, No. 7, 06.2006, p. 793-802.

Research output: Contribution to journalArticle

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AB - 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. Patients and Methods. Twenty-five children (age >1 year) with Stage 4 neuroblastoma were enrolled. First and third cycles consisted of cyclophosphamide (4 gm/m 2) and carboplatin (400 mg/m 2). Second and fourth cycles consisted of carboplatin (1 gm/m 2), and etoposide (450 mg/m 2). 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 close 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 VCPR (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. Conclusion. 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.

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