1.0 OBJECTIVES 
1.1 To establish the safety and toxicity of high-dose carboplatin (CBDCA) and 
etoposide (VP-16) with autologous marrow support in pediatric patients in 
remission of Stage D (disseminated) neuroblaistoma. 
1.2 To obtain preliminary efficiency data on the value of CBDCAAHPlb and 
ABMT in eradication of minimal residual neuroblastoma. 
1.3 To transduce marker genes into autologous marrow to determine; 
A) Whether the source of marrow disease/relapse after ABMT is residual 
malignant cells in the harvested marrow or residual disease in the 
patient. 
B) The contribution of marrow autografts to autologous reconstitution. 
2.0 BACKGROUND 
2.1 Autologous Bone Marrow Transplantation 
Autologous bone marrow transplantation (ABMT) is increasingly used to treat 
malignant disease. The underlying therapeutic concept is that storage of 
marrow harvested in clinical/bone marrow remission allows the patient 
subsequently to be exposed to chemoradiation that would be lethal were it not 
for the availability of stored autologous marrow for rescue. The hope is that 
the increased dose of chemoradiation will cure a higher proportion of patients 
that would be possible with conventional therapy. In addition, autologous 
bone marrow transplantation may allow the generation of endogenous 
activated killer cells with antineoplastic function. 
2.2 Use of Carboplatin/Etoposide and ABMT in Neuroblastoma 
Although most patients with Stage D neuroblastoma enter remission with 
conventional chemotherapy, more than 80% relapse within 3-5 years. Higher 
doses of effective drugs might improve these results. Both carboplatin and 
etoposide have been combined in a chemotherapy regimen with autologous 
marrow support in a Phase I study conducted at St. Jude Children’s Research 
Hospital from 1989-1990. Thirty patients with various solid tumors (16 
neuroblastoma, 6 medulloblastoma, and 6 brain tumors and 2 non-Hodgkins 
lymphoma) received this drug combination in a dose escalating design. The 
major dose-limiting toxicity was hematologic with severe pancytopenia present 
after a course of therapy. The median time to reach an absolute granulocyte 
count >500/mm^ after ABMT was 28 days (range - 16 to 69). The median 
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Recombinant DNA Research, Volume 14 
