1.0 OBJECTIVES 
1.1 To establish the response rate and further characterize the toxicity of high- 
dose carboplatin (CBDCA) and etoposide (VP-16) with autologous marrow 
support in previously treated pediatric patients with recurrent or refractory 
neuroblastoma. 
1.2 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 
Both of these agents 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 time to reach a platelet count ^50,000/mm^ was 30 days 
(range - 15 to 56). Twelve patients received a second course of identical 
therapy with similar times to engraftment and without evidence of cumulative 
toxicity. Other less frequently seen toxicides included mucositis, nausea. 
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Recombinant DNA Research, Volume 14 
