Pre-IDE Submission: Clinical Protocol 
Neuroblastoma Bone Marrow Purging System 
BAXTER HEALTHCARE CORPORATION, HYLAND DIVISION 
patients in this study will receive unpurged as well as purged 
marrow, and because most or all patients will receive growth 
factors, it is likely that our average time to marrow recovery will 
be less than 43 days. Due to the small sample size, however, it 
is likely that statistical comparisons will not be informative. 
Efficacy End Points: 
(3) As indicated previously, preclinical studies have established the 
ability of immunomagnetic purging to remove 3-4 logs of tumor 
cells from mononuclear cell suspensions. In the clinical setting, 
the administration of a bone marrow graft containing 1 x 10 8 
nucleated cells per kg body weight for a 60 kg individual would 
involve 6 x 10 9 nucleated cells. In order to demonstrate a 3 log 
reduction of tumor cells with the most sensitive assay currently 
available (by immunocytology, 1 tumor cell in 100,000 bone 
marrow cells), the above graft would have to be contaminated with 
a minimum of 6 x 10 7 tumor cells. Although a proportion of 
harvested marrows is expected to be positive by immunocytology 
following induction therapy (30-40% of new patients and about 
80% of relapse patients), the level of infiltration is normally 
significantly below the levels indicated above. Due to this usually 
low infiltration of tumor cells into bone marrow following 
induction therapy, as well as the intent to render patients negative 
by routine histology prior to transplantation, statistical validation 
of device performance (removal of 3-3.5 logs of tumor cells) is not 
possible with the current sensitivity of tumor cell detection. 
In those marrows negative by routine histology, but positive by 
immunocytology, performance of the device will be demonstrated 
by removal of tumor cells to undetectable levels at the sensitivity 
Recombinant DNA Research, Volume 16 
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