Pre-IDE Submission: Clinical Protocol 
Neuroblastoma Bone Marrow Purging System 
BAXTER HEALTHCARE CORPORATION, HYLAND DIVISION 
6. 1.1.4 Mechanism of Relapse 
Although autologous bone marrow transplantation (ABMT) may offer advantages over 
conventional chemotherapy, the major cause of treatment failure in neuroblastoma 
remains relapse or disease progression. When ABMT is used for solid tumors, relapse 
generally occurs at the site of the original disease, implying that supra-lethal 
chemo-radiotherapy has not eradicated the primary tumor, or that the disease 
preferentially reseeds to the site of the primary. 
The mechanism of relapse following ABMT is less clear for malignancies such as 
neuroblastoma which often involve the bone marrow (Moss et al, 1991). Two 
mechanisms have been proposed. The first is based on the observation that relapse is 
more frequent in patients who have received autologous, as opposed to allogeneic 
transplants. It is thought that alloreactive T lymphocytes present in the allogeneic bone 
marrow play a major role in eradicating residual tumor cells in the recipient. Since these 
cells are absent in autologous marrow, the higher relapse rate in ABMT patients may be 
due to the absence of this antitumor lymphocytic response. 
An alternative explanation is that, even though the autologous marrow is harvested when 
the patient is in clinical remission, it nonetheless contains residual malignant cells. 
Disease relapse may originate from these cells. Three reports attribute fatal pulmonary 
relapse following ABMT with unpurged marrow to the presence of neuroblastoma cells 
in the graft (Glorieux et al, 1986; Graeve et al, 1988). 
The introduction of immunocytological testing, which can detect 1 tumor cell among 
100,000 hematopoietic cells, has greatly improved the sensitivity of detecting marrow 
involvement (Moss et al, 1991). Using this method an additional 15-20% of patients are 
found to have marrow disease at diagnosis, and 40-50% are positive for tumor 
involvement after induction therapy for marrow harvest (Moss et al, 1991). The clinical 
significance of these persistent tumor cells has not yet been determined. However, it is 
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Recombinant DNA Research, Volume 16 
