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, diarrhea, electrolyte 
abnormalities, elevations of hepatic transaminases and serum creatinine. The 
non-hematologic drug limiting toxicity was mucositis. 
Although this was primarily a Phase I study, antitumor responses were noted. 
There was one complete remission lasting 373 days and 16 partial remissions. 
In this study we propose to estimate the efficacy and further characterize the 
toxicity of carboplatin/ etoposide and autologous marrow support in pediatric 
patients currently in remission of stage D (disseminated) neuroblastoma. 
In addition, we plan to use gene marking of an aliquot of the harvested 
marrow to study the mechanism of relapse and of autologous reconstitution. 
2.3 Mechanism of Relapse 
Although ABMT may offer advantages over conventional chemotherapy, the 
major cause of treatment failure remains relapse or disease progression. When 
ABMT is undertaken for solid tumors, relapse is generally at the site of 
original disease, implying that supralethal chemo-radiotherapy has not 
eradicated the malignancy. The mechanism of relapse is less clear following 
ABMT for malignancies such as neuroblastoma which may involve the BM. 
As the incidenee and rapidity of relapse in these diseases is often greater after 
autologous BMT than it is after allogeneic marrow transplantation, two 
explanations have been offered. The first is that the alloreactive T 
lymphocytes present in allogeneic marrow have a major role in recognition and 
elimination of residual host malignant cells. Since these cells are absent from 
autologous marrow, relapse is more likely after autologous BMT. This 
explanation suggests that relapse occurs for the same reason as relapse after 
ABMT for marrow sparing solid tumors - persistence of residual disease in the 
host. An alternative explanation is that even though cryopreserved autologous 
marrow is harvested in remission, it nonetheless contains residual malignant 
cells. In this case, relapse is due to residual disease not in the host, but in the 
rescuing marrow . It is likely that both factors contribute to relapse, although 
the relative contribution of each in any given disease is unknown. 
The mechanism of relapse following ABMT for malignancy derived from or 
involving the marrow is an important issue to resolve. The fear that stored 
marrow contains residual malignant cells has led to intensive investigation of 
the value of marrow purging prior to storage and subsequent reinfusion. 
Purging may be undertaken with monoclonal antibodies, with cytotoxic agents 
Recombinant DNA Research, Volume 14 
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