Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of new strategies for dose intensification using peripheral blood stem cell or autologous purged bone marrow rescue has raised expectations for cure in advanced neuroblastoma, although conflicting reports exist regarding the efficacy of these approaches. Using risk groups based on both biological and clinical staging, the Children's Cancer Group (CCG) has conducted a series of pilot studies to test new induction, consolidation and myeloablative regimens to attempt to improve outcome. We summarise below the outcome and prognostic factor analysis for the pilot chemotherapy trial, CCG-(CCG-321P2), and the use of high dose myeloablative chemoradiotherapy with allogeneic (CCG-321P1) or autologous purged bone marrow rescue (CCG-321P3) for high risk neuroblastoma patients who were progression-free at the end of induction chemotherapy. After autologous bone marrow transplantation (ABMT), progression-free survival (PFS) at 4 years was 38% (median follow-up 4 years). Prognostic factors for relapse after ABMT included pre-BMT disease status, bone marrow tumour content at harvest, extent of primary resection at diagnosis, and time to ABMT. MYCN amplification, age, stage, and pre-BMT myeloablative regimen were not significant. Allogeneic BMT did not have a better outcome than ABMT. In a retrospective, non-randomised comparison of ABMT and chemotherapy, there was a significant difference in PFS for stage IV patients. High risk subgroups possibly benefiting from ABMT could be identified, including those with tumour MYCN amplification, over 2 years at diagnosis, and those not in complete remission at the end of induction. A randomised prospective trial comparing myeloablative therapy with ABMT to continuous infusion consolidation chemotherapy is currently underway in CCG to determine the relative benefit.
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PMID:Role of myeloablative therapy in improved outcome for high risk neuroblastoma: review of recent Children's Cancer Group results. 757 71

To determine whether neuroblastomas acquire a sustained drug-resistant phenotype from exposure to chemotherapeutic agents given to patients in vivo, we studied neuroblastoma cell lines established at different points of therapy: six at diagnosis before therapy (DX), six at progressive disease during induction therapy (PD-Ind), and five at relapse after intensive chemoradiotherapy and bone marrow transplantation (PD-BMT). Cells were maintained in the absence of drug selective pressure. Dose-response curves of melphalan, cisplatin, carboplatin, doxorubicin, and etoposide for the cell line panel were determined by measuring cytotoxicity with a 96-well-plate digital imaging microscopy (DIMSCAN) microassay. Drug resistance of cell lines progressively increased with the intensity of therapy delivered in vivo. The greatest resistance was seen in PD-BMT cell lines: IC90 values in PD-BMT cell lines were higher than clinically achievable drug levels by 1-37 times for melphalan, 1-9 times for carboplatin, 25-78 times for cisplatin, 6-719 times for doxorubicin, and 3-52 times for etoposide. Genomic amplification of MYCN did not correlate with resistance. Cross-resistance by Pearson correlation (r > or = 0.6) was observed between: (a) cisplatin + doxorubicin; (b) carboplatin + cisplatin, etoposide, or melphalan; (c) etoposide + cisplatin, melphalan, or doxorubicin. These data indicate that during therapy, neuroblastomas can acquire resistance to cytotoxic drugs because of the population expansion of tumor cells possessing stable genetic or epigenetic alterations that confer resistance.
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PMID:Drug resistance patterns of human neuroblastoma cell lines derived from patients at different phases of therapy. 985 71