ROLE OF MYELOABLATIVE THERAPY IN IMPROVED OUTCOME FOR HIGH-RISK NEUROBLASTOMA - REVIEW OF RECENT CHILDRENS CANCER GROUP RESULTS

The use of new strategies for dose intensification using peripheral bl ood stem cell or autologous purged bone marrow rescue has raised expec tations for cure in advanced neuroblastoma, although conflicting repor ts 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 induct ion, consolidation and myeloablative regimens to attempt to improve ou tcome. We summarise below the outcome and prognostic factor analysis f or the pilot chemotherapy trial, CCG-(CCG-321P2), and the use of high dose myeloablative chemoradiotherapy with allogeneic (CCG-321P1) or au tologous purged bone marrow rescue (CCG-321P3) for high risk neuroblas toma patients who were progression-free at the end of induction chemot herapy. After autologous bone marrow transplantation (ABMT), progressi on-free survival (PFS) at 4 years was 38% (median follow-up 4 years). Prognostic factors for relapse after ABMT included pre-BMT disease sta tus, bone marrow tumour content at harvest, extent of primary resectio n 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-randomis ed comparison of ABMT and chemotherapy, there was a significant differ ence in PFS for stage IV patients. High risk subgroups possibly benefi ting from ABMT could be identified, including those with tumour MYCN a mplification, over 2 years at diagnosis, and those not in complete rem ission at the end of induction. A randomised prospective trial compari ng myeloablative therapy with ABMT to continuous infusion consolidatio n chemotherapy is currently underway in CCG to determine the relative benefit.