Pergamon European~~~lofCancerVol.31A,No.4,pp.572-575,1995 Elsevier Science Ltd Primed in Great Britain Role of Myeloablative Therapy in Improved Outcome for High Risk Neuroblastoma: Review of Recent Children’s Cancer Group Results K.K. Matthay, M.C. O’Leary, N.K. Ramsay, J. Villablanca, C.P. Reynolds, J.B. Atkinson, G.M. Haase, D.O. Stram and R.C. Seeger zyxwvutsrqponmlkjihgfedc 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-321Pl) 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. zyxwvutsrqponmlkjihgfedcba 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. Keywords: neuroblastoma, bone marrow transplantation, prognostic factors, allogeneic, autologous zyxwvutsrqponmlkji EurJ Cancer, Vol. 31A, No. 4, pp. 572-575,1995 INTRODUCTION MYELOABLATIVE therapy followed by bone marrow or peripheral blood stem cell rescue is under extensive investigation for treatment of childhood high risk neuroblastoma, because of the persistently dismal outcome with conventional chemotherapy [l]. Some previous reports of such treatment, using either allogeneic or autologous bone marrow transplantation (BMT), Correspondence to K.K. Matthay. K.K. Matthay is at the Department of Pediatrics, University of Cahfor- nia, San Francisco, California 94143; M.C. O’Leary is at the Department of Pediatrics, Minneapolis Children’s Medical Center, Minneapolis, Minnesota 55404; N.K. Ramsay is at the University of Minnesota School of Medicine, Minneapolis 55455; G.M. Haase is at the Department of Surgery, Children’s Hospital, Denver, Colorado; D.O. Stram is at the Department of Preventive Medicine, C.P. Reynolds is at the Department of Pathology, R.C. Seeger and J. Villablanca are at the Department of Pediatrics; and J.B. Atkinson is at the Department of Surgery, Univer- sity of Southern California and Children’s Hospital, Los Angeles, and Children’s Cancer Group, Arcadia, California 91066, U.S.A. have suggested an improved outcome compared with historical patients treated with standard chemotherapy [2-71. However, no prospective randomised trial has yet been com- pleted to control for bias in patient selection. In addition, the necessity for bone marrow purging to remove autologous tumour cells and the relative benefits of autologous compared with allogeneic BMT have not been elucidated. These issues will be examined below in the context of three recent concomitant Children’s Cancer Group (CCG) pilot studies for high risk neuroblastoma: CCG-321P2 using combination chemotherapy for 1 year, CCG-321Pl using myeloablative chemoradiotherapy and allogeneic BMT, and CCG-321P3, using myeloablative chemotherapy and autologous purged BMT. PATIENTS AND METHODS Three pilot studies were open to high risk neuroblastoma from CCG institutions, including CCG-321P2, open to accrual from 18 September 1986 to 1 February 1991; CCG-321P1, open to accrual from 10 February 1986 to 3 October 1991, and CCG- 572