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Improved survival at 2 and 5 years in the LMCE1 unselected group of 72 children with stage IV neuroblastoma older than 1 year of age at diagnosis: is cure possible in a small subgroup?

The objectives of this study were to determine (1) the role of selection before bone marrow transplantation (BMT), (2) the role of vincristine, melphalan, and total body irradiation (TBI) as consolidation of induction therapy for stage IV over 12 months at diagnosis, and (3) the role of immunomagnetic purging in metastatic neuroblastoma. Among 72 consecutive unselected patients, 10 were not grafted (four died at induction: two in complete remission [CR], two in partial remission [PR]); three had bone marrow progression before harvest; one had uncontrolled progression; and two had parental refusal). Sixty-two patients were grafted (23 in CR/very good PR [VGPR] and 39 in PR). Among the 62, 33 were consolidated with at least 90% excision of their initial tumor excised (53.2%), 15 with catecholamine secretions (24.2%), 22 with minor bone marrow involvement (35.5%), and 31 with positive bone scan (50%). Median observation time is 59 months. Progression-free survival (PFS) for the 10 excluded patients was 20% at 2 years and 0% at 4 years. PFS for the grafted population (n = 62) is 40% at 2 years, 20% at 4 years, and 13% at 7 years. No difference was observed between patients grafted in CR/VGPR or in PR. However, a group of 19 children was grafted resulting in complete normalization of metastasis (regardless of primary-site tumor status). In this group, PFS at 59 months was 38% with no relapses up to 7 years post-BMT. A group of 31 patients with no bone involvement at BMT was also identified. PFS at 5 years is 30% compared with 12% for bone-positive patients at BMT. Moreover, the 11 children presenting at diagnosis with no bone involvement (Evans stage IVS or stage C Memphis) and consolidated with BMT had PFS at 5 years of 50% with no late relapses. A subgroup of stage IV neuroblastoma patients older than 1 year of age at diagnosis may be curable with this therapeutic approach, and the use of multivariate analyses to search for prognostic factors is warranted in currently existing international registries.