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?

Abstract

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.

The LMCE5 unselected cohort of 25 children consecutively diagnosed with untreated stage 4 neuroblastoma over 1 year at diagnosis

“…There was no difference on univariate analysis between patients in CR-VGPR after induction vs others, nor those who had cleared their skeletal uptake after induction therapy, nor those more or less than 2 years old at diagnosis. These results compare with a similar cohort of 72 patients previously reported by our group (LMCE1 8% of PFS at 14 years) (Philip et al, 1991). However, it is worse than the cohort of 99 patients included in LMCE3 study: 29% at 7 years from diagnosis: P50.07 (Figure 2) (Frappaz et al, 2000).…”

“…The aim of these studies was to enrol every child presenting with metastatic neuroblastoma in each of the participating institutions and in this way to report unbiased series. The LMCE1 study reported a cohort of 72 children, who received standardised induction and megatherapy (Philip et al, 1987(Philip et al, , 1991. It demonstrated that after induction, the subgroup of children who showed persistent signs of metastases on bone scan had significantly shorter survival.…”

“…The Lyon-Marseille-Curie East of France group (LMCE) previously published the LMCE1 and LMCE3 studies. These concerned unselected cohorts of children successively seen at diagnosis with metastatic NB (Philip et al, 1987(Philip et al, , 1991Frappaz et al, 2000). The LMCE1 used a single strategy: all patients received similar induction chemotherapy followed by surgery and a vincristine -melphalan -Total Body Irradiation (TBI) consolidation regimen in chemosensitive patients (Philip et al, 1987(Philip et al, , 1991.…”

“…These concerned unselected cohorts of children successively seen at diagnosis with metastatic NB (Philip et al, 1987(Philip et al, , 1991Frappaz et al, 2000). The LMCE1 used a single strategy: all patients received similar induction chemotherapy followed by surgery and a vincristine -melphalan -Total Body Irradiation (TBI) consolidation regimen in chemosensitive patients (Philip et al, 1987(Philip et al, , 1991. This study and the report of the European Bone Marrow Transplantation Study Group suggested that clearance of skeletal uptake on bone scan after induction therapy defines a better prognosis subgroup that contains 40% of the population and have a 40% PFS at 5 years (versus 10%).…”

Central nervous system metastases in neuroblastoma

“…5 Patients who had incomplete responses received subsequent consolidation therapy with carboplatin. Patients without disease progression received high-dose chemotherapy regimens, which contained either melphalan, total body irridation (TBI), and vincristine 6 or melphalan and busulfan 7 , followed by HSCT.…”