Busulphan-melphalan as a myeloablative therapy (MAT) for high-risk neuroblastoma: Results from the HR-NBL1/SIOPEN trial.

• DOI: 10.1200/jco.2011.29.18_suppl.2
• Publication Date: 2017-02-23T18:42:09Z
• Authors: R. L. Ladenstein; U. Poetschger; R. Luksch; P. Brock; V. Castel; I. Yaniv; V. Papadakis; G. Laureys; J. Malis; W. Balwierz; E. Ruud; P. Kogner; H. Schroeder; A. Forjaz De Lacerda; M. Beck Popovic; P. Bician; M. Garami; T. Trahair; A. D. Pearson; D. Valteau Couanet
• Keywords: Melphalan; Carboplatin

2 Background: The HR-NBL1 trial of the European SIOP Neuroblastoma Group randomised MAT regimens with primary aim to demonstrate superiority based on event free survival (EFS). Methods: At randomisation closure, 1,577 high-risk neuroblastoma patients (944 males) had been included since 2002; INSS stage 4 disease (1,369 pts) > 1 year, infants (65 and II III (143 any age MYCN amplification. Response eligibility criteria prior after Rapid COJEC Induction (J Clin Oncol, 2010) ± courses TVD (Cancer, 2003) complete bone marrow remission ≤ 3, but improved, mIBG positive spots. were BuMel (oral busulfan till 2006, 4x150mg/m in equal doses, or 2006 intravenous use according body weight melphalan 140mg/m /day) CEM (carboplatin ctn. infusion [4xAUC 4.1mg/ml.min/day], etoposide [4x338mg/m day 4x200mg/m /day*], [3x70mg/m /day 3x60mg/m /day*. *reduced if GFR<100ml/min/1.73m ]). A minimum 3x10E6 CD34/kgBW PBSC requested. VOD prophylaxis ursadiol, not prophylactic defibrotide. Local control surgery radiotherapy 21 Gy. total 598 (296 BuMel, 302 CEM). median at was 3 years (1-17.2) a follow up years. Results: last analysis, Peto rule p<0.001 met. significant difference EFS favour (3-years 49% vs 33%) observed as well for overall OS 60% 48%, p=0.004). This mainly related relapse progression incidence, which significantly (p<0.001) lower (48% 60%). severe toxicity rate 100 (ICU toxic deaths) below 10%, higher (p=0.014). acute death 3% 5% (NS). profile favours regimen spite incidence 18% (grade 3:5%). Based these results following advice from DMC, closed early. Conclusions: demonstrated be superior hence is recommended standard treatment.