Background: The INES 99.4 trial (JCO 2009,27(7):1014-9) for MYCN amplified (MNA) infants using 6 courses of CBDCA-Vp16/CADO showed early progressions or non-response in 30%. Two-year overall survival (OS) was 30% (SE, 0.08) with median survival of 12 months. Aims are to report risk factors and outcomes for patients < 18 months with MNA neuroblastoma treated on HR-NBL1/SIOPEN. Methods: From 2006-2022, patients < 18 months with MNA INSS stages > 1 were eligible. All infants received Rapid Cojec induction, eventually 2 TVDs, Busulfan-Melphalan as high-dose treatment and could receive Dinutuximab- beta immunotherapy. Toddlers (12-18 months) followed the HR-NBL1/SIOPEN respective eligibility criteria. Results: Median age at diagnosis was 1.2 years in 414 patients (median follow up 7 years): 56% were male; 18.6% had localised tumours, 6.8% stage 4S and 75% stage 4. The predominant primary tumour site was abdominal (85%). Rapid Cojec was used in 85%, BUMEL in 89% and 26% received Dinutuximab-beta. Multiple metastatic compartments were reported in 82% of stage 4. Five-year event-free (5y-EFS) and overall survival (5y-OS) was 0.46±0.03 and 0.51±0.03. Stage 2,3&4S patients had a better 5y-EFS of 0.64±0.03 (p < 0.005) (5y-OS:0.66±0.06), compared to stage 4 with 0.41±0.03 (OS:0.46±0.03). Infants’ 5y-EFS was superior with 0.53±0.04 (5y-OS:0.57±0.04) (p = 0.015) over the toddlers with 5y-EFS 0.42±0.03 (5y-OS:0.46±0.03). Patients with bone marrow (BM) and skeletal metastases ± other sites (MS) did worse (p < 0.005) with a 5y-EFS of 0.31±0.04 (5y-OS:0.36±0.04) whilst other metastatic combinations revealed outcomes above 0.50 ±0.03. LDH (2x > normal) predicted a worse 5y-EFS of 0.43±0.03 (5y-OS:0.46±0.03) (p < 0.001) versus normal LDH (5y-EFS 0.71±0.07; 5y-OS:0.80±0.06). EFS multivariable analysis at diagnosis (MVA) showed independent significance for stage 4 (p-value 0.0139; HR: 1.608) and LDH (p-value 0.0042; HR: 2,237), but not for age. In stage 4 patients MVA on EFS found LDH (p-value 0.0098; HR: 2,567) and BM/skeleton involvement (p-value 0.0024; HR: 1,693) as independent risk predictors. In maintenance Dinutuximab-beta had a major impact on 5y-EFS in stage 4 patients with 0.69±0.05(5y-OS:0.71±0.05) vs. 0.41±0-07 (0.46±0.07) for those treated with 13-cis retinoic acid (p = 0.002 & p = 0.001), but not on others. Conclusions: In HR-NBL1/SIOPEN outcomes improved with almost half of patients alive at 5 years and only few late events. Clinical trial information: NCT01704716.