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Effect of high-dose chemotherapy plus stem cell rescue on the survival of patients with neuroblastoma modified by MYCN gene gain/amplification and remission status: a nationwide registration study in Japan


In high-risk neuroblastoma, the presence of an MYCN gain/amplification (MYCN-GA) is not always a risk factor of cancer-specific death. We herein examined the effect modification of high-dose chemotherapy with autologous hematopoietic stem cell rescue (HDC-autoSCR) in terms of the interaction between MYCN status and remission status (complete remission or very good partial remission [CR/VGPR] vs. partial remission or less [≤PR]). The present study recruited patient data from 1992 to 2017 in the Japan Society of Hematopoietic Cell Transplantation’s national registry. The MYCN status was known in 586 of 950 patients with a single course of HDC-autoSCR. Cumulative hazard curves for neuroblastoma-specific death showed that a subgroup with MYCN-GA and ≤PR had a significantly poorer prognosis than three other subgroups, namely, the MYCN-NGA/ ≤ PR, MYCN-NGA/CR/VGPR, and MYCN-GA/CR/VGPR subgroups even after adjusting for non-infants and stage IV disease (hazard ratio: 2.79; 95% confidence interval: 1.91–4.09; P < 0.001). The interaction between MYCN-GA and ≤PR was significant (pinteraction = 0.006). Hence, the patients with MYCN-GA with non-remission status at HDC-autoSCR had a significantly poorer prognosis than the other subgroups, suggesting that HDC-autoSCR may be effective in patients with CR/VGPR regardless of MYCN gene status and in patients with MYCN-NGA regardless of remission status.

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Fig. 1: Flow-chart of study inclusion.
Fig. 2: Effect of remission status.
Fig. 3: Effect of remission status and MYCN status.
Fig. 4: Effect of remission status and MYCN status in patients with non-stage IV neuroblastoma.
Fig. 5: Effect of remission status and MYCN status in non-infant patients with stage IV neuroblastoma.


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We thank Mr. James Robert Valera for his assistance with editing the paper. We thank all the clinicians and hospital and health center staff who provided us with valuable data from the Japan Society for Hematopoietic Cell Transplantation registry.

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Drafting of the paper: YS. Conception and design: YS, KM, YT. Data analysis and interpretation: YS, KM, YT, MU. Data collection and critical revision: CK, YY, KK, KW, YK, HG, AK, KO, YK, JF, MI, AS, YA.

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Correspondence to Yuya Saito.

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Saito, Y., Urashima, M., Takahashi, Y. et al. Effect of high-dose chemotherapy plus stem cell rescue on the survival of patients with neuroblastoma modified by MYCN gene gain/amplification and remission status: a nationwide registration study in Japan. Bone Marrow Transplant 56, 2173–2182 (2021).

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