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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

Bone Marrow Transplantation volume 56, pages 2173–2182 (2021)Cite this article

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Abstract

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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Acknowledgements

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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Authors and Affiliations

  1. Department of Hematology/Oncology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan

    Yuya Saito & Yuki Yuza

  2. Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan

    Yuya Saito & Mitsuyoshi Urashima

  3. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yoshiyuki Takahashi

  4. Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, Japan

    Atsushi Ogawa

  5. Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan

    Chikako Kiyotani & Kimikazu Matsumoto

  6. Department of Hematology/Oncology, Saitama Children’s Medical Center, Saitama, Japan

    Katsuyoshi Koh

  7. Department of Hematology and Oncology, Shizuoka Children’s Hospital, Shizuoka, Japan

    Kenichiro Watanabe

  8. Department of Hematology and Oncology, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan

    Yoshiyuki Kosaka

  9. Division of Hematology/Oncology, Kanagawa Children’s Medical Center, Yokohama, Japan

    Hiroaki Goto

  10. Department of Pediatric Oncology, Fukushima Medical University Hospital, Fukushima, Japan

    Atsushi Kikuta

  11. Department of Pediatric Hematology/Oncology, Osaka City General Hospital, Osaka, Japan

    Keiko Okada

  12. Department of Pediatrics, Kyushu University Hospital, Fukuoka, Japan

    Yuhki Koga

  13. Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan

    Junya Fujimura

  14. Department of Hematology/Oncology, Osaka Women’s and Children’s Hospital, Osaka, Japan

    Masami Inoue

  15. Department of Hematology and Oncology, Miyagi Children’s Hospital, Sendai, Japan

    Atsushi Sato

  16. Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yoshiko Atsuta

  17. Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan

    Yoshiko Atsuta

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  1. Yuya Saito
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Contributions

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). https://doi.org/10.1038/s41409-021-01303-z

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