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Long-term follow-up of high-risk neuroblastoma survivors treated with high-dose chemotherapy and stem cell transplantation rescue

Bone Marrow Transplantation volume 56, pages 1984–1997 (2021)Cite this article

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Abstract

Intensive treatments including high-dose chemotherapy (HDC) with autologous stem cell rescue have improved high-risk neuroblastoma (HRNB) survival. We report the long-term health status of 145 HRNB survivors, alive and disease-free 5 years post HDC. Median follow-up was 15 years (range = 5–34). Six patients experienced late relapses, 11 developed second malignant neoplasms (SMNs), and 9 died. Event-free and overall survivals 20 years post HDC were 82% (95% CI = 70%–90%) and 89% (78%–95%), respectively. Compared with the French general population, the standardized mortality ratio was 19 (95% CI = 8.7–36.1; p < 0.0001) and the absolute excess risk was 37.6 (19.2–73.5). Late effects were observed in 135/145 patients (median = 3 events/patient); 103 had at least one severe event. SMNs arose at a median of 20 years post HDC and included carcinoma (n = 5), sarcoma (2), acute myeloid leukemia (2), melanoma (1), and malignant glioma (1). Non-oncologic health events included dental maldevelopment (60%), severe hearing loss (20% cumulative probability at 15 years), hepatic focal nodular hyperplasia (14%), thyroid (11%), cardiac (8%), and renal (7%) diseases and growth retardation (height-for-age z-score ≤ −2 for 21%). Gonadal insufficiency was near-universal after busulfan (40/43 females, 33/35 males). Severe late effects are frequent and progressive in HRNB survivors needing systematic very long-term follow-up.

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Fig. 1: Participants flow diagram.
Fig. 2: Event-free and overall survival (EFS and OS) Kaplan–Meier curves of the 145 patients included in this study (patients treated for neuroblastoma with highdose chemotherapy followed by autologous stem cell rescue, ASCR, at Gustave Roussy in 1980–2012, alive and disease-free at 5-year post transplant).
Fig. 3: Cumulative probability curves of second health events.

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Acknowledgements

We acknowledge Lucy Metayer (MD) for her proofreading and editing work and Juliana Ollivier (psychology student) for data collection on psychological interviews.

Funding

The Gustave Roussy Foundation, The French Ligue Against Cancer (“Equipe Labélisée” Program), The Fondation ARC (POPHARC program), and The French National Research Agency (ANR, HOPE-EPI project).

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Authors and Affiliations

  1. Département de Cancérologie de l’Enfant et de l’Adolescent, Gustave Roussy, Villejuif, France

    Sandrine Haghiri, Chiraz Fayech, Christelle Dufour, Claudia Pasqualini, Dominique Valteau-Couanet & Brice Fresneau

  2. Université Paris-Saclay, Inserm, Epidémiologie des radiations, CESP, Villejuif, France

    Imène Mansouri, Amel Boumaraf, Amel Belhout, Neige Journy, Vincent Souchard, Giao Vu-Bezin, Cristina Veres, Nadia Haddy, Florent De Vathaire & Brice Fresneau

  3. Département de Radiothérapie Oncologique, Gustave Roussy, Villejuif, France

    Stéphanie Bolle & Cristina Veres

  4. Unité de Psycho-Oncologie, Gustave Roussy, Villejuif, France

    Sophie Rivollet

  5. Université de Paris, Inserm, ECEVE UMR 1123, Paris, France

    Agnès Dumas

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Haghiri, S., Fayech, C., Mansouri, I. et al. Long-term follow-up of high-risk neuroblastoma survivors treated with high-dose chemotherapy and stem cell transplantation rescue. Bone Marrow Transplant 56, 1984–1997 (2021). https://doi.org/10.1038/s41409-021-01258-1

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