Late effects in high-risk neuroblastoma survivors treated with high-dose chemotherapy and stem cell rescue

Pediatr Blood Cancer. 2019 Jan;66(1):e27421. doi: 10.1002/pbc.27421. Epub 2018 Aug 27.

Abstract

Background: Current treatment strategies have improved the outcome of high-risk neuroblastoma (HRNB) at the cost of increasing acute and late effects of treatment. Although high-dose chemotherapy with stem cell rescue (HDC-SCR) has replaced total body irradiation (TBI) based HRNB therapy, late effects of therapy remain a significant concern.

Objectives: To describe late effects prevalence, severity, and risks after HDC-SCR.

Methods: Retrospective chart review of relapse-free HRNB survivors ≥1 year after single HDC-SCR between 2000 and 2015 at Fred Hutchinson Cancer Research Center.

Results: Sixty-one survivors (30 males) were eligible. Median age (years) at SCR was 3.5 years (range 0.7-27 years) and median posttransplant follow-up was 5.4 years (1.2-16.3 years) . Fifty-three (86.9%) survivors developed late effects that increased over time (P < 0.001) and varied in severity from grade 1 (35) to grade 5 (1). These were unrelated to gender or age. High-frequency hearing loss seen in 82% of survivors was the most common abnormality present and 43% of those required hearing aids. Seventeen (27.9%) survivors developed dental late effects and these were most common in children <2 years of age at transplant (P = 0.008). Other toxicities included endocrine (18%), orthopedic (14.8 %), renal (3.9%), melanotic nevi (8.2%), neuropsychological impairments (8.2%), subsequent malignancies (4.9%), pulmonary (4.9%), cardiac (4.9%), and focal nodular liver hyperplasia (3.3%). At 9 years posttransplant, the median height and weight Z-scores were significantly lower than Z-scores at the time of HDC-SCR (-0.01/-1.08, P < 0.001; -0.14/-0.78, P = 0.005).

Conclusion: Avoidance of TBI does not mitigate the need to provide diligent, ongoing surveillance for late effects.

Keywords: high-dose chemotherapy; late effects; neuroblastoma.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Cancer Survivors / statistics & numerical data*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Disease Progression
  • Endocrine System Diseases / etiology*
  • Female
  • Follow-Up Studies
  • Growth Disorders / etiology*
  • Humans
  • Induction Chemotherapy
  • Infant
  • Male
  • Neuroblastoma / therapy*
  • Prognosis
  • Retrospective Studies
  • Stem Cell Transplantation / adverse effects*
  • Survival Rate
  • Transplantation, Autologous
  • Young Adult