Tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk neuroblastoma: results of SMC NB-2004 study

Bone Marrow Transplant. 2013 Jan;48(1):68-73. doi: 10.1038/bmt.2012.86. Epub 2012 May 28.

Abstract

From January 2004 to December 2008, 50 consecutive patients with high-risk neuroblastoma were assigned to receive tandem HDCT (high-dose chemotherapy)/auto-SCT after nine cycles of induction chemotherapy. CEC (carboplatin + etoposide + cyclophosphamide) regimen and TM (thiotepa + melphalan)-TBI regimen (or TM regimen for stage 3 patients) were the first and second HDCT regimens. Local radiotherapy, differentiation therapy with 13-cis-retinoid acid and immunotherapy with interleukin-2 were given after tandem HDCT/auto-SCT. Of the 50 patients, 49 underwent a first HDCT/auto-SCT and 47 underwent a second HDCT/auto-SCT. The tumor relapsed or progressed in 14 patients, secondary malignancy developed in one patient and one patient died from chronic lung disease. Therefore, 34 patients remained event free with a median follow-up of 54.5 months (range, 14-94 months) from diagnosis. The probabilities of 5-year OS and EFS for all 50 patients were 77.0% (95% confidence interval (CI), 63.7-90.3) and 71.4% (95% CI, 58.7-84.1), respectively. However, all patients who remained event free for >3 years after tandem HDCT/auto-SCT experienced late adverse effects. Chemotherapeutic dose-escalation strategy using tandem HDCT/auto-SCT was very encouraging for survival. However, further studies incorporating newer treatment modalities are needed to reduce late adverse effects without jeopardizing the survival rate.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Neoplasms / diagnosis
  • Bone Neoplasms / pathology
  • Bone Neoplasms / secondary
  • Bone Neoplasms / therapy
  • Child
  • Child, Preschool
  • Combined Modality Therapy / adverse effects
  • DNA Copy Number Variations
  • Feasibility Studies
  • Humans
  • Induction Chemotherapy* / adverse effects
  • Infant
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / adverse effects
  • Interleukin-2 / therapeutic use
  • Isotretinoin / administration & dosage
  • Isotretinoin / adverse effects
  • Isotretinoin / therapeutic use
  • N-Myc Proto-Oncogene Protein
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasm Staging
  • Neuroblastoma / diagnosis
  • Neuroblastoma / pathology
  • Neuroblastoma / secondary
  • Neuroblastoma / therapy*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Prognosis
  • Prospective Studies
  • Radiotherapy / adverse effects
  • Radiotherapy / methods*
  • Stem Cell Transplantation* / adverse effects
  • Survival Analysis
  • Transplantation, Autologous
  • Whole-Body Irradiation / adverse effects

Substances

  • Antineoplastic Agents
  • IL2 protein, human
  • Interleukin-2
  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Neoplasm Proteins
  • Nuclear Proteins
  • Oncogene Proteins
  • Isotretinoin