Tandem High-dose Chemotherapy and Autologous Stem Cell Rescue in Patients With High-risk Neuroblastoma
Tandem High-dose Chemotherapy and Autologous Stem Cell Rescue in Patients With High-risk Neuroblastoma
The purpose of this study is to evaluate the efficacy and toxicity of tandem HDCT/ASCR in
 children with high-risk neuroblastoma. In the present study, a single arm trial of tandem
 HDCT/ASCR will be carried out. In the present study, the investigators will investigate
 whether tandem HDCT/ASCR might improve the survival of patients with high-risk neuroblastoma
 with acceptable toxicity.
The prognosis of high-risk neuroblastoma after conventional chemoradiotherapy is generally
 poor. Therefore, a strategy using high-dose chemotherapy and autologous stem cell rescue
 (HDCT/ASCR) has been explored to improve the prognosis of patients with high-risk
 neuroblastoma. This strategy is based on the hypothesis that dose escalation might improve
 the survival of children with high-risk neuroblastoma. The results of randomized trials
 comparing HDCT/ASCR with chemotherapy alone showed a better event-free survival (EFS) in the
 HDCT/ASCR arm than in the continuous chemotherapy arm. However, the overall EFS was
 unsatisfactory.

 In this context, investigators have examined the efficacy of double or triple tandem
 HDCT/ASCR to further improve the outcome of high-risk neuroblastoma patients. George et al.
 carried out a single arm trial of tandem transplantation as consolidation therapy, and
 reported improved long-term survival (5-year progression-free survival 47%) with acceptable
 toxicity. Kletzel et al. also conducted a single arm trial of triple tandem transplantation
 and reported improved survival (3-year EFS 57%). They demonstrated that further dose
 escalation using sequential HDCT/ASCR might result in further improvements in the survival of
 patients with high-risk neuroblastoma.

 Investigators in the present study also carried out tandem transplantation as consolidation
 therapy, and reported improved long-term survival (5-year progression-free survival 62%) with
 acceptable toxicity. However, throughout our previous study, multiple modifications were made
 in the treatment plan, which resulted in significant variability over time between patients.
 This variability may create doubt as to whether tandem HDCT/ASCR itself resulted in the
 improved outcome. In addition, toxic death rate was relatively high (15.4%), although final
 survival rate was very high (best survival rate ever reported). Therefore, prospective study
 is needed to evaluate the efficacy and toxicity of tandem HDCT/ASCR.
Inclusion Criteria:

 -  Patients with high-risk neuroblastoma

 -  Patients with intermediate-risk neuroblastoma if gross tumor remained after surgery

 Exclusion Criteria:

 -  Patients with progressive disease before high-dose chemotherapy

 -  Patients whose parents want to stop or change the planned treatment

 -  Patients with organ toxicities of NCI grade >2 before high-dose chemotherapy