Trial Information

Tandem High-dose Chemotherapy and Autologous Stem Cell Rescue in Patients With High-risk Neuroblastoma

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.