Deciding on transplant is a very hard decision for families undergoing treatment.  Here are some useful articles and information on treatment for high-risk neuroblastoma (>1 year of age at diagnosis, stage 4 or 3 with MYCN amplification, or unfavorable histopathology) that was helpful for us along the way.

In 1977, Professor Tim McElwain suggested that high dose consolidation chemotherapy might destroy tumor cells resistant to conventional doses of the combination induction treatment then in use for children with advanced neuroblastoma and thereby improve their prognosis.  He chose single agent melphalan in his pilot study.  Since then, several trials have continued to examine the benefit of transplant for neuroblastoma treatment.

Randomized Trials

  • European ENSG-1 – randomized study with 167 Stage III and Stage IV patients enrolled between 1982 and 1985.  Published results showed showed an advantage for ABMT vs. CC.
  • CCG3891 – randomized study with 539 high-risk patients enrolled between 1991 and 1996 (434 Stage IV, 72 Stage III, and 33 other).  Published intial and long-term results showed an advantage in EFS but not OS for ABMT with TBI vs. CC.  Additional reports from this study discussing Stage III, metastatic sites, and radiation were also published.
  • German Cooperative NB97 – randomized study with 295 Stage IV and Stage I-III with MYCN amplification between 1997 and 2002.  Puslished results showed an advantage for ASCT vs. CC.  From 1997 to November 2002, patients received ch14.18 after both ASCT and CC but was stopped afterwards as no positive effect on EFS or OS were demonstrated.  Cis-ra was substituted for ch14.18 from November 2002 until the end of the trial.  Patients with MYCN amplification had an increased EFS from ASCT vs. CC.

Non-Randomnized Trials

  • CCC-321 – non-randomized study with 207 Stage IV patients enrolled between 1985 and 1994. Published results showed an advantage for ABMT vs. CC. However, there were no clear advantages to certain subsets of Stage IV patients.

Following the publication of CCG3891, transplant became the standard of care for the COG.  To build on the positive results, several trials were conducted to see whether adding additional rounds of high dose chemotherapy with stem cell rescue would further improve results.

  • Dana Farber / CHOP Trial (CHP594) – non-randomized study with 39 patients enrolled between 1994 and 1998.  Published initial and long-term results showed a good prognosis for patients undergoing tandem transplants.
  • Chicago Triple Transplant – non-randomized study with 22 patients enrolled between 1995 and 2000.  Published results showed a good prognosis for patients undergoing triple transplants.
  • Atlanta Pilot Study
  • Korean Study
  • European Study

After results from several non-randomized trials suggested that multiple transplants could be an advantage over a single transplant, the COG began testing this in a randomized trial ANBL00532.

In addition to testing whether one or multiple transplants were more effective, several studies also examined the impact of various chemotherapy drugs given as part of the transplant.

  • CCG3891 – used a CEM regime

Currently, most of the world uses stem cell transplant as the standard of care in high-risk neuroblastoma.  The exception is Memorial Sloan-Kettering (“MSKCC”) who has found in its internal data that a stem cell transplant makes no difference in survival for patients treated with antibodies.  In their opinion, 3F8 is just as effective in clearing minimal residual disease as a stem cell transplant.