Tumor growth due to maturation should be differentiated from tumor progression by performing a biopsy and reviewing histology. Patients may have persistent maturing disease with metaiodobenzylguanidine (mIBG) uptake that does not affect outcome. When neuroblastoma recurs in a child originally diagnosed with high-risk disease, the prognosis is usually poor despite additional intensive therapy.[2,3,4,5] However, it is often possible to gain many additional months of life for these patients with alternative chemotherapy regimens.[6,7] Clinical trials are appropriate for these patients and may be offered. Information about ongoing clinical trials is available from the NCI Web site.
The International Neuroblastoma Risk Group Project performed a decision-tree analysis of clinical and biological characteristics (defined at diagnosis) associated with survival after relapse in 2,266 patients with neuroblastoma entered on large clinical trials in well-established clinical trials groups around the world. 
Overall survival (OS) in the entire relapse population was 20%.
Among patients with all stages of disease at diagnosis, MYCN amplification predicted a poorer prognosis, measured as 5-year OS.
Among patients diagnosed with International Neuroblastoma Staging System (INSS) stage 4 without amplification, age older than18 months and high lactate dehydrogenase (LDH) level predicted poor prognosis.
Among patients with MYCN amplification, stages 1 and 2 have a better prognosis than stages 3 and 4.
Among patients with MYCN-nonamplified who are not stage 4, patients with hyperdiploidy had a better prognosis than patients with diploidy in those younger than 18 months, while among those older than 18 months, differentiating tumors did much better than undifferentiated and poorly differentiated tumors.
Significant prognostic factors determined at diagnosis for postrelapse survival include the following:
Time from diagnosis to first relapse.
LDH level, ploidy, and histologic grade of tumor differentiation (to a lesser extent).
The Children's Oncology Group (COG) experience with recurrence in low-risk and intermediate-risk neuroblastoma is that the majority of recurrences can be salvaged. The COG reported a 3-year event free survival (EFS) of 88% and an OS of 96% in intermediate-risk patients and a 5-year EFS of 89% and OS of 97% in low-risk patients.[8,9] Moreover, in most patients originally diagnosed with low-risk or intermediate-risk disease, local recurrence or recurrence in the 4S pattern may be treated successfully without hematopoietic stem cell transplantatio.