Outcome
The median follow-up duration of all living patients was 9.2 years
(range = 5.5–14.0 years). During this period, 20 patients relapsed. Of
those 20 patients, 1 developed secondary myelodysplastic syndrome 13
years after the initial treatment for high-risk neuroblastoma. The
5-year EFS and overall survival (OS) rates from treatment initiation
were 41.5% ± 7.7% and 56.1% ± 7.8%, respectively (Figure
1 ). The outcomes were not significantly different between the three
institutions. Although 15 patients needed dose reduction of thiotepa and
melphalan according to their Ccr results, the outcomes were not
significantly different (Supporting Information Figure S1 ). The
5-year EFS and OS of patients who showed CR/VGPR/PR before HDC were
50.0% ± 8.6% and 67.6% ± 8.0%, respectively. The 5-year EFS rate of
patients with a good remission status (CR/VGPR) before HDC was
significantly superior compared to patients with a poor remission status
(78.6% ± 11.0% vs. 22.2% ± 8.0%; P = 0.00041) (Figure
2A ). Similarly, the 5-year OS rate of patients with a good remission
status (CR/VGPR) before HDC was significantly superior compared to
patients with a poor remission status (92.9% ± 6.9% vs. 37.0% ±
9.3%; P = 0.00019).
Table 1 summarizes prognostic effects according to univariate
analysis. Patients with bone metastasis showed a significantly lower
5-year EFS compared to patients without bone metastasis (32.3% ± 8.4%
vs. 70.0% ± 14.5%; P = 0.021). Eight patients who underwent
tandem SCT showed significantly poorer prognosis compared to those who
didn’t undergo tandem SCT (P = 0.012). Interestingly, the 5-year
EFS rate of MYCN -amplified high-risk neuroblastoma patients was
significantly superior compared to MYCN -non-amplified high-risk
neuroblastoma patients (60.9% ± 10.2% vs. 16.7% ± 8.8%; P =
0.000065) (Figure 2B ). Similarly, the 5-year OS rate ofMYCN -amplified high-risk neuroblastoma patients was significantly
superior compared to MYCN -non-amplified high-risk neuroblastoma
patients (73.9% ± 9.2% vs. 33.3% ± 11.1%; P = 0.00018)
(Figure 2B ). Even when the outcome was analyzed in each group,
which showed a good response to induction chemotherapy (CR/VGPR) and
poor response, MYCN -amplification was associated with good
prognoses (P = 0.094 in CR/VGPR patients, P = 0.019 in non-CR/VGPR
patients) (Supporting Figure S2 ). Of note,MYCN -amplified high-risk neuroblastoma patients who showed good
response to induction chemotherapy showed good long-term outcomes
(5-year EFS = 81.8%). Among four significant prognostic factors (INRC
before HDC, MYCN amplification, bone metastasis, and tandem SCT),
backward stepwise selection eliminated bone marrow metastasis and tandem
SCT in multivariate analysis. Finally, the strongest prognostic factor
for EFS was MYCN amplification (hazard ratio = 0.29; 95%
confidence interval = 0.12–0.66). Similarly, MYCN amplification
and INRC before HDC were also chosen as significant prognostic factors
for OS in multivariable analysis. Table 2 describes the details
of multivariate analysis.