Treatment
All 41 patients underwent multimodality treatment with induction
chemotherapy, surgical resection, and/or radiation for local control
according to each institution’s policy. The induction chemotherapeutics
used varied, although most of them were previously reported as
efficacious for neuroblastoma, including platinum, anthracycline, and
alkylators.16–18 The response to induction
chemotherapy was assessed according to the International Neuroblastoma
Response Criteria (INRC).14
After induction chemotherapy, patients underwent the double-conditioning
regimen with auto-SCT, which comprised 2 cycles of thiotepa and
melphalan at a 1-week interval8. Thiotepa (age ≥ 2
years, 200 mg/m2/day; age < 2 years, 8
mg/kg/day) and melphalan (age ≥ 2 years, 70 mg/m2/day;
age < 2 years, 1.5 mg/kg/day) were administered on days −12,
−11, −5, and −4. If creatinine clearance (Ccr) was <100
mL/min/1.73 m2 in patients aged ≥2 years, the dosage
was principally adjusted before and during HDC using the following
formula: given dose (mg/m2) = (Ccr/100) × 200
mg/m2/day (thiotepa) or 70 mg/m2/day
(melphalan). The details of this regimen are reported
elsewhere.9
Some patients received retinoic acid and/or second SCT using cord blood
stem cells according to the institution’s policy, while no patients
underwent GD-2 antibody therapy.
Surgical resection of the primary tumor was conducted at the adequate
time point on the basis of the feasibility of resection during induction
chemotherapy or post-HDC. In some patients, surgical resection was
planned after HDC regardless of tumor resectability during induction
chemotherapy because the feasibility of the delayed local control
strategy was shown in Japanese nationwide phase 2
study.19
Radiation therapy was administered against the residual tumor at the
primary site and/or metastatic sites; however, the criteria for
determining the target sites for irradiation varied from institution to
institution.
Toxicity was assessed from day 1 of the double-conditioning regimen to
day 100 after auto-SCT or day 1 of the second conditioning regimen on
the basis of the Common Terminology Criteria for Adverse Events version
4.0. Sinusoidal obstruction syndrome (SOS) was diagnosed according to
Baltimore criteria.20 Thrombotic microangiopathy (TMA)
was diagnosed according to BMT-CTN criteria.21 In
addition, regimen-related death was defined as death due to any adverse
event occurring within the study period.