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.