Patient Characteristics
Forty-three patients with refractory or relapsed neuroblastoma had undergone a total of 131 cycles of IREC therapy (Table 1 ). The median age at diagnosis was 3.3 years (range, 1.2–22.7). All patients were classified as high-risk based on the International Neuroblastoma Risk Group classification. At the commencement of IREC therapy, 41 patients (95%) were <18 years of age and the median age (range) was 4.8 (1.8–25.7) years. Twenty patients (47%) were male. Eleven patients (26%) were refractory to the initial chemotherapies, and seven patients (16%) had relapsed before IREC. According to the Lansky (<16 years of age) or Karnofsky performance status scores (≥16 years of age) at the start of IREC, one patient scored 50, two patients scored 60 and 70 respectively, while the rest of the patients were normally active (score ≥80). All 43 patients had previously been treated with combination chemotherapy, including ICE, TOPO-CY, and irinotecan with TMZ [median cycles of chemotherapy: 10 (range 2–24)]. Before IREC, seven patients (16%) had received autologous peripheral blood stem cell transplantation, and three (7%) patients had received cord blood transplantation.
Based on the UGT1A1 genotyping analysis, patients were divided into wild-type group (−/− ) (20 patients), heterozygous group (*28/− and *6/− ) (17 patients), and homozygous group (*28/*28 , *6/*6 , and *28/*6 ) (6 patients).