Tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk neuroblastoma: Results of SMC NB-2004 study

Abstract

, 50 consecutive patients with high-risk neuroblastoma were assigned to receive tandem HDCT (high-dose chemotherapy)/auto-SCT after nine cycles of induction chemotherapy. CEC (carboplatin þ etoposide þ cyclophosphamide) regimen and TM (thiotepa þ melphalan)-TBI regimen (or TM regimen for stage 3 patients) were the first and second HDCT regimens. Local radiotherapy, differentiation therapy with 13-cis-retinoid acid and immunotherapy with interleukin-2 were given after tandem HDCT/auto-SCT. Of the 50 patients, 49 underwent a first HDCT/auto-SCT and 47 underwent a second HDCT/auto-SCT. The tumor relapsed or progressed in 14 patients, secondary malignancy developed in one patient and one patient died from chronic lung disease. Therefore, 34 patients remained event free with a median follow-up of 54.5 months (range, 14-94 months) from diagnosis. The probabilities of 5-year OS and EFS for all 50 patients were 77.0% (95% confidence interval (CI), 63.7-90.3) and 71.4% (95% CI, 58.7-84.1), respectively. However, all patients who remained event free for 43 years after tandem HDCT/auto-SCT experienced late adverse effects. Chemotherapeutic dose-escalation strategy using tandem HDCT/auto-SCT was very encouraging for survival. However, further studies incorporating newer treatment modalities are needed to reduce late adverse effects without jeopardizing the survival rate.

Incorporation of high-dose 131I-metaiodobenzylguanidine treatment into tandem high-dose chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma: results of the SMC NB-2009 study

“…Induction treatments were the same as those in the SMC NB-2004 study [10]. Briefly, nine cycles of chemotherapy were administered during induction treatment.…”

“…HDCT regimens were also the same as in the NB-2004 study [10], except that TBI (3.33 Gy/day on days −3, −2, −1) in the second HDCT/auto-SCT was replaced with 131 I-MIBG treatment in the NB-2009 study (Table 1). CEC (carboplatin + etoposide + cyclophosphamide) and TM (thiotepa + melphalan) with 131 I-MIBG treatment were used as the first and second HDCT regimen, respectively.…”

“…Treatments after tandem HDCT/auto-SCT were also the same in the NB-2004 study [10]. Briefly, local radiotherapy (RT) to the site of the primary tumor (15 Gy/1.5 Gy for complete resection of the primary tumor and 21.6 Gy/1.8 Gy or 30.6 Gy/1.8 Gy for incomplete resection according to the residual 123 I-MIBG or PET uptake) was administered to all patients approximately 6 weeks after the second HDCT/auto-SCT.…”

“…We previously reported the results of a single-arm prospective trial (SMC NB-2004 study) using tandem HDCT/auto-SCT for high-risk neuroblastoma [10], which was designed based on the results of retrospective analysis of our early experience between the late 1990s and early 2000s [7]. In the NB-2004 study, nine cycles of induction chemotherapy were administered before tandem HDCT/auto-SCT, and total-body irradiation (TBI) was incorporated into the second HDCT/auto-SCT.…”

Treatment of High-Risk Neuroblastoma

“…в Корее проводилось иссле-дование по применению тандемной ВХТ с транс-плантацией ПСК у пациентов с нейробластомой группы высокого риска [27]. В исследование вошли 50 пациентов: 45 (90%) пациентов с 4-й стадией болезни, 5 (10%) -с 3-й стадией.…”