Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Grade Gliomas in Children and Adolescents

Abstract

With the aim to investigate the outcome of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) for high-grade gliomas (HGGs), we retrospectively reviewed the medical records of 30 patients with HGGs (16 glioblastomas, 7 anaplastic astrocytomas, and 7 other HGGs) between 2006 and 2015. Gross or near total resection was possible in 11 patients. Front-line treatment after surgery was radiotherapy (RT) in 14 patients and chemotherapy in the remaining 16 patients including 3 patients less than 3 years of age. Eight of 12 patients who remained progression free and 5 of the remaining 18 patients who experienced progression during induction treatment underwent the first HDCT/auto-SCT with carboplatin + thiotepa + etoposide (CTE) regimen and 11 of them proceeded to the second HDCT/auto-SCT with cyclophosphamide + melphalan (CyM) regimen. One patient died from hepatic veno-occlusive disease (VOD) during the second HDCT/auto-SCT; otherwise, toxicities were manageable. Four patients in complete response (CR) and 3 of 7 patients in partial response (PR) or second PR at the first HDCT/auto-SCT remained event free: however, 2 patients with progressive tumor experienced progression again. The probabilities of 3-year overall survival (OS) after the first HDCT/auto-SCT in 11 patients in CR, PR, or second PR was 58.2% ± 16.9%. Tumor status at the first HDCT/auto-SCT was the only significant factor for outcome after HDCT/auto-SCT. There was no difference in survival between glioblastoma and other HGGs. This study suggests that the outcome of HGGs in children and adolescents after HDCT/auto-SCT is encouraging if the patient could achieve CR or PR before HDCT/auto-SCT.

Keywords: Autologous Stem Cell Transplantation; Brain Tumor; Children; High-dose Chemotherapy; High-grade Glioma.

Fig. 1

Flow of patients. Treatment flow and outcome of all patients are illustrated. HGGs = high-grade gliomas, PD = progressive disease, HDCT = high-dose chemotherapy, ICH = intracranial hemorrhage, HDCT1 = first high-dose chemotherapy, Tx = Treatment, HDCT2 = second high-dose chemotherapy, Ds = disease, DOD = died of disease, TRM = treatment-related mortality, VOD = veno-occlusive disease.

Fig. 2

Response to tandem HDCT/auto-SCT. Responses before and after HDCT/auto-SCT are illustrated. A total of 13 patients (CR in 4, PR in 4, PR2 in 3, and PD in 2) underwent the first HDCT/auto-SCT and 11 of them proceeded to the second HDCT/auto-SCT. Overall, 7 patients are alive after HDCT/auto-SCT. HDCT/auto-SCT = high-dose chemotherapy and autologous stem cell transplantation, CR = complete response, PR = partial response, PR2 = second PR, PD = progressive disease, CCR = continuous, HDCT1 = first high-dose chemotherapy, HDCT2 = second high-dose chemotherapy, TRM = treatment-related mortality.

Fig. 3

Survival from diagnosis. The probability of 3-year OS (A) is higher than that in 14 patients during 5 years (2001–2005) prior to the present study period, most of whom were treated with conventional modalities alone, although the EFS rate is not different (B). Subtotal or less resection of the primary tumor is associated with inferior EFS (C). There is no difference in survival between glioblastoma and other HGGs (D). HGGs = high-grade gliomas, NTR = near total resection, STR = subtotal resection, OS = overall survival, EFS = event-free survival.

Fig. 4

Survival after first HDCT/auto-SCT. Survival analysis was confined only to 13 patients who underwent the first HDCT/auto-SCT. The probabilities of 3-year OS and EFS after the first HDCT/auto-SCT are 55.4% ± 16.1% and 43.1% ± 14.8%, respectively (A). Tumor status less than PR at the first HDCT/auto-SCT is associated with inferior EFS (B). There is no difference in survival between glioblastoma and other HGGs (C). HDCT/auto-SCT = high-dose chemotherapy and autologous stem cell transplantation, OS = overall survival, EFS = event-free survival, CR = complete response, PR = partial response, PR2 = second PR, PD = progressive disease, HGGs = high-grade gliomas.