Tandem high-dose chemotherapy with topotecan–thiotepa–carboplatin and melphalan–etoposide–carboplatin regimens for pediatric high-risk brain tumors
High-dose chemotherapy (HDC) and autologous stem-cell transplantation (auto-SCT) are used to improve the survival of children with high-risk brain tumors who have a poor outcome with the standard treatment. This study aims to evaluate the outcome of HDC/auto-SCT with topotecan–thiotepa–carboplatin and melphalan–etoposide–carboplatin (TTC/MEC) regimens in pediatric brain tumors.
We retrospectively analyzed the data of 33 children (median age 6 years) who underwent HDC/auto-SCT (18 tandem and 15 single) with uniform conditioning regimens.
Eleven patients aged < 3 years at diagnosis were eligible for HDC/auto-SCT to avoid or defer radiotherapy. In addition, nine patients with high-risk medulloblastoma (presence of metastasis and/or postoperative residual tumor ≥ 1.5 cm2), eight with other high-risk brain tumor (six CNS primitive neuroectodermal tumor, one CNS atypical teratoid/rhabdoid tumor, and one pineoblastoma), and five with relapsed brain tumors were enrolled. There were three toxic deaths, and two of which were due to pulmonary complications. The main reason for not performing tandem auto-SCT was due to toxicities and patient refusal. The event-free survival (EFS) and overall survival (OS) rates of all patients were 59.4% and 80.0% at a median follow-up with 49.1 months from the first HDC/auto-SCT, respectively. The EFS/OS rates of patients aged < 3 years at diagnosis, high-risk medulloblastoma, other high-risk brain tumor, and relapsed tumors were 50.0/81.8%, 87.5/85.7%, 66.7/88.9%, and 20.0/60.0%, respectively.
Although tandem HDC/auto-SCT with TTC/MEC regimens showed promising survival rates, treatment modifications are warranted to reduce toxicities. The survival rates with relapsed brain tumors were unsatisfactory despite HDC/auto-SCT, and further study is needed.
KeywordsAutologous stem-cell transplantation Chemotherapy Brain neoplasms Medulloblastoma Pediatrics
Absolute neutrophil count
Acute respiratory distress syndrome
Atypical teratoid/rhabdoid tumor
Autologous stem-cell transplantation
Chroid plexus carcinoma
Central nervous system
Growth hormone deficiency
Peripheral blood stem-cell mobilization
Primitive neuroectodermal tumor
This research was supported by the Seoul National University Research Grant in 2016 (800-20160150) and by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (2016M3A9D3026905).
Compliance with ethical standards
Conflicts of interests
The authors declare that they have no conflict of interest.
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