International Journal of Clinical Oncology

, Volume 24, Issue 12, pp 1515–1525 | Cite as

Tandem high-dose chemotherapy with topotecan–thiotepa–carboplatin and melphalan–etoposide–carboplatin regimens for pediatric high-risk brain tumors

  • Jung Yoon Choi
  • Hyoung Jin KangEmail author
  • Kyung Taek Hong
  • Che Ry Hong
  • Yun Jeong Lee
  • June Dong Park
  • Ji Hoon Phi
  • Seung-Ki Kim
  • Kyu-Chang Wang
  • Il Han Kim
  • Sung-Hye Park
  • Young Hun Choi
  • Jung-Eun Cheon
  • Kyung Duk Park
  • Hee Young Shin
Original Article



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.


Autologous stem-cell transplantation Chemotherapy Brain neoplasms Medulloblastoma Pediatrics 



Adrenocorticotropic hormone


Absolute neutrophil count


Acute respiratory distress syndrome


Atypical teratoid/rhabdoid tumor


Autologous stem-cell transplantation




Chroid plexus carcinoma


Central nervous system


Complete response


Craniospinal radiotherapy




Event-free survival


Growth hormone deficiency


High-dose chemotherapy






Overall survival




Peripheral blood stem-cell mobilization


Primitive neuroectodermal tumor


Partial response


Sensorineural-hearing loss


Treatment-related mortality





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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Copyright information

© Japan Society of Clinical Oncology 2019

Authors and Affiliations

  • Jung Yoon Choi
    • 1
    • 2
  • Hyoung Jin Kang
    • 1
    • 2
    Email author
  • Kyung Taek Hong
    • 1
    • 2
  • Che Ry Hong
    • 1
    • 2
  • Yun Jeong Lee
    • 1
  • June Dong Park
    • 1
  • Ji Hoon Phi
    • 3
  • Seung-Ki Kim
    • 3
  • Kyu-Chang Wang
    • 3
  • Il Han Kim
    • 2
    • 4
  • Sung-Hye Park
    • 5
  • Young Hun Choi
    • 6
  • Jung-Eun Cheon
    • 6
  • Kyung Duk Park
    • 1
    • 2
  • Hee Young Shin
    • 1
    • 2
  1. 1.Department of PediatricsSeoul National University College of MedicineSeoulRepublic of Korea
  2. 2.Seoul National University Cancer Research InstituteSeoulRepublic of Korea
  3. 3.Division of Pediatric NeurosurgerySeoul National University College of MedicineSeoulRepublic of Korea
  4. 4.Department of Radiation OncologySeoul National University College of MedicineSeoulRepublic of Korea
  5. 5.Department of PathologySeoul National University College of MedicineSeoulRepublic of Korea
  6. 6.Department of RadiologySeoul National University College of MedicineSeoulRepublic of Korea

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