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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

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

Autologous stem-cell transplantation Chemotherapy Brain neoplasms Medulloblastoma Pediatrics 

Abbreviations

ACTH

Adrenocorticotropic hormone

ANC

Absolute neutrophil count

ARDS

Acute respiratory distress syndrome

ATRT

Atypical teratoid/rhabdoid tumor

Auto-SCT

Autologous stem-cell transplantation

CE

Cyclophosphamide-melphalan

CPC

Chroid plexus carcinoma

CNS

Central nervous system

CR

Complete response

CSRT

Craniospinal radiotherapy

CTE

Carboplatin–thiotepa–etoposide

EFS

Event-free survival

GHD

Growth hormone deficiency

HDC

High-dose chemotherapy

MBL

medulloblastoma

MEC

Melphalan–etoposide–carboplatin

OS

Overall survival

PBL

Pineoblastoma

PBSCM

Peripheral blood stem-cell mobilization

PNET

Primitive neuroectodermal tumor

PR

Partial response

SNHL

Sensorineural-hearing loss

TRM

Treatment-related mortality

TTC

Topotecan–thiotepa–carboplatin

Notes

Acknowledgements

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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