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

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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.

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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

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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).

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Authors and Affiliations

  1. Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea

    Jung Yoon Choi, Hyoung Jin Kang, Kyung Taek Hong, Che Ry Hong, Yun Jeong Lee, June Dong Park, Kyung Duk Park & Hee Young Shin

  2. Seoul National University Cancer Research Institute, Seoul, Republic of Korea

    Jung Yoon Choi, Hyoung Jin Kang, Kyung Taek Hong, Che Ry Hong, Il Han Kim, Kyung Duk Park & Hee Young Shin

  3. Division of Pediatric Neurosurgery, Seoul National University College of Medicine, Seoul, Republic of Korea

    Ji Hoon Phi, Seung-Ki Kim & Kyu-Chang Wang

  4. Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea

    Il Han Kim

  5. Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea

    Sung-Hye Park

  6. Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea

    Young Hun Choi & Jung-Eun Cheon

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  1. Jung Yoon Choi
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Choi, J.Y., Kang, H.J., Hong, K.T. et al. Tandem high-dose chemotherapy with topotecan–thiotepa–carboplatin and melphalan–etoposide–carboplatin regimens for pediatric high-risk brain tumors. Int J Clin Oncol 24, 1515–1525 (2019). https://doi.org/10.1007/s10147-019-01517-8

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