J Korean Neurosurg Soc.  2018 May;61(3):393-401. 10.3340/jkns.2018.0039.

Tandem High-dose Chemotherapy and Autologous Stem Cell Transplantation in Children with Brain Tumors : Review of Single Center Experience

• Sung KW
• Lim DH
• Shin HJ

• KMID: 2417364
• DOI: http://doi.org/10.3340/jkns.2018.0039

Abstract

The prognosis of brain tumors in children has improved for last a few decades. However, the prognosis remains dismal in patients with recurrent brain tumors. The outcome for infants and young children in whom the use of radiotherapy (RT) is very limited because of unacceptable long-term adverse effect of RT remains poor. The prognosis is also not satisfactory when a large residual tumor remains after surgery or when leptomeningeal seeding is present at diagnosis. In this context, a strategy using high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) has been explored to improve the prognosis of recurrent or high-risk brain tumors. This strategy is based on the hypothesis that chemotherapy dose escalation might result in improvement in survival rates. Recently, the efficacy of tandem HDCT/auto-SCT has been evaluated in further improving the outcome. This strategy is based on the hypothesis that further dose escalation might result in further improvement in survival rates. At present, the number of studies employing tandem HDCT/auto-SCT for brain tumors is limited. However, results of these pilot studies suggest that tandem HDCT/auto-SCT may further improve the outcome. In this review, we will summarize our single center experience with tandem HDCT/auto-SCT for recurrent or high-risk brain tumors.

Keyword

Brain neoplasms; Child; High-dose chemotherapy; Autologous stem cell transplantation

MeSH Terms

Brain Neoplasms*
Brain*
Child*
Diagnosis
Drug Therapy*
Humans
Infant
Neoplasm, Residual
Pilot Projects
Prognosis
Radiotherapy
Stem Cell Transplantation*
Stem Cells*
Survival Rate

Reference

References

1. Baek HJ, Park HJ, Sung KW, Lee SH, Han JW, Koh KN, et al. Myeloablative chemotherapy and autologous stem cell transplantation in patients with relapsed or progressed central nervous system germ cell tumors: results of Korean Society of Pediatric Neuro-Oncology (KSPNO) S-053 study. J Neurooncol. 114:329–338. 2013.

2. Berthold F, Boos J, Burdach S, Erttmann R, Henze G, Hermann J, et al. Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. Lancet Oncol. 6:649–658. 2005.

3. Bouffet E, Doz F, Demaille MC, Tron P, Roche H, Plantaz D, et al. Improving survival in recurrent medulloblastoma: earlier detection, better treatment or still an impasse? Br J Cancer. 77:1321–1326. 1998.

4. Chi SN, Gardner SL, Levy AS, Knopp EA, Miller DC, Wisoff JH, et al. Feasibility and response to induction chemotherapy intensified with highdose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma. J Clin Oncol. 22:4881–4887. 2004.

5. Copeland DR, deMoor C, Moore BD 3rd, Ater JL. Neurocognitive development of children after a cerebellar tumor in infancy: a longitudinal study. J Clin Oncol. 17:3476–3486. 1999.

6. Duffner PK, Horowitz ME, Krischer JP, Friedman HS, Burger PC, Cohen ME, et al. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med. 328:1725–1731. 1993.

7. Fangusaro J, Finlay J, Sposto R, Ji L, Saly M, Zacharoulis S, et al. Intensive chemotherapy followed by consolidative myeloablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) in young children with newly diagnosed supratentorial primitive neuroectodermal tumors (sPNETs): report of the Head Start I and II experience. Pediatr Blood Cancer. 50:312–318. 2008.

8. Finlay JL, Boyett JM, Yates AJ, Wisoff JH, Milstein JM, Geyer JR, et al. Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Childrens cancer group. J Clin Oncol. 13:112–123. 1995.

9. Finlay JL, Zacharoulis S. The treatment of high grade gliomas and diffuse intrinsic pontine tumors of childhood and adolescence: a historical - and futuristic - perspective. J Neurooncol. 75:253–266. 2005.

10. Gardner SL, Asgharzadeh S, Green A, Horn B, McCowage G, Finlay J. Intensive induction chemotherapy followed by high dose chemotherapy with autologous hematopoietic progenitor cell rescue in young children newly diagnosed with central nervous system atypical teratoid rhabdoid tumors. Pediatr Blood Cancer. 51:235–240. 2008.

11. George RE, Li S, Medeiros-Nancarrow C, Neuberg D, Marcus K, Shamberger RC, et al. High-risk neuroblastoma treated with tandem autologous peripheral-blood stem cell-supported transplantation: long-term survival update. J Clin Oncol. 24:2891–2896. 2006.

12. Kletzel M, Katzenstein HM, Haut PR, Yu AL, Morgan E, Reynolds M, et al. Treatment of high-risk neuroblastoma with triple-tandem high-dose therapy and stem-cell rescue: results of the Chicago Pilot II Study. J Clin Oncol. 20:2284–2292. 2002.

13. Kortmann RD, Kühl J, Timmermann B, Mittler U, Urban C, Budach V, et al. Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of the German prospective randomized trial HIT ‘91. Int J Radiat Oncol Biol Phys. 46:269–279. 2000.

14. Lee JW, Lim DH, Sung KW, Lee HJ, Yi ES, Yoo KH, et al. Tandem highdose chemotherapy and autologous stem cell transplantation for highgrade gliomas in children and adolescents. J Korean Med Sci. 32:195–203. 2017.

15. Lee SH, Son MH, Sung KW, Choi YB, Lee NH, Yoo KH, et al. Toxicity of tandem high-dose chemotherapy and autologous stem cell transplantation using carboplatin-thiotepa-etoposide and cyclophosphamidemelphalan regimens for malignant brain tumors. J Neurooncol. 120:507–513. 2014.

16. Mason WP, Grovas A, Halpern S, Dunkel IJ, Garvin J, Heller G, et al. Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors. J Clin Oncol. 16:210–221. 1998.

17. Matthay KK, Reynolds CP, Seeger RC, Shimada H, Adkins ES, Haas-Kogan D, et al. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children’s oncology group study. J Clin Oncol. 27:1007–1013. 2009.

18. Merchant TE, Sherwood SH, Mulhern RK, Rose SR, Thompson SJ, Sanford RA, et al. CNS germinoma: disease control and long-term functional outcome for 12 children treated with craniospinal irradiation. Int J Radiat Oncol Biol Phys. 46:1171–1176. 2000.

19. Modak S, Gardner S, Dunkel IJ, Balmaceda C, Rosenblum MK, Miller DC, et al. Thiotepa-based high-dose chemotherapy with autologous stemcell rescue in patients with recurrent or progressive CNS germ cell tumors. J Clin Oncol. 22:1934–1943. 2004.

20. Mulhern RK, Merchant TE, Gajjar A, Reddick WE, Kun LE. Late neurocognitive sequelae in survivors of brain tumours in childhood. Lancet Oncol. 5:399–408. 2004.

21. Park JE, Kang J, Yoo KH, Sung KW, Koo HH, Lim DH, et al. Efficacy of high-dose chemotherapy and autologous stem cell transplantation in patients with relapsed medulloblastoma: a report on the Korean Society for Pediatric Neuro-Oncology (KSPNO)-S-053 study. J Korean Med Sci. 25:1160–1166. 2010.

22. Pérez-Martínez A, Lassaletta A, González-Vicent M, Sevilla J, Díaz MA, Madero L. High-dose chemotherapy with autologous stem cell rescue for children with high risk and recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors. J Neurooncol. 71:33–38. 2005.

23. Sposto R, Ertel IJ, Jenkin RD, Boesel CP, Venes JL, Ortega JA, et al. The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. A report from the Childrens Cancer Study Group. J Neurooncol. 7:165–177. 1989.

24. Sung KW, Lee SH, Yoo KH, Jung HL, Cho EJ, Koo HH, et al. Tandem highdose chemotherapy and autologous stem cell rescue in patients over 1 year of age with stage 4 neuroblastoma. Bone Marrow Transplant. 40:37–45. 2007.

25. Sung KW, Lim DH, Lee SH, Yoo KH, Koo HH, Kim JH, et al. Tandem highdose chemotherapy and auto-SCT for malignant brain tumors in children under 3 years of age. Bone Marrow Transplant. 48:932–938. 2013.

26. Sung KW, Lim DH, Lee SH, Yoo KH, Koo HH, Kim JH, et al. Tandem high-dose chemotherapy and autologous stem cell transplantation for anaplastic ependymoma in children younger than 3 years of age. J Neurooncol. 107:335–342. 2012.

27. Sung KW, Lim DH, Son MH, Lee SH, Yoo KH, Koo HH, et al. Reduceddose craniospinal radiotherapy followed by tandem high-dose chemotherapy and autologous stem cell transplantation in patients with highrisk medulloblastoma. Neuro Oncol. 15:352–359. 2013.

28. Sung KW, Lim DH, Yi ES, Choi YB, Lee JW, Yoo KH, et al. Tandem high-dose chemotherapy and autologous stem cell transplantation for atypical teratoid/rhabdoid tumor. Cancer Res Treat. 48:1408–1419. 2016.

29. Taylor RE, Bailey CC, Robinson KJ, Weston CL, Walker DA, Ellison D, et al. Outcome for patients with metastatic (M2-3) medulloblastoma treated with SIOP/UKCCSG PNET-3 chemotherapy. Eur J Cancer. 41:727–734. 2005.

30. Zeltzer PM, Boyett JM, Finlay JL, Albright AL, Rorke LB, Milstein JM, et al. Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children’s Cancer Group 921 randomized phase III study. J Clin Oncol. 17:832–845. 1999.