J Korean Med Sci.  2010 Aug;25(8):1160-1166. 10.3346/jkms.2010.25.8.1160.

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

• Park JE
• Kang J
• Yoo KH
• Sung KW
• Koo HH
• Lim DH
• Shin HJ
• Kang HJ
• Park KD
• Shin HY
• Kim IH
• Cho BK
• Im HJ
• Seo JJ
• Park HJ
• Park BK
• Ahn HS

• KMID: 1714036
• DOI: http://doi.org/10.3346/jkms.2010.25.8.1160

Abstract

The efficacy and toxicity of high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) were investigated for improving the outcomes of patients with relapsed medulloblastoma. A total of 15 patients with relapsed medulloblastoma were enrolled in the KSPNO-S-053 study from May 2005 to May 2007. All patients received approximately 4 cycles of salvage chemotherapy after relapse. Thirteen underwent HDCT/ASCT; CTE and CM regimen were employed for the first HDCT (HDCT1) and second HDCT (HDCT2), respectively, and 7 underwent HDCT2. One transplant related mortality (TRM) due to veno-occlusive disease (VOD) occurred during HDCT1 but HDCT2 was tolerable with no further TRM. The 3-yr overall survival probability and event-free survival rates +/-95% confidence intervals (CI) were 33.3+/-12.2% and 26.7% +/-11.4%, respectively. When analysis was confined to only patients who had a complete response (CR) or partial response (PR) prior to HDCT, the probability of 3-yr overall survival rates +/-95% CI was 40.0+/-15.5%. No patients with stable disease (SD) or progressive disease (PD) survived. Survival rates from protocol KSPNO-S-053 are encouraging and show that tumor status prior to HDCT/ASCT is an important factor to consider for improving survival rates of patients with relapsed medulloblastoma.

Keyword

Recurrence; Medulloblastoma; Transplantation, Autologous; Tandem; Hematopoietic Stem Cell Transplantation

MeSH Terms

Adolescent
Cerebellar Neoplasms/drug therapy/mortality/*therapy
Child
Child, Preschool
Combined Modality Therapy
Disease-Free Survival
Female
*Hematopoietic Stem Cell Transplantation
Humans
Male
Medulloblastoma/drug therapy/mortality/*therapy
Neoplasm Recurrence, Local/drug therapy/mortality/*therapy
Republic of Korea
Salvage Therapy
Transplantation, Autologous
Young Adult

Figure

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  Fig. 1 Overview of KSPNO-S-053 protocol for relapsed medulloblastoma. CR, complete response; PR, partial response; PD, progressive disease; SD, stable disease.

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  Fig. 2 (A) Event free and overall survival of all patients at 3 year survival from diagnosis of relapsed tumor (n=15). (B) Event free and overall survival of the patients who received HDCT from when diagnosis of relapsed tumor (n=13). (C) Overall survival of the patients who received HDCT in pre-HDCT CR or PR status vs. SD or PD status from 1st HDCT (n=10).

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  Fig. 3 Study progression following salvage chemotherapy (n=13). *2nd HDCT was refused by a patient's guardian. CR, complete response; PR, partial response; PD, progressive disease; SD, stable disease.

Reference

1. Bouffet E, Doz F, Demaille MC, Tron P, Roche H, Plantaz D, Thyss A, Stephan JL, Lejars O, Sariban E, Buclon M, Zucker JM, Brunat-Mentigny M, Bernard JL, Gentet JC. Improving survival in recurrent medulloblastoma: earlier detection, better treatment or still an impasse? Br J Cancer. 1998. 77:1321–1326.

2. Finlay JL, Goldman S, Wong MC, Cairo M, Garvin J, August C, Cohen BH, Stanley P, Zimmerman RA, Bostrom B, Geyer JR, Harris RE, Sanders J, Yates AJ, Boyett JM, Packer RJ. The Children's Cancer Group. Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. J Clin Oncol. 1996. 14:2495–2503.

3. Shih CS, Hale GA, Gronewold L, Tong X, Laningham FH, Gilger EA, Srivastava DK, Kun LE, Gajjar A, Fouladi M. High-dose chemotherapy with autologous stem cell rescue for children with recurrent malignant brain tumors. Cancer. 2008. 112:1345–1353.

4. Perez-Martinez A, Lassaletta A, Gonzalez-Vicent M, Sevilla J, Diaz 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. 2005. 71:33–38.

5. Lee SH, Yoo KH, Sung KW, Kim JY, Cho EJ, Koo HH, Chung SE, Kang SW, Oh SY, Ham DI, Kim YD. Tandem high-dose chemotherapy and autologous stem cell rescue in children with bilateral advanced retinoblastoma. Bone Marrow Transplant. 2008. 42:385–391.

6. Sung KW, Lee SH, Yoo KH, Jung HL, Cho EJ, Koo HH, Lee SK, Kim J, Lim DH, Suh YL, Kim DW. Tandem high-dose chemotherapy and autologous stem cell rescue in patients over 1 year of age with stage 4 neuroblastoma. Bone Marrow Transplant. 2007. 40:37–45.

7. Butturini AM, Jacob M, Aguajo J, Vander-Walde NA, Villablanca J, Jubran R, Erdreich-Epstein A, Marachelian A, Dhall G, Finlay JL. High-dose chemotherapy and autologous hematopoietic progenitor cell rescue in children with recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors. Cancer. 2009. 115:2956–2963.

8. Grodman H, Wolfe L, Kretschmar C. Outcome of patients with recurrent medulloblastoma or central nervous system germinoma treated with low dose continuous intravenous etoposide along with dose-intensive chemotherapy followed by autologous hematopoietic stem cell rescue. Pediatr Blood Cancer. 2009. 53:33–36.

9. Foreman NK, Schissel D, Le T, Strain J, Fleitz J, Quinones R, Giller R. A study of sequential high dose cyclophosphamide and high dose carboplatin with peripheral stem-cell rescue in resistant or recurrent pediatric brain tumors. J Neurooncol. 2005. 71:181–187.

10. Sung KW, Yoo KH, Cho EJ, Koo HH, Lim do H, Shin HJ, Ahn SD, Ra YS, Choi ES, Ghim TT. High-dose chemotherapy and autologous stem cell rescue in children with newly diagnosed high-risk or relapsed medulloblastoma or supratentorial primitive neuroectodermal tumor. Pediatr Blood Cancer. 2007. 48:408–415.

11. Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006. 7:813–820.

12. Fagioli F, Biasin E, Mastrodicasa L, Sandri A, Ferrero I, Berger M, Vassallo E, Madon E. High-dose thiotepa and etoposide in children with poor-prognosis brain tumors. Cancer. 2004. 100:2215–2221.

13. Gururangan S, Krauser J, Watral MA, Driscoll T, Larrier N, Reardon DA, Rich JN, Quinn JA, Vredenburgh JJ, Desjardins A, McLendon RE, Fuchs H, Kurtzberg J, Friedman HS. Efficacy of high-dose chemotherapy or standard salvage therapy in patients with recurrent medulloblastoma. Neuro-oncol. 2008. 10:745–751.

14. Cheuk DK, Lee TL, Chiang AK, Ha SY, Chan GC. Autologous hematopoietic stem cell transplantation for high-risk brain tumors in children. J Neurooncol. 2008. 86:337–347.

15. Rosenfeld A, Kletzel M, Duerst R, Jacobsohn D, Haut P, Weinstein J, Rademaker A, Schaefer C, Evans L, Fouts M, Goldman S. A phase II prospective study of sequential myeloablative chemotherapy with hematopoietic stem cell rescue for the treatment of selected high risk and recurrent central nervous system tumors. J Neurooncol. 2010. 97:247–255.