J Korean Med Sci.  2012 Sep;27(9):1066-1072. 10.3346/jkms.2012.27.9.1066.

Clinical Results of High-Dose Chemotherapy Followed by Autologous Peripheral Blood Stem Cell Transplantation in Children with Advanced Stage Rhabdomyosarcoma

• Kim NK
• Kim HS
• Suh CO
• Kim HO
• Lyu CJ

• KMID: 1782141
• DOI: http://doi.org/10.3346/jkms.2012.27.9.1066

Abstract

Regardless of improvement in cure of Rhabdomyosarcoma (RMS), the results in treatment of advanced stage of RMS in children are still dismal. Recently, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (HDC/APBSCT) has been tried to manage the advanced high-risk RMS patients. We investigated the effectiveness of HDC/APBSCT by reviewing the clinical records of high-risk pediatric RMS patients in single institute database. Over twenty years, 37 patients were diagnosed as RMS with high-risk at the time of first diagnosis. These patients were classified as two groups according to treatment method. The first group was HDC/APBSCT and the other was conventional multi-agent chemotherapy group. Differences of clinical results between the two groups were analyzed. The median age of patients was 5 yr, ranging from 6 months to 15 yr. The 5-yr event free survival rate (EFS) of all patients was 24.8% +/- 4.8%. HDC/APBSCT group and conventional multi-agent chemotherapy group were 41.3% +/- 17.8% and 16.7% +/- 7.6% for 5-yr EFS, respectively (P = 0.023). There was a significant difference in the result of HDC/APBSCT between complete remission or very good partial response group and poor response group (50% +/- 20.4% vs 37.5% +/- 28.6%, P = 0.018). HDC/APBSCT can be a promising treatment modality in high-risk RMS patients.

Keyword

Rhabdomyosarcoma; Children; Chemotherapy; Bone Marrow Transplantation

MeSH Terms

Adolescent
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
Carboplatin/administration & dosage
Child
Child, Preschool
Disease-Free Survival
Etoposide/administration & dosage
Female
Humans
Ifosfamide/administration & dosage
Infant
Male
*Peripheral Blood Stem Cell Transplantation
Retrospective Studies
Rhabdomyosarcoma/*drug therapy/mortality/pathology
Survival Rate
Transplantation, Autologous
Treatment Outcome
Etoposide
Ifosfamide
Carboplatin

Figure

• 

  Fig. 1 Event-free survival rates. Patients with advanced rhabdomyosarcoma (A). Patients with high risk rhabdomyosarcoma, according to high dose chemotherapy and autologous peripheral blood stem cell transplantation or not (B) the status at the time of hematopoietic stem cell transplantation (C) high dose chemotherapy and autologous peripheral blood stem cell transplantation or not (D).

Reference

1. Maurer HM, Beltangady M, Gehan EA, Crist W, Hammond D, Hays DM, Heyn R, Lawrence W, Newton W, Ortega J, et al. The Intergroup Rhabdomyosarcoma Study-I. A final report. Cancer. 1988. 61:209–220.

2. Maurer HM, Gehan EA, Beltangady M, Crist W, Dickman PS, Donaldson SS, Fryer C, Hammond D, Hays DM, Herrmann J, et al. The Intergroup Rhabdomyosarcoma Study-II. Cancer. 1993. 71:1904–1922.

3. Crist W, Gehan EA, Ragab AH, Dickman PS, Donaldson SS, Fryer C, Hammond D, Hays DM, Herrmann J, Heyn R, et al. The Third Intergroup Rhabdomyosarcoma Study. J Clin Oncol. 1995. 13:610–630.

4. Raney RB, Anderson JR, Barr FG, Donaldson SS, Pappo AS, Qualman SJ, Wiener ES, Maurer HM, Crist WM. Rhabdomyosarcoma and undifferentiated sarcoma in the first two decades of life: a selective review of intergroup rhabdomyosarcoma study group experience and rationale for Intergroup Rhabdomyosarcoma Study V. J Pediatr Hematol Oncol. 2001. 23:215–220.

5. Breneman JC, Lyden E, Pappo AS, Link MP, Anderson JR, Parham DM, Qualman SJ, Wharam MD, Donaldson SS, Maurer HM, et al. Prognostic factors and clinical outcomes in children and adolescents with metastatic rhabdomyosarcoma--a report from the Intergroup Rhabdomyosarcoma Study IV. J Clin Oncol. 2003. 21:78–84.

6. Baker KS, Anderson JR, Link MP, Grier HE, Qualman SJ, Maurer HM, Breneman JC, Wiener ES, Crist WM. Benefit of intensified therapy for patients with local or regional embryonal rhabdomyosarcoma: results from the Intergroup Rhabdomyosarcoma Study IV. J Clin Oncol. 2000. 18:2427–2434.

7. Nath SV, Prince HM, Choong PF, Toner GC. Durable remissions are rare following high dose therapy with autologous stem cell transplantation for adults with "paediatric" bone and soft tissue sarcomas. Int Semin Surg Oncol. 2005. 2:12.

8. Breitfeld PP, Meyer WH. Rhabdomyosarcoma: new windows of opportunity. Oncologist. 2005. 10:518–527.

9. Pizzo PA, Poplack DG. Principles and practice of pediatric oncology. 2006. 5th ed. Philadelphia: Lippincott Williams & Wilkins;976.

10. Arndt C, Tefft M, Gehan E, Anderson J, Jenson M, Link M, Donaldson S, Breneman J, Wiener E, Webber B, et al. A feasibility, toxicity, and early response study of etoposide, ifosfamide, and vincristine for the treatment of children with rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study (IRS) IV pilot study. J Pediatr Hematol Oncol. 1997. 19:124–129.

11. Arndt CA, Nascimento AG, Schroeder G, Schomberg PJ, Neglia JP, Sencer SF, Silberman TL, Moertel CL, Tillisch JK, Miser JS. Treatment of intermediate risk rhabdomyosarcoma and undifferentiated sarcoma with alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide. Eur J Cancer. 1998. 34:1224–1229.

12. Van Winkle P, Angiolillo A, Krailo M, Cheung YK, Anderson B, Davenport V, Reaman G, Cairo MS. Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: the Children's Cancer Group (CCG) experience. Pediatr Blood Cancer. 2005. 44:338–347.

13. Atra A, Pinkerton R. High-dose chemotherapy in soft tissue sarcoma in children. Crit Rev Oncol Hematol. 2002. 41:191–196.

14. Matsubara H, Makimoto A, Higa T, Kawamoto H, Takayama J, Ohira M, Yokoyama R, Beppu Y, Takaue Y. Possible benefits of high-dose chemotherapy as intensive consolidation in patients with high-risk rhabdomyosarcoma who achieve complete remission with conventional chemotherapy. Pediatr Hematol Oncol. 2003. 20:201–210.

15. Misawa A, Hosoi H, Tsuchiya K, Iehara T, Sawada T, Sugimoto T. Regression of refractory rhabdomyosarcoma after allogeneic stem-cell transplantation. Pediatr Hematol Oncol. 2003. 20:151–155.

16. Williams BA, Williams KM, Doyle J, Stephens D, Greenberg M, Malkin D, Pappo AS. Metastatic rhabdomyosarcoma: a retrospective review of patients treated at the hospital for sick children between 1989 and 1999. J Pediatr Hematol Oncol. 2004. 26:243–247.

17. Hale GA. Autologous hematopoietic stem cell transplantation for pediatric solid tumors. Expert Rev Anticancer Ther. 2005. 5:835–846.

18. Ek ET, Choong PF. The role of high-dose therapy and autologous stem cell transplantation for pediatric bone and soft tissue sarcomas. Expert Rev Anticancer Ther. 2006. 6:225–237.

19. Doelken R, Weigel S, Schueler F, Doelken G, Beck JF. Poor outcome of two children with relapsed state stage IV alveolar rhabdomyosarcoma after allogeneic stem cell transplantation. Pediatr Hematol Oncol. 2005. 22:699–703.

20. Modak S, Guo HF, Humm JL, Smith-Jones PM, Larson SM, Cheung NK. Radioimmunotargeting of human rhabdomyosarcoma using monoclonal antibody 8H9. Cancer Biother Radiopharm. 2005. 20:534–546.

21. Garcia-Alonso I, Palomares T, Alonso-Varona A, Castro B, Del Olmo M, Portugal V, Mendez J. Effects of all-trans retinoic acid on tumor recurrence and metastasis. Rev Esp Enferm Dig. 2005. 97:240–248.