Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Autografting

High-dose thiotepa and hematopoietic stem cell transplantation in pediatric malignant mesenchymal tumors: a phase II study

Bone Marrow Transplantation volume 26, pages 627–632 (2000)Cite this article

Abstract

The prognosis of metastatic malignant mesenchymal tumors (MMT) remains poor. Given the chemosensitivity of these neoplasms, a phase II study of high-dose thiotepa (HDT) was performed to evaluate the efficacy of this drug in this particular subset of pediatric tumors. Between 1986 and 1998, 18 patients, previously treated with conventional therapy for metastatic or refractory MMT, entered the study. Thiotepa was administered at a daily dose of 300 mg/m2 for 3 consecutive days. Hematopoietic stem cell rescue, consisting of bone marrow transplantation or peripheral stem cell transplantation, was performed 2 days after completion of HDT. A response exceeding 50% was observed in 6/18 patients (response rate 33%). Toxicity was severe but never led to death. HDT used at a dose of 900 mg/m2 yields measurable anti-tumor activity in previously treated patients. The next step in these particularly poor prognosis metastatic MMT will be to investigate HDT combined with other drugs, known to be efficient at high doses. Bone Marrow Transplantation (2000) 26, 627–632.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Standford S, Saarinen U, Warkentin P et al. High-dose N-N′-N″ triethylenethiophosphoramid in pediatric phase I-II autologous bone marrow transplantation studies Exp Hematol 1988 16: 503 (Abstr. 176)

    Google Scholar 

  2. Lucidarme N, Valteau-Couanet D, Oberlin O et al. Phase II of high-dose thiotepa and hematopoietic stem cell transplantation in children with solid tumors Bone Marrow Transplant 1998 22: 535–540

    Article  CAS  Google Scholar 

  3. Rodary C, Flamant F, Donaldson SS . An attempt to use a common staging system in rhabdomyosarcoma: a report of an international workshop initated by the International Society of Pediatric Oncology (SIOP) Bull Cancer 1988 75: 213–223

    CAS  PubMed  Google Scholar 

  4. Flamant F, Hill C . The improvement in survival associated with combined chemotherapy in chilhood rhabdomyosarcoma. A historical comparaison of 345 patients in the same center Cancer 1984 53: 2417–2421

    Article  CAS  Google Scholar 

  5. Flamant F, Rodary C, Rey C et al. Treatment of non metastatic rhabdomyosarcomas in chilhood and adolescence. Result of the second study of the International Society of Pediatric Oncology: MMT 84 Eur J Cancer 1998 34: 1050–1062

    Article  CAS  Google Scholar 

  6. Stevens MCG, Oberlin O, Rey A et al. Non metastatic rhabdomyosarcoma: experience from the SIOP MMT 89 study Med Pediatr Oncol 1994 23: 171 (Abstr.O6)

    Google Scholar 

  7. Stevens MCG, Oberlin O, Rey A et al. Progress in the treatment of non-metastatic rhabdomyosarcoma (RMS): a report from the SCOP MMT 89 and 95 studies Med Ped Oncol 1999 33: 177 (Abstr. O-142)

    Google Scholar 

  8. Avril M, Hartmann O, Valteau-Couanet D et al. Anti-infective prophylaxis with ceftazidime and teicoplanin in children undergoing high-dose chemotherapy and bone marrow transplantation Pediatr Hematol Oncol 1994 11: 63–73

    Article  CAS  Google Scholar 

  9. Bearman SI, Appelbaum FR, Buckner CD et al. Regimen related toxicity in patients undergoing bone marrow transplantation J Clin Oncol 1988 6: 1562–1568

    Article  CAS  Google Scholar 

  10. Standards options and recommendations for clinical care of rhabdomyosarcoma and others soft tissue sarcoma in children Bull Cancer 1998 85: 1015–1042

  11. Crist WM, Gehan EA, Beltangady M et al. The third intergroup rhabdomyosarcoma study J Clin Oncol 1995 13: 610–630

    Article  CAS  Google Scholar 

  12. Koscielniak E, Rodary C, Flamant F et al. Metastatic rhabdomyosarcoma and histologically similar tumors in childhood: a retrospective European multi-center analysis Med Pediatr Oncol 1992 20: 209–214

    Article  CAS  Google Scholar 

  13. Carli M, Colombatti R, Oberlin O et al. High-dose melphalan with autologous stem-cell rescue in metastatic rhabdomyosarcoma J Clin Oncol 1999 17: 2796–2803

    Article  CAS  Google Scholar 

  14. Atra A, Pinkerton CR . Autologous stem cell transplantation in solid tumors of childhood Ann Med 1996 28: 159–164

    Article  CAS  Google Scholar 

  15. Wolff SN, Herzig RH, Fay JW et al. High-dose N, N′, N″-triethilenethiophosphoramide (thiotepa) with autologous bone marrow transplantation: phase I studies Semin Oncol 1990 17: 2–6

    CAS  PubMed  Google Scholar 

  16. Geyer JR, Balis FM, Krailo MD et al. A phase II study of thiotepa in children with recurrent solid tumor malignancies: a Children's Cancer Group study Invest New Drugs 1996 13: 337–342

    Article  CAS  Google Scholar 

  17. Kletzel M, Abella EM, Sandler ES et al. Thiotepa and cyclophosphamide with stem cell rescue for consolidation therapy for children with high risk neuroblastoma: a phase I/II study of the pediatric blood and marrow transplant consortium J Pediatr Hematol Oncol 1998 20: 49–54

    Article  CAS  Google Scholar 

  18. Kalifa C, Hartmann O, Demeocq F et al. High-dose busulfan and thiotepa with autologous bone marrow transplantation in childhood malignant brain tumors: a phase II study Bone Marrow Transplant 1992 9: 227–233

    CAS  PubMed  Google Scholar 

  19. Saarinen UM, Hovi L, . Mäkipernaa High-dose thiotepa with autologous bone marrow rescue in pediatric solid tumors Bone Marrow Transplant 1991 8: 369–376

    CAS  PubMed  Google Scholar 

  20. Walterhouse DO, Hoover ML, Marymont MA . High-dose chemotherapy followed by peripheral blood stem cell rescue for metastatic rhabdomyosarcoma: the experience at Chicago children's memorial hospital Med Pediatr Oncol 1999 32: 88–92

    Article  CAS  Google Scholar 

  21. Koscielniak E, Klingebiel TH, Peters C et al. Do patients with metastatic and recurrent rhabdomysarcoma benefit from high-dose therapy with hematopoietic rescue? Report of the German/Austrian pediatric bone marrow transplantation group Bone Marrow Transplant 1997 19: 227–231

    Article  CAS  Google Scholar 

  22. Hara J, Osugi Y, Ohta H et al. Double conditioning consisting of thiotepa, melphalan and busulfan with stem cell rescue for the treatment of pediatrics solid tumors Bone Marrow Transplant 1998 22: 7–12

    Article  CAS  Google Scholar 

  23. Pinkerton CR . Megatherapy in childhood sarcoma. A decade of phase II studies: what next Bone Marrow Transplant 1992 10: (Suppl.2) 19

    Google Scholar 

  24. Pinkerton CR, Ladenstein R, Chauvin F . Megatherapy with autologous bone marrow rescue in advance rhabdomyosarcoma. The EBMT group experience EBMT XVIII Meeting 1992; 160 (Abstr.225)

    Google Scholar 

  25. Hartmann O, Vassal G, Valteau D et al. Autologous bone marrow transplantation in pediatric solid tumors: phase II studies Bone Marrow Transplant 1991 7: 106–111

    PubMed  Google Scholar 

  26. Pappo AS, Bowman LC, Furman WL et al. A phase II trial of high-dose methotrexate in previously untreated children and adolescents with high risk unresectable or metastatic rhabdomyasarcoma J Pediatr Hematol Oncol 1997 19: 438–442

    Article  CAS  Google Scholar 

  27. Carli M, Colombatti R, Pinkerton R et al. Prognostic factors in children with metastatic rhabdomyosarcoma: results of the European intergroup studies (EIS) MMT’89 and MMT’91 Med Pediatr Oncol 1997 29: 324 (Abstr.O-32)

    Article  Google Scholar 

Download references

Acknowledgements

We thank L Saint Ange for editing and L Morin for her incomparable support.

Author information

Authors and Affiliations

  1. Service d'Oncologie Pédiatrique, Institut Gustave Roussy, Villejuif, France

    L Lafay-Cousin, O Hartmann & O Oberlin

  2. Service d'Hématolo-Oncologie Pédiatrique, Centre Hospitalier Universitaire Saint Jacques, Besançon, France

    P Plouvier

  3. Service d'Hématolo-Oncologie, Centre Hospitalier Universitaire, Nantes, France

    F Méchinaud

  4. Service de Pédiatrie, Centre Hospitalier Universitaire, Caen, France

    P Boutard

Authors
  1. L Lafay-Cousin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O Hartmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P Plouvier
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F Méchinaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P Boutard
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. O Oberlin
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lafay-Cousin, L., Hartmann, O., Plouvier, P. et al. High-dose thiotepa and hematopoietic stem cell transplantation in pediatric malignant mesenchymal tumors: a phase II study. Bone Marrow Transplant 26, 627–632 (2000). https://doi.org/10.1038/sj.bmt.1702573

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1702573

Keywords

This article is cited by

Search

Advanced search

Quick links