Skip to main content

Advertisement

Log in

High-dose chemotherapy and autologous peripheral blood stem cell transplantation in adult patients with high-risk or advanced Ewing and soft tissue sarcoma

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Despite the availability of combined-modality treatment for Ewing sarcoma (ES) and soft tissue sarcomas (STS), results from independent groups still indicate a poor prognosis for high-risk and metastasized patients. The benefit of high-dose chemotherapy (HDCT) with autologous peripheral blood stem cell transplantation (ASCT) as compared to standard treatment is not defined.

Methods

Here, we report of HDCT in 35 consecutive adult patients with poor-risk ES or rhabdomyosarcoma (n = 11) and STS (n = 24) undergoing ASCT between July 1992 and March 2003. At a median follow-up of 100.6 months after ASCT, 11 patients are alive, with nine in sustained complete remission (CR) and each one in partial remission (PR) and stable disease. Median overall survival (OS) from ASCT was 17.1 months. Response to pretreatment, Karnofsky index > 80%, R 0 resection and first-line ASCT were associated with long-term OS (p < 0.05).

Conclusion

These data indicate that (1) patients achieving a CR or PR following induction, with preserved performance status and R 0 resection may benefit from ASCT and (2) that this can be an useful therapeutic modality in a subset of patients, in some achieving remarkable responses.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Atra A, Whelan JS, Calvagna V, Shankar AG, Ashley S, Shepherd V, Souhami RL, Pinkerton CR (1997) High-dose busulphan/melphalan with autologous stem cell rescue in Ewing’s sarcoma. Bone Marrow Transplant 20:843–846

    Article  PubMed  CAS  Google Scholar 

  • Barker LM, Pendergrass TW, Sanders JE, Hawkins DS (2005) Survival after recurrence of Ewing’s sarcoma family of tumors. J Clin Oncol 23:4354–4362

    Article  PubMed  Google Scholar 

  • Blay JY, Bouhour D, Ray-Coquard I, Dumontet C, Philip T, Biron P (2000) High-dose chemotherapy with autologous hematopoietic stem-cell transplantation for advanced soft tissue sarcoma in adults. J Clin Oncol 18:3643–3650

    PubMed  CAS  Google Scholar 

  • Burdach S, van Kaick B, Laws HJ, Ahrens S, Haase R, Korholz D, Pape H, Dunst J, Kahn T, Willers R, Engel B, Dirksen U, Kramm C, Nurnberger W, Heyll A, Ladenstein R, Gadner H, Jurgens H, Go el U (2000) Allogeneic and autologous stem-cell transplantation in advanced Ewing tumor: an update after long-term follow-up from two centers of the European intergroup study EICESS. Stem-cell transplant programs at Dusseldorf University Medical Center, Germany and St. Anna Kinderspital, Vienna, Austria. Ann Oncol 11:1451–1462

    Article  PubMed  CAS  Google Scholar 

  • Burgert EO Jr, Nesbit ME, Garnsey LA, Gehan EA, Herrmann J, Vietti TJ, Cangir A, Tefft M, Evans R, Thomas P (1990) Multimodal therapy for the management of nonpelvic, localized Ewing’s sarcoma of bone: intergroup study IESS-II. J Clin Oncol 8:1514–1524

    PubMed  Google Scholar 

  • Clark MA, Fisher C, Judson I, Thomas JM (2005) Soft-tissue sarcomas in adults. N Engl J Med 353:701–711

    Article  PubMed  CAS  Google Scholar 

  • Craft AW, Cotterill SJ, Bullimore JA, Pearson D (1997) Long-term results from the first UKCCSG Ewing’s tumours study (ET-1). United Kingdom children’s cancer study group (UKCCSG) and the medical research council bone sarcoma working party. Eur J Cancer 33:1061–1069

    Article  PubMed  CAS  Google Scholar 

  • Craft A, Cotterill S, Malcolm A, Spooner D, Grimer R, Souhami R, Imeson J, Lewis I (1998) Ifosfamide-containing chemotherapy in Ewing’s sarcoma: the second United Kingdom children’s cancer study group and the medical research council Ewing’s tumor study. J Clin Oncol 16:3628–3633

    PubMed  CAS  Google Scholar 

  • Cotterill SJ, Ahrens S, Paulussen M, Jurgens HF, Voute PA, Gadner H, Craft AW (2000) Prognostic factors in Ewing’s tumor of bone: analysis of 975 patients from European intergroup cooperative Ewing’s sarcoma study group. J Clin Oncol 18:3108–3114

    PubMed  CAS  Google Scholar 

  • Diaz MA, Vicent MG, Madero L (1999) High-dose busulfan/melphalan as conditioning for autologous PBSC transplantation in pediatric patients with solid tumors. Bone Marrow Transplant 24:1157–1159

    Article  PubMed  CAS  Google Scholar 

  • Du S, Lawrence EJ, Strzelecki D, Rajput P, Xia SJ, Gottesman DM, Barr FG (2005) Co-expression of alternatively spliced forms of PAX3, PAX7, PAX3-FKHR and PAX7-FKHR with distinct DNA binding and transactivation properties in rhabdomyosarcoma. Int J Cancer 115:85–92

    Article  PubMed  CAS  Google Scholar 

  • Engelhardt M, Douville J, Behringer D, Jahne A, Smith A, Henschler R, Lange W (2001) Hematopoietic recovery of ex vivo perfusion culture expanded bone marrow and unexpanded peripheral blood progenitors after myeloablative chemotherapy. Bone Marrow Transplant 27:249–259

    Article  PubMed  CAS  Google Scholar 

  • Evans RG, Nesbit ME, Gehan EA, Garnsey LA, Burgert O Jr, Vietti TJ, Cangir A, Tefft M, Thomas P, Askin FB (1991) Multimodal therapy for the management of localized Ewing’s sarcoma of pelvic and sacral bones: a report from the second intergroup study. J Clin Oncol 9:1173–1180

    PubMed  CAS  Google Scholar 

  • Fischmeister G, Zoubek A, Jugovic D, Witt V, Ladenstein R, Fritsch G, Hocker P, Gadner H, Kovar H (1999) Low incidence of molecular evidence for tumour in PBPC harvests from patients with high risk Ewing tumours. Bone Marrow Transplant 24:405–409

    Article  PubMed  CAS  Google Scholar 

  • Fizazi K, Dohollou N, Blay JY, Guerin S, Le Cesne A, Andre F, Pouillart P, Tursz T, Nguyen BB (1998) Ewing’s family of tumors in adults: multivariate analysis of survival and long-term results of multimodality therapy in 182 patients. J Clin Oncol 16:3736–3743

    PubMed  CAS  Google Scholar 

  • Gronchi A, Casali PG, Mariani L, Miceli R, Fiore M, Lo Vullo S, Bertulli R, Collini P, Lozza L, Olmi P, Rosai J (2005) Status of surgical margins and prognosis in adult soft tissue sarcomas of the extremities: a series of patients treated at a single institution. J Clin Oncol 23:96–104

    Article  PubMed  CAS  Google Scholar 

  • Harousseau JL (1999) Optimizing peripheral blood progenitor cell autologous transplantation in multiple myeloma. Haematologica 84:548–553

    PubMed  CAS  Google Scholar 

  • Hawkins D, Barnett T, Bensinger W, Gooley T, Sanders J (2000) Busulfan, melphalan, and thiotepa with or without total marrow irradiation with hematopoietic stem cell rescue for poor-risk Ewing-sarcoma-family tumors. Med Pediatr Oncol 34:328–337

    Article  PubMed  CAS  Google Scholar 

  • Horowitz ME, Kinsella TJ, Wexler LH, Belasco J, Triche T, Tsokos M, Steinberg SM, McClure L, Longo DL, Steis RG (1993) Total-body irradiation and autologous bone marrow transplant in the treatment of high-risk Ewing’s sarcoma and rhabdomyosarcoma. J Clin Oncol 11:1911–1918

    PubMed  CAS  Google Scholar 

  • Huang HY, Illei PB, Zhao Z, Mazumdar M, Huvos AG, Healey JH, Wexler LH, Gorlick R, Meyers P, Ladanyi M (2005) Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse. J Clin Oncol 23:548–558

    Article  PubMed  CAS  Google Scholar 

  • Issels RD (1995) Soft tissue sarcomas—what is currently being done. Eur J Surg Oncol 21:471–474

    Article  PubMed  CAS  Google Scholar 

  • Jenkin RD, Al-Fawaz I, Al-Shabanah MO, Allam A, Ayas M, Memon M, Rifai S, Schultz HP (2001) Metastatic Ewing sarcoma/PNET of bone at diagnosis: prognostic factors-a report from Saudi Arabia. Med Pediatr Oncol 37:383–389

    Article  PubMed  CAS  Google Scholar 

  • Kasper B, Lehnert T, Bernd L, Mechtersheimer G, Goldschmidt H, Ho AD, Egerer G (2004) High-dose chemotherapy with autologous peripheral blood stem cell transplantation for bone and soft-tissue sarcomas. Bone Marrow Transplant 34:37–41

    Article  PubMed  CAS  Google Scholar 

  • Kushner BH, Meyers PA (2001) How effective is dose-intensive/myeloablative therapy against Ewing’s sarcoma/primitive neuroectodermal tumor metastatic to bone or bone marrow? The memorial Sloan-Kettering experience and literature review. J Clin Oncol 19:870–880

    PubMed  CAS  Google Scholar 

  • Marina N, Meyers PA (2005) High-dose therapy and stem-cell rescue for Ewing’s family of tumors in second remission. J Clin Oncol 23:4262–4264

    Article  PubMed  Google Scholar 

  • Marina NM, Pappo AS, Parham DM, Cain AM, Rao BN, Poquette CA, Pratt CB, Greenwald C, Meyer WH (1999) Chemotherapy dose-intensification for pediatric patients with Ewing’s family of tumors and desmoplastic small round-cell tumors: a feasibility study at St. Jude children’s research hospital. J Clin Oncol 17:180–190

    PubMed  CAS  Google Scholar 

  • Meyers PA, Krailo MD, Ladanyi M, Chan KW, Sailer SL, Dickman PS, Baker DL, Davis JH, Gerbing RB, Grovas A, Herzog CE, Lindsley KL, Liu-Mares W, Nachman JB, Sieger L, Wadman J, Gorlick RG (2001) High-dose melphalan, etoposide, total-body irradiation, and autologous stem-cell reconstitution as consolidation therapy for high-risk Ewing’s sarcoma does not improve prognosis. J Clin Oncol 19:2812–2820

    PubMed  CAS  Google Scholar 

  • Oberlin O, Deley MC, Bui BN, Gentet JC, Philip T, Terrier P, Carrie C, Mechinaud F, Schmitt C, Babin-Boillettot A, Michon J, French Society of Paediatric Oncology (2001) Prognostic factors in localized Ewing’s tumours and peripheral neuroectodermal tumours: the third study of the French society of paediatric oncology (EW88 study). Br J Cancer 85:1646–1654

    Article  PubMed  CAS  Google Scholar 

  • Paulussen M, Ahrens S, Burdach S, Craft A, Dockhorn-Dworniczak B, Dunst J, Frohlich B, Winkelmann W, Zoubek A, Jurgens H (1998) Primary metastatic (stage IV) Ewing tumor: survival analysis of 171 patients from the EICESS studies. European intergroup cooperative Ewing sarcoma studies. Ann Oncol 9:275–281

    Article  PubMed  CAS  Google Scholar 

  • Pinkerton CR, Bataillard A, Guillo S, Oberlin O, Fervers B, Philip T (2001) Treatment strategies for metastatic Ewing’s sarcoma. Eur J Cancer 37:1338–1344

    Article  PubMed  CAS  Google Scholar 

  • Rosito P, Mancini AF, Rondelli R, Abate ME, Pession A, Bedei L, Bacci G, Picci P, Mercuri M, Ruggieri P, Frezza G, Campanacci M, Paolucci G (1999) Italian cooperative study for the treatment of children and young adults with localized Ewing sarcoma of bone: a preliminary report of 6 years of experience. Cancer 86:421–428

    Article  PubMed  CAS  Google Scholar 

  • Sluga M, Windhager R, Lang S, Heinzl H, Krepler P, Mittermayer F, Dominkus M, Zoubek A, Kotz R (2001) A long-term review of the treatment of patients with Ewing’s sarcoma in one institution. Eur J Surg Oncol 27:569–573

    Article  PubMed  CAS  Google Scholar 

  • Stewart DA, Gyonyor E, Paterson AH, Arthur K, Temple W, Schachar NS, Klassen J, Brown C, Russell JA (1996) High-dose melphalan +/− total body irradiation and autologous hematopoietic stem cell rescue for adult patients with Ewing’s sarcoma or peripheral neuroectodermal tumor. Bone Marrow Transplant 18:315–318

    PubMed  CAS  Google Scholar 

  • Strauss SJ, McTiernan A, Driver D, Hall-Craggs M, Sandison A, Cassoni AM, Kilby A, Michelagnoli M, Pringle J, Cobb J, Briggs T, Cannon S, Witt J, Whelan JS (2003) Single center experience of a new intensive induction therapy for Ewing’s family of tumors: feasibility, toxicity, and stem cell mobilization properties. J Clin Oncol 21:2974–2981

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Yaniv I, Cohen IJ, Stein J, Zilberstein J, Liberzon E, Atlas O, Grunshpan A, Sverdlov Y, Ash S, Zaizov R, Avigad S (2004) Tumor cells are present in stem cell harvests of Ewings sarcoma patients and their persistence following transplantation is associated with relapse. Pediatr Blood Cancer 42:404–409

    Article  PubMed  CAS  Google Scholar 

  • Zeiser R, Deschler B, Bertz H, Finke J, Engelhardt M (2004) Extramedullary vs medullary relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) in multiple myeloma (MM) and its correlation to clinical outcome. Bone Marrow Transplant 34:1057–1065

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank the internal reviewer in our institution and Dr. Jürgen Heinz for critical reading of the manuscript and valuable comments. We thank Mrs. I. Matt and our entire transplantation staff for their excellent support and patient care.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Engelhardt.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Engelhardt, M., Zeiser, R., Ihorst, G. et al. High-dose chemotherapy and autologous peripheral blood stem cell transplantation in adult patients with high-risk or advanced Ewing and soft tissue sarcoma. J Cancer Res Clin Oncol 133, 1–11 (2007). https://doi.org/10.1007/s00432-006-0137-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-006-0137-1

Keywords

Navigation