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:

Retinoblastoma

High-dose chemotherapy with autologous stem cell rescue in children with retinoblastoma

Bone Marrow Transplantation volume 31, pages 281–284 (2003)Cite this article

Summary:

Children with metastatic retinoblastoma are considered to have a poor prognosis after conventional chemotherapy. We used high-dose chemotherapy (HDC) with peripheral hematopoietic stem cell transplantation in such patients in an attempt to improve their survival. Four patients with bone marrow metastases and one child with extraorbital disease were treated with HDC after achieving complete remission by enucleation and conventional chemotherapy. The child with extraorbital tumor was the only one to receive local irradiation. The conditioning regimen included thiotepa (900 mg/m2), etoposide (40 mg/kg) and carboplatin (1.5 g/m2) in four patients, and BCNU (300 mg/m2), cyclophosphamide (6.8 g/m2) and etoposide (1.6 g/m2) in one child. Hematologic recovery occurred without delay in all patients. The main toxicities were diarrhea, mucositis and infectious complications. No toxic deaths or any major late toxicities were observed. The child treated with the BCNU regimen developed a meningeal relapse 10 months after HDC, which was partially resected and treated with conventional chemotherapy, but not with radiotherapy. He is in complete remission (CR) 105 months off treatment. The other patients are in CCR for 107, 57, 9 and 8 months after HDC. HDC with thiotepa, etoposide and carboplatin may represent a curative option for children with extrabulbar or disseminated retinoblastoma responsive to chemotherapy. It may control occult CNS disease. The necessity to irradiate these children and the curative potential of this strategy for patients with bulky CNS disease remain to be determined.

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. Donaldson SS, Egbert PR, Lee W . In: Pizzo PA, Poplack DG (eds). Principles and Practice of Pediatric Oncology. JB Lippincott: Philadelphia, 1993, pp 683–696.

    Google Scholar 

  2. German Childhood Cancer Registry Annual Report 2000, Mainz, Germany, 2002, p 71, available at http://www.Kinderkrebsregister.de

  3. Shields CL, Shields JA, Baez K et al. Optic nerve invasion of retinoblastoma. Metastatic potential and clinical risk factors. Cancer 1994; 73: 692–698.

    Article  CAS  Google Scholar 

  4. Khelfaoui F, Valdidire P, Auperin A et al. Histopathologic risk factors in retinoblastoma, a retrospective study of 172 patients treated in a single institution. Cancer 1996; 77: 1206–1213.

    Article  CAS  Google Scholar 

  5. Grabowski EF, Abramson DH . Intraocular und extraocular retinoblastoma. Hematol Oncol Clin North Am 1987; 1: 721–735.

    Article  CAS  Google Scholar 

  6. Doz F, Khelfaoui F, Mosseri V et al. The role of chemotherapy in orbital involvement of retinoblastoma. The experience of a single institution with 33 patients. Cancer 1994; 74: 722–732.

    Article  CAS  Google Scholar 

  7. Schwartzman E, Chantado G, Fanddińo A et al. Results of a stage-based-protocol for the treatment of retinoblastoma. J Clin Oncol 1996; 14: 1532–1536.

    Article  Google Scholar 

  8. Namouni F, Doz F, Tanguy ML et al. High-dose chemotherapy with carboplatin, etoposide and cyclosphosphamide followed by haematopoietic stem cell rescue in patients with high risk retinoblastoma: a SFOP and SFGM study. Eur J Cancer 1997; 33: 2368–2375.

    Article  CAS  Google Scholar 

  9. Howarth C, Meyer D, Hustu HO et al. Stage-related combined modality treatment of retinoblastoma. Results of a prospective study. Cancer 1980; 45: 851–858.

    Article  CAS  Google Scholar 

  10. White L . Chemotherapy in retinoblastoma: current status and future directions. Am J Pediatr Hematol Oncol 1991; 13: 189–201.

    Article  CAS  Google Scholar 

  11. Pratt CB, Fontanesi J, Chenaille P et al. Chemotherapy for extraocular retinoblastoma. Pediatr Hematol Oncol 1996; 11: 301–309.

    Article  Google Scholar 

  12. Doz F, Neuenschwander S, Plantaz D et al. Etoposide and carboplatin in extraocular retinoblastoma: a study by the Société Française d'Oncologie Pédiatrique. J Clin Oncol 1995; 13: 902–909.

    Article  CAS  Google Scholar 

  13. Bornfeld N, Schüler A, Beckrakis N et al. Preliminary results of primary chemotherapy in retinoblastoma. Klin. Päediatr. 1997; 209: 216–221.

    Article  CAS  Google Scholar 

  14. Saleh RA, Cross S, Cassano W et al. Metastatic retinoblastoma successfully treated with immunomagnetic purged autologous bone marrow transplantation. Cancer 1988; 62: 2301–2303.

    Article  CAS  Google Scholar 

  15. Saarinen UM, Sariola H, Hovi L et al. Recurrent disseminated retinoblastoma treated by high-dose chemotherapy, total body irradiation and autologous bone marrow rescue. Am J Pediatr Hematol Oncol 1991; 13: 315–319.

    Article  CAS  Google Scholar 

  16. Heidemann RL, Cole DE, Balis F et al. Phase I and pharmaco-qkinetic evaluation of thiotepa in the cerebrospinal fluid and plasma of pediatric patients: evidence for dose-dependent plasma clearance of thiotepa. Cancer Res 1989; 49: 736–741.

    Google Scholar 

  17. ÓDwyer PJ, Lacreta F, Engstrom PF et al. Phase I/pharmacokinetic reevaluation of thiotepa. Cancer Res 1991; 51: 3171–3176.

    Google Scholar 

  18. Saarinen UM, Hovi L, Mäkipernan A et al. High-dose thiotepa with autologous bone marrow rescue in pediatric solid tumors. Bone Marrow Transplant 1991; 8: 369–376.

    CAS  Google Scholar 

  19. Lucidarme N, Valteau-Couanet D, Oberlin O et al. Phase II study 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 

  20. Laffay-Cousin I, 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 2000; 26: 627–632.

    Article  Google Scholar 

  21. Eder JP, Elias A, Shea TC et al. A phase I–II study of cyclophosphamide, thiotepa, and carboplatin with autologous bone marrow transplantation in solid tumor patients. J Clin Oncol 1990; 8: 1239–1245.

    Article  CAS  Google Scholar 

  22. Pession A, Prete A, Locatelli F et al. Phase I study of high-dose thiotepa with busulfan, etoposide, and autologous stem cell support in children with disseminated solid tumors. Med Pediatr Oncol 1999; 33: 450–454.

    Article  CAS  Google Scholar 

  23. Worth LL, Tran H, Petropopoulos D et al. Hematopoietic stem cell transplantation for childhood myeloid malignancies after high-dose thiotepa, busulfan and cyclophosphamide. Bone Marrow Transplant 1999; 24: 947–952.

    Article  CAS  Google Scholar 

  24. Richard L, Heidemann E, Douglass R et al. High-dose chemotherapy and autologous bone marrow rescue followed by interstitial and external-beam radiotherapy in newly diagnosed pediatric malignant gliomas. J Clin Oncol 1993; 8: 1458–1465.

    Google Scholar 

  25. Jonathan L, Goldmann S, Wong M et al. 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; 9: 2495–2503.

    Google Scholar 

  26. Dunkel IJ, Boyett JM, Yates A et al. High-dose carboplatin, thiotepa and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. J Clin Oncol 1998; 16: 222–228.

    Article  CAS  Google Scholar 

  27. Papadopoulos KP, Garvin JH, Fetell M et al. High-dose thiotepa and etoposide-based regimens with autologous hepatopoietic support for high-risk or recurrent CNS tumors in children and adults. Bone Marrow Transplant 1998; 22: 661–667.

    Article  CAS  Google Scholar 

  28. Hertzberg H, Kremens B, Velten I et al. Recurrent disseminated retinoblastoma in a 7-year-old-girl treated successfully by high-dose chemotherapy and CD34-selected autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 2001; 27: 653–655.

    Article  CAS  Google Scholar 

  29. Dunkel IJ, Aledo A, Kernan NA et al. Successful treatment of metastatic retinoblastoma. Cancer 2000; 89: 2117–2121.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, University Hospitals of Essen, Germany

    B Kremens, R Wieland & W Havers

  2. Department of Pediatrics, University of Homburg/Saar, Germany

    H Reinhard

  3. Department of Pediatrics, University of Erlangen, Germany

    J D Beck

  4. Department of Pediatrics, University of Frankfurt/Main, Germany

    T Klingebiel

  5. Department of Pediatrics of Klinikum Schwerin, Germany

    D Neubert

  6. Department of Ophthalmology, University of Essen, Germany

    N Bornfeld

Authors
  1. B Kremens
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Wieland
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H Reinhard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D Neubert
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J D Beck
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T Klingebiel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N Bornfeld
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. W Havers
    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

Kremens, B., Wieland, R., Reinhard, H. et al. High-dose chemotherapy with autologous stem cell rescue in children with retinoblastoma. Bone Marrow Transplant 31, 281–284 (2003). https://doi.org/10.1038/sj.bmt.1703832

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703832

Keywords

This article is cited by

Search

Advanced search

Quick links