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Autologous Transplant

High-dose BCNU followed by autologous hematopoietic stem cell transplantation in supratentorial high-grade malignant gliomas: a retrospective analysis of 114 patients

Summary:

Conventional treatment of high-grade glioma includes maximal surgical resection followed by external radiation therapy. Despite this treatment, the prognosis for patients is poor. High doses of chemotherapy might be another way to increase the response rate and median survival. Increasing doses of BCNU might be more effective, but also provokes unacceptable myelotoxicity. This dose-limiting toxicity can be circumvented by using autologous blood stem cell rescue. We report our experience of high-dose BCNU followed by transplantation of autologous hematopoietic stem cells in 114 patients with high-grade gliomas. Of the 114 gliomas, 78 were glioblastoma multiforme (GM) (68%), 24 anaplastic astrocytomas (AA) (21%), and 12 anaplastic oligodendrogliomas (OD) (11%). Complete surgical resection was performed for 22 patients (18 GM and 4 AA). The median age was 44 years (range 17–65). A total of 84 patients received autologous hematopoietic stem cells from bone marrow harvest, while 30 patients received granulocyte colony-stimulating factor followed by apheresis and received peripheral blood progenitor cells (PBPC). High dose of BCNU (800 mg/m2) was given at least 1 month after neurosurgery. Bone marrow or PBPC was transplanted 48–72 h after chemotherapy. Radiotherapy was started approximately 40 days after transplantation to a total of 60 Gy. Median follow-up was 89 months (19–163). The overall survival (OS) was, respectively, 12 months for GM, 37 months for OD and 81 months for AA. Histological type appeared to be the main discriminating factor, with a worse prognosis for GM. Within the GM population, age, completeness of surgery, and response appeared to be one important prognostic factors. The AA and OD populations were small to reliably assess prognostic factors. On multivariate analysis, the main prognostic factors were histologic type, quality of surgery, and age (P<0.005). Five of 114 patients had lethal complications from the procedure. Four of these patients had a Karnovsky performance score (KPS) of 60%. The protocol thus appears to be feasible but patients should be selected for KPS more than 70%. We observed long-term survivors, although the OS and the time to treatment failure seem to be comparable to that described for other treatment. Additional pilot studies are unlikely to reveal more than a modest benefit from this procedure and therefore a randomized study should be performed.

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References

  1. Fine HA, Dear KB, Loeffler JS et al. Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer 1993; 71: 2585–2597.

    Article  CAS  Google Scholar 

  2. Levin VA . Management of gliomas, medulloblastoma and CNS germ cell tumors. In: Cavalli F, Hansen HH, Kaye SB (ed). Textbook of Medical Oncology. Martin Dunitz: London, 1997, p 309.

    Google Scholar 

  3. Surawicz TS, Davis F, Freels S et al. Brain tumor survival: results from the National Cancer Data Base. J Neuro-oncol 1998; 40: 151–160.

    Article  CAS  Google Scholar 

  4. Prados MD, Russo C . Chemotherapy of brain tumors. Semin Surg Oncol 1998; 14: 8895.

    Article  Google Scholar 

  5. Forsyth PA, Roa WH . Primary central nervous system tumors in adults. Curr Treat Options Neurol 1999; 1: 377–394.

    Article  CAS  Google Scholar 

  6. Gerosa MA, Di Stefano E, Olivi A . VM-26 monochemotherapy trial in the treatment of recurrent supratentorial gliomas: preliminary report. Surg Neurol 1981; 15: 128–134.

    Article  CAS  Google Scholar 

  7. Levin VA . Chemotherapy for brain tumors of astrocytic and oligodendroglial lineage: the past decade and where we are heading. Neuro-oncol 1999; 1: 69–80.

    Article  CAS  Google Scholar 

  8. Cairncross G, Macdonald D, Ludwin S, et al. Chemotherapy for anaplastic oligodendroglioma. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1994; 12: 2013–2021.

    Article  CAS  Google Scholar 

  9. Huncharek M, Muscat J, Geschwind JF . Multi-drug versus single agent chemotherapy for high grade astrocytoma ; results of a meta-analysis. Anticancer Res 1998; 18: 4693–4697.

    CAS  PubMed  Google Scholar 

  10. Stewart LA and the Glioma Meta-analysis triallists (GMT) Group. Chemotherapy in adult high-grade glioma: a systemic review and meta-analysis of individual patient data from randomised trials. Lancet 2002; 359: 1011–1018.

    Article  CAS  Google Scholar 

  11. Newton HB, Bromberg J, Junck L, Page MA, Greenberg HS . Comparison between BCNU and procarbazine chemotherapy for treatment of gliomas. J Neurooncol 1993; 15: 257–263.

    Article  CAS  Google Scholar 

  12. Hildebrand J, Badjou R, Collard-Ronge E et al. Treatment of brain giomas with high dose of CCNU and autologous bone marrow transplantation. Biomedicine 1980; 32: 71–75.

    CAS  PubMed  Google Scholar 

  13. Hochberg FH, Parker LM, Takvorian T et al. High-dose BCNU with autologous bone marrow rescue for recurrent glioblastoma multiforme. J Neurosurg 1981; 54: 455–460.

    Article  CAS  Google Scholar 

  14. Takvorian T, Parker LM, Hochberg FH, Canellos GP . Autologous bone-marrow transplantation: host effects of high-dose BCNU. J Clin Oncol 1983; 1: 610–620.

    Article  CAS  Google Scholar 

  15. Mortimer JE, Hewlett JS, Bay J, Livingston RB . High dose BCNU with autologous bone marrow rescue in the treatment of recurrent malignant gliomas. J Neuro-oncol 1983; 1: 269–273.

    Article  CAS  Google Scholar 

  16. Phillips GL, Wolff SN, Fay JW et al. Intensive 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) monochemotherapy and autologous marrow transplantation for malignant glioma. J Clin Oncol 1986; 4: 639–645.

    Article  CAS  Google Scholar 

  17. Johnson DB, Thompson JM, Corwin JA et al. Prolongation of survival for high-grade malignant gliomas with adjuvant high-dose BCNU and autologous bone marrow transplantation. J Clin Oncol 1987; 5: 783–789.

    Article  CAS  Google Scholar 

  18. Mbidde EK, Selby PJ, Perren TJ et al. High dose BCNU chemotherapy with autologous bone marrow transplantation and full dose radiotherapy for grade IV astrocytoma. Br J Cancer 1988; 58: 779–782.

    Article  CAS  Google Scholar 

  19. Biron P, Vial C, Chauvin F et al. Strategy including surgery, high dose BCNU followed by ABMT and radiotherapy in supratentorial high grade astrocytomas: a report of 98 patients. In: Dicke KA, Armitage JO, Dicke-Evinger MJ (ed). Autologous Bone Marrow Transplantation: Proceedings of the Fifth International Symposium. University of Nebraska Medical Center: Omaha, 1991, pp 637–645.

    Google Scholar 

  20. Linassier C, Benboubker L, Velut S et al. High-dose BCNU with ABMT followed by radiation therapy in the treatment of supratentorial glioblastoma multiforme. Bone Marrow Transplant 1996; 18 (Suppl 1): S69–S72.

    PubMed  Google Scholar 

  21. Fleming TR . One sample multiple testing procedure for pahse II clinical trials. Biometrics 1982; 38: 143–151.

    Article  CAS  Google Scholar 

  22. Kaplan E, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  23. Kwiatkowski F, Girard M, Hacene K, Berlie J . Sem: a suitable statistical software adaptated for research in oncology. Bull Cancer 2000; 87: 715–721.

    CAS  PubMed  Google Scholar 

  24. Brem H, Mahaley Jr MS, Vick NA et al. Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas. J Neurosurg 1991; 74: 441–446.

    Article  CAS  Google Scholar 

  25. Mahaley Jr MS, Whaley RA, Blue M, Bertsch L . Central neurotoxicity following intracarotid BCNU chemotherapy for malignant gliomas. J Neuro-oncol 1986; 3: 297–314.

    Article  Google Scholar 

  26. Recht L, Fram RJ, Strauss G et al. Preirradiation chemotherapy of supratentorial malignant primary brain tumors with intracarotid cis-platinum (CDDP) and i.v. BCNU. A phase II trial. Am J Clin Oncol 1990; 13: 125–131.

    Article  CAS  Google Scholar 

  27. Legros M, Fleury J, Bay JO et al. rhGM-CSF vs placebo following rhGM-CSF-mobilized PBPC transplantation: a phase III double-blind randomized trial. Bone Marrow Transplant 1997; 19: 209–213.

    Article  CAS  Google Scholar 

  28. Lacroix M, Abi-Said D, Fourney DR et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 2001; 95: 190–198.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank AMGEN and the Ligne nationale contre la cancer, comitë du Puy de Dôme, for their support.

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Durando, X., Lemaire, JJ., Tortochaux, J. et al. High-dose BCNU followed by autologous hematopoietic stem cell transplantation in supratentorial high-grade malignant gliomas: a retrospective analysis of 114 patients. Bone Marrow Transplant 31, 559–564 (2003). https://doi.org/10.1038/sj.bmt.1703889

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