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:

Conditioning Regimens

Intensive conditioning regimen of etoposide (VP-16), cyclophosphamide and carmustine (VCB) followed by autologous hematopoietic stem cell transplantation for relapsed and refractory Hodgkin's lymphoma

Bone Marrow Transplantation volume 41, pages 613–619 (2008)Cite this article

Abstract

Several high-dose therapy regimens are used for autologous hematopoietic stem cell transplantation (auto-HSCT) for relapsed and refractory Hodgkin's lymphoma (HL) with variable disease response. An intensified regimen of etoposide (VP-16) 2400 mg/m2, cyclophosphamide 7200 mg/m2 and carmustine (BCNU) 600 mg/m2 (VCB) pre-auto-HSCT was developed to overcome disease recurrence. A total of 43 relapsed and refractory HL patients underwent auto-HSCT between January 1992 and December 2004. At day 100 there were 37 (86%) complete responses. A total of 40 patients survived beyond day 100, 14 of whom subsequently relapsed/progressed. At a median follow-up of 4.9 years (range 1.5–11.4 years), 26 patients (60%) are alive and disease free. Five-year actuarial event-free survival (EFS) was 53% (95% CI 35–70%) and median EFS was 5.9 years. Median progression-free and overall survivals have not been reached. EFS was reduced with an increasing number of prognostic factors (Karnofsky performance status, KPS <90, chemotherapy-resistant disease and ⩾3 chemotherapy regimens prior to transplant ⩽1 vs ⩾2; P=0.049). Grade III–IV regimen-related toxicity was 9% (n=4). The 1-year cumulative incidence of interstitial pneumonitis (IP) was 36%, however only two patients died of IP complications. Disease progression was the most common cause of death (n=10, 23%). Intensive VCB is an effective and well-tolerated preparative regimen for relapsed and refractory HL auto-HSCT.

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

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Aisenberg AC . Problems in Hodgkin's disease management. Blood 1999; 93: 761–779.

    CAS  PubMed  Google Scholar 

  2. Bonfante V, Santoro A, Viviani S, Devizzi L, Balzarotti M, Soncini F et al. Outcome of patients with Hodgkin's disease failing after primary MOPP-ABVD. J Clin Oncol 1997; 15: 528–534.

    Article  CAS  PubMed  Google Scholar 

  3. Fung HC, Nademanee AP . Approach to Hodgkin's lymphoma in the new millennium. Hematol Oncol 2002; 20: 1–15.

    Article  PubMed  Google Scholar 

  4. Longo DL, Glatstein E, Duffey PL, Young RC, Ihde DC, Bastian AW et al. Alternating MOPP and ABVD chemotherapy plus mantle-field radiation therapy in patients with massive mediastinal Hodgkin's disease. J Clin Oncol 1997; 15: 3338–3346.

    Article  CAS  PubMed  Google Scholar 

  5. Andre M, Henry-Amar M, Pico JL, Brice P, Blaise D, Kuentz M et al. Comparison of high-dose therapy and autologous stem-cell transplantation with conventional therapy for Hodgkin's disease induction failure: a case–control study. Societe Francaise de Greffe de Moelle. J Clin Oncol 1999; 17: 222–229.

    Article  CAS  PubMed  Google Scholar 

  6. Anselmo AP, Meloni G, Cavalieri E, Proia A, Enrici RM, Funaro D et al. Conventional salvage chemotherapy vs high-dose therapy with autografting for recurrent or refractory Hodgkin's disease patients. Ann Hematol 2000; 79: 79–82.

    Article  CAS  PubMed  Google Scholar 

  7. Bierman PJ, Bagin RG, Jagannath S, Vose JM, Spitzer G, Kessinger A et al. High dose chemotherapy followed by autologous hematopoietic rescue in Hodgkin's disease: long-term follow-up in 128 patients. Ann Oncol 1993; 4: 767–773.

    Article  CAS  PubMed  Google Scholar 

  8. Horning SJ, Chao NJ, Negrin RS, Hoppe RT, Long GD, Hu WW et al. High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: analysis of the Stanford University results and prognostic indices. Blood 1997; 89: 801–813.

    CAS  PubMed  Google Scholar 

  9. Lazarus HM, Loberiza Jr FR, Zhang MJ, Armitage JO, Ballen KK, Bashey A et al. Autotransplants for Hodgkin's disease in first relapse or second remission: a report from the autologous blood and marrow transplant registry (ABMTR). Bone Marrow Transplant 2001; 27: 387–396.

    Article  CAS  PubMed  Google Scholar 

  10. Lazarus HM, Rowlings PA, Zhang MJ, Vose JM, Armitage JO, Bierman PJ et al. Autotransplants for Hodgkin's disease in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol 1999; 17: 534–545.

    Article  CAS  PubMed  Google Scholar 

  11. Linch DC, Winfield D, Goldstone AH, Moir D, Hancock B, McMillan A et al. Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial. Lancet 1993; 341: 1051–1054.

    Article  CAS  PubMed  Google Scholar 

  12. Moskowitz CH, Kewalramani T, Nimer SD, Gonzalez M, Zelenetz AD, Yahalom J . Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin's disease. Br J Haematol 2004; 124: 645–652.

    Article  PubMed  Google Scholar 

  13. Nademanee A, O'Donnell MR, Snyder DS, Schmidt GM, Parker PM, Stein AS et al. High-dose chemotherapy with or without total body irradiation followed by autologous bone marrow and/or peripheral blood stem cell transplantation for patients with relapsed and refractory Hodgkin's disease: results in 85 patients with analysis of prognostic factors. Blood 1995; 85: 1381–1390.

    CAS  PubMed  Google Scholar 

  14. Rapoport AP, Rowe JM, Kouides PA, Duerst RA, Abboud CN, Liesveld JL et al. One hundred autotransplants for relapsed or refractory Hodgkin's disease and lymphoma: value of pretransplant disease status for predicting outcome. J Clin Oncol 1993; 11: 2351–2361.

    Article  CAS  PubMed  Google Scholar 

  15. Sureda A, Arranz R, Iriondo A, Carreras E, Lahuerta JJ, Garcia-Conde J et al. Autologous stem-cell transplantation for Hodgkin's disease: results and prognostic factors in 494 patients from the Grupo Espanol de Linfomas/Transplante Autologo de Medula Osea Spanish Cooperative Group. J Clin Oncol 2001; 19: 1395–1404.

    Article  CAS  PubMed  Google Scholar 

  16. Sweetenham JW, Taghipour G, Milligan D, Blystad AK, Caballero D, Fassas A et al. High-dose therapy and autologous stem cell rescue for patients with Hodgkin's disease in first relapse after chemotherapy: results from the EBMT. Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 1997; 20: 745–752.

    Article  CAS  PubMed  Google Scholar 

  17. Yuen AR, Rosenberg SA, Hoppe RT, Halpern JD, Horning SJ . Comparison between conventional salvage therapy and high-dose therapy with autografting for recurrent or refractory Hodgkin's disease. Blood 1997; 89: 814–822.

    CAS  PubMed  Google Scholar 

  18. Longo DL, Duffey PL, Young RC, Hubbard SM, Ihde DC, Glatstein E et al. Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin's disease after combination chemotherapy: the low probability for cure. J Clin Oncol 1992; 10: 210–218.

    Article  CAS  PubMed  Google Scholar 

  19. Hahn T, Benekli M, Wong C, Moysich KB, Hyland A, Michalek AM et al. A prognostic model for prolonged event-free survival after autologous or allogeneic blood or marrow transplantation for relapsed and refractory Hodgkin's disease. Bone Marrow Transplant 2005; 35: 557–566.

    Article  CAS  PubMed  Google Scholar 

  20. Phillips GL, Wolff SN, Herzig RH, Lazarus HM, Fay JW, Lin HS et al. Treatment of progressive Hodgkin's disease with intensive chemoradiotherapy and autologous bone marrow transplantation. Blood 1989; 73: 2086–2092.

    CAS  PubMed  Google Scholar 

  21. Stiff PJ, Unger JM, Forman SJ, McCall AR, LeBlanc M, Nademanee AP et al. The value of augmented preparative regimens combined with an autologous bone marrow transplant for the management of relapsed or refractory Hodgkin disease: a Southwest Oncology Group phase II trial. Biol Blood Marrow Transplant 2003; 9: 529–539.

    Article  PubMed  Google Scholar 

  22. Sureda A, Constans M, Iriondo A, Arranz R, Caballero MD, Vidal MJ et al. Prognostic factors affecting long-term outcome after stem cell transplantation in Hodgkin's lymphoma autografted after a first relapse. Ann Oncol 2005; 16: 625–633.

    Article  CAS  PubMed  Google Scholar 

  23. Wheeler C, Eickhoff C, Elias A, Ibrahim J, Ayash L, McCauley M et al. High-dose cyclophosphamide, carmustine, and etoposide with autologous transplantation in Hodgkin's disease: a prognostic model for treatment outcomes. Biol Blood Marrow Transplant 1997; 3: 98–106.

    CAS  PubMed  Google Scholar 

  24. Bolwell BJ, Kalaycio M, Goormastic M, Dannley R, Andresen SW, Lichtin A et al. Progressive disease after ABMT for Hodgkin's disease. Bone Marrow Transplant 1997; 20: 761–765.

    Article  CAS  PubMed  Google Scholar 

  25. Arranz R, Tomas JF, Gil-Fernandez JJ, Martinez-Chamorro C, Granados E, Alegre A et al. Autologous stem cell transplantation (ASCT) for poor prognostic Hodgkin's disease (HD): comparative results with two CBV regimens and importance of disease status at transplant. Bone Marrow Transplant 1998; 21: 779–786.

    Article  CAS  PubMed  Google Scholar 

  26. Fleming DR, Wolff SN, Fay JW, Brown RA, Lynch JP, Bolwell BJ et al. Protracted results of dose-intensive therapy using cyclophosphamide, carmustine, and continuous infusion etoposide with autologous stem cell support in patients with relapse or refractory Hodgkin's disease: a phase II study from the North American Marrow Transplant Group. Leuk Lymphoma 1999; 35: 91–98.

    Article  CAS  PubMed  Google Scholar 

  27. Reece DE, Barnett MJ, Connors JM, Fairey RN, Fay JW, Greer JP et al. Intensive chemotherapy with cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation for relapsed Hodgkin's disease. J Clin Oncol 1991; 9: 1871–1879.

    Article  CAS  PubMed  Google Scholar 

  28. Wheeler C, Antin JH, Churchill WH, Come SE, Smith BR, Bubley GJ et al. Cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation in refractory Hodgkin's disease and non-Hodgkin's lymphoma: a dose-finding study. J Clin Oncol 1990; 8: 648–656.

    Article  CAS  PubMed  Google Scholar 

  29. Bearman SI, Appelbaum RF, Buckner CD, Petersen FB, Fisher LD, Clift RA et al. Regimen-related toxicity in patients undergoing bone marrow transplantation. J Clin Oncol 1988; 6: 1562–1568.

    Article  CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

  31. Bierman PJ, Anderson JR, Freeman MB, Vose JM, Kessinger A, Bishop MR et al. High-dose chemotherapy followed by autologous hematopoietic rescue for Hodgkin's disease patients following first relapse after chemotherapy. Ann Oncol 1996; 7: 151–156.

    Article  CAS  PubMed  Google Scholar 

  32. Crilley P, Lazarus H, Topolsky D, Ciobanu N, Creger RJ, Fox RM et al. Comparison of preparative transplantation regimens using carmustine/etoposide/cisplatin or busulfan/etoposide/cyclophosphamide in lymphoid malignancies. Semin Oncol 1993; 20 (Suppl 4): 50–54.

    CAS  PubMed  Google Scholar 

  33. Kroger N, Hoffknecht M, Hanel M, Kruger W, Zeller W, Stockschlader M et al. Busulfan, cyclophosphamide and etoposide as high-dose conditioning therapy in patients with malignant lymphoma and prior dose-limiting radiation therapy. Bone Marrow Transplant 1998; 21: 1171–1175.

    Article  CAS  PubMed  Google Scholar 

  34. Lazarus HM, Crilley P, Ciobanu N, Creger RJ, Fox RM, Shina DC et al. High-dose carmustine, etoposide, and cisplatin and autologous bone marrow transplantation for relapsed and refractory lymphoma. J Clin Oncol 1992; 10: 1682–1689.

    Article  CAS  PubMed  Google Scholar 

  35. Moskowitz CH, Nimer SD, Zelenetz AD, Trippett T, Hedrick EE, Filippa DA et al. A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood 2001; 97: 616–623.

    Article  CAS  PubMed  Google Scholar 

  36. Evens AM, Altman JK, Mittal BB, Hou N, Rademaker A, Patton D et al. Phase I/II trial of total lymphoid irradiation and high-dose chemotherapy with autologous stem-cell transplantation for relapsed and refractory Hodgkin's lymphoma. Ann Oncol 2007; 18: 679–688.

    Article  CAS  PubMed  Google Scholar 

  37. Caballero MD, Rubio V, Rifon J, Heras I, Garcia-Sanz R, Vazquez L et al. BEAM chemotherapy followed by autologous stem cell support in lymphoma patients: analysis of efficacy, toxicity and prognostic factors. Bone Marrow Transplant 1997; 20: 451–458.

    Article  CAS  PubMed  Google Scholar 

  38. Chopra R, Linch DC, McMillan AK, Blair S, Patterson KG, Moir D et al. Mini-BEAM followed by BEAM and ABMT for very poor risk Hodgkin's disease. Br J Haematol 1992; 81: 197–202.

    Article  CAS  PubMed  Google Scholar 

  39. Chopra R, McMillan AK, Linch DC, Yuklea S, Taghipour G, Pearce R et al. The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease. A single-center eight-year study of 155 patients. Blood 1993; 81: 1137–1145.

    CAS  PubMed  Google Scholar 

  40. Geisler CH, Hansen MM, Andersen NS, Brown P, Christensen LD, Dickmeiss E et al. BEAM+autologous stem cell transplantation in malignant lymphoma: 100 consecutive transplants in a single center. Efficacy, toxicity and engraftment in relation to stem-cell source and previous treatment. Eur J Haematol 1998; 61: 173–182.

    Article  CAS  PubMed  Google Scholar 

  41. Smith AG, Long SG, Janmohammed RM, Macdonald DF, Leyland MJ, Milligan DW et al. BEAM autografting in lymphoma—experience at one centre. Leuk Lymphoma 1992; 7 (Suppl): 23–28.

    Article  PubMed  Google Scholar 

  42. Demirer T, Weaver CH, Buckner CD, Petersen FB, Bensinger WI, Sanders J et al. High-dose cyclophosphamide, carmustine, and etoposide followed by allogeneic bone marrow transplantation in patients with lymphoid malignancies who had received prior dose-limiting radiation therapy. J Clin Oncol 1995; 13: 596–602.

    Article  CAS  PubMed  Google Scholar 

  43. Weaver CH, Appelbaum FR, Petersen FB, Clift R, Singer J, Press O et al. High-dose cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation in patients with lymphoid malignancies who have received dose-limiting radiation therapy. J Clin Oncol 1993; 11: 1329–1335.

    Article  CAS  PubMed  Google Scholar 

  44. Jones RB, Matthes S, Kemme D, Dufton C, Kernan S . Cyclophosphamide, cisplatin, and carmustine: pharmacokinetics of carmustine following multiple alkylating-agent interactions. Cancer Chemother Pharmacol 1994; 35: 59–63.

    Article  CAS  PubMed  Google Scholar 

  45. Jones RB, Matthes S, Shpall EJ, Fisher JH, Stemmer SM, Dufton C et al. Acute lung injury following treatment with high-dose cyclophosphamide, cisplatin, and carmustine: pharmacodynamic evaluation of carmustine. J Natl Cancer Inst 1993; 85: 640–647.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dr Roy Jones, Pharmaceutical Development Center, The University of Texas MD Anderson Cancer Center, for helpful discussion regarding carmustine pharmacokinetics and we acknowledge the patients who participated in this study, the Roswell Park Cancer Institute nursing staff and supportive care personnel and the referring doctors.

Author information

Author notes

  1. M Benekli and S L Smiley: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Gazi University Faculty of Medicine, Ankara, Turkey

    M Benekli

  2. Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA

    S L Smiley, T Younis, M S Czuczman, F Hernandez-Ilizaliturri, M Battiwalla, S Padmanabhan, P L McCarthy Jr & T Hahn

  3. Blood and Marrow Transplantation Program, Roswell Park Cancer Institute, Buffalo, NY, USA

    S L Smiley, M Battiwalla, P L McCarthy Jr & T Hahn

  4. Department of Pediatrics, Roswell Park Cancer Institute, Buffalo, NY, USA

    B Bambach

Authors
  1. M Benekli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S L Smiley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Younis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M S Czuczman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F Hernandez-Ilizaliturri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B Bambach
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Battiwalla
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S Padmanabhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P L McCarthy Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. T Hahn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S L Smiley.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Benekli, M., Smiley, S., Younis, T. et al. Intensive conditioning regimen of etoposide (VP-16), cyclophosphamide and carmustine (VCB) followed by autologous hematopoietic stem cell transplantation for relapsed and refractory Hodgkin's lymphoma. Bone Marrow Transplant 41, 613–619 (2008). https://doi.org/10.1038/sj.bmt.1705951

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705951

Keywords

This article is cited by

Search

Advanced search

Quick links