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 Manuscript
  • Published:

Lymphoma

A prospective study of intensive induction therapy with high-dose consolidation in patients with aggressive non-Hodgkin's lymphoma and two or three adverse prognostic factors

Leukemia volume 14, pages 2159–2165 (2000)Cite this article

Abstract

Patients with nhl and two or three factors of the international prognostic index (ipi) have a poor prognosis. we performed a prospective trial of intensive induction therapy followed with high-dose consolidation in such patients to determine the feasibility of this approach, as well as the response rate and survival. untreated patients with aggressive lymphoma under the age of 60 with two or three adverse prognostic factors (disseminated stage, increased serum ldh, ecog performance status >1) were prospectively included between June 1995 and April 1998 in a trial evaluating intensive induction chemotherapy with the ACE regimen (adriamycin day 1; cyclophosphamide days 1–2; etoposide days 1–3), with G-CSF support. Patients in complete remission after induction received one course of intensification with stem cell support (BEAM regimen), whereas patients in partial response received two intensifications (BEAM, then ICE regimens). Thirty-three patients (median age 38 years) were included. All patients presented WHO grade 4 leukopenia and 84% grade 3–4 thrombocytopenia during induction. There was one toxic death during induction. Twenty-nine patients proceeded to high-dose consolidation, including 12 patients who received a second high-dose treatment. The overall response rate was 88% (95% CI 76–99%), both after induction therapy and treatment completion. Thirty-nine percent of the patients had achieved complete remission after induction, and 73% after treatment completion. With a median follow-up after treatment onset of 29 months, the projected 3-year overall survival was 71% (95% CI 64–78%) and the event-free survival 58% (95% CI 50–66%). Event-free survival was significantly shorter in patients who did not achieve CR after induction therapy or after treatment completion. Early therapeutic intensification after intensive induction chemotherapy is feasible in patients with poor prognosis aggressive NHL and shows promising response and survival rates.

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
Figure 4

Similar content being viewed by others

References

  1. Shipp MA . A predictive model for aggressive NHL: the international non-Hodgkin's lymphoma prognostic factors project New Engl J Med 1994 329: 987–994

    Google Scholar 

  2. Shipp MA, Abeloff MD, Antman KH, Carroll G, Hagenbeek A, Loeffler M, Montserrat E, Radford JA, Salles G, Schmitz N, Symann M, Armitage JO, Philip T, Coiffier B . International consensus conference on high-dose therapy with hematopoietic stem cell transplantation in aggressive non-Hodgkin's lymphomas: report of the jury J Clin Oncol 1999 17: 423–429

    Article  CAS  PubMed Central  Google Scholar 

  3. Gisselbrecht C, Lepage E, Morel P, Lederlin P, Coiffier B, Tilly H, Bosly A, Gabarre J, Briere J, Fillet G, Molina T, Reyes F . Short and intensified treatment with autologous stem cell transplantation versus ACVB regimen in poor prognosis aggressive lymphoma. Prognostic factors of induction failure Ann Oncol 1996 7: (Suppl. 7) 18

    Google Scholar 

  4. Haioun C, Lepage E, Gisselbrecht C, Bastion Y, Coiffier B, Brice P, Bosly A, Dupriez B, Nouvel C, Tilly H, Lederlin P, Biron P, Briere J, Gaulard P, Reyes F . Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin's lymphoma: updated results of the prospective study LNH87–2. Groupe d'Etude des Lymphomes de l'Adulte J Clin Oncol 1997 15: 1131–1137

    Article  CAS  PubMed Central  Google Scholar 

  5. Cortelazzo S, Rossi A, Viero P, Bellavita P, Marchioli R, Marfisi RM, Rambaldi A, Barbui T . BEAM chemotherapy and autologous haemopoietic progenitor cell transplantation as front-line therapy for high-risk patients with diffuse large cell lymphoma Br J Haematol 1997 99: 379–385

    Article  CAS  PubMed Central  Google Scholar 

  6. Mills W, Chopra R, McMillan A, Pearce R, Linch DC, Goldstone AH . BEAM chemotherapy and autologous bone marrow transplantation for patients with relapsed or refractory non-Hodgkin's lymphoma J Clin Oncol 1995 13: 588–595

    Article  CAS  PubMed Central  Google Scholar 

  7. Moskowitz CH, Bertino JR, Glassman JR, Hedrick EE, Hunte S, Coady-Lyons N, Agus DB, Goy A, Jurcic J, Noy A, O'Brien J, Portlock CS, Straus DS, Childs B, Frank R, Yahalom J, Filippa D, Louie D, Nimer SD, Zelenetz AD . Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral blood progenitor cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma J Clin Oncol 1999 17: 3776–3785

    Article  CAS  PubMed Central  Google Scholar 

  8. Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin F . Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma New Engl J Med 1995 333: 1540–1545

    Article  CAS  PubMed Central  Google Scholar 

  9. Bosly A, Coiffier B, Gisselbrecht C, Tilly H, Auzanneau G, Andrien F, Herbrecht R, Legros M, Devaux Y, Jaubert J, Pignon B, Michaux JL, Humblet Y, Dupriez B, Thyss A, Lederlin P . Bone marrow transplantation prolongs survival after relapse in aggressive-lymphoma patients treated with the LNH-84 regimen J Clin Oncol 1992 10: 1615–1623

    Article  CAS  PubMed Central  Google Scholar 

  10. Rapoport AP, Lifton R, Constine LS, Duerst RE, Abboud CN, Liesveld JL, Packman CH, Eberly S, Raubertas RF, Martin BA, Flesher WR, Kouides PA, DiPersio JF, Rowe JM . Autotransplantation for relapsed or refractory non-Hodgkin's lymphoma (NHL): long-term follow-up and analysis of prognostic factors Bone Marrow Transplant 1997 19: 883–890

    Article  CAS  PubMed Central  Google Scholar 

  11. Freedman AS, Takvorian T, Neuberg D, Mauch P, Rabinowe SN, Anderson KC, Soiffer RJ, Spector N, Grossbard M, Robertson MJ, Blake K, Coral F, Canellos GP, Ritz J, Nadler LM . Autologous bone marrow transplantation in poor-prognosis intermediate-grade and high-grade B cell non-Hodgkin's lymphoma in first remission: a pilot study J Clin Oncol 1993 11: 931–936

    Article  CAS  Google Scholar 

  12. Waits TM, Greco FA, Greer JP, Johnson DH, Wolff SN, Stein RS, McMaster ML, Hainsworth JD . Effective therapy for poor-prognosis non-Hodgkin's lymphoma with 8 weeks of high-dose-intensity combination chemotherapy J Clin Oncol 1993 11: 943–949

    Article  CAS  Google Scholar 

  13. Prince HM, Crump M, Imrie K, Stewart AK, Girouard C, Brandwein JM, Carstairs K, Pantalony D, Scott G, Sutcliffe S, Sutton DM, Tsang R, Keating A . Intensive therapy and autotransplant for patients with an incomplete response to front-line therapy for lymphoma Ann Oncol 1996 7: 1043–1049

    Article  CAS  Google Scholar 

  14. Stoppa AM, Bouabdallah R, Chabannon C, Novakovitch G, Vey N, Camerlo J, Blaise D, Xerri L, Resbeut M, Di Stefano D, Bardou VJ, Gastaut JA, Maraninchi D . Intensive sequential chemotherapy with repeated blood stem cell support for untreated poor-prognosis non-Hodgkin's lymphoma J Clin Oncol 1997 15: 1722–1729

    Article  CAS  Google Scholar 

  15. Shipp MA, Neuberg D, Janicek M, Canellos GP, Shulman LN . High-dose CHOP as initial therapy for patients with poor-prognosis aggressive non-Hodgkin's lymphoma: a dose-finding pilot study J Clin Oncol 1995 13: 2916–2923

    Article  CAS  Google Scholar 

  16. Stahel RA, Jost LM, Kroner T, Dommann-Scherrer C, Maurer R, Glanzmann C, Jacky E, Pichert G, Pestalozzi B, Marincek B, Sauter C, Honegger H . A prospective study of risk-adapted therapy for large cell non-Hodgkin's lymphoma with VACOP-B followed by high-dose CBV and autologous progenitor cell transplantation for high-risk patients in remission Br J Haematol 1999 104: 763–769

    Article  CAS  Google Scholar 

  17. Juliusson G, Liliemark J . Dose escalation of high-dose cyclophosphamide and etoposide with high-dose doxorubicin (CDE) and filgrastim for poor-risk non-Hodgkin's lymphoma Ann Oncol 1996 7: 1037–1041

    Article  CAS  Google Scholar 

  18. Caballero MD, Amigo ML, Hernandez JM, Vazquez L, del Canizo C, Gonzalez M, Garcia R, San Miguel JF . Alternating mini-BEAM/ESHAP as salvage therapy for refractory non-Hodgkin's lymphomas Ann Hematol 1997 74: 79–82

    Article  CAS  Google Scholar 

  19. Bouabdallah R, Stoppa AM, Rossi JF, Lepeu G, Coso D, Xerri L, Ladaique P, Chabannon C, Blaise D, Bardou VJ, Alzieu C, Gastaut JA, Maraninchi D . Intensive sequential chemotherapy (ISC 95) with growth factors and blood stem cell support in high-intermediate and high-risk (IPI 2 and IPI 3) aggressive non-Hodgkin's lymphoma: an oligocentric report on 42 patients Leukemia 1999 13: 950–956

    Article  CAS  Google Scholar 

  20. Lee SM, Ryder WD, Clemons MJ, Morgenstern GR, Chang J, Scarffe JH, Radford JA . Treatment outcome and prognostic factors for relapse after high-dose chemotherapy and peripheral blood stem cell rescue for patients with poor risk high grade non-Hodgkin's lymphoma Bone Marrow Transplant 1999 24: 271–277

    Article  CAS  PubMed Central  Google Scholar 

  21. Nademanee A, Molina A, O'Donnell MR, Dagis A, Snyder DS, Parker P, Stein A, Smith E, Planas I, Kashyap A, Spielberger R, Fung H, Wong KK, Somlo G, Margolin K, Chow W, Sniecinski I, Vora N, Blume KG, Niland J, Forman SJ . Results of high-dose therapy and autologous bone marrow/stem cell transplantation during remission in poor-risk intermediate- and high-grade lymphoma: international index high and high-intermediate risk group Blood 1997 90: 3844–3852

    Article  CAS  PubMed Central  Google Scholar 

  22. Cortelazzo S, Rossi A, Bellavita P, Oldani E, Viero P, Buelli M, Rambaldi A, Barbui T . Clinical outcome after autologous transplantation in non-Hodgkin's lymphoma patients with high international prognostic index (IPI) Ann Oncol 1999 10: 427–432

    Article  CAS  PubMed Central  Google Scholar 

  23. Pettengell R, Radford JA, Morgenstern GR, Scarffe JH, Harris M, Woll PJ, Deakin DP, Ryder D, Wilkinson PM, Crowther D . Survival benefit from high-dose therapy with autologous blood progenitor-cell transplantation in poor-prognosis non-Hodgkin's lymphoma J Clin Oncol 1996 14: 586–592

    Article  CAS  PubMed Central  Google Scholar 

  24. Sweetenham JW, Liberti G, Pearce R, Taghipour G, Santini G, Goldstone AH . High-dose therapy and autologous bone marrow transplantation for adult patients with lymphoblastic lymphoma: results of the European Group for Bone Marrow Transplantation J Clin Oncol 1994 12: 1358–1365

    Article  CAS  PubMed Central  Google Scholar 

  25. Sweetenham JW, Pearce R, Taghipour G, Blaise D, Gisselbrecht C, Goldstone AH . Adult Burkitt's and Burkitt-like non-Hodgkin's lymphoma – outcome for patients treated with high-dose therapy and autologous stem-cell transplantation in first remission or at relapse: results from the European Group for Blood and Marrow Transplantation J Clin Oncol 1996 14: 2465–2472

    Article  CAS  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Service d'Hématologie, Centre Hospitalier Lyon Sud, Pierre Bénite Cedex, 69495, France

    C Dumontet, C Thieblemont, D Espinouse, F Bouafia, O Hequet, G Salles & B Coiffier

Authors
  1. C Dumontet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Thieblemont
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Espinouse
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F Bouafia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. O Hequet
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G Salles
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B Coiffier
    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

Dumontet, C., Thieblemont, C., Espinouse, D. et al. A prospective study of intensive induction therapy with high-dose consolidation in patients with aggressive non-Hodgkin's lymphoma and two or three adverse prognostic factors. Leukemia 14, 2159–2165 (2000). https://doi.org/10.1038/sj.leu.2401955

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2401955

Keywords

Search

Advanced search

Quick links