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Lymphomas

A long-term follow-up of 33 patients with non-Hodgkin's lymphoma who received the BEAM high-dose intensification regimen with cytokine support only and no transplant

Leukemia volume 18, pages 1717–1721 (2004)Cite this article

Abstract

High-dose intensification and autologous stem-cell transplantation (ASCT) is widely used to consolidate patients with non-Hodgkin's lymphoma (NHL), who have reached a stage of minimal residual disease. However, patients with persisting marrow and/or blood involvement and those who fail peripheral blood hemopoietic progenitor mobilization are excluded from ASCT. For such patients with no available graft to infuse, we developed 15 years ago, before the anti-CD20 monoclonal antibody therapeutic era, the use of the BEAM pretransplant regimen followed only by the administration of three cytokines (erythropoietin, granulocyte colony-stimulating factor, granulocyte–macrophage colony-stimulating factor). We report here on the long-term follow-up of 33 patients treated with this approach. In all, 33 NHL patients underwent the BEAM (carmustine, VP-16, cytosine–arabinoside, melphalan) followed by the administration of the three cytokines from January 1994–2000. A backup marrow, albeit infiltrated by tumor cells, had been collected earlier and stored in all. A total of 30 patients (91%) recovered normal hematopoiesis. In total, 32 patients (97%) recovered neutrophils (>500/μl) at a median of 19 days and 30 patients (91%) recovered platelets (>20 000/μl) at a median of 26 days. Age, richness of backup graft and blood–hemoglobin level at intensification had an impact on the time for hematopoietic recovery (P=0.014, P=0.014, P=0.048). The median follow-up was 62 months. Five patients died from toxicity related to the procedure. Eight patients relapsed and died. A total of 20 patients (61%) are alive, 16 (49%) in complete remission. A 5-year disease-free survival was 52±9%, relapse incidence 35±16%, mortality due to the procedure 12±12% and overall survival 61±10%. The BEAM regimen is not myeloablative. The BEAM+3CK procedure is a feasible therapeutic option that has shown efficacy in poor risk NHL patients who were not eligible for autografting because of persisting marrow/blood tumor contamination, or poor hemopoietic progenitor harvesting. It is unclear today whether some of these patients would have cleared their marrow/peripheral blood with the additional use of anti-CD20 treatment, thereby making the classical approach (BEAM followed by the infusion of a clean autograft) feasible.

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References

  1. Haioun C, Lepage E, Gisselbrecht C, Bastion Y, Coiffier B, Brice P et al. Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin's lymphoma: updated results of the prospective study LNH-87-2. Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol 1997; 15: 1131–1137.

    Article  CAS  Google Scholar 

  2. Gianni AM, Bregni M, Siena S, Brambilla C, Di Nicola M, Lombardi F et al. High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. N Engl J Med 1997; 336: 1290–1297.

    Article  CAS  Google Scholar 

  3. Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemosensitive-chemotherapy non-Hodgkin's lymphoma. N Engl J Med 1995; 333: 1540–1545.

    Article  CAS  Google Scholar 

  4. Fouillard L, Laporte JPh, Labopin M, Lesage S, Isnard F, Douay L et al. Autologous stem-cell transplantation for non-Hodgkin's lymphomas: the role of graft purging and radiotherapy posttransplantation – results of a retrospective analysis of 120 patients autografted in a single institution. J Clin Oncol 1998; 16: 2803–2816.

    Article  CAS  Google Scholar 

  5. Apostolidis J, Gupta RK, Grenzelias D, Johnson PW, Pappa VI, Summers KE et al. High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: long-term clinical and molecular follow-up. J Clin Oncol 2000; 18: 527–536.

    Article  CAS  Google Scholar 

  6. Colombat P, Cornillet P, Deconinck E, Tourani JM, Gardembas M, Delain M et al. Value of autologous stem cell transplantation with purged bone marrow a first-line therapy for follicular lymphoma with high tumour burden: a GOELAMS phase II study. Bone Marrow Transplant 2000; 26: 971–977.

    Article  CAS  Google Scholar 

  7. Vose JM, Anderson JR, Kessinger A, Bierman PJ, Coccia P, Reed EC et al. High-dose chemotherapy and autologous stem-cell transplantation for aggressive non-Hodgkin's lymphoma. J Clin Oncol 1993; 11: 1846–1851.

    Article  CAS  Google Scholar 

  8. Williams CD, Goldstone AH, Pearce RM, Philip T, Hartmann O, Colombat P et al. Purging of bone marrow in autologous bone marrow transplantation for non-Hodgkin's lymphoma: a case-matched comparison with unpurged cases by the European Blood and Marrow Transplant Lymphoma Registry. J Clin Oncol 1996; 14: 2454–2464.

    Article  CAS  Google Scholar 

  9. Gribben JG, Neuberg D, Freedman AS, Roy DC, Blake KW, Woo SD et al. Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma. Blood 1993; 81: 3449–3457.

    CAS  Google Scholar 

  10. Freedman AS, Friedberg J, Gribben JG . High dose therapy for follicular lymphoma. Oncology 2000; 329: 321–326.

    Google Scholar 

  11. Sharp JG, Kessinger A, Mann S, Crouse DA, Armitage JO, Bierman P et al. Outcome of high-dose therapy and autologous transplantation in non-Hodgkin's lymphoma based on the presence of tumor in the marrow or infused hematopoietic harvest. J Clin Oncol 1996; 14: 214–219.

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  13. Fine JP, Gray RJ . A proportional hazards model for the subdistribution of a competing risk. JASA 1999; 94: 496–509.

    Article  Google Scholar 

  14. Fouillard L, Gorin N, Laporte JPh, Douay L, Isnard F, Najman A . Recombinant human granulocyte macrophage colony stimulating factor+the BEAM regimen instead of autologous bone marrow transplantation. Lancet 1989; 1: 1460.

    Article  CAS  Google Scholar 

  15. Laporte JPh, Fouillard L, Douay L, Eugene-Jolchine I, Isnard F, Stachowiak J et al. GM-CSF instead of autologous bone-marrow transplantation after the BEAM regimen. Lancet 1991; 338: 601–602.

    Article  CAS  Google Scholar 

  16. Douay L . Experimental culture conditions are critical for ex vivo expansion of hematopoietic cells: review. J Haematother Stem Cell Res 2001, 341–346.

  17. Pierelli L, Menichella G, Scambia G, Teofili L, Iovino S, Serafini R et al. In vitro and in vivo effects of recombinant human erythropoietin plus recombinant human G-CSF on human haemopoietic progenitor cells. Bone Marrow Transplant 1994; 14: 23–30.

    CAS  PubMed  Google Scholar 

  18. Filip S, Vanasek J, Blaha M, Mericka P, Vavrova J, Podzimek K . The increase of the rate of hemopoietic recovery and clinical benefit of the erythropoietin (EPO) and granulocyte-stimulating factor (G-CSF) with peripheral blood progenitor cells after intensive cyclic chemotherapy in high risk breast cancer patients. Neoplasma 1999; 46: 166.

    CAS  PubMed  Google Scholar 

  19. Locatelli F, Zecca M, Pedrazzoli P, Prete L, Quaglini S, Comoli P et al. Use of recombinant human erythropoietin after bone marrow transplantation in pediatric patients with acute leukemia: effect on erythroid repopulation in autologous vs allogeneic transplantation. Bone Marrow Transplant 1994; 13: 403–410.

    CAS  PubMed  Google Scholar 

  20. Locatelli F, Zecca M, Ponchio L, Beguin Y, Giorgiani G, Maccario R et al. Pilot trial of combined administration of erythropoietin and granulocyte colony-stimulating factor to children undergoing allogeneic bone marrow transplantation. Bone Marrow Transplant 1994; 14: 23–30.

    Google Scholar 

  21. Laporte JPh, Lesage S, Woler M, Parlier Y, Daguenel A, Najman A et al. Administration of three cytokines instead of bone marrow tranplantation in a HIV+ patient with high-grade lymphoma. Eur J Haematol 1994, 123–125.

  22. Tothova E, Kafkova A, Guman T, Stecova N, Fricova M . Efficiency of in vivo purging with autologous stem cell transplantation and monoclonal antibody in B-cell lymphomas. Neoplasma 2003; 50: 22–25.

    CAS  PubMed  Google Scholar 

  23. Holmberg LA, Boeckh M, Hooper H, Leisenring W, Rowley S, Heimfeld S et al. Increased incidence of CMV disease after autologous CD34 selected peripheral blood stem cell transplantation. Blood 1999; 94: 4029.

    CAS  PubMed  Google Scholar 

  24. Fouillard L, Laporte JPh, Douay L, Lesage S, Najman A, Gourmelon P et al. In vivo expansion of reinfused autologous peripheral blood stem cells after a myeloablative regimen, as an alternative to ex vivo expansion pretransplantation: an intriguing observation in a patient autografted twice. Bone Marrow Transplant 1999; 24: 1151–1152.

    Article  CAS  Google Scholar 

  25. Blaise D, Faucher C, Vey N, Caraux J, Maraninchi D, Chabannon C . Rescue of hemopoiesis by a combination of growth factors including stem-cell factor. Lancet 2000; 14: 1325–1326.

    Article  Google Scholar 

  26. Bomberger C, Singh-Jairam M, Rodey G, Guerriero A, Yeager AM, Fleming WH et al. Lymphoid reconstitution after autologous PBSC transplantation with FACS-sorted CD34+ hematopoietic progenitors. Blood 1998; 91: 2588–2600.

    CAS  PubMed  Google Scholar 

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Author notes

  1. M Yeshurun

    Present address: Institute of Hematology, The Chaim Cheba Medical Centre, Tel-Hashomer and Sackler School of Medicine, Tel-Aviv University, Israel

  2. C Cailliot

    Present address: , Amgen, France

Authors and Affiliations

  1. Department of Hematology and Cell Therapy, Hôpital Saint Antoine, Paris, France

    J Ph Laporte, M Yeshurun, L Fouillard, M Labopin, C Cailliot, S Lesage, F Isnard, A Najman & N-C Gorin

  2. Laboratoire de Recherche sur la thérapie cellulaire et la radioprotection accidentelle EA 1638, Centre hospitalo-universitaire Saint Antoine, Université Paris VI and Assistance Publique AP-HP, Paris, France

    J Ph Laporte, M Yeshurun, L Fouillard, M Labopin, C Cailliot, S Lesage, F Isnard, A Najman & N-C Gorin

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  1. J Ph Laporte
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Correspondence to J Ph Laporte.

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Laporte, J., Yeshurun, M., Fouillard, L. et al. A long-term follow-up of 33 patients with non-Hodgkin's lymphoma who received the BEAM high-dose intensification regimen with cytokine support only and no transplant. Leukemia 18, 1717–1721 (2004). https://doi.org/10.1038/sj.leu.2403427

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