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  • Original Article
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In vivo Purging

Rituximab in vivo purging is safe and effective in combination with CD34-positive selected autologous stem cell transplantation for salvage therapy in B-NHL

Bone Marrow Transplantation volume 29, pages 769–775 (2002)Cite this article

Abstract

The purpose of this study was to evaluate feasibility and efficacy of Rituximab included into a sequential salvage protocol for CD20+ B-NHL in relapse or induction failure. Twenty-seven patients with CD20+ B-NHL in relapse or induction failure received Rituximab combined with DexaBEAM (R-DexaBEAM) for stem cell mobilization. Additional ex vivo selection of CD34-positive cells was performed using the CliniMacs device. Two doses of Rituximab were included in the high-dose therapy regimen (HDT). R-DexaBEAM was well tolerated and 26 of 27 patients mobilized sufficient numbers of CD34+ blood stem cells. Application of R-DexaBEAM resulted in significant depletion of peripheral B cells. No treatment-related deaths occurred after HDT and all patients showed stable engraftment of hematopoesis. Combined immunodeficiency was observed post HDT and eight patients developed CMV antigenemia. Remission rate post HDT was 96% (CR, 24/26; PR, 1/26). Overall and progression-free survival (PFS) at 16 months post HDT (range 6–27) is 95% and 77%, respectively. With regard to histology, PFS was 71% in aggressive lymphoma (n = 11), 74% in indolent FCL (n = 10) and 100% in MCL (n = 5). The treatment protocol has proven feasible, with high purging efficiency and encouraging remission rates.

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References

  1. Philip T, Guglielmi C, Hagenbeek A et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma (see comments) New Engl J Med 1995 333: 1540 1545

    Article  CAS  PubMed  Google Scholar 

  2. Haioun C, Lepage E, Gisselbrecht C et al. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87–2 protocol – a groupe d'Etude des lymphomes de l'Adulte study J Clin Oncol 2000 18: 3025 3030

    Article  CAS  PubMed  Google Scholar 

  3. Takvorian T, Canellos GP, Ritz J et al. Prolonged disease-free survival after autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma with a poor prognosis New Engl J Med 1987 316: 1499 1505

    Article  CAS  PubMed  Google Scholar 

  4. Freedman AS, Neuberg D, Mauch P et al. Long-term follow-up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma Blood 1999 94: 3325 3333

    CAS  PubMed  Google Scholar 

  5. Brenner MK, Rill DR, Moen RC et al. Gene-marking to trace origin of relapse after autologous bone-marrow transplantation Lancet 1993 341: 85 86

    Article  CAS  PubMed  Google Scholar 

  6. Deisseroth AB, Zu Z, Claxton D et al. Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in CML Blood 1994 83: 3068 3076

    CAS  PubMed  Google Scholar 

  7. Freedman AS, Gribben JG, Neuberg D et al. High-dose therapy and autologous bone marrow transplantation in patients with follicular lymphoma during first remission Blood 1996 88: 2780 2786

    CAS  PubMed  Google Scholar 

  8. Tobinai K, Kobayashi Y, Narabayashi M et al. Feasibility and pharmacokinetic study of a chimeric anti-CD20 monoclonal antibody (IDEC-C2B8, rituximab) in relapsed B-cell lymphoma. The IDEC-C2B8 Study Group Ann Oncol 1998 9: 527 534

    Article  CAS  PubMed  Google Scholar 

  9. Maloney DG, Grillo-Lopez AJ, White CA et al. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma Blood 1997 90: 2188 2195

    CAS  PubMed  Google Scholar 

  10. Czuczman MS, Grillo-Lopez AJ, White CA et al. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy J Clin Oncol 1999 17: 268 276

    Article  CAS  PubMed  Google Scholar 

  11. Buckstein R, Imrie K, Spaner D et al. Stem cell function and engraftment is not affected by ‘in vivo purging’ with rituximab for autologous stem cell treatment for patients with low-grade non-Hodgkin's lymphoma Semin Oncol 1999 26: 115 122

    CAS  PubMed  Google Scholar 

  12. Coiffier B, Haioun C, Ketterer N et al. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study Blood 1998 92: 1927 1932

    CAS  PubMed  Google Scholar 

  13. Foran JM, Gupta RK, Cunningham D et al. A UK multicentre phase II study of rituximab (chimaeric anti-CD20 monoclonal antibody) in patients with follicular lymphoma, with PCR monitoring of molecular response Br J Haematol 2000 109: 81 88

    Article  CAS  PubMed  Google Scholar 

  14. Foran JM, Cunningham D, Coiffier B et al. Treatment of mantle-cell lymphoma with Rituximab (chimeric monoclonal anti-CD20 antibody): analysis of factors associated with response Ann Oncol 2000 11 (Suppl. 1): 117 121

    Article  Google Scholar 

  15. Tsai D, Moore H, Hardy C et al. Rituximab (anti-CD20 monoclonal antibody) therapy for progressive intermediate-grade non-Hodgkin's lymphoma after high-dose therapy and autologous peripheral stem cell transplantation Bone Marrow Transplant 1999 24: 521 526

    Article  CAS  PubMed  Google Scholar 

  16. Voso MT, Pantel G, Wets M et al. In vivo depletion of B cells using a combination of high-dose cytosine arabinoside/mitoxantrone and rituximab for autografting in patients with non-Hodgkin's lymphoma Br J Haematol 2000 109: 729 735

    Article  CAS  PubMed  Google Scholar 

  17. Schumm M, Lang P, Taylor G et al. Isolation of highly purified autologous and allogeneic peripheral CD34+ cells using the CliniMACS device J Hematother 1999 8: 209 218

    Article  CAS  PubMed  Google Scholar 

  18. Sutherland DR, Anderson L, Keeney M et al. The ISHAGE guidelines for CD34+ cell determination by flow cytometry. International Society of Hematotherapy and Graft Engineering J Hematother 1996 5: 213 226

    Article  CAS  PubMed  Google Scholar 

  19. Nicholson J, Hearn T, Cross G et al. 1997 revised guidelines for performing CD4+ T-cell determination in persons infected with human immunodefficiency virus MMWR 1997 46: 1 27

    Google Scholar 

  20. Gribben J, Freedman A, Neuberg D et al. Immunolgic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma New Engl J Med 1991 325: 1525 1533

    Article  CAS  PubMed  Google Scholar 

  21. Cheson BD, Horning SJ, Coiffier B et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group J Clin Oncol 1999 17: 1244 1253

    Article  CAS  PubMed  Google Scholar 

  22. Kaplan F, Meier P . Nonparametric estimation for incomplete observations J Am Stat Assoc 1958 52: 457 481

    Article  Google Scholar 

  23. McLaughlin P, Grillo-Lopez AJ, Link BK et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program J Clin Oncol 1998 16: 2825 2833

    Article  CAS  PubMed  Google Scholar 

  24. Magni M, Di Nicola M, Devizzi L et al. Successful in vivo purging of CD34-containing peripheral blood harvests in mantle cell and indolent lymphoma: evidence for a role of both chemotherapy and rituximab infusion Blood 2000 96: 864 869

    CAS  PubMed  Google Scholar 

  25. Kolbe K, Domkin D, Derigs HG et al. Infectious complications during neutropenia subsequent to peripheral blood stem cell transplantation Bone Marrow Transplant 1997 19: 143 147

    Article  CAS  PubMed  Google Scholar 

  26. Offidani M, Corvatta L, Olivieri A et al. Infectious complications after autologous peripheral blood progenitor cell transplantation followed by G-CSF Bone Marrow Transplant 1999 24: 1079 1087

    Article  CAS  PubMed  Google Scholar 

  27. Nagafuji K, Eto T, Hayashi S et al. Fatal cytomegalovirus interstitial pneumonia following autologous peripheral blood stem cell transplantation. Fukuoka Bone Marrow Transplantation Group Bone Marrow Transplant 1998 21: 301 303

    Article  CAS  PubMed  Google Scholar 

  28. Divine M, Boutolleau D, Delfau-Larue MH et al. Poor lymphocyte recovery following CD34-selected autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma Br J Haematol 1999 105: 349 360

    Article  CAS  PubMed  Google Scholar 

  29. Ramsey DJ, Schey SA . Cytomegalovirus colitis after autologous transplantation for multiple myeloma Br J Haematol 2000 110: 894 896

    Article  CAS  PubMed  Google Scholar 

  30. Horwitz S, Breslin S, Negrin R et al. Adjuvant Rituximab after autologous perhiperal blood stem cell transplantation results in delayed immune reconstitution without increase in infectious complications Blood 2000 96: 384a

    Google Scholar 

  31. Holmberg LA, Boeckh M, Hooper H et al. Increased incidence of cytomegalovirus disease after autologous CD34-selected peripheral blood stem cell transplantation Blood 1999 94: 4029 4035

    CAS  PubMed  Google Scholar 

  32. Jonjic S, Pavic I, Polic B et al. Antibodies are not essential for the resolution of primary cytomegalovirus infection but limit dissemination of recurrent virus J Exp Med 1994 179: 1713 1717

    Article  CAS  PubMed  Google Scholar 

  33. Singhal S, Powles R, Treleaven J et al. Cytomegaloviremia after autografting for leukemia: clinical significance and lack of effect on engraftment Leukemia 1997 11: 835 838

    Article  CAS  PubMed  Google Scholar 

  34. Bilgrami S, Aslanzadeh J, Feingold JM et al. Cytomegalovirus viremia, viruria and disease after autologous peripheral blood stem cell transplantation: no need for surveillance Bone Marrow Transplant 1999 24: 69 73

    Article  CAS  PubMed  Google Scholar 

  35. Boeckh M, Stevens-Ayers T, Bowden RA . Cytomegalovirus pp65 antigenemia after autologous marrow and peripheral blood stem cell transplantation J Infect Dis 1996 174: 907 912

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We gratefully acknowledge the support by Gertrud Feldmann and the excellent technical assistance of Ursula Petrat-Benzaim, Brigitte Schuch, Sabine Mielke and Kristina Schäfer. This study was supported by the Deutsche Krebshilfe and the Forschungsverbund, grant numbers 70–2427 and 70–2428 and approved by the Deutsche Krebsgesellschaft.

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  1. IIIrd Department of Medicine, Johannes Gutenberg-University, Mainz and Hospital Kemperhof, Koblenz, Germany

    T Flohr, G Hess, K Kolbe, H Gamm, H Nolte, T Stanislawski, C Huber & HG Derigs

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  1. T Flohr
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Flohr, T., Hess, G., Kolbe, K. et al. Rituximab in vivo purging is safe and effective in combination with CD34-positive selected autologous stem cell transplantation for salvage therapy in B-NHL. Bone Marrow Transplant 29, 769–775 (2002). https://doi.org/10.1038/sj.bmt.1703515

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