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Rituximab added to an intensified salvage chemotherapy program followed by autologous stem cell transplantation improved the outcome in relapsed and refractory aggressive non-Hodgkin lymphoma

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Abstract

We investigated the addition of rituximab to an intensified salvage program followed by a myeloablative course with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). Patients with relapsed or progressive aggressive NHL were treated with two cycles of conventional salvage chemotherapy (DHAP) followed by high-dose sequential chemotherapy (cyclophosphamide, methotrexate with vincristine and etoposide) and a final myeloablative course (BEAM) with ASCT. Rituximab (375 mg/m2) was administered at each treatment cycle. This cohort was compared with a historical control group of patients treated with the same chemotherapy but without rituximab. Patients from both groups were matched by duration of first remission and lactate dehydrogenase serum levels. Forty-five patients were treated with chemotherapy and 22 with immunochemotherapy. The overall response rates (ORR) at the final evaluation were 63% for the immunochemotherapy group and 42% for the chemotherapy group (p = 0.330). In the historical controlled analysis freedom from second failure (FF2F) at 2 years in the immunochemotherapy group was 57% and overall survival (OS) was 77%. FF2F in the chemotherapy group was 18% (p = 0.0051) and OS was 37% (p = 0.0051). In the matched-pair analysis, FF2F was 58% in the immunochemotherapy group compared to 16% in the chemotherapy group (p = 0.0517); OS was 74 vs 33%, respectively (p = 0.0424). The toxicity was tolerable and comparable in both groups. The addition of rituximab to an intensified salvage chemotherapy regimen seems to improve the prognosis. However, only prospective randomized trial can offer sufficient data of the value of rituximab in relapsed and refractory aggressive NHL.

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References

  1. Benekli M, Hahn T, Shafi F, Qureshi A, Alam AR, Czuczman MS, Bernstein ZP, Chanan-Khan AA, Becker JL, McCarthy PL (2003) Effect of rituximab on peripheral Blood stem cell mobilization and engraftment kinetics in non-Hodgkin’s lymphoma patients. Bone Marrow Transplant 32:139–143

    Article  PubMed  CAS  Google Scholar 

  2. Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242

    Article  PubMed  CAS  Google Scholar 

  3. Czuczman MS, Weaver R, Alkuzweny B, Berlfein J, Grillo-Lopez AJ (2004) Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin’s lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol 22:4711–4716

    Article  PubMed  CAS  Google Scholar 

  4. Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA, Miller TP (1993) Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Engl J Med 328:1002–1006

    Article  PubMed  CAS  Google Scholar 

  5. Galimberti S, Guerrini F, Morabito F, Palumbo GA, Di Raimondo F, Papineschi F, Caracciolo F, Fazzi R, Cervetti G, Cuzzocrea A, Petrini M (2003) Quantitative molecular evaluation in autotransplant programs for follicular lymphoma: efficacy of in vivo purging by Rituximab. Bone Marrow Transplant 32:57–63

    Article  PubMed  CAS  Google Scholar 

  6. Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T (2004) Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly × 4 schedule. Blood 103:4416–4423

    Article  PubMed  CAS  Google Scholar 

  7. Gianni AM, Bonadonna G (1989) High dose chemo-radiotherapy for sensitive tumors: is sequential better than concurrent drug delivery? Eur J Cancer Clin Oncol 25:1027–1030

    Article  PubMed  CAS  Google Scholar 

  8. Gianni AM, Siena S, Bregni M, Lombardi F, Gandola L, Di Nicola M, Magni M, Peccatori F, Valagussa P, Bonadonna G (1993) High-dose sequential chemo-radiotherapy with peripheral Blood progenitor cell support for relapsed or refractory Hodgkin’s disease—a 6-year update. Ann Oncol 4:889–891

    PubMed  CAS  Google Scholar 

  9. Gianni AM, Bregni M, Siena S, Brambilla C, Di Nicola M, Lombardi F, Gandola L, Tarella C, Pileri A, Ravagnani F, Valagussa P, Bonadonna G (1997) High-dose chemotherapy and autologous Bone Marrow Transplantation compared with MACOP-B in aggressive B-cell lymphoma. N Engl J Med 336:1290–1297

    Article  PubMed  CAS  Google Scholar 

  10. Golay J, Zaffaroni L, Vaccari T, Lazzari M, Borleri GM, Bernasconi S, Tedesco F, Rambaldi A, Introna M (2000) Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood 95:3900–3908

    PubMed  CAS  Google Scholar 

  11. Haioun C, Lepage E, Gisselbrecht C, Salles G, Coiffier B, Brice P, Bosly A, Morel P, Nouvel C, Tilly H, Lederlin P, Sebban C, Briere J, Gaulard P, Reyes F (2000) 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 18:3025–3030

    PubMed  CAS  Google Scholar 

  12. Hofmeister JK, Cooney D, Coggeshall KM (2000) Clustered CD20 induced apoptosis: src-family kinase, the proximal regulator of tyrosine phosphorylation, calcium influx, and caspase 3-dependent apoptosis. Blood Cells Mol Dis 26:133–143

    Article  PubMed  CAS  Google Scholar 

  13. Horwitz SM, Negrin RS, Blume KG, Breslin S, Stuart MJ, Stockerl-Goldstein KE, Johnston LJ, Wong RM, Shizuru JA, Horning SJ (2004) Rituximab as adjuvant to high-dose therapy and autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma. Blood 103:777–783

    Article  PubMed  CAS  Google Scholar 

  14. Josting A, Reiser M, Rueffer U, Salzberger B, Diehl V, Engert A (2000) Treatment of primary progressive Hodgkin’s and aggressive non-Hodgkin’s lymphoma: is there a chance for cure? J Clin Oncol 18:332–339

    PubMed  CAS  Google Scholar 

  15. Josting A, Sieniawski M, Glossmann JP, Staak O, Nogova L, Peters N, Mapara M, Dorken B, Ko Y, Metzner B, Kisro J, Diehl V, Engert A (2005) High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin’s lymphoma: results of a multicenter phase II study. Ann Oncol 16:1359–1365

    Article  PubMed  CAS  Google Scholar 

  16. Kaya H, Keung YK, Case D, Cruz JM, Perry JJ, Radford JE, Hurd DD (2002) Efficacy and safety of monoclonal anti-CD20 antibody (rituximab) for the treatment of patients with recurrent low-grade non-Hodgkin’s lymphoma after high-dose chemotherapy and autologous hematopoietic cell transplantation. Biol Blood Marrow Transplant 8:544–549

    Article  PubMed  CAS  Google Scholar 

  17. Kewalramani T, Zelenetz AD, Hedrick EE, Donnelly GB, Hunte S, Priovolos AC, Qin J, Lyons NC, Yahalom J, Nimer SD, Moskowitz CH (2000) High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis. Blood 96:2399–2404

    PubMed  CAS  Google Scholar 

  18. Kewalramani T, Zelenetz AD, Nimer SD, Portlock C, Straus D, Noy A, O’Connor O, Filippa DA, Teruya-Feldstein J, Gencarelli A, Qin J, Waxman A, Yahalom J, Moskowitz CH (2004) Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood 103:3684–3688

    Article  PubMed  CAS  Google Scholar 

  19. Khouri IF, Saliba RM, Hosing C, Okoroji GJ, Acholonu S, Anderlini P, Couriel D, De Lima M, Donato ML, Fayad L, Giralt S, Jones R, Korbling M, Maadani F, Manning JT, Pro B, Shpall E, Younes A, McLaughlin P, Champlin RE (2005) Concurrent administration of high-dose rituximab before and after autologous stem-cell transplantation for relapsed aggressive B-cell non-Hodgkin’s lymphomas. J Clin Oncol 23:2240–2247

    Article  PubMed  CAS  Google Scholar 

  20. Magni M, Di Nicola M, Devizzi L, Matteucci P, Lombardi F, Gandola L, Ravagnani F, Giardini R, Dastoli G, Tarella C, Pileri A, Bonadonna G, Gianni AM (2000) 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 96:864–869

    PubMed  CAS  Google Scholar 

  21. Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A, Levy R (1994) Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood 84:2457–2466

    PubMed  CAS  Google Scholar 

  22. Marcus R, Imrie K, Belch A, Cunningham D, Flores, E, Catalano J, Solal-Celigny P, Offner F, Walewski J, Raposo J, Jack A, Smith P (2005) CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 105:1417–1423

    Article  PubMed  CAS  Google Scholar 

  23. 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 (1999) 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 17:3776–3785

    PubMed  CAS  Google Scholar 

  24. Norton L, Simon R (1986) The Norton–Simon hypothesis revisited. Cancer Treat Rep 70:163–169

    PubMed  CAS  Google Scholar 

  25. Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL (1995) Autologous Bone Marrow Transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med 333:1540–1545

    Article  PubMed  CAS  Google Scholar 

  26. Shan D, Ledbetter JA, Press OW (2000) Signaling events involved in anti-CD20-induced apoptosis of malignant human B cells. Cancer Immunol Immunother 48:673–683

    Article  PubMed  CAS  Google Scholar 

  27. Shea TC, Mason JR, Storniolo AM, Newton B, Breslin M, Mullen M, Ward DM, Miller L, Christian M, Taetle R (1992) Sequential cycles of high-dose carboplatin administered with recombinant human granulocyte-macrophage colony-stimulating factor and repeated infusions of autologous peripheral-blood progenitor cells: a novel and effective method for delivering multiple courses of dose-intensive therapy. J Clin Oncol 10:464–473

    PubMed  CAS  Google Scholar 

  28. Vose JM, Zhang MJ, Rowlings PA, Lazarus HM, Bolwell BJ, Freytes CO, Pavlovsky S, Keating A, Yanes B, van Besien K, Armitage JO, Horowitz MM (2001) Autologous transplantation for diffuse aggressive non-Hodgkin’s lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol 19:406–413

    PubMed  CAS  Google Scholar 

  29. Voso MT, Pantel G, Weis M, Schmidt P, Martin S, Moos M, Ho AD, Haas R, Hohaus S (2000) 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 109:729–735

    Article  PubMed  CAS  Google Scholar 

  30. Zinzani PL, Tani M, Molinari AL, Stefoni V, Zuffa E, Alinari L, Gabriele A, Bonifazi F, Salvucci M, Tura S, Baccarani M (2002) Ifosfamide, epirubicin and etoposide regimen as salvage and mobilizing therapy for relapsed/refractory lymphoma patients. Haematologica 87:816–821

    PubMed  CAS  Google Scholar 

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Amendment

Participating institutions:

  1. 1.

    University Hospital Cologne, First Department of Internal Medicine, Germany

  2. 2.

    Carl-Thiem-Hospital Cottbus, Second Medical Hospital, Germany

  3. 3.

    University Hospital Charitè Berlin, Section for Hematology/Oncology, Germany

  4. 4.

    University Hospital Bonn, Department of Internal Medicine, Germany

  5. 5.

    Klinikum Oldenburg, Department II of Internal Medicine, Germany

  6. 6.

    University Hospital Lübeck, Section for Hematology/Oncology, Germany

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Authors and Affiliations

  1. Department I of Internal Medicine, University Hospital Cologne, Kerpener Str. 62, 50924, Cologne, Germany

    Michal Sieniawski, Oliver Staak, Jan-Peter Glossmann, Helena Scheuß, Andreas Engert & Andreas Josting

  2. German Hodgkin Study Group, University Hospital Cologne, 50924, Cologne, Germany

    Thorsten Reineke & Volker Diehl

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  1. Michal Sieniawski
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  2. Oliver Staak
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  7. Andreas Engert
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Correspondence to Michal Sieniawski.

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Sieniawski, M., Staak, O., Glossmann, JP. et al. Rituximab added to an intensified salvage chemotherapy program followed by autologous stem cell transplantation improved the outcome in relapsed and refractory aggressive non-Hodgkin lymphoma. Ann Hematol 86, 107–115 (2007). https://doi.org/10.1007/s00277-006-0210-5

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  • DOI: https://doi.org/10.1007/s00277-006-0210-5

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