Annals of Hematology

, Volume 91, Issue 4, pp 561–570 | Cite as

Treatment of B cell lymphoma with chemotherapy plus rituximab: a survival benefit can be demonstrated in the routine data of a regional cancer registry

  • Stefan W. KrauseEmail author
  • Michael Gerken
  • Reinhard Andreesen
  • Ferdinand Hofstädter
  • Monika Klinkhammer-Schalke
Original Article


Combination of standard chemotherapy with rituximab led to improved disease control in patients with B cell lymphoma in clinical trials. We wanted to know if a similar benefit could be demonstrated in the routine data of a regional population-based cancer registry. We searched the registry of the Regensburg Tumor Center for B cell non-Hodgkin lymphomas diagnosed between 1998 and 2006 and compared overall survival of patients receiving any first-line chemotherapy with or without rituximab. Comparing registry data to death certificates, an 86% coverage within the registry was estimated. In the aggressive lymphoma group, 133 patients received rituximab-containing chemotherapy resulting in a 5-year survival of 69.6%, whereas 205 patients received chemotherapy alone with a significantly inferior 5-year survival of 56.8%. First-line chemotherapy with rituximab in 81 patients with indolent lymphoma also led to improved 5-year survival compared to 134 patients without rituximab (69.7% vs. 51.8%), primarily observed among patients with follicular lymphoma (84.7% vs. 52.0%). These data confirm the standard use of rituximab as first-line therapy in diffuse large B cell lymphomas as well as in indolent lymphoma. Furthermore, they support the collection of treatment data including detailed information on systemic therapy in cancer registries to be used for outcomes research.


Lymphoma Non-Hodgkin Chemotherapy Rituximab Cancer registry 



The authors would like to thank the medical documentation assistants of the cancer registry, notably Christine Glötzl, Martina Kirchberger, and Doris Weinberger, for their contribution regarding a standardized encoding of the non-Hodgkin lymphomas and all members of the Tumorzentrum who contributed data to the registry.


This study was not supported by pharmaceutical companies. SWK has received travel support from Roche. RA has received support for scientific meetings from Roche. The other authors have not reported any potential conflicts of interest.


  1. 1.
    Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD (2000) The World Health Organization classification of neoplastic diseases of the haematopoietic and lymphoid tissues: report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997. Histopathology 36(1):69–86PubMedCrossRefGoogle Scholar
  2. 2.
    Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (2008) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. WHO, GenevaGoogle Scholar
  3. 3.
    Lieberman PH, Filippa DA, Straus DJ, Thaler HT, Cirrincione C, Clarkson BD (1986) Evaluation of malignant lymphomas using three classifications and the working formulation. 482 cases with median follow-up of 11.9 years. Am J Med 81(3):365–380PubMedCrossRefGoogle Scholar
  4. 4.
    Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, Newman RA, Hanna N, Anderson DR (1994) Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83(2):435–445PubMedGoogle Scholar
  5. 5.
    Maloney DG, Grillo-Lopez AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, Janakiraman N, Foon KA, Liles TM, Dallaire BK, Wey K, Royston I, Davis T, Levy R (1997) IDEC-C2B8 (rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood 90(6):2188–2195PubMedGoogle Scholar
  6. 6.
    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(4):235–242PubMedCrossRefGoogle Scholar
  7. 7.
    Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trumper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M (2008) Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol 9(2):105–116PubMedCrossRefGoogle Scholar
  8. 8.
    Pfreundschuh M, Trumper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, Lopez-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M (2006) CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 7(5):379–391PubMedCrossRefGoogle Scholar
  9. 9.
    Forstpointner R, Dreyling M, Repp R, Hermann S, Hanel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Bock HP, Wandt H, Unterhalt M, Hiddemann W (2004) The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 104(10):3064–3071PubMedCrossRefGoogle Scholar
  10. 10.
    Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, Reiser M, Metzner B, Harder H, Hegewisch-Becker S, Fischer T, Kropff M, Reis HE, Freund M, Wormann B, Fuchs R, Planker M, Schimke J, Eimermacher H, Trumper L, Aldaoud A, Parwaresch R, Unterhalt M (2005) Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 106(12):3725–3732PubMedCrossRefGoogle Scholar
  11. 11.
    Buske C, Hoster E, Dreyling M, Eimermacher H, Wandt H, Metzner B, Fuchs R, Bittenbring J, Woermann B, Hohloch K, Hess G, Ludwig WD, Schimke J, Schmitz S, Kneba M, Reiser M, Graeven U, Klapper W, Unterhalt M, Hiddemann W (2009) The addition of rituximab to front-line therapy with CHOP (R-CHOP) results in a higher response rate and longer time to treatment failure in patients with lymphoplasmacytic lymphoma: results of a randomized trial of the German Low-Grade Lymphoma Study Group (GLSG). Leukemia 23(1):153–161PubMedCrossRefGoogle Scholar
  12. 12.
    Schulz H, Bohlius JF, Trelle S, Skoetz N, Reiser M, Kober T, Schwarzer G, Herold M, Dreyling M, Hallek M, Engert A (2007) Immunochemotherapy with rituximab and overall survival in patients with indolent or mantle cell lymphoma: a systematic review and meta-analysis. J Natl Cancer Inst 99(9):706–714PubMedCrossRefGoogle Scholar
  13. 13.
    Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, Hensel M, Hopfinger G, Hess G, von Grunhagen U, Bergmann M, Catalano J, Zinzani PL, Caligaris-Cappio F, Seymour JF, Berrebi A, Jager U, Cazin B, Trneny M, Westermann A, Wendtner CM, Eichhorst BF, Staib P, Buhler A, Winkler D, Zenz T, Bottcher S, Ritgen M, Mendila M, Kneba M, Dohner H, Stilgenbauer S (2010) Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 376(9747):1164–1174PubMedCrossRefGoogle Scholar
  14. 14.
    Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R, MacPherson N, O’Reilly S, Spinelli JJ, Sutherland J, Wilson KS, Gascoyne RD, Connors JM (2005) Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol 23(22):5027–5033PubMedCrossRefGoogle Scholar
  15. 15.
    Pulte D, Gondos A, Brenner H (2008) Ongoing improvement in outcomes for patients diagnosed as having non-Hodgkin lymphoma from the 1990s to the early 21st century. Arch Intern Med 168(5):469–476PubMedCrossRefGoogle Scholar
  16. 16.
    Molina A (2008) A decade of rituximab: improving survival outcomes in non-Hodgkin’s lymphoma. Annu Rev Med 59:237–250PubMedCrossRefGoogle Scholar
  17. 17.
    Luminari S, Cesaretti M, Rashid I, Mammi C, Montanini A, Barbolini E, Bellei M, Pennese E, Sirotti MA, Marcheselli L, Partesotti G, Bari A, Maiorana A, Bonacorsi G, Federico M (2007) Incidence, clinical characteristics and survival of malignant lymphomas: a population-based study from a cancer registry in northern Italy. Hematol Oncol 25(4):189–197PubMedCrossRefGoogle Scholar
  18. 18.
    Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B (2005) Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol 23(18):4117–4126PubMedCrossRefGoogle Scholar
  19. 19.
    Ardeshna KM, Smith P, Norton A, Hancock BW, Hoskin PJ, MacLennan KA, Marcus RE, Jelliffe A, Vaughan G, Hudson LDC (2003) Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet 362(9383):516–522PubMedCrossRefGoogle Scholar
  20. 20.
    Lenz G, Dreyling M, Hoster E, Wormann B, Duhrsen U, Metzner B, Eimermacher H, Neubauer A, Wandt H, Steinhauer H, Martin S, Heidemann E, Aldaoud A, Parwaresch R, Hasford J, Unterhalt M, Hiddemann W (2005) Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol 23(9):1984–1992PubMedCrossRefGoogle Scholar
  21. 21.
    Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, Dolken G, Naumann R, Knauf W, Freund M, Rohrberg R, Hoffken K, Franke A, Ittel T, Kettner E, Haak U, Mey U, Klinkenstein C, Assmann M, von Grunhagen U (2007) Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol 25(15):1986–1992PubMedCrossRefGoogle Scholar
  22. 22.
    Marcus R, Imrie K, Solal-Celigny P, Catalano JV, Dmoszynska A, Raposo JC, Offner FC, Gomez-Codina J, Belch A, Cunningham D, Wassner-Fritsch E, Stein G (2008) Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol 26(28):4579–4586PubMedCrossRefGoogle Scholar
  23. 23.
    Dana BW, Dahlberg S, Nathwani BN, Chase E, Coltman C, Miller TP, Fisher RI (1993) Long-term follow-up of patients with low-grade malignant lymphomas treated with doxorubicin-based chemotherapy or chemoimmunotherapy. J Clin Oncol 11(4):644–651PubMedGoogle Scholar
  24. 24.
    Peterson BA, Petroni GR, Frizzera G, Barcos M, Bloomfield CD, Nissen NI, Hurd DD, Henderson ES, Sartiano GP, Johnson JL, Holland JF, Gottlieb AJ (2003) Prolonged single-agent versus combination chemotherapy in indolent follicular lymphomas: a study of the cancer and leukemia group B. J Clin Oncol 21(1):5–15PubMedCrossRefGoogle Scholar
  25. 25.
    Bachy E, Brice P, Delarue R, Brousse N, Haioun C, Le Gouill S, Delmer A, Bordessoule D, Tilly H, Corront B, Allard C, Foussard C, Bosly A, Coiffier B, Gisselbrecht C, Solal-Celigny P, Salles G (2010) Long-term follow-up of patients with newly diagnosed follicular lymphoma in the prerituximab era: effect of response quality on survival—a study from the groupe d'etude des lymphomes de l'adulte. J Clin Oncol 28(5):822–829PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Stefan W. Krause
    • 4
    • 5
    Email author
  • Michael Gerken
    • 1
  • Reinhard Andreesen
    • 1
    • 3
  • Ferdinand Hofstädter
    • 1
    • 2
  • Monika Klinkhammer-Schalke
    • 1
  1. 1.Tumorzentrum RegensburgRegensburgGermany
  2. 2.Institute of PathologyUniversity HospitalRegensburgGermany
  3. 3.Department of Hematology and Medical OncologyUniversity Hospital RegensburgRegensburgGermany
  4. 4.Department of Hematology and Medical OncologyUniversity Hospital ErlangenErlangenGermany
  5. 5.Medizinische Klinik 5-Hämatologie und Internistische OnkologieKlinikum der Universität ErlangenErlangenGermany

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