Annals of Hematology

, Volume 97, Issue 2, pp 277–287 | Cite as

R-hyper-CVAD versus R-CHOP/cytarabine with high-dose therapy and autologous haematopoietic stem cell support in fit patients with mantle cell lymphoma: 20 years of single-center experience

  • Fabienne Widmer
  • Stefan Balabanov
  • Davide Soldini
  • Panagiotis Samaras
  • Bernhard Gerber
  • Markus G. Manz
  • Jeroen S. Goede
Original Article


Standard of care for untreated mantle cell lymphoma (MCL) is still debated. At the University Hospital Zurich, advanced MCL in physically fit patients is treated either with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone induction followed by consolidating high-dose chemotherapy and autologous stem cell support (R-CHOP/HD-ASCT), or with rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate-cytarabine (R-hyper-CVAD/MTX-AraC) without consolidating HD-ASCT upon physicians’ and patients’ choice. We retrospectively analysed the outcome and therapy tolerance in patients with MCL treated with R-CHOP/HD-ASCT or R-hyper-CVAD/MTX-AraC at the University Hospital Zurich between January 1996 and January 2016. Forty-three patients were included; 29 patients received R-CHOP/HD-ASCT and 14 patients R-hyper-CVAD/MTX-AraC. Mean age at diagnosis was 54.4 years (range 38–68 years). Thirty-five patients (81.4%) completed the entire first-line therapy (n = 24 in the R-CHOP/HD-ASCT group, n = 11 in the R-hyper-CVAD group). Of those, all patients responded and 97% achieved a complete remission (CR). With a mean follow-up of 5.7 years 10-year progression-free survival (PFS) for all patients was 32% and overall survival (OS) was 76%, with no difference between the two therapy groups. Complication-induced hospitalisation rate, haematological toxicity and economic burden were significantly higher in the R-hyper-CVAD therapy group. In contrast, quality of life and global health state were better in the R-hyper-CVAD therapy group. Both first-line therapies showed similar outcome with a median OS longer than 10 years. Due to significantly lower haematological toxicity and lower economic burden, we recommend R-CHOP/HD-ASCT as first-line therapy in fit adult patients with advanced MCL.


R-CHOP/HD-ASCT R-hyper-CVAD/MTX-AraC Mantle cell lymphoma Health-related quality of life Economic burden 



We thank the patients for their willingness to participate.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Swerdlow SH, Campo E, Seto M, Müller-Hermelink HK (2008) Mantle cell lymphoma. In: Swerdlow SH, Campo E, Harris NL et al (eds) WHO-classification of tumours of haematopoietic and lymphoid tissues ,4th edn. IARC Press, Lyon, pp 229–232Google Scholar
  2. 2.
    Federal Statistical Office (BFS), Section for demography and migration (2016) Population size and population composition. Federal Statistical Office Website. Accessed 02 Aug 2016
  3. 3.
    Dreyling M, Geisler C, Hermine O, Kluin-Nelemans HC, le Gouill S, Rule S, Shpilberg O, Walewski J, Ladetto M, on behalf of the ESMO Guidelines Working Group (2014) Newly diagnosed and relapsed mantle cell lymphoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 25(Suppl 3):iii83–iii92. CrossRefPubMedGoogle Scholar
  4. 4.
    Geisler C, Kolstad A, Laurell A et al (2012) Nordic MCL2 trial update: six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem-cell support: still very long survival but late relapses do occur. Br J Haematol 158(3):355–362. CrossRefPubMedGoogle Scholar
  5. 5.
    Chihara D, Cheah CY, Westin JR, Fayad LE, Rodriguez MA, Hagemeister FB, Pro B, McLaughlin P, Younes A, Samaniego F, Goy A, Cabanillas F, Kantarjian H, Kwak LW, Wang ML, Romaguera JE (2016) Rituximab plus hyper-CVAD alternating with MTX/Ara-C in patients with newly diagnosed mantle cell lymphoma: 15-year follow-up of a phase II study from the MD Anderson Cancer Center. Br J Haematol 172(1):80–88. CrossRefPubMedGoogle Scholar
  6. 6.
    Vose JM (2015) Mantle cell lymphoma: 2015 update on diagnosis, risk-stratification, and clinical management. Am J Hematol 90(8):739–745. CrossRefPubMedGoogle Scholar
  7. 7.
    Dreyling M, Lenz G, Hoster E, van Hoof A, Gisselbrecht C, Schmits R, Metzner B, Truemper L, Reiser M, Steinhauer H, Boiron JM, Boogaerts MA, Aldaoud A, Silingardi V, Kluin-Nelemans HC, Hasford J, Parwaresch R, Unterhalt M, Hiddemann W (2005) Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL network. Blood 105(7):2677–2684. CrossRefPubMedGoogle Scholar
  8. 8.
    Romaguera JE, Fayad LE, Feng L, Hartig K, Weaver P, Rodriguez MA, Hagemeister FB, Pro B, McLaughlin P, Younes A, Samaniego F, Goy A, Cabanillas F, Kantarjian H, Kwak L, Wang M (2010) Ten-year follow-up after intense chemoimmunotherapy with rituximab-HyperCVAD alternating with rituximab-high dose methotrexate/cytarabine (R-MA) and without stem cell transplantation in patients with untreated aggressive mantle cell lymphoma. Br J Haematol 150(2):200–208. PubMedGoogle Scholar
  9. 9.
    Bernstein SH, Epner E, Unger JM, LeBlanc M, Cebula E, Burack R, Rimsza L, Miller TP, Fisher RI (2013) A phase II multicenter trial of hyperCVAD MTX/Ara-C and rituximab in patients with previously untreated mantle cell lymphoma; SWOG 0213. Ann Oncol 24(6):1587–1593. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    LaCasce AS, Vandergrift JL, Rodriguez MA, Abel GA, Crosby AL, Czuczman MS, Nademanee AP, Blayney DW, Gordon LI, Millenson M, Vanderplas A, Lepisto EM, Zelenetz AD, Niland J, Friedberg JW (2012) Comparative outcome of initial therapy for younger patients with mantle cell lymphoma: an analysis from the NCCN NHL database. Blood 119(9):2093–2099. CrossRefPubMedGoogle Scholar
  11. 11.
    Lefrère F, Delmer A, Levy V, Delarue R, Varet B, Hermine O (2004) Sequential chemotherapy regimens followed by high-dose therapy with stem cell transplantation in mantle cell lymphoma: an update of a prospective study. Haematologica 89(10):1275–1276PubMedGoogle Scholar
  12. 12.
    Pott C, Hoster E, Beldjord K et al (2010) R-CHOP/R-DHAP compared to R-CHOP induction followed by high dose therapy with autologous stem cell transplantation induces higher rates of molecular remission in MCL: results of the MCL younger intergroup trial of the European MCL Network. ASH Annu Meet Abstr 116:965Google Scholar
  13. 13.
    Delarue R, Haioun C, Ribrag V, Brice P, Delmer A, Tilly H, Salles G, van Hoof A, Casasnovas O, Brousse N, Lefrere F, Hermine O, for the Groupe d'Etude des Lymphomes de l'Adulte (GELA) (2013) CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d’Etude des Lymphomes de l’Adulte. Blood 121(1):48–53. CrossRefPubMedGoogle Scholar
  14. 14.
    Van’t Veer MB, de Jong D, MacKenzie M et al (2009) High-dose Ara-C and beam with autograft rescue in R-CHOP responsive mantle cell lymphoma patients. Br J Haematol 144(4):524–530. CrossRefGoogle Scholar
  15. 15.
    Hermine O, Hoster E, Walewski J, Bosly A, Stilgenbauer S, Thieblemont C, Szymczyk M, Bouabdallah R, Kneba M, Hallek M, Salles G, Feugier P, Ribrag V, Birkmann J, Forstpointner R, Haioun C, Hänel M, Casasnovas RO, Finke J, Peter N, Bouabdallah K, Sebban C, Fischer T, Dührsen U, Metzner B, Maschmeyer G, Kanz L, Schmidt C, Delarue R, Brousse N, Klapper W, Macintyre E, Delfau-Larue MH, Pott C, Hiddemann W, Unterhalt M, Dreyling M (2016) Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL younger): a randomised, open-label, phase 3 trial of the European mantle cell lymphoma network. Lancet 388(10044):565–575. CrossRefPubMedGoogle Scholar
  16. 16.
    Romaguera JE, Fayad L, Rodriguez MA, Broglio KR, Hagemeister FB, Pro B, McLaughlin P, Younes A, Samaniego F, Goy A, Sarris AH, Dang NH, Wang M, Beasley V, Medeiros LJ, Katz RL, Gagneja H, Samuels BI, Smith TL, Cabanillas FF (2005) High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. J Clin Oncol 23(28):7013–7023. CrossRefPubMedGoogle Scholar
  17. 17.
    Hoster E, Dreyling M, Klapper W, Gisselbrecht C, van Hoof A, Kluin-Nelemans HC, Pfreundschuh M, Reiser M, Metzner B, Einsele H, Peter N, Jung W, Wörmann B, Ludwig WD, Dührsen U, Eimermacher H, Wandt H, Hasford J, Hiddemann W, Unterhalt M, German Low Grade Lymphoma Study Group (GLSG), European Mantle Cell Lymphoma Network (2008) A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood 111(2):558–565. CrossRefPubMedGoogle Scholar
  18. 18.
    [no authors listed] (1993) A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med 329(14):987–994. doi: CrossRefGoogle Scholar
  19. 19.
    Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordstrom M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundstrom C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E, for the Nordic Lymphoma Group (2008) Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood 112(7):2687–2693. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V, International Harmonization Project on Lymphoma (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25(5):579–586. CrossRefPubMedGoogle Scholar
  21. 21.
    National Institutes of Health and National Cancer Institute of the U.S. Department of Health and Human Services (2009) Common terminology criteria for adverse events (CTCAE) version 4.03. National Cancer Institute Enterprise vocabulary services. Accessed 20 Mar 2016
  22. 22.
    Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, Haes JCJM, Kaasa S, Klee M, Osoba D, Razavi D, Rofe PB, Schraub S, Sneeuw K, Sullivan M, Takeda F (1993) The European Organisation for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85(5):365–376. CrossRefPubMedGoogle Scholar
  23. 23.
    Fayers PM, Aaronson NK, Bjordal K et al (2001) The EORTC QLQ-C30 scoring manual, 3rd edn. European Organisation for Research and Treatment of Cancer, BrusselsGoogle Scholar
  24. 24.
    Osoba D, Rodrigues G, Myles J, Zee B, Pater J (1998) Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol 16(1):139–144. CrossRefPubMedGoogle Scholar
  25. 25.
    Hjermstad MJ, Fayers PM, Bjordal K, Kaasa S (1998) Health-related quality of life in the general Norwegian population assessed by the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire: the QLQ=C30 (+ 3). J Clin Oncol 16(3):1188–1196. CrossRefPubMedGoogle Scholar
  26. 26.
    Schwarz R, Hinz A (2001) Reference data for the quality of life questionnaire EORTC QLQ-C30 in the general German population. Eur J Cancer 37(11):1345–1351. CrossRefPubMedGoogle Scholar
  27. 27.
    Merli F, Luminari S, Ilariucci F, Petrini M, Visco C, Ambrosetti A, Stelitano C, Caracciolo F, di Renzo N, Angrilli F, Carella AM, Capodanno I, Barbolini E, Galimberti S, Federico M (2012) Rituximab plus HyperCVAD alternating with high dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma, a multicentre trial from Gruppo Italiano Studio Linfomi. Br J Haematol 156(3):346–353. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Fabienne Widmer
    • 1
  • Stefan Balabanov
    • 1
  • Davide Soldini
    • 2
  • Panagiotis Samaras
    • 3
  • Bernhard Gerber
    • 1
    • 4
  • Markus G. Manz
    • 1
  • Jeroen S. Goede
    • 1
    • 5
  1. 1.Division of HaematologyUniversity Hospital and University of ZurichZurichSwitzerland
  2. 2.Institute for Surgical PathologyUniversity Hospital and University of ZurichZurichSwitzerland
  3. 3.Division of OncologyUniversity Hospital and University of ZurichZurichSwitzerland
  4. 4.Division of HaematologyOncology Institute of Southern SwitzerlandBellinzonaSwitzerland
  5. 5.Division of Oncology and HaematologyKantonsspital WinterthurWinterthurSwitzerland

Personalised recommendations