Skip to main content
SpringerLink
Log in

Mantle cell lymphoma: Therapeutic strategies are different from CLL

  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

In contrast to the typical course of chronic lymphocytic lymphoma and despite an indolent lymphoma-like presentation, the clinical outcome of mantle cell lymphoma (MCL) is dismal, with a median survival time of 3 years and virtually no long-term survivors. Most patients are diagnosed with advanced stage III/IV disease. Although clinical studies did not prove a clear superiority of anthracyclin-containing combinations, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like regimens represent the standard therapeutic approach in MCL. Recent randomized studies have shown a benefit of a combined immunochemotherapy strategy (chemotherapy plus rituximab) increasing the complete and overall response rates, whereas further followup is pending for evaluation of the progression-free and overall survival. In patients younger than 65 years, a dose-intensive consolidation comprising high-dose radiochemotherapy and subsequent autologous stem cell transplantation after a CHOP-like induction results in an improved progression-free survival. However, despite the benefits of this multimodal approach, most patients relapse even after high-dose therapy. The only curative approach is allogeneic stem cell transplantation, which may be adapted to the elderly MCL patient cohort by modified dose-reduced conditioning regimens. Prospective randomized trials remain critical to further improve the clinical course of MCL with the addition of newer treatment modalities, such as radioactively labeled antibodies and targeted therapies (eg, flavopiridol and PS-341).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Medeiros LJ, van Krieken JH, Jaffe ES, Raffeld M: Association of bcl-1 rearrangements with lymphocytic lymphoma of intermediate differentiation. Blood 1990, 76:2086–2090.

    PubMed  CAS  Google Scholar 

  2. Rosenberg CL, Wong E, Petty EM, et al.: PRAD1, a candidate BLC1 oncogene: mapping and expression in centrocytic lymphoma. Proc Natl Acad Sci U S A 1991, 88:9638–9642.

    Article  PubMed  CAS  Google Scholar 

  3. Hiddemann W, Dreyling M, Tiemann M, et al.: Mantle cell lymphomas. Haematologica 1999, 84(Suppl 10):93–95. A short and precise description of the clinical characteristics of MCL.

    Google Scholar 

  4. Jaffe ES, Campo E, Raffeld M: Mantle cell lymphoma. Semin Hematol 1999, 36:115–127. An excellent histomorphologic characterization of MCL.

    PubMed  Google Scholar 

  5. Yatabe Y, Suzuki R, Matsuno Y, et al.: Morphological spectrum of cyclin D1-positive mantle cell lymphoma: study of 168 cases. Pathol Int 2001, 51:747–761.

    Article  PubMed  CAS  Google Scholar 

  6. Ruskone-Fourmestraux A, Delmer A, Lavergne A, et al.: Multiple lymphomatous polyposis of the gastrointestinal tract: prospective clinicopathologic study of 31 cases. Groupe D’etude des Lymphomes Digestifs. Gastroenterology 1997, 112:7–16.

    Article  PubMed  CAS  Google Scholar 

  7. Oinonen R, Franssila K, Elonen E: Central nervous system involvement in patients with mantle cell lymphoma. Ann Hematol 1999, 78:145–149.

    Article  PubMed  CAS  Google Scholar 

  8. Bosch F, Lopez-Guillermo A, Campo E, et al.: Mantle cell lymphoma: presenting features, response to therapy, and prognostic factors. Cancer 1998, 82:567–575.

    Article  PubMed  CAS  Google Scholar 

  9. Weisenburger DD, Vose JM, Greiner TC, et al.: Mantle cell lymphoma. A clinicopathologic study of 68 cases from the Nebraska Lymphoma Study Group. Am J Hematol 2000, 64:190–196.

    Article  PubMed  CAS  Google Scholar 

  10. Andersen NS, Jensen MK, de Nully Brown P, Geisler CH: A Danish population-based analysis of 105 mantle cell lymphoma patients: incidences, clinical features, response, survival and prognostic factors. Eur J Cancer 2002, 38:401–408.

    Article  PubMed  CAS  Google Scholar 

  11. Dreyling M: The increasing role of prognostic factors in the choice of treatment: mantle cell lymphoma [abstract]. Ann Oncology 2002, 13(Suppl 2):18.

    Google Scholar 

  12. Frank C, Zierhut D, Schulz-Ertner D, Wannenmacher M: Centroblastic-centrocytic non-Hodgkin’s lymphoma stage I-III: patterns of failure following radiotherapy. Strahlenther Onkol 2001, 177:597–603.

    Article  PubMed  CAS  Google Scholar 

  13. Zucca E, Roggero E, Pinotti G, et al.: Patterns of survival in mantle cell lymphoma. Ann Oncol 1995, 6:257–262.

    PubMed  CAS  Google Scholar 

  14. Meusers P, Engelhard M, Bartels H, et al.: Multicentre randomized therapeutic trial for advanced centrocytic lymphoma: anthracycline does not improve the prognosis. Hematol Oncol 1989, 7:365–380.

    Article  PubMed  CAS  Google Scholar 

  15. Zinzani PL, Magagnoli M, Moretti L, et al.: Randomized trial of fludarabine versus fludarabine and idarubicin as frontline treatment in patients with indolent or mantle cell lymphoma. J Clin Oncol 2000, 18:773–779.

    PubMed  CAS  Google Scholar 

  16. Decaudin D, Bosq J, Tertian G, et al.: Phase II trial of fludarabine monophosphate in patients with mantle cell lymphomas. J Clin Oncol 1998, 16:579–583.

    PubMed  CAS  Google Scholar 

  17. Samaha H, Dumontet C, Ketterer N, et al.: Mantle cell lymphoma: a retrospective study of 121 cases. Leukemia 1998, 12:1281–1287.

    Article  PubMed  CAS  Google Scholar 

  18. Foran JM, Rohatiner AZ, Coiffier B, et al.: Multicenter phase II study of fludarabine phosphate for patients with newly diagnosed lymphoplasmacytoid lymphoma, Waldenstrom’s macroglobulinemia, and mantle cell lymphoma. J Clin Oncol 1999, 17:546–553.

    PubMed  CAS  Google Scholar 

  19. Rummel MJ, Chow KU, Karakas T, et al.: Reduced-dose cladribine (2-CdA) plus mitoxantrone is effective in the treatment of mantle cell and low grade non-Hodgkin’s lymphoma. Eur J Cancer 2002, 38:1739–1746.

    Article  PubMed  CAS  Google Scholar 

  20. Hiddemann W, Dreyling M, Unterhalt M: Rituximab plus chemotherapy in follicular and mantle cell lymphomas. Semin Oncol 2003, 30(Suppl 2):16–20. This paper presents the results of the first randomized study in MCL, suggesting the benefits of combined immunochemotherapy (R-FCM).

    Article  PubMed  CAS  Google Scholar 

  21. Cohen BJ, Moskowitz C, Straus D, et al.: Cyclophosphamide/ fludarabine (CF) is active in the treatment of mantle cell lymphoma. Leuk Lymphoma 2001, 42:1015–1022. Despite the small and inhomogenous patient population, this study confirms the efficacy of a fludarabine-containing regimen in patients with MCL.

    Article  PubMed  CAS  Google Scholar 

  22. Touati M, Fitoussi O, Jaccard A, Petit B: DHAP regimen for relapsed or refractory low grade lymphomas: a study of 86 cases. Blood 2002, 100:302b.

    Google Scholar 

  23. Lefrere F, Delmer A, Suzan F, et al.: Sequential chemotherapy by CHOP and DHAP regimens followed by highdose therapy with stem cell transplantation induces a high rate of complete response and improves event-free survival in mantle cell lymphoma: a prospective study. Leukemia 2002, 16:587–593. This phase II study strongly suggests the superiority of a highdose cytarabine-containing chemotherapy in comparison to a standard CHOP regimen.

    Article  PubMed  CAS  Google Scholar 

  24. Romaguera JE, Khouri IF, Kantarjian HM, et al.: Untreated aggressive mantle cell lymphoma: results with intensive chemotherapy without stem cell transplant in elderly patients. Leuk Lymphoma 2000, 39:77–85. The results of this dose-intensified MD Anderson (Houston, TX) approach in patients with MCL are remarkable. In addition, this alternating concept was feasible in an elderly patient cohort.

    PubMed  CAS  Google Scholar 

  25. Seymour JF, Grigg AP, Szer J, Fox RM: Cisplatin, fludarabine, and cytarabine: a novel, pharmacologically designed salvage therapy for patients with refractory, histologically aggressive or mantle cell non-Hodgkin’s lymphoma. Cancer 2002, 94:585–593.

    Article  PubMed  CAS  Google Scholar 

  26. Teodorovic I, Pittaluga S, Kluin-Nelemans JC, et al.: Efficacy of four different regimens in 64 mantle cell lymphoma cases: clinicopathologic comparison with 498 other non-Hodgkin’s lymphoma subtypes. European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group. J Clin Oncol 1995, 13:2819–2826.

    PubMed  CAS  Google Scholar 

  27. Coiffier B, Haioun C, Delaby P, et al.: Phase II study of PEG-Itron in combination with chemotherapy for the treatment of first line patients with follicular lymphoma who need to be treated [abstract]. Blood 2001, 98:604a.

    Article  Google Scholar 

  28. Bukowski RM, Tendler C, Cutler D, et al.: Treating cancer with PEG Intron: pharmacokinetic profile and dosing guidelines for an improved interferon-alpha-2b formulation. Cancer 2002, 95:389–396.

    Article  PubMed  CAS  Google Scholar 

  29. Foran JM, Rohatiner AZ, Cunningham D, et al.: European phase II study of rituximab (chimeric anti-CD20 monoclonal antibody) for patients with newly diagnosed mantle cell lymphoma and previously treated mantle cell lymphoma, immunocytoma, and small B-cell lymphocytic lymphoma. J Clin Oncol 2000, 18:317–324.

    PubMed  CAS  Google Scholar 

  30. Ghielmini M, Schmitz SF, Burki K, et al.: The effect of rituximab on patients with follicular and mantle cell lymphoma. Swiss Group for Clinical Cancer Research (SAKK). Ann Oncol 2000, 11:123–126.

    Article  PubMed  Google Scholar 

  31. Demidem A, Lam T, Alas S, et al.: Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs. Cancer Biother Radiopharm 1997, 12:176–177.

    Google Scholar 

  32. Howard OM, Gribben JG, Neuberg DS, et al.: Rituximab and CHOP induction therapy for newly diagnosed mantle cell lymphoma: molecular complete responses are not predictive of progression-free survival. J Clin Oncol 2002, 20:1288–1294. This is the first full paper describing, in more detail, the effect of combined immunochemotherapy (R-CHOP) in patients with MCL. A rather short remission duration was observed.

    Article  PubMed  CAS  Google Scholar 

  33. Hiddemann W, Unterhalt M, Dreyling M, et al.: The addition of rituximab (R) to combination chemotherapy (CT) improves the treatment of mantle cell lymphomas (MCL): results of two prospective randomized studies by the German Low Grade Lymphoma Study Group (GLSG) [abstract]. Blood 2002, 100:92a. These studies showed a superior overall survival after combined immunochemotherapy (R-FCM) in relapsed MCL.

    Google Scholar 

  34. Gopal AK, Rajendran JG, Petersdorf SH, et al.: Highdose chemo-radioimmunotherapy with autologous stem cell support for relapsed mantle cell lymphoma. Blood 2002, 99:3158–3162. Although the number of patients is small, this study is a proof of principle for the radioimmunochemotherapy in the therapy-refractory entity of MCL.

    Article  PubMed  CAS  Google Scholar 

  35. Behr TM, Griesinger F, Riggert J, et al.: High-dose myeloablative radioimmunotherapy of mantle cell non-Hodgkin lymphoma with the iodine-131-labeled chimeric anti-CD20 antibody C2B8 and autologous stem cell support. Results of a pilot study. Cancer 2002, 94(Suppl 4):1363–1372.

    Article  PubMed  CAS  Google Scholar 

  36. Stewart DA, Vose JM, Weisenburger DD, et al.: The role of high-dose therapy and autologous hematopoietic stem cell transplantation for mantle cell lymphoma. Ann Oncol 1995, 6:263–266.

    PubMed  CAS  Google Scholar 

  37. Milpied N, Gaillard F, Moreau P, et al.: High-dose therapy with stem cell transplantation for mantle cell lymphoma: results and prognostic factors, a single center experience. Bone Marrow Transplant 1998, 22:645–650.

    Article  PubMed  CAS  Google Scholar 

  38. Hiddemann W, Dreyling MH, Pfreundschuh M, et al.: Myeloablative radiochemotherapy followed by autologous stem cell transplantation leads to a significant prolongation of the event-free survival in patients with mantle cell lymphoma (MCL): results of a prospective randomized European intergroup study [abstract]. Blood 2001, 98:861a. The first prospectively randomized study that confirms the benefit of an intensive consolidation concerning progressionfree survival in patients with MCL.

    Google Scholar 

  39. Andersen NS, Donovan JW, Borus JS, et al.: Failure of immunologic purging in mantle cell lymphoma assessed by polymerase chain reaction detection of minimal residual disease. Blood 1997, 90:4212–4221.

    PubMed  CAS  Google Scholar 

  40. 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.

    PubMed  CAS  Google Scholar 

  41. Kroger N, Hoffknecht M, Kruger W, et al.: Allogeneic bone marrow transplantation for refractory mantle cell lymphoma. Ann Hematol 2000, 79:578–580.

    Article  PubMed  CAS  Google Scholar 

  42. Martinez C, Carreras E, Rovira M, et al.: Patients with mantle cell lymphoma relapsing after autologous stem cell transplantation may be rescued by allogeneic transplantation. Bone Marrow Transplant 2000, 26:677–679.

    Article  PubMed  CAS  Google Scholar 

  43. Berdeja JG, Jones RJ, Zahurak ML, et al.: Allogeneic bone marrow transplantation in patients with sensitive low-grade lymphoma or mantle cell lymphoma. Biol Blood Marrow Transplant 2001, 7:561–567.

    Article  PubMed  CAS  Google Scholar 

  44. Khouri FI, Saliba RM, Younes A, et al.: Allogeneic transplantation for poor risk mantle cell lymphoma (MCL): chemosensitivity predicts superior outcome [abstract]. Blood 2002, 100:416a.

    Google Scholar 

  45. Lin TS, Howard OM, Neuberg DS, et al.: Seventy-two hour continuous infusion flavopiridol in relapsed and refractory mantle cell lymphoma. Leuk Lymphoma 2002, 43:793–797.

    Article  PubMed  CAS  Google Scholar 

  46. Pham L, Tamayo A, Lo P, et al.: Anti-tumor activity of the proteasome inhibitor PS-341 in mantle cell lymphoma B cells [abstract]. Blood 2001, 98:465a.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine III, University Hospital Grosshadern/LMU, Marchioninistrasse 15, 81377, Munich, Germany

    Martin Dreyling MD

Authors
  1. Wolfgang Hiddemann MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin Dreyling MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hiddemann, W., Dreyling, M. Mantle cell lymphoma: Therapeutic strategies are different from CLL. Curr. Treat. Options in Oncol. 4, 219–226 (2003). https://doi.org/10.1007/s11864-003-0023-x

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-003-0023-x

Keywords

Search

Navigation