Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Hematopoietic SCT for mantle cell lymphoma: is it the standard of care?

Bone Marrow Transplantation volume 45, pages 1379–1387 (2010)Cite this article

Subjects

Abstract

The role of hematopoietic SCT (HSCT) in mantle cell lymphoma (MCL) remains controversial. Most studies that support the utility of this approach were small phase II single-institution studies with highly selected patient populations. Furthermore, recent evidence suggesting initial observation as opposed to immediate therapy in MCL, coupled with the availability of newer therapeutic agents, complicates the role of HSCT and argues for conducting large phase III studies. In this review, we discuss the limitation of current evidence and the lack of large definitive studies. We then analyze the data on HSCT in relapsed MCL and as a frontline approach propose applying the new prognostic index, MIPI (MCL International Prognostic Index), in the decision making.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ . Cancer statistics, 2009. CA Cancer J Clin 2009; 59: 225–249.

    Article  PubMed  Google Scholar 

  2. Velders GA, Kluin-Nelemans JC, De Boer CJ, Hermans J, Noordijk EM, Schuuring E et al. Mantle-cell lymphoma: a population-based clinical study. J Clin Oncol 1996; 14: 1269–1274.

    Article  CAS  PubMed  Google Scholar 

  3. Zucca E, Stein H, Coiffier B . European Lymphoma Task Force (ELTF): report of the workshop on mantle cell lymphoma (MCL). Ann Oncol 1994; 5: 507–511.

    Article  CAS  PubMed  Google Scholar 

  4. Fernandez V, Hartmann E, Ott G, Campo E, Rosenwald A . Pathogenesis of mantle-cell lymphoma: all oncogenic roads lead to dysregulation of cell cycle and DNA damage response pathways. J Clin Oncol 2005; 23: 6364–6369.

    Article  CAS  PubMed  Google Scholar 

  5. Banks PM, Chan J, Cleary ML, Delsol G, De Wolf-Peeters C, Gatter K et al. Mantle cell lymphoma. A proposal for unification of morphologic, immunologic, and molecular data. Am J Surg Pathol 1992; 16: 637–640.

    Article  CAS  PubMed  Google Scholar 

  6. Gomez Pescie M, Denninghoff V, Garcia A, Rescia C, Avagnina A, Elsner B . [Mantle cell lymphoma vs atypical chronic lymphocytic leukemia. Use of immunohistochemistry, flow cytometry and molecular biology for their adequate typing]. Medicina (B Aires) 2005; 65: 419–424.

    Google Scholar 

  7. Kelemen K, Peterson LC, Helenowski I, Goolsby CL, Jovanovic B, Miyata S et al. CD23+ mantle cell lymphoma: a clinical pathologic entity associated with superior outcome compared with CD23− disease. Am J Clin Pathol 2008; 130: 166–177.

    Article  PubMed  Google Scholar 

  8. Hoster E, Dreyling M, Klapper W, Gisselbrecht C, van Hoof A, Kluin-Nelemans HC et al. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood 2008; 111: 558–565.

    Article  CAS  PubMed  Google Scholar 

  9. Determann O, Hoster E, Ott G, Wolfram BH, Loddenkemper C, Leo Hansmann M et al. Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group. Blood 2008; 111: 2385–2387.

    Article  CAS  PubMed  Google Scholar 

  10. Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M et al. 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 2008; 112: 2687–2693.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Evens AM, Winter JN, Hou N, Nelson BP, Rademaker A, Patton D et al. A phase II clinical trial of intensive chemotherapy followed by consolidative stem cell transplant: long-term follow-up in newly diagnosed mantle cell lymphoma. Br J Haematol 2008; 140: 385–393.

    Article  CAS  PubMed  Google Scholar 

  12. Romaguera JE, Fayad L, Rodriguez MA, Broglio KR, Hagemeister FB, Pro B et al. 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 2005; 23: 7013–7023.

    Article  CAS  PubMed  Google Scholar 

  13. Pfreundschuh M . Factors predictive for response of follicular and mantle-cell lymphoma to rituximab. Nat Clin Pract Oncol 2006; 3: 184–185.

    Article  CAS  PubMed  Google Scholar 

  14. Witzig TE . Current treatment approaches for mantle-cell lymphoma. J Clin Oncol 2005; 23: 6409–6414.

    Article  CAS  PubMed  Google Scholar 

  15. Howard OM, Gribben JG, Neuberg DS, Grossbard M, Poor C, Janicek MJ 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.

    Article  CAS  PubMed  Google Scholar 

  16. Lenz G, Dreyling M, Hoster E, Wormann B, Duhrsen U, Metzner B et al. 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 2005; 23: 1984–1992.

    Article  CAS  PubMed  Google Scholar 

  17. Khouri IF, Romaguera J, Kantarjian H, Palmer JL, Pugh WC, Korbling M et al. Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma. J Clin Oncol 1998; 16: 3803–3809.

    Article  CAS  PubMed  Google Scholar 

  18. Fayad L, Thomas D, Romaguera J . Update of the M. D. Anderson Cancer Center experience with hyper-CVAD and rituximab for the treatment of mantle cell and Burkitt-type lymphomas. Clin Lymphoma Myeloma 2007; 8 (Suppl 2): S57–S62.

    Article  CAS  PubMed  Google Scholar 

  19. Epner E, Unger J, Miller T, Rimzsa L, Spier C, Leblanc M et al. A multi center trial of hyperCVAD+Rituxan in patients with newly diagnosed mantle cell lymphoma. Blood 2007; 110. Abstract no. 387.

  20. Kahl BS, Longo WL, Eickhoff JC, Zehnder J, Jones C, Blank J et al. Maintenance rituximab following induction chemoimmunotherapy may prolong progression-free survival in mantle cell lymphoma: a pilot study from the Wisconsin Oncology Network. Ann Oncol 2006; 17: 1418–1423.

    Article  CAS  PubMed  Google Scholar 

  21. Kisselev AF, Goldberg AL . Proteasome inhibitors: from research tools to drug candidates. Chem Biol 2001; 8: 739–758.

    Article  CAS  PubMed  Google Scholar 

  22. Fisher RI, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S et al. Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol 2006; 24: 4867–4874.

    Article  PubMed  Google Scholar 

  23. Kane RC, Dagher R, Farrell A, Ko CW, Sridhara R, Justice R et al. Bortezomib for the treatment of mantle cell lymphoma. Clin Cancer Res 2007; 13 (18 Part 1): 5291–5294.

    Article  CAS  PubMed  Google Scholar 

  24. Belch A, Kouroukis CT, Crump M, Sehn L, Gascoyne RD, Klasa R et al. A phase II study of bortezomib in mantle cell lymphoma: the National Cancer Institute of Canada Clinical Trials Group trial IND.150. Ann Oncol 2007; 18: 116–121.

    Article  CAS  PubMed  Google Scholar 

  25. Kahl B, Chang J, Eickhoff J, Gilbert L, Rogers E, Werndli J et al. VcR-CVAD produces a high complete response rate in untreated mantle cell lymphoma: a phase ii study from the Wisconsin oncology network. Blood 2008; 112. Abstract no. 265.

  26. Rini BI . Temsirolimus, an inhibitor of mammalian target of rapamycin. Clin Cancer Res 2008; 14: 1286–1290.

    Article  CAS  PubMed  Google Scholar 

  27. Ansell SM, Inwards DJ, Rowland Jr KM, Flynn PJ, Morton RF, Moore Jr DF et al. Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma: a phase 2 trial in the North Central Cancer Treatment Group. Cancer 2008; 113: 508–514.

    Article  CAS  PubMed  Google Scholar 

  28. Witzig TE, Geyer SM, Ghobrial I, Inwards DJ, Fonseca R, Kurtin P et al. Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol 2005; 23: 5347–5356.

    Article  CAS  PubMed  Google Scholar 

  29. Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C et al. Phase III study to evaluate temsirolimus compared with investigator's choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 2009; 27: 3822–3829.

    Article  CAS  PubMed  Google Scholar 

  30. Damaj G, Lefrere F, Delarue R, Varet B, Furman R, Hermine O . Thalidomide therapy induces response in relapsed mantle cell lymphoma. Leukemia 2003; 17: 1914–1915.

    Article  CAS  PubMed  Google Scholar 

  31. Tempescul A, Ianotto JC, Morel F, Marion V, De Braekeleer M, Berthou C . Lenalidomide, as a single agent, induces complete remission in a refractory mantle cell lymphoma. Ann Hematol 2009; 88: 921–922.

    Article  PubMed  Google Scholar 

  32. Habermann TM, Lossos IS, Justice G, Vose JM, Wiernik PH, McBride K et al. Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma. Br J Haematol 2009; 145: 344–349.

    Article  CAS  PubMed  Google Scholar 

  33. Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D et al. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. J Clin Oncol 2005; 23: 3383–3389.

    Article  CAS  PubMed  Google Scholar 

  34. Herold M, Schulze A, Niederwieser D, Franke A, Fricke HJ, Richter P et al. Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin's lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19). J Cancer Res Clin Oncol 2006; 132: 105–112.

    Article  CAS  PubMed  Google Scholar 

  35. Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med 1995; 333: 1540–1545.

    Article  CAS  PubMed  Google Scholar 

  36. Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY et al. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med 1987; 316: 1493–1498.

    Article  CAS  PubMed  Google Scholar 

  37. Meehan KR, Pritchard RS, Leichter JW, Littenberg B, Welch HG . Autologous bone marrow transplantation versus chemotherapy in relapsed/refractory non-Hodgkin's lymphoma: estimates of long-term survival from the recent literature. Am J Hematol 1995; 50: 116–123.

    Article  CAS  PubMed  Google Scholar 

  38. Vose JM, Bierman PJ, Weisenburger DD, Lynch JC, Bociek Y, Chan WC et al. Autologous hematopoietic stem cell transplantation for mantle cell lymphoma. Biol Blood Marrow Transplant 2000; 6: 640–645.

    Article  CAS  PubMed  Google Scholar 

  39. Gopal AK, Rajendran JG, Petersdorf SH, Maloney DG, Eary JF, Wood BL et al. High-dose chemo-radioimmunotherapy with autologous stem cell support for relapsed mantle cell lymphoma. Blood 2002; 99: 3158–3162.

    Article  CAS  PubMed  Google Scholar 

  40. Robinson SP, Goldstone AH, Mackinnon S, Carella A, Russell N, de Elvira CR et al. Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the lymphoma working party of the European group for blood and bone marrow transplantation. Blood 2002; 100: 4310–4316.

    Article  CAS  PubMed  Google Scholar 

  41. Robinson S, Schmitz N, Taghipour G, Sureda A . Reduced intensity allogeneic stem cell transplantation for mantle cell lymphoma is associated with substantial late transplant related mortality and a poor outcome in patients with chemoresistant disease. Blood 2004; 104: Abstract no. 2260.

  42. Robinson S, Sureda A, Canals C, Vernant J, Milpied N, Finke J et al. Identification of prognostic factors predicting the outcome of reduced intensity allogeneic stem cell transplantation in mantle cell lymphoma. An analysis from the lymphoma working party of the EBMT. Blood 2008; 112: Abstract no. 457.

  43. Khouri IF, Lee MS, Romaguera J, Mirza N, Kantarjian H, Korbling M et al. Allogeneic hematopoietic transplantation for mantle-cell lymphoma: molecular remissions and evidence of graft-versus-malignancy. Ann Oncol 1999; 10: 1293–1299.

    Article  CAS  PubMed  Google Scholar 

  44. Milpied N, Gaillard F, Moreau P, Mahe B, Souchet J, Rapp MJ 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  CAS  PubMed  Google Scholar 

  45. Freedman AS, Neuberg D, Gribben JG, Mauch P, Soiffer RJ, Fisher DC et al. High-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation in mantle-cell lymphoma: no evidence for long-term remission. J Clin Oncol 1998; 16: 13–18.

    Article  CAS  PubMed  Google Scholar 

  46. Vigouroux S, Gaillard F, Moreau P, Harousseau JL, Milpied N . High-dose therapy with autologous stem cell transplantation in first response in mantle cell lymphoma. Haematologica 2005; 90: 1580–1582.

    CAS  PubMed  Google Scholar 

  47. Thieblemont C, Antal D, Lacotte-Thierry L, Delwail V, Espinouse D, Michallet AS et al. Chemotherapy with rituximab followed by high-dose therapy and autologous stem cell transplantation in patients with mantle cell lymphoma. Cancer 2005; 104: 1434–1441.

    Article  CAS  PubMed  Google Scholar 

  48. Murali S, Winton E, Waller EK, Heffner LT, Lonial S, Flowers C et al. Long-term progression-free survival after early autologous transplantation for mantle-cell lymphoma. Bone Marrow Transplant 2008; 42: 529–534.

    Article  CAS  PubMed  Google Scholar 

  49. Vandenberghe E, Ruiz de Elvira C, Loberiza FR, Conde E, Lopez-Guillermo A, Gisselbrecht C et al. Outcome of autologous transplantation for mantle cell lymphoma: a study by the European Blood and Bone Marrow Transplant and Autologous Blood and Marrow Transplant Registries. Br J Haematol 2003; 120: 793–800.

    Article  PubMed  Google Scholar 

  50. Gianni AM, Cortelazzo S, Magni M, Martelli M . Rituximab: enhancing stem cell transplantation in mantle cell lymphoma. Bone Marrow Transplant 2002; 29 (Suppl 1): S10–S13.

    Article  PubMed  Google Scholar 

  51. Dreger P, Rieger M, Seyfarth B, Hensel M, Kneba M, Ho AD et al. Rituximab-augmented myeloablation for first-line autologous stem cell transplantation for mantle cell lymphoma: effects on molecular response and clinical outcome. Haematologica 2007; 92: 42–49.

    Article  CAS  PubMed  Google Scholar 

  52. Dreyling M, Lenz G, Hoster E, Van Hoof A, Gisselbrecht C, Schmits R et al. 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 2005; 105: 2677–2684.

    Article  CAS  PubMed  Google Scholar 

  53. Mangel J, Leitch HA, Connors JM, Buckstein R, Imrie K, Spaner D et al. Intensive chemotherapy and autologous stem-cell transplantation plus rituximab is superior to conventional chemotherapy for newly diagnosed advanced stage mantle-cell lymphoma: a matched pair analysis. Ann Oncol 2004; 15: 283–290.

    Article  CAS  PubMed  Google Scholar 

  54. Foran JM, Cunningham D, Coiffier B, Solal-Celigny P, Reyes F, Ghielmini M 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  PubMed  Google Scholar 

  55. Ghielmini M, Schmitz SF, Cogliatti S, Bertoni F, Waltzer U, Fey MF et al. Effect of single-agent rituximab given at the standard schedule or as prolonged treatment in patients with mantle cell lymphoma: a study of the Swiss Group for Clinical Cancer Research (SAKK). J Clin Oncol 2005; 23: 705–711.

    Article  CAS  PubMed  Google Scholar 

  56. Schulz H, Bohlius JF, Trelle S, Skoetz N, Reiser M, Kober T et al. Immunochemotherapy with rituximab and overall survival in patients with indolent or mantle cell lymphoma: a systematic review and meta-analysis. J Natl Cancer Inst 2007; 99: 706–714.

    Article  CAS  PubMed  Google Scholar 

  57. Forstpointner R, Unterhalt M, Dreyling M, Bock HP, Repp R, Wandt H et al. Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood 2006; 108: 4003–4008.

    Article  CAS  PubMed  Google Scholar 

  58. Martin P, Chadburn A, Christos P, Weil K, Furman RR, Ruan J et al. Outcome of deferred initial therapy in mantle-cell lymphoma. J Clin Oncol 2009; 27: 1209–1213.

    Article  PubMed  Google Scholar 

  59. Khouri IF, Saliba RM, Okoroji GJ, Acholonu SA, Champlin RE . Long-term follow-up of autologous stem cell transplantation in patients with diffuse mantle cell lymphoma in first disease remission: the prognostic value of beta2-microglobulin and the tumor score. Cancer 2003; 98: 2630–2635.

    Article  PubMed  Google Scholar 

  60. Ghielmini M, Zucca E . How I treat mantle cell lymphoma. Blood 2009; 114: 1469–1476.

    Article  CAS  PubMed  Google Scholar 

  61. Nickenig C, Dreyling M, Hoster E, Pfreundschuh M, Trumper L, Reiser M et al. Combined cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) improves response rates but not survival and has lower hematologic toxicity compared with combined mitoxantrone, chlorambucil, and prednisone (MCP) in follicular and mantle cell lymphomas: results of a prospective randomized trial of the German Low-Grade Lymphoma Study Group. Cancer 2006; 107: 1014–1022.

    Article  CAS  PubMed  Google Scholar 

  62. Ketterer N, Salles G, Espinouse D, Dumontet C, Neidhardt-Berard EM, Moullet I et al. Intensive therapy with peripheral stem cell transplantation in 16 patients with mantle cell lymphoma. Ann Oncol 1997; 8: 701–704.

    Article  CAS  PubMed  Google Scholar 

  63. Maris MB, Sandmaier BM, Storer BE, Chauncey T, Stuart MJ, Maziarz RT et al. Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma. Blood 2004; 104: 3535–3542.

    Article  CAS  PubMed  Google Scholar 

  64. Khouri IF, Lee MS, Saliba RM, Jun G, Fayad L, Younes A et al. Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma. J Clin Oncol 2003; 21: 4407–4412.

    Article  CAS  PubMed  Google Scholar 

  65. Morris E, Thomson K, Craddock C, Mahendra P, Milligan D, Cook G et al. Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. Blood 2004; 104: 3865–3871.

    Article  CAS  PubMed  Google Scholar 

  66. Gianni AM, Magni M, Martelli M, Di Nicola M, Carlo-Stella C, Pilotti S et al. Long-term remission in mantle cell lymphoma following high-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting (R-HDS regimen). Blood 2003; 102: 749–755.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Hematology and Oncology, Lutheran General Hospital, Park Ridge, IL, USA

    C Nabhan & J D Bitran

  2. Department of Medicine, Lutheran General Hospital, Park Ridge, IL, USA

    A Ragam

  3. Division of Hematology and Oncology, Northwestern Feinberg School of Medicine, Chicago, IL, USA

    J Mehta

Authors
  1. C Nabhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Ragam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J D Bitran
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C Nabhan.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nabhan, C., Ragam, A., Bitran, J. et al. Hematopoietic SCT for mantle cell lymphoma: is it the standard of care?. Bone Marrow Transplant 45, 1379–1387 (2010). https://doi.org/10.1038/bmt.2010.77

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2010.77

Keywords

Search

Advanced search

Quick links