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:

Stem cell transplant for Waldenström macroglobulinemia: an underutilized technique

Bone Marrow Transplantation volume 47, pages 1147–1153 (2012)Cite this article

Subjects

Abstract

Waldenström macroglobulinemia is a highly chemosensitive lymphoplasmacytic lymphoma with response rates of 90% to first-line chemotherapy. The fraction of patients undergoing stem cell transplant for this disorder appears to be lower than that of patients with multiple myeloma. The indolent nature and favorable genetic profile should make Waldenström an ideal disorder for autologous stem cell transplant, with high response rates that are durable. We review the literature on autologous and allogeneic transplants for Waldenström macroglobulinemia and conclude that autologous transplant is effective and underutilized in the management of this disorder. Allogeneic transplant should be considered investigational and used only in the context of a clinical trial or when other chemotherapeutic options have been exhausted.

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

Similar content being viewed by others

References

  1. Waldenström J . Forty years with the gamma globulins. Scand J Immunol 1987; 25: 211–218.

    Article  Google Scholar 

  2. Fonseca R, Hayman S . Waldenström macroglobulinaemia. Br J Haematol 2007; 138: 700–720.

    Article  CAS  Google Scholar 

  3. Ghobrial IM, Fonseca R, Gertz MA, Plevak MF, Larson DR, Therneau TM et al. Prognostic model for disease-specific and overall mortality in newly diagnosed symptomatic patients with Waldenstrom macroglobulinaemia. Br J Haematol 2006; 133: 158–164.

    Article  Google Scholar 

  4. Ansell SM, Kyle RA, Reeder CB, Fonseca R, Mikhael JR, Morice WG et al. Diagnosis and management of Waldenström macroglobulinemia: Mayo stratification of macroglobulinemia and risk-adapted therapy (mSMART) guidelines. Mayo Clin Proc 2010; 85: 824–833.

    Article  Google Scholar 

  5. Vitolo U, Ferreri AJ, Montoto S . Lymphoplasmacytic lymphoma-Waldenstrom's macroglobulinemia. Crit Rev Oncol Hematol 2008; 67: 172–185.

    Article  Google Scholar 

  6. Ocio EM, Schop RF, Gonzalez B, Van Wier SA, Hernandez-Rivas JM, Gutierrez NC et al. 6q deletion in Waldenström macroglobulinemia is associated with features of adverse prognosis. Br J Haematol 2007; 136: 80–86.

    Article  CAS  Google Scholar 

  7. Gertz MA, Rue M, Blood E, Kaminer LS, Vesole DH, Greipp PR . Multicenter phase 2 trial of rituximab for Waldenström macroglobulinemia (WM): an Eastern Cooperative Oncology Group Study (E3A98). Leuk Lymphoma 2004; 45: 2047–2055.

    Article  CAS  Google Scholar 

  8. Kyle RA, Greipp PR, Gertz MA, Witzig TE, Lust JA, Lacy MQ et al. Waldenström's macroglobulinaemia: a prospective study comparing daily with intermittent oral chlorambucil. Br J Haematol 2000; 108: 737–742.

    Article  CAS  Google Scholar 

  9. Yang K, Tan J, Wu T . Alkylating agents for Waldenstrom's macroglobulinaemia. Cochrane Database Syst Rev 2009, CD006719.

  10. Treon SP, Hunter Z, Barnagan AR . CHOP plus rituximab therapy in Waldenstrom's macroglobulinemia. Clin Lymphoma 2005; 5: 273–277.

    Article  CAS  Google Scholar 

  11. Ioakimidis L, Patterson CJ, Hunter ZR, Soumerai JD, Manning RJ, Turnbull B et al. Comparative outcomes following CP-R, CVP-R, and CHOP-R in Waldenström's macroglobulinemia. Clin Lymphoma Myeloma 2009; 9: 62–66.

    Article  CAS  Google Scholar 

  12. Dhodapkar MV, Jacobson JL, Gertz MA, Crowley JJ, Barlogie B . Prognostic factors and response to fludarabine therapy in Waldenstrom's macroglobulinemia: an update of a US intergroup trial (SWOG S9003). Semin Oncol 2003; 30: 220–225.

    Article  Google Scholar 

  13. Weber DM, Dimopoulos MA, Delasalle K, Rankin K, Gavino M, Alexanian R . 2-Chlorodeoxyadenosine alone and in combination for previously untreated Waldenstrom's macroglobulinemia. Semin Oncol 2003; 30: 243–247.

    Article  CAS  Google Scholar 

  14. Agathocleous A, Rohatiner A, Rule S, Hunter H, Kerr JP, Neeson SM et al. Weekly versus twice weekly bortezomib given in conjunction with rituximab, in patients with recurrent follicular lymphoma, mantle cell lymphoma and Waldenström macroglobulinaemia. Br J Haematol 2010; 151: 346–353.

    Article  CAS  Google Scholar 

  15. Ghobrial IM, Xie W, Padmanabhan S, Badros A, Rourke M, Leduc R et al. Phase II trial of weekly bortezomib in combination with rituximab in untreated patients with Waldenström Macroglobulinemia. Am J Hematol 2010; 85: 670–674.

    Article  CAS  Google Scholar 

  16. Merchionne F, Procaccio P, Dammacco F . Waldenström's macroglobulinemia: an overview of its clinical, biochemical, immunological and therapeutic features and our series of 121 patients collected in a single center. Crit Rev Oncol Hematol (e-pub ahead of print 28 October 2010).

  17. Ghobrial IM, Gertz M, Laplant B, Camoriano J, Hayman S, Lacy M et al. Phase II trial of the oral mammalian target of rapamycin inhibitor everolimus in relapsed or refractory Waldenstrom macroglobulinemia. J Clin Oncol 2010; 28: 1408–1414.

    Article  CAS  Google Scholar 

  18. Ghobrial IM, Roccaro A, Hong F, Weller E, Rubin N, Leduc R et al. Clinical and translational studies of a phase II trial of the novel oral Akt inhibitor perifosine in relapsed or relapsed/refractory Waldenstrom's macroglobulinemia. Clin Cancer Res 2010; 16: 1033–1041.

    Article  CAS  Google Scholar 

  19. Leleu X, Gay J, Roccaro AM, Moreau AS, Poulain S, Dulery R et al. Update on therapeutic options in Waldenström macroglobulinemia. Eur J Haematol 2009; 82: 1–12.

    Article  CAS  Google Scholar 

  20. Garcia-Sanz R, Ocio EM . Novel treatment regimens for Waldenström's macroglobulinemia. Expert Rev Hematol 2010; 3: 339–350.

    Article  CAS  Google Scholar 

  21. Leleu X, Soumerai J, Roccaro A, Hatjiharissi E, Hunter ZR, Manning R et al. Increased incidence of transformation and myelodysplasia/acute leukemia in patients with Waldenström macroglobulinemia treated with nucleoside analogs. J Clin Oncol 2009; 27: 250–255.

    Article  Google Scholar 

  22. Carney DA, Westerman DA, Tam CS, Milner A, Prince HM, Kenealy M et al. Therapy-related myelodysplastic syndrome and acute myeloid leukemia following fludarabine combination chemotherapy. Leukemia 2010; 24: 2056–2062.

    Article  CAS  Google Scholar 

  23. Dimopoulos MA, Mateos MV, Richardson PG, Schlag R, Khuageva NK, Shpilberg O et al. Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiple myeloma: subanalysis of the phase 3 VISTA study. Eur J Haematol 2011; 86: 23–31.

    Article  CAS  Google Scholar 

  24. Cavaletti G, Jakubowiak AJ . Peripheral neuropathy during bortezomib treatment of multiple myeloma: a review of recent studies. Leuk Lymphoma 2010; 51: 1178–1187.

    Article  CAS  Google Scholar 

  25. Chng WJ, Schop RF, Price-Troska T, Ghobrial I, Kay N, Jelinek DF et al. Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma. Blood 2006; 108: 2755–2763.

    Article  CAS  Google Scholar 

  26. Gribben JG . Stem cell transplantation in chronic lymphocytic leukemia. Biol Blood Marrow Transplant 2009; 15 (1 Suppl): 53–58.

    Article  Google Scholar 

  27. Tam CS, Khouri I . The role of stem cell transplantation in the management of chronic lymphocytic leukaemia. Hematol Oncol 2009; 27: 53–60.

    Article  CAS  Google Scholar 

  28. Dimopoulos MA, Kastritis E, Christoulas D, Migkou M, Gavriatopoulou M, Gkotzamanidou M et al. Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies. Leukemia 2010; 24: 1769–1778.

    Article  CAS  Google Scholar 

  29. Chang H, Samiee S, Li D, Patterson B, Chen CI, Stewart AK . Analysis of IgH translocations, chromosome 13q14 and 17p13.1(p53) deletions by fluorescence in situ hybridization in Waldenstrom's macroglobulinemia: a single center study of 22 cases. Leukemia 2004; 18: 1160–1162. Erratum in: Leukemia 2004; 18: 1564.

    Article  CAS  Google Scholar 

  30. Schmid JR, Kiely JM, Tauxe WN, Owen Jr CA . In vitro DNA and RNA synthesis in human bone marrow cells: a study of 12 normal subjects and 12 patients with lymphoplasmocytic disorders. Blood 1966; 27: 310–318.

    CAS  PubMed  Google Scholar 

  31. Latreille J, Barlogie B, Johnston D, Drewinko B, Alexanian R . Ploidy and proliferative characteristics in monoclonal gammopathies. Blood 1982; 59: 43–51.

    CAS  PubMed  Google Scholar 

  32. Sacco A, Issa GC, Zhang Y, Liu Y, Maiso P, Ghobrial IM et al. Epigenetic modifications as key regulators of Waldenstrom's Macroglobulinemia biology. J Hematol Oncol 2010; 3: 38.

    Article  Google Scholar 

  33. Nichols GL, Skerrett DL . Peripheral blood stem cell mobilization and harvesting after fludarabine therapy for low-grade lymphoma and chronic lymphocytic leukemia. Stem Cells Dev 2005; 14: 3–35.

    Article  CAS  Google Scholar 

  34. Dimopoulos MA, Gertz MA, Kastritis E, Garcia-Sanz R, Kimby EK, Leblond V et al. Update on treatment recommendations from the Fourth International Workshop on Waldenstrom's Macroglobulinemia. J Clin Oncol 2009; 27: 120–126.

    Article  Google Scholar 

  35. Gertz MA . Current status of stem cell mobilization. Br J Haematol 2010; 150: 647–662.

    Article  CAS  Google Scholar 

  36. Trotman J, Presgrave P, Kwan Y, Tiley C, Estell J, Watson AM et al. Consensus guidelines for ‘rainy day’ autologous stem cell harvests in New South Wales. Intern Med J 2008; 38: 229–234.

    Article  CAS  Google Scholar 

  37. Caravita T, Siniscalchi A, Tendas A, Cupelli L, Dentamaro T, Natale G et al. High-dose therapy with autologous PBSC transplantation in the front-line treatment of Waldenstrom's macroglobulinemia. Bone Marrow Transplant 2009; 43: 587–588.

    Article  CAS  Google Scholar 

  38. Yang L, Wen B, Li H, Yang M, Jin Y, Yang S et al. Autologous peripheral blood stem cell transplantation for Waldenstrom's macroglobulinemia. Bone Marrow Transplant 1999; 24: 929–930.

    Article  CAS  Google Scholar 

  39. Desikan R, Dhodapkar M, Siegel D, Fassas A, Singh J, Singhal S et al. High-dose therapy with autologous haemopoietic stem cell support for Waldenström's macroglobulinaemia. Br J Haematol 1999; 105: 993–996.

    Article  CAS  Google Scholar 

  40. Anagnostopoulos A, Dimopoulos MA, Aleman A, Weber D, Alexanian R, Champlin R et al. High-dose chemotherapy followed by stem cell transplantation in patients with resistant Waldenstrom's macroglobulinemia. Bone Marrow Transplant 2001; 27: 1027–1029.

    Article  CAS  Google Scholar 

  41. Munshi NC, Barlogie B . Role for high-dose therapy with autologous hematopoietic stem cell support in Waldenstrom's macroglobulinemia. Semin Oncol 2003; 30: 282–285.

    Article  CAS  Google Scholar 

  42. Fassas A, Barlogie B, Ward S, Rasmussen E, van Rhee F, Zangari M et al. High-dose treatment (HDT) and autologous stem cell transplant (ASCT) in Waldenstrom's macroglobulinemia (WM) patients (pts): a single center experience [abstract]. J Clin Oncol 2005; 23 (16S): 6661.

    Article  Google Scholar 

  43. Anagnostopoulos A, Giralt S . Stem cell transplantation (SCT) for Waldenstrom's macroglobulinemia (WM). Bone Marrow Transplant 2002; 29: 943–947.

    Article  CAS  Google Scholar 

  44. Tournilhac O, Leblond V, Tabrizi R, Gressin R, Senecal D, Milpied N et al. Transplantation in Waldenstrom's macroglobulinemia: the French experience. Semin Oncol 2003; 30: 291–296.

    Article  CAS  Google Scholar 

  45. Anagnostopoulos A, Hari PN, Perez WS, Ballen K, Bashey A, Bredeson CN et al. Autologous or allogeneic stem cell transplantation in patients with Waldenstrom's macroglobulinemia. Biol Blood Marrow Transplant 2006; 12: 845–854.

    Article  Google Scholar 

  46. Kyriakou C, Canals C, Taghipour G, Gisselbrecht C, Mazza P, Kazmi M et al. Autologous stem cell transplantation (ASCT) for patients with Waldenstrom's macroglobulinaemia: an analysis of 201 cases from the European Bone Marrow Transplant Registry (EBMT) [abstract]. Haematologica 2007; 92 (S2): 228.

    Google Scholar 

  47. Dhedin N, Tabrizi R, Bulabois PE, Le Gouill S, Coiteux V, Dartigeas C et al. Hematopoietic stem cell transplantation (HSCT) in Waldenstrom macroglobulinemia (WM): update of the French experience in 54 cases. Haematologica 2007; 92 (S): 228.

    Google Scholar 

  48. Gilleece MH, Pearce R, Linch DC, Wilson M, Towlson K, Mackinnon S et al. The outcome of haemopoietic stem cell transplantation in the treatment of lymphoplasmacytic lymphoma in the UK: a British Society Bone Marrow Transplantation study. Hematology 2008; 13: 119–127.

    Article  Google Scholar 

  49. Kyriakou C, Canals C, Sibon D, Cahn JY, Kazmi M, Arcese W et al. High-dose therapy and autologous stem-cell transplantation in Waldenstrom macroglobulinemia: the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2010; 28: 2227–2232.

    Article  CAS  Google Scholar 

  50. Martino R, Shah A, Romero P, Brunet S, Sierra J, Domingo-Albos A et al. Allogeneic bone marrow transplantation for advanced Waldenstrom's macroglobulinemia. Bone Marrow Transplant 1999; 23: 747–749.

    Article  CAS  Google Scholar 

  51. Ueda T, Hatanaka K, Kosugi S, Kishino BI, Tamaki T . Successful non-myeloablative allogeneic peripheral blood stem cell transplantation (PBSCT) for Waldenström's macroglobulinemia with severe pancytopenia. Bone Marrow Transplant 2001; 28: 609–611.

    Article  CAS  Google Scholar 

  52. Stakiw J, Kim DH, Kuruvilla J, Gupta V, Messner H, Lipton JH . Evidence of graft-versus-Waldenstrom's macroglobulinaemia effect after allogeneic stem cell transplantation: a single centre experience. Bone Marrow Transplant 2007; 40: 369–372.

    Article  CAS  Google Scholar 

  53. Meniane JC, El-Cheikh J, Faucher C, Furst S, Bouabdallah R, Blaise D et al. Long-term graft-versus-Waldenström macroglobulinemia effect following reduced intensity conditioning allogeneic stem cell transplantation. Bone Marrow Transplant 2007; 40: 175–177.

    Article  Google Scholar 

  54. Yamamoto R, Takaori-Kondo A, Kanda J, Imada K, Ichinohe T, Ishikawa T et al. Durable remission of large B-cell lymphoma transformed from lymphoplasmacytic lymphoma/Waldenström macroglobulinemia successfully treated with sequential immunochemotherapy followed by reduced-intensity allogeneic stem cell transplantation. Bone Marrow Transplant 2008; 41: 591–593.

    Article  CAS  Google Scholar 

  55. Anagnostopoulos A, Aleman A, Giralt S . Autologous and allogeneic stem cell transplantation in Waldenstrom's macroglobulinemia: review of the literature and future directions. Semin Oncol 2003; 30: 286–290.

    Article  Google Scholar 

  56. Garnier A, Robin M, Larosa F, Golmard JL, Le Gouill S, Coiteux V et al. Allogeneic hematopoietic stem cell transplantation allows long-term complete remission and curability in high-risk Waldenstrom's macroglobulinemia: results of a retrospective analysis of the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. Haematologica 2010; 95: 950–955.

    Article  Google Scholar 

  57. Kyriakou C, Canals C, Cornelissen JJ, Socie G, Willemze R, Ifrah N et al. Allogeneic stem-cell transplantation in patients with Waldenström macroglobulinemia: report from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2010; 28: 4926–4934.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    M A Gertz, R A Kyle & S M Ansell

  2. Division of Hematology/Oncology, Mayo Clinic, Scottsdale, AZ, USA

    C B Reeder

Authors
  1. M A Gertz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C B Reeder
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R A Kyle
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S M Ansell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M A Gertz.

Ethics declarations

Competing interests

Dr Gertz reports financial project support from Celgene, Millennium, Neotope, Eisai Inc, Lilly Research Laboratories, OptumHealth Education, Research to Practice, Physicians’ Education Resource and Amgen Inc.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gertz, M., Reeder, C., Kyle, R. et al. Stem cell transplant for Waldenström macroglobulinemia: an underutilized technique. Bone Marrow Transplant 47, 1147–1153 (2012). https://doi.org/10.1038/bmt.2011.175

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2011.175

Keywords

This article is cited by

Search

Advanced search

Quick links