Skip to main content

Advertisement

SpringerLink
Log in

Treatment of Waldenstrom’s Macroglobulinemia

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

Opinion statement

Waldenstrom’s macroglobulinemia is defined by bone marrow lymphoplasmacytic infiltration and by production of monoclonal IgM. Treatment is employed only to symptomatic patients. Alkylating agents (chlorambucil), nucleoside analogues and rituximab are reasonable choices for primary therapy. Combination therapy either with nucleoside analogues with alkylating agents and/or rituximab or rituximab with chemotherapy such as CHOP or cyclophosphamide are also reasonable frontline treatment options for WM patients. Several factors should be taken into account when choosing the most appropriate primary treatment. These factors include the age of the patient and possible co-morbidities, the presence of cytopenias and especially thrombocytopenia, the presence of symptoms and signs indicative of hyperviscosity, the need for rapid disease control due to severe symptoms, significant splenomegaly or lymphadenopathy, symptomatic peripheral neuropathy and whether the patient is candidate for autologous stem cell transplantation. For patients with refractory or relapsing disease, the use of an alternate first-line agent is reasonable. Outside the setting of a clinical trial, the administration of high-dose therapy should be reserved only for patients refractory to alkylating agents, purine nucleoside and rituximab. For patients who develop resistance to all three classes of agents, alemtuzumab, thalidomide with or without dexamethasone or bortezomib could be tried.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Owen RG, Treon SP, Al-Katib A, et al.: Developing diagnostic criteria in Waldenstrom’s macroglobulinemia. Semin Oncol 2003, 30:196–200.

    Google Scholar 

Important consensus panel report which provided a clear clinical and pathological definition of WM

  1. Kyle RA, Treon SP, Alexanian R, et al. (2003) Prognostic markers and criteria to initiate therapy in Waldenstrom’s macroglobulinemia: consensus panel recommendations from the second international workshop on Waldenstrom’s macroglobulinemia. Semin Oncol 30:116–120

    Article  PubMed  Google Scholar 

  2. Gertz MA, Anagnostopoulos A, Anderson K, et al.: Treatment recommendations in Waldenstrom’s macroglobulinemia: consensus panel recommendations from the second international workshop on Waldenstrom’s macroglobulinemia. Semin Oncol 2003, 30:121–126.

    Google Scholar 

Consensus panel recommendations on the treatment options of previously untreated and pretreated patients with WM

  1. Dimopoulos MA, Kyle RA, Anagnostopoulos A, Treon SP (2005) Diagnosis and management of Waldenstrom’s macroglobulinemia. J Clin Oncol 23:1564–1577

    Article  PubMed  Google Scholar 

  2. Kyle RA, Greipp PR, Gertz MA, et al. (2000) Waldenstrom’s macroglobulinaemia: a prospective study comparing daily with intermittent oral chlorambucil. Br J Haematol 108: 737–742

    Article  PubMed  CAS  Google Scholar 

  3. Dimopoulos MA, Panayiotidis P, Moulopoulos LA, et al. (2000) Waldenstrom’s macroglobulinemia: clinical features, complications, and management. J Clin Oncol 18:214–226

    PubMed  CAS  Google Scholar 

  4. Annibali O, Petrucci MT, Martini V, et al. (2005) Treatment of 72 newly diagnosed Waldenstrom macroglobulinemia cases with oral melphalan, cyclophosphamide, and prednisone: results and cost analysis. Cancer 103: 582–587

    Article  PubMed  Google Scholar 

  5. Dhodapkar MV, Jacobson JL, Gertz MA, et al. (2003) Prognostic factors and response to fludarabine therapy in Waldenstrom’s macroglobulinemia: an update of a US intergroup trial (SW0G S9003). Semin Oncol 30:220–225

    Article  PubMed  Google Scholar 

  6. Dimopoulos MA, Kantarjian H, Weber D, et al. (1994) Primary therapy of Waldenstrom’s macroglobulinemia with 2-chlorodeoxyadenosine. J Clin Oncol 12:2694–2698

    PubMed  CAS  Google Scholar 

  7. Hellmann A, Lewandowski K, Zaucha JM, et al. (1999) Effect of a 2-hour infusion of 2-chlorodeoxyadenosine in the treatment of refractory or previously untreated Waldenstrom’s macroglobulinemia. Eur J Haematol 63:35–41

    Article  PubMed  CAS  Google Scholar 

  8. Delannoy A, Van Den Neste E, Michaux JL, et al. (1999) Cladribine for Waldenstrom’s macroglobulinaemia. Br J Haematol 104:933–934

    Article  PubMed  CAS  Google Scholar 

  9. Leblond V, Levy V, Maloisel F, et al. (2001) Multicenter, randomized comparative trial of fludarabine and the combination of cyclophosphamide-doxorubicin-prednisone in 92 patients with Waldenstrom macroglobulinemia in first relapse or with primary refractory disease. Blood 98:2640–2644

    Article  PubMed  CAS  Google Scholar 

  10. Dimopoulos MA, Weber D, Delasalle KB, et al. (1995) Treatment of Waldenstrom’s macroglobulinemia resistant to standard therapy with 2-chlorodeoxyadenosine: identification of prognostic factors. Ann Oncol 6:49–52

    PubMed  CAS  Google Scholar 

  11. Betticher DC, Hsu Schmitz SF, Ratschiller D, et al. (1997) Cladribine (2-CDA) given as subcutaneous bolus injections is active in pretreated Waldenstrom’s macroglobulinaemia. Swiss Group for Clinical Cancer Research (SAKK). Br J Haematol 99:358–363

    Article  PubMed  CAS  Google Scholar 

  12. Anagnostopoulos A, Dimopoulos MA, Aleman A, et al. (2001) High-dose chemotherapy followed by stem cell transplantation in patients with resistant Waldenstrom’s macroglobulinemia. Bone Marrow Transplant 27:1027–1029

    Article  PubMed  CAS  Google Scholar 

  13. Desikan R, Dhodapkar M, Siegel D, et al. (1999) High-dose therapy with autologous haemopoietic stem cell support for Waldenstrom’s macroglobulinaemia. Br J Haematol 105: 993–996

    Article  PubMed  CAS  Google Scholar 

  14. Dreger P, Glass B, Kuse R, et al. (1999) Myeloablative radiochemotherapy followed by reinfusion of purged autologous stem cells for Waldenstrom’s macroglobulinaemia. Br J Haematol 106: 115–118

    Article  PubMed  CAS  Google Scholar 

  15. Anagnostopoulos A, Hari PN, Perez WS, et al. (2006) Autologous or allogeneic stem cell transplantation in patients with Waldenstrom’s macroglobulinemia. Biol Blood Marrow Transplant 12: 845–854

    Article  PubMed  Google Scholar 

  16. Tournilhac O, Leblond V, Tabrizi R, et al. (2003) Transplantation in Waldenstrom’s macroglobulinemia—the French experience. Semin Oncol 30:291–296

    Article  PubMed  CAS  Google Scholar 

  17. Anderson LD Jr., Sandmaier BM, Maris MB, et al. (2006) Nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) for refractory Waldenstrom’s macroglobulinemia (WM): evidence for a Graft-versus-WM Effect. ASH Annu Meet Abstracts 108: 3034.

    Google Scholar 

  18. Gertz MA, Rue M, Blood E, et al. (2004) Multicenter phase 2 trial of rituximab for Waldenstrom macroglobulinemia (WM): an Eastern Cooperative Oncology Group Study (E3A98). Leuk Lymphoma 45:2047–2055

    Article  PubMed  CAS  Google Scholar 

  19. Dimopoulos MA, Zervas C, Zomas A, et al. (2002) Treatment of Waldenstrom’s macroglobulinemia with rituximab. J Clin Oncol 20:2327–2333

    Article  PubMed  CAS  Google Scholar 

  20. Treon SP, Emmanouilides C, Kimby E, et al. (2005) Extended rituximab therapy in Waldenstrom’s macroglobulinemia. Ann Oncol 16:132–138

    Article  PubMed  CAS  Google Scholar 

  21. Ghobrial IM, Fonseca R, Greipp PR, et al. (2004) Initial immunoglobulin M ’flare’ after rituximab therapy in patients diagnosed with Waldenstrom macroglobulinemia: an Eastern Cooperative Oncology Group Study. Cancer 101: 2593–2598

    Article  PubMed  CAS  Google Scholar 

  22. Treon SP, Branagan AR, Hunter Z, et al. (2004) Paradoxical increases in serum IgM and viscosity levels following rituximab in Waldenstrom’s macroglobulinemia. Ann Oncol 15:1481–1483

    Article  PubMed  CAS  Google Scholar 

  23. Weber DM, Dimopoulos MA, Delasalle K, et al. (2003) 2-Chlorodeoxyadenosine alone and in combination for previously untreated Waldenstrom’s macroglobulinemia. Semin Oncol 30:243–247

    Article  PubMed  CAS  Google Scholar 

  24. Dimopoulos MA, Hamilos G, Efstathiou E, et al. (2003) Treatment of Waldenstrom’s macroglobulinemia with the combination of fludarabine and cyclophosphamide. Leuk Lymphoma 44:993–996

    Article  PubMed  CAS  Google Scholar 

  25. Tamburini J, Levy V, Chaleteix C, et al. (2005) Fludarabine plus cyclophosphamide in Waldenstrom’s macroglobulinemia: results in 49 patients. Leukemia 19:1831–1834

    Article  PubMed  CAS  Google Scholar 

  26. Tam CS, Seymour JF, Prince HM, et al. (2006) Treatment-related myelodysplasia following fludarabine combination chemotherapy. Haematologica 91:1546–1550

    PubMed  CAS  Google Scholar 

  27. Treon SP, Branagan A, Wasi P, et al. (2004) Combination therapy with rituximab and fludarabine in Waldenstrom’s macroglobulinemia. ASH Annu Meet Abstracts 104:753.

    Google Scholar 

  28. Hensel M, Villalobos M, Kornacker M, et al. (2005) Pentostatin/cyclophosphamide with or without rituximab: an effective regimen for patients with Waldenstrom’s macroglobulinemia/lymphoplasmacytic lymphoma. Clin Lymphoma Myeloma 6:131–135

    Article  PubMed  Google Scholar 

  29. Vargaftig J, Pegourie-Bandelier B, Mahe B, et al. (2006) Fludarabine plus cyclophosphamide and rituximab (RFC) in Waldenstrom’s macroglobulinemia (WM): Results in 21 Patients (pts). ASH Annu Meet Abstracts 108:4727.

    Google Scholar 

  30. Dimopoulos MA, Anagnostopoulos A, Kyrtsonis MC, et al. (2006) Primary treatment of Waldenstrom’s macroglobulinemia (WM) with dexamethasone, rituximab and cyclophosphamide. ASH Annu Meet Abstracts 108:128.

    Google Scholar 

  31. Buske C, Dreyling MH, Eimermacher H, et al. (2004) Combined immuno-chemotherapy (R-CHOP) results in significantly superior response rates and time to treatment failure in first line treatment of patients with lymphomplasmocytoid/ic immunocytoma (LP-IC) – results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). ASH Annu Meet Abstracts 104:162.

    Google Scholar 

  32. Dimopoulos MA, Tsatalas C, Zomas A, et al. (2003) Treatment of Waldenstrom’s macroglobulinemia with single-agent thalidomide or with the combination of clarithromycin, thalidomide and dexamethasone. Semin Oncol 30:265–269

    Article  PubMed  CAS  Google Scholar 

  33. Treon SP, Hunter Z, Patterson CJ, Branagan AR (2005) Thalidomide in combination with rituximab is active in Waldenstrom’s macroglobulinemia and may overcome poor response determinants associated with rituximab monotherapy. ASH Annu Meet Abstracts 106:2442.

    Google Scholar 

  34. Treon SP, Patterson CJ, Hunter ZR, Branagan AR (2005) Phase II study of CC-5013 (Revlimid) and rituximab in Waldenstrom’s macroglobulinemia: preliminary safety and efficacy results. ASH Annu Meet Abstracts 106:2443.

    Google Scholar 

  35. Dimopoulos MA, Anagnostopoulos A, Kyrtsonis MC, et al. (2005) Treatment of relapsed or refractory Waldenstrom’s macroglobulinemia with bortezomib. Haematologica 90:1655–1658

    PubMed  CAS  Google Scholar 

  36. Treon SP, Soumerai JD, Patterson CJ, et al. (2006) Bortezomib, dexamethasone and rituximab (BDR) is a highly active regimen in the primary therapy of Waldenstrom’s macroglobulinemia: planned interim results of WMCTG clinical trial 05–180. ASH Annu Meet Abstracts 108:2765.

    Google Scholar 

  37. Owen R, Rawstron AC, Osterborg A, et al. (2003) Activity of alemtuzumab (Mabcampath) in relapsed/refractory Waldenstrms macroglobulinemia. ASH Annu Meet Abstracts 102:2380.

    Google Scholar 

  38. Hunter ZR, Boxer M, Kahl B, et al. (2006) Phase II study of alemtuzumab in lymphoplasmacytic lymphoma: results of WMCTG trial 02-079. J Clin Oncol (Meeting Abstracts) 24:7523.

    Google Scholar 

  39. Treon SP, Gertz MA, Dimopoulos M, et al.: Update on treatment recommendations from the third international workshop on Waldenstrom’s Macroglobulinemia. Blood 2006, 107:3442–3446.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Therapeutics, University of Athens School of Medicine, Alexandra Hospital, 80 Vas. Sofias, Athens, 11528, Greece

    Meletios A. Dimopoulos MD & Athanasios Anagnostopoulos MD

Authors
  1. Meletios A. Dimopoulos MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Athanasios Anagnostopoulos MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Meletios A. Dimopoulos MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dimopoulos, M.A., Anagnostopoulos, A. Treatment of Waldenstrom’s Macroglobulinemia. Curr. Treat. Options in Oncol. 8, 144–153 (2007). https://doi.org/10.1007/s11864-007-0016-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-007-0016-2

Keywords

Search

Navigation