Update on Treatment Recommendations From the Fourth International Workshop on Waldenström's Macroglobulinemia

2009 ◽  
Vol 27 (1) ◽  
pp. 120-126 ◽  
Author(s):  
Meletios Athanasios Dimopoulos ◽  
Morie A. Gertz ◽  
Efstathios Kastritis ◽  
Ramon Garcia-Sanz ◽  
Eva K. Kimby ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Alkylating Agents ◽  
International Workshop ◽  
Autologous Transplantation ◽  
Nucleoside Analogs ◽  
Waldenström’S Macroglobulinemia ◽  
First Line ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Waldenström macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder characterized by lymphoplasmacytic bone marrow infiltration along with an immunoglobulin M (IgM) monoclonal gammopathy. Patients with disease-related cytopenias, bulky adenopathy or organomegaly, symptomatic hyperviscosity, severe neuropathy, amyloidosis, cryoglobulinemia, cold agglutinin disease, or evidence of disease transformation should be considered for immediate therapy. Initiation of therapy should not be based on serum IgM levels alone, and asymptomatic patients should be observed. Individual patient considerations should be considered when deciding on a first-line agent including the presence of cytopenias, need for rapid disease control, age, and candidacy for autologous transplantation. Therapeutic outcomes should be evaluated using updated criteria. As part of the Fourth International Workshop on Waldenström's Macroglobulinemia, a consensus panel updated its recommendations on both first-line and salvage therapy in view of recently published and ongoing clinical trials. The panel considered encouraging results from recent studies of first-line combinations such as rituximab with nucleoside analogs with or without alkylating agents or with cyclophosphamide-based therapies (eg, cyclophosphamide, doxorubicin, vincristine, and prednisone or cyclophosphamide and dexamethasone) or the combination of rituximab with thalidomide. Such therapeutic approaches are likely to yield responses at least as good as, if not better than, monotherapy with any of the alkylating agents, nucleoside analogs, or rituximab. In the salvage setting, reuse of a first-line regimen or use of a different regimen should be considered along with bortezomib, alemtuzumab, autologous transplantation, and, in selected circumstances, allogeneic transplantation. Finally, the panel reaffirmed its encouragement of the active enrollment of patients with WM onto innovative clinical trials whenever possible.

Diagnosis and Management of Waldenstrom's Macroglobulinemia

2005 ◽  
Vol 23 (7) ◽  
pp. 1564-1577 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Robert A. Kyle ◽  
Athanasios Anagnostopoulos ◽  
Steven P. Treon
Keyword(s):  
Stem Cell ◽  
Alkylating Agents ◽  
Nucleoside Analogs ◽  
Primary Treatment ◽  
Low Grade ◽  
Waldenström’S Macroglobulinemia ◽  
Monoclonal Protein ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Purpose To review the diagnostic criteria, prognostic factors, response criteria, and treatment options of patients with Waldenstrom's macroglobulinemia (WM). Methods A review of published reports was facilitated by the use of a MEDLINE computer search and by manual search of the Index Medicus. Results WM should be regarded as a distinct clinicopathologic entity and confined to those patients with lymphoplasmacytoid lymphoma who have demonstrable serum immunoglobulin M monoclonal protein. Treatment decisions should rely on specific clinical and laboratory criteria. Initiation of therapy should not be based on serum monoclonal protein levels per se. The three main choices for systemic primary treatment of symptomatic patients with WM include alkylating agents (chlorambucil), nucleoside analogs (fludarabine and cladribine), and the monoclonal antibody rituximab. There are no data from prospective randomized studies to recommend the use of one first-line agent over another, although consideration of a patient's candidacy for autologous stem-cell transplantation (ASCT) should be taken into account to avoid stem cell–damaging agents. There are preliminary data to suggest that combinations of nucleoside analogs and alkylating agents with or without rituximab may improve response rates at the expense of higher toxicity. Conclusion WM is a distinct low-grade lymphoproliferative disorder. When therapy is indicated, alkylating agents, nucleoside analogs, and rituximab are reasonable choices. Several factors, including the presence of cytopenias, need for rapid disease control, candidacy for ASCT, age, and comorbidities, should be taken into consideration when choosing the most appropriate primary treatment.

Activity of fludarabine in previously treated Waldenström's macroglobulinemia: a report of 71 cases. Groupe Coopératif Macroglobulinémie.

1998 ◽  
Vol 16 (6) ◽  
pp. 2060-2064 ◽  
Author(s):  
V Leblond ◽  
T Ben-Othman ◽  
E Deconinck ◽  
A L Taksin ◽  
J L Harousseau ◽  
...  
Keyword(s):  
Alkylating Agents ◽  
Nucleoside Analogs ◽  
Median Number ◽  
Immunoglobulin M ◽  
Waldenström’S Macroglobulinemia ◽  
Secondary Resistance ◽  
Failure Group ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

PURPOSE There is no consensus on the treatment of patients with Waldenström's macroglobulinemia (WM) who develop primary or secondary resistance to frontline therapies. We report our experience on the activity and toxicity of fludarabine in 71 patients with WM resistant to prior chemotherapy regimens. PATIENTS AND METHODS From January 1991 to June 1995, 71 patients were included in this retrospective study. The median age, median time from diagnosis to treatment, median immunoglobulin M (IgM) level, and median number of previous treatments were 68 years (range, 42 to 81), 5.9 years (range, 0.6 to 20), 35 g/L (range, 5 to 126), and two (range, one to four), respectively. RESULTS Seventy-one patients received a median of six courses of fludarabine. Twenty-one (30%) responded with a partial response and 50 (70%) were considered as treatment failures. Forty-six patients died: 10 in the responder group and 36 in the failure group. Twenty-five patients were alive with a median follow-up time of 34 months. The overall median survival time of all treated patients was 23 months. The time to treatment failure was 32 months. The only factor that favorably influenced the response to fludarabine was a longer interval between the first treatment and the start of fludarabine. Pretreatment factors associated with shorter survival in the entire population were hemoglobin level less than 95 g/L (P = .02) and platelet count less than 75 x 10(9)/L (P = .02). CONCLUSION The responses rate in this population with a poor prognosis is close to that reported in shorter series. Patients with WM who are resistant to alkylating agents should be identified early, so that salvage therapy with nucleoside analogs can be started without delay.

Waldenström’s Macroglobulinemia: Clinical Features, Complications, and Management

2000 ◽  
Vol 18 (1) ◽  
pp. 214-214 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Panayiotis Panayiotidis ◽  
Lia A. Moulopoulos ◽  
Petros Sfikakis ◽  
Marinos Dalakas
Keyword(s):  
Clinical Features ◽  
Nucleoside Analogs ◽  
Low Grade ◽  
Waldenström’S Macroglobulinemia ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
The Impact ◽  
Waldenström's Macroglobulinemia

PURPOSE: To review the clinical features, complications, and treatment of Waldenström’s macroglobulinemia, a low-grade lymphoproliferative disorder that produces monoclonal immunoglobulin (Ig) M. METHODS: A review of published reports was facilitated by the use of a MEDLINE computer search and by manual search of the Index Medicus. RESULTS: The clinical manifestations associated with Waldenström’s macroglobulinemia can be classified according to those related to direct tumor infiltration, to the amount and specific properties of circulating IgM, and to the deposition of IgM in various tissues. Asymptomatic patients should be followed without treatment. For symptomatic patients, standard treatment consists primarily of oral chlorambucil; nucleoside analogs, such as fludarabine and cladribine, are effective in one third of previously treated patients and in up to 80% of previously untreated patients. Preliminary evidence suggests that anti-CD20 monoclonal antibody may be active in about 30% of previously treated patients and that high-dose therapy with autologous stem-cell rescue is effective in most patients, including some with resistance to nucleoside analogs. CONCLUSION: Waldenström’s macroglobulinemia has a wide clinical spectrum that practicing physicians need to recognize early to reach the correct diagnosis. When therapy is indicated, oral chlorambucil is the standard primary treatment, but cladribine or fludarabine can be used when a rapid cytoreduction is desirable. Prospective randomized trials are required to elucidate the impact of nucleoside analogs on patients’ survival. A nucleoside analog is the treatment of choice for patients who have been previously treated with an alkylating agent.

Overview on clinical trials in Waldenstrom's macroglobulinemia

2014 ◽  
Vol 4 (12) ◽  
pp. 1139-1154
Author(s):  
Alessandra Tedeschi ◽  
Anna Maria Frustaci ◽  
Paola Picardi ◽  
Enrica Morra
Keyword(s):  
Clinical Trials ◽  
Waldenström’S Macroglobulinemia ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

scholarly journals Waldenström's macroglobulinemia - a review

2014 ◽  
Vol 60 (5) ◽  
pp. 490-499 ◽  
Author(s):  
Susana Coimbra ◽  
Rafael Neves ◽  
Margarida Lima ◽  
Luís Belo ◽  
Alice Santos-Silva
Keyword(s):  
Bone Marrow ◽  
Autologous Transplantation ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Response To Therapy ◽  
Lymphoid Cells ◽  
Waldenström’S Macroglobulinemia ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Waldenström's macroglobulinemia (WM) is a lymphoproliferative disease of B lymphocytes, characterized by a lymphoplasmocytic lymphoma in the bone marrow and by IgM monoclonal hypergammaglobulinemia. It was first described in 1944 by Jan Gösta Waldenström, reporting two patients with oronasal bleeding, lymphadenopathy, anemia, thrombocytopenia, high erythrocyte sedimentation rate and serum viscosity, normal radiography and bone marrow infiltrated by lymphoid cells. The WM is a rare disease with a typically indolent clinical course, affecting mainly individuals aged between 63 and 68 years. Most patients have clinical signs and symptoms related to hyperviscosity resulting from IgM monoclonal gammopathy, and/or cytopenias resulting from bone marrow infiltration by lymphoma. The differential diagnosis with other lymphomas is essential for the assessment of prognosis and therapeutic approach. Treatment of patients with asymptomatic WM does not improve the quality of life of patients, or increase their survival, being recommended, therefore, their follow-up. For the treatment of symptomatic patients, alkylating agents, purine analogs and anti-CD20 monoclonal antibodies are used. However, the disease is incurable and the response to therapy is not always favorable. Recent studies have shown promising results with bortezomib, an inhibitor of proteasomes, and some patients respond to thalidomide. In patients with relapse or refractory to therapy, autologous transplantation may be indicated. The aim of this paper is to describe in detail the current knowledge on the pathophysiology of WM, main clinical manifestations, diagnosis, prognosis and treatment.

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