Update on recommendations for assessing response from the Third International Workshop on Waldenstrom's Macroglobulinemia.
ABSTRACT This report by an international consensus panel updates current recommendations for defining clinical response in Waldenstrom's macroglobulinemia (WM). The previously published response criteria incorporated parameters for monoclonal protein reduction and/or improvement of marrow and nodal involvement, and included definitions of complete and partial remissions. The criteria have been updated to include minor response and stable disease categories. In addition, the criteria now recognize that delayed responses after treatment with nucleoside analogues and biologic agents and the time point for assessing response in patients with WM should be considered so as to not miss or miscategorize a response. The new criteria should therefore help in better delineating responses to therapy in patients with WM, particularly with the wide use of nucleoside analogues and biologically based agents for this disease.
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ABSTRACT: This report represents a further update of the consensus panel criteria for the assessment of clinical response in patients with Waldenström macroglobulinaemia (WM). These criteria have been updated in light of further data demonstrating an improvement in categorical responses with new drug regimens as well as acknowledgement of the fact that such responses are predictive of overall outcome. A number of key changes are proposed but challenges do however remain and these include the variability in kinetics of immunoglobulin M (IgM) reduction with different treatment modalities and the apparent discrepancy between IgM and bone marrow/tissue response noted with some regimens. Planned sequential bone marrow assessments are encouraged in clinical trials.British Journal of Haematology 11/2012; · 4.94 Impact Factor
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ABSTRACT: CD52 is expressed on malignant cells in lymphoplasmacytic lymphoma (LPL), including IgM-secreting Waldenström macroglobulinemia (WM). We examined the activity of alemtuzumab in 28 symptomatic LPL (27 IgM and 1 IgA) patients. The median prior number of therapies for these patients was 2 (range, 0-5) and 43% had refractory disease. Patients received alemtuzumab at 30 mg IV 3 times weekly for up to 12 weeks after test dosing, and also received hydrocortisone, acyclovir, and Bactrim or equivalent prophylaxis. Patients had a complete response (n = 1), a partial response (n = 9), or a MR (n = 11) for an overall and major response rate of 75% and 36%, respectively. Median serum Ig decreased from 3510 to 1460 mg/dL (P < .001 at best response). With a median follow-up of 64 months, the median time to progression was 14.5 months. Hematologic and infectious complications, including CMV reactivation, were more common in previously treated patients and were indirectly associated with 3 deaths. Long-term follow-up revealed late-onset autoimmune thrombocytopenia (AITP) in 4 patients at a median of 13.6 months after therapy, which contributed to 1 death. Alemtuzumab is an active therapy in patients with LPL, but short- and long-term toxicities need to be carefully weighed against other available treatment options. Late AITP is a newly recognized complication of alemtuzumab in this patient population. This study is registered at www.clinicaltrials.gov as NCT00142181.Blood 05/2011; 118(2):276-81. · 9.06 Impact Factor
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ABSTRACT: The definition of Waldenström macroglobulinemia (WM), originally described in 1944, has been refined substantially over time. The current fourth edition of the World Health Organization of lymphoid neoplasms, in large part, adopted criteria proposed for WM at a consensus conference in 2002. WM is defined as lymphoplasmacytic lymphoma involving the bone marrow associated with a serum immunoglobulin (Ig) M paraprotein of any concentration. Morphologically, WM is composed of a variable mixture of lymphocytes, plasmacytoid lymphocytes, and plasma cells. Immunophenotypically, the neoplastic cells express monotypic IgM and light chain: B lymphocytes express pan-B-cell antigens and surface Ig are usually negative for CD5 and CD10; and plasma cells are typically positive for CD138, CD38, CD45, cytoplasmic Ig, and CD19 (in a substantial subset of cases). The putative cell of origin of WM is a postantigen selected memory B-cell that has undergone somatic hypermutation. The most common cytogenetic abnormality in WM is del(6q), usually in the region 6q23-24.3, present in 40% to 50% of cases. IGH gene translocations are rare and recurrent chromosomal translocations or gene aberrations have not been identified in WM. Here, we provide a historical perspective of WM, review clinical and pathologic aspects of the disease as it is currently defined, and discuss some practical issues in the differential diagnosis of WM that pathologists encounter in the signout of cases.Advances in anatomic pathology 01/2012; 19(1):11-27. · 3.22 Impact Factor