Lymphoplasmacytic Bone Marrow Infiltration Research Articles

Immunoglobulin M Monoclonal Gammopathies of Undetermined Significance and Indolent Waldenström's Macroglobulinemia Recognize the Same Determinants of Evolution Into Symptomatic Lymphoid Disorders: Proposal for a Common Prognostic Scoring System

To evaluate the clinicohematologic variables at diagnosis that are prognostically related to neoplastic progression in patients with immunoglobulin M (IgM) monoclonal gammopathies of undetermined significance (MGUS), and indolent Waldenström's macroglobulinemia (IWM), and propose a scoring system to identify subsets of patients at different risk. We evaluated 217 patients with IgM MGUS and 201 with IWM (male-female ratio, 131:86 and 117:84; mean age, 63.7 and 63.6 years, respectively) diagnosed on the basis of serum monoclonal component (MC) levels and bone marrow lymphoplasmacytic infiltration degree. The variables selected by univariate analyses were multivariately investigated; on the basis of their individual relative hazards, a scoring system was devised to identify subsets of patients at different risk of evolution. After a median follow-up of 56.1 and 60.2 months, 15 of 217 MGUS and 45 of 201 IWM patients, respectively, required chemotherapy for symptomatic WM (13 and 36), non-Hodgkin's lymphoma (2 and 6) and amyloidosis (0 and 3). The median time to evolution (TTE) was not reached for MGUS and was 141.5 months for IWM. The variables adversely related to evolution were qualitatively the same in both groups: MC levels, Hb concentrations and sex. A scoring system based on these parameters identified three risk groups with highly significant differences in TTE in both groups (P < .0001). MGUS and IWM identify disease entities with different propensities for symptomatic neoplastic evolution. As both have the same prognostic determinants of progression, we propose a practical scoring system that, identifying different risks of malignant evolution, may allow an individualized clinical approach.

Differential Diagnosis of Waldenström's Macroglobulinemia and Other B-Cell Disorders

Waldenström's macroglobulinemia (WM) is characterized by lymphoplasmacytic infiltration of bone marrow and/or other tissues and by the presence of serum monoclonal immunoglobulin M ([IgM], without cutoff limit). Differential diagnosis from other B-cell disorders (BCDs) is usually easy based on clinical, morphologic, histopathologic, immunophenotypic, and genetic features. However, all BCDs potentially produce monoclonal IgM. In this study we reviewed the medical files of 130 patients with IgM-secreting BCDs. Eighty-four patients were diagnosed with WM, 5 with IgM-monoclonal gammopathy of undetermined significance (MGUS), and 41 with other BCDs (9 with B-cell chronic lymphocytic leukemia, 5 with small lymphocytic lymphoma, 14 with marginal zone lymphoma, 5 with mantle-cell lymphoma, 2 with follicular lymphoma, 2 with diffuse large B-cell lymphoma, 2 with cryoglobulinemia, and 2 with low-grade lymphoma not otherwise specified). Median IgM levels were 3215 mg/dL in WM, 840 mg/dL in IgM-MGUS, and 285 mg/dL in other BCDs (5 had IgM levels > 1500 mg/dL). In 10% of non-WM BCDs, monoclonal IgM was found only when more sensitive immunofixation methods were used. Forty-four percent of patients with BCDs (splenic marginal zone lymphoma or small lymphocytic lymphoma) had diagnoses that corresponded to that of WM. Careful diagnosis requires the concomitant evaluation of all parameters of BCDs together. Marginal zone lymphoma is the most frequently overlapping entity. Special attention should be given to mantle cell lymphoma in its atypical forms. Research in this field should continue to further clarify the disease entities that overlap with WM. New technology such as gene-expression profile techniques may contribute to this purpose.

Prognostic Factors for Transformation in Asymptomatic Immunoglobulin M Monoclonal Gammopathies

We evaluated the risk of transformation of asymptomatic immunoglobulin (Ig) M monoclonal gammopathy (aIgM-MG) into symptomatic lymphoproliferative disease in 384 patients, in subgroups of patients with IgM MG of undetermined significance (MGUS) and smoldering Waldenström's macroglobulinemia (sWM). One hundred seventy-two patients with aIgM-MG with bone marrow (BM) histopathology and immunophenotyping were available for analysis. After a median of 45 months (range, 12-233 months), 45 cases of aIgM-MG (11.7%) evolved into lymphoproliferative disease, as follows: symptomatic WM (n = 41), non-Hodgkin's lymphoma (NHL; n = 2), IgM multiple myeloma (IgM-MM; n = 1), and primary amyloidosis (n = 1). Cumulative transformation probability at 5 and 10 years was 8% and 29%, respectively. The parameters significantly correlated with evolution were, at univariate analysis, BM lymphoplasmacytic infiltration, high erythrocyte sedimentation rate, hemoglobin (Hb) level, IgM size, and peripheral lymphocytosis; at multivariate analysis, the parameters were IgM size and peripheral lymphocytosis, with Hb level associated with a trend toward higher progression risk. Of the 138 cases of IgM-MGUS, 14 (10.1%) evolved (13 WM, 1 IgM-MM) after a median of 75 months (range, 12-117 months); of the 34 cases of sWM, 13 (38.2%) progressed to WM after 55 months (range, 13-154 months). In patients with IgM-MGUS, event-free survival at 5 and 10 years was 95% and 83%, respectively, and in patients with sWM, 77% and 42%, respectively (P = 0.0001). Among patients with aIgM-MG, those at high risk of evolution are patients with sWM, a distinct entity with clear BM evidence of NHL.