Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure

<p>Abstract</p> <p>Background</p> <p>Monoclonal free light chains (FLCs) frequently cause rapidly progressive renal failure in patients with multiple myeloma. Immunoassays which provide quantitative measurement of FLCs in serum, have now been adopted into screening algorithms for multiple myeloma and other lymphoproliferative disorders. The assays indicate monoclonal FLC production by the presence of an abnormal κ to λ FLC ratio (reference range 0.26–1.65). Previous work, however, has demonstrated that in patients with renal failure the FLC ratio can be increased above normal with no other evidence of monoclonal proteins suggesting that in this population the range should be extended (reference range 0.37–3.1). This study evaluated the diagnostic sensitivity and specificity of the immunoassays in patients with severe renal failure.</p> <p>Methods</p> <p>Sera from 142 patients with new dialysis-dependent renal failure were assessed by serum protein electrophoresis (SPE), FLC immunoassays and immunofixation electrophoresis. The sensitivity and specificity of the FLC ratio's published reference range was compared with the modified renal reference range for identifying patients with multiple myeloma; by receiver operating characteristic curve analysis.</p> <p>Results</p> <p>Forty one patients had a clinical diagnosis of multiple myeloma; all of these patients had abnormal serum FLC ratios. The modified FLC ratio range increased the specificity of the assays (from 93% to 99%), with no loss of sensitivity. Monoclonal FLCs were identified in the urine from 23 of 24 patients assessed.</p> <p>Conclusion</p> <p>Measurement of serum FLC concentrations and calculation of the serum κ/λ ratio is a convenient, sensitive and specific method for identifying monoclonal FLC production in patients with multiple myeloma and acute renal failure. Rapid diagnosis in these patients will allow early initiation of disease specific treatment, such as chemotherapy plus or minus therapies for direct removal of FLCs.</p

Serum syndecan-1, basic fibroblast growth factor and osteoprotegerin in myeloma patients at diagnosis and during the course of the disease

Neovascularisation and bone resorption are related to myeloma disease activity. Objectives: To investigate the possible prognostic importance of serum syndecan-1, basic fibroblast growth factor (bFGF) and osteoprotegerin (OPG) levels, the relationship between them, with parameters of disease activity and the effect of treatment on their levels.&lt;LF&gt;Patients and Methods: Twenty-seven patients were studied from diagnosis and an additional five from remission, for a median follow-up of 40 months. Twenty-three patients received chemotherapy plus bisphosphonates and nine only bisphosphonates. Sera from 11 healthy individuals (HI) were used as controls. Cytokines were determined by commercially available enzyme-linked immunosorbent assays (ELISA) kits. Results: In HI, median syndecan-1 was 40 ng/mL (28-75), bFGF 8 pg/mL (7-30), OPG 35 pg/mL (4-100). Pretreatment median serum syndecan-1 was 177.5 ng/mL (34-3500), bFGF 11.5 pg/mL (8-65) and OPG 100 pg/mL (4-1000). Pretreatment syndecan-1, bFGF and OPG serum levels were increased in patients compared with HI (P = 0.001, 0.03 and 0.01, respectively). Syndecan-1 and bFGF levels were correlated with stage (P = 0.004 and 0.03, respectively). Both syndecan-1 and OPG levels were correlated with beta(2)M (P = 0.04 and 0.01, respectively). Patients with elevated syndecan-1 and bFGF serum levels had shorter survival than patients with normal levels (P = 0.01 and 0.05, respectively). After chemotherapy syndecan-1 and OPG levels were found to be decreased in responders and syndecan-1 level was reduced in patients receiving bisphosphonates alone. Conclusions: Pretreatment syndecan-1, bFGF and OPG levels were found to be increased at diagnosis. Syndecan-1 and OPG fluctuated according to MM activity. Elevated serum syndecan-1 and bFGF levels predicted short survival

Predictive factors for response to rituximab in Waldenstrom&apos;s macroglobulinemia

Rituximab is an active agent for the treatment of Waldenstrom’s macroglobulinemia. However, many patients do not respond to this agent and several others develop secondary resistance. In order to identify clinical and laboratory parameters that could predict a higher likelihood for response, we evaluated 54 patients who were treated with single-agent rituximab. Twenty-four patients (44%)exhibited &gt;= 50% reduction of serum monoclonal protein. Previously untreated and pretreated patients had the same probability for response. Low response rates were noted in patients with serum monoclonal protein level &gt;= 40 g/L (17%) and serum albumin level &lt; 35 g/L (14%). Furthermore, a multivariate analysis indicated that high serum monoclonal protein and low albumin were the dominant variables associated with shorter time to progression. The presence of 2, 1, or none of these variables was associated with median times to progression of 4 months, 11 months, and approximately 48 months, respectively. We conclude that patients with low levels of monoclonal protein and normal albumin are the best candidates for treatment with rituximab

Primary lung involvement in Waldenstrom&apos;s macroglobulinaemia - Report of two cases and review of the literature

Pulmonary involvement in Waldenstrom’s macroglobulinaemia (WM) occurs in 3-5% of cases, but lung involvement without bone marrow infiltration is extremely rare, We report 2 patients who presented with bilateral consolidations on chest X-ray and non-specific symptoms and were treated for a long period of time for pulmonary infections until the diagnosis was made by open lung biopsy, Both patients presented high monoclonal IgM in the serum and one also had blood lymphoplasmacytosis. Trephine bone biopsy and bone marrow smears were normal and there was no other site of involvement. Along with the presentation of our patients, we review the literature, discuss some of the possible underlying mechanisms and raise the attention of clinicians to this rare manifestation of the disease. Copyright (C) 2001 S. Karger AG, Basel

The international staging system for multiple myeloma is applicable in symptomatic Waldenstrom&apos;s macroglobulinemia

Several studies have indicated that age, hemoglobin and serum albumin are among the most important prognostic factors for survival of patients with Waldenstrom’s macroglobulinemia (WM). Furthermore, recent data indicate that serum b2-microglobulin may be also significant. The recently proposed International Staging System (ISS) for multiple myeloma is based on serum albumin and b2-microglobulin. We designed a study to assess this model in patients with WM. Our analysis included 83 previously untreated patients with WM who required systemic treatment and in whom pretreatment values for both serum albumin and b2-microglobulin were available. Based on these variables the patients were stratified into three ISS stages. Stage I: albumin greater than or equal to3.5 g/dl and b2-microglobulin &lt;3.5 mg/dl, stage II: albumin &lt;3.5 g/dl and b2-microglobulin &lt;3.5 mg/gl or b2-microglobulin 3.5 - 5.5 mg/dl and stage III: b2-microglobulin &gt;5.5 mg/dl. Low albumin (&lt;3.5 g/dl) and high b2-microglobulin (&gt;= 3.5 mg/dl) were recorded in 45% and 52% of patients respectively. The distribution of patients in the three ISS stages was: stage I: 30%, stage II: 43% and stage III: 27%. The median overall survival from the date of treatment initiation was 115 months. The median survival according to ISS was not reached for stage I, 116 months for stage II and 54 months for stage III ( P = 0.02). Our analysis indicated that the recently proposed ISS for multiple myeloma could stratify the patients with WM into three distinct subgroups with significantly different survival times. If this model is validated in independent series, it could provide a new staging system for WM based on readily available and reproducible variables