Evaluation of cerebrospinal clonal gene rearrangement in newly diagnosed non-Hodgkin's lymphoma patients.

Overt central nervous system (CNS) involvement in aggressive non-Hodgkin's lymphoma (NHL) is rare at diagnosis. Much effort is put to identify risk factors for occult CNS involvement, and the risk assessment of CNS relapse. Prophylactic treatment carries risk of adverse events and its efficacy is not clear. Detection of cerebrospinal fluid molecular gene rearrangement (GRR) as a method to detect occult disease has been studied in acute leukemia and primary CNS lymphoma. To date, the capacity of a positive GRR in newly diagnosed NHL patients to predict CNS relapse has not been addressed. We retrospectively studied the prognostic value of GRR in cerebrospinal fluid samples of 148 newly diagnosed patients with high grade NHL. We demonstrate that positive GRR at diagnosis does not affect PFS or OS and did not predict CNS relapse. However, although numbers were small, repeated positive samples (≥ 2) correlated with a higher risk for CNS relapse (p = 0.048), possibly stressing the need for an aggressive preventive approach.

The use of serum free light chain dimerization patterns assist in the diagnosis of AL amyloidosis.

The discrimination between benign and malignant forms of plasma cell dyscrasia (PCD) is often difficult. Free light chain monomer-dimer pattern analysis (FLC-MDPA) may assist in solving this dilemma and distinguish between AL amyloidosis and benign PCD. Serum samples of patients with AL amyloidosis and benign PCD were analysed in a blinded manner. Quantitative Western blotting was performed to estimate dimerization and clonality indices, and thereby determine the source of the tested samples, as derived either from benign or malignant PCD. The findings obtained by the FLC-MDPA were compared with the actual diagnosis. Of 37 samples from patients with active AL amyloidosis, 34 (91·9%) fulfilled dimerization criteria for diagnosis of AL amyloidosis. Of the 45 samples from patients with benign PCD, 10 (21·2%) tested falsely positive or gave an inconclusive result. Thus, the sensitivity of the analysis was 92·5% with a remarkable negative predictive value of 91·9%. In addition, of 20 patients who were in complete or very good partial remission, only one tested positive. By multivariate analysis, FLC-MDPA was the best independent marker predicting AL amyloidosis (odds ratio of 84). The FLC-MDPA offers a highly effective tool in the diagnostic assessment of patients with PCD.

Serum Hevylite® assay in the differential diagnosis of patients with high suspicion of AL Amyloidosis.

INTRODUCTION: AL amyloidosis (AL) is a malignant form of plasma cell dyscrasia (PCD). It is insidious, and its end-organ damage can mimic that of common diseases. At diagnosis, routine tests for monoclonal protein are insufficient for the differential diagnosis. We hypothesized that Hevylite® (HLC) isotype patterns may help discriminate between AL and benign PCD states. METHODS: Serum samples of patients with a high clinical suspicion of AL were prospectively tested for IgGκ, IgGλ, IgAκ, IgAλ, IgMκ, and IgMλ concentrations and ratios using Hevylite® assays in a blinded manner. The results were correlated with the final diagnosis. RESULTS: Of the 99 samples analyzed, 46 were newly diagnosed AL, and the majority, 38 (82.6%), presented with suppression of at least one HLC isotype. Of the 53 benign PCD patients, 36 (67.9%) presented with elevation of at least one HLC isotype. By multivariate analysis, Hevylite® was the best independent test predictor of AL amyloidosis. HLC suppression had an odds ratio (OR) of 14.591, and elevation an OR of 10.149, and thus were significant variables in the diagnosis and exclusion of AL. Furthermore, patients with both HLC suppression, together with no elevation, had an OR of 316.69 to be diagnosed with AL rather than a benign PCD. CONCLUSIONS: Hevylite® HLC analysis for Ig isotypes patterns offers an effective non-invasive tool in the evaluation of patients with high suspicion of AL and may assist further explorative decisions for diagnosis.

The prognostic value of bone marrow involvement at the molecular level in aggressive lymphoma.

We retrospectively studied the prognostic role of molecular (gene rearrangement, GRR) bone marrow (BM) involvement in diffuse large B-cell lymphoma (DLBCL, 424 patients) and in peripheral T-cell lymphoma (PTCL, 67 patients). When correlating BM GRR to histological findings at diagnosis, the GRR test was more sensitive (p = 0.036) but less specific (p < 0.0001) in PTCL than in DLBCL. For DLBCL (but not PTCL), a positive BM GRR correlated with advanced stage (p = 0.0001) and high IPI (p = 0.002), and worsened the progression free survival (PFS) (p = 0.05) and overall survival (OS) (p = 0.01), irrespective of rituximab treatment. Histologic negative/GRR positive cases had worse PFS/OS (p < 0.0001) than histologic/GRR double negative cases, however BM GRR was not an independent prognostic survival factor. End-of-treatment BM GRR did not predict survival. We conclude that BM GRR is unjustified as a prognostic tool for PTCL and should be reserved for a subset of DLBCL patients with negative histology of the BM.