Low-dose bortezomib and dexamethasone as primary therapy in elderly patients with WaldenstrÓ§m macroglobulinemia.

OBJECTIVE: This retrospective study was designed to determine the efficacy and safety of low-dose bortezomib and dexamethasone (lBD) in elderly Chinese patients with WaldenstrÓ§m macroglobulinemia (WM). METHODS: Ten patients with WM aged over 60 years received first-line treatment with lBD. RESULTS: The median age was 70 years (range, 61-77 years). The overall response rate was 80%, including 1 patient who achieved a complete response, 1 patient with very good partial response, and 6 patients with a partial response. Median time to response was 1.8 months after treatment with lBD. Six (60%) patients achieved a partial response, including 2 (20%) patients who had a more than 75% reduction in serum immunoglobulin M levels. A rapid reduction in paraprotein was observed in three patients who received plasmapheresis. After a median follow-up period of 36 months, all patients were still alive and six had no disease progression. The estimated median time to progression was 39 months (range, 15-60 months). The most common adverse events were anemia, thrombocytopenia, neuropathy, and neutropenia. Peripheral neuropathy was the most common non-hematological toxicity in six (60%) patients, but did not result in the discontinuation of bortezomib. CONCLUSIONS: Our findings show that lBD is an effective and tolerable treatment regimen for elderly patients with WM.

One-step molecular detection of the MYD88 L265P mutation by unlabeled probe genotyping analysis.

The aim of our study was to establish an unlabeled probe genotyping approach for rapid detection of the MYD88 L265P mutation in the differential diagnosis of WaldenstrÓ§m macroglobulinemia patients. Analytical and clinical validation of the assay was performed using serially diluted amplicon-cloned standards, 14 clinical bone marrow aspirate samples, and 30 peripheral blood samples from healthy donors, respectively. The analytical validation results showed that the assay is able to reproducibly identify as low as 10% of the L265P mutant. Clinical validation results showed improved detection sensitivity for the L265P mutation compared to Sanger sequencing. With the simplicity, cost-effectiveness, specificity and rapidity, we foresee that the unlabeled probe HRM assay is a good alternative to substitute current established methods for routine diagnostic testing of the MYD88 L265P mutation.

Amyloid-like IgM deposition neuropathy with multiple mononeuropathies and generalized neuropathy.

Amyloid-like IgM deposition neuropathy is a distinct entity in the setting of IgM monoclonal gammopathy in which endoneurial perivascular entire IgM-particle accumulation leads to a painful sensory followed by motor peripheral neuropathy. We report a 77-year-old man presenting with progressive multiple mononeuropathies starting with painless right foot drop. Electrodiagnostic studies showed severe axonal sensory-motor neuropathy superimposed by multiple mononeuropathies. Laboratory investigations were remarkable for biclonal gammopathy of IgM kappa, IgA lambda and severe sudomotor and mild cardiovagal autonomic dysfunction. A right sural nerve biopsy showed multifocal axonal neuropathy, prominent microvasculitis, and prominent large endoneurial deposits of Congo-red negative amorphous material. Laser dissected mass spectrometry-based proteomics identified IgM kappa deposit without serum amyloid-P protein. This case has several distinctive features, including motor preceding sensory involvement, prominent IgM-kappa proteinaceous deposits replacing most of the endoneurium, a prominent inflammatory component, and improvement of motor strength after immunotherapy.

Retrospective analysis of prognostic factors for WaldenstrÓ§m macroglobulinemia: a multicenter cooperative study in Japan.

Although population-based cancer registries have reported lower incidence of WaldenstrÓ§m macroglobulinemia (WM) in East Asia than in Western countries, previous retrospective analyses have found the clinical features of WM to be similar in these two populations. To clarify the characteristics of Japanese WM patients, we retrospectively analyzed clinical and laboratory characteristics, treatments, outcomes, and prognostic factors in 93 patients with WM. Based on the Second International Workshop on WM (IWWM-2) criteria, symptomatic WM was found in 73 (78.5%) and asymptomatic WM in 20 (21.5%) of cases examined. The median overall survival (OS) was similar to that in reports from Western countries. Patients receiving treatment regimens including rituximab exhibited significantly better survival than those not given rituximab. Although prognostic factors for WM in Western countries may not apply to Japanese patients, our finding that newly diagnosed WM patients with pleural effusion have a poorer prognosis suggests that this may be a novel predictor of adverse prognosis in symptomatic WM.