Waldenström macroglobulinaemia: the key questions

Abstract

SummaryIn this review, the key issues that pertain to Waldenstr€ om disease are discussed in a concise question-and-answer format. Diagnosis, prognosis, and indications for state-of-the-art therapy are updated. Current therapies presented at the 7th International Workshop for Waldenstr€ om Macroglobulinaemia are included.

Update in Waldenström’s Macroglobulinemia

“…IgM-MGUS is characterized by the presence of an IgM monoclonal protein, less than 10% clonal lymphoplasmacytic bone marrow cells, and no symptoms attributable to tumor mass or infiltrations [4]. It is a precursor state for WM.…”

“…Approximately 2% of IgM MGUS patients evolve to a B-cell malignancy per year, with most of these individuals progressing to WM [5]. Smoldering WM is characterized by an IgM monoclonal protein, clonal lymphoplasmacytic bone marrow infiltration greater than 10%, no symptoms attributable to tumor mass or infiltration, and no IgM-mediated symptoms [4]. Clinical features are related to disease burden, such as cytopenias, organomegaly and constitutional symptoms, or to IgM paraprotein such as hyper viscosity syndrome, hemolytic anemia, immune complex vasculitis and amyloidosis or to autoantibody specificity such as peripheral neuropathy, cold hemagglutinin disease and acquired von Willebrand disease [2].…”

“…LPC may be detected in the cerebrospinal fluid, the meninges and/ or the cerebral parenchyma [6]. WM patients are at increased risk for second malignancies, including transformation to DLBCL (5-10%), myelodysplastic syndrome, acute myeloid leukemia and solid cancers [4]. Development of bulky rapidly enlarging lymph node masses, extranodal disease and marked elevation in serum lactate dehydrogenase are suggestive of transformation to DLBCL [2].…”

“…Development of bulky rapidly enlarging lymph node masses, extranodal disease and marked elevation in serum lactate dehydrogenase are suggestive of transformation to DLBCL [2]. The genomic landscape of WM is characterized by highly recurring MYD88 (>90% of cases) resulting in a protein change from leucine to proline at amino acid position 265 [4].…”

“…MYD88 mutation is not unique to WM. It distinguished WM from overlapping entities such as marginal zone lymphoma, chronic lymphocytic leukemia, and multiple myeloma, wherein MYD88L265P was either absent or infrequently observed (<10%) [4]. CXCR4 is mutated in 30% of WM patients.…”