We report here the successful treatment of cold
agglutinin-associated refractory
hemolysis with
bortezomib in a patient with Waldenström's
macroglobulinemia (WM). A 78-year-old man was referred to our hospital with cold hemagglutinemia of unknown cause. Laboratory examination revealed a
hemoglobin concentration of 6.9 g/dL, serum
IgM concentration of 1904 mg/dL, and a titer of cold
hemagglutinin of over ×8192. Serum immunoelectrophoresis demonstrated monoclonal
protein of the
IgM-κ type. A bone marrow aspirate showed many lymphoplasmacytic cells, which were positive for CD19, CD20, CD38, and cytoplasmic μ and κ light chains. A diagnosis of WM-associated cold hemagglutinemia was made. Because of
red blood cell transfusion-dependency, we treated him with intravenous
fludarabine, oral
melphalan-
prednisolone,
cyclophosphamide, and
melphalan, and two courses of R-CHOP in sequence with a marked decrease of serum
IgM (928 mg). We then started weekly
bortezomib plus
dexamethasone (BD)
therapy, as he was still transfusion-dependent. Soon after the initiation of BD, he achieved transfusion independence, with a further decrease in serum levels of
IgM and marked improvement of
anemia. Interestingly, his marrow abnormal lymphocytes were later found not to carry the MYD88 L265P mutation. The successful treatment with
bortezomib for WM lacking this mutation is discussed.