title: Successful treatment of refractory cold hemagglutinemia in MYD88 L265P mutation-negative Waldenström's macroglobulinemia with bortezomib.
abstract: 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.
authors: Department of Hematology, Shinko Hospital, 4-47 Wakihama-cho, 1-chome, Chuo-ku, Kobe, 651-0072, Japan.
authors: Mayuko
authors: M
authors: Izumi
authors: Hiroko
authors: H
authors: Tsunemine
authors: Yasuhiro
authors: Y
authors: Suzuki
authors: Akihiro
authors: A
authors: Tomita
authors: Toshiko
authors: T
authors: Kusumoto
authors: Taiichi
authors: T
authors: Kodaka
authors: Kiminari
authors: K
authors: Itoh
authors: Takayuki
authors: T
authors: Takahashi
mesh_terms: D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000378:metabolism; D000069286:Bortezomib / Q000008:administration & dosage / Q000627:therapeutic use*; D003449:Cryoglobulinemia / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D004252:DNA Mutational Analysis; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D016896:Treatment Outcome; D008258:Waldenstrom Macroglobulinemia / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*
chemical_list: D053594:Myeloid Differentiation Factor 88; D000069286:Bortezomib