International Journal of Hematology

, Volume 102, Issue 2, pp 238–243 | Cite as

Successful treatment of refractory cold hemagglutinemia in MYD88 L265P mutation-negative Waldenström’s macroglobulinemia with bortezomib

  • Mayuko Izumi
  • Hiroko Tsunemine
  • Yasuhiro Suzuki
  • Akihiro Tomita
  • Toshiko Kusumoto
  • Taiichi Kodaka
  • Kiminari Itoh
  • Takayuki TakahashiEmail author
Case Report


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.


Waldenström’s macroglobulinemia Cold hemagglutinemia Hemolytic anemia MYD88 L265P mutation Bortezomib 


Conflict of interest

The authors disclose that they have no conflicts of interest with any individuals or companies.


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Copyright information

© The Japanese Society of Hematology 2015

Authors and Affiliations

  • Mayuko Izumi
    • 1
  • Hiroko Tsunemine
    • 1
  • Yasuhiro Suzuki
    • 2
  • Akihiro Tomita
    • 2
  • Toshiko Kusumoto
    • 3
  • Taiichi Kodaka
    • 1
  • Kiminari Itoh
    • 1
  • Takayuki Takahashi
    • 1
    Email author
  1. 1.Department of HematologyShinko HospitalKobeJapan
  2. 2.Department of Hematology and OncologyNagoya University Graduate School of MedicineNagoyaJapan
  3. 3.Department of Laboratory MedicineKobe Medical Center General HospitalKobeJapan

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