Successful treatment of refractory cold hemagglutinemia in MYD88 L265P mutation-negative Waldenström’s macroglobulinemia with bortezomib
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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.
KeywordsWaldenström’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.
- 1.Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML, et al. Clinicopathological definition of Waldenström’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenström’s Macroglobulinemia. Semin Oncol. 2003;30:110–5.PubMedCrossRefGoogle Scholar
- 2.Sweldrow SH, Berger F, Pileri SA, Harris NL, Jaffe ES, Stein H. lymphoplasmacytic lymphoma. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, et al., editors. World Health Organization (WHO) classification of tumors. Lyon, France, International Agency for Research on Cancer: Pathology and genetics tumors of haematopoietic and lymphoid tissues; 2008. p. 194–5.Google Scholar
- 14.Dacie JV. Auto-immune haemolytic anaemia (AIHA): cold antibody syndromes I idiopathic types: clinical presentation and haematological findings. In: Dacie JV, editor. The Haemolytic Anaemias. Churchhill: Livingstone; 1992. p. 210–39.Google Scholar
- 16.Hunter ZR, Xu L, Yang G, Zhou Y, Liu X, Cao Y, et al. The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B cell lymphomagenesis. Blood. 2014;123:1637–46.PubMedCrossRefGoogle Scholar
- 19.Dimopoulos MA, García-Sanz R, Gavriatopoulou M, Morel P, Kyrtsonis MC, Michalis E, et al. Primary therapy of Waldenström macroglobulinemia (WM) with weekly bortezomib, low-dose dexamethasone, and rituximab (BOR): long-term results of a phase 2 study of the European myeloma network (EMN). Blood. 2013;122:3276–82.PubMedCrossRefGoogle Scholar