Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Am J Hematol. 2019 Feb;94(2):266-276. doi: 10.1002/ajh.25292. Epub 2018 Oct 17.
Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity.
Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in >90% of patients and is found in the majority of IgM monoclonal gammopathy of undetermined significance patients.
Age, hemoglobin level, platelet count, β2 microglobulin, and monoclonal IgM concentrations are characteristics that are predictive of outcomes.
RISK-ADAPTED THERAPY: Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-monotherapy is inferior to regimens that combine it with bendamustine, an alkylating agent, a proteosome inhibitor, or ibrutinib. Purine nucleoside analogs are active but usage is declining for less toxic alternatives. The preferred Mayo Clinic induction is rituximab and bendamustine. Potential for stem cell transplantation should be considered in selected younger patients.
Bortezomib, fludarabine, thalidomide, everolimus, ibrutinib, carfilzomib, lenalidomide, and bendamustine have all been shown to have activity in relapsed WM. Given WM's natural history, reduction of therapy toxicity is an important part of treatment selection.
华氏巨球蛋白血症（WM）是一种伴有免疫球蛋白 M（IgM）单克隆蛋白的淋巴浆细胞淋巴瘤。临床特征包括贫血、血小板减少、肝脾肿大、淋巴结病，极少数情况下还会出现高粘滞血症。
骨髓中存在 IgM 单克隆蛋白，伴≥10%的克隆性淋巴浆细胞可确诊。超过 90%的患者可检测到 MYD88 中的 L265P 突变，且该突变存在于大多数意义未明的单克隆 IgM 血症患者中。
年龄、血红蛋白水平、血小板计数、β2 微球蛋白和单克隆 IgM 浓度是预测结局的特征。
并非所有符合 WM 标准的患者都需要治疗；这些患者可以在出现症状之前进行观察。利妥昔单抗单药治疗不如联合苯达莫司汀、烷化剂、蛋白酶体抑制剂或伊布替尼的方案有效。嘌呤核苷类似物具有活性，但由于毒性较低的替代药物的使用，其使用率正在下降。Mayo 诊所推荐的诱导治疗方案是利妥昔单抗联合苯达莫司汀。在选择年轻患者时，应考虑进行干细胞移植的可能性。
硼替佐米、氟达拉滨、沙利度胺、依维莫司、伊布替尼、卡非佐米、来那度胺和苯达莫司汀已被证明对复发性 WM 具有活性。鉴于 WM 的自然病程，降低治疗毒性是治疗选择的重要组成部分。
