Department of Haematology, APHP Hôpital Pitié-Salpétrière, Paris, France.
Br J Haematol. 2018 Jun;181(6):737-751. doi: 10.1111/bjh.15202. Epub 2018 Apr 10.
Waldenström macroglobulinaemia (WM) is a rare, indolent B-cell lymphoproliferative disorder characterized by cellular involvement in bone marrow and monoclonal IgM production. Symptoms can be related to cytopenias, tumoural involvement, or IgM-related disorders. Somatic mutations in the MYD88 gene have been described in the majority of WM cases. The mutation is responsible for a gain-of-function and induces activation of nuclear factor-κB, for DNA transcription and cell survival. It seems that MYD88 mutation is associated with better prognosis and better response to some treatment. Treatments are started when WM is symptomatic, following systematic biological and morphological assessments. Therapeutic choice depends on age, frailty and urgent efficacy need. In first line, the majority of patients are treated with monoclonal anti-CD20 antibody-based regimens combined with cytotoxic chemotherapy. Rituximab, cyclophosphamide and dexamethasone remain the most commonly used regimen with good safety. Nevertheless, increasing numbers of new drugs are becoming available or are in development. Proteasome inhibitors, such as bortezomib or carfilzmib, showed good and rapid responses. Bruton tyrosine kinase (BTK) inhibitor demonstrated excellent results and is now available for relapse/refractory disease or as first line for some patients. This review highlights the diagnostic procedures and therapeutic approaches in WM.
华氏巨球蛋白血症（WM）是一种罕见的惰性 B 细胞淋巴增殖性疾病，其特征是骨髓细胞受累和单克隆 IgM 产生。症状可能与细胞减少症、肿瘤浸润或 IgM 相关疾病有关。大多数 WM 病例中都描述了 MYD88 基因的体细胞突变。该突变负责获得功能，并诱导核因子-κB 的激活，进行 DNA 转录和细胞存活。似乎 MYD88 突变与更好的预后和对某些治疗的更好反应有关。当 WM 出现症状时，会根据系统的生物学和形态学评估开始治疗。治疗选择取决于年龄、虚弱程度和紧急疗效需求。在一线治疗中，大多数患者接受基于单克隆抗 CD20 抗体的方案联合细胞毒性化疗。利妥昔单抗、环磷酰胺和地塞米松仍然是最常用的方案，具有良好的安全性。然而，越来越多的新药正在或正在开发中。蛋白酶体抑制剂，如硼替佐米或卡非佐米，显示出良好和快速的反应。布鲁顿酪氨酸激酶（BTK）抑制剂显示出优异的结果，现在可用于复发/难治性疾病，或作为某些患者的一线治疗。本综述强调了 WM 的诊断程序和治疗方法。
