Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Am J Hematol. 2018 Nov;93(11):1384-1393. doi: 10.1002/ajh.25254. Epub 2018 Oct 2.
Symptomatic hyperviscosity is a well-established phenomenon in Waldenström macroglobulinemia (WM). Monoclonal IgM can variably impact intrinsic serum viscosity, leading to widely disparate symptomatic thresholds for development of hyperviscosity-related symptoms. Data regarding the predictors of symptomatic hyperviscosity and outcomes related to this complication remain scarce and a recent study proposed that IgM >6000 mg/dL be considered a new criterion for initiating therapy in otherwise asymptomatic (smoldering) WM to pre-empt hyperviscosity-related injury. Herein, we attempt to identify predictors of the development of symptomatic hyperviscosity and its impact in patients with WM. Of 997 WM patients evaluated from January, 1996 through June, 2017, symptomatic hyperviscosity was observed in 130 (13%) patients. Overall survival (OS) of these 130 patients was similar to that of patients without symptomatic hyperviscosity (median: 11.5 vs 11.6 years; P = 0.63). On multivariate-analysis, only viscosity >1.8 cp (risk ratio: 4.0, P = 0.02) assessed at the time of WM diagnosis was an independent predictor for the development of subsequent symptomatic hyperviscosity. Among patients with smoldering WM and IgM >6000 mg/dL at diagnosis (n = 13) who were managed expectantly, the median time-to-initial therapy was 6.9 years and only 15% developed hyperviscosity-related symptoms subsequently. In summary, the occurrence of symptomatic hyperviscosity does not impact OS. Serum viscosity at diagnosis of WM, and not IgM concentration, represents the single most important independent predictor for development of subsequent hyperviscosity-related symptoms. Patients with smoldering WM and high serum IgM can be safely observed in the absence of any indications per the Consensus recommendations to initiate WM-directed therapy.
症状性高粘血症是瓦尔登斯特伦巨球蛋白血症（WM）中的一种既定现象。单克隆 IgM 可不同程度地影响内源性血清粘度，从而导致出现高粘血症相关症状的症状阈值差异很大。有关症状性高粘血症的预测因素以及与该并发症相关的结果的数据仍然很少，最近的一项研究提出，将 IgM >6000mg/dL 视为开始治疗否则无症状（惰性）WM 的新标准，以预防高粘血症相关损伤。在此，我们试图确定 WM 患者发生症状性高粘血症及其影响的预测因素。在 1996 年 1 月至 2017 年 6 月期间评估的 997 名 WM 患者中，有 130 名（13%）患者出现症状性高粘血症。这些 130 名患者的总生存（OS）与无症状性高粘血症患者相似（中位数：11.5 年与 11.6 年；P=0.63）。在多变量分析中，WM 诊断时评估的仅粘度>1.8cp（风险比：4.0，P=0.02）是随后发生症状性高粘血症的独立预测因素。在诊断时患有惰性 WM 和 IgM >6000mg/dL 的患者中（n=13），期望进行管理，初始治疗的中位时间为 6.9 年，只有 15%的患者随后出现高粘血症相关症状。总之，症状性高粘血症的发生并不影响 OS。WM 诊断时的血清粘度，而不是 IgM 浓度，是预测随后发生高粘血症相关症状的最重要的独立预测因素。根据 Consensus 建议，患有惰性 WM 和高血清 IgM 的患者在没有任何指示的情况下可以安全观察，无需开始 WM 靶向治疗。
