Objective: To evaluate the clinical characteristics, MYD88(L265P) mutation, CXCR4(W)HIM mutation and prognosis in patients with Waldenström macroglobulinemia (WM). Methods: The clinical characteristics, International Prognostic Scoring System for symptomatic WM (WPSS) , and overall survival (OS) were retrospectively assayed in 93 patients with newly diagnosed WM at Peking Union Medical College Hospital during January 2000 to August 2016. The MYD88(L265P) mutation and CXCR4(W)HIM mutation were tested among 34 patients. Results: The median age of the 93 patients was 64 years (range, 33-85 years) with a male-to-female ratio of 2.44. According to WPSS, we included 16 (17.2%) low-risk, 44 (47.3%) intermediate-risk and 33 (35.5%) high-risk patients. Eight patients had secondary amyloidosis. With a median follow-up of 44 (1-201) months, the median OS was 84 months. Cox regression multifactor analysis showed WPSS risk group (HR=2.342, 95% CI 1.111-4.950, P=0.025) , whether patients had secondary amyloidosis (HR=5.538, 95% CI 1.958-15.662, P=0.001) and whether patients received new drugs (HR=3.392, 95% CI 1.531-7.513, P=0.003) were independent factors associated with OS. We have investigated the presence of the MYD88(L265P) and CXCR4(WHIM) mutation in 34 patients and found that MYD88(L265P) mutation was occurred in 32 patients (94.1%) and CXCR4(WHIM) mutation was occurred in 8 patients (23.5%). Seven of 8 patients who harbored CXCR4(WHIM)-mutated also exhibited the MYD88(L)265P mutation. Patients with MYD88(L265P)CXCR4(WHIM) vs MYD88(L265P)CXCR4(WT) presented with more severe anemia, lower platelet level, higher M protein level and more hyper-viscosity syndrome. Conclusion: WPSS risk group, whether patients had secondary amyloidosis or received new drugs are independent factors for OS in WM. MYD88(L265P) and CXCR4(WHIM) mutation, the most common somatic variants in WM, often occur together and impact the clinical presentation.
目的： 总结93例华氏巨球蛋白血症（WM）患者的临床特征、MYD88(L265P)及CXCR4(WHIM)突变情况、治疗选择和生存预后。 方法： 回顾性分析2000年1月至2016年8月在北京协和医院初诊的症状性WM患者的临床特征、国际预后指数评分（WPSS）和总体生存（OS）；其中34例患者检测了MYD88(L265P)和CXCR4(WHIM)突变。 结果： 93例患者男女比例为2.44∶1，中位年龄64（33~85）岁。WPSS分层：低危组16例（17.2%），中危组44例（47.3%），高危组33例（35.5%）。中位随访44（1~201）个月，中位OS期为84个月。Cox多因素分析显示：WPSS危险分层（HR=2.342，95% CI 1.111~4.950，P=0.025）、继发淀粉样变性（HR=5.538，95% CI 1.958~15.662，P=0.001）以及新药治疗（HR=3.392，95% CI 1.531~7.513，P=0.003）均是影响患者OS的独立预后因素。34例患者中32例（94.1%）存在MYD88(L265P)突变，8例（23.5%）存在CXCR4(WHIM)突变。MYD88 (L265P)CXCR4(WHIM)突变组（7例）较MYD88 (L265P)CXCR4(WT)组（25例）患者的贫血更重、血小板计数更低、M蛋白水平更高、高黏滞症状更多见，差异有统计学意义（P值均<0.05）。 结论： WM患者的预后较好，WPSS评分、是否继发淀粉样变性以及是否使用新药治疗是影响其预后的独立因素。WM患者的MYD88(L265P)突变率高，而CXCR4(WHIM)突变多与MYD88(L265P)突变伴发出现，其突变与一些临床特征相关。.
Keywords: Mutation; Myeloid Differentiation Factor 88; Receptors, CXCR4; Waldenström macroglobulinemia.