华氏巨球蛋白血症患者的临床特征、MYD88(L265P)、CXCR4(WHIM)突变和预后：单中心93例回顾性分析

OBJECTIVE: To evaluate the clinical characteristics, MYD88(L265P) mutation, CXCR4(WHIM) 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(WHIM) 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(L265P) 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.