真性红细胞增多症患者发生血栓栓塞、骨髓纤维化及急性白血病转化危险因素的研究

目的了解真性红细胞增多症（PV）患者的病程特点，评价PV治疗及其与血栓栓塞、骨髓纤维化、白血病转化等的相关性；探讨影响PV患者生存的预后因素。方法分析287例PV患者的临床特点、实验室参数及治疗情况。根据其血栓栓塞、骨髓纤维化、继发造血及非造血系统恶性肿瘤和死亡情况，探讨影响PV患者生存的预后因素。结果287例患者中位随访时间46（8-360）个月。115例（40.1％）发生血栓栓塞事件208次，其中59例（51．34％）发生2次以上或2个部位以上栓塞。栓塞事件多发生于PV诊断时或诊断前2年内。高龄、既往血栓栓塞病史及疗效不理想是血栓栓塞的危险因素。具备2项以上不良指标者血栓栓塞发生率明显高。190例骨髓活检患者中36例（18．9％）PV患者发生骨髓纤维化，骨髓纤维化发生于发病后80（8—190）个月内，发病时外周血白细胞计数升高、脾大，烷化剂及羟基脲应用是并发骨髓纤维化的危险因素。2例发生急性髓系白血病转化；1例发生非造血系统恶性肿瘤；1例发生淋巴瘤。13例死亡，其中9例（69、2％）死于血栓栓塞，2例（15．4％）死于白血病，消化道出血和多脏器功能衰竭各1例。结论PV患者血栓栓塞发生率较高，骨髓纤维化发生时间较早。影响生存的主要因素是血栓栓塞及进展为白血病。

The risk factors for thrombosis, myelofibrosis and leukemia transformation in patients with polycythemia vera

OBJECTIVE: To reassess the natural history of polycythemia vera (PV) in Chinese and evaluate the relationship between the incidence of thrombosis, post-polycytheamic myelofibrosis with myeloid metaplasia( PPMM) , leukemia transformation and the therapeutic outcome and prognostic factors. METHODS: The clinical manifestations, laboratory parameters and treatment were retrospectively analyzed in 287 patients with PV. Univariate analysis of prognostic factors was performed using Log-rank model and multivariate analysis using COX model in term of the incidence of thrombsis, PPMM, hematologic or non hematologic cancers and mortality. RESULTS: Of the 287 patients, the median follow-up time was 46 (8-360) months. 208 thromboses were recorded in 115 patients. Twice or more thrombotic events occurred on 59 patients (51.34%). Most of these episodes occurred either at presentation or in the 2 years before diagnosis. Elder patients, prior thrombosis, poor response to therapy were associated with poor prognosis. With these three adverse prognostic factors, the patients could be separated into different risk groups. The incidence of thrombosis was higher in high risk group. 36 patients progressed to PPMM, the median time to PPMM was 80 (7-190) months. Higher WBC count, splenomegaly and treatment with alkylatin agent and hydroxycarbamide (HU) were associated with poor prognosis. 2 cases progressed to AML. 1 to lymphoma and 1 to nonhematologic cancer. 13 patients died, the cause of death was fatal thrombosis in 9 and AML in 2. CONCLUSION: The incidence of thromboembolism is higher and the time to myelofibrosis was shorter in Chinese PV patients than in western PV patients. The main factors that influence the survival of PV patients are thrombimbolism and leukemia transformation.