急性早幼粒细胞白血病合并弥漫性血管内凝血的临床研究

Clinical analysis of acute promyelocytic leukemia with disseminated intravascular coagulation

目的分析急性早幼粒细胞白血病(APL)并发弥漫性血管内凝血(DIC)的临床、实验室特征及治疗情况,探索DIC死亡的危险因素。方法对2004年1月至2010年9月中国医科大学附属第一医院血液科收治的156例初治APL患者进行病例总结与分析。结果 156例患者中64例(41.0%)合并DIC,中位发生时间为10d。APL合并DIC患者出血广泛且严重,微血管栓塞表现少见。合并DIC患者完全缓解率为63%,早期病死率为33%,达完全缓解时间为44(25～78)d,治疗中并发维甲酸综合征占17%,与非DIC组比较差异有统计学意义(P=0.000、0.035、0.001、0.029)。维甲酸联合砷剂治疗可缩短DIC治愈时间。DIC组患者复发率为20%,明显高于非DIC组(8%,P=0.031)。DIC组患者总生存时间为12(0.1～65)个月,5年总生存(OS)率为(56±7)%,与非DIC组相比差异有统计学意义(P=0.001);DIC组无复发生存(RFS)时间为17.5(3～65)个月,5年RFS率为(74±8)%,与非DIC组差异无统计学意义(P=0.052)。多因素分析显示血浆纤维蛋白原(Fbg)、外周血白细胞数、生存状态评分(PS评分)是APL合并DIC死亡的危险因素。结论 DIC是APL最严重的并发症之一,为APL致死及导致不良预后的直接原因,应早期诊断。血浆Fbg<1.0g/L、白细胞>20×109/L、PS评分2～4分预示DIC高危、病死率极高,应早期进行维甲酸及砷剂联合诱导治疗。

Objective To analyze the clinical features and treatment of acute promyelocytic leukemia（APL）with disseminated intravascular coagulation（DIC） and to investigate the risk factors associated with the death.Methods From January 2004 to September.2010 medical records of 156 newly diagnosed patients with acute promyelocytic leukemia in the First Affiliated Hospital of China Medical University were reviewed.Results There were 156 APL patients,of whom 64 cases complicated DIC with inception rate of 41.0%,the median time of DIC occurred is in the 10th day.APL with DIC mergers widespread and serious bleeding,a rare performance of microvascular thrombosis.Of all the APL patients with DIC,the remission rate（CR） was 63%,the early death rate（ED） was 33%,time for remission was 25~78 d with an average time of 44 d and retinoic acid syndrome（RAS） was 17%,there were significant differences compared with the non-DIC groups（P=0.000,0.035,0.001 and 0.029）.ATRA combined with arsenic trioxide（ATO） shortened the DIC time.The relapse rate of DIC group was 20%,higher than that of non-DIC group（P=0.031）.The overall survival time of DIC group is 12（0.1～65）months,5-year OS rate was（56±7）%,higher than that of non-DIC group（P=0.001）.But there were no significant differences between the two groups in relapse-free survival time（P=0.052）.Univariate analysis identified three pretreatment variables associated with the death： initial fibrinogen level,white blood cell count and performance status.Conclusion DIC is the most serious complication of APL and the direct cause of death.The initial fibrinogen level1.0 g/L,white blood cell count20×109/L and performance status 2～4 points indicates high mortality.The combination of ATRA and ATO should be used in the induced treatment in the early time.