异基因造血干细胞移植相关血栓性微血管病16例报告并文献复习

Allogeneic hematopoietic stem cell transplantation associated thrombotic microangiopathy： 16 cases report and literature review

目的分析异基因造血干细胞移植（allo—HSCT）相关血栓性微血管病（TA-TMA）患者临床特征、疗效及转归。方法回顾性分析2013年1月至2015年6月于苏州大学附属第一医院接受allo—HSCT后发生TA—TMA的16例患者临床资料。结果纳入研究的852例allo-HSCT患者，16例（1．9％）发生TA—TMA，中位随访时间14个月，1年累计发生率为（2．3±0．6）％。16例患者中，男7例，女9例，中位年龄4l（12-54）岁，中位发病时间为移植后72（21-525）d，PLT中位数为20（11-36）×10^9／L，HGB中位数为74（56-99）g／L，LDH中位水平为762（309-1049）U／L，外周血破碎红细胞比例中位数为3％（2％-13％），所有患者ADAMTS13活性均〉60％。10例出现精神症状，7例肌酐水平升高。TA—TMA确诊后的主要治疗措施为钙调磷酸酶体抑制剂的减停、激素及血浆置换疗法，8例经治疗后病情得以控制，治疗有效；8例患者治疗无效死亡。治疗无效组8例患者中5例合并急性肠道移植物抗宿主病（GVHD），治疗有效组患者无一例合并肠道GVHD；8例治疗无效患者中5例外周血破碎红细胞比例〉5％，而治疗有效组破碎红比例最高为4％；治疗无效患者LDH及肌酐中位水平均高于治疗有效组，分别为826（674-1310）U／L对636（309-941）U／L及127（70-215）μmol／L对56（22-101）μmol／L。结论TA—TMA是allo—HSCT后的一类严重并发症，可导致全身多器官功能损伤，即使采取治疗早期病死率仍较高，疗效与病情轻重及有无并发症有关。

Objective To analyze the clinical characteristics, treatment and prognosis of 16 allogeneic hematopoietic stem cell transplantation （allo-HSCT） -associated thrombotic microangiopathy （TA-TMA） patients. Methods The clinical data of 16 TA-TMA cases in 852 patients following allo- HSCT from Jan. 2013 to Jun. 2015 in the First Affiliated Hospital of Soochow University were retrospectively analyzed. Results Of all the 852 allo-HSCT recipients, 16 patients were diagnosed as TATMA and the 1-year cumulative incidence of TA-TMA was （2.3±0.6）%. Among them, there were 9 males and 7 females, the median age was 41-year-old （12-54）, and the median times of diagnosis of TA-TMA were 72 （21-525） days after HSCT. Additionally, the median platelet counts, hemoglobin, percentage of schistocytes and Lactate dehydrogenase （LDH） levels were 20 （11-36）×10^9/L, 74 （56-99） g/L, 3% （2%- 13%） and 762（309-1 049） U/L, respectively. All 16 cases have normal ADAMTS13 level （over 60%）, 10 patients had neurologic dysfunction and elevated creatinine were seen in 7. The major treatment of TA-TMA was withdrawn of calcineurin inhibitors, plasma exchange and corticosteroids. Finally, 8 patients achieved response after treatment and the other patients died of poor response. Compared with TA-TMA who achieved remission after therapy, those who got no response after interventions presented acute GVHD and they had higher schistocytes （62.5% cases 〉 5% vs all cases ≤4% ）, LDH [ 826 （674-1 310） U/L vs 636 （309-941） U/L] and serum creatinine levels [127 （70-215） μmol/L vs 56 （22- 101） μmol/L]. Conclusion TA-TMA was a severe complication after allo-HSCT, it could progress to multi-organ injury and was associated with poor outcome, the therapeutic efficacy depends on disease severity and coexisted complications.