急性移植物抗宿主病患者发生移植相关血栓性微血管病的危险因素及预后分析

  目的 探讨急性移植物抗宿主病（aGVHD）患者中移植相关血栓性微血管病（TA-TMA）发生的危险因素和影响TA-TMA预后的因素。方法 选取356例在北京大学血液病研究所接受异基因造血干细胞移植后发生aGVHD的患者为研究人群，选取33例移植后发生TA-TMA的患者作为病例组，以危险集抽样的方法在同一队列中随机选取年龄和随访时间匹配的患者组成对照组（77例）。比较两组间的危险因素和预后情况。结果 TA-TMA的中位发生时间为移植后3.5（1.2~23.0）个月。TA-TMA发病距aGVHD诊断的中位时间为25（7~257）d。aGVHD发生时间、起始严重程度、一线治疗失败及二线治疗中使用他克莫司与aGVHD患者发生TA-TMA独立相关，具有2种以上危险因素的患者TA-TMA风险明显升高（OR=210.0，P=0.000）。22例（66.7%）TA-TMA患者死亡，而进展型TA-TMA是预后的惟一不良影响因素。各种治疗方法均不能改善TA-TMA患者的预后。结论 aGVHD的多种特点与TA-TMA相关，便于筛选出aGVHD合并TA-TMA的高危患者，并指导选择更合理的治疗方案。   

The risk factors and prognosis of transplant-associated thrombotic microangiopathy following acute graft-versus-host disease

Objective To investigate the risk factors and prognosis of transplant-associated thrombotic microangiopathy (TA-TMA) following acute graft-versus-host disease (aGVHD), and to evaluate the factors that might influence the prognosis of TA-TMA.Methods A nested case-control study was designed. Cases with TA-TMA (n=33) and controls (n=77) matched for age at allogeneic hematopoietic stem cell transplantation (allo-HSCT) and length of follow-up were identified from a cohort of 356 patients who suffered from aGVHD after allo-HSCT between 2009 and 2011.Results The median time to presentation of TA-TMA was 3.5 （1.2-23.0） months post-HSCT. The median time from diagnosis and first-line treatment failure of aGVHD to TA-TMA diagnosis was 25 (7-257) days and 15(5-257) days, respectively. aGVHD occurring beyond 60 days after allo-HSCT, initial grade Ⅲ-Ⅳ aGVHD, first-line treatment failure and receiving tacrolimus as second-line treatment were independently associated with the occurrence of TA-TMA, and patients with two or more risk factors were at higher risk (OR=210.0, P=0.000). Twenty-two(66.7%) TA-TMA patients died. Progressive TA-TMA was the significantly adverse factor affecting the survival of TA-TMA cases. None of therapies could improve prognosis of patients with TA-TMA.Conclusion Many characteristics of aGVHD were associated with TA-TMA, which help us to identify the individuals who are at higher risk of developing TA-TMA following aGVHD and to select the more reasonable GVHD therapeutic strategies.