New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT
New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT
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DOI：
10.1182/bloodadvances.2019001315
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发表时间：
2020-06-09
期刊：
影响因子：
7.5
通讯作者：
Veys, Paul
中科院分区：
文献类型：
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作者：
Elfeky, Reem;Lucchini, Giovanna;Veys, Paul
本研究旨在确定接受造血干细胞移植（HSCT）的儿童发生移植相关血栓性微血管病（TA-TMA）的风险状况。 2013 年至 2016 年间，439 名儿童在英国 2 个跨区域中心接受了 474 例 HSCT。 HSCT 后平均 153 天，441 例可评估病例中，有 25 例 (5.6%) 发生 TA-TMA，没有中心变异的证据。性别、基础疾病、调理强度、全身照射调理、钙调神经磷酸酶抑制剂的使用、静脉闭塞性疾病和病毒再激活不影响 TA-TMA 的发展。供体类型：匹配的兄弟姐妹供体/匹配的家庭供体与匹配的无关供体与不匹配的无关供体/单倍体-HSCT，显示出TA-TMA发展趋势，分别为1.8%、6.1%和8.3%。活动性合并症的存在与 TA-TMA 风险增加相关； 13% vs 没有合并症的情况下为 3.7%。接受 > 1 次移植的患者发生 TA-TMA 的风险高出三倍。急性移植物抗宿主病 (aGVHD) III 至 IV 级患者的 TA-TMA 率显着高于 0 至 II 级急性移植物抗宿主病 (aGVHD) 患者。多变量分析显示，存在活动性合并症、>1 次移植、III 至 IV 级 aGVHD 是 TA-TMA 的危险因素（优势比 [OR]：分别为 5.1、5.2 和 26.9），而使用环孢素 A/他克莫司为基础的 GVHD 预防不是 TA-TMA 的危险因素（OR：0.3）。活动性合并症、后续移植和 III 至 IV 级 aGVHD 是 TA-TMA 的重要危险因素。 TA-TMA可能代表血管GVHD的一种形式，因此，持续控制aGVHD对于防止与GVHD相关的TA-TMA恶化很重要。
This study aimed to identify a risk profile for development of transplant-associated thrombotic microangiopathy (TA-TMA) in children undergoing hematopoietic stem cell transplantation (HSCT). Between 2013 and 2016, 439 children underwent 474 HSCTs at 2 supraregional United Kingdom centers. At a median of 153 days post-HSCT, TA-TMA occurred among 25 of 441 evaluable cases (5.6%) with no evidence of center variation. Sex, underlying disease, intensity of the conditioning, total body irradiation-based conditioning, the use of calcineurin inhibitors, venoocclusive disease, and viral reactivation did not influence the development of TA-TMA. Donor type: matched sibling donor/matched family donor vs matched unrelated donor vs mismatched unrelated donor/haplo-HSCT, showed a trend toward the development of TA-TMA in 1.8% vs 6.1% vs 8.3%, respectively. Presence of active comorbidity was associated with an increased risk for TA-TMA; 13% vs 3.7% in the absence of comorbidity. The risk of TA-TMA was threefold higher among patients who received >1 transplant. TA-TMA rates were significantly higher among patients with acute graft-versus-host disease (aGVHD) grades III to IV vs aGVHD grade 0 to II. On multivariate analysis, the presence of active comorbidity, >1 transplant, aGVHD grade III to IV were risk factors for TA-TMA (odds ratio [OR]: 5.1, 5.2, and 26.9; respectively), whereas the use of cyclosporine A/tacrolimus-based GVHD prophylaxis was not a risk factor for TA-TMA (OR: 0.3). Active comorbidity, subsequent transplant, and aGVHD grades III to IV were significant risk factors for TA-TMA. TA-TMA might represent a form of a vascular GVHD, and therefore, continuing control of aGVHD is important to prevent worsening of TA-TMA associated with GVHD.