Transplantation Research Center, Brigham and Women's Hospital, Boston, Massachusetts.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Biol Blood Marrow Transplant. 2018 Nov;24(11):2344-2353. doi: 10.1016/j.bbmt.2018.05.010. Epub 2018 May 11.
Transplantation-associated thrombotic microangiopathy (TA-TMA) is a serious complication of hematopoietic stem cell transplantation (HSCT). We characterized the incidence, risk factors, and long-term outcomes associated with TA-TMA by performing a comprehensive review of all adult patients (n = 1990) undergoing allogeneic HSCT at the Dana Farber Cancer Institute/Brigham and Women's Hospital between 2005 and 2013. Using the City of Hope criteria, we identified 258 patients (13%) with "definite" TMA and 508 patients (26%) with "probable" TMA. Mismatched donor transplantation (subdistribution hazard ratio [sHR], 1.79; 95% confidence interval [CI], 1.17 to 2.75; P = .007), sirolimus-containing graft-versus-host disease prophylaxis (sHR, 1.73; 95% CI, 1.29 to 2.34; P < .001), myeloablative conditioning (sHR, 1.93, 95% CI, 1.38 to 2.68; P < .001), and high baseline lactate dehydrogenase (LDH) level (sHR, 1.64; 95% CI, 1.26 to 2.13; P < .001) were associated with definite TMA. Moreover, positive cytomegalovirus serostatus (sHR, 1.41; 95% CI, 1.16 to 1.71; P < .001), high and very high disease risk index (sHR, 1.48; 95% CI, 1.12 to 1.96, P = .007), and high baseline LDH level (sHR, 1.25; 95% CI, 1.05 to 1.49; P = .011) were associated with probable TMA. In multivariable analyses, definite and probable TMA were each independently associated with higher mortality (HR, 5.24; 95% CI, 4.43 to 6.20 and HR, 2.12; 95% CI, 1.84 to 2.44, respectively), and long-term kidney dysfunction (HR, 5.43; 95% CI, 4.61 to 6.40 and HR, 2.20; 95% CI, 1.92 to 2.51, respectively). Definite and probable TMA were also independently associated with an increased risk of nonrelapse mortality and shorter progression-free survival. Our findings indicate that TA-TMA is common following HSCT and is independently associated with increased risk of death and kidney dysfunction.
移植相关血栓性微血管病(TA-TMA)是造血干细胞移植(HSCT)的严重并发症。我们通过对 2005 年至 2013 年在丹娜法伯癌症研究所/布莱根妇女医院接受异基因 HSCT 的所有成年患者(n=1990)进行全面回顾,描述了 TA-TMA 的发生率、危险因素和长期结局。使用希望之城标准,我们确定了 258 例(13%)“明确”TMA 和 508 例(26%)“可能”TMA。供者不匹配移植(亚分布风险比 [sHR],1.79;95%置信区间 [CI],1.17 至 2.75;P=0.007)、包含西罗莫司的移植物抗宿主病预防(sHR,1.73;95%CI,1.29 至 2.34;P<0.001)、清髓性调理(sHR,1.93,95%CI,1.38 至 2.68;P<0.001)和高基线乳酸脱氢酶(LDH)水平(sHR,1.64;95%CI,1.26 至 2.13;P<0.001)与明确 TMA 相关。此外,巨细胞病毒血清阳性(sHR,1.41;95%CI,1.16 至 1.71;P<0.001)、高和极高疾病风险指数(sHR,1.48;95%CI,1.12 至 1.96,P=0.007)和高基线 LDH 水平(sHR,1.25;95%CI,1.05 至 1.49;P=0.011)与可能的 TMA 相关。在多变量分析中,明确和可能的 TMA 与更高的死亡率(HR,5.24;95%CI,4.43 至 6.20 和 HR,2.12;95%CI,1.84 至 2.44)和长期肾功能障碍(HR,5.43;95%CI,4.61 至 6.40 和 HR,2.20;95%CI,1.92 至 2.51)独立相关,明确和可能的 TMA 也与非复发死亡率增加和无进展生存期缩短独立相关。我们的研究结果表明,TA-TMA 在 HSCT 后很常见,与死亡风险和肾功能障碍增加独立相关。