Acosta-Medina Aldo A, Sridharan Meera, Go Ronald S, Moyer Ann M, Leung Nelson, Willrich Maria Alice V, Wolf Robert, Kassis Rabee, Manasrah Almothana, Kohorst Mira A, Durani Urshila, Matin Aasiya, Hefazi Mehrdad, Kenderian Saad J, Mangaonkar Abhishek A, Shah Mithun V, Litzow Mark R, Hogan William J, Dingli David, Alkhateeb Hassan B
Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Am J Hematol. 2025 May;100(5):830-839. doi: 10.1002/ajh.27651. Epub 2025 Mar 6.
Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial dysfunction syndrome observed after allogeneic hematopoietic cell transplant (alloHCT). Our aim was to externally validate the impact of high-risk features on the clinical outcomes of adult patients meeting the updated TA-TMA harmonizing criteria. Between 2005 and 2022, 99 patients were diagnosed with TA-TMA at Mayo Clinic Rochester (incidence 6.2%) after a median of 137 days post alloHCT (IQR: 34-283 days). The development of TA-TMA was associated with an inferior overall survival posttransplant (HR: 3.8, 95% CI: 2.97-4.72). High-risk features, including concomitant infection, acute graft-versus-host disease (GVHD), and organ dysfunction, were associated with poor survival, while LDH elevation was not associated with inferior outcomes. The most common treatment strategy for TA-TMA was discontinuation of calcineurin or mTOR inhibitors in 80 (81%) patients. Thirty (37.5%) patients experienced worsening of GVHD with this strategy, of which 26 (86.7%) patients had died at last follow-up. The most common cause of death among these patients was worsening GVHD (69%; n = 18), followed by infection (11%; n = 3), disease relapse (8%; n = 2), other/unknown causes (8%; n = 2), or TA-TMA (4%; n = 1). Objective response rate (ORR) to initial treatment for the cohort was 56.6%. Eculizumab was used in 11 patients with an observed ORR of 70%, including 5 complete responses. In conclusion, TA-TMA remains a significant contributor to non-relapse mortality and is associated with worse survival following alloHCT. Not all high-risk features, particularly LDH elevation, have consistently demonstrated a negative impact in adult cohorts. Patients with TA-TMA may benefit from immune suppression dose adjustment, rather than a discontinuation, and the addition of complement-directed therapy, particularly among high-risk patients.
移植相关血栓性微血管病（TA-TMA）是一种在异基因造血细胞移植（alloHCT）后观察到的内皮功能障碍综合征。我们的目的是对外验证高危特征对符合更新后的TA-TMA统一标准的成年患者临床结局的影响。2005年至2022年期间，梅奥诊所罗切斯特院区有99例患者在alloHCT后中位137天（四分位间距：34-283天）被诊断为TA-TMA（发病率6.2%）。TA-TMA的发生与移植后总体生存率较低相关（风险比：3.8，95%置信区间：2.97-4.72）。包括合并感染、急性移植物抗宿主病（GVHD）和器官功能障碍在内的高危特征与生存不良相关，而乳酸脱氢酶（LDH）升高与较差结局无关。TA-TMA最常见的治疗策略是80例（81%）患者停用钙调神经磷酸酶或mTOR抑制剂。30例（37.5%）患者采用该策略后GVHD恶化，其中26例（86.7%）患者在最后一次随访时死亡。这些患者最常见的死亡原因是GVHD恶化（69%；n = 18），其次是感染（11%；n = 3）、疾病复发（8%；n = 2）、其他/不明原因（8%；n = 2）或TA-TMA（4%；n = 1）。该队列初始治疗的客观缓解率（ORR）为56.6%。11例患者使用了依库珠单抗，观察到的ORR为70%，包括5例完全缓解。总之，TA-TMA仍然是导致非复发死亡率的重要因素，并且与alloHCT后的较差生存相关。并非所有高危特征，特别是LDH升高，在成年队列中都一直显示出负面影响。TA-TMA患者可能从免疫抑制剂量调整而非停用中获益，以及从补充定向治疗中获益，特别是在高危患者中。
