Hematopoietic Cellular Therapy Program, Department of Medicine, University of Chicago Medicine, Chicago, IL.
Department of Hematological Malignancies and Stem Cell Transplantation, Research Institute of Marques de Valdecilla (IDIVAL), Santander, Spain.
Blood Adv. 2022 Nov 22;6(22):5898-5907. doi: 10.1182/bloodadvances.2022007381.
Endothelial activation and stress index (EASIX) predicts nonrelapse mortality (NRM) when assessed before hematopoietic cell transplantation (HCT). We sought to determine whether changes in EASIX after HCT may be an informative marker of NRM. We evaluated 509 adults who underwent reduced intensity, unmodified (N = 149, 29%), or myeloablative ex vivo CD34+-selected allogeneic HCT (allo-HCT) (N = 306, 71%) between 2008 and 2016. Patients who underwent unmodified allo-HCT received tacrolimus-based graft-versus-host disease (GVHD) prophylaxis, whereas CD34+-selected patients received no planned immunosuppression. EASIX (lactate dehydrogenase × creatinine/platelet count) was calculated continuously until 1-year after HCT. Log transformation using base 2 (log2) was applied to all EASIX variables to reduce skew. In total, 360 patients (71%) received CD34+-selected and 149 (29%) unmodified allo-HCT. Among all patients, EASIX scores increased rapidly, peaked at day +8, then declined rapidly until day +33. Thereafter, scores declined gradually but remained above the pre-HCT baseline. In unmodified HCT, scores appeared higher over time than in CD34+-selected patients. EASIX discrimination of NRM was highest around day +180 (concordance index = 0.85) in both platforms, but the prognostic impact of EASIX across time points differed between the 2 platforms. Mean EASIX scores were higher in men (mean log2 +0.52) and in patients who developed grade 2 to 4 GVHD (+0.81) and lower in patients who received matched vs mismatched donors (-0.81, all P < .01). EASIX scores are dynamic and variably concordant with NRM when analyzed longitudinally, and patterns differ between HCT platforms. Compared to pre-HCT evaluation, post-HCT EASIX scores may better predict risk of NRM as patients acquire additional endothelial injury and toxicities.
内皮细胞激活和应激指数 (EASIX) 可预测造血细胞移植 (HCT) 前的非复发死亡率 (NRM)。我们试图确定 HCT 后 EASIX 的变化是否可以作为 NRM 的信息标志物。我们评估了 2008 年至 2016 年间接受低强度、未修饰 (N=149，29%) 或体外 CD34+选择的同种异体 HCT (allo-HCT) (N=306，71%) 的 509 名成年人。接受未修饰 allo-HCT 的患者接受他克莫司为基础的移植物抗宿主病 (GVHD) 预防，而 CD34+选择的患者未接受计划免疫抑制。EASIX(乳酸脱氢酶×肌酐/血小板计数)在 HCT 后 1 年内连续计算。所有 EASIX 变量均采用以 2 为底的对数转换 (log2) 以减少偏度。共有 360 名患者 (71%) 接受了 CD34+选择，149 名患者 (29%) 接受了未修饰的 allo-HCT。在所有患者中，EASIX 评分迅速升高，在第+8 天达到峰值，然后迅速下降，直到第+33 天。此后，评分逐渐下降，但仍高于 HCT 前基线。在未修饰的 HCT 中，随着时间的推移，评分似乎高于 CD34+选择的患者。在两个平台中，EASIX 对 NRM 的区分度在第+180 天左右最高 (一致性指数=0.85)，但 EASIX 在不同时间点的预后影响在两个平台之间有所不同。男性的平均 EASIX 评分较高 (平均 log2+0.52)，发生 2 至 4 级 GVHD 的患者评分较高 (+0.81)，而接受匹配供体与不匹配供体的患者评分较低 (-0.81，均 P<0.01)。EASIX 评分是动态的，并且在进行纵向分析时与 NRM 大致一致，并且在 HCT 平台之间存在差异。与 HCT 前评估相比，HCT 后 EASIX 评分可能更好地预测 NRM 风险，因为患者会出现额外的内皮损伤和毒性。
