患者报告的结果 (PRO) 捕捉健康的主观社会决定因素 (SDOH)，它可以通过压力反应途径影响健康结果。逆境保守转录反应（CTRA）是一种应激介导的促炎症转录组模式，与不良造血细胞移植（HCT）结果有关。本研究探讨了同种异体 HCT 受者移植前 CTRA 与患者报告的 SDOH 之间的关系。在这项横断面研究中，HCT 前 SDOH 相关 PRO 包括 36 项简短健康调查 (SF-36) 和癌症治疗骨髓移植功能评估 (FACT-BMT)。 CTRA 通过全血样本的 RNA 测序进行评估，利用混合效应线性回归模型将 CTRA 表达与 PRO 评分相关联，同时控制年龄、性别、种族、疾病和体能状态。在 n=121 名患者中，中位年龄为 54 岁，其中 42% 为女性，91% 为白人。在 FACT-BMT 分数较低的参与者中，CTRA 升高（p=0.003），包括一般部分（p=0.003）和 BMT 特定部分（p=0.014）。影响是由社会福祉领域驱动的（p=0.0001）。这对应于患者报告的 SDOH 中 4-SD 范围内 CTRA RNA 表达的 8-15% 差异。辅助生物信息学分析证实了健康与促炎转录通路活性（CREB、NF-kB 和 AP-1）降低之间的关联。总之，经历不利社会条件的 HCT 患者在移植前血液样本中表现出较高的 CTRA 表达。这些数据突出了社会福祉和社区背景的生物学后遗症，并提出了社会梯度对 HCT 结果影响的潜在分子机制。针对这一途径可以优化这一高危人群的治疗结果。版权所有 © 2023 美国血液学会。

Patient-reported outcomes (PROs) capture subjective social determinants of health (SDOH), which can affect health outcomes through the stress response pathway. The Conserved Transcriptional Response to Adversity (CTRA) is a stress-mediated pro-inflammatory transcriptomic pattern that has been linked to adverse hematopoietic cell transplant (HCT) outcomes. This study examined the association of pre-transplant CTRA with patient-reported SDOH in allogeneic HCT recipients. In this cross-sectional study, pre-HCT SDOH-related PROs included the 36-Item Short Form Health Survey (SF-36) and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT). CTRA was assessed by RNA sequencing of whole blood specimens, with mixed effects linear regression models relating CTRA expression to PRO scores while controlling for age, sex, race, disease, and performance status. Among n=121 patients, median age was 54 years, 42% were female, and 91% White. CTRA was elevated in participants reporting lower scores on the FACT-BMT (p=0.003), including the General (p=0.003) and BMT-specific (p=0.014) components. Effects were driven by the Social Well-Being domain (p=0.0001). This corresponded to an 8-15% difference in CTRA RNA expression across a 4-SD range in patient-reported SDOH. Ancillary bioinformatics analyses confirmed the association of well-being with reduced pro-inflammatory transcription pathway activity (CREB, NF-kB, and AP-1). In conclusion, HCT patients who experience unfavorable social conditions show elevated CTRA expression in pre-transplant blood samples. These data highlight the biologic sequelae of social well-being and community context and suggest a potential molecular mechanism for the impact of social gradients in HCT outcomes. Targeting this pathway could optimize outcomes in this high-risk population.Copyright © 2023 American Society of Hematology.