Humes H David, Luckritz Kera, Gorga Stephen, Plomaritas Katie, Hoatlin Sara, Humes Michael, Yessayan Lenar
Department of Internal Medicine (Nephrology), University of Michigan, Ann Arbor, MI, USA.
Innovative Biotherapies, Ann Arbor, MI , USA.
Pediatr Nephrol. 2025 Jun 21. doi: 10.1007/s00467-025-06798-y.
How does a physician decide to use a recently FDA-approved life-saving device in a desperately ill child in which little prior clinical experience is available? This report presents a pediatric patient with neutropenic septic shock and multiorgan failure (MOF) with a 95% chance of death and the availability of a therapeutic device with a completely new approach to treat sepsis. This device, called the selective cytopheretic device (SCD), is a first-in-class autologous immune cell directed therapy. The SCD, when integrated into an extracorporeal blood circuit, has been shown to bind activated neutrophils and monocytes. With a simple pharmacologic maneuver within the device, the bound cells in real time are immunomodulated from a highly pro-inflammatory state to a less inflammatory phenotype. These transformed cells are then released back into the systemic circulation thereby tempering the systemic hyperinflammatory disorder. Since this cell directed therapy focuses on neutrophils, the processing of these cells in a neutropenic state may be a substantive risk resulting in further immunosuppression. On the other hand, the immunomodulation of the circulating neutrophils and monocytes, although sparse, may be beneficial to disrupt the dysregulated inflammatory state responsible for ongoing tissue damage and organ dysfunction. Prior clinical SCD trials excluded patients with neutropenia so that no prior clinical experience was available to make a difficult decision. This report presents the way the medical team approached these issues and made a therapeutic plan that resulted in a positive clinical outcome for the patient.
面对一个身患重病、生命垂危的儿童,而此前几乎没有临床经验可供参考,医生该如何决定是否使用一种最近刚获美国食品药品监督管理局(FDA)批准的救生设备呢?本报告介绍了一名患有中性粒细胞减少性脓毒性休克和多器官功能衰竭(MOF)、死亡几率达95%的儿科患者,以及一种采用全新方法治疗败血症的治疗设备。这种设备称为选择性血细胞去除设备(SCD),是一流的自体免疫细胞导向疗法。已证实,SCD集成到体外血液回路中时,能结合活化的中性粒细胞和单核细胞。通过在设备内进行简单的药理操作,实时将结合的细胞从高度促炎状态免疫调节为炎症较轻的表型。然后将这些转化后的细胞释放回体循环,从而缓解全身炎症亢进症。由于这种细胞导向疗法聚焦于中性粒细胞,在中性粒细胞减少状态下处理这些细胞可能会带来实质性风险,导致进一步的免疫抑制。另一方面,循环中的中性粒细胞和单核细胞的免疫调节虽然作用有限,但可能有助于打破导致持续组织损伤和器官功能障碍的失调炎症状态。此前SCD的临床试验排除了中性粒细胞减少症患者,因此没有先前的临床经验可用于做出艰难的决策。本报告介绍了医疗团队处理这些问题的方式,并制定了一个治疗方案,最终使患者获得了积极的临床结果。