Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA; Division of Hematology and Oncology, Moffitt Cancer Center, University of South Florida, Tampa, Florida, USA; The Mikael Rayaan Foundation Global Transplantation and Cellular Therapy Consortium, Kansas City, Kansas, USA.
Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA; The Mikael Rayaan Foundation Global Transplantation and Cellular Therapy Consortium, Kansas City, Kansas, USA.
Transpl Immunol. 2024 Dec;87:102135. doi: 10.1016/j.trim.2024.102135. Epub 2024 Oct 4.
Idiopathic Pneumonia Syndrome (IPS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a life-threatening complication with high morbidity and mortality. IPS is thought to arise from damage caused by various inflammatory mediators. This study assesses the effectiveness of Ruxolitinib, a Janus Kinase (JAK) 1 and 2 inhibitor that blocks cytokine production, in combination with corticosteroids (CS) for managing IPS after allo-HSCT, compared to the conventional use of CS alone in a case series and a systematic review of previously published literature.
The study includes a retrospective case series of three patients treated for IPS with Ruxolitinib and CS from the University of Kansas Medical Center and a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement 2020 guidelines. The systematic review encompassed seven studies involving 346 cases including three cases from the case series. Statistical analyses were conducted using SPSS v.25.
The case series included three patients with IPS after allo-HSCT who received ruxolitinib and CS with favorable results. All patients showed substantial improvement with no IPS-associated mortality. Two of the three patients in the case series were discharged on a 2 L nasal cannula, which was later discontinued during follow-up visits, while the third was discharged on room air. There was marked improvement observed on the computed tomography (CT) following the use of ruxolitinib. Of the total 346 cases included in the systematic review, the median age was 46.6 years (Range 5-72), and 62 % were males. The primary disorders were acute leukemia (52 %), chronic myeloid leukemia (12 %), myelodysplastic syndrome (11 %), Lymphoma (10 %), and others (21 %). Stem cell sources were peripheral blood (45 %), bone marrow (49 %), and cord blood (6 %). Donor types involved match unrelated (55 %), match related (36 %), and mismatched related (4.5 %). Most patients received myeloablative conditioning (81 %). Acute GVHD was observed in 47 %, and chronic GVHD in 38 %. The primary treatment was CS (96 %), with limited use of ruxolitinib (1 %) and etanercept (9.5 %). The mortality rate was 63.3 %, whereas in our case series with the use of ruxolitinib, it was zero.
The combination of Ruxolitinib and CS for treating IPS post-allo-HSCT suggested promising results in the case series, with favorable response and improved survival by blocking the cytokine production contributing to IPS. The significant mortality difference in the systematic review supports the need for innovative treatment approaches, highlighting the potential role of Ruxolitinib in CS-refractory cases. Despite the positive outcomes in the case series, the absence of randomized controlled trials emphasizes the necessity for further research.
异基因造血干细胞移植（allo-HSCT）后特发性肺炎综合征（IPS）是一种具有高发病率和死亡率的危及生命的并发症。IPS 被认为是由各种炎症介质引起的损伤引起的。本研究评估了 Ruxolitinib 的有效性，Ruxolitinib 是一种 Janus 激酶（JAK）1 和 2 抑制剂，可阻断细胞因子的产生，与单独使用皮质类固醇（CS）相比，在一项病例系列研究和对先前发表文献的系统评价中，联合 CS 治疗 allo-HSCT 后 IPS 的效果。
该研究包括来自堪萨斯大学医学中心的三名接受 Ruxolitinib 和 CS 治疗 IPS 的患者的回顾性病例系列研究，以及根据 2020 年首选报告项目（PRISMA）声明进行的系统评价。系统评价包括七项研究，涉及 346 例病例，其中包括病例系列中的三个病例。使用 SPSS v.25 进行统计分析。
病例系列包括三名 allo-HSCT 后患有 IPS 的患者，他们接受了 Ruxolitinib 和 CS 治疗，结果良好。所有患者均显示出明显改善，且无 IPS 相关死亡。病例系列中的三名患者中有两名在接受 Ruxolitinib 治疗后在 2L 鼻插管下出院，随后在随访期间停用，第三名在空气房间出院。使用 Ruxolitinib 后观察到 CT 明显改善。在系统评价中纳入的 346 例总病例中，中位年龄为 46.6 岁（范围 5-72），62%为男性。主要疾病为急性白血病（52%）、慢性髓性白血病（12%）、骨髓增生异常综合征（11%）、淋巴瘤（10%）和其他（21%）。干细胞来源为外周血（45%）、骨髓（49%）和脐带血（6%）。供体类型涉及匹配无关（55%）、匹配相关（36%）和不匹配相关（4.5%）。大多数患者接受了清髓性预处理（81%）。观察到急性移植物抗宿主病（GVHD）47%，慢性 GVHD 38%。主要治疗方法为 CS（96%），Ruxolitinib（1%）和依那西普（9.5%）的使用有限。死亡率为 63.3%，而在我们使用 Ruxolitinib 的病例系列中，死亡率为零。
allo-HSCT 后使用 Ruxolitinib 和 CS 联合治疗 IPS 在病例系列中显示出有希望的结果，通过阻断导致 IPS 的细胞因子产生，具有良好的反应和提高的生存率。系统评价中显著的死亡率差异支持需要创新的治疗方法，突出了 Ruxolitinib 在 CS 难治性病例中的潜在作用。尽管病例系列中的结果为阳性，但缺乏随机对照试验强调了进一步研究的必要性。
