El Jurdi Najla, Herzog Shannon, Shanley Ryan, Holtan Shernan G, MacMillan Margaret L, Weisdorf Daniel J
Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota; Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota; Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
Transplant Cell Ther. 2024 Jun;30(6):616-625. doi: 10.1016/j.jtct.2024.03.011. Epub 2024 Mar 11.
Response to treatment of chronic graft-versus-host disease (cGVHD) may help predict prognosis and outcomes. We hypothesized that the response of cGVHD to treatment and the ability to taper immunosuppression define distinct treatment response categories that differ in terms of risk factors and prognosis. Our aim was to determine specific clinical characteristics and outcomes associated with 3 distinct cGVHD treatment response groups based on the response to and duration of immunosuppressive therapy (IST) as treatment-sensitive (TS), treatment-resistant (TR), and treatment-dependent (TD) cGVHD. This retrospective single-institution cohort study included 1142 consecutive adult and pediatric recipients of allogeneic hematopoietic cell transplantation (HCT) performed for malignant and nonmalignant disorders at the University of Minnesota between 2008 and 2016. All donor, graft, conditioning regimen, and GVHD prophylaxis strategies were included, but only patients who commenced systemic treatment within 30 days of cGVHD diagnosis were included. A total of 185 patients who developed cGVHD necessitating IST within 30 days of cGVHD diagnosis were included in this analysis. At 1 year after cGVHD onset, 13% of the patients were TS, 27% were TD, and 60% were TR (including 14% deceased), whereas at 2 years after cGVHD onset, 29% were TS, 5% were TD, and 66% were TR (including 22% deceased). In a landmark analysis starting at 1 year after cGVHD onset, 5-year failure-free survival (FFS) and overall survival (OS) were lowest in the TR group (FFS, 38%; OS, 70%), with comparable outcomes in the TD (74% and 82%, respectively) and TS (79% for both) groups. Compared to no cGVHD, TR cGVHD was associated with worse OS at 5 years after cGVHD (hazard ratio, 2.09 versus no cGVHD; 95% confidence interval, 1.3 to 3.3; P < .01). Our findings suggest that refining cGVHD classification into 3 treatment response states defines important predictors of early and late clinical outcomes and identifies patients needing more effective treatment.
慢性移植物抗宿主病（cGVHD）的治疗反应可能有助于预测预后和结局。我们假设，cGVHD对治疗的反应以及逐渐减少免疫抑制的能力定义了不同的治疗反应类别，这些类别在危险因素和预后方面存在差异。我们的目的是根据免疫抑制治疗（IST）的反应和持续时间，确定与3种不同的cGVHD治疗反应组相关的特定临床特征和结局，即治疗敏感型（TS）、治疗抵抗型（TR）和治疗依赖型（TD）cGVHD。这项回顾性单机构队列研究纳入了2008年至2016年间在明尼苏达大学为恶性和非恶性疾病接受异基因造血细胞移植（HCT）的1142例连续成年和儿科受者。所有供体、移植物、预处理方案和GVHD预防策略均被纳入，但仅纳入在cGVHD诊断后30天内开始全身治疗的患者。本分析纳入了185例在cGVHD诊断后30天内发生需要IST的cGVHD患者。在cGVHD发病后1年，13%的患者为TS，27%为TD，60%为TR（包括14%死亡）；而在cGVHD发病后2年，29%为TS，5%为TD，66%为TR（包括22%死亡）。在一项从cGVHD发病后1年开始的标志性分析中，TR组的5年无失败生存率（FFS）和总生存率（OS）最低（FFS为38%；OS为70%），TD组（分别为74%和82%）和TS组（均为79%）的结局相当。与无cGVHD相比，TR cGVHD在cGVHD后5年的OS较差（风险比，与无cGVHD相比为2.09；95%置信区间，1.3至3.3；P <.01）。我们的研究结果表明，将cGVHD分类细化为3种治疗反应状态可定义早期和晚期临床结局的重要预测因素，并识别出需要更有效治疗的患者。
