10岁以下儿童和10岁以上儿童/成人慢性移植物抗宿主病的风险生物标志物

IF 7.1 1区医学 Q1 HEMATOLOGY

Blood advances Pub Date : 2025-09-18 DOI:10.1182/bloodadvances.2025016624

Anna Crawford Ferreira, Debjani Dutta, Courtney M Rowan, Jamie Renbarger, Kenneth R Cooke, Paul A Carpenter, Robert A Krance, Christine N Duncan, Conrad Russell Y Cruz, David A Jacobsohn, Catherine M Bollard, Elizabeth Hill, Sophie Paczesny

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引用次数: 0

摘要

目前缺乏对儿科患者同种异体造血细胞移植（HCT）后慢性GVHD （cGVHD）风险生物标志物的评估。我们对318例患者进行了前瞻性研究：（129例儿童≤10岁，189例儿童/成人≤10岁）。6种血浆生物标志物[CXCL9，白细胞介素-1受体样1 (IL1RL1)，再生胰岛衍生-3- α (REG3α)，基质金属肽酶-3 (MMP3)， dickkopf-WNT信号通路抑制剂-3 （DKK3）和sCD163]在hct后第100天(D)进行评估。我们对cGVHD进行了D100里程碑分析，对≤10年和bbb10年进行了分层，并使用约登指数对标记进行了二分类。在两组中，IL1RL1与未来cGVHD相关：≤10年[风险比（HR） 95%可信区间（CI）： 2.35 (1.08, 5.12), p=0.03]和>10年[HR (95% CI): 2.09 (1.22, 3.59), p=0.01]， DKK3:≤10年[HR (95% CI): 2.39 (1.05, 5.42), p=0.04]和>10年[HR (95% CI): 2.10 (1.20, 3.66), p=0.01]。CXCL9、REG3α和MMP3与bb0 ~ 10岁患者的cGVHD相关[HR (95% CI): CXCL9: 2.37 (1.08, 5.21), p=0.03；REG3α: 1.71 (1.03, 2.82), p=0.04；MMP3: 2.36 (1.33, 4.16), p=0.003]。该5个指标组cGVHD风险在儿童≤10岁和儿童/成人>10年的AUC分别为0.71和0.72，在儿童≤10岁和儿童/成人>10年中/重度cGVHD风险在儿童≤10年和儿童/成人>10年的AUC分别为0.86和0.80。5种生物标志物（IL1RL1、REG3α、MMP3、DKK3和sCD163）与两组TRM相关。hct后3个月测量的生物标志物可预测≤10岁儿童和10岁以下儿童/成人cGVHD和TRM的易感性和/或预后，允许额外的风险分层。

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Risk Biomarkers of Chronic Graft-versus-host disease in Children aged 10 years or younger and Children/adults Older than 10 years.

Assessment of risk biomarkers of chronic GVHD (cGVHD) after allogeneic hematopoietic cell transplantation (HCT) in pediatric patients is lacking. We conducted a prospective study of 318 patients: (129 children ≤10 years and 189 children/adults >10 years). Six plasma biomarkers [CXCL9, interleukin-1 receptor-like 1 (IL1RL1), regenerating-islet-derived-3-alpha (REG3α), matrix metallopeptidase-3 (MMP3), dickkopf-WNT signaling pathway inhibitor-3 (DKK3), and sCD163] were assessed at Day (D)100 post-HCT. We performed D100 landmark analyses for cGVHD, stratifying at ≤10 years vs >10 yr and dichotomizing markers using Youden's index. IL1RL1 is associated with future cGVHD in both groups: ≤10 years [hazard ratio (HR) 95% confidence interval (CI): 2.35 (1.08, 5.12), p=0.03] and >10 years [HR (95% CI): 2.09 (1.22, 3.59), p=0.01], as is DKK3: ≤10 years [HR (95% CI): 2.39 (1.05, 5.42), p=0.04] and >10 years [HR (95% CI): 2.10 (1.20, 3.66), p=0.01]. CXCL9, REG3α, and MMP3 are associated with cGVHD in patients >10 years [HR (95% CI): CXCL9: 2.37 (1.08, 5.21), p=0.03; REG3α: 1.71 (1.03, 2.82), p=0.04; MMP3: 2.36 (1.33, 4.16), p=0.003]. This 5-marker panel has an AUC of 0.71 in children ≤10 years and 0.72 in children/adults >10 years for cGVHD risk, and 0.86 in children ≤10 years and 0.80 in children/adults >10 years for moderate/severe cGVHD risk. A 5-biomarker panel (IL1RL1, REG3α, MMP3, DKK3, and sCD163) was associated with TRM in both groups. Biomarkers measured 3 months post-HCT predict susceptibility and/or are prognostic for cGVHD and TRM in both children aged ≤10 years and children/adults >10 years, allowing for additional risk stratification.

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来源期刊

Blood advances Medicine-Hematology

CiteScore

12.70

自引率

2.70%

发文量

840

期刊介绍： Blood Advances, a semimonthly medical journal published by the American Society of Hematology, marks the first addition to the Blood family in 70 years. This peer-reviewed, online-only, open-access journal was launched under the leadership of founding editor-in-chief Robert Negrin, MD, from Stanford University Medical Center in Stanford, CA, with its inaugural issue released on November 29, 2016. Blood Advances serves as an international platform for original articles detailing basic laboratory, translational, and clinical investigations in hematology. The journal comprehensively covers all aspects of hematology, including disorders of leukocytes (both benign and malignant), erythrocytes, platelets, hemostatic mechanisms, vascular biology, immunology, and hematologic oncology. Each article undergoes a rigorous peer-review process, with selection based on the originality of the findings, the high quality of the work presented, and the clarity of the presentation.