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

Abstract

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.