Risk biomarkers of chronic GVHD in children aged 10 years or younger and children/adults older than 10 years

Abstract

Assessment of risk biomarkers of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT) in pediatric patients is lacking. We conducted a prospective study of 318 patients (129 children aged ≤10 years and 189 children/adults aged >10 years). Six plasma biomarkers (C-X-C motif chemokine ligand 9 [CXCL9], interleukin-1 receptor-like 1 [IL1RL1], regenerating islet-derived 3-α [REG3α], matrix metallopeptidase-3 [MMP3], dickkopf-WNT signaling pathway inhibitor-3 [DKK3], and sCD163) were assessed at day 100 after HCT. We performed day-100 landmark analyses for cGVHD, stratifying at age ≤10 years vs >10 years and dichotomizing markers using the Youden index. IL1RL1 associated with future cGVHD in both age groups, as did DKK3. CXCL9, REG3α, and MMP3 are associated with cGVHD in patients aged >10 years. This 5-marker panel has an area under the curve (AUC) of 0.71 in children aged ≤10 years and 0.72 in children/adults aged >10 years for cGVHD risk, and an AUC of 0.86 in children aged ≤10 years and 0.80 in children/adults aged >10 years for moderate/severe cGVHD risk. A 5-biomarker panel (IL1RL1, REG3α, MMP3, DKK3, and sCD163) was associated with transplant-related mortality (TRM) in both age 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 aged >10 years, allowing for additional risk stratification.