Key Points

  • Post-HCT landmark analyses showed that ST2, TNFR1, and REG3α are associated with NRM in children ≤10 years and children/adults >10 years

  • When pre-HCT biomarkers were included, ST2 remained significantly associated with NRM only in children ≤10 years

Assessment of prognostic biomarkers of Non-Relapse Mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT) in the pediatric age group is lacking. To address this need, we conducted a prospective cohort study (NCT02194439). 415 patients at six centers: 170 children ≤10 years and 245 subjects >10 years, including both children and adults were accrued from 2013 to 2018. Four plasma biomarkers [stimulation-2 (ST2), interleukin-6, regenerating-islet-derived-3-alpha (REG3α) and tumor-necrosis-factor-receptor-1 (TNFR1)] were assessed pre-HCT and at days +7, +14, +21 post-HCT. We performed landmark analyses for NRM, dichotomizing the cohort at ≤10 years and using each biomarker median as a cutoff for high and low risk groups. Post-HCT biomarker analysis showed that ST2 (>26 ng/mL), TNFR1 (>3441 pg/mL), and REG3α (>25 ng/mL) are associated with NRM in both children ≤10 years [Hazard Ratio (HR) Confidence Intervals (CI): ST2: 9.13 (2.74-30.38), p=0.0003; TNFR1: 4.29 (1.48-12.48), p=0.0073; REG3α: 7.28 (2.05-25.93), p=0.0022] and children/adults >10 years [HR (CI): ST2: 2.60 (1.15-5.86), p=0.021; TNFR1: 2.09 (0.96-4.58), p=0.06; REG3α: 2.57 (1.19-5.55), p=0.016]. When pre-HCT biomarkers were included, only ST2 remained significant in both cohorts. After adjustment for significant covariates (race/ethnicity, malignant disease, graft, GVHD prophylaxis), ST2 remained associated with NRM only in recipients ≤10 years [HR(CI): 4.82 (1.89-14.66), p=0.0056]. Assays of ST2, TNFR1, REG3α in the first 3 weeks following HCT have prognostic value for NRM in both children and adults. ST2 prior to HCT is a prognostic biomarker for NRM in children ≤10 years allowing for additional stratification.

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