TY - JOUR
T1 - Assessment of ST2 for risk of death following graft-versus-host disease in pediatric and adult age groups
AU - Rowan, Courtney M.
AU - Pike, Francis
AU - Cooke, Kenneth R.
AU - Krance, Robert
AU - Carpenter, Paul A.
AU - Duncan, Christine
AU - Jacobsohn, David A.
AU - Bollard, Catherine M.
AU - Cruz, Conrad Russell Y.
AU - Malatpure, Abhijeet
AU - Farag, Sherif S.
AU - Renbarger, Jamie
AU - Liu, Hao
AU - Bakoyannis, Giorgos
AU - Hanash, Samir
AU - Paczesny, Sophie
N1 - Publisher Copyright:
© 2020 by The American Society of Hematology.
PY - 2020/4/23
Y1 - 2020/4/23
N2 - Assessment of prognostic biomarkers of nonrelapse 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 with 415 patients at 6 centers: 170 were children age 10 years or younger and 245 were patients older than age 10 years (both children and adults were accrued from 2013 to 2018). The following 4 plasma biomarkers were assessed pre-HCT and at days17,114, and121 post-HCT: Stimulation-2 (ST2), tumor necrosis factor receptor 1 (TNFR1), regenerating islet-derived protein 3a (REG3a), and interleukin-6 (IL-6).We performed landmark analyses for NRM, dichotomizing the cohort at age 10 years or younger 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 REG3a (>25 ng/mL) are associated with NRMin children age 10 years or younger (ST2: Hazard ratio [HR], 9.13; 95% confidence interval [CI], 2.74-30.38; P = .0003; TNFR1: HR, 4.29; 95% CI, 1.48-12.48; P5 .0073; REG3a: HR, 7.28; 95% CI, 2.05-25.93; P =.0022); and in children and adults older than age 10 years (ST2: HR, 2.60; 95% CI, 1.15-5.86; P = .021; TNFR1: HR, 2.09; 95% CI, 0.96-4.58; P = .06; and REG3a: HR, 2.57; 95% CI, 1.19-5.55; P = .016). When pre-HCT biomarkers were included, only ST2 remained significant in both cohorts. After adjustment for significant covariates (race/ethnicity, malignant disease, graft, and graft-versus-host-disease prophylaxis), ST2 remained associated with NRM only in recipients age 10 years or younger (HR, 4.82; 95% CI, 1.89-14.66; P = .0056). Assays of ST2, TNFR1, and REG3a in the first 3 weeks after HCT have prognostic value for NRM in both children and adults. The presence of ST2 before HCT is a prognostic biomarker for NRM in children age 10 years or younger allowing for additional stratification.
AB - Assessment of prognostic biomarkers of nonrelapse 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 with 415 patients at 6 centers: 170 were children age 10 years or younger and 245 were patients older than age 10 years (both children and adults were accrued from 2013 to 2018). The following 4 plasma biomarkers were assessed pre-HCT and at days17,114, and121 post-HCT: Stimulation-2 (ST2), tumor necrosis factor receptor 1 (TNFR1), regenerating islet-derived protein 3a (REG3a), and interleukin-6 (IL-6).We performed landmark analyses for NRM, dichotomizing the cohort at age 10 years or younger 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 REG3a (>25 ng/mL) are associated with NRMin children age 10 years or younger (ST2: Hazard ratio [HR], 9.13; 95% confidence interval [CI], 2.74-30.38; P = .0003; TNFR1: HR, 4.29; 95% CI, 1.48-12.48; P5 .0073; REG3a: HR, 7.28; 95% CI, 2.05-25.93; P =.0022); and in children and adults older than age 10 years (ST2: HR, 2.60; 95% CI, 1.15-5.86; P = .021; TNFR1: HR, 2.09; 95% CI, 0.96-4.58; P = .06; and REG3a: HR, 2.57; 95% CI, 1.19-5.55; P = .016). When pre-HCT biomarkers were included, only ST2 remained significant in both cohorts. After adjustment for significant covariates (race/ethnicity, malignant disease, graft, and graft-versus-host-disease prophylaxis), ST2 remained associated with NRM only in recipients age 10 years or younger (HR, 4.82; 95% CI, 1.89-14.66; P = .0056). Assays of ST2, TNFR1, and REG3a in the first 3 weeks after HCT have prognostic value for NRM in both children and adults. The presence of ST2 before HCT is a prognostic biomarker for NRM in children age 10 years or younger allowing for additional stratification.
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U2 - 10.1182/BLOOD.2019002334
DO - 10.1182/BLOOD.2019002334
M3 - Article
C2 - 31972009
AN - SCOPUS:85089835827
SN - 0006-4971
VL - 135
SP - 1428
EP - 1437
JO - Blood
JF - Blood
IS - 17
ER -