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Region Hovedstaden - en del af Københavns Universitetshospital
E-pub ahead of print

Pre-Transplantation Plasma ST2 Level as a Prognostic Biomarker of 1-Year Non-Relapse Mortality in Allogeneic Hematopoietic Cell Transplantation

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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BACKGROUND: Soluble ST2 is established as a prognostic biomarker of non-relapse mortality (NRM) when measured early after allogeneic hematopoietic cell transplantation (HCT). However, less is known about the prognostic value of ST2 measured before transplantation.

OBJECTIVE: We hypothesized that the pre-transplantation plasma ST2 level was associated with 1-year NRM and could add to our current prognostic assessment. Moreover, we aimed to investigate the associations between pre-transplantation plasma ST2 levels and patient characteristics and other plasma biomarkers and to reproduce previous associations between post-transplantation plasma ST2 levels and transplant outcomes.

STUDY DESIGN: We conducted a cohort study of 374 adults who received an allogeneic HCT at our center between July 2015 and December 2019 (median age 59 years; 55% received non-myeloablative conditioning). ST2 was measured by an enzyme-linked immunosorbent assay in stored plasma samples obtained pre-transplantation (at a median of 23 days before HCT) and post-transplantation at days +7 and +14. A logistic regression model of 1-year NRM was fitted using an a priori-defined set of covariates consisting of age, the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and conditioning intensity (myeloablative vs. non-myeloablative), to which the pre-transplantation ST2 level was added as a variable to assess its incremental prognostic value. Models were also fitted of 1-year all-cause mortality, relapse, and grade II-IV acute graft-versus-host disease (GvHD) for pre- and post-transplantation ST2 levels.

RESULTS: The median pre-transplantation plasma ST2 level was 20.4 ng/ml (Q1, Q3: 15.2, 27.2 ng/ml). Pre-transplantation ST2 levels were higher in males (median 22.2 vs. 18.1 ng/ml in females, p < 0.001) and were correlated with HCT-CI (Spearman's ρ = 0.18, p < 0.001), body mass index (ρ = 0.10, p = 0.05), and plasma levels of C-reactive protein (ρ = 0.34, p < 0.001), creatinine (ρ = 0.17, p = 0.001), and albumin (ρ = -0.17, p < 0.001). Pre-transplantation ST2 levels added prognostic information about 1-year NRM to age, HCT-CI, and conditioning intensity (adjusted odds ratio [OR] of 1-year NRM per 10 ng/ml increase in ST2: 1.32; 95% confidence interval [CI]: 1.05, 1.65, p = 0.02). While adding pre-transplantation ST2 levels did not notably improve model discrimination (ΔAUC = 0.675-0.674 = 0.001), it increased the diversity of the predicted risks (Likelihood ratio test p = 0.02). Pre-transplantation ST2 levels were also prognostic of 1-year all-cause mortality (adjusted OR per 10 ng/ml increase: 1.23; 95% CI: 1.02, 1.48, p = 0.03), but not of relapse (p = 0.47) or acute GvHD (p = 0.81). Plasma ST2 levels at day +7 were prognostic of 1-year NRM, all-cause mortality, relapse, and acute GvHD, whereas levels at day +14 were prognostic of 1-year NRM and all-cause mortality.

CONCLUSION: Pre-transplantation plasma ST2 levels added prognostic information about 1-year NRM to age, HCT-CI, and conditioning intensity. Our results suggest that ST2 has potential as a biomarker of pre-transplantation vulnerability and that it should be considered in future developments of prediction models of NRM after allogeneic HCT.

OriginalsprogEngelsk
TidsskriftTransplantation and cellular therapy
ISSN2666-6367
DOI
StatusE-pub ahead of print - 11 nov. 2022

Bibliografisk note

Copyright © 2022. Published by Elsevier Inc.

ID: 85822138