Composite biomarker panel for prediction of severity and diagnosis of acute GVHD with T-cell-depleted allogeneic stem cell transplants-single centre pilot study

J Clin Pathol. 2017 Oct;70(10):886-890. doi: 10.1136/jclinpath-2017-204399. Epub 2017 Apr 27.

Abstract

Aims: Acute graft-versus-host disease (aGVHD) is a leading cause of morbidity and mortality following allogeneic haematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the clinical utility of a composite biomarker panel to help identify individuals at risk of developing aGVHD, and to help predict and differentiate between severity of aGVHD following T-cell-depleted allogeneic HSCT.

Methods: We retrospectively analysed our cohort of biopsy confirmed patients with aGVHD, who underwent T-cell-depleted HSCT and matched them with negative controls without any evidence of aGVHD. Post-transplant serum samples on days 0 and 7 and at onset of aGVHD were analysed for elafin, regenerating islet-derived 3-α, soluble tumour necrosis factor receptor-1, soluble interleukin-2 receptor-α and hepatocyte growth factor. Biomarker data were combined as composite panels A-F (table 2) using logistic regression analysis. Receiver operating characteristic analysis was performed to study sensitivity and specificity of the composite panels.

Results: Our composite biomarker panels significantly differentiated between aGVHD and no GVHD patients at time of onset (panel E) and reliably predicted severity of GVHD grades at days 0 and 7 post-transplant (panels B and D). The area under the curve for the composite panel at time of onset was 0.65 with specificity, sensitivity, positive and negative predictive values of 100%, 55.6%, 100% and 78.9%, respectively (p=0.03).

Conclusions: This pilot data support the usefulness of these composite biomarker panels in the prediction of severity and diagnosis of aGVHD in patients undergoing T-cell-depleted reduced intensity allogeneic HSCT.

Keywords: DIAGNOSTICS; GVH; HAEMATO-ONCOLOGY; IMMUNOCOMPRISED HOST; STEM CELL TRANSPLANTS.

MeSH terms

  • Adult
  • Area Under Curve
  • Biomarkers / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Graft vs Host Disease / blood
  • Graft vs Host Disease / diagnosis*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • ROC Curve
  • Retrospective Studies
  • Sensitivity and Specificity
  • T-Lymphocytes / immunology
  • Transplantation, Homologous

Substances

  • Biomarkers