Prediction of graft-versus-host disease: a biomarker panel based on lymphocytes and cytokines

Ann Hematol. 2017 Jul;96(7):1127-1133. doi: 10.1007/s00277-017-2999-5. Epub 2017 Apr 26.

Abstract

Graft-versus-host disease (GvHD) still belongs to the major challenges after allogeneic hematopoietic stem cell transplantation (HSCT). Immune-suppressive therapy against GvHD is a double-edged sword due to risk of infections and relapse. The ability to adapt prophylactic treatment according to the probability of severe GvHD would be an essential advantage for the patients. We analyzed different biomarkers for their potential to predict the development of GvHD in 28 patients who underwent allogeneic HSCT. Blood was taken once directly after hematopoietic engraftment. In this study, patients were monitored for 12 months after HSCT for the occurrence of acute GvHD or acute/chronic GvHD overlap syndrome. Soluble IL-2 receptor and CD4/CD8 T cell ratio were independently associated with the occurrence of GvHD in the observation period. However, the largest area under the receiver operating characteristic curve with 0.90 was observed when a 5-parameter biomarker score based on CD4+ T cells, CD8+ T cells, CD19- CD21+ precursor B cells, CD4/CD8 T cell ratio, and soluble IL-2 receptor was used to predict GvHD. In addition, CD8+ T cell levels above 2.3% of all mononuclear cells after engraftment may predict relapse-free survival at least for 12 months. In summary, we found a new biomarker panel for prediction of GvHD which is featured by established laboratory assays and high statistical significance. In order to introduce the biomarker panel into routine clinical protocols, we suggest performing a larger multi-center study.

Keywords: Biomarker; Graft-versus-host disease; Hematopoietic stem cell transplantation; Relapse-free survival.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Biomarkers / blood
  • Biomarkers / metabolism*
  • CD4-CD8 Ratio
  • CD8-Positive T-Lymphocytes / metabolism
  • Cytokines / blood
  • Cytokines / metabolism*
  • Female
  • Graft vs Host Disease / diagnosis*
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / metabolism
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocyte Count
  • Lymphocytes / metabolism*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Receptors, Interleukin-2 / blood
  • Receptors, Interleukin-2 / metabolism
  • Time Factors
  • Transplantation, Homologous
  • Young Adult

Substances

  • Biomarkers
  • Cytokines
  • Receptors, Interleukin-2