Association of Serum Ferritin Levels Before Start of Conditioning With Mortality After alloSCT - A Prospective, Non-interventional Study of the EBMT Transplant Complications Working Party

Front Immunol. 2020 Apr 15;11:586. doi: 10.3389/fimmu.2020.00586. eCollection 2020.

Abstract

Elevated serum ferritin levels occur due to iron overload or during inflammation and macrophage activation. A correlation of high serum ferritin levels with increased mortality after alloSCT has been suggested by several retrospective analyses as well as by two smaller prospective studies. This prospective multicentric study aimed to study the association of ferritin serum levels before start of conditioning with alloSCT outcome. Patients with acute leukemia, lymphoma or MDS receiving a matched sibling alloSCT for the first time were considered for inclusion, regardless of conditioning. A comparison of outcomes between patients with high and low ferritin level was performed using univariate analysis and multivariate analysis using cause-specific Cox model. Twenty centers reported data on 298 alloSCT recipients. The ferritin cut off point was determined at 1500 μg/l (median of measured ferritin levels). In alloSCT recipients with ferritin levels above cut off measured before the start of conditioning, overall survival (HR = 2.5, CI = 1.5-4.1, p = 0.0005) and progression-free survival (HR = 2.4, CI = 1.6-3.8, p < 0.0001) were inferior. Excess mortality in the high ferritin group was due to both higher relapse incidence (HR = 2.2, CI = 1.2-3.8, p = 0.007) and increased non-relapse mortality (NRM) (HR = 3.1, CI = 1.5-6.4, p = 0.002). NRM was driven by significantly higher infection-related mortality in the high ferritin group (HR = 3.9, CI = 1.6-9.7, p = 0.003). Acute and chronic GVHD incidence or severity were not associated to serum ferritin levels. We conclude that ferritin levels can serve as routine laboratory biomarker for mortality risk assessment before alloSCT.

Keywords: biomarker; ferritin; immunology; iron metabolism; stem cell; transplantation.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / blood*
  • Female
  • Ferritins / blood*
  • Graft vs Host Disease / epidemiology*
  • Hematologic Neoplasms / blood
  • Hematologic Neoplasms / therapy*
  • Humans
  • Male
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation / adverse effects
  • Peripheral Blood Stem Cell Transplantation / mortality*
  • Postoperative Complications / epidemiology
  • Prospective Studies
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Ferritins