Enhanced labile plasma iron and outcome in acute myeloid leukaemia and myelodysplastic syndrome after allogeneic haemopoietic cell transplantation (ALLIVE): a prospective, multicentre, observational trial.

Abstract

BACKGROUND:

The effect of systemic iron overload on outcomes after allogeneic haemopoietic cell transplantation (HCT) has been a matter of substantial debate. We aimed to investigate the predictive value of both stored (MRI-derived liver iron content) and biologically active iron (enhanced labile plasma iron; eLPI) on post-transplantation outcomes in patients with acute myeloid leukaemia or myelodysplastic syndrome undergoing allogenic HCT.

METHODS:

The prospective, multicentre, observational, ALLogeneic Iron inVEstigators (ALLIVE) trial recruited patients at five centres in Germany. We enrolled patients with acute myeloid leukaemia or myelodysplastic syndrome undergoing allogeneic HCT. Patients underwent cytotoxic conditioning for a median of 6 days (IQR 6-7) before undergoing allogeneic HCT and were followed up for up to 1 year (±3 months) post-transplantation. eLPI was measured in serum samples with the FeROS eLPI kit (Aferrix, Tel-Aviv, Israel) and values greater than 0·4 μmol/L were considered to represent raised eLPI. Liver iron content was measured by MRI. The primary endpoints were the quantitative delineation of eLPI dynamics during allogeneic HCT and the correlation coefficient between liver iron content before HCT and dynamic eLPI (eLPIdyn; maximum eLPI minus baseline eLPI). All patients with available data were included in all analyses. This is the final analysis of this completed trial, which is registered with ClinicalTrials.gov, number NCT01746147.

FINDINGS:

Between Dec 13, 2012, and Dec 23, 2014, 112 patients underwent allogeneic HCT. Liver iron content before allogeneic HCT was not significantly correlated with eLPIdyn (ρ=0·116, p=0·22). Serum eLPI concentrations rapidly increased during conditioning, and most (79 [73%] of 108) patients had raised eLPI by the day of transplantation. Patients with a pretransplant liver iron content greater than or equal to 125 μmol/g had an increased incidence of non-relapse mortality (20%, 95% CI 14-26) compared with those with lower concentrations (7%, 2-12; p=0·039) at day 100. Patients who had raised eLPI at baseline also had a significantly increased incidence of non-relapse mortality at day 100 (33%, 15-52) compared with those who had normal eLPI at baseline (7%, 2-13; p=0·00034).

INTERPRETATION:

eLPI is a possible biological mediator of iron-related toxicity. Peritransplantation eLPI-scavenging strategies could be explored in prospective interventional clinical trials for patients with systemic iron overload.

FUNDING:

The Technical University of Dresden and Novartis.

• Authors: Martin Wermke, Julia Eckoldt, Katharina S Götze, Stefan A Klein, Gesine Bug, Liesbeth C de Wreede, Michael Kramer, Friedrich Stölzel, Malte von Bonin, Johannes Schetelig, Michael Laniado, Verena Plodeck, Wolf-Karsten Hofmann, Gerhard Ehninger, Martin Bornhäuser, Dominik Wolf, Igor Theurl, Uwe Platzbecker
• Journal: The Lancet. Haematology (Lancet Haematol) Vol. 5 Issue 5 Pg. e201-e210 (May 2018) ISSN: 2352-3026 [Electronic] England
• PMID: 29628397 (Publication Type: Journal Article, Multicenter Study, Observational Study)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Iron

Topics

• Aged
• Female
• Hematopoietic Stem Cell Transplantation (mortality)
• Humans
• Iron (analysis, blood)
• Iron Overload (blood, complications, diagnostic imaging)
• Leukemia, Myeloid, Acute (complications, mortality, therapy)
• Liver (diagnostic imaging)
• Male
• Middle Aged
• Myelodysplastic Syndromes (complications, mortality, therapy)
• Prospective Studies
• Transplantation Conditioning
• Transplantation, Homologous
• Treatment Outcome