Abstract
Retrospective, surrogate marker-based studies have found inconsistent associations between systemic iron overload (SIO) and adverse outcome in patients undergoing allogeneic stem cell transplantation (allo-SCT). As a consequence, the impact of SIO in this context remains under debate. The aim of this study was to test whether the objective pretransplant quantification of liver-iron content (LIC) by magnetic resonance imaging (MRI) could circumvent these limitations and conclusively define the prognostic relevance of SIO. The correlation between pretransplant LIC and surrogate parameters as well as the impact of SIO on posttransplant outcome was assessed within an observational study of patients (n = 88) with either myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) undergoing allo-SCT. Ferritin levels of 1,000 ng/mL or more provided only poor specificity (31.8%) for predicting elevated LIC (≥125 μmol/g) and even higher thresholds (≥2,500 ng/mL) lacked an association with nonrelapse mortality (NRM). In contrast, LIC 125 μmol/g or more was a significant risk factor for NRM in uni- and multivariate analysis (HR = 2.98; P = 0.016). Multivariate Cox-regression further showed that LIC 125 μmol/g or more was associated with a decreased overall survival (HR = 2.24, P = 0.038), whereas ferritin or transfusion burden were not. SIO reflected by LIC is an independent negative prognostic factor for posttransplant outcome in patients with AML and MDS undergoing allo-SCT. Therefore, MRI-based LIC, and not interference-prone serum markers such as ferritin, should be preferred for pretransplant risk stratification and patient selection in future clinical trials.
Highlights
Systemic iron overload (SIO) is a frequent clinical feature in thalassemia and nontransfusion-induced iron overload conditions, such as hemochromatosis
Multivariate Cox-regression further showed that liver-iron content (LIC) 125 mmol/g or more was associated with a decreased overall survival (HR 1⁄4 2.24, P 1⁄4 0.038), whereas ferritin or transfusion burden were not
SIO reflected by LIC is an independent negative prognostic factor for posttransplant outcome in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allo-SCT
Summary
Systemic iron overload (SIO) is a frequent clinical feature in thalassemia and nontransfusion-induced iron overload conditions, such as hemochromatosis. Evidence from the clinical course of these patients indicates that iron-associated toxic effects are expected when liver-iron content (LIC) exceeds a threshold of 90 to 125 mmol/g (5–7 mg/g) dry weight, and is associated with liver fibrosis as well as cardiac and pancreatic insufficiency [4]. Body iron load steadily increases during the course of the disease, resulting in SIO being present in almost all patients at the time of allogeneic stem cell transplantation As disease-inherent cytopenia precludes direct quantification of body iron content (e.g., with liver biopsies), most of our current knowledge on SIO in this context is based on surrogate parameters, which are not entirely iron specific. Serum ferritin levels are especially difficult to interpret in a
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