MRI-Based Liver Iron Content Predicts for Nonrelapse Mortality in MDS and AML Patients Undergoing Allogeneic Stem Cell Transplantation

Abstract

Purpose: 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.Experimental Design: 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 ¼ 88) with either myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) undergoing allo-SCT.Results: Ferritin levels of 1,000 ng/mL or more provided only poor specificity (31.8%) for predicting elevated LIC (!125 mmol/g) and even higher thresholds (!2,500 ng/mL) lacked an association with nonrelapse mortality (NRM). In contrast, LIC 125 mmol/g or more was a significant risk factor for NRM in uni-and multivariate analysis (HR ¼ 2.98; P ¼ 0.016). Multivariate Cox-regression further showed that LIC 125 mmol/g or more was associated with a decreased overall survival (HR ¼ 2.24, P ¼ 0.038), whereas ferritin or transfusion burden were not.Conclusions: 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.

Phase IV open-label study of the efficacy and safety of deferasirox after allogeneic stem cell transplantation

“…Several prospective studies and a multi-center meta-analysis examining the impact of elevated LIC on HSCT outcomes came to different conclusions regarding the prognostic relevance of LIC in HSCT, mainly due to the use of different LIC thresholds. [17][18][19][20][21] However, an LIC threshold of over 7 mg Fe/g dw has been associated with a decrease in overall survival and non-relapse mortality. 19,20 In the meta-analysis performed by Armand, …”

Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet

“…In addition, elevated pretransplantation serum ferritin levels were found to be associated with lower survival rates in patients with MDS who underwent allogeneic SCT, suggesting that iron overload may affect transplantation outcome for patients with MDS, as it does in thalassemia. [254][255][256][257][258][259] Several studies have investigated the use of iron-chelating agents in MDS patients with transfusion-dependent anemia. A report on MDS patients receiving desferrioxamine as a continuous, subcutaneous 12-hour infusion by pump found that this chelating agent induced effective iron depletion in a significant proportion of patients.…”

The Impact of Iron Overload on Transplant-Related Complications and Prognosis of Acute Leukemias.

“…serum TS plus ferritin and/or radiological tests and/or liver biopsy) to define iron overload. 1,2,3,8,12 Some of them found a relationship between iron overload and post-transplant survival. 2,3 On the other hand some others did not.…”

“…1,2,3,8,12 Some of them found a relationship between iron overload and post-transplant survival. 2,3 On the other hand some others did not. 1,12 Interestingly the relationship between iron overload and VOD, probably the most expected specific transplant complication in patients with liver injury, was not reported in any of these studies considered to have adequate methodologies for detection of iron overload.…”

“…1,2 Patients with hematologic malignancies commonly have an elevated serum ferritin prior to HSCT. However, the relationship between serum ferritin and parenchymal iron overload in leukemic patients may not be correlated.…”