Elevated Pre-HCT Iron Levels Predictive of Worse Survival Outcomes in AML/MDS

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The ALLIVE trial sought to determine if eLPI levels were predictive of iron-related toxicity and mortality after HCT in patients with AML or MDS.
The ALLIVE trial sought to determine if eLPI levels were predictive of iron-related toxicity and mortality after HCT in patients with AML or MDS.

Elevated levels of biologically active iron (enhanced labile plasma iron [eLPI]) may be predictive of iron-related toxicity and mortality after allogeneic hematopoietic cell transplantation (HCT) among patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), according to a study published in The Lancet Haematology.

Systemic iron overload is typically associated with poor outcomes in hematologic diseases. Previous studies have linked elevated serum iron levels to nonrelapse mortality in the context of hematologic malignancies, but these findings require further exploration.

For the prospective Allogeneic Iron Investigators (ALLIVE) trial, researchers measured the stored iron (MRI-derived liver iron content) and eLPI of 112 patients with AML or MDS undergoing allogeneic HCT. Patients with serum levels greater than 0.4 µmol/L were considered to have elevated eLPI levels. They received cytotoxic conditioning for a median of 6 days, and were followed up for up to 1 year posttransplantation.

Analysis revealed that high levels of stored iron before undergoing HCT was not significantly associated with elevated eLPI. Serum eLPI increased quickly during conditioning, and approximately 73% of patients had elevated eLPI on the day of transplant.

Patients with pretransplant liver iron levels 125 µmol/g or higher had a 20% increased incidence of nonrelapse mortality compared with patients with lower levels 100 days posttransplant (P =.039).

Patients with an elevated pretransplant eLPI had a 33% increased incidence of nonrelapse mortality compared with patients with normal eLPI levels after 100 days (P =.00034).

The results of the study demonstrate that iron toxicity is associated with worsened outcomes in the context of allogeneic HCT for hematologic cancers. The authors concluded that “in view of these data, we believe that prospective interventional trials on iron scavenging strategies are warranted to further investigate this hypothesis.”

Reference

1. Wermke M, Eckoldt J, Gotze KS, et al. Enhanced labile plasma iron and outcome in acute myeloid leukaemia and myelodysplastic syndrome after allogeneic haemopoietic transplantation (ALLIVE): a prospective, multicentre, observational trial [published online April 5, 2018]. Lancet Haematol. doi: 10.1016/S2352-3026(18)30036-X

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