Characterization of transfusion-derived iron deposition in childhood cancer survivors

Abstract

Background: Childhood cancer survivors (CCS) receiving packed red blood cell (PRBC) transfusions may have increased risk for vital organ iron deposition causing serious late effects.

Methods: This cross-sectional cohort study of a CCS cohort quantified organ iron content by magnetic resonance imaging. Iron status by serum markers and hemochromatosis gene mutation status were assessed.

Results: Seventy-five patients who had received a range (0-392 mL/kg) of cumulative PRBC transfusion volumes were enrolled (median age 14 years, range 8-25.6 years at evaluation). Median follow-up time was 4.4 years, and median time since last transfusion was 4.9 years. Cancer diagnoses included acute lymphoblastic or myelogenous leukemia (ALL/AML; n = 33) and solid tumors (n = 42). Liver and pancreatic iron concentrations were elevated in 36 of 73 (49.3%) and 19 of 72 (26.4%) subjects, respectively. Cardiac iron concentration was not increased in this cohort. In multivariate analysis, cumulative PRBC volume (P < 0.0001) and older age at diagnosis (P < 0.0001) predicted elevated liver iron concentration.

Conclusions: Iron overload (IO) may occur in children and adolescents/young adults treated for cancer and is associated with cumulative PRBC transfusion volume and age at diagnosis.

Impact: These findings have implications for development of monitoring and management guidelines for cancer patients and survivors at risk for IO, exploration of the additive risk of liver/pancreatic damage from chemotherapeutic exposures, and health education to minimize further liver/pancreatic damage from exposures such as excessive alcohol intake and hepatotoxic medications.