Iron overload in patients with acute leukemia or MDS undergoing myeloablative stem cell transplantation

Abstract

Patients with hematologic malignancies undergoing allogeneic stem cell transplantation (HSCT) commonly have an elevated serum ferritin prior to HSCT, which has been associated with increased mortality after transplantation. This has led to the suggestion that iron overload is common and deleterious in this patient population. However, the relationship between serum ferritin and parenchymal iron overload in such patients is unknown. We report a prospective study of 48 patients with acute leukemia (AL) or myelodysplastic syndromes (MDS) undergoing myeloablative HSCT, using magnetic resonance imaging (MRI) to estimate liver iron content (LIC) and cardiac iron. The median (and range) pre-HSCT value of serum ferritin was 1549 ng/mL (20-6989); serum hepcidin, 59 ng/mL (10-468); labile plasma iron, 0 LPI units (0.0-0.9). Eighty-five percent of patients had hepatic iron overload (HIO), and 42% had significant HIO (LIC ≥5.0 mg/gdw). Only 1 patient had cardiac iron overload. There was a strong correlation between pre-HSCT serum ferritin and estimated LIC (r = .75), which was mostly dependent on prior transfusion history. Serum hepcidin was appropriately elevated in patients with HIO. Labile plasma iron elevation was rare. A regression calibration analysis supported the hypothesis that elevated pre-HSCT LIC is significantly associated with inferior post-HSCT survival. These results contribute to our understanding of the prevalence, mechanism, and consequences of iron overload in HSCT.

Figure 1

Distribution of pretransplantation serum ferritin and liver iron content (estimated by MRI). (A) Serum ferritin (in ng/mL); (B) Liver iron content (in mg/g dry weight).

Figure 2

Relationship between liver iron content, ferritin, and transfusion history. (A) Scatterplot of liver iron content (in mg/g dry weight) versus serum ferritin (in ng/mL); (B) Liver iron content versus adjusted serum ferritin (see text for details); (C) Liver iron content versus number of prior red cell units transfused. Dotted lines were fit to data using a cubic spline.