Baseline Serum Ferritin Predicts Rate of Infection in Patients with Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndrome.

Gloria Mattiuzzi, MD1, Hesham M. Amin, MD, MSC2, Hagop Kantarjian, MD1, Guillermo Garcia-Manero, MD*,1 and Jorge Cortes, MD1

Author address: 

1 Leukemia, U.T. M.D. Anderson Cancer Center, Houston, TX, USA, 2 Hematopathology, U.T. M.D. Anderson Cancer Center, Houston, TX, USA


Poster Board I-637 Excess iron adversely affects the phagocytic, chemotactic and bactericidal activities of neutrophils and monocytes; inhibits the activity of natural killer cells and macrophages, and enhances the ability of microbes to grow in various host tissues. Iron overload has also been described to be an important risk factor for the development of mucormycosis. Serum ferritin is a surrogate marker of iron overload. Studies in recipients of bone marrow transplantation showed that elevated pre-transplant serum ferritin levels (as markers of iron overload) were associated with a high incidence of infection-related mortality. Objective: 1) To evaluate iron overload as a predictor of infection in patients with acute myelogenous leukemia (AML) or high risk myelodysplastic syndrome (HR-MDS) undergoing chemotherapy (CHEMO); 2) to compare baseline bone marrow iron stores (BMIS) versus baseline serum ferritin as predictor of infections. Methods: Patients with AML or HR-MDS who underwent induction or first salvage CHEMO were included in this prospective observational study. BMIS was analyzed at baseline (prior CHEMO) in bone marrow aspirate smears by standard staining techniques. BMIS was evaluated using a light microscope and graded on a scale of 0 to 6, with a score of 1 to 3 considered normal. Serum ferritin levels were measured at baseline. Invasive fungal infections (IFI) were defined as probable or proven according to the EORTC-MSG criteria. Bacterial infections were defined by the presence of fever and positive culture from a sterile site. Ferritin values were considered normal if they fell in the range of 10ng/mL 291ng/mL. Results: 112 patients were evaluated. Median age was 69 years (23-84 years) and 49% were female; 97% received induction CHEMO for AML. Fortysix patients developed at least one infectious episode from day 1 of chemotherapy until chemotherapy response was assessed (median days to response = 28). Nineteen patients developed bacterial infections, 9 patients developed fungal [2 candidiasis; 3 proven and 4 probable aspergillosis] and 18 patients had clinically but not microbiologically documented infections (cellulitis, pneumonia, neutropenic colitis). Baseline BMIS and serum ferritin were evaluable in 83 and 112 patients, respectively (Table 1). Median baseline ferritin was significantly higher in patients who developed any infection compare to that of patients without infections (p = 0.018). In addition, patients who developed IFI had higher median baseline ferritin to those without IFI (p=0.039). There were no significant differences in the baseline BMIS between patients without infection and those who developed any infection (p= 0.94) or an IFI (p= 0.71). Conclusions: To our knowledge, this is the first report that shows that serum baseline ferritin can be used as predictor of infection, including bacterial, fungi and non- microbiologically documented infections, in patients with acute leukemia. Although iron overload has been described to be a risk factor for mucormycosis; our data shows that iron overload may be a risk factor for any type of IFI, including yeast and mold infections. Baseline serum ferritin seems to be a better predictor of infections than baseline bone marrow iron stores. These results indicate that the treatment of iron overload may have a potential role in the prevention of infections in patients with acute myelogenous leukemia or high risk myelodysplastic syndrome undergoing chemotherapy. Disclosures: Mattiuzzi: Novartis: Research Funding. Footnotes * Asterisk with author names denotes non-ASH members.

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Full conference title: 

51st American Society of Haematologists Annual Meeting
    • ASH 51st (2009)