Does iron overload really matter in stem cell transplantation?

Abstract

A growing body of evidence suggests that iron overload is associated with inferior outcomes after myeloablative allogeneic hematopoietic stem cell transplantation (HSCT). However, all of those studies used surrogate markers of iron overload, especially serum ferritin, and most had a retrospective design. We conducted a prospective observational study in patients with myelodysplastic syndrome or acute leukemia undergoing myeloablative HSCT. Forty-five patients who were followed for over 1 year, with serial measurements of serum iron parameters, as well as liver and cardiac magnetic resonance imaging. There was no significant increase in ferritin, liver or cardiac iron content in the 12 months following HSCT. Although serum ferritin still appeared to have prognostic significance, as previously reported, pre-HSCT iron overload (as reflected in liver iron content) was not associated with increased mortality, relapse, or graft-versus-host disease. These results raise the possibility that the adverse prognostic impact of pre-HSCT hyperferritinemia may be related to factors independent of iron overload.

Figure 1. Post-HSCT changes in LIC and ferritin

The changes in LIC (squares) and ferritin (triangles) between 0 and 12 months are plotted against the number of transfused red cell units in that period. The Spearman correlation coefficient between LIC change and red cell units was 0.5, and between ferritin change and red cell units 0.5.

Figure 2. Outcomes after transplantation, stratified by severe iron overload (LIC > 5 mg/gdw) for the patients in the observational study

(A) Overall survival; (B) Progression-free survival; (C) Cumulative incidence of relapse; (D) Cumulative incidence of non-relapse mortality.

Figure 3

Overall survival for the 45 patients in the observational study, stratified by pre-HSCT serum ferritin.