Iron Overload Adversely Affects Survival and Increases Risk of Graft-Versus-Host Disease and Blood Stream Infections after Allogeneic Hematopoietic Stem Cell Transplantation.

Background: Iron overload, mainly from multiple red cell transfusions is common in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic disorders. Although the adverse impact of iron overload on survival of patients undergoing HSCT for thalassemia are well established, the impact of iron overload on the transplant outcome and complications in non-thalassemic patients is less clear.

Methods: Serum ferritin level, a marker of tissue iron overload was measured immediately prior to initiation of transplant conditioning in adult patients undergoing myeloablative HSCT from matched sibling or unrelated donors. The effect of elevated pretransplant ferritin (defined as ferritin over 1000ng/ml) on day 100 mortality, acute graft-versus-host disease (GVHD), infectious complications were assessed.

Results: Data on 190 patients were analyzed for day 100 mortality, overall survival, the combined endpoint of incidence of acute GVHD (Grade II or above) or death within 100 days and the combined endpoint of blood stream infection or death within 100 days. In univariate analysis, the high ferritin group had increased day 100 mortality (20% vs 9%, P=0.04), decreased overall survival (log-rank test: P-value=0.004), increased acute GVHD/death (63% vs 43%, P=0.009) and increased incidence of blood stream infections/death (60% vs 44%, P=0.04). In a multivariate analysis, high ferritin was associated with increased risk of death (Cox Model: hazard ratio 2.28, P-value=0.004), increased day 100 mortality (generalized linear models (GLM) odds ratio 3.82, P-value=0.013), increased incidence of acute GVHD/death (GLM odds ratio 3.11, P-value=0.001) and increased risk of blood stream infections/death (GLM odds ratio 1.99, P-value=0.032). The results remained similar when serum ferritin was considered a continuous variable.

Conclusions: Elevated serum ferritin adversely impacts day 100 mortality and overall survival after allogeneic HSCT. In addition, high serum ferritin also increases the likelihood of acute GVHD and blood stream infections after allogeneic HSCT.