Pre-Transplant Hyperferritinemia Is Associated with Low Incidence of Chronic Gvhd, High Relapse Rate and Impaired Survival in Patients with Hematological Malignancies after Allogeneic HSCT

Background: Iron overload is common after allogeneic hematopoietic stem cell transplantation and may cause liver damage. High pre-transplantation serum ferritin levels have been reported to be associated with impaired survival post transplantation in patients with acute myeloid leukemia or myelodysplastic syndrome.

Design and Methods: We performed a retrospective study of 309 adult patients with haematological malignancies who underwent allogeneic hematopoietic stem cell transplantation after myeloablative (51%) or non-myeloablative conditioning (49%). The aim was to determine the incidence of hyperferritinemia and iron overload and the effects of these conditions on graft versus host disease, relapse and survival in patients with blood disorders who receive allogeneic stem cell grafts.

Results: For overall survival and for relapse-free survival, only high pretransplantation ferritin (>400ug/l) and advanced stage of disease were significant in multivariable analysis. High pretransplantation ferritin and advanced stage of disease were also significant for relapse risk at 3 years, but ferritin was not significant for non-relapse mortality. In multivariate analysis, ferritin, age, type of donor, and previous transplantation were significant factors for cGVHD at one year.

Conclusions: Hyperferritinemia was associated with lower risk of cGVHD and increased risk of relapse and death, but not with increased non-relapse mortality. The lower rate of cGVHD among patients with high ferritin levels can be explained by an immunosuppressive effect of ferritin, reducing graft versus host disease and graft versus leukaemia effect, resulting in increased risk of relapse and impaired chance of survival. Therefore, these conditions might be best explained by an immunosuppressive effect of ferritin and not by a direct toxic effect.