Prognostic Impact of Elevated Pretransplant Serum Ferritin in Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract

Iron overload is a well-established adverse prognostic factor in patients who undergo hematopoietic stem-cell transplantation (HSCT) for thalassemia and appears to play a similar role in patients with acute leukemia and myelodysplastic syndrome. We report the results of a large study of consecutive patients undergoing myeloablative allogeneic transplantation to assess the influence of pretransplantation ferritin on treatment-related mortality (TRM), graft-versus-host disease (GVHD) and survival. Pretransplantation ferritin, obtained within 100 days preceding transplant, was available on 222 consecutive patients ≥18 years of age undergoing allogeneic HSCT from 10/20/2000 to 12/04/2006. Transplantation was performed for various disorders (AML n= 105, ALL= 44, CML= 25, MDS= 19, NHL=18, and other= 11) and mainly with busulfan-based preparation (n=153). One hundred twenty four donors were siblings and 98 unrelated. The median patient age was 43 years. Median ferritin level was 1433 ng/ml (range 7–17029). Seventy-five patients had ferritin levels >1910 ng/ml. Median follow-up for surviving patients was 2.5 years. Recursive partitioning analysis identified significantly lower survival for patients with serum ferritin >1910 ng/ml as shown: ESTIMATED SURVIVAL BY PRETRANSPLANTATION FERRITIN LEVEL [Display omitted] Age, gender, disease, disease status at transplant, interval from diagnosis to transplant, number of prior chemotherapy regimens, prior radiation therapy, ferritin, albumin, AST, Alkaline phosphatase, LDH, preparative regimen and CD 34+ dose elevated were assessed. In a multivariable model for survival, elevated ferritin was a significant,independent,adverse prognostic factor for survival (p=0.011, HR=1.68). The addition of albumin, a negative acute phase reactant, did not change the prognostic impact of elevated ferritin. Patients with ferritin >1910 ng/ml had a higher incidence of TRM(p=0.046), as illustrated below: INCIDENCE OF TRM BY FERRITIN LEVELS [Display omitted] This siginificantly higher incidence of TRM occured despite a significantly lower incidence of chronic GVHD (p=0.019) and a trend towards a lower incidence of acute GVHD (p=0.10) in patients with elevated ferritin levels. The incidences of hepatic venoocclusive disease and relapse mortality were not different between the two groups.Conclusions: Elevated ferritin is an independent adverse risk factor in a large group of patients undergoing myeloablative transplantation for various diseases. Higher TRM occured despite the association of elevated ferritin with a significantly decreased incidence of chronic GVHD, consistent with an immunosuppressive effect demonstrated in other settings. Trials should be undertaken to analyze the benefit of iron chelation therapy prior to BMT in patients with iron overload.