Prognostic Impact of Posttransplantation Serum Ferritin In Allogeneic Stem Cell Transplantation for Leukemia or Myelodysplastic Syndrome.
Authors: Kanamori Heiwa , Tachibana Takayoshi , Numata Ayumi , Tanaka Masatsugu , Ishigatsubo Yoshiaki , Maruta Atsuo 
Published: October 2019

Abstract
Abstract 3444

Background:
Although pretransplantation iron overload is an adverse prognostic factor in patients undergoing allogeneic stem cell transplantation (SCT), the impact of posttransplantation iron overload on the outcome is not clear. In this study, we retrospectively assessed the association of the posttransplantation serum ferritin level with the result of transplantation in patients surviving for 1 year or more after SCT.

Patients and Methods:
The serum level of ferritin, a marker of iron overload, was measured at the time of preconditioning and then annually in adult patients who underwent SCT between January 2000 and December 2008. Patients who received repeat transplantation or died within 1 year after the first SCT were excluded. There were 107 patients (pts), including 51 pts with acute myeloid leukemia, 30 pts with acute lymphoblastic leukemia, 14 pts with myelodysplastic syndrome, and 12 pts with chronic myelogenous leukemia. Their median age was 41 years (range: 16–60 years), with 52 males and 55 females. The disease risk at transplantation was standard risk in 82 pts and high risk in 25 pts. Myeloablative preconditioning was employed for 87 pts and reduced-intensity preconditioning was done for 20 pts. Bone marrow transplantation, peripheral blood stem cell transplantation, and cord blood transplantation were performed in 74, 25, and 8 pts, respectively. The serum ferritin level was categorized as low (< 1000 ng/ml) or high (≥ 1000 ng/ml). Patients who had one or more high ferritin levels after SCT were classified into the high ferritin group.

Results:
The median serum ferritin level before transplantation and 1, 2, 3, 4 and 5 years after SCT was 770 (n=107), 695 (n=75), 590 (n=65), 552 (n=61), 476 (n=51), and 430 (n=44) ng/ml, respectively. The median amount of red blood cells (RBC) transfused within 1 year after SCT was 6 units (range: 0–128). Patients receiving more than 6 units of RBC had significantly higher serum ferritin levels from 1 to 3 years after SCT. Patients with chronic graft-versus-host disease (cGVHD) showed significantly higher serum ferritin levels from 2 to 4 years after SCT compared to patients without chronic GVHD. There was no significant difference between the low and high pretransplantation ferritin groups with respect to 5-year overall survival (OS) (78% vs 82%, p=0.329). On univariate analysis, factors associated with worse 5-year OS included a high disease risk at transplantation (vs standard risk: 60 vs 87%, p=0.009), higher amount of RBC transfusion after SCT (vs lower: 73 vs 87%, p=0.015), the presence of cGVHD (vs absence: 73 vs 90%, p=0.023) and a high ferritin level after SCT (vs low ferritin: 64 vs 91%, p<0.001). A high ferritin after SCT was independently associated with worse 5-year OS according to multivariate analysis (relative to low ferritin; hazard ratio (HR), 3.42; 95% confidence interval (CI), 1.21–9.71; p=0.021). In addition multivariate analysis showed that a high disease risk (HR, 2.64; CI, 1.05–6.58; p=0.037) and a high ferritin level after SCT (HR, 5.24; CI, 1.94–14.27; p=0.001) were independent determinants of 5-year disease-free survival. Furthermore, the cumulative incidence of relapse was significantly higher in patients without cGVHD (HR, 3.44; CI, 1.19–9.92; p=0.023) and those with high ferritin levels after SCT (HR, 5.53; CI, 1.86–16.45, p=0.002). The cumulative non-relapse mortality rate was significantly higher in patients with cGVHD and high ferritin levels after SCT according to univariate, but not multivariate, analysis.

Conclusions:
Elevation of the serum ferritin level after SCT was significantly associated with a worse outcome for patients surviving more than 1 year, although various factors including RBC transfusion and/or cGVHD might have a role in the increase of posttransplantation serum ferritin. These results might help to decide which patients should be treated with iron chelating therapy after SCT.

Disclosures:
No relevant conflicts of interest to declare.