Prognostic impact of iron parameters in patients undergoing allo-SCT

Abstract

Iron overload contributes to increased transplant-related mortality, and serum ferritin is typically used to detect iron overload. Other iron parameters have received limited attention. We studied serum ferritin, transferrin, transferrin saturation, iron, soluble transferrin receptor (sTfR) and C-reactive protein (CRP) levels in 230 consecutive patients undergoing myeloablative allo-SCT. All iron parameters were significantly associated with survival. When analyzed individually, both sTfR and transferrin saturation were superior in prognostic power to ferritin (areas under the curve in receiver operating characteristic analysis: 0.670, 0.715, and 0.657, respectively). A combination of ferritin and transferrin saturation had the highest prognostic power: Patients with ferritin below the 30th percentile (<802 ng/mL) showed excellent survival (70±6% at 5 years), while transferrin saturation above the 80th percentile (≥69%) pointed to a high risk of transplant failure (5-year survival 5±5%). The remaining patients showed an intermediate outcome (5-year survival 52±5%). The prognostic impact of iron parameters was independent of other factors such as stage, conditioning regimen and CRP level, and operated similarly across diseases. Iron overload strongly influenced the outcome of allo-SCT. Low pre-transplant ferritin levels indicate a population at low risk, high transferrin saturations and a subgroup of patients with very poor outcome.

Iron Overload in Allogeneic Hematopoietic Cell Transplantation Outcome: A Meta-Analysis

“…The details of the 4 cohorts and the 276 patients included in this analysis have been previously published 4,14,15,22 . The median age was 52 (range, 18–74) years.…”

“…Alternatively, because ferritin is an acute phase reactant, its elevation in serum may betray inflammatory states including active infection or more advanced disease status, which are expected to confer an adverse prognosis in HCT independent of iron overload. There are at present 4 published studies that have directly assessed the impact of pre-HCT LIC on outcome, but differ in their conclusion despite their generally similar design 4,14,15,22 . We therefore undertook an individual patient data meta-analysis of all 4 studies, with the aim of clarifying whether pre-HCT LIC is, like SF, associated with worse OS or NRM.…”

Decitabine as a First-Line Treatment for Older Adults Newly Diagnosed with Acute Myeloid Leukemia

“…Ferritin is a well-known indicator of the body's iron store and has various activities, such as that of an acute phase reactant, antioxidant, or growth factor for AML cell lines 2223. Hyperferritinemia is a poor risk factor in patients with hematologic malignancies, probably because of the adverse impact of body iron accumulation in transfusion-dependent patients 24252627. However, hyperferritinemia might also affect prognosis through mechanisms other than iron accumulation, because several studies have demonstrated that even patients with hyperferritinemia at diagnosis without prior transfusion have poor prognosis 2829.…”

Hyperferritinemia at diagnosis predicts relapse and overall survival in younger AML patients with intermediate-risk cytogenetics

“…Several studies have indicated that high pre-transplantation ferritin levels were strongly associated with greater risk of relapse and lower overall survival [2][3][4][5]. In these patients, hyperferritinemia is mainly due to transfusion relatediron overload [6].…”