Abstract
Elevated serum ferritin levels occur due to iron overload or during inflammation and macrophage activation. A correlation of high serum ferritin levels with increased mortality after alloSCT has been suggested by several retrospective analyses as well as by two smaller prospective studies. This prospective multicentric study aimed to study the association of ferritin serum levels before start of conditioning with alloSCT outcome. Patients with acute leukemia, lymphoma or MDS receiving a matched sibling alloSCT for the first time were considered for inclusion, regardless of conditioning. A comparison of outcomes between patients with high and low ferritin level was performed using univariate analysis and multivariate analysis using cause-specific Cox model. Twenty centers reported data on 298 alloSCT recipients. The ferritin cut off point was determined at 1500 μg/l (median of measured ferritin levels). In alloSCT recipients with ferritin levels above cut off measured before the start of conditioning, overall survival (HR = 2.5, CI = 1.5–4.1, p = 0.0005) and progression-free survival (HR = 2.4, CI = 1.6–3.8, p < 0.0001) were inferior. Excess mortality in the high ferritin group was due to both higher relapse incidence (HR = 2.2, CI = 1.2–3.8, p = 0.007) and increased non-relapse mortality (NRM) (HR = 3.1, CI = 1.5–6.4, p = 0.002). NRM was driven by significantly higher infection-related mortality in the high ferritin group (HR = 3.9, CI = 1.6–9.7, p = 0.003). Acute and chronic GVHD incidence or severity were not associated to serum ferritin levels. We conclude that ferritin levels can serve as routine laboratory biomarker for mortality risk assessment before alloSCT.
Highlights
Allogeneic stem cell transplantation is a curative treatment option for patients suffering from hematological malignancies and some other diseases
A higher percentage of sex mismatch transplants in the direction of female to male were observed in the group of patients with ferritin above cut off before Allogeneic stem cell transplantation (alloSCT)
We found that overall survival (OS) and progression free survival (PFS) of alloSCT recipients with ferritin levels above cut off measured before start of conditioning were significantly shorter as compared with the low ferritin cohort (Figure 1A, OS univariate hazard ratio (HR) = 2.3, CI = 1.4–3.6, p = 0.00041; multivariate HR = 2.5, CI = 1.5–4.1, p = 0.0005) (Figure 1B, PFS univariate HR = 2.1, CI = 1.4–3.2, p = 0.00014; multivariate HR = 2.4, CI = 1.6–3.8, p < 0.0001)
Summary
Allogeneic stem cell transplantation (alloSCT) is a curative treatment option for patients suffering from hematological malignancies and some other diseases. Mortality in the first months/years after alloSCT is mainly due to leukemia relapse, infections or graft-versus-host disease (GVHD). In all these clinical situations serum ferritin, an acute phase and iron binding protein, has been demonstrated to be elevated [6,7,8,9,10,11,12,13]. Based on this background results, several retrospective studies and metaanalyses have suggested that serum ferritin may be of use as a biomarker during alloSCT [7, 14,15,16,17,18]
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