Serum ferritin is an iron overload marker and an acute phase reactant. It has been reported that ferritin levels >1000 or 1500 ng/ml pre-Hematopoietic Stem Cell Transplantation (HSCT) are associated with higher rates of Transplant Related Mortality (TRM), mucositis, Graft versus Host Disease (GVHD) and infections.
We have retrospectively analyzed the pre-transplant serum ferritin levels in 300 consecutive patients undergone HSCT in our Hospital from January 2005 to June 2012. Patients were classified according to serum ferritin (< and >700 ng/ml, < and >1000 ng/ml, < and >1500 ng/ml) and we have analyzed: overall survival, acute and chronic GVHD, infections (bacterial, fungal and cytomegalovirus), mucositis, interstitial pneumonitis, hepatic veno-oclussive disease, relapse, TRM-100 days and TRM-1 year. Statistical analysis was performed using the SPSS 17.1 programe. We used Kaplan-Meier, LogRank, T- student and Chi-square tests.
In our series 152 patients (51%) were undergoing autologous HSCT and 148 (49%) were undergoing allogeneic HSCT (21% Reduced Intensity Conditioning regimen). The median follow up was 15 months, and the overall survival was 59 ± 4% at 5 years (autologous 57 ± 7% and allogeneic 60 ± 5%). TRM-100 days was 1.97% (3 patients) in the autologous group and 8.78% (13 patients) in the allogeneic group. TRM-1 year was 2.63% (4 patients) and 17.56% (26 patients) in the autologous and allogeneic group respectively. In the allogeneic group TRM-1 year was due to GVHD (10.1%), infection (5.4%) and others (2%).
Serum ferritin mean pre-HSCT in the global series was 1095 ng/ml (range: 6–11203): autologous 713 ng/ml (range: 8–7120) and allogeneic 1487 ng/ml (range: 6–11203). Serum ferritin was >700 ng/ml in 49% (147 patients), (18% autologous and 31% allogeneic) and <700 ng/ml in 51% (autologous: 32% and allogeneic: 19%).
Serum ferritin >700 ng/ml was correlated with worse outcome in survival (50% ± 5% vs 67 ± 6%; p=0.001), and higher TRM-1year (>700 ng/ml 8% vs <700 ng/ml 1.9%; p=0.043). Neither TRM-100 days nor probability of relapse were higher in patients with > 700 ng/ml.
In patients with ferritin levels pre-HSCT >700 ng/ml we observed more incidence of infections (bacteremia: p=0.001, autologous and allogeneic), fungal infections (p=0.001 in allogeneic) and Cytomegalovirus infection (p=0.03 in allogeneic).
Serum ferritin levels >700 ng/ml were associated with higher incidence of aGVHD grade III-IV (p=0.002), mainly intestinal aGHVD (p=0.014) but we did not find higher incidence of chronic GVHD in the allogeneic group. We found no statistical differences in the incidence of mucositis, interstitial pneumonitis and hepatic veno-oclussive disease between patients with serum ferritin levels > or <700 ng/ml in the global series.
Similar results to those of serum ferritin levels >700 ng/ml were obtained when we analyzed ferritin levels >1000 and >1500 ng/ml except for higher incidence rate of chronic GVHD with ferritin >1000 and 1500 ng/ml in the allogeneic group.
The cut-off of serum ferritin > 700 ng/ml pre-HSCT is correlated with worse outcome after transplantation with higher TRM-1 year due to higher incidence of infections and aGVHD. Further studies about the possible benefit of iron chelation therapy pre-HSCT are necessary.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.