Influence of Iron Overload on Immunosuppressive Therapy in Children with Severe Aplastic Anemia

Abstract

Children with severe aplastic anemia (AA) require multiple transfusions of the red blood cells during the immunosuppressive therapy. This leads to iron overload and manifests as elevated levels of ferritin in blood. The aim of this study was a retrospective analysis of the influence of the elevated serum ferritin on the overall survival, event-free survival, the risk of relapse, and response to treatment in children with AA during immunosuppressive therapy. We analyzed 38 children with AA (19 girls, 19 boys, aged 2-17 years) treated according to the obligatory protocol for AA in Poland. The response rate was assessed on days 84, 112, and 360. Patients were divided into three groups: group I consisted of children with ferritin below 285 ng/mL (6 children), group II with ferritin between 286 and 1,000 ng/mL (13 children), and group III ferritin>1,000 ng/mL (19 children). Kaplan-Meier plot was used to estimate the overall survival and event-free survival. We found the overall survival did not differ between the three groups. Event-free survival was significantly shorter (p=0.03) in patients with ferritin levels>1,000 ng/mL compared with the groups with ferritin bellow 1,000 ng/mL. The time to relapse was significantly shorter in group III than in the other two groups (p=0.02). We also found the differences in the treatment response at day 84 (p=0.03) and day 112 (p<0.0001) of immunosuppressive therapy. These findings confirm a negative influence of iron overload in children with AA on the effect of treatment and the risk of relapse.

Subclinical left ventricular dysfunction in children after hematopoietic stem cell transplantation for severe aplastic anemia: a case control study using speckle tracking echocardiography

“…The HSCT involves pre-HSCT conditioning chemotherapy, immunosuppresive therapy, and corticosteroids for the treatment of GVHD, which might adversely affect myocarial function and be potential risk factors for the development of late cardiac complications after HSCT 17) . In addition, SAA patients need multiple transfusions for supportive management, which inevitably leads to iron overload in the systemic organs 5 6) . Since humans have no mechanism for iron excretion, cumulative iron overload leads to iron toxicity with organ dysfunction and damage.…”

“…Late cardiovascular complications are supposed to be uncommon in this population because SAA patients are rarely exposed to well-known cardiotoxic agents such as anthracyclines, which are widely used in pediatric cancer patients. However, SAA patients require multiple transfusions as a pre-HSCT supportive care, which may inevitably lead to systemic organ iron overload 5 6) . Iron overloading in the cardiac tissues can progress to iron overload cardiomyopathy and heart failure, which are the major causes of late death in patients with transfusion-dependent hematologic disease 7) .…”

From Biology to Clinical Practice: Iron Chelation Therapy With Deferasirox

“…Using imaging techniques (MRI), IOL was observed in the liver in 76.4% of patients (including AA) and in the heart in 19.2% (74). The presence of an IOL in patients with severe AA reduces the efficacy of the immunosuppressive therapy and increases the risk of a relapse, confirming that it is a negative prognostic factor for the outcome of these patients (75).…”

“…At the current time, there are no specific standardized criteria for starting ICT in patients with AA. The serum ferritin threshold value >1,000 ng/ml can be used as a rule of thumb (75,(77)(78)(79)(80).…”

Iron Overload Adversely Effects Bone Marrow Haematogenesis via SIRT-SOD2-MROS in a Process Ameliorated by Curcumin

“…Iron overload is common in patients with haematological disorders due to long-term repeated red cell transfusion, congenital iron overload disease, and a subclass of anaemia characterized by ineffective haematogenesis, leading to excess iron deposition throughout the body. Such iron overload causes tissue damage and organ dysfunction and eventually leads to the mortality and morbidity associated with anaemia-related diseases 1,2 . There is accumulating clinical evidence that iron overload has a suppressive effect on haematogenesis and that iron chelation therapy can improve this condition [3][4][5][6][7] .…”