Initial serum ferritin predicts number of therapeutic phlebotomies to iron depletion in secondary iron overload

Abstract Introduction: Iron metabolism plays an important role in hematopoiesis and immune response. In the present project, body iron stores and factors affecting iron storage such as HFE genotype and the number of blood transfusions were evaluated in patients after allogeneic hematopoietic cell transplantation (HCT). In patients with iron overload, the effect of phlebotomy (PT) on iron stores was analysed in correlation to HFE mutations. Patients and methods: Serum ferritin was measured in 201 consecutive patients transplanted from January 2001 to December 2004 at the University of Leipzig. After excluding patients with normal body iron (serum ferritin levels between 30–400 ng/ml) and patients surviving less than 4 months after HCT, 61 patients (31 males/30 females; median age 48 y) treated with PT were evaluated. Diagnoses included acute leukemias (n=29; 48%), chronic leukemias (n=15; 24%), MDS (n=8; 13%) and others (n=9; 15%). 33 patients (54%) were conditioned with Cyclophosphamid 120 mg/kg and 12 Gy TBI. Patients with unrelated donors received ATG 15 mg/kg/day for 3 days. The remaining patients (n=28; 46%) were treated with Fludarabin 30 mg/m2/day for 3 days and TBI 2 Gy applied once. Donors were matched related in 21 (34%) and matched unrelated in 40 (66%) patients. HFE genotype of patients and donors were analysed by real time PCR using a LightCycler, Roche. The effectiveness of PT was assessed by serum ferritin and liver function test evaluation. Results: The majority of patients after HCT (n=172; 86%) had iron overload with a median ferritin of 1697 ng/ml. From these, 61 patients received PT. These patients received a median of 28 (range 2–102) units of blood transfusions. Acute GvHD ≥ grade II was present in 25 (41%) and chronic GvHD in 19 (31%) patients. Elevated SGPT/SGOT and AP were detected in 34 (56%) and 39 (64%) patients respectively. Mutations in the HFE gene were found in 14 (25%) prior to HCT: heterozygosity (het) for H63D (n=10), for C282Y (n=3) and homozygosity for H63D (n=1). Similarly, 22 donors (40%) showed het. for H63D (n=12), for C282Y (n=4) and for S65C (n=4). Two donors were homozygous for S65C. After HCT, all pts expressed donor HFE genotype. PT was performed every 2 weeks with a median of 200 ml blood removed in one session. Interestingly, median Hemoglobin (Hb) rose under PT (p<0.0001). PT resulted in a significant depletion of iron stores (p<0.0001), improvement in SGPT/SGOT (p=0.002), bilirubin (p<0.0001), and AP (p=0.01). In multivariate analysis, a slower rate of iron depletion significantly correlated with mutated donor HFE genotype (p=0.002). In such patients less iron/ml blood were removed per PT and more often PT were required compared to patients with wildtype HFE donors. Conclusions: Iron overload is a frequent complication after HCT. PT is highly effective in removing excess iron and improving Hb and liver function associated with iron overload after HCT. Patients transplanted from a donor with a mutant HFE gene showed slower iron depletion kinetics by PT compared to patients transplanted from donors with wildtype HFE. The role of donor HFE genotype is currently being analysed in patients after HCT.

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Quantification by Superconducting Quantum Interference Device (SQUID) of Iron Overload after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).

Blood ◽

10.1182/blood.v112.11.2134.2134 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2134-2134

Author(s):

Alessandro Busca ◽

Michele Falda ◽

Paola Manzini ◽

Sergio D’antico ◽

Franco Locatelli ◽

...

Keyword(s):

Risk Factor ◽

Iron Overload ◽

Median Time ◽

Serum Ferritin ◽

Fungal Infections ◽

Ferritin Level ◽

Unrelated Donor ◽

Iron Depletion ◽

Hematopoietic Stem ◽

The Impact

Abstract Introduction. Iron overload (IO) is an adverse prognostic factor in patients who undergo allogeneic HSCT for thalassemia and appears to play a similar role in patients with other hematological disorders. Estimation of IO is primarily based on serum ferritin, however many confounding factors particularly in HSCT recipients may result in frequent ferritin overestimation. Aim of the study was to quantify IO by SQUID after HSCT and evaluate the impact on hepatic function and infections. Additionally, the feasibility of iron-depletion has been investigated. Methods. Between December 2005 and December 2007, 102 consecutive pts who were admitted at our outpatient department have been analyzed. Patients received HSCT from a matched sibling (n=66), a partially matched relative (n=4) or a matched unrelated donor (n=32). Primary diagnosis included acute leukemia/MDS in 61% of cases. Assessment of IO after HSCT included serum ferritin and in those with hyperferritinemia (> 1000 ng/ml), liver iron concentration (LIC) was evaluated by SQUID magnetic susceptometry. Iron removal therapy was offered to patients with moderate (LIC 1000–2000 microg/gww) or severe (LIC >2000 microg/gww) IO. Results. Patients who were in complete remission underwent ferritin assessment at a median time of 578 days from transplantation. Fifty-seven had a ferritin level below the threshold of 1000 ng/ml; in this cohort the median time from HSCT to ferritin assessment was 1006 days, significantly different from the median time of 183 days of the 45 patients who had a ferritin level > 1000 ng/ml. LIC evaluated by SQUID was available for 42/45 patients with elevated ferritin values. Overall, 29 patients had moderate to severe IO: median LIC values were 1493 microg/gww (range 1030–3253 microg/gww). Thirteen patients had normal LIC values (LIC<400 microg/gww) despite high serum ferritin levels. Multivariate analysis showed a significant correlation between ferritin levels > 1000 ng/ml and the occurrence of liver dysfunction defined by the presence of at least one abnormal liver function test (LFT) on two or more occasions (OR 6.8; 95%CI 2.2–20.6); the correlation hold the statistical significance even including into the multivariate model the different time of ferritin assessment. In addition, the rate of proven/probable invasive fungal disease was significantly higher among patients with hyperferritinemia as compared to patients with normal ferritin levels (13% vs 0%; p=.006). Nineteen of the 23 patients considered eligible to iron depletion, underwent regular phlebotomy: 9 patients completed the program after a median time of 10 months (range 3–13 months), reaching the target of ferritin < 500 ng/ml; for 6 patients the program is still ongoing, while 4 patients discontinued the phlebotomy protocol (relapse n=2; hypotension, n=1; progressive anemia, n=1). In 8/9 patients who were revaluated by SQUID at the end of iron depletion program there was a significant decrease of LIC (median 1368 microg/gww to 606 microg/gww; p=.005) that parallels changes of serum ferritin; one patient did not show e remarkable reduction of LIC despite serum ferritin normalization.. Three of the 4 patients ineligible to phlebotomy were successfully treated with deferasirox and 1 patient was treated with deferoxamine. Conclusion. The measurement of LIC obtained by SQUID documented the presence of moderate/severe IO in 69% of the patients with high ferritin levels. Our preliminary data showed that in HSCT recipients, high ferritin level is an independent risk factor for the occurrence of abnormal LFTs and IO may be considered a potential risk factor for fungal infections. A phlebotomy program resulted feasible in 65% of the patients who might benefit from a procedure of iron depletion

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Iron Overload in a Patient with Non-Transfusion-Dependent Hemoglobin H Disease and Borderline Serum Ferritin: Can We Rely on Serum Ferritin for Monitoring in This Group of Patients?

Case Reports in Oncology ◽

10.1159/000507653 ◽

2020 ◽

Vol 13 (2) ◽

pp. 668-673

Author(s):

Mohammad Ali ◽

Mohamed A. Yassin ◽

Maya Aldeeb

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Ferritin Level ◽

The Body ◽

Gastrointestinal Absorption ◽

Specific Method ◽

Increased Risk ◽

Endocrine Organs ◽

Secondary Iron Overload ◽

Hemoglobin H Disease

Secondary iron overload is a common complication in the context of hematological diseases, as iron accumulates due to different mechanisms including chronic transfusion, increased gastrointestinal absorption, chronic hemolysis and underlying genetic defects leading to an increase in gastrointestinal absorption of iron. Since the body does not have a mechanism to excrete excess iron, it gets deposited in the heart, endocrine organs, and the liver with the latest being affected less commonly than in primary iron overload disorders like hemochromatosis. Patients with hemoglobin H disease, which is a type of α-thalassemia, are usually transfusion independent, except in occasions where an external stressful factor leads to a drop in hemoglobin and necessitates blood transfusion. Despite this, secondary iron overload is commonly encountered in these patients due to increased gastrointestinal absorption of iron. To avoid the complications associated with iron overload, these patients are usually monitored with serum ferritin, which is an inexpensive widely available method to monitor iron overload. MRI of the liver (Ferriscan) is a more sensitive and specific method to monitor these patients and avoid the long-lasting and sometimes irreversible effect of secondary iron overload. Here we present an interesting case of a patient with hemoglobin H disease, who was monitored with serum ferritin. She had a serum ferritin level considered as a borderline risk for morbidities secondary to iron overload, and an MRI of her liver (Ferriscan) showed significant iron deposition in the liver associated with increased risk of complications secondary to iron overload.

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The Superiority of T2*MRI Over Serum Ferritin in the Evaluation of Secondary Iron Overload in a Chronic Kidney Disease Patient: A Case Report

Journal of Blood Medicine ◽

10.2147/jbm.s319591 ◽

2021 ◽

Vol Volume 12 ◽

pp. 665-670

Author(s):

Abdulrahman Al-Mashdali ◽

Tahiya Alyafei ◽

Mohamed Yassin

Keyword(s):

Chronic Kidney Disease ◽

Case Report ◽

Kidney Disease ◽

Iron Overload ◽

Serum Ferritin ◽

Chronic Kidney Disease Patient ◽

Disease Patient ◽

Secondary Iron Overload ◽

T2 Mri

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Antioxidant micronutrients in children with thalassaemia in Egypt

Eastern Mediterranean Health Journal ◽

10.26719/2002.8.4-5.490 ◽

2002 ◽

Vol 8 (4-5) ◽

pp. 490-495

Author(s):

M. R. Nasr

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Iron ◽

Tissue Injury ◽

Inverse Correlation ◽

Serum Levels ◽

Serum Retinol ◽

Micronutrient Status ◽

Secondary Iron Overload ◽

The Relationship

Repeated blood transfusions in patients with thalassaemia subject them to peroxidative tissue injury by secondary iron overload. To study the relationship between iron overload and antioxidant micronutrient status among children with thalassaemia, we measured serum levels of vitamins A and E, zinc, selenium, and copper in 64 children with beta-thalassaemia major and 63 age- and sex-matched controls. All of these elements were significantly lower in the thalassaemic children compared with controls. There was a highly significant inverse correlation between serum ferritin and serum retinol levels, and significant inverse correlations between serum iron and retinol and between serum iron and selenium. Serum ferritin showed a significant positive correlation with duration of chelation and transfusion treatments. Ways are needed to counteract this oxidative damage and its deleterious effect on the prognosis of thalassaemia.

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