scholarly journals 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?

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.

scholarly journals Noninvasive assessment of iron overload by magnetic resonance imaging

2020 ◽  
Vol 19 (3) ◽  
pp. 158-163
Author(s):  
E. E. Nazarova ◽  
D. A. Kupriyanov ◽  
G. A. Novichkova ◽  
G. V. Tereshchenko
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Iron Concentration ◽  
The Body ◽  
Iron Accumulation ◽  
Resonance Imaging

The assessment of iron accumulation in the body is important for the diagnosis of iron overload syndrome or planning and monitoring of the chelation therapy. Excessive iron accumulation in the organs leads to their toxic damage and dysfunction. Until recently iron estimation was performed either directly by liver iron concentration and/or indirectly by measuring of serum ferritin level. However, noninvasive iron assessment by Magnetic resonance imaging (MRI) is more accurate method unlike liver biopsy or serum ferritin level test. In this article, we demonstrate the outlines of non-invasive diagnostics of iron accumulation by MRI and its specifications.

Deferasirox for the Treatment of Transfusional Iron Overload in Sickle Cell Anemia. Preliminary Results

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2879-2879
Author(s):  
Rodolfo D Cancado ◽  
Maria Cristina A Olivato ◽  
Paula Bruniera ◽  
Carlos Chiattone
Keyword(s):  
Serum Creatinine ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Sickle Cell Anemia ◽  
The Body ◽  
Once Daily ◽  
Body Iron ◽  
Endocrine Organs ◽  
The Impact

Abstract The majority of patients with sickle cell anaemia have received repeated blood transfusions by adulthood. Because the body has no physiological mechanism to actively excrete the excess of iron, chelation therapy is important for the management of iron overload and its complications, including iron deposition into the liver, heart and endocrine organs, eventual death. While studies are limited, progressive iron loading and subsequent tissue injury in sickle cell disease appears similar to other transfused populations. Deferasirox (Exjade, ICL670) is a once-daily, oral iron chelator that is approved for the first-line treatment of chronic transfusional iron overload. Its safety, tolerability and efficacy in reducing body iron burden have been demonstrated in patients with β-thalassaemia major and in other chronic transfusion-dependent anaemias. The objectives of this prospective, non-randomised, phase IV trial were to evaluate the iron overload status, before and after one year-treatment with deferasirox, using liver iron concentration (LIC) by MRI of the liver, MRI cardiac (Cardiac T2*), serum ferritin and the impact of deferasirox treatment on these measurements, and to evaluate the safety and tolerability of this drug. A total of 30 patients with sickle cell anemia and iron overload, defined as the use of ≥ 20 units of RBC units and/or two plasma ferritin levels ≥ 1000 mcg/L during the 6 months preceding enrollment, received starting dose of 20mg/kg/day of deferasirox. Efficacy was assessed monthly by measuring change from baseline in serum ferritin levels. Safety was evaluated on a monthly basis according to the incidence and type of adverse events and measurement of laboratory parameters, including serum creatinine and liver enzyme levels. Mean (range) age 26.4 ± 12.3y (9–49), 83% female, 93% afrodescendent, 60% on regular blood transfusion, mean deferasirox exposure 30.1 ± 5.6 weeks (16–39), mean MRI hepatic (LIC, μmol/g) 233.0 ± 98.8 (45 – 350), mean MRI cardiac (Cardiac T2*, ms) 41.20 ± 5.46 (27.52 – 51.19). Median ± SD and mean (range) serum ferritin level (mcg/L) at baseline and 6 months varied from 2315.5 ± 1083.9 to 2062.5 ± 1320.8 (p=0.032) and 2012.0 (1013–6074) to 1654.0 (688–6729), respectively. The proportion of patients with serum ferritin levels < 2000, 2000- <3000 and ≥ 3000 mcg/L from baseline to 6 months by percentage of patients changed from 50% to 60%, 26.7% to 26.7% and 23.3% to 13.3%, respectively. The most common drug-related AEs were mild, transient diarrhea (23.3%), headache (20.0%) and nausea (16.7%). Maculo-papular skin rash and serum creatinine increases upper limit of normal were observed in 2 (6.7%) patients. No patient experienced progressive increases in serum creatinine or renal failure. Our preliminary data, over 6-month-period of treatment, confirms that deferasirox is effective and generally well tolerated in pediatric and adult patients, and appears to have similar efficacy to deferoxamine in reducing body iron burden in transfused patients with sickle cell anemia. The availability of deferasirox as a once-daily, oral alternative would potentially facilitate improved compliance, and thereby reduce morbidity and mortality from iron overload.

scholarly journals “Efficacy and Safety of Deferasirox in Pediatric Thalassemia Patients: Experience from a Tertiary Care Children Hospital of Bangladesh”

2021 ◽  
Vol 8 (09) ◽  
pp. 5621-5626
Author(s):  
Belayet Hossain ◽  
Selimuzza Man ◽  
Nilufer Akhter Chowdhury Banu ◽  
Abdul Wahab
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Ferritin Level ◽  
Tertiary Care ◽  
Growth Failure ◽  
The Body ◽  
Beta Thalassemia ◽  
Optimum Dose ◽  
Efficacy And Safety ◽  
Hemoglobin E

Background: Thalassemia is an inherited hemoglobin disorder; mostly require life-long blood transfusions, leading to chronic iron overload which causes growth failure, delayed sexual development in adolescents and vital organ dysfunctions. So, children with thalassemia need lifelong iron chelation therapy. Hence, this study conducted with the aim of to evaluate efficacy and safety of Deferasirox in pediatric thalassemia patients. Materials and methods: This is an observational, prospective, single-centered hospital-based study conducted in a tertiary care teaching hospital from June 2018 to December 2019. Total sixty children (age 2-18 years) with beta thalassemia major and hemoglobin E beta thalassemia with iron overload were enrolled to commence deferasirox. Efficacy and safety we observed by measuring serum ferritin three monthly and SGPT, SGOT & serum creatinine monthly. Results: The serum ferritin level of 72% patients reduced significantly after 12 months in comparison to baseline level. There was no serious adverse effect except mild abdominal pain, nausea & vomiting and transaminitis. Conclusion: Deferasirox is efficacious in reducing iron overload of the body when administer at optimum dose over at least one year and presenting a safe as well as convenient alternative for most of the transfusion dependent pediatric thalassemia patients.

scholarly journals Serum ferritin levels are associated with carotid atherosclerosis in Chinese postmenopausal women: the Shanghai Changfeng Study

2015 ◽  
Vol 114 (7) ◽  
pp. 1064-1071 ◽  
Author(s):  
Hui Ma ◽  
Huandong Lin ◽  
Yu Hu ◽  
Xiaoming Li ◽  
Wanyuan He ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Serum Ferritin ◽  
Carotid Atherosclerosis ◽  
Ferritin Level ◽  
Oral Glucose ◽  
Model Assessment ◽  
Cvd Risk ◽  
Carotid Plaques ◽  
Increased Risk ◽  
Fourth Quartile

Postmenopausal women are at increased risk of CVD: the increased serum ferritin level may be involved in the pathogenesis. The aim of the present study is to investigate the relationship of ferritin and carotid atherosclerosis in postmenopausal women. A total of 1178 postmenopausal women (mean age, 60·8 years) were enrolled from the Changfeng Study. A standard interview, anthropometric measurements and laboratory analyses were performed for each participant. Bilateral CIMT (carotid intima–media thickness) were measured using ultrasonography, and the presence of carotid plaques was assessed. Serum ferritin was measured using electrochemiluminescence immunoassay. The results showed that serum ferritin was 181·9 (sd 65·8) ng/ml in the postmenopausal women. Multivariate, linear, stepwise regression analysis demonstrated that age (standardised β = 0·233, P< 0·001), alanine transaminase (standardised β = 0·194, P< 0·001), log homeostasis model assessment index for insulin resistance (standardised β = 0·181, P< 0·001), TAG (standardised β = 0·083, P= 0·003), Hb (standardised β = 0·080, P= 0·004) and PPG (2-h glucose levels following a 75-g oral glucose challenge) (standardised β = 0·079, P= 0·004) were independently associated with serum ferritin. Compared with the ferritin level of subjects in the first quartile, that in the fourth quartile had greater CIMT, and higher prevalence of carotid plaque. After adjusting for conventional CVD risk factors, Hb, leucocytes, log urine albumin:creatinine ratio and liver function, the ferritin level of postmenopausal women in the fourth quartile had a 1·587-fold increased risk of carotid plaques relative to those in the lowest quartile. In conclusion, these results suggest that serum ferritin is independently and positively associated with carotid atherosclerosis in postmenopausal women and that ferritin may be implicated in atherosclerosis.

Assessment of Iron Overload in a Cohort of Sri Lankan Patients with Transfusion Dependent Beta Thalassaemia and its Correlation with Pathogenic Variants in HBB, HFE, SLC40A1, and TFR2 Genes

2021 ◽  
Author(s):  
Ruwangi Dissanayake ◽  
Nayana Samarasinghe ◽  
Samantha Waidyanatha ◽  
Sajeewani Pathirana ◽  
Vajira HW Dissanayake ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Sri Lankan ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
The Mean ◽  
One Year ◽  
Next Generation Sequencing Ngs ◽  
T2 Mri ◽  
Generation Sequencing

Abstract Background. Iron overload (IO) is a complication in transfusion dependent beta thalassaemmia (TDT). Pathogenic variants in genes involving iron metabolism may confer increased risk of IO. The objective of this study was to determine the magnitude of the cardiac and hepatic IO and determine whether pathogenic variants in HFE, SLC40A1 and TFR2 genes increase the risk of IO in a cohort of TDT patients in Sri Lanka.Materials and Methods. Fifty-seven (57) patients with TDT were recruited for this study. Serum ferritin was done once in 3 months for one year in all. Those who were ≥ 8 years of age underwent T2* MRI of the liver and heart. Fifty-two (52) patients underwent next generation sequencing (NGS) to identify pathogenic variants in HBB, HFE, SLC40A1 and TFR2 genes.Results. The mean age (SD) of this cohort was 9.5 (±4.6) years. It comprised of 30 (52.6%) boys and 27 (47.4%) girls. The mean serum ferritin was 3405 (±2670.5) ng/dl. Hepatic IO was seen in 38 (95%) patients and cardiac IO was seen in 17 (42.5%) patients. All patients with cardiac IO were asymptomatic and had normal echocardiogrammes. There was no statistically significant correlation between serum ferritin and hepatic or cardiac IO.32 (61.5%), 18 (34.6%), 2 (3.8%) of patients were homozygotes, compound heterozygotes and heterozygotes for pathogenic variants in the HBB gene. 9 (17.3%) and 3 (5.8%) patients were heterozygotes for pathogenic variants of HFE and SLC40A1 genes respectively. There were no pathogenic variants for the TfR2 gene. The heterozygotes of the pathogenic variants of the HFE and SLC40A1 genes were not at increased risk of IO.Conclusions. Cardiac T2* MRI helps to detect cardiac IO prior to the onset of symptoms when the echocardiogramme is normal. It is important to perform hepatic and cardiac MRI T2* to detect IO in patients with TDT.

scholarly journals Tissue doppler imaging in thalassemia major patients: correlation between systolic and diastolic function with serum ferritin level

2012 ◽  
Vol 52 (4) ◽  
pp. 187 ◽  
Author(s):  
Syarif Rohimi ◽  
Najib Advani ◽  
Sudigdo Sastroasmoro ◽  
Bambang Mardiyono ◽  
Sukman Tulus Putra ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Tissue Doppler Imaging ◽  
Negative Correlation ◽  
Serum Ferritin Level ◽  
Systolic Function ◽  
Ferritin Level ◽  
Tissue Doppler ◽  
Doppler Imaging ◽  
Number Of Patients

Background Thalassemia is a major public health problem inIndonesia. Cardiac diseases remain as the main cause of death inthese patients due to iron overload. Although the T2* magneticresonance imaging has been considered as the gold standard forassessing cardiac iron overload but it has limited availability.The tissue doppler imaging (TDI) echocardiography, a fairly newand easy method that is suggested, can detect early abnormalmyocardial iron overload.Objective To assess myocardial systolic and diastolic functionof thalassemic patients using TDI and examine their correlationwith serum ferritin level.Methods A cross􀁌sectional study was conducted from January toMarch 2011 at the Harapan Kita Women and Children Hospital.We performed clinical examination, serum ferritin level, as wellas conventional and tissue doppler echocardiography on allsubjects.Results We included 34 regularly􀁌tranfused patients, of which17 were boys. The mean age of the subjects was 11.6 (SD 4.7years, range 2.6 􀁌 20 years). Mean pulse rate and blood pressurewere within normal range. Hemoglobin level at inclusion rangedfrom 5.8 to 6 g/dL. Almost all patients did not receive regularchelation therapy. Median serum ferritin level was 6275 ng/mL(range 2151 - 17,646 ng/mL). Conventional echocardiographyshowed normal systolic function, but some diastolic dysfunctionswere found including E wave abnormalites in 4 patients, A waveabnormalites in 3, and E/A ratio abnormalites found in 3. TheTDI showed decreased systolic function (Sa wave abnormality) in9 patients and diastolic dysfunctions (Ea wave abnormality in 11patients and Aa wave abnormaly in 2). No abnormality was foundin Ea/Aa and ElEa ratios. There was a weak negative correlationbetween ferritin level and Sa wave and Ea wave respectively anda moderately negative correlation between ferritin level and Ea/Aa ratio. There was no correlation between serum ferritin andAa wave or ElEa ratio.Conclusion TDI identifies a greater number of patients Mthsystolic and diastolic myocardial dysfunction than was revealedby conventional echocardiography. There was a weak negativecorrelation between serum ferritin to Sa wave and Ea wave, and amoderately negative correlation between ferritin and Ea/Aa ratio.There was no correlation between serum ferritin and Aa wave orElEa ratio. [paediatr Indones. 2012;52:187,93].

scholarly journals Assessment of serum Ferritin level and its correlation with HbA1c in Diabetic Nephropathy

2020 ◽  
Vol 11 (2) ◽  
pp. 46-51
Author(s):  
Madhura Navule Siddappa ◽  
Kowsalya Ramprasad
Keyword(s):  
Diabetic Nephropathy ◽  
Glycemic Control ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Pearson Correlation ◽  
The Body ◽  
Control Group ◽  
Type Ii

Background: Serum ferritin levels reflecting the body iron stores, is known to be elevated in type 2 Diabetes Mellitus. However its association with diabetic complications including Diabetic nephropathy (DN), and overall glycemic control needs to be validated. Aims and Objectives: The aim of this study was to find the Serum Ferritin level abnormalities in DM patients with nephropathy in comparison with DM patients without nephropathy and to find correlation of Serum Ferritin (SF) levels with levels of Glycated Hemoglobin (HbA1c) in patients with diabetic nephropathy. Materials and Methods: This is a retrospective study, which included eighty five registered patients with Type 2 DM (44 Type II DM without nephropathy cases and 41 cases of Type II DM with nephropathy). SF and HbA1c was estimated in all cases across both the groups and were compared with age and sex matched controls and analysed. Results: Serum Ferritin levels were higher in diabetics with nephropathy compared to diabetics without nephropathy (p<0.0001). SF levels were higher in diabetic groups compared to control group (p <0.001).The correlation between HbA1c and SF was assessed among all cases of DM with nephropathy group using pearson correlation test and it showed a significantly positive correlation (r=0.431) with a SF (mean = 938±148) and HbA1c (mean = 9.2±2.02). Conclusion: Serum ferritin levels positively correlate with HbA1c levels in Type II DM cases with nephropathy, which suggests that serum Ferritin levels can be used as a surrogate marker of glycemic control in Type II DM with nephropathy.

scholarly journals LONGITUDINAL STUDY ON LIVER FUNCTIONS IN PATIENTS WITH THALASSEMIA MAJOR BEFORE AND AFTER DEFERASIROX (DFX) THERAPY

2014 ◽  
Vol 6 (1) ◽  
pp. e2014025 ◽  
Author(s):  
Ashraf Tawfik Soliman ◽  
Mohamed Yassin ◽  
Fawzia AlYafei ◽  
Lolwa Al-Naimi ◽  
Noora Almarri ◽  
...  
Keyword(s):  
Liver Function ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Negative Correlation ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Growth Potential ◽  
Igf I ◽  
Liver Functions

With regular blood transfusion and iron chelation therapy, most patients with thalassemia major (BTM) now survive beyond the third decade of life . Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are important causes of liver pathology. Iron chelation with desferrioxamine (Desferal)  reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The recent use of Deferasirox (Exjade- DFX ), an  oral single dose therapy has improved the compliance to chelation therapy.Aims: To study the long-term liver functions in BMT patients, seronegative for liver infections before versus after DFX therapy in relation to ferritin level and IGF-I level.Methods: Liver function tests including: serum bilirubin, alanine transferase (ALT), aspartate transferase (AST) , albumin, insulin-like growth factor – I (IGF-I) and serum ferritin concentrations were followed every 6 months in 40 patients with BTM, with hepatitis negative screening (checked every year), for at  least   five years of DFO therapy and 4-5 years of DFX therapy .Results: DFX  therapy (20 mg/kg/day)  significantly decreased serum ferritin level in patients with BTM, this was associated with significant decrease in serum ALT, AST, ALP and increase in IGF-I concentrations. Albumin concentrations did not change after DFX treatment. ALT and AST levels were correlated significantly with serum  ferritin concentrations ( r = 0.45 and 0.33 respectively , p < 0.05) . IGF-I concentrations were correlated significantly with serum ALT (r= 0.26, p = 0.05) but not with AST, ALP, bilirubin or albumin levels.The negative correlation between serum ferritin concentrations and ALT suggests that impairment of hepatic function negatively affects IGF-I synthesis in these patients due to iron toxicity, even in the absence of hepatitis.Conclusions: Some impairment of liver function can occur in hepatitis negative BMT patients with iron overload. The use of DFX was associated with mild but significant reduction of ALT, AST and ALP and increase in IGF-I levels. The negative correlation between IGF-I and ALT concentrations suggest that preventing hepatic dysfunction may improve the growth potential in these patients.

Prognostic Impact of Elevated Serum Ferritin in Patients Undergoing Myeloablative Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 595-595 ◽  
Author(s):  
Philippe Armand ◽  
Corey S. Cutler ◽  
Haesook T. Kim ◽  
Vincent T. Ho ◽  
John Koreth ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Iron Overload ◽  
Cell Transplantation ◽  
Serum Ferritin ◽  
Ferritin Level ◽  
Elevated Serum ◽  
Albumin Level ◽  
Prognostic Impact ◽  
Disease Free

Abstract Patients undergoing allogeneic stem cell transplantation (alloSCT) for hematologic malignancies are often highly transfused, and thus at risk for transfusion-associated iron overload. In other settings, such as thalassemia or hemochromatosis, iron overload has been associated with organ toxicity, particularly hepatotoxicity, as well as with an increased susceptibility to infection. Since hepatic and infectious complications are frequent and life-threatening in patients undergoing alloSCT, iron overload could potentially be an important contributor to treatment-related morbidity and mortality after transplantation. We studied 935 consecutive patients who underwent myeloablative alloSCT at our institution between 1997 and 2005. A pre-transplant serum ferritin level, which we used as a surrogate measure of iron load, was available for 600 of the 935 patients (64%). The median ferritin level was 864ng/ml. The percentage of patients with serum ferritin ≥1000ng/ml was 47%. This percentage varied significantly between disease types, being lowest (6%) in patients with CML and highest (79%) in patients with AML. A ferritin level ≥1000ng/ml was associated with significantly worse overall and disease-free survival, as shown in the figure. Figure Figure This was confirmed in proportional hazards models using the following covariates: age, type and stage of disease, cytogenetic risk group for AML and MDS, conditioning regimen, HLA match, graft source, GVHD prophylaxis regimen, CMV serostatus, gender, prior transplant, and year of transplantation. In this model, the hazard ratio for mortality associated with ferritin ≥1000ng/ml was 1.7 (95%CI=1.3 to 2.4, p=0.0005). In competing risks regression analysis, using the same covariates, an elevated serum ferritin was associated with a significant increase in non-relapse mortality (NRM) (HR=1.6, p=0.02), but not with a significant increase in the risk of relapse. The greatest impact of elevated serum ferritin on survival and NRM was in patients with MDS (HR for mortality=3.0, p=0.001). Because serum ferritin is an acute phase reactant, we performed the same analyses using pre-transplant albumin level as an additional covariate that could reflect general inflammatory state. Although albumin level was of independent prognostic significance, its inclusion in the multivariate models did not alter the conclusions. Finally, in logistic regression analyses, elevated serum ferritin was associated with a non-significant increase in the risk of veno-occlusive disease (OR=1.6, p=0.09), but not in an increased risk of acute GVHD (OR=0.9, p=0.4) or specifically of acute liver GVHD (OR=1.2, p=0.5). Conclusions: in patients undergoing myeloablative alloSCT, and particularly in those with MDS, an elevated serum ferritin is associated with significantly higher NRM, as well as significantly lower disease-free and overall-survival. Our results could be helpful in estimating prognosis for patients who are candidates for myeloablative alloSCT. They also pave the way for prospective trials on the impact of iron overload and on the possible beneficial role of iron chelation in this patient population.

A Prognostic Model for Predicting the Impact of Comorbidities on Survival of Patients with Myelodysplastic Syndromes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2453-2453 ◽  
Author(s):  
Matteo G. Della Porta ◽  
Luca Malcovati ◽  
Erica Travaglino ◽  
Cristiana Pascutto ◽  
Margherita Maffioli ◽  
...  
Keyword(s):  
Heart Failure ◽  
Iron Overload ◽  
Myelodysplastic Syndromes ◽  
Cardiac Death ◽  
Multivariable Analysis ◽  
Risk Groups ◽  
Increased Risk ◽  
Secondary Iron Overload ◽  
Transfusion Dependency ◽  
The Impact

Abstract Myelodysplastic syndromes (MDS) occur mainly in older persons, and these patients are likely to have comorbidities. We studied the impact of comorbidities on non-leukemic death (NLD) and overall survival (OS) in MDS patients with the aim of developing a specific prognostic index. Eight hundred forty consecutive patients receiving a diagnosis of MDS at Policlinico San Matteo, Pavia, Italy, between 1992 and 2006 were retrospectively evaluated. One or more comorbidities were present in 455/840 (54%) patients: the older the age, the higher their prevalence (P&lt;0.001). Cardiac disease was observed in 25% of patients, liver disease in 16%, diabetes in 11%, prior solid tumor in 10%, nephropathy and pulmonary disease in 4%. Non-leukemic causes of death included cardiac failure (63%), infection (24%) and hemorrhage (7%). In a Cox analysis with age, sex, WHO category, cytogenetics and transfusion-dependency as time-dependent covariates, the presence of one or more comorbidities significantly affected both the risk of NLD (HR=1.91, P=0.001) and OS (HR=1.51, P=0.01), while it did not influence the risk of leukemic progression. The negative effect of comorbidities on OS was more evident in patients without excess of blasts (HR=1.8 P=0.007), while it retained a borderline significance in patients with more advanced disease (P=0.05). By including comorbidities as distinct entities in multivariable analysis, cardiac failure, liver or pulmonary disease, and solid tumors were found to independently affect the risk of NLD (HR=3.7, HR=2.08, HR=2.07 HR=2.23, respectively; P values from &lt;0.001 to 0.033). Based on results of uni- and multivariable analysis, we developed a prognostic model for predicting the effect of comorbidities on NLD and OS. For each comorbidity, risk scores were estimated from the coefficients of the Cox regression. This MDS-specific comorbidity index (MDS-CI) allowed us to identify 3 groups of patients with different probability of NLD and OS (HR 2.78, P&lt;0.001; HR 1.67 P=0.001), and provided a better stratification than the available non MDS-specific indices. Focusing on WPSS categories [J Clin Oncol2007; 25:3503–10], MDS-CI significantly stratified survival of patients with very-low, low and intermediate risk groups (P&lt;0.001), while it had no effect in high and very-high risk groups. We then investigated the relationship between transfusion-dependency, secondary iron overload and comorbidities. Heart failure (28% vs. 18% P=0.001) and cardiac death (69% vs 55% P=0.03) were significantly more frequent in transfusion-dependent patients. In a Cox analysis with time-dependent covariates, transfusion-dependent patients showed an increased risk of NLD (HR=2.12 P=&lt;0.001), heart failure (HR 1.34 P=0.03), and cardiac death (HR 2.99 P=0.01). The development of secondary iron overload significantly affected the risk of NLD and OS (HR=1.25 and 1.16 respectively, P&lt;0.001), and this effect was maintained after adjusting for transfusion burden. Iron overload specifically increased the risk of developing heart failure (HR=1.17, P&lt;0.001). In summary, the presence of non-hematological comorbidities significantly worsens the survival of MDS patients. Transfusion-dependency and secondary iron overload are associated with an increased risk of cardiac complications and cardiac death. The MDS-CI might be a useful tool for clinical decision making in patients with myelodysplastic syndromes.

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