Efthimia Vlachaki

MRI assessment of liver iron content in thalassamic patients with three different protocols: comparisons and correlations

Our aim was to assess liver iron content, in thalassaemic patients, by using three different MR protocols and compare their data. Ninety‐four thalassaemic patients (44 M and 50 F, mean age 25.82 ± 8.3 yrs), were enrolled in the study. In each patient, three measurements of the liver iron content were performed, with the use of a single imager, equipped with a 1.5 Tesla magnet. Liver R2* was measured on gradient‐echo sequence. Calculation of MR‐HIC values was based on an algorithm using liver to muscle (L/M) ratios in five axial gradient‐echo sequences. Finally, determination of liver R2 employed a 16‐echo, spin‐echo pulse sequence. Additionally, myocardial R2* value was determined for each patient. Results showed that all three magnetic resonance imaging (MRI) methods were highly correlated to each other and significantly correlated to serum ferritin concentrations. Liver R2 method showed an increased sensitivity in detecting liver iron contents in the upper range. No correlation occurred between each liver MRI parameter and myocardial R2* values. Finally, we managed to provide formulae for equating values obtaining with any of these three MRI methods.

Comparison of effects of different long-term iron-chelation regimens on myocardial and hepatic iron concentrations assessed with T2* magnetic resonance imaging in patients with β-thalassemia major

The aim of this study was to compare the effect of different long-term chelation regimens on heart and liver iron stores with the use of T2* magnetic resonance imaging (MRI) in patients with transfusion-dependent β-thalassemia major. Sixty-four patients (28 men, 36 women; mean age, 26.49 ± 5.8 years) were enrolled in the study. The 3 groups were based on the chelation therapy received. The first group (19 patients) received deferiprone (DFP) (75 mg/kg per day orally), the second group (23 patients) received deferoxamine (DFO) (30–50 mg/kg per day subcutaneously at least 5 times/week), and the third group (22 patients) received a combination of DFO (30–50 mg/kg per day, 2–3 days/week) and DFP (75 mg/kg per day, 7 days/week). MRI scans were acquired with an imager equipped with a 1.5 T magnet, and the data included myocardial and hepatic iron measurements obtained by means of T2*, and ventricular volumes and ejection fractions obtained with standard cardiovascular MRI techniques. The results revealed that the DFP and the combined groups had significantly less myocardial iron than the DFO group (mean myocardial T2*, 35.77 ± 18.3 milliseconds and 38.05 ± 15.3 milliseconds versus 23.77 ± 13 milliseconds [P =.02, andP =.001], respectively). On the contrary, the DFP group had a significantly higher hepatic iron content than the DFO and combined groups (mean hepatic T2*, 3.29 ± 2.5 milliseconds versus 8.16 ± 8.4 milliseconds and 11.3 ±10.9 milliseconds [P =.014, andP =.003], respectively). No correlation was observed between myocardial T2* and hepatic T2* values (r =-0.043;P =.37). Myocardial T2* values were inversely correlated with age (r =-0.249;P =.024) and positively correlated with both left and right ventricular ejection fractions (r = 0.33 [P =.004], andr = 0.279 [P =.014], respectively). Finally, liver T2* was strongly and inversely correlated with serum ferritin concentration (r =-0.465;P =.001). In conclusion, combined chelation therapy seems to sum the beneficial effects of DFO and DFP with respect to hepatic and myocardial iron. Because myocardial iron is not related to measurements of serum ferritin or hepatic T2*, important decisions on clinical management relating to cardiac risk should not rely on these conventional parameters. Thus, the use of MRI for assessing myocardial iron should be adopted in the routine clinical management of patients with β-thalassemia major.

Peripheral blood haematopoietic progenitor cells in patients with beta thalassaemia major receiving desferrioxamine or deferiprone as chelation therapy.

Objectives: The main adverse effect of deferiprone is the development of neutropenia, which occurs via an unknown mechanism. We aimed to gain insight into the pathogenesis of deferiprone‐induced neutropenia by assessing the peripheral blood haematopoietic progenitor cells. Methods: Sixteen patients with beta thalassaemia were studied; nine (Group A) were receiving desferrioxamine and seven (Group B) deferiprone. Ten healthy individuals comprised the control group (Group C). Results: Granulocyte‐erythrocyte‐monocyte‐megakaryocyte colony forming units were significantly more in Groups A and B compared with Group C. Granulocyte‐macrophage colony forming units (CFU‐GM) were significantly more in Group B compared with Group C. Macrophage colony forming units were significantly less in Group B compared with Group C. Granulocyte colony forming units (CFU‐G) were significantly more in Group A compared with Group C. We found a trend in the difference in the number of CFU‐G between patients’ groups (P = 0.123). Adding serum from patients receiving deferiprone to cultures of controls resulted in a maturation arrest of the granulocytic lineage. Conclusion: Our findings point to a maturation arrest at the level of CFU‐GM as a potential mechanism of deferiprone‐induced neutropenia.

Poor correlations between measurements of bone quality by quantitative ultrasound sonography and dual energy X‐ray absorptiometry in patients with β‐thalassaemia major

Objectives:  Osteopenia/osteoporosis is a major component of morbidity even in young patients with β‐thalassaemia major. Dual energy X‐ray absorptiometry (DXA) is the reference method for determining bone mineral density (BMD). Quantitative ultrasound sonography (QUS) for bone measurement is a relatively new, inexpensive and radiation‐free method that could serve as an alternative to DXA. Our aim was to assess bone status in thalassaemic patients both with QUS and DXA and, consequently, to investigate the degree of correlation between the two methods.

Elevated serum parathormone levels are associated with myocardial iron overload in patients with β-thalassaemia major

Objectives:  Despite advances in conventional treatment, iron‐induced cardiomyopathy is still the most frequent cause of death among patients with β‐thalassaemia major. Recent studies have correlated increased myocardial iron content to decreased levels of vitamin D in thalassaemic patients. The aim of this study was to measure parathormone (PTH) and metabolites of vitamin D and consequently to investigate whether these parameters predispose to myocardial iron overload in patients with β‐thalassaemia major.

Deferiprone-related arthropathy of the knee in a thalassemic patient: report of a case and review of the literature

Deferiprone (DFP), the first oral iron chelator, has been used in patients with β-thalassemia major to reduce serum ferritin levels and total iron burden, leading to decreased cardiac iron levels. Major side effects include embryotoxicity, agranulocytosis, zinc deficiency and gastrointestinal disorders, while arthropathy is rarely reported. Herein, we present a 29-year-old male patient with β-thalassemia major, who developed severe arthritis of both knees while under deferiprone therapy. Arthritis was managed successfully with non-steroid antiinflammatory drugs after DFP withdrawal.

Parotid gland oncocytoma: a case report

Oncocytomas are a rare group of neoplasms of the parotid gland which have been correlated to various viral infections. We report the first case of a patient with parotid oncocytoma and a previous history of chronic HBV infection.

Is Deferasirox Implicated in Multiple Organ Failure in a Patient With Homozygous β-Thalassemia?

We herein report a case of a thalassemic-patient who was on deferasirox chelation therapy and admitted to the emergency department because of fever, diffuse abdominal pain and altered mental status. Despite the appropriate treatment he died two days later due to cardiac arrest. As we failed to recognize any etiology and the patients’ relatives denied a post mortem examination due to religious reasons, we cannot provide any additional data. However, we are wondering whether this incident might be related to deferasirox.

Is liver stiffness really unrelated to liver iron concentration

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Pure red cell aplasia complicating B cell small lymphocytic lymphoma: a case report

Pure red cell aplasia (PRCA) is characterized by severe normocytic, normochromic anemia, reticulocytopenia and absence of erythroblasts from an otherwise normal bone marrow [1]. According to PRCA classification, secondary forms are associated with thymoma, hematologic malignancies, solid tumors, systemic autoimmune diseases, drugs, viruses and chronic renal failure [2]. The association of B cell small lymphocytic non-Hodgkin lymphoma with PRCA is considered to be extremely rare [1]. In this case report, we present a patient with PRCA and B cell lymphocytic lymphoma. A 70-year-old male patient, undergoing trans-urethral prostatectomy for benign prostate hyperplasia, was found with leukocytosis (WBC = 27,000/lL), lymphocytosis (65%) and normocytic, normochromic anemia (Hb = 7 g/ L), during pre-operative investigation. After successful operation, he was referred to our department for further investigation. Previous medical history was unremarkable. Physical examination revealed hepato-splenomegaly and peripheral lymphadenopathy. Extensive screening for viruses (HBV, HCV, HIV, PARVO B19, etc.) proved negative; no immunological abnormalities suggesting an underlying systemic autoimmune disease were detected. Reticulocyte count was\0.5%. Bone marrow aspiration revealed diffuse infiltration by lymphocytes with complete absence of erythroblasts (\3%) and normal megacaryocytes. Peripheral blood immunophenotype and lymph node biopsy led to the diagnosis of CD20 (?) B cell small lymphocytic lymphoma. Additionally, peripheral blood immunophenotyping revealed FMC7 (?) and CD5(-). The patient was administered combined therapy with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) in 21-day intervals; prednisolone was administered uninterruptedly. Unfortunately, he suffered an acute allergic reaction to rituximab and the drug was discontinued. After three cycles of CHOP, lymphadenopathy and leukocytosis were markedly improved; however, anemia was refractory and maintained by frequent blood transfusions (approximately 3–4 units of packed RBCs every 2 weeks). Cyclosporine A (dose 5 mg/ kg) was added to the therapeutic regimen; after 1 month, the patient needed no further transfusions and he managed to complete eight cycles of CHOP. After 18 months of follow up, the patient remains in remission, regarding both PRCA and B cell lymphoma. Treatment with low-dose cyclosporine A (5 mg/kg) was continued with no further need for RBC transfusions and no adverse effects. Diagnosis of PRCA relies mainly on the absence of erythroblasts from the bone marrow combined with reticulocytopenia. A defined upper cut-off value of erythroblasts required for diagnosis is still controversial; different studies advocate values ranging from 0.5 to 5% [3]. In this patient, there was almost complete absence of erythroblasts, as well as low reticulocyte count. The pathogenetic basis of PRCA remains to be elucidated; nevertheless, evidence support involvement of immune mechanisms, such as marrow infiltration by CD8? T cells and cell-mediated cytotoxicity [4]. Latest reports on the favorable outcome of refractory PRCA with rituximab suggests B cell involvement [5, 6]. It is possible, though, that multiple factors contribute to disease pathophysiology E. Vlachaki (&) K. Tselios S. Charalambidou E. Ioannidou I. Klonizakis Hematology Unit, 2nd Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Konstantinoupoleos St. 49, 54642 Thessaloniki, Greece e-mail: efivlachaki@yahoo.gr