The effect of measurement area size on the reliability of myocardial iron load measurement in cardiac magnetic resonance imaging examinations of thalassemia patients

Background/aim: The aim of this study was to evaluate the intraobserver and interobserver reliability of cardiac T2* MRI measurements in different region of interest (ROI) sizes. Materials and methods: Cardiac T2* MRIs of 24 thalassemia major patients were evaluated. Two different ROI sizes were used for measurement. In the first measurement, an ROI approximately 5 mm in diameter was used in the interventricular septal myocardium. In the other method, the whole ventricular septal myocardium was used as the measurement. The intraobserver and interobserver variabilities were assessed with the intraclass correlation coefficient (ICC). Results: The measurement of the first observer, the ICC of the small-sized ROI (ssROI), was 0.869, and the measurement for the second observer, the ICC of the ssROI, was 0.659. The ICC of the whole-septal ROI (wsROI) was 0.991 for the first observer and 0.980 for the second observer. Interobserver variability, for the mean measurement, was 0.442 for the ICC of ssROI and 0.883 for the ICC of wsROI. Conclusion: For the evaluation of myocardial iron load with T2* MRI we suggest making measurements with ROI, including all of the interventricular septum, as a consequence of high intraobserver and interobserver consistency.

ß2-Microglobulin, Neutrophil Gelatinase-Associated Lipocalin, and Endocan Values in Evaluating Renal Functions in Patients with ß-Thalassemia Major.

Chronic anemia, transfusion-associated iron deposition, and chelating agents lead to renal impairment in ß-thalassemia (ß-thal) patients. The present study aimed to determine the most reliable and practical method in assessing and predicting renal injury in ß-thal major (ß-TM) patients. Therefore, we assessed the predictive values of urine ß2-microglobulin (ß2-MG) and neutrophil gelatinase-associated lipocalin (NGAL) levels, their ratios to urine creatinine, and serum endocan level. Sixty ß-TM patients and 30 healthy controls were included. Renal functions of the patients and controls were evaluated by means of urine protein/creatinine ratio, urine ß2-MG, urine NGAL, and serum endocan level. The ß-TM and control groups were comparable in terms of the demographic characteristics. Of the ß-TM patients, 26.7% had glomerular hyperfiltration and 41.7% had proteinuria. Compared with the control group, the ß-TM group had significantly higher levels of urine protein/creatinine, urine ß2-MG, urine ß2-MG/creatinine, urine NGAL, urine NGAL/creatinine, and serum endocan. These parameters did not differ between the chelating agent subgroups in the patient group. Urine ß2-MG/creatinine and NGAL/creatinine ratios were the parameters with high specificity in predicting proteinuria. There were significant correlations of urine ß2-MG, urine NGAL, and serum endocan levels with serum ferritin concentration. Urine ß2-MG/creatinine, NGAL/creatinine, and protein/creatinine ratios were correlated with each other in the patient group. Positive correlations of urine ß2-MG, urine NGAL, and serum endocan levels with serum ferritin concentration indicated that iron deposition was associated with endothelial damage and renal injury.

Retrospective evaluation of children with immune thrombocytopenic purpura and factors contributing to chronicity.

OBJECTIVE: Immune thrombocytopenic purpura (ITP) is the most common cause of acquired thrombocytopenia children. The aim of this retrospective study is to describe presenting features and clinical characteristics of ITP and evaluate clinical course, treatment modalities, and complications and determine the effects of preceding infection history, age, gender, treatment modality, and admission platelet count on chronicity. METHOD: Two hundred and eleven patients who were diagnosed ITP and followed-up in Department of Pediatric Hematology, Ankara Children Hematology Oncology Education and Research Hospital between January 2008 and September 2012 were included. Age of the patients, gender, date of admission, date of diagnosis, complaint in the application, previous infection and laboratory tests were recorded. RESULTS: Mean age of the patients on diagnosis was 5.4 ± 4.1 years. The female/male ratio was 1.03. The clinical courses were determined as acute or chronic in 72% and 28% of patients respectively. Mean age at diagnosis was significantly higher in chronic ITP (p < 0.01). Chronic course was significantly higher in female patients (p < 0.05). The most frequent complaint was bruises on the skin (68%). The most common physical examination findings were petechiae, purpura and ecchymosis (89%). Patients with a history of past infection (53.6%) and who had serologically positive infection (15.6%) frequently had acute course (p < 0.01). The most common serologically positive infection was Rubella. The mean platelet count was significantly higher in chronic ITP (p < 0.01). In the initial treatment of patients admitted in the acute phase, megadose methylprednisolone (MDMP) was used in 31% of patients, intravenous immune globulin (IVIG) in 55% of patients and anti-D in 2% of patients while 12% did not receive any treatment. There were no significant differences between the recurrence rate and treatment modality (p > 0.05). CONCLUSION: In our study, in females and in patients without any history of past infection, platelet count >20 × 109/L and initial diagnosis age > 10 years were found to increase the probability of chronic disease, which is compatible with the literature.

The Incidence of Ototoxicity in Patients Using Iron Chelators.

OBJECTIVE: In this study, we aimed to detect the incidences of ototoxicity in patients with hemoglobinopathies taking deferoxamine (DFO), deferiprone, and deferasirox using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) scale to obtain more objective data. MATERIALS AND METHODS: Fifty-five transfusion-dependent patients were evaluated in this study. The NCI CTCAE scale was used to assess ototoxicity levels. The average ferritin and hemoglobin levels, the type of iron chelator, and the duration of therapy of all the patients were recorded. RESULTS: Ototoxicity was observed in 15 patients (31.9 %), all of whom were taking DFO. The median age was 19.5 (6-43) in patients without ototoxicity and 29 (16-50) in those with ototoxicity; this difference was statistically significant (p<0.05). The median ferritin and pre-tx Hb levels were 1391 ng/mL and 9.06 mg/dL, respectively, in patients with ototoxicity and 986.7 ng/mL and 9.24 mg/dL, respectively, in those without ototoxicity; these differences were not significant (p>0.05). Ototoxicity was not observed in the eight patients who used only deferasirox and deferiprone. CONCLUSION: The ototoxicity incidence with DFO at doses below 50 mg/kg/day was 27.3%. Deferiprone and deferasirox were not associated with ototoxic effects in patients taking these drugs.

Prophylactic acyclovir and preemptive ganciclovir to prevent cytomegalovirus disease in children after hematopoietic stem cell transplant.

OBJECTIVES: The purpose of this study was to evaluate the effectiveness of acyclovir prophylaxis and preemptive ganciclovir treatment in preventing cytomegalovirus disease in children who underwent hematopoietic stem cell transplant. MATERIALS AND METHODS: We reviewed the clinical records of 66 children (36 boys, 30 girls; mean age, 9 ± 5 y; age range, 2-20 y) who underwent hematopoietic stem cell transplant at Ankara Children's Hematology and Oncology Hospital, Bone Marrow Transplantation Unit, between April 2010 and March 2012. RESULTS: In these 66 children, 61 children (92.4%) received allogeneic transplant; 50 children (76.9%) received a myeloablative regimen; and 14 children (21.2%) received anti-thymocyte globulin as part of the conditioning regimen. All children received acyclovir prophylaxis from the beginning of conditioning regimen until 100 days after transplant, and children received preemptive treatment with ganciclovir when cytomegalovirus DNAemia ≥ 400 copies/mL on 2 tests or ≥ 1000 copies/mL on 1 test. There were 19 children (28.8%) who had cytomegalovirus reactivation during median follow-up 381 days (range, 100-720 d). Cytomegalovirus disease was observed in only 2 patients (10.5%); 1 patient had cytomegalovirus hepatitis and 1 patient had cytomegalovirus gastrointestinal disease. Both patients were cured of cytomegalovirus with treatment for 1 month. There was no death attributable to cytomegalovirus reactivation and/or disease. Febrile neutropenia, acute graft-versus-host disease, and steroid use were more frequent in patients who had cytomegalovirus than did not have cytomegalovirus reactivation. The risk of cytomegalovirus reactivation was increased 5-fold in patients who used steroids. CONCLUSIONS: Acyclovir prophylaxis and preemptive treatment with ganciclovir may be effective in preventing cytomegalovirus disease in most children who have hematopoietic stem cell transplant.

Adjuvant corticosteroid therapy in hepatosplenic candidiasis-related iris.

Candida infections are the most frequent infections in neutropenic patients. Hepatosplenic candidiasis (HSC) is a part of disseminated Candida infection that occurs most commonly in patients with hematologic malignancies treated with chemotherapy and requires protracted antifungal therapy. During invasive mycosis with rapid resolution of immunosuppression, immune reconstitution inflammatory syndrome (IRIS) which mimics treatment failure, drug toxicity or breakthrough infections may occur. Manifestation period, histopathologic findings and favorable effect of steroids to its inflammatory symptoms strongly suggest that HSC belongs to the invasive fungal infection induced IRIS. We present a child with B cell-acute lymphoblastic leukemia who developed HSC and addition of corticosteroid therapy to antifungal treatment achieved rapid resolution of the clinical symptoms and laboratory findings.

Deferasirox therapy in children with Fanconi aplastic anemia.

Thirty-nine children with Fanconi aplastic anemia (FAA) have been followed up in our center between January 2008 and November 2010. Eight of these children (20%) with a transfusional iron overload had been undergoing deferasirox treatment during the study period. In the English literature, transfusional iron overload and the use of an iron chelator in children with FAA has not yet been evaluated. Here, we have presented the effectivity and tolerability of deferasirox in children with FAA and a transfusional iron overload. Before the deferasirox treatment, the mean serum ferritin level was 3377 ± 2200 ng/mL. After a mean 13.6-month treatment duration, the mean ferritin level decreased to 2274 ± 1300 ng/mL (P<0.05). In our series, 3 patients had renal and 3 had hepatic toxicity during the treatment. Two patients had peliosis hepatis and 2 had congenital renal abnormalities before the treatment. There may be differences in the side-effect profiles of deferasirox treatment in patients with FAA. In our series, despite the low number of cases, nephrotoxicity and hepatotoxicity were common side effects instead of gastrointestinal disturbances reported in other studies. Deferasirox is an oral, easily applicable, and effective iron chelator; baseline hepatotoxicity and nephrotoxicity may increase the development of toxic side effects in children with FAA. Patients with FAA receiving deferasirox treatment should be followed up closely for these side effects.

Unilateral exudative retinal detachment as the sole presentation of relapsing acute lymphoblastic leukemia.

Ocular findings are rarely the initial symptom of leukemia, although up to 90% of all leukemia patients have fundus changes during the course of the disease. Herein we report a relapsing acute lymphoblastic leukemia patient with thesole presentation of sudden visual loss and exudative retinal detachment. An 8-year-old boy with acute lymphoblasticleukemia developed sudden visual loss during his first remission period. Bullous retinal detachment with total afferentpupillary defect was observed. Orbital magnetic resonance imaging revealed an intraocular mass lesion; simultaneouslyobtained bone marrow and cerebrospinal fluid samples showed no evidence of leukemic cells. Following local irradiation,and systemic and intrathecal chemotherapy the mass disappeared. Local irradiation, and systemic and intrathecalchemotherapy effectively controlled the isolated ocular relapse of acute lymphoblastic leukemia and eliminated the needfor enucleation.

Treatment of Priapism with Automated Red Cell Exchange and Hyperbaric Oxygen in an 11-year-old Patient with Sickle Cell Disease.

Priapism affects up to 50% of all males with sickle cell disease, and there is no standard treatment. Delayed and unsuccessful treatment leads to corporal fibrosis and impotence. It is therefore necessary to determine the best treatment methods for this complication in order to offer effective interventions to all affected patients. Herein we report an 11-year-old patient with sickle cell disease that presented with priapism 72 h after onset, and was successfully treated with automated red cell exchange and hyperbaric oxygen following unsuccessful surgical and conventional interventions.

Relation of soluble endothelial protein C receptor and cytokines after allogeneic hematopoietic stem cell transplantation.

AIM: The objective of this study was to elucidate the effects of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), interleukin 2 (IL-2), interleukin 6 (IL-6), and interleukin 8 (IL-8) on the expression of soluble endothelial protein C receptor (sEPCR) in the pathogenesis of thrombotic complications after hematopoietic stem cell transplantation (HSCT). METHODS: The relationship between plasma concentrations of proinflammatory cytokines (TNF-α, IL-1ß, IL-2, IL-6, and IL-8) and sEPCR was evaluated in 32 consecutive allogeneic hematopoietic stem cell-transplanted patients prior to conditioning regimen and randomly once between +5 and +30 days after transplantation and compared these results with 20 healthy controls. RESULTS: Soluble endothelial protein C receptor levels did not indicate any significant difference between pre- and posttransplantation period, and sEPCR levels showed a significantly negative correlation between IL-6 and IL-8 (sEPCR and IL-6, r = -.43, P < .01; sEPCR and IL-8, r = -.57, P < .01). There was no correlation between sEPCR levels and TNF-α, IL-1ß, or IL-2 (sEPCR and TNF-α, r = -.13, P > .05; sEPCR and IL-1ß, r = -.1, P ≥ .05; sEPCR and IL-2, r = -.07, P > .05). CONCLUSIONS: Our results suggest that the production of sEPCR was not affected by allogeneic HSCT. Soluble endothelial protein C receptor did not show any positive correlation between these proinflammatory cytokines (TNF-α, IL-1ß, IL-2, IL-6, and IL-8), on the contrary a significantly negative correlation was determined between sEPCR and either IL-6 or IL-8. This negative correlation may be a protective mechanism in the pathway of protein C activation.

A different interaction between parathyroid hormone, calcitriol and serum aluminum in chronic kidney disease; a pilot study.

BACKGROUND/AIMS: Aluminum (Al) is an ingredient of a variety of foodstuffs and medications as well as of domestic water supplies. The patients with chronic kidney disease (CKD) are more susceptible to bone toxicity of Al. The aim of the study was to investigate the interactions between serum Al, parathyroid hormone (PTH) and active vitamin-D in CKD. METHODS: A total of 10 pediatric patients with CKD and 20 healthy controls were enrolled in study. The blood calcium, aluminum, PTH, alkaline phosphatase and phosphorus were evaluated at onset and following a regimen of oral 1,25 dihydroxycholecalciferol (1,25 DHC) for 4 weeks. RESULTS: Although median values of PTH, calcium, phosphorus and alkaline phosphatase did not differ (P > 0.05) after calcitriol administration, the aluminum levels (median: 27.2 ng/ml, range: 11.3-175) declined significantly (median: 3.8 ng/ml, range: 0.64-11.9) after a regimen of oral 1,25 DHC for 4 weeks in all participants (P < 0.05). The median levels of aluminum after 1,25 DHC did not show statistically significant difference with median aluminum levels of healthy controls (median: 2.5 ng/ml, range: 0.2-33.2) (P < 0.05). CONCLUSION: Calcitriol may lead to decline in serum Al levels in CKD patients.

The role of tumor necrosis factor-alpha -308 G/A and transforming growth factor-beta 1 -915 G/C polymorphisms in childhood idiopathic thrombocytopenic purpura.

OBJECTIVE: To increase our understanding of the etiology of idiopathic thrombocytopenic purpura (ITP) some cytokine gene polymorphisms were analyzed for susceptibility to the disease. The aim of this study was to investigate the role of tumor necrosis factor-alpha (TNF-α) -308 G/A and transforming growth factor-beta 1 (TGF-ß1) -915 G/C polymorphisms in the development and clinical progression of childhood ITP. METHODS: In all, 50 pediatric patients with ITP (25 with acute ITP and 25 with chronic ITP) and 48 healthy controls were investigated via LightCycler® PCR analysis for TNF-α -308 G/A and TGF-ß1 -915 G/C polymorphisms. RESULTS: The frequency of TNF-α -308 G/A polymorphism was 20%, 16%, and 22.9% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05). The frequency of TGF-ß1 -915 G/C polymorphism was 16%, 8%, and 8.3% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05). The risk of developing ITP and clinical progression were not associated with TNF-α -308 G/A (OR: 0.738, 95% CI: 0.275-1.981, and OR: 0.762, 95% CI: 0.179-3.249) or TGF-ß1 -915 G/C (OR: 1.5, 95% CI: 0.396-5.685, and OR: 0.457, 95% CI: 0.076-2.755) polymorphisms. CONCLUSION: The frequency of TNF-α -308 G/A and TGF-ß1 -915 G/C polymorphisms did not differ between pediatric ITP patients and healthy controls, and these polymorphisms were not associated with susceptibility to the development and clinical progression of the disease.

Serum sickness-like syndrome after immunoglobulin M-enriched polyclonal immunoglobulin.

Medication reactions, infectious etiologies, graft vs. host disease, serum sickness, and serum sickness-like reaction are the most common conditions that cause skin fever and rashes in immunosuppressed patients. In addition to this long list of diseases, severity of the primary disease and deterioration in the patient's health status can make the diagnosis difficult. Furthermore, cutaneous and histological similarities in these mentioned conditions can be confounding. Here, we present a 16-year-old male patient with acute myeloid leukemia suffering from skin rashes and fever that appeared following a chemotherapy course leading to bone marrow suppression. We aim to discuss the differential diagnosis and share the diagnostic challenges that we already have experienced after immunoglobulin M-enriched polyclonal immunoglobulin.

High dose calcitriol in osteopetrorickets.

Osteopetrorickets is a rare autosomal recessive disorder of osteoclast function characterized by abnormally dense bone and failure of resorption of calcified cartilage. Rickets is a paradoxical complication of osteopetrosis, resulting from the inability of the osteoclasts to maintain a normal calcium-phosphorus balance in the extracellular fluid. We report a patient with an unusual case of infantile osteopetro-rickets who was admitted with anterior fontanel bulging and was treated with haploidentical bone marrow transplantation.

An autoimmune lymphoproliferative syndrome initially diagnosed as Evans syndrome.

Autoimmune lymphoproliferative syndrome (ALPS) is a rare childhood disorder characterized by chronic non-malignant lymphoproliferation and autoimmunity. Patients with ALPS frequently exhibit episodic and intermittent, severe autoimmune- induced hemolytic anemia, thrombocytopenia or combined cytopenias. The co-occurrence of immune-mediated cytopenias, autoimmune thrombocytopenia and autoimmune hemolytic anemia is also known as Evans syndrome. This report describes a child who presented with Evans syndrome symptoms and who, after the detection of increased percentage of double negative T cell population in the peripheral blood, was diagnosed as ALPS. He received several courses of treatment including glucocorticoids, cyclosporine A (Cs A), and intravenous immunoglobulin (IVIG) without any clinical benefit and was treated with the antimalarial drug Fansidar®. With administration of Fansidar® (half tablet per week; containing 250 mg of pyrimethamine and 12.5 mg of sulfadoxine) combined with immunosuppressive drugs, clinical status and laboratory findings temporarily improved. After two months, the patient underwent laparoscopic splenectomy because of worsening of thrombocytopenia refractory to the treatment. There was a transient beneficial effect from splenectomy. We were unable to stop immunosuppressive therapy and Fansidar®; however, this combined therapy was successful in decreasing the number of hospitalizations and controlled his clinical symptoms more effectively for six months. Unfortunately, he was admitted to a regional hospital with high fever and died at the age of three.