Evaluation of electrocardiographic markers of cardiac arrhythmic events and their correlation with cardiac iron overload in patients with ß-thalassemia major.

Iron overload is associated with an increased risk of atrial and ventricular arrhythmias. Data regarding the relationship between electrocardiographic parameters of atrial depolarisation and ventricular repolarisation with cardiac T2* MRI are scarce. Therefore, we aimed to investigate these electrocardiographic parameters and their relationship with cardiac T2* value in patients with ß-thalassemia major. In this prospective study, 52 patients with ß-thalassemia major and 52 age- and gender-matched healthy patients were included. Electrocardiographic measurements of QT, T peak to end interval, and P wave intervals were performed by one cardiologist who was blind to patients' data. All patients underwent MRI for cardiac T2* evaluation. Cardiac T2* scores less than 20 ms were considered as iron overload. P wave dispersion, QTc interval, and the dispersions of QT and QTc were significantly prolonged in ß-thalassemia major patients compared to controls. Interestingly, we found prolonged P waves, QT and T peak to end dispersions, T peak to end intervals, and increased T peak to end/QT ratios in patients with T2* greater than 20 ms. No significant correlation was observed between electrocardiographic parameters and cardiac T2* values and plasma ferritin levels. In conclusion, our study demonstrated that atrial depolarisation and ventricular repolarisation parameters are affected in ß-thalassemia major patients and that these parameters are not correlated with cardiac iron load.

Congenital Neutropenia Patient With Hypomorphic Biallelic CSF3R Mutation Responding to GCSF.

Congenital neutropenia (CN) is a rare disorder, and the most common gene responsible for CN is ELANE. Furthermore, the mutations of HAX1, G6PC3, and JAGN1 genes may cause CN. These patients generally find great benefit from subcutaneous administration of Granulocyte Colony Stimulating Factor (GCSF). In recent years, Biallelic Colony Stimulating Factor 3 Receptor (CSF3R) mutations have been described as an underlying defect of CN in several children. In contrast to the previous group, the patients who have a CSF3R mutation do not respond to GCSF treatment. Here, we present a CN patient with hypomorphic biallelic CSF3R mutation responding to GCSF.

Proven and probable invasive fungal infections in children with acute lymphoblastic leukaemia: results from an university hospital, 2005-2013.

Despite improvements in diagnosis and treatment, invasive fungal infections (IFIs) are still a major cause of morbidity and mortality in immunocompromised patients. The data on IFI among children with acute lymphoblastic leukaemia (ALL) are still scarce, and our aim was to estimate the risk, aetiology and outcome of proven and probable IFIs in children with ALL who did not receive primary prophylaxis over an 8-year period. Between January 2005 and February 2013, 125 children who were treated for ALL at the Pediatric Hematology Department of the Medical School of Ege University were retrospectively reviewed. Proven and probable IFIs were defined according to revised definitions of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. The proven and probable IFI incidence was 30/125 (24%). Profound neutropenia was detected in 18 (60%) patients, and prolonged neutropenia was detected in 16 (53.3%) of the patients. The most isolated agents were non-albicans Candida spp. The crude and attributable mortality was 20% and 13.3% respectively. Profound neutropenia was associated with mortality (P < 0.05). The younger patients were especially at risk for proven IFI. Prolonged neutropenia, to be in the induction phase of chemotherapy, and profound neutropenia were found to be the most common predisposing factors for IFI episodes.

Diffuse Alveolar Hemorrhage as a Life-Threatening Feature of Juvenile Onset Systemic Lupus Erythematosus: A Case-Based Review.

Diffuse alveolar hemorrhage is an uncommon but serious complication of systemic lupus erythematosus (SLE). We reported a 17-year-old boy with idiopathic thrombocytopenic purpura, who admitted with pallor and petechiae. He had Coombs positive hemolytic anemia and thrombocytopenia (hemoglobin 6.2g/dL, platelets 10,000/mm3 and lactate dehydrogenase 1024U/L), cough, tachypnea, and desaturation in the room air. Chest radiograph revealed bilateral diffuse alveolar opacities and computed tomography showed bilateral diffuse alveolar infiltrates and ground-glass opacity consistent with pulmonary hemorrhage. Anti-nuclear antibody (ANA) was 1:640 with positive Ro and anti-phospholipid antibodies, low C3 and C4, but negative anti-double-stranded DNA. He was treated with pulse methylprednisolone followed by tapering doses of steroids and with 6 doses of intravenous cyclophosphamide once every two weeks followed by mycophenolate mofetil. He had no relapse in the following 3 years. The case was reported to emphasise this life-threatening complication of juvenile-onset SLE and we reviewed the literature.

Fertility in Patients with Thalassemia and Outcome of Pregnancies: A Turkish Experience

Objective: In recent years, the rates of marriage and pregnancy are increasing in patients with thalassemia major. The aim of the present study was to investigate the fertility rate of thalassemic patients and the course of pregnancies in terms of mother and infant health. Materials and Methods: In this observational study patients with major hemoglobinopathy were evaluated regarding marital status, the need for assisted reproductive techniques, fertility rate, iron status, and pregnancy complications. Results: Seventeen female patients gave birth to 21 healthy infants. About one-third of the patients needed assisted reproductive techniques. Thalassemia major patients showed increased serum ferritin levels from 1203±1206 µg/L at baseline to 1880±1174 µg/L at the end of pregnancy. All babies are still alive and healthy. Conclusion: Pregnancy in patients with thalassemia can be safe for the mother and newborn with close monitoring and a multidisciplinary approach.

Hypertension and Life-Threatening Bleeding in Children with Relapsed Acute Myeloblastic Leukemia Treated with FLT3 Inhibitors.

Experiences with new multikinase inhibitors are limited, especially in children. In this report we summarize our experience with 2 patients with relapsed acute myeloblastic leukemia (AML), one with FMS-like tyrosine kinase-3-internal tandem duplication mutation and the other with a single base mutation (D835Y). Both patients received sorafenib, one for 19 days and the other for 42 days, with clofarabine-including chemotherapy. One additionally received sunitinib for a total of 20 days. Both patients developed severe pancytopenia, hypertension, life-threatening bleedings from the gastrointestinal system, and, finally, intrapulmonary hemorrhage. Although both reached severe aplasia of the bone marrow without blastic infiltration, death occurred with neutropenic sepsis.

Rare severe mycotic infections in children receiving empirical caspofungin treatment for febrile neutropenia.

Empirical antifungal therapy is most often given to patients with leukemia. However breakthrough fungal infections under antifungal therapy are not uncommon. Four children, with hematologic malignant disease developed mycotic breakthrough infections while on empirical caspofungin treatment for a median of 14 (range 11-19) days. Trichosporon asahii was detected in the blood culture of two patients and Geotrichum capitatum in the other two (one patient also had positive cerebrospinal fluid culture). Because the patients' clinical situation worsened, voriconazole was empirically added for two patients three and five days before the agent was detected. The first sterile blood culture was obtained 3-7 days of voriconazole treatment. All patients reached clear cultures but one patient died. One patient with central nervous system infection with G. capitatum had severe neurological sequelae. Very severe fungal infections can occur during empirical caspofungin therapy. Therefore, patients should be followed closely.