Efforts have been undertaken to find an alternative approach to packed red cell transfusion (PRCT) in major beta-thalassemia. Augmentation of fetal hemoglobin (HbF) by hydroxyurea (HU) has been reported to be less effective in this condition as compared to sickle cell anemia due to molecular heterogeneity of the former disease. HU efficacy and its relation to Xmn1 polymorphism and IVSII-1 mutation was evaluated in major beta-thalassemics. Forty-five patients, M/F ratio 0.8, aged 6-33 years, received oral HU, 20 mg/kg per day, 4 days per week and daily1 mg folic acid. Thirty-six patients were PRCT dependent (group A) and nine independent (group B). The aim was to stabilize or increase pre-PRCT Hb over 10.0+/-0.5 g/dl and to reduce the need or cease the PRCT in group A and to increase Hb level and curb the ineffective erythropoesis, e.g., splenomegaly, facial bone deformity, in group B. HU was administered for at least 6 months (mean: 9 months) and discontinued in case of response failure. Screening for Xmn1 polymorphism and IVSII-1 mutation was carried out in most patients. In group A, 25 patients have become PRCT independent for a period of 2.5-7.3 years (mean: 4 years). The mean Hb, pre-HU 10.0 and post-HU 10.7 g/dl (range: 8.8-13.7 g/dl), mean serum ferritin pre- and post-HU was1877 and 525 ng/ml. The PRCT requirement was reduced in one patient, and ten patients did not respond. In group B HU has been given over 3.3 years (range: 2.8-4.8 years), Hb increased from 9.3 to 10.4/dl, and there was no tangible progression of ineffective erythropoesis. Responders in both groups expressed more comfort with this regimen. Xmn1 and IVSII-1 (homo- and/or heterozygosis) are relevant markers in most responding patients. Molecular determination of genetic markers in early childhood will help to identify candidates for pharmacological HbF switching by HU.

BackgroundHeart failure resulting from myocardial iron deposition is the most important cause of death in β-thalassemia major (TM) patients. Cardiac T2*magnetic resonance imaging (MRI), echocardiography, and serum ferritin level serve as diagnostic methods for detecting myocardial iron overload. In this study, we aimed to evaluate the relationship between the above-mentioned methods.MethodsT2*MRI and echocardiographic measurement of left ventricular (LV) systolic and diastolic function were performed in 63 patients. Serum ferritin level was measured. The relationships between all assessments were evaluated.ResultsThere were 40 women and 23 men with a mean age of 23.7±5.1 years (range, 15-35 years). There was no statistically significant correlation between serum ferritin level and LV systolic and diastolic function (P=0.994 and P=0.475, respectively). T2*MRI results had a significant correlation with ferritin level; 63.6% of patients with serum ferritin level >2,000 ng/mL had abnormal cardiac MRI, while none of the patients with ferritin level <1,000 ng/mL had abnormal cardiac MRI (P=0.001). There was no significant correlation between MRI findings and LV systolic function (P=1.00). However, we detected a significant difference between LV diastolic function and cardiac siderosis (P=0.03)ConclusionMRI findings are a good predictor of future cardiac dysfunction, even in asymptomatic TM patients; however, diastolic dysfunction may happen prior to cardiac siderosis in some patients, and echocardiography is able to diagnose this diastolic dysfunction while T2*MRI shows normal findings.

The DAL/GPOH-HD-based treatment approach proved to achieve long-term sustained cure even in children with advanced HD disease. The essentially outpatient diagnosis and treatment modus did not compromise the disease outcome, and was well tolerated and accepted by the patients and their parents. The employed drugs are easily available and affordable. This treatment approach is suitable for ambulatory use in developing countries. However, male infertility remains the major obstacle to procarbazine and cyclophosphamide use.

Intra-abdominal fibromatosis (IAF) is a rare benign neoplasm arising from the abdominal fibrous tissue, mostly in the mesentery. IAF is characterized by a tendency to infiltrate the surrounding vessels and vital structures and recurrence after usually incomplete surgical removal. Accordingly, IAF is associated with considerable morbidity and mortality. The authors report on a boy who presented with a large IAF at the age of 5 years. Within 6 months after initial presentation, he underwent 4 subsequent abdominal explorations for diagnosis, tumor reduction, and intestinal obstructions. IAF was confirmed by the presence of vimentin and absence of other biological cell markers. Due to accelerated tumor growth and deteriorated general condition, as a last resort, a chemotherapy trial with vincristin and methotrexate was carried out. This regimen proved to be effective in reducing the tumor burden and improving the patient's general condition. Outcome of IAF depends on early diagnosis and complete tumor resection, and, if indicated, timely employment of neo/adjuvant chemotherapy. Radiotherapy must be considered in life-threatening conditions as the last resort in a growing child [2-4].

This report emphasises (1) the importance of the emergence of gram-negative organisms in the pathogenesis of overwhelming post-splenectomy infections in thalassaemics, irrespective of their age and splenectomy interval, (2) the necessity to start immediate intravenous treatment with broad spectrum antibiotics in febrile individuals and (3) to draw attention to the need of a well designed study of this problem and its prevention.In thalassaemia major, ineffective erythropoesis causes chronic haemolytic anaemia resulting in extramedullary haematopoesis, iron overload and organ dysfunction. Regular packed red cell transfusion (PRCT) to maintain the pre-PRCT level at 10.5±0.5 g/dl and iron chelating with desferrioxamine to keep the serum ferritin (SF) <2,000 ng/ml have been effective in suppressing the ineffective erythropoesis and reducing the iron burden, thus improving life quality and expectancy and delaying splenomegaly [6]. Splenectomy (SE), as indicated by increased PRCT requirement, splenomegaly and hypersplenism, is now carried out in late adolescence. Having lost the protective immune function of the spleen, patients become life-long prone to overwhelming post-splenectomy infections (OPSI) and have a higher infection rate and susceptibility to OPSI in comparison to those undergoing SE for, e.g. hereditary spherocytosis, idiopathic thrombocytopenia and trauma. OPSI are caused predominantly by encapsulated Streptococcus pneumoniae (50%-60%) with a mortality rate of 60% and less frequently by Haemophilus influenzae and Neisseria meningitidis. Infections caused by Klebsiella spp., Pseudomonas aeruginosa, E. coli, Salmonella spp. and Staphyolococcus aureus have also been reported. The current infection prophylaxis targets the encapsulated pathogens and consists of pre-SE immunisations and post-SE penicillin prophylaxis to provide protection against bacterial strains, not covered by antipneumococcal vaccine and to protect those who fail to have immune response [1,3,4,5].Of 101 homozygous b-thalassaemics managed in our department, 54 have undergone SE (increased PRCT requirement and splenomegaly). Occurrence of gramnegative OPSI in the last decade prompted us to evaluate its frequency in this cohort. The female/male ratio was 1:3, age range 8-43 years, mean age at SE 11.8 years and post-SE follow-up of 1-36 years. All patients received antipneumococcal vaccine 2 weeks prior to SE and thereafter oral prophylactic penicillin 125 mg or 250 mg twice daily according to their age. Anti-pneumococcal booster vaccination was administered at 5-year intervals. The survey revealed only eight episodes of OPSI in seven patients (13%), three males and four females, age range 10-21 years, SE interval 2-11 years, mean 5.8 years. Three patients had diabetes mellitus and one had hepatitis B. All patients presented with high fever, two had hepatic abscess, one sepsis followed 2 months later by hepatic abscess and pleuropneumonia, one multiple brain abscesses, one purulent arthritis and septic meningitis and two had purulent meningiti...