Rituximab-based immunosuppression for autoimmune haemolytic anaemia in infants.

We report a case series of four infants with severe autoimmune haemolytic anaemia (AIHA) who responded to treatment with rituximab and cyclosporine after having failed first line therapy with high-dose steroid (prednisolone 4-8 mg/kg/d). Rituximab was started at 11-90 d from onset due to continued haemolysis; three infants also received cyclosporine A. Three of four infants reached complete response, defined as normal haemoglobin, reticulocytes and negative indices of haemolysis, at 7-21 months from diagnosis. In long-term follow-up two infants remained disease-free with normal immunology, one had undefined immunodeficiency and one had autoimmune lymphoproliferative syndrome.

Plasma oxysterols in normal and cholestatic children as indicators of the two pathways of bile acid synthesis.

BACKGROUND: No information is available on the hepatic and extrahepatic pathways of bile acid synthesis in normal children and in pediatric cholestatic liver diseases. METHODS: To explore the changes of the two pathways of bile acid synthesis during development, plasma concentrations of 7alpha-hydroxycholesterol and 27-hydroxycholesterol were measured in 50 healthy children (1 month-14 years) and compared to 18 adult controls. We also measured plasma oxysterols in 31 patients with pediatric cholestatic liver disease. RESULTS: A progressive increase of plasma concentrations of both 27-hydroxycholesterol and 7alpha-hydroxycholesterol was found with age. In children with cystic fibrosis-associated liver disease plasma concentrations of 27-hydroxycholesterol were significantly lower compared to age-matched controls (5.6+/-0.5 vs. 12.8+/-1.1 microg/dl; p<0.001) and paralleled significantly lower concentrations of total cholesterol. In infants with biliary atresia plasma concentrations of 27-hydroxycholesterol were significantly higher compared to age-matched controls (8.8+/-0.8 vs. 4.4+/-0.6 microg/dl, p<0.001) paralleling significantly higher concentrations of total cholesterol while 7alpha-hydroxycholesterol resulted significantly lower (1.2+/-0.2 vs. 2.3+/-0.3 microg/100 mg of total cholesterol; p=0.011). CONCLUSIONS: Our data suggest that both pathways of bile acid synthesis reach a state of maturity only after the age of 4 years and are significantly influenced also in children by liver function and intestinal absorption of cholesterol.

Costs, quality of life, treatment satisfaction and compliance in patients with beta-thalassemia major undergoing iron chelation therapy: the ITHACA study.

OBJECTIVES: Iron chelation treatment (ICT) in beta-thalassemia major (beta-TM) patients undergoing blood transfusions can cause low satisfaction, low compliance, with possible negative consequences on treatment success, patients' wellbeing, and costs. The purpose was to estimate the societal burden attributable to beta-TM in terms of direct and indirect costs, health-related quality-of-life (HRQoL), satisfaction and compliance with ICT in patients undergoing transfusions and ICT. RESEARCH DESIGN AND METHODS: The naturalistic, multicenter, longitudinal Italian-THAlassemia-Cost-&-Outcomes-Assessment (ITHACA) cost-of-illness study was conducted involving patients of any age, on ICT for at least 3 years, who were enrolled at 8 Italian Thalassemia Care Centers. Costs were estimated from the societal perspective, quantified with tariffs, prices, or net earnings valid in 2006. RESULTS: One-hundred and thirty-seven patients were enrolled (median age = 28.3, 3-48 years, 49.6% male) and retrospectively observed for a median of 11.6 months. Mean direct costs were euro1242/patient/month, 55.5% attributable to ICT, 33.2% attributable to transfusions. Relevant quantity and quality of productivity was lost. Both physical and mental components of HRQoL were compromised. Little difficulties remembering to take ICT and positive satisfaction with the perceived effectiveness of therapy were declared, but not good levels of satisfaction with acceptance, perception of side effects and burden of ICT. CONCLUSIONS: The management of beta-TM patients undergoing transfusions and ICT is efficacious, although costly, but overall benefits were not always perceived as optimal by patients. Efforts must be focused to improve patients' acceptance and satisfaction with their therapy; this would contribute to a better compliance and hence an increase in treatment effectiveness and patients' overall wellbeing, with expected improved allocation of human and economic resources.

High rate of human herpesvirus-8 seroprevalence in thalassemic patients in Italy.

BACKGROUND: The potential risk of acquiring infection by the novel human herpesvirus-8 (HHV-8) through blood derivatives is still debated. OBJECTIVES: In the present study, we determined HHV-8 seroprevalence in beta-thalassemic patients living in Italy. STUDY DESIGN: We have analysed 86 patients from Sardinia, an island characterised by a high diffusion of HHV-8, as well as 33 thalassemics from the area of Rome, where a lower rate of HHV-8 infection has been reported. These data have been compared with HHV-8 seroprevalence found in healthy controls living in the same areas of the assayed patients. RESULTS AND CONCLUSIONS: A three-fold increase in HHV-8 seroprevalence was found among thalassemic patients when compared to control groups taken from the same regions (17.6% versus 5.1%). This risk factor was statistically significant when considering the Sardinians alone (P = 0.01) and the entire population analysed in the present survey (P = 0.0006). In the Roman area also an increased seroprevalence in thalassemic subjects was found (12.1% versus 4.6%) but it was not statistically significant (P = 0.2). HHV-8 is sporadically present in the blood of healthy individuals and it is unknown whether the virus eventually present in donors' blood is completely cleared by the treatments which blood undergoes before red cells are transfused. Based on these considerations, we hypothesise that multiply transfused subjects living in areas at high HHV-8 prevalence present an increased risk of being infected.

Osteonecrosis: An emerging complication of intensive chemotherapy for childhood acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: Osteonecrosis (ON) is a potentially disabling complication of combination chemotherapy including high doses of steroids. The incidence and main risk factors for symptomatic ON have been investigated in a large group of children treated with high-dose steroids, prednisone and dexamethasone for childhood acute lymphoblastic leukemia (ALL). DESIGN AND METHODS: From May 1995 to December 1999, 1421 patients <18 years old, with newly diagnosed non-B ALL, were registered in the AIEOP-ALL 95 study. Their data were reviewed to identify patients who developed symptomatic ON. For those who were positively identified additional data were requested concerning ON-related symptoms, treatment and outcome. RESULTS: Overall, 15 of the 1421 patients developed symptomatic ON (1.1%) in a total of 29 sites. The estimated 5-year cumulative risk for clinically diagnosed ON was 1.6% (SE 0.4). The incidence was significantly higher among females (p=0.01) and older patients, with a peak rate of 7.4% (2.3) among those aged 10 to 17 years (p<0.0001). When the two factors, i.e. age and gender were combined, there was a striking increase in the risk among female patients aged 10 to 17 years. The median time between the diagnosis of ALL and that of ON was 17 months (range 8-45). The hip was the most frequently involved (19/29) site. INTERPRETATION AND CONCLUSIONS: Symptomatic ON occurred in only 1.1% of patients treated with BFM-type, intensive chemotherapy for childhood ALL. Female adolescents appear to be the subset of patients with the highest risk of ON, especially when categorized as having high risk leukemia and thus administered higher cumulative doses of dexamethasone.