GoCART

Cellular therapies manufactured from cells of haematopoietic origin, such as CAR-T-cell therapies, provide a revolutionary treatment for patients suffering from haematological diseases. Nonetheless, there are considerable challenges in the implementation of these therapies in this rapidly evolving field. These challenges include but are not limited to the complexity of the supply chains for these living drugs and the management of side effects, requiring centre qualification as well as additional and ongoing education of health care professionals; the long-term follow-up of patients treated with therapies with curative intent; the myriad regulatory requirements at the European Union and local level; and reimbursement of the treatments by budget-constrained authorities

Comparison of home fortification with two iron formulations among Kenyan children: Rationale and design of a placebo-controlled non-inferiority trial.

INTRODUCTION: Home fortification powders containing iron and other micronutrients have been recommended by World Health Organisation to prevent iron deficiency anaemia in areas of high prevalence. There is evidence, however, that home fortification at this iron dose may cause gastrointestinal adverse events including diarrhoea. Providing a low dose of highly absorbable iron (3 mg iron as NaFeEDTA) may be safer because the decreased amount of iron in the gut lumen can possibly reduce the burden of these adverse effects whilst resulting in similar or higher amounts of absorbed iron. OBJECTIVE: To show non-inferiority of home fortification with 3 mg iron as NaFeEDTA compared with 12.5 mg iron as encapsulated ferrous fumarate, with haemoglobin response as the primary outcome. DESIGN: 338 Kenyan children aged 12-36 months will be randomly allocated to daily home fortification with either: a) 3 mg iron as NaFeEDTA (experimental treatment), b) 12.5 mg iron as encapsulated ferrous fumarate (reference), or c) placebo. At baseline, after 30 days of intervention and within 100 days post-intervention, blood samples will be assessed for primary outcome (haemoglobin concentration), iron status markers, Plasmodium parasitaemia and inflammation markers. Urine and stool samples will be assessed for hepcidin concentrations and inflammation, respectively. Adherence will be assessed by self-reporting, sachet counts and by an electronic monitoring device. CONCLUSION: If daily home fortification with a low dose of iron (3 mg NaFeEDTA) has similar or superior efficacy to a high dose (12.5 mg ferrous fumarate) then it would be the preferred choice for treatment of iron deficiency anaemia in children

Daily home fortification with iron as ferrous fumarate versus NaFeEDTA : A randomised, placebo-controlled, non-inferiority trial in Kenyan children

Background: We aimed to show the non-inferiority of home fortification with a daily dose of 3 mg iron in the form of iron as ferric sodium ethylenediaminetetraacetate (NaFeEDTA) compared with 12.5 mg iron as encapsulated ferrous fumarate in Kenyan children aged 12-36 months. In addition, we updated a recent meta-analysis to assess the efficacy of home fortification with iron-containing powders, with a view to examining diversity in trial results. Methods: We gave chemoprevention by dihydroartemisinin-piperaquine, albendazole and praziquantel to 338 afebrile children with haemoglobin concentration ≥70 g/L. We randomly allocated them to daily home fortification for 30 days with either placebo, 3 mg iron as NaFeEDTA or 12.5 mg iron as encapsulated ferrous fumarate. We assessed haemoglobin concentration (primary outcome), plasma iron markers, plasma inflammation markers and Plasmodium infection in samples collected at baseline and after 30 days of intervention. We conducted a meta-analysis of randomised controlled trials in pre-school children to assess the effect of home fortification with iron-containing powders on anaemia and haemoglobin concentration at end of intervention. Results: A total of 315 children completed the 30-day intervention period. At baseline, 66.9% of children had inflammation (plasma C-reactive protein concentration >5 mg/L or plasma α 1-acid glycoprotein concentration >1.0 g/L); in those without inflammation, 42.5% were iron deficient. There was no evidence, either in per protocol analysis or intention-to-treat analysis, that home fortification with either of the iron interventions improved haemoglobin concentration, plasma ferritin concentration, plasma transferrin receptor concentration or erythrocyte zinc protoporphyrin-haem ratio. We also found no evidence of effect modification by iron status, anaemia status and inflammation status at baseline. In the meta-analysis, the effect on haemoglobin concentration was highly heterogeneous between trials (I 2: 84.1%; p value for test of heterogeneity: <0.0001). Conclusions: In this population, home fortification with either 3 mg iron as NaFeEDTA or 12.5 mg iron as encapsulated ferrous fumarate was insufficiently efficacious to assess non-inferiority of 3 mg iron as NaFeEDTA compared to 12.5 mg iron as encapsulated ferrous fumarate. Our finding of heterogeneity between trial results should stimulate subgroup analysis or meta-regression to identify population-specific factors that determine efficacy. Trial Registration: The trial was registered with ClinicalTrials.gov ( NCT02073149 ) on 25 February 2014.</p

Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia

BACKGROUND A single-group, phase 1–2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia. METHODS In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months. RESULTS Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P=0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34% and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group Β) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome. CONCLUSIONS The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects