Allogeneic, donor-derived, second-generation, CD19-directed CAR-T cells for the treatment of pediatric relapsed/refractory BCP-ALL.

Autologous CD19-directed chimeric antigen receptor (CAR)-T cells have shown unprecedented efficacy in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, patients either relapsing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or displaying profound lymphopenia and/or rapidly progressing disease often cannot access autologous products. These hurdles may be overcome by allogeneic, donor-derived CAR-T cells.

Paediatric Strategy Forum for medicinal product development of chimeric antigen receptor T-cells in children and adolescents with cancer: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

The seventh multi-stakeholder Paediatric Strategy Forum focused on chimeric antigen receptor (CAR) T-cells for children and adolescents with cancer. The development of CAR T-cells for patients with haematological malignancies, especially B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), has been spectacular. However, currently, there are scientific, clinical and logistical challenges for use of CAR T-cells in BCP-ALL and other paediatric malignancies, particularly in acute myeloid leukaemia (AML), lymphomas and solid tumours.

Safety profile of - 17 years of GSK's passive post-marketing surveillance.

Introduction: This paper reports 17 years of passive safety surveillance of routine use of the pediatric hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus- type b-conjugate vaccine (DTPa-HBV-IPV/Hib, , GSK).

Methods: Global post-licensure passive surveillance data collected in GSK's central safety database since DTPa-HBV-IPV/Hib's launch (2000) are described.

Results: The most common spontaneously reported adverse events (AEs) after DTPa-HBV-IPV/Hib vaccination in children were fever (reporting rate: 7.

Hexavalent vaccines: increasing options for policy-makers and providers. A review of the data supporting interchangeability (substitution with vaccines containing fewer antigens) and mixed schedules from the same manufacturer.

Introduction: Combination vaccines improve vaccine uptake and open the infant immunization space for additional vaccines. Hexavalent vaccines have been marketed since 2000. Infanrix hexa (combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine, DTPa-HBV-IPV/Hib, GSK) is longest on the market, providing 16 years post-marketing experience.

Immunization of preterm infants with GSK's hexavalent combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine: A review of safety and immunogenicity.

Background: Infants with history of prematurity (<37 weeks gestation) and low birth weight (LBW, <2500 g) are at high risk of infection due to functional immaturity of normal physical and immunological defense mechanisms. Despite current recommendations that infants with history of prematurity/LBW should receive routine immunization according to the same schedule and chronological age as full-term infants, immunization is often delayed.

Methods: Here we summarize 10 clinical studies and 15 years of post-marketing safety surveillance of GSK's hexavalent vaccine (DTPa-HBV-IPV/Hib), a combined diphtheria-tetanus-acellular-pertussis-hepatitis-B-inactivated-poliovirus-Haemophilus influenzae-type-b (Hib) conjugate vaccine, when administered alone, or co-administered with pneumococcal conjugate, rotavirus, and meningococcal vaccines and respiratory syncytial virus IgG to infants with history of prematurity/LBW in clinical trials.

Maternal immunization: where are we now and how to move forward?

Pregnancy and the postpartum period are associated with elevated risks to both mother and infant from infectious disease. Vaccination of pregnant women, also called maternal immunization, has the potential to protect pregnant women, foetuses and infants from several vaccine-preventable diseases. Maternal immunoglobulin G antibodies are actively transferred through the placenta to provide passive immunity to new-borns during the first months of life, until the time for infant vaccinations or until the period of greatest susceptibility has passed.

A review of Haemophilus influenzae disease in Europe from 2000-2014: challenges, successes and the contribution of hexavalent combination vaccines.

The development of diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type b (Hib) conjugate vaccine combinations culminated with hexavalent vaccines, the largest, most complex vaccine combinations in the immunization calendar. Hexavalent vaccines are used widely in Europe and are co-administered with multiple other recommended vaccines. Hib immunogenicity may reduce when combined with acellular pertussis antigens, or in some co-administrations.

Lasting immune memory against hepatitis B in 12-13-year-old adolescents previously vaccinated with 4 doses of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy.

Background: Vaccinating infants against hepatitis B virus (HBV) is the most effective way of preventing the disease. However, since HBV exposure can increase during adolescence, it is essential that antibody persistence is maintained. We evaluated the antibody persistence and immune memory against hepatitis B, in 12-13 y olds who had received complete primary + booster vaccination with diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenza type b (DTPa-HBV-IPV/Hib) vaccine in infancy.

Differential effects of olanzapine and risperidone on plasma adiponectin levels over time: results from a 3-month prospective open-label study.

Second-generation antipsychotics (SGA), especially clozapine and olanzapine, are associated with an increased metabolic risk. Recent research showed that plasma adiponectin levels, an adipocyte-derived hormone that increases insulin sensitivity, vary in the same way in schizophrenic patients as in the general population according to gender, adiposity and metabolic syndrome (MetS). The aim of the present study was to investigate whether different SGAs differentially affect plasma adiponectin levels independent of body mass index (BMI) and MetS status.

The effect of antipsychotic medication on sexual function and serum prolactin levels in community-treated schizophrenic patients: results from the Schizophrenia Trial of Aripiprazole (STAR) study (NCT00237913).

Background: The aim of this paper is to evaluate the effect of antipsychotics for the treatment of schizophrenia in a community based study on sexual function and prolactin levels comparing the use of aripiprazole and standard of care (SOC), which was a limited choice of three widely used and available antipsychotics (olanzapine, quetiapine or risperidone) (The Schizophrenia Trial of Aripiprazole [STAR] study [NCT00237913]).

Method: This open-label, 26-week, multi-centre, randomised study compared aripiprazole to SOC (olanzapine, quetiapine or risperidone) in patients with schizophrenia (DSM-IV-TR criteria). The primary effectiveness variable was the mean total score of the Investigator Assessment Questionnaire (IAQ) at Week 26.

A cross-sectional evaluation of adiponectin plasma levels in patients with schizophrenia and schizoaffective disorder.

Background: In recent years, several studies showed increased rates of hyperglycaemia, diabetes, dyslipidemia, metabolic syndrome as well as cardiovascular disease in schizophrenic patients. The underlying mechanism, however, is poorly understood. Adiponectin is a recently identified adipocyte-derived protein, with low adiponectin levels being associated with metabolic abnormalities such as obesity, insulin resistance and type 2 diabetes.

Predicted risk of diabetes and coronary heart disease in patients with schizophrenia: aripiprazole versus standard of care.

Objective: Patients with schizophrenia are at increased risk of developing diabetes mellitus and cardiovascular disease. Furthermore, some atypical antipsychotics are associated with metabolic disturbances, which augment the risk for these comorbid conditions. In clinical trials, effects on metabolic parameters with aripiprazole are similar to those with placebo and superior to those with olanzapine, and the Schizophrenia Trial of Aripiprazole (STAR) demonstrated comparable efficacy of aripiprazole versus standard of care (SoC; physicians' selection of quetiapine, olanzapine, or risperidone).

Preference of medicine and patient-reported quality of life in community-treated schizophrenic patients receiving aripiprazole vs standard of care: results from the STAR study.

Objective: To evaluate quality of life and patient preference for schizophrenia treatment in a community based study comparing the use of aripiprazole to the standard of care (SOC).

Method: This open-label, 26-week, multi-centre, randomised study compared aripiprazole with SOC (olanzapine, quetiapine or risperidone) in patients with schizophrenia (DSM-IV-TR criteria). The primary effectiveness variable was the mean total score of the Investigator Assessment Questionnaire (IAQ) at Week 26.

Major changes in glucose metabolism, including new-onset diabetes, within 3 months after initiation of or switch to atypical antipsychotic medication in patients with schizophrenia and schizoaffective disorder.

Objective: To investigate 3-month changes in glucose metabolism in a naturalistic sample of patients with schizophrenia newly started on or switched to specific atypical antipsychotic medication therapy.

Method: One hundred eighty-three patients were evaluated before initiation and 3 months after with a 75-g glucose load oral glucose tolerance test (OGTT). Data were collected between November 2003 and January 2007.

Typical and atypical antipsychotics differentially affect long-term incidence rates of the metabolic syndrome in first-episode patients with schizophrenia: a retrospective chart review.

Unlabelled: The presence of the metabolic syndrome (MetS) is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of MetS in patients with schizophrenia at the onset of the disorder and specifically no data on patients treated in the era when only first-generation antipsychotics were available.

Methods: Data from a historic cohort of consecutively admitted first-episode patients with schizophrenia treated with first-generation antipsychotics (FGAs) were compared with an age and sex matched series of consecutive first-episode patients treated only with second-generation antipsychotics (SGAs).

Prevalence of diabetes and the metabolic syndrome in a sample of patients with bipolar disorder.

Objectives: The presence of metabolic abnormalities is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of the metabolic abnormalities in disorders other than schizophrenia in which antipsychotic medication is part of routine treatment.

Methods: Sixty consecutive patients with bipolar disorder (BD) at our university psychiatric hospital and affiliate services were entered in an extensive prospective metabolic study including an oral glucose tolerance test.

A multicentre, randomized, naturalistic, open-label study between aripiprazole and standard of care in the management of community-treated schizophrenic patients Schizophrenia Trial of Aripiprazole: (STAR) study.

Background: Naturalistic effectiveness trials of atypical antipsychotics are needed to provide broader information on efficacy, safety, and tolerability in patients with schizophrenia treated in a community practice setting.

Method: In this 26-week, open-label, multicentre study, patients with schizophrenia requiring a switch in antipsychotic medication because current medication was not well tolerated and/or clinical symptoms were not well controlled were randomized to receive aripiprazole or an atypical antipsychotic standard of care (SOC) treatment (i.e.

Treatment with rosuvastatin for severe dyslipidemia in patients with schizophrenia and schizoaffective disorder.

Background: Mortality rates in patients with schizophrenia are double compared to those in the general population, with cardiovascular disease causing 50% of the excess. Lowering low-density lipoprotein (LDL) cholesterol is recognized as a primary target for the prevention of cardiovascular mortality according to the National Cholesterol Education Program-Adult Treatment Panel III. Use of lipid-lowering drugs such as statins is recommended when lifestyle changes are not sufficient to reach the LDL goal.

Pharmacological treatment of severe dyslipidaemia in patients with schizophrenia.

Mortality rates in patients with schizophrenia are double compared with the general population, with cardiovascular disease causing 50% of the excess. Lowering low-density lipoprotein cholesterol is recognized as a primary target for the prevention of cardiovascular mortality. The effects of lipid-lowering treatment were evaluated in patients with schizophrenia.

Screening for diabetes and other metabolic abnormalities in patients with schizophrenia and schizoaffective disorder: evaluation of incidence and screening methods.

Objective: To assess the diagnostic properties of 2 different screening guidelines for the detection of diabetes in patients diagnosed with schizophrenia.

Method: Over a 2-year period (November 2003-November 2005), 415 patients with schizophrenia were screened with a full laboratory screening and a 75-g oral glucose tolerance test (OGTT). The sensitivity of 2 screening strategies was compared with the "gold standard": the OGTT.

Body weight and self-esteem in patients with schizophrenia evaluated with B-WISE.

Background: Metabolic abnormalities and weight gain are an important problem in patients with schizophrenia. An instrument to evaluate body image and self-esteem related to weight has recently been developed (B-WISE). The first objective was to evaluate whether the findings of the original validation study could be confirmed in a European sample.

A case series: evaluation of the metabolic safety of aripiprazole.

Metabolic abnormalities occur frequently in patients treated with antipsychotics and are of growing concern to clinicians. This study sought to determine whether antipsychotic-associated metabolic abnormalities identified through intensive monitoring can be reversed by switching to aripiprazole. Recent evidence suggests that aripiprazole may exhibit a favorable metabolic safety profile.