Real-World data on efficacy of L-glutamine in preventing sickle cell disease-related complications in pediatric and adult patients.

Background: L-glutamine has been shown to play an important role in the regulation of oxidative stress which is one of the key contributors to the pathophysiology of sickle cell disease (SCD). In a Phase 3 clinical trial, L-glutamine demonstrated a significant reduction in SCD-related complications including vaso-occlusive crises (VOCs), hospitalizations, and acute chest syndrome (ACS) compared to placebo in patients with SCD. Objective: The primary objective was to confirm the efficacy of L-glutamine (Endari®) therapy in pediatric and adult patients with SCD at follow-up time points of 24, 48 and 72 weeks. Methods: In the observational study, nineteen patients with SCD were treated orally with L-glutamine twice daily for 72 weeks. Clinical and laboratory parameters were measured at baseline and follow-up time points. Patients with severe VOC and ACS were hospitalized. Blood transfusion was given in case of ACS and uncontrolled pain associated with VOC despite administration of the highest dose of intravenous (IV) narcotic. Results: Compared to baseline, patients had significantly fewer pain crises (median change from 3.0 to 0.0; P < 0.00001), hospitalizations (median change from 3.0 to 0.0; P < 0.00001), days of hospitalization (median change from 15.0 to 0.0; P < 0.00001), and blood transfusions (median change from 3.0 to 0.0; P < 0.00001) at 24, 48, and 72 weeks following L-glutamine therapy. Moreover, there was a drastic decrease in the number of ACS events during this time. A significant increase was observed in mean hemoglobin levels and hematocrit proportions from baseline to 72 weeks (P < 0.001). Conversely, compared to baseline, mean reticulocyte counts and lactate dehydrogenase (LDH) levels were considerably lower at follow-up time points (P = 0.003 and P < 0.001, respectively). No patient reported treatment-related adverse events. Conclusion: Although the sample size was small, our data clearly demonstrated that L-glutamine therapy was safe and significantly improved clinical outcomes and hemolysis parameters in patients with SCD.

The Impact of Ethnicity on the Response to Eltrombopag in Patients With Immune Thrombocytopenia (ITP) in Qatar: A Single Institution Experience.

BACKGROUND: Eltrombopag olamine (ELT) is a synthetic nonpeptide with a low molecular weight that has been investigated in various phase-3 studies and shown to be efficacious at a typical dose of 50 mg. Varied ethnic groups have reported different responses to ELT. AIM: The aim is to examine the efficacy of ELT in Asian and Arab patients with immune thrombocytopenia (ITP) from the Indian subcontinent by starting with (12.5 mg, as a minimum dose) and gradually increasing to a maximum dose of 50 mg. METHODS: Between January 2015 and January 2019, we reviewed the electronic health records of non-Arab Asian (n = 17) versus Arab (n = 41) patients who were ≥18 years old, residing in Qatar, and with confirmed diagnoses with chronic ITP and under active treatment with a platelet count of 30,000/L, and bleeding symptoms. Following receiving ELT for three months or longer at various dosages, patients' response was examined. RESULTS: After three months of ELT therapy, the response rate (platelet count of 50,000/L) was equivalent in non-Arab (88.2%) versus Arab (87.5%) patients. However, to achieve an adequate response, 26% of Arab patients required a lower dose of 12.5 or 25 mg, and 41.5% required a higher dose of 50 mg. CONCLUSION:  In adult chronic ITP patients, ELT is typically well-tolerated and delivers the desired outcomes. In 67.5% of Arab patients, smaller dosages of ELT (12.5-50 mg) were helpful in sustaining acceptable PLT levels. This helps patients get the most benefit at the lowest feasible dose, reducing toxicity and expense.

Jadenu® Substituting Exjade® in Iron Overloaded ß-Thalassemia Major (BTM) Patients: A Preliminary Report of the Effects on the Tolerability, Serum Ferritin Level, Liver Iron Concentration and Biochemical Profiles.

INTRODUCTION: Due to the chronic nature of chelation therapy and the adverse consequences of iron overload, patient adherence to therapy is an important issue. Jadenu ® is a new oral formulation of deferasirox (Exjade ®) tablets for oral suspension. While Exjade® is a dispersible tablet that must be mixed in liquid and taken on an empty stomach, Jadenu ® can be taken in a single step, with or without a light meal, simplifying administration for the treatment of patients with chronic iron overload. This may significantly improve the compliance to treatment of patients with ß-thalassemia major (BMT). The aim of this study was to evaluate the drug tolerability and the effects of chelation therapy on serum ferritin concentration, liver iron concentration (LIC) and biochemical profiles in patients with BMT and iron overload. PATIENTS AND METHODS: Twelve selected adult patients BMT (mean age: 29 years; range:15-34 years) were enrolled in the study. All patients were on monthly regular red cell transfusion therapy to keep their pre-transfusional hemoglobin (Hb) level not less than 9 g/dL. They were on Exjade® therapy (30 mg/kg per day) for two years or more before starting Jadenu® therapy (14-28 mg/kg/day). The reason for shifting from Deferasirox® to Jadenu® therapy was lack of tolerability, as described by patients, such as nausea, vomiting, diarrhea, stomach pain. Most of them also reported that Deferasirox® was not palatable. Lab investigations included monthly urine analysis and measurement of their serum concentrations of creatinine, fasting blood glucose (FBG), serum ferritin, alkaline phosphatase (ALP), alanine transferase (ALT), aspartate transferase (AST) and albumin concentrations. LIC was measured using FerriScan ®. Thyroid function, vitamin D and serum parathormone, before and one year after starting Jadenu ® therapy, were also assessed. RESULTS: Apart from some minor gastrointestinal complaints reported in 3 BMT patients that did not require discontinuation of therapy, other side effects were not registered during the treatment. Subjectively, patients reported an improvement in the palatability of Jadenu® compared to Exjade® therapy in 8 out of 12 BMT patients. A non-significant decrease in LIC measured by FerriScan® and serum ferritin levels was observed after one year of treatment with Jadenu®. A significant positive correlation was found between serum ferritin level and LIC measured by the FerriScan® method. LIC and serum ferritin level correlated significantly with ALT level (r = 0.31 and 0.45 respectively, p < 0.05). No significant correlation was detected between LIC and other biochemical or hormonal parameters. CONCLUSIONS: Our study shows that short-term treatment with Jadenu ® is safe but is associated with a non-significant decrease in LIC and serum ferritin levels. Therefore, there is an urgent need for adequately-powered and high-quality trials to assess the clinical efficacy and the longterm outcomes of new deferasirox formulation.

Thrombocytosis in a male patient with acute promyelocytic leukaemia during all-trans retinoic (ATRA) acid treatment.

We present a rather uncommon side effect observed in a 20-year-old man with acute promyelocytic leukemia during treatment with ATRA. He developed a high platelet counts reaching up to 1655×109/L on day 29 of ATRA treatment, and started to recover spontaneously on day 33 of treatment, without any change in ATRA, or adding any cytoreduction therapy. No complications associated with thrombocytosis were observed. IL-6 seems to play an important role in the pathogenesis of the thrombocytosis induced by ATRA. However, it is unclear what are the precipitating factors for this rare phenomenon and whether it is caused by certain predisposing factors that might be related to patient's, disease pathogenesis or other unknown factors.

Cost-effectiveness research in cancer therapy: a systematic review of literature trends, methods and the influence of funding.

OBJECTIVE: To perform a first-time analysis of the cost-effectiveness (CE) literature on chemotherapies, of all types, in cancer, in terms of trends and change over time, including the influence of industry funding. DESIGN: Systematic review. SETTING: A wide range of cancer-related research settings within healthcare, including health systems, hospitals and medical centres. PARTICIPANTS: All literature comparative CE research of drug-based cancer therapies in the period 1986 to 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes are the literature trends in relation to journal subject category, authorship, research design, data sources, funds and consultation involvement. An additional outcome measure is the association between industry funding and study outcomes. ANALYSIS: Descriptive statistics and the χ2, Fisher exact or Somer's D tests were used to perform non-parametric statistics, with a p value of <0.05 as the statistical significance measure. RESULTS: Total 574 publications were analysed. The drug-related CE literature expands over time, with increased publishing in the healthcare sciences and services journal subject category (p<0.001). The retrospective data collection in studies increased over time (p<0.001). The usage of prospective data, however, has been decreasing (p<0.001) in relation to randomised clinical trials (RCTs), but is unchanging for non-RCT studies. The industry-sponsored CE studies have especially been increasing (p<0.001), in contrast to those sponsored by other sources. While paid consultation involvement grew throughout the years, the declaration of funding for this is relatively limited. Importantly, there is evidence that industry funding is associated with favourable result to the sponsor (p<0.001). CONCLUSIONS: This analysis demonstrates clear trends in how the CE cancer research is presented to the practicing community, including in relation to journals, study designs, authorship and consultation, together with increased financial sponsorship by pharmaceutical industries, which may be more influencing study outcomes than other funding sources.