Evaluation of Eltrombopag in Thrombocytopenia Post Hematopoietic Cell Transplantation: Rertrospective Observational Trial.

BACKGROUND: Thrombocytopenia remains a life-threatening late complication of HCT with an incidence of 5-20%. Currently, there is no approved drug for the treatment of persistent thrombocytopenia post HCT and platelet transfusion is the maintain stay of treatment. Eltrombopag is approved for the treatment of thrombocytopenia associated with different diseases, however; data on eltrombopag treatment post HCT are limited. METHODS: This is a retrospective cohort study evaluating the effect of eltrombopag on platelet recovery in patients with persistent thrombocytopenia post HCT. The primary endpoint was platelet recovery to ≥ 20,000/µL for 7 consecutive days without transfusion support after starting eltrombopag. Secondary endpoint was platelet recovery to ≥ 50,000/µL for 7 consecutive days. RESULTS: Twenty-one patients were included. Twelve (75%) of 16 patients became independent from platelet transfusions. Median time from starting eltrombopag to last transfusion was 60 days (range, 9-226 days). Ten (63%) of 16 transfusion dependent patients with platelet count < 20,000/µL achieved the primary endpoint. Seven (33%) patients of 21 included had successful platelet recovery (ie, ≥50,000/µL without transfusion support) and the median time to platelet recovery in patients who achieved it was 32 days (range, 13-265 days). Ten patients (48%) were able to successfully discontinue eltrombopag without recurrence of thrombocytopenia. CONCLUSION: Our findings demonstrated that eltrombopag appears to have a clinically significant impact on platelet recovery in persistent thrombocytopenic patients post HCT.

Synthesis of docosahexaenoic acid-loaded silver nanoparticles for improving endothelial dysfunctions in experimental diabetes.

OBJECTIVE: To investigate the ability of docosahexaenoic acid (DHA)-loaded silver nanoparticles (AgNPs) in facilitating the incorporation of DHA in the cell membrane, improve cell membrane structure, and attenuate endothelial dysfunction in experimental diabetes. METHODS: DHA/AgNPs were prepared using a nanoprecipitation technique. Fifty male albino rats were used in this study; 10 of them were served as the control group and 40, as the experimental groups, were injected with streptozotocin. Then, the experimental groups were subdivided into diabetic, diabetic treated with DHA, diabetic treated with AgNPs, and diabetic treated with DHA/AgNPs groups. RESULTS: DHA/AgNPs have small spherical size as proved from ultraviolet-visible spectroscopy, transmission electron microscope, dynamic light scattering, and scanning electron microscope techniques. Cell membrane cholesterol and triglycerides showed a significant elevation in the diabetic group compared to the control, but treatment with DHA and DHA/AgNPs caused a significant reduction in both. Treatment with AgNPs and DHA/AgNPs caused a significant improvement in asymmetric dimethylarginine and nitric oxide levels compared to the diabetic group. Cell membrane fatty acids showed that omega-6 polyunsaturated fatty acids (PUFAs) were significantly elevated, while omega-3 PUFA were significantly reduced in the diabetic group compared to the control. There is a significant improvement in the levels of fatty acids in all groups after treatment with DHA, silver, or DHA/AgNPs. CONCLUSION: DHA/AgNPs are potent agents for the improvement of diabetic complication and endothelial dysfunction in experimental diabetes.

Intracranial hypertension secondary to high dose cytosine arabinoside - A case study.

We report a rare case of intracranial hypertension following high dose cytosine arabinoside (HiDAC) in a 20-year-old man, with precursor B-cell acute lymphoblastic leukemia (ALL). A five drug induction protocol for ALL was initiated; post induction consolidation was with HiDAC (3 g/m2 IV every 12 h on days 1, 3 and 5). Post consolidation, cytogenetic remission was attained and he received an intensification and maintenance regimen for ALL, for a period of approximately 24 months. Four months following the completion of his treatment, the patient relapsed within the central nervous system (CNS). Intravenous salvage chemotherapy was initiated using a combination of fludarabine 30 mg/m2, followed by cytarabine 2 g/m2 4 h later on days 1 through 5 (FA). On day # 23 of FA, he developed a severe headache. A gadolinium-enhanced brain magnetic resonance imaging (MRI) revealed increased intracranial pressure. On day # 25, ophthalmology examination suggested bilateral papilledema. He was started on acetazolamide 250 mg twice daily. He had spontaneous resolution of his symptoms. The patient had no recurrence of papilledema or any other neurological symptoms. Intracranial hypertension secondary to HiDAC, is an exceedingly rare complication and is not regularly associated as a common side effect of cytarabine administration. Prompt action in diagnosing and treating intracranial hypertension will save the patient from consequences, such as loss of vision, that are prevalent in this condition.

Flaxseed oil reduces oxidative stress and enhances brain monoamines release in streptozotocin-induced diabetic rats.

This study was performed to investigate the biochemical effect of flaxseed oil on oxidative stress and brain monoamines release in streptozotocin-induced diabetic rats. Sixty male albino rats were divided into following four groups (15 for each group): control group, flaxseed oil group, diabetic group, and flaxseed oil-treated diabetic group. Serum glucose, insulin, pentosidine, plasma advanced oxidation protein products (AOPPs), and plasma total antioxidant capacity were estimated. Brain neurotransmitters, malondialdehyde (MDA), and nitric oxide (NO) were also determined. The mean values of serum pentosidine and plasma AOPP showed a significant decrease in treated diabetic group as compared to their values in the diabetic group. Also, brain neurotransmitters levels were improved after treatment with flaxseed. Brain MDA and NO were increased significantly in the diabetic group, while they were significantly decreased after treatment. Brain NO and brain MDA had a significant positive correlation with pentosidine, AOPP, and neurotransmitters. We concluded that flaxseed oil supplementation may be useful in the treatment of brain dysfunction in diabetes.

Introduction of vincristine mini-bags and an assessment of the subsequent risk of extravasation.

INTRODUCTION: Numerous international organisations have advocated the preparation of vincristine in small volume intravenous bags in order to eliminate inadvertent intrathecal administration. However, the risk of extravasation is a significant deterrent, and adoption of this practice has been variable and only hesitantly accepted in the clinical setting. PURPOSE: We carried out a study with the aims of establishing the incidence of reported extravasation of vincristine administration to paediatric and adult patients in mini-bags; here we describe motivating factors and barriers faced by clinical staff. The secondary aim was to support the need for change and implementation of the international recommendations. METHODS: Chemotherapy-certified nurses completed a survey spanning August 2009 to August 2011, to ascertain the incidence of extravasation associated with the administration of vincristine in mini-bags. RESULTS: This period captured 421 occasions of vincristine administration in 25-ml or 50-ml mini-bags (in 0.9% sodium chloride). The median age of patients was 13 years (range 2.5 months to 99 years). Vincristine was administered through peripheral lines (26.4%), portacath (52.0%), PICC line (15.9%) and Hickman line (5.7%). The majority of infusions were over at least 10 minutes (50.1%). There were no cases of extravasation reported. CONCLUSIONS: The administration of vincristine in small volume intravenous bags was safe, practical, and feasible in all patient groups. The successful implementation of the international recommendations for vincristine administration in mini-bags to eliminate potential inadvertent intrathecal administration was dependent on stakeholder buy-in.

Allogeneic matched-sibling hematopoietic cell transplantation for AML: comparable outcomes between Eastern Mediterranean (EMBMT) and European (EBMT) centers.

Allogeneic hematopoietic cell transplantation (HCT) activity significantly increased in the Eastern Mediterranean area over the past decade. However, comparative outcomes with longer established centers, especially European Blood and Marrow Transplantation (EBMT) centers, have not been reported. We compared outcomes of matched-sibling allogeneic HCT between East Mediterranean Blood and Marrow Transplantation (EMBMT) and EBMT centers for adult patients with AML in first CR using myeloablative conditioning. We matched 431 patients from EMBMT with 431 patients from EBMT centers according to patient, disease and transplant characteristics. EMBMT recipients and donors were more likely to be CMV seropositive. There were no significant differences in the incidence of acute or chronic GVHD, or the 3-year cumulative incidence of non-relapse mortality (NRM) and relapse incidence (RI) between the two groups (NRM: EMBMT=16% vs EBMT=11), (RI: EMBMT=13% vs EBMT=19%). Notably, the 3-year leukemia-free survival (LFS) and OS were similar between the groups (LFS: EMBMT=70±2% vs EBMT=69±3%), (OS: EMBMT=74±2% vs EBMT=73±2%). Despite differences in socioeconomics, health resources and transplant experience, matched-sibling allogeneic HCT outcomes in emerging centers in the EMBMT region appear similar to EBMT centers.

A simplified method for autologous stem cell transplantation in multiple myeloma.

BACKGROUND AND OBJECTIVES: We evaluated the efficacy and safety of non-cryopreserved storage of autologous hematopoietic stem cells with no post-transplant granulocyte colony-stimulating factor (G-CSF) support in adult patients undergoing autologous stem cell transplantation (ASCT) for multiple myeloma (MM). DESIGN AND SETTING: Retrospective review of patients undergoing ASCT from May 2009 to July 2011. PATIENTS AND METHODS: Autologous stem cell were mobilized using G-CSF. Leukapheresis to harvest stem cells was performed on day -2 and -1. The grafts were kept in a conventional blood bank refrigerator at 4°C until reinfusion on day 0. The conditioning regimen consisted of melphalan 200 mg/m2 in all patients. The post-chemotherapy myeloablative phase was managed without growth factors. RESULTS: Between May 2009 to July 2011, 54 adults with MM were treated in our center in Oran. The median age at ASCT was 55 years (range, 35-65). There were 37 males and 17 females. The median harvested CD34+ cell count was 3.60X106/kg (range, 1.90 to 10.52). All patients had neutrophil engraftment on the median of day 10 (range, 6-17) and platelet transfusion independence on the median of day 13 (range 9-24). In the 47 evaluable patients the median post-transplant overall survival had not been reached; the estimated overall survival at 30 months was 93.8% (0.05%) , and the estimated disease-free survival at 27 months was 93.6% (0.05%). CONCLUSION: High-dose chemotherapy and ASCT using non-cryopreserved stem cells and no G-CSF support is safe and feasible in the treatment of MM under our work conditions in developing countries.