Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Despite its indolent clinical course, therapy refractoriness and disease progression still represent an unmet clinical need. Before the advent of pathway inhibitors, chemoimmunotherapy (CIT) was the commonest option for CLL treatment and is still widely used in areas with limited access to pathway inhibitors. Several biomarkers of refractoriness to CIT have been highlighted, including the unmutated status of immunoglobulin heavy chain variable genes and genetic lesions of TP53, BIRC3 and NOTCH1. In order to overcome resistance to CIT, targeted pathway inhibitors have become the standard of care for the treatment of CLL, with practice-changing results obtained through the inhibitors of Bruton tyrosine kinase (BTK) and BCL2. However, several acquired genetic lesions causing resistance to covalent and noncovalent BTK inhibitors have been reported, including point mutations of both BTK (e.g., C481S and L528W) and PLCG2 (e.g., R665W). Multiple mechanisms are involved in resistance to the BCL2 inhibitor venetoclax, including point mutations that impair drug binding, the upregulation of BCL2-related anti-apoptotic family members, and microenvironmental alterations. Recently, immune checkpoint inhibitors and CAR-T cells have been tested for CLL treatment, obtaining conflicting results. Potential refractoriness biomarkers to immunotherapy were identified, including abnormal levels of circulating IL-10 and IL-6 and the reduced presence of CD27+CD45RO− CD8+ T cells.

Imatinib (Glivec(®)/Gleevec(®)) has shown long-term efficacy and safety in randomized trials. No large-scale studies have prospectively assessed the benefit-risk profile of an imatinib copy drug. We prospectively evaluated the response of patients with chronic myeloid leukemia in chronic phase in one institution. Patients with a complete hematologic response (n = 126) switched from branded imatinib to an imatinib copy drug. Subsequently, all patients switched back to the branded imatinib. Many patients in this study had a loss of hematologic response and tolerability issues with the imatinib copy drug. Hematologic response and tolerability improved upon retreatment with branded Glivec.

Objective: Rosmarinus officinalis L. is an aromatic perennial herb with fragrant evergreen needle-like leaves, and it is member species of Lamiaceae family raised from Mediterranean region. The aims of the study were isolation, quantification, and identification of rosmarinic acid of R. officinalis leaves and essential oil analysis using various chromatographic and spectroscopic methods, and also cytotoxic and antibacterial investigation against different species of bacteria. Methods:It was isolated by preparative HPLC and preparative TLC, and then it was determined by HPTLC. The identification and the structural elucidation of isolated rosmarinic acid were performed by H-nuclear magnetic resonance, electrospray ionization mass spectrometry (MS), infrared, and ultraviolet. Essential oil was analyzed by Gas Chromatography/Mass. Results:Results highlighted that rosmarinic acid content was 0.9% and the oil content was 1.8%, and R. officinalis chemotypes of Iraqi rosemary oil were camphor 23.04%, 1, 8-cineole 14.01%, and terpinen-4-ol 13.8%. The rosemary chemotype characterized as a high concentration of terpinen-4-ol and good inhibition effect of rosemary methanolic extract against different species bacteria: Enterococcus faecalis, Staphylococcus saprophyticus, Acinetobacter baumannii, and Proteus mirabilis. Conclusions:The plant has a good content of rosemary phytochemicals and antibacterial effect, so the plantation of rosemary in Iraq has been successes. These isolated compounds are a suitable candidate for further clinical and pharmacological study.

Background: Smoking is a well-known related factor for many health problems in a human being through different ways of exposure. Objectives: Thie aim of the study was to examine the effects of different types of cigarette smoking on hemoglobin level, high sensitive C-Reactive Protein (hsCRP), Malondialdehyde (MDA), and IgE levels in healthy adult subjects. Methods: One hundred seventy-one healthy adult females and males were included in this study. They divided into four groups: cigarette, shisha, passive smokers, and non-smokers groups. Serum samples from all groups analyzed for hemoglobin, hsCRP, IgE, and malondialdehyde level. Results: The mean MDA, IgE, and hemoglobin levels significantly increased in both smokers (cigarette and Shisha groups) and passive smokers than in non-smokers group (p<0.05). The hsCRP levels were significantly increased (p<0.05) in cigarette and Shisha smokers compared to non-smokers. At the same time, there was a non-significant relationship between passive smoker in comparison to non-smokers (p>0.05). Conclusion: This study concluded that smoking, including cigarette and shisha, even passive smoking harmed health through increasing Malondialdehyde, serum IgE and hs-CRP levels in the body.

Objective: Imatinib mesylate, a tyrosine kinase inhibitor, is presently the drug of choice for chronic myeloid leukemia (CML). During therapy, a few patients may develop hematological and non-hematological adverse effects. Materials and Methods: The aim of this study was to evaluate the safety of imatinib therapy in patients with CML. Between December 2007 and October 2009 two hundred patients with CML in chronic phase were included in the study. Written informed consent was obtained from all patients prior to the start of the study. Imatinib was started at 400 mg orally daily. Patients were monitored carefully for any adverse effects. Complete blood count, liver, and renal function tests were done once in 2 weeks during the first month and on a monthly basis during follow-up. Toxicities that encountered were graded as per the National Cancer Institute common toxicity criteria version 2. Both hematologic and non-hematologic toxicities were managed with short interruptions of treatment and supportive measures, but the daily dose of imatinib was not reduced below 300 mg/day.Results: Two hundred CML patients in chronic phase were included in this study; the male:female ratio was 0.7:1 with mean age 39.06±13.21 years (ranged from 15-81 years). The study showed that the commonest hematological side effects were grade 2 anemia (12.5%) followed by leukopenia (8%) and thrombocytopenia (4%), while the most common non-hematological adverse effects were superficial edema and weight gain (51.5%), followed by musculoskeletal pain (35.5%), then gastro-intestinal symptoms (vomiting, diarrhea) (19%). Fluid retention was the commonest side effect, which responded to low-dose diuretics. The drug was safe and well tolerated. There were no deaths due to toxicity.Conclusion: Imatinib mesylate a well-tolerated drug, and all undesirable effects could be ameliorated easily. The most common hematological and non-hematological side effects were anemia and fluid retention, respectivelyConflict of interest:None declared.