Determination of etiology in patients admitted due to isolated leukopenia.

Patients with isolated leukopenia pose difficulties in diagnosis because there is no related guideline in the literature. In this study, our aim was to evaluate the clinical and laboratory associations of isolated, nonspecific (not related to neutropenia) leukopenia. In this retrospective data review study, patients who were admitted to Hacettepe University Hematology Outpatient Clinic between 2014 and 2019 due to leukopenia were evaluated. The patients with anemia (other than iron deficiency) or thrombocytopenia were excluded. Clinical and laboratory data and the final diagnoses (if present) of the remaining cases and especially of those without neutropenia (the most difficult group to diagnose) were evaluated. One hundred sixty-nine patients were included in the study. One hundred forty-four (85.2%) patients were female and 25 (14.8%) were male. One hundred ten of them had 1500/µL or higher neutrophil count. In these nonneutropenic cases, the etiological factors contributing to leukopenia were as follows: iron deficiency anemia (21.8%), other autoimmune/autoinflammatory diseases (17.3%), autoimmune thyroid disease (21.8%), autoimmune laboratory tests (2.7%), drugs (12.7%), infection (5.5%), hematopoietic disorder (2.7%), hypersplenism (2.7%), radiotherapy sequel (1.8%), and B12 deficiency (1.8%). No etiology was recognized in 44 patients. On the other hand, the etiological factors in patients with neutrophil count <1500/µL were as follows; iron deficiency anemia (10.2%), other autoimmune/autoinflammatory diseases (17%), autoimmune thyroid disease (5.1%), autoimmune laboratory tests (8.5%), drugs (8.5%), infection (6.8%), hematopoietic disorder (11.9%), hypersplenism (1.7%), radiotherapy sequel (1.7%), and B12 deficiency (1.7%). No etiology was recognized in 25 patients. Physicians ordered bone marrow examination more frequently in patients with neutropenia. If isolated antinuclear antibody positivity was also considered in favor of autoimmunity, 91/169 (53.8%) cases had an autoimmune diagnosis or laboratory finding. In the present study, the most frequent reasons of isolated leukopenia in nonneutropenic patients are found as iron deficiency anemia, other autoimmune/autoinflammatory diseases, and autoimmune thyroid disease. In neutropenic patients, the most frequent reasons of isolated leukopenia are found as iron deficiency anemia, autoimmune/autoinflammatory diseases, and hematopoietic disorders. Therefore, autoimmunity is detected as an important factor leading to isolated leukopenia.

The impact of At1r inhibition via losartan on the anti-leukaemic effects of doxorubicin in acute myeloid leukaemia.

INTRODUCTION: Bone marrow renin-angiotensin system(RAS) modulates acute myeloid leukaemia(AML).The aim of this study is to clarify the relationships between RAS and AML, and to show the effect of losartan and doxorubicin treatment in AML cell lines. METHODS: AML cell lines including CESS, HL-60, MO-1, P31/FUJ, GDM-1 and KASUMI-3 were used as models in this study. RESULTS: After treating the six AML cell lines with a combination of losartan and doxorubicin, they were divided into two groups based on their behaviour: one became more sensitive to drug treatment (Group A) and the other had no change observed in behaviour after drug treatment (Group B). In silico analyses showed that Group A is involved in cellular apoptosis, while Group B is involved in tumour angiogenesis further supporting the in vitro results. CONCLUSION: The combined treatment of the AML cell lines with losartan and doxorubicin resulted in an increase in sensitivity of some of the cell lines. Those leukaemic cells are modulated via the induction of apoptosis, whereas the other cells resistant to the drug treatment are closely related to tumour angiogenesis indicating that RAS-AT1R seems to be differently expressed in different leukaemic blast cells and tumour microenvironments. Pharmaco-biological actions of RAS inhibitors may be different in distinct leukaemic cells based on the pathological behaviour of AML genomic subtypes.

Discontinuation of Imatinib Mesylate could Improve Renal Impairment in Chronic Myeloid Leukemia.

We aim to report a CML case that had fluid retention and serum creatinine increase under long-term imatinib mesylate (IM) treatment. A 68-year-old woman was diagnosed with chronic myeloid leukemia, and IM was started in 2002 with a dose of 400 mg/day. She had achieved complete hematological, molecular and cytogenetic remission under IM treatment. In September 2015, her creatinine level was 1.7 mg/dl. In May 2016, she was admitted to our hospital with dyspnea. Hypervolemia secondary to fluid retention was detected in our patient. Her laboratory tests results showed hemoglobin 9.7 gr/dl, white blood cell 7.6x103/µl, platelet 157x103/µl, creatinine 3.2 mg/dl, blood urea nitrogen (BUN) 88 mg/dl. In her X-ray chest film, bilateral pleural effusion was detected. The effusion was detected as transuda. The other reasons of pleural effusion were excluded and the development of pleural effusion was considered secondary to IM. IM was also considered responsible for the acute rise of serum creatinine levels of our patient. Therefore for these two reasons IM was stopped. After the discontinuation of IM, her creatinine levels decreased to 1.6 mg/dl and her pleural effusions disappeared. IM treatment was considered as the reason of serum creatinine elevation since serum creatinine levels decreased after the discontinuation of IM. All of the side-effects disappeared after discontinuation of IM.

Immunosuppression-associated posterior reversible encephalopathy syndrome in an acute leukemia case.

Posterior reversible encephalopathy syndrome (PRES) was described in 1996. Herein, we aimed to report an immunosuppression- related PRES case. A 34-year-old woman was diagnosed as t-cell acute lymphoblastic leukemia and allogeneic hematopoietic stem cell transplantation (HSCT) was performed. Cyclosporine was given for GVHD prophylaxis in addition to the other routine medications of HSCT. She was hospitalized for acute renal failure and due to the possible contribution of acute renal failure cyclosporine was stopped. Tacrolimus was started for GVHD prophylaxis at a dose of 1 mg/day. However, fifteen days after the initiation of tacrolimus, blurred vision occurred in our patient. Petechial bleeding sites were detected in bilateral cerebral and cerebellar hemisphere by MR imaging. Tacrolimus dosage was reduced to 0.5 mg/day. She had hypertension which was difficult to control and followed-up in the intensive care unit. She had seizures. Control cranial MR resulted as diffusion limitation in bilateral cerebellar hemisphere, bilateral occipital and frontal-parietal regions with vasogenic edema findings; contrast involvement in left frontal-parietal and right cerebellar regions. She had vision loss and lethargy. Control cranial MR favored PRES syndrome secondary to immunosuppression. Hypertensive state was taken under control with antihypertensive treatment and all immunosuppressive agents were stopped. Two weeks later her clinical condition was slightly improved. MR test which was conducted 2 weeks after the diagnosis revealed the regression of PRES lesions. The characteristic signs on neuroimaging are the symmetrical white matter edema in the posterior cerebral hemispheres, particularly the parietal- occipital regions. In conclusion, PRES rarely develops secondary to the immunosuppressive agents and the clinicians should suspect and promptly diagnose PRES which might cause otherwise serious irreversible clinical complications.

Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma.

OBJECTIVE: Multiple myeloma (MM) is currently incurable due to refractory disease relapse even under novel anti-myeloma treatment. In silico studies are effective for key decision making during clinicopathological battles against the chronic course of MM. The aim of this present in silico study was to identify individual genes whose expression profiles match that of the one generated by cytotoxicity experiments for bortezomib. MATERIALS AND METHODS: We used an in silico literature mining approach to identify potential biomarkers by creating a summarized set of metadata derived from relevant information. The E-MTAB-783 dataset containing expression data from 789 cancer cell lines including 8 myeloma cell lines with drug screening data from the Wellcome Trust Sanger Institute database obtained from ArrayExpress was "Robust Multi-array analysis" normalized using GeneSpring v.12.5. Drug toxicity data were obtained from the Genomics of Drug Sensitivity in Cancer project. In order to identify individual genes whose expression profiles matched that of the one generated by cytotoxicity experiments for bortezomib, we used a linear regression-based approach, where we searched for statistically significant correlations between gene expression values and IC50 data. The intersections of the genes were identified in 8 cell lines and used for further analysis. RESULTS: Our linear regression model identified 73 genes and some genes expression levels were found to very closely correlated with bortezomib IC50 values. When all 73 genes were used in a hierarchical cluster analysis, two major clusters of cells representing relatively sensitive and resistant cells could be identified. Pathway and molecular function analysis of all the significant genes was also investigated, as well as the genes involved in pathways. CONCLUSION: The findings of our present in silico study could be important not only for the understanding of the genomics of MM but also for the better arrangement of the targeted anti-myeloma therapies, such as bortezomib.

Qualitative/Chemical Analyses of Ankaferd Hemostat and Its Antioxidant Content in Synthetic Gastric Fluids.

INTRODUCTION: Ankaferd hemostat (ABS) is the first topical haemostatic agent involving the red blood cell-fibrinogen interactions. The antihemorrhagic efficacy of ABS has been tested in controlled clinical trials. The drug induces the formation of an encapsulated complex protein web with vital erythroid aggregation. The aim of this study is to detect the essential toxicity profile and the antioxidant molecules inside ABS. METHODS: The pesticides were analyzed by GC-MS and LC-MS. The determination by ICP-MS after pressure digestion was performed for the heavy metals. HPLC was used for the detection of mycotoxins. Dioxin Response Chemically Activated Luciferase Gene Expression method was used for the dioxin evaluation. TOF-MS and spectra data were evaluated to detect the antioxidants and other molecules. RESULTS: TOF-MS spectra revealed the presence of several antioxidant molecules (including tocotrienols, vitamin E, tryptophan, estriol, galangin, apigenin, oenin, 3,4-divanillyltetrahydrofuran, TBHQ, thymol, BHA, BHT, lycopene, glycyrrhetinic acid, and tomatine), which may have clinical implications in the pharmacobiological actions of ABS. CONCLUSION: The safety of ABS regarding the presence of heavy metals, pesticides, mycotoxins, GMO and dioxins, and PCBs was demonstrated. Thus the present toxicological results indicated the safety of ABS. The antioxidant content of ABS should be investigated in future studies.