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 7.6x10(3)/mu l, platelet 157x10(3)/mu l, 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.WoSScopu

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.PubMedScopu

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.PubMedWoSScopu

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

The Impact Of Iron Overload On Transplant-Related Complications And Prognosis Of Acute Leukemias

The impacts of serum iron parameters and/or radiological evidence of systemic iron overload on the prognosis of hematopoietic stem cell transplantation (HSCT) in acute leukemia are controversial. Unfortunately, some of the studies evaluating iron overload in transplant setting did not precisely show the patients with iron overload, mainly due to ignoring consideration of transferrin saturation along with hyperferritinemia for elimination of non-iron overload etiologies of hyperferritinemia. The aim of this study is to assess the effect of iron overload on transplantation related complications and prognosis in acute leukemia. Patients who undergone allogeneic HSCT for acute leukemia in Hacettepe University Medical School Department of Hematology were screened retrospectively in order to find cases with serum iron tests within 9 months before transplant. The endpoints investigated were overall and disease-free survivals, acute and chronic graft-versus-host disease and veno-oclussive disease (VOD). There were 84 patients suitable for inclusion. When various ferritin plus transferrin saturation (TS) cut-off values were investigated for a possible relationship with major transplant-related complications/results only ferritin>2000 plus TS>45% was found to have an association with VOD at borderline significance (p=0.067). In conclusion, we observed a non-significant borderline relationship between iron overload and post-transplant VOD. We did not confirm other post-transplant complications reported in the literature. It must be noticed that although many studies intended to investigate the relationship between iron status and transplant outcomes, only a few of them have really looked for the effect of iron overload.WoSScopu

Idelalisib At The Crossroads Of B-Cell Lymphoproliferative Disorders

Phosphatidylinositol 3-kinases (PI3Ks) are considered as lipid kinases that are very active in the pathobiology of lymphoproliferative disorders (LPDs). Idelalisib, a selective inhibitor of the delta isoform of PI3K, provides significant clinical efficacy and has an acceptable side-effect profile in the treatment of B-LPDs. The aim of this review is to outline the pharmacobiological basis of idelalisib that is located at the crossroads of B-LPDs. The PI3K signaling pathway with downstream targets including Akt is involved in hematologic malignancies and lymphomas. Idelalisib has been most widely studied in chronic lymphoid leukemia (CLL) and B-lymphoma. The activity of idelalisib in high-risk FL with early relapse following front line immunochemotherapy was recently shown. The unique immunological toxicity pattern of idelalisib was also decribed in this review. Further clinical investigations will help for the better selection of the subsets of the patients with B-LPD that would be best candidates for the clinical utilization of idelalisib. Other indications such as marginal zone lymphoma, mantle cell lymphoma, Waldenstrom's Macroglobulinemia and other B-cell disorders could likely to be expanded. Future clinical and experimental data combined with the next-generation genomics strategies and personalized medicine for the treatment of malignant disorders will enlightened us for better placement of idelalisib in the treatment algorithm of the patients.WoSScopu

The Impact Of Jak1/Jak2 Inhibitor Ruxolitinib On The Spleen Size And Symptom Burden In Myeloproliferative Diseases

Ruxolitinib as a JAK1 and JAK2 inhibitor drug has recently been approved for the treatment of patients with high-or intermediate-risk myelofibrosis with symptomatic splenomegaly. Clinical development of ruxolitinib has currently focused on the Ph* negative myeloproliferative neoplastic disorders (MPN). The aim of this study is to assess the impact of ruxolitinib treatment on the clinical course of Ph* negative myeloproliferative disorders. Forty-three patients who were under ruxolitinib treatment and followed-up between years 1987-2015 in Hacettepe University Medical School Hematology Clinic and Ondokuz Mayis University Hematology Clinic with myeloproliferative disease without Philadephia chromosome translocation were retrospectively analyzed. The constitutional symptoms were decreased in 97% of patients after ruxolitinib treatment. The mean spleen sizes before and after ruxolitinib treatment were 229 +/- 35 versus 202 +/- 31 mm, respectively (p<0.001). In this study, we observed a reduction in spleen size after ruxolitinib treatment in Turkish patients with MPN and this reduction was statistically significant. Moreover, nearly all of the MPN patients' constitutional symptoms were improved. Those observations are concordant with other geographical MPN data obtained from different countries. Further experimental and clinical studies into the efficacy and safety of ruxolitinib in patients with MPN are necessary to elucidate its role in special subgroups of MPN patients, such as patients undergoing hematopoietic stem cell transplantation and the patients with vascular disorders such as hepatoportal thrombosis.WoSScopu

Generic Imatinib Mesylate is as Effective as Original Glivec in the Clinical Management of CML

Unsustainable drug prices in chronic myeloid leukemia (CML) and cancer may be causing harm to patients. The aim of this multi-center study is to assess the efficacy of generic imatinib mesylate (IM) over Glivec in terms of hematological, cytogenetic, and molecular responses in CML. The data of 120 CML patients, who were treated with generic or original form of IM, were obtained from six different hematology clinics in Turkey between the years of 2009-2014 and analyzed retrospectively. Initial evaluation revealed that only one patient who was using original molecule switched to second generation tyrosine kinase inhibitor (TKI). In this period, hematological response(HR) was observed in 99.2% of the patients, cytogenetic response (CR) was observed in 88.7% of the patients (47 of 53), and molecular response (MR) was observed in 75% of the patients. Clinicians had a tendency to prefer generic molecules in each sequent visit, and this switch rate was statistically significant (p<0.001). 11 patients, who were using original molecules during all cohorts, switched to second generation TKI. On the other hand, only one patient, who was using generic molecules, switched to second generation TKI. Our paper may help to clarify the doubts about the efficacy of generic IM compared to original molecule. In our study we did not find any significant difference in HR, CR, and MR for original and generic drugs in each visit. Herein, we find low rates of need to switch to second generation TKIs with generic IM and no difference in treatment responses between generic and original molecules that confirms the non-inferiority of generic TKIs over original molecules