14 research outputs found

    Tki-Related Platelet Dysfunction Does Not Correlate With Bleeding In Patients With Chronic Phase-Chronic Myeloid Leukemia With Complete Hematological Response

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    Bleeding has been reported in patients with chronic myeloid leukemia (CML) using tyrosine kinase inhibitors (TKIs). In this study, we aimed to evaluate platelet functions and associated bleeding symptoms in patients with CML using TKIs. A standardized questionnaire that was developed for inherited bleeding disorders (ISTH/SSC Bleeding Assessment Tool) was used to score bleeding symptoms in 68 chronic phase patients with CML receiving imatinib (n = 47), dasatinib (n = 15), or nilotinib (n = 6). Light transmission aggregometry was used for platelet function testing. None of the patients had major bleeding (score > 3). Minor bleeding was observed in 25.6% and 20% of the patients in imatinib and dasatinib treatment groups. Impaired/decreased platelet aggregation was observed in 29.8% of imatinib treatment group, 50% of nilotinib group, and 40% of dasatinib group. A secondary aggregation abnormality compatible with the release defect was observed in 26% of patients with CML; 25.5%, 33.3%, and 16.7% of patients receiving imatinib, dasatinib, and nilotinib, respectively. No correlation was found between bleeding symptoms and the impaired platelet function. We can conclude that TKIs may impair in vitro platelet aggregation but this impairment is not associated with bleeding diathesis.PubMedWoSScopu

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

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    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

    Pediatric Chemotherapeutic Regimen (Bfm-95) is Superior for Overall Survival in Adult Acute Lymphoblastic Leukemia

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    Acute lymphoblastic leukemia (ALL) is a neoplastic disease characterized by clonal malignant proliferation of the lymphoid blast cells. The aim of this study is to compare chemotherapy, pediatric regimen BFM-95 protocol with adult ALL protocols in our patient cohort. We retrospectively collected data of patients aged 17 and older who were registered to database of our Hematology Department as acute lymphocytic leukemia between the years 2003-2016. Demographic data,chemotherapy protocols,side effects due to chemotherapy,disease free survivals (DFS) and overall survivals(OS) of remaining 101 patients were compared. The mean age of the patients was 33.6 +/- 14.5 ages.80% of patients were B-ALL,15% were T-ALL, 5% were in Ph+ ALL phenotype.Coagulopathy was seen more in patients receiving BFM-95 (p= 0.002). There was no significant difference among the protocols except for the coagulopathy. The complete remission rate (CR) was 100% in the BFM-95 protocol group, 70% in the Hyper-CVAD group and 60% in the CALGB receiving group. Three-year OS rate was 89% in patients receiving BFM-95, 41% in patients receiving Hyper-CVAD and 53% in CALGB group (p= 0.022).Since patients receiving BFM-95 are under 40 years of age, in order to be able to evaluate the BFM-95 protocol more clearly, OS is examined separately in patients under 40 years of age and it was found that OS was again significantly high in BFM-95 group (p= 0.014). The BFM-95 protocol has been shown to be well tolerated and to improve survival in adult patients when careful in terms of L-asparaginase and steroid-dependent side effects.WoSScopu

    Renin angiotensin system genes are biomarkers for personalized treatment of acute myeloid leukemia with Doxorubicin as well as etoposide.

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    Despite the availability of various treatment protocols, response to therapy in patients with Acute Myeloid Leukemia (AML) remains largely unpredictable. Transcriptomic profiling studies have thus far revealed the presence of molecular subtypes of AML that are not accounted for by standard clinical parameters or by routinely used biomarkers. Such molecular subtypes of AML are predicted to vary in response to chemotherapy or targeted therapy. The Renin-Angiotensin System (RAS) is an important group of proteins that play a critical role in regulating blood pressure, vascular resistance and fluid/electrolyte balance. RAS pathway genes are also known to be present locally in tissues such as the bone marrow, where they play an important role in leukemic hematopoiesis. In this study, we asked if the RAS genes could be utilized to predict drug responses in patients with AML. We show that the combined in silico analysis of up to five RAS genes can reliably predict sensitivity to Doxorubicin as well as Etoposide in AML. The same genes could also predict sensitivity to Doxorubicin when tested in vitro. Additionally, gene set enrichment analysis revealed enrichment of TNF-alpha and type-I IFN response genes among sensitive, and TGF-beta and fibronectin related genes in resistant cancer cells. However, this does not seem to reflect an epithelial to mesenchymal transition per se. We also identified that RAS genes can stratify patients with AML into subtypes with distinct prognosis. Together, our results demonstrate that genes present in RAS are biomarkers for drug sensitivity and the prognostication of AML

    Renin angiotensin system genes are biomarkers for personalized treatment of acute myeloid leukemia with Doxorubicin as well as etoposide.

    No full text
    Despite the availability of various treatment protocols, response to therapy in patients with Acute Myeloid Leukemia (AML) remains largely unpredictable. Transcriptomic profiling studies have thus far revealed the presence of molecular subtypes of AML that are not accounted for by standard clinical parameters or by routinely used biomarkers. Such molecular subtypes of AML are predicted to vary in response to chemotherapy or targeted therapy. The Renin-Angiotensin System (RAS) is an important group of proteins that play a critical role in regulating blood pressure, vascular resistance and fluid/electrolyte balance. RAS pathway genes are also known to be present locally in tissues such as the bone marrow, where they play an important role in leukemic hematopoiesis. In this study, we asked if the RAS genes could be utilized to predict drug responses in patients with AML. We show that the combined in silico analysis of up to five RAS genes can reliably predict sensitivity to Doxorubicin as well as Etoposide in AML. The same genes could also predict sensitivity to Doxorubicin when tested in vitro. Additionally, gene set enrichment analysis revealed enrichment of TNF-alpha and type-I IFN response genes among sensitive, and TGF-beta and fibronectin related genes in resistant cancer cells. However, this does not seem to reflect an epithelial to mesenchymal transition per se. We also identified that RAS genes can stratify patients with AML into subtypes with distinct prognosis. Together, our results demonstrate that genes present in RAS are biomarkers for drug sensitivity and the prognostication of AML

    Incidence and risk factors for hepatic sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation: A retrospective multicenter study of Turkish hematology research and education group (ThREG)

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    Hepatic sinusoidal obstruction syndrome (HSOS) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively evaluated the incidence, risk factors, treatment and survival for HSOS after allo-HSCT in Turkey. We also reported our experience of defibrotide (DF) for HSOS prophylaxis in high-risk (HR) patients. Across Turkey, 1153 patients from 10 centers were enrolled in the study. We evaluated the medical records of patients who were treated with allo-SCT between January 2012 and December 2015. The study included 1153 patients (687 males/466 females) with median age of 38 (15 - 71) years. The incidence of HSOS was 7.5 % (n = 86). The incidences of HSOS in the HR/DF +, HR/DF- and standard risk (SR) group were 8%, 66.7 % and 6.2 %, respectively. The rate of HSOS development was not statistically different between HR/DF + and SR group (p = 0.237). HSOS prophylaxis (defibrotide) was significantly decreased HSOS-related mortality (p = 0.004). The incidence of HSOS was found similar to literature in this large Turkish cohort. Defibrotide prophylaxis appears to be associated with low incidence of HSOS development and reduced HSOS-related mortality. Although these results are promising, future studies are needed to support the efficacy of defibrotide prophylaxis in patients with risk of HSOS
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