Molecular Management Of Chronic Lymphocytic Leukemia: Towards A Chemotherapy-Free Approach

B-cell receptor (BCR) signaling is implicated as a pivotal pathway in tumorigenesis in B-cell malignancies. The inhibitors of Bruton's tyrosine kinase (BTK) and phosphatidylinositide 3-kinase-delta (PI3K), modulating BCR signaling, have included into the clinical studies and demonstrated high response rates in B-cell lymphoproliferative diseases such as chronic lymphocytic leukemia (CLL). The imbalance between proliferation and apoptosis is the novel target in the treatment of CLL. The newly developed targeted molecular agents such as idelalisib (CAL-101 or GS-1101), ibrutinib (PCI-32765), BCL-2 inhibitors (ABT-263 (navitoclax) and ABT-199 (venetoclax)), chimeric antigen receptors (CART19 cells), novel monoclonal antibodies, and immunomodulatory drugs try to balance between survival and programmed cell death in the pathobiology of the disease. The ongoing clinical trials focusing on the combinations of kinase inhibitors with monoclonal antibodies and other pro-apoptotic agents may lead to the chemotherapy-free protocols for the indolent incurable long disease course of B-CLL. With the greater clinical experience following more widespread use of novel molecules, the optimal combination therapies in the treatment-naive and relapsed/refractory patients will be determined, resulting in more individualized therapeutic strategies for patients with CLL.WoSScopu

Spinal Myeloid Sarcoma In Two Non-Leukemic Patients

Myeloid sarcoma, formerly termed granulocytic sarcoma or chloroma, consists of neoplastic granulocytic precursors and myeloblasts. Isolated chloromas (granulocytic sarcomas) are rare tumors. Spinal complications of chloromas, such as cord compression secondary to epidural tumor or cauda equine syndrome have been described but are rare. We herein report two cases with spinal granulocytic sarcomas in non-leukemic patients. The case of a previously healthy 22-year-old man diagnosed with multiple spinal granulocytic sarcomas with no evidence of bone marrow or other hematological involvement is described. And, a 43-year-old woman diagnosed cervical spinal granulocytic sarcoma with no evidence of bone marrow or other hematological involvement is described. The tumor was totally removed by microsurgery. The histopathological examination was consistent with granulocytic sarcoma. Granulocytic sarcoma should be considered in the differential diagnosis of an epidural mass in patients with or without acute leukemia, because early diagnosis followed by appropriate combined chemotherapy and radiation may obviate surgical intervention and eventually prevent leukemic transformation.WoSScopu

The Factors Affecting Early Death In Newly Diagnosed Apl Patients

Background and aim: In the past, acute promyelocytic leukemia (APL) was considered as one of the most rapidly lethal form of acute myeloid leukemia (AML). The objective of this study was to assess clinical parameters affecting early death (ED) in patients with APL. Materials and methods: Forty-three patients with APL who were diagnosed at Hacettepe University Hospital between the years of 2005 and 2018 were evaluated. Results: In univariate analyses, presentation with hemorrhage, DIC or infection at diagnosis, ECOG performance score, blast percentage on bone marrow, Sanz score, leukocyte, thrombocyte, fibrinogen and LDH levels were found to be statistically significantly different between patients with ER and patients without ED. In multivariate analysis, presentation with hemorrhage, DIC or infection at diagnosis, ECOG performance score, blast percentage on bone marrow, Sanz score, leukocyte, thrombocyte, fibrinogen, and LDH levels were found to be independent factors that are related with higher rate of ED in 30 days after treatment. Conclusion: Induction chemotherapy should be started as soon as possible after diagnosis of APL. Improving ED rates may become the greatest challenge for the future treatment of the diseases.Wo

Acute In Vitro Effects of Abs (Ankaferd Hemostat) on The Lymphoid Neoplastic Cells (B-Cll And Raji Tumor Cell Lines)

ABS (Ankaferd Hemostat) has emerged as a novel haemostatic agent of plant origin. Its ability to interact with entire proteins including cell surface receptors and/or blood proteins plus tissue proteins revealed novel functions of ABS to biologic systems especially tumor associated transcription factors. Thus, in our study, we aimed to investigate the effects of ABS on lymphoid neoplastic cells in vitro. We showed that Ankaferd treated B-CLL cells (at doses 0.5, 1 and 2 mu g/mL) ceased to inflate and more than 50% of tumor cells were died compared to 0.1 and 0.25 mu g/mL doses. Additionally, transformation of B-CLL cells to the blastic aggressive lymphoid forms was prevented by addition of Ankaferd to culture medium. The results have given the clues of anti-neoplastic effects at higher doses (>0.5 mu g/mL) and induction of cellular differentiation at lower doses (<0.5 mu g/mL) and proposed future advances in treatment of neoplastic bleedings.WoSScopu

Identification of clinical and simple laboratory variables predicting responsible gastrointestinal lesions in patients with iron deficiency anemia

<p>Iron deficiency anemia (IDA) is a frequent disorder. Also, it may be a sign of underlying serious diseases. Iron deficiency points to an occult or frank bleeding lesion when occurred in men or postmenopausal women. In this study, we aimed to evaluate the diagnostic yield of endoscopy in patients with IDA and to define predictive factors of gastrointestinal (GI) lesions causing IDA. Ninety-one patients (77 women, 14 men; mean age: 43 years) who were decided to have esophago-duodenoscopy and/or colonoscopy for iron deficiency anemia were interviewed and responded to a questionnaire that included clinical and biochemical variables. The endoscopic findings were recorded as GI lesions causing IDA or not causing IDA. Endoscopy revealed a source of IDA in 18.6 % of cases. The risk factors for finding GI lesions causing IDA were as follows: male gender (p= 0.004), advanced age (&#62; 50 years) (p= 0.010), weight loss (over 20% of total body weight lost in last 6 month) (p= 0.020), chronic diarrhea (p= 0.006), change of bowel habits (p= 0.043), epigastric tenderness (p= 0.037), raised carcinoembryonic antigen (CEA) level (normal range: 0-7 ng/mL) (p= 0.039), &#60; 10 gr/dl hemoglobin (Hb) level (p=0.054). None of these risk factors had been present in 21 (23%) women younger than 51 years. In this group, no patient had any GI lesion likely to cause IDA (negative predictive value= 100%). In multivariate analysis, advanced age (p=0.017), male gender (p&#60; 0.01) and weight lost (p=0.012) found that associated with GI lesions in all patients. It may be an appropriate clinical approach to consider these risk factors when deciding for gastrointestinal endoscopic evaluation in iron deficiency anemia.</p

Effective Molecular Monitoring and the Proper Management of Pleural Effusion During the First-Line Dasatinib Administration in Cml

Dasatinib is considered an effective treatment agent in imatinib-resistant and newly diagnosed chronic phase CML patients. Patients receiving dasatinib 100 mg once daily regime suffered significantly fewer thrombocytopenia and pleural effusion events than those receving 70 mg twice daily. Effective molecular monitoring and the proper management of pleural effusion during the first-line dasatinib administration in CML are essential. Pleural effusion may develop any time of the treatment and is easily managed by treatment interruption, dose reduction and supportive therapy. In this article, we intended to assess the rational of managing CML and pleural effusion that successfully managed with dose reduction and supportive care.Wo

Iron Overload Pattern in Multiple Myeloma at Diagnosis Its Important Clinical Associations

As a plasmaproliferative disorder, multiple myeloma (MM) is not expected to cause IO and actually there are no reports on this condition in MM. In this retrospective study, we evaluated serum iron test results in MM patients at diagnosis in order to find the frequency of IO. Iron overload pattern (IOP) was described as increased transferring saturation (> 45%) in the presence of normal to increased serum iron and ferritin levels. Among 90 newly diagnosed MM patients (54 male, 36 female, and the median age: 61 years, range: 31-86)IOP was found in 17 cases (17/90, 19%). There was a close association between lambda light chain type paraproteinemia and IOP (13/17 in IOP cohort vs 26/73 lambda paraproteinemia, p= 0.003). Half of the MM patients (7/14) with free lambda light chain paraproteinemia had IOP. The main reason of the elevated TS was increased serum iron level in IOP patients, 144 (+/- 71) vs 57 (+/- 24) pg/ml (p<.001). Four out of 17 IOP patients had extramedullary involvement and this was significantly more frequent than the other patients. Although high International Staging System risk disease (stage 2 or 3) was more frequent in IOP patients (15/15 vs 51/68, p= 0.03), we could not observe any difference regarding treatment response, and survival between these cases and others. In conclusion, IO is also not infrequent MM at diagnosis and it has some clinical associations.WoSScopu

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

Bone Marrow Iron Staining Is a Reliable Test For Elimination of Iron Deficiency Anemia Rather Than Its Diagnosis

Iron deficiency anemia (IDA) is the most frequent type of anemia. The use of biochemical markers is a challenging way of diagnosis in case of inflammation and functional iron deficiency. The role of bone marrow aspirate iron staining is criticized because it is an invasive method and has no accurate standardization. This study was planned to find the value of bone marrow iron staining in diagnosis of iron deficiency. Four hundred and seven cases who had bone marrow aspirate iron staining and simultaneous serum iron tests have been reviewed retrospectively and 47 such cases were evaluated prospectively. Bone marrow iron was negative in 125 (%30.7) cases in retrospective cohort. There was significant differences in serum iron, ferritin, transferrin saturation between bone marrow iron negative and positive cohorts (p<0.001). Low serum transferrin saturation (<15%) and ferritin (<15 ng/ml) levels are consistent with iron deficiency. On this standard, in both retrospective and prospective cohorts, rates for specificiy (85.5% and 90.4%, respectively) and negative predictivity (97.5% and 100%, respectively) of bone marrow iron staining were relatively high compared with the sensitivity and positive predictivity of the same test. The results of this study show that the evaluation of bone marrow iron staining is a more reliable test for the elimination of IDA rather than its diagnosis.WoSScopu