Subscribe: MedWorm: Chronic Leukemia
Preview: MedWorm: Chronic Leukemia

MedWorm: Chronic Leukemia provides a medical RSS filtering service. Over 7000 RSS medical sources are combined and output via different filters. This feed contains the latest news and research in the Chronic Leukemia category.

Last Build Date: Tue, 29 Mar 2016 16:49:00 +0100


Mp63-01 a proposal for a novel peri-operative mortality risk assessment tool in contemporary patients treated with radical cystectomy

Mon, 28 Mar 2016 19:24:08 +0100

The Charlson comorbidity index (CCI) is the most widely used index score in retrospective analyses. However, several comorbid conditions included in this index, such as sever liver disease, AIDS, leukemia/lymphoma, are never seen in patients candidate to radical cystectomy (RC). Some other comorbid conditions, such as diabetes, and chronic pulmonary disease, are very frequently seen. Conversely, other conditions that are not accounted within that CCI index may represent better predictors of perioperative mortality. (Source: The Journal of Urology)

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Targeting the mTOR Pathway in Leukemia

Sun, 27 Mar 2016 22:00:00 +0100

This article is protected by copyright. All rights reserved (Source: Journal of Cellular Biochemistry)

Cardiac tamponade as a symptom of the blast crisis of chronic myeloid leukemia

Sun, 27 Mar 2016 22:00:00 +0100

Publication date: Available online 28 March 2016 Source:The Kaohsiung Journal of Medical Sciences Author(s): Chiung-Tang Huang, Shih-Hao Yu, Yi-Hsien Chen, Sheng-Fung Lin (Source: The Kaohsiung Journal of Medical Sciences)

Bcl6 modulation of acute lymphoblastic leukemia response to chemotherapy.

Sun, 27 Mar 2016 05:28:02 +0100

This study suggests that marrow microenvironment regulation of BCL6 in ALL is one factor that may be involved in the transition between proliferative and quiescent states of ALL cells. Utilizing ALL cell lines, and primary patient tumor cells we observed that tumor cell BCL6 protein abundance is decreased in the presence of primary human bone marrow stromal cells (BMSC) and osteoblasts (HOB). Chemical inhibition, or shRNA knockdown, of BCL6 in ALL cells resulted in diminished ALL proliferation. As many chemotherapy regimens require tumor cell proliferation for optimal efficacy, we investigated the consequences of constitutive BCL6 expression in leukemic cells during co-culture with BMSC or HOB. Forced chronic expression of BCL6 during co-culture with BMSC or HOB sensitized the tumor to che...

Ibrutinib for Lymphocytic Leukemia Prompts Skin and Nail ChangesIbrutinib for Lymphocytic Leukemia Prompts Skin and Nail Changes

Fri, 25 Mar 2016 18:56:24 +0100

Although generally well tolerated, ibrutinib, a Bruton tyrosine kinase inhibitor effective against chronic lymphocytic leukemia (CLL), may lead to nail and hair abnormalities, according to a new report. Reuters Health Information (Source: Medscape Medical News Headlines)

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Aberrant activation of CaMKIIγ accelerates chronic myeloid leukemia blast crisis

Thu, 24 Mar 2016 23:00:00 +0100

Aberrant activation of CaMKIIγ accelerates chronic myeloid leukemia blast crisis Leukemia advance online publication, March 25 2016. doi:10.1038/leu.2016.53 Authors: Y Gu, W Zheng, J Zhang, X Gan, X Ma, Z Meng, T Chen, X Lu, Z Wu, W Huang & R Xu (Source: Leukemia)

Analysis of racial variations in disease characteristics, treatment patterns, and outcomes of patients with chronic lymphocytic leukemia

Thu, 24 Mar 2016 23:00:00 +0100

This article is protected by copyright. All rights reserved. (Source: American Journal of Hematology)

CD19‐CAR engineered NK‐92 cells are sufficient to overcome NK cell resistance in B‐cell malignancies

Thu, 24 Mar 2016 05:43:33 +0100

Abstract Many B‐cell acute and chronic leukaemias tend to be resistant to killing by natural killer (NK) cells. The introduction of chimeric antigen receptors (CAR) into T cells or NK cells could potentially overcome this resistance. Here, we extend our previous observations on the resistance of malignant lymphoblasts to NK‐92 cells, a continuously growing NK cell line, showing that anti‐CD19‐CAR (αCD19‐CAR) engineered NK‐92 cells can regain significant cytotoxicity against CD19 positive leukaemic cell lines and primary leukaemia cells that are resistant to cytolytic activity of parental NK‐92 cells. The ‘first generation’ CAR was generated from a scFv (CD19) antibody fragment, coupled to a flexible hinge region, the CD3ζ chain and a Myc‐tag and cloned into a retrovir...

Single nucleotide polymorphisms in apoptosis pathway are associated with response to imatinib therapy in chronic myeloid leukemia

Thu, 24 Mar 2016 00:00:00 +0100

The mechanism of action of imatinib is known to involve the Fas-mediated apoptosis pathway. Consequently inter-individual variations in this apoptosis pathway might be associated with imatinib response or resi... (Source: Journal of Translational Medicine)

Human Cytotoxic T Lymphocytes Form Dysfunctional Immune Synapses with B Cells Characterized by Non-Polarized Lytic Granule Release

Wed, 23 Mar 2016 23:00:00 +0100

In this study, we have explored the underlying basis for CTL suppression in the context of B cell malignancies. We document that human B cells have an intrinsic ability to resist killing by freshly isolated cytotoxic T cells (CTLs), but are susceptible to lysis by IL-2 activated CTL blasts and CTLs isolated from immunotherapy-treated patients with chronic lymphocytic leukemia (CLL). Impaired killing was associated with the formation of dysfunctional non-lytic immune synapses characterized by the presence of defective linker for activation of T cells (LAT) signaling and non-polarized release of the lytic granules transported by ADP-ribosylation factor-like protein 8 (Arl8). We propose that non-lytic degranulation of CTLs are a key regulatory mechanism of evasion through which B cells may ...

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Clinical impact of MYD88 mutations in chronic lymphocytic leukemia

Wed, 23 Mar 2016 23:00:00 +0100

(Source: Blood)

Autoimmune cytopenias in patients with chronic lymphocytic leukemia treated with ibrutinib.

Wed, 23 Mar 2016 23:00:00 +0100

Authors: Vitale C, Ahn IE, Sivina M, Ferrajoli A, Wierda WG, Estrov Z, Konoplev SN, Jain N, O' Brien S, Farooqui M, Keating MJ, Wiestner A, Burger JA PMID: 27013651 [PubMed - as supplied by publisher] (Source: Haematologica)

Alvocidib (flavopiridol) for the treatment of chronic lymphocytic leukemia.

Wed, 23 Mar 2016 16:51:02 +0100

Authors: Wiernik PH Abstract INTRODUCTION: Alvocidib, which has orphan drug designation in chronic lymphocytic leukemia (CLL) from the FDA and the EMA, is a plant-derived semisynthetic flavone that acts as a cyclin-dependent kinase inhibitor. It induces apoptosis in CLL cells in vitro and was introduced into clinical trials in CLL as an intravenous infusion in 1997, which proved disappointing. Since the drug avidly binds to plasma proteins, higher serum concentrations were required for clinical antileukemia activity than those suggested by in vitro studies. Subsequent studies utilizing bolus plus infusional doses revealed significant activity against CLL, even in patients with unfavorable characteristics. However, significant toxicity including high rates of major tumor lysis syndr...

Simplifying procedure for prediction of resistance risk in CML patients — Test of sensitivity to TKI ex vivo

Tue, 22 Mar 2016 23:00:00 +0100

Publication date: May 2016 Source:Blood Cells, Molecules, and Diseases, Volume 58 Author(s): Markéta Žáčková, Tereza Macháčková-Lopotová, Zuzana Ondráčková, Kateřina Kuželová, Hana Klamová, Jana Moravcová Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have dramatically improved chronic myeloid leukemia therapy. While imatinib remains to be the first line therapy, about 30% of patients develop resistance or intolerance to this drug and are recommended to switch to other TKIs. Nilotinib and dasatinib are currently implemented into the first line therapy and other inhibitors have already entered the clinical practice. This opens further questions on how to select the best TKI for each patient not only during the therapy but also at diagnosis. The individualized t...

Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

Tue, 22 Mar 2016 23:00:00 +0100

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the ...

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease [Hematologic Malignancy]

Tue, 22 Mar 2016 23:00:00 +0100

Conclusion Allogeneic anti-CD19 CAR T cells can effectively treat B-cell malignancies that progress after alloHSCT. The findings point toward a future when antigen-specific T-cell therapies will play a central role in alloHSCT. (Source: Journal of Clinical Oncology)

Evolutionary Dynamics of Chronic Myeloid Leukemia Progression: the Progression-Inhibitory Effect of Imatinib

Tue, 22 Mar 2016 23:00:00 +0100

Abstract The t(9;22) translocation that causes chronic myeloid leukemia (CML) drives both transformation and the progression process that eventually results in the disease changing to acute leukemia. Constitutively activated Bcr-Abl signaling in CML creates high levels of reactive oxygen species (ROS) that produce 8-oxo-guanine in DNA; this is mutagenic and causes chronic phase (CP) progression to blast phase (BP). We modeled three types of mutations involved in this progression: mutations that result in myeloid progenitor cells proliferating independently of external growth factors; mutations causing failure of myeloid progenitor cells to differentiate; and mutations that enable these cells to survive independently of attachment to marrow stroma. We further modeled tyrosine kinas...

Peripheral arterial occlusive disease during ponatinib therapy after failure of imatinib: a case report

Tue, 22 Mar 2016 23:00:00 +0100

Summary What is known and objectivePeripheral vascular adverse events have been reported with ponatinib treatment in chronic myeloid leukaemia (CML) after failure of dasatinib or nilotinib. We here report peripheral arterial occlusive disease (PAOD) in a patient who had previously received only imatinib as tyrosine kinase inhibitor. Case descriptionThe patient was a 70‐year‐old man with no history of cardiovascular disease. He developed arterial hypertension 5 months after the initiation of ponatinib and PAOD 41 months later. What is new and conclusionPeripheral arterial occlusive disease can occur several years after the initiation of ponatinib in patients who had previously received only imatinib. Long‐term surveillance is required for preventing the complications of ponatinib‐as...

Reduction in Cell Viability and in Homeobox Protein Levels Following in Vitro Exposure to δ-tocopherol in Acute Myeloid Leukemia.

Tue, 22 Mar 2016 23:00:00 +0100

In this study, we screened the efficacy of δ-T against six cell lines representing a wide spectrum of hematologic malignancies: Jurkat (acute T-cell leukemia), K-562 (chronic myeloid leukemia), KG-1 [acute myeloid leukemia (AML)], THP-1 (acute monocytic leukemia), TOM-1 (acute lymphoblastic leukemia), and UMCL01-101 (AIDS-associated diffuse large B-cell lymphoma). Interestingly, the AML cell line KG-1 was the only one to be significantly affected at concentrations of δ-T as low as 20 µM. The antileukemic activity of δ-T in AML was verified in a set of primary cells collected from patients newly diagnosed with AML. Apoptotic induction and cell cycle arrest explained the efficacy of δ-T against KG-1 cells. The mechanism of cell growth inhibition of δ-T was through downregulation of cy...

Trends in survival of chronic lymphocytic leukemia patients in Germany and the USA in the first decade of the twenty-first century

Tue, 22 Mar 2016 00:00:00 +0100

Recent population-based studies in the United States of America (USA) and other countries have shown improvements in survival for patients with chronic lymphocytic leukemia (CLL) diagnosed in the early twenty-... (Source: Journal of Hematology and Oncology)

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Mortality and Vascular Events Among Elderly Patients With Chronic Myeloid Leukemia: A Retrospective Analysis of Linked SEER-Medicare Data

Mon, 21 Mar 2016 23:00:00 +0100

Conclusion Elderly patients with CML had greater mortality and greater rates of MI, stroke, PE, and PAD than did noncancer patients. The event rates were not elevated among the TKI-treated (primary imatinib) patients, suggesting that the VE risk in these patients with CML was driven primarily by the underlying factors associated with CML. Micro-Abstract Tyrosine-kinase inhibitor (TKI) treatment of chronic myeloid leukemia (CML) can be associated with vascular events (VEs). We examined the event rates and mortality among elderly patients with and without CML using linked cancer registry and Medicare claims data from 2003 to 2010. The patients with CML had greater mortality and VE rates. The rates were not elevated among the TKI (primarily imatinib)-treated patients, suggesting the VE risk ...

Evans syndrome secondary to chronic lymphocytic leukaemia: presentation, treatment, and outcome

Mon, 21 Mar 2016 23:00:00 +0100

In conclusion, ES secondary to CLL is a difficult-to-treat complication, characterised by adverse biological features and clinical outcome. (Source: Annals of Hematology)

Detection of chromosomal changes in chronic lymphocytic leukemia using classical cytogenetic methods and FISH: application of rich mitogen mixtures for lymphocyte cultures

Mon, 21 Mar 2016 23:00:00 +0100

One of the research methods of prognostic value in chronic lymphocytic leukemia (CLL) is cytogenetic analysis. This method requires the presence of appropriate B-cell mitogens in cultures in order to obtain a high mitotic index. The aim of our research was to determine the most effective methods of in vitro B-cell stimulation to maximize the number of metaphases from peripheral blood cells of patients with CLL for classical cytogenetic examination, and then to correlate the results with those obtained using fluorescence in situ hybridization (FISH). The study group involved 50 consecutive patients with CLL. Cell cultures were maintained with the basic composition of culture medium and addition of respective stimulators. We used the following stimulators: Pokeweed Mitogen (PWM), 12-O-tetrad...

Id: 26: exploring the longitudinal transcriptomic landscape of tyrosine kinase inhibitor treatment response in chronic myeloid leukemia patients

Mon, 21 Mar 2016 23:00:00 +0100

The interpretation and implementation of large-scale genetic profiles into clinical practice remains a challenge despite substantial growth in our understanding of genetic contributors to drug response. Most current omic studies focus on identifying genetic features that are distinct between normal and tumor samples, but fail to capture the dynamics of association between omic profiles, treatment response and disease progression over time. The focus of this research is to analyze the longitudinal transcriptomic profile of chronic myeloid leukemia patients (CML) in context of tyrosine kinase inhibitor (TKI) treatment and clinical status. The main objectives were to compare a series of post-TKI treatment transcriptome profiles to their baseline levels, and characterize the impact of TKI trea...

Id: 54: cutaneous mucormycosis in a patient with chronic lymphocytic leukemia: a pharmacological dilemma

Mon, 21 Mar 2016 23:00:00 +0100

Mucormycosis is an infection caused by fungi from the Mucoromycotina group. The clinical manifestations are dependent of the portal of entry and immune status of the human host. Patients with hematological malignancies on treatment causing immune suppression are at higher risk of mucormycosis. The number of medications to treat mucormycosis is very limited, in contrast with the development of medications with novel mechanisms of action against hematological malignancies. A patient with chronic lymphocytic leukemia (CLL) receiving ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, developed a skin lesion in left leg after local trauma. He developed progressive inflammation around trauma site, and fever. His lesion did not respoond to broad-spectrum antibiotic use. Biopsy of lesion revea...

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Leukemic stem cell quantification in newly diagnosed chronic myeloid leukemia patients predicts response to nilotinib therapy.

Mon, 21 Mar 2016 23:00:00 +0100

CONCLUSION: The proportion of LSCs at diagnosis, as analyzed by two independent methodologies, reflects the biology of the disease and appeared as a prognostic and response-predictive marker in CML patients subjected to first-line nilotinib therapy. PMID: 27006491 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Characterization and automatic screening of reactive and abnormal neoplastic B lymphoid cells from peripheral blood.

Mon, 21 Mar 2016 14:06:02 +0100

CONCLUSION: The excellent automatic screening of the three groups of normal, reactive, and abnormal lymphocytes is useful as it discriminates between malignancy and not malignancy. The discrimination of the five groups of abnormal lymphoid cells is encouraging toward the idea that the system could be an automated image-based screening method to identify blood involvement by a variety of B lymphomas. PMID: 26995648 [PubMed - as supplied by publisher] (Source: International Journal of Laboratory Hematology)

Lymphocytosis after treatment with dasatinib in chronic myeloid leukemia: Effects on response and toxicity

Mon, 21 Mar 2016 00:00:00 +0100

CONCLUSIONSOverall, lymphocytosis occurred and persisted in many dasatinib‐treated patients in all phases of CML. Its presence was associated with higher response rates, significantly longer response durations, and increased overall survival, suggesting an immunomodulatory effect. Prospective studies are warranted to characterize the functional activity of these cells and to assess whether an immunologic effect against CML is detectable. Cancer 2016. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. (Source: Cancer)

Peripheral blood late mixed chimerism in leucocyte subpopulations following allogeneic stem cell transplantation for childhood malignancies: does it matter?

Mon, 21 Mar 2016 00:00:00 +0100

Summary The impact of persistent mixed chimerism (MC) after haematopoietic stem cell transplantation (HSCT) remains unclarified. We investigated the incidence of MC in peripheral blood beyond day +50 after HSCT and its impact on rejection, chronic graft‐versus‐host disease (c‐GvHD) and relapse in 161 children receiving allogeneic HSCT for haematological malignancies. The 1‐year incidence of late MC was 26%. Spontaneous conversion to complete donor chimerism (CC) occurred in 43% of patients as compared to 62% after donor lymphocyte infusions. No graft rejection occurred. The 1‐year incidence of c‐GvHD was 20 ± 7% for MC, and 18 ± 4% for CC patients (P = 0·734). The 3‐year cumulative incidence of relapse (CIR) according to chimerism status at days +50 and +100 was 22 ...

Metabolite profiling of (14)C-omacetaxine mepesuccinate in plasma and excreta of cancer patients.

Sun, 20 Mar 2016 23:00:00 +0100

The objective was to investigate the metabolite profile of omacetaxine in plasma, urine and faeces samples collected up to 72 h after a single 1.25-mg/m(2) subcutaneous dose of (14)C-omacetaxine in cancer patients. High-performance liquid chromatography mass spectrometry (MS) (high resolution) in combination with off-line radioactivity detection was used for metabolite identification. In total, six metabolites of omacetaxine were detected. The reactions represented were mepesuccinate ester hydrolysis, methyl ester hydrolysis, pyrocatechol conversion from the 1,3-dioxole ring. Unchanged omacetaxine was the most prominent omacetaxine-related compound in plasma. In urine, unchanged omacetaxine was also dominant, together with 4'-DMHHT. In feces very little unchanged omacetaxine was found an...

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Chronic lymphocytic leukemia therapy: new targeted therapies on the way.

Sun, 20 Mar 2016 17:00:02 +0100

We present preclinical and clinical data from phase I to III studies in order to describe efficacy and side effect profile of these new drugs. Data are derived from peer-reviewed articles indexed in PubMed and from abstracts presented at major international meetings. Expert opinion Ibrutinib and idelalisib are challenging the role of chemo-immunotherapy in CLL therapy in the frontline and relapsed disease settings. High-risk CLL patients particularly benefit from these new agents. Venetoclax and obinutuzumab are other effective agents added to our therapeutic armamentarium. Studies to better define the optimal use of these drugs, alone, or rather in combination or sequenced are underway. PMID: 26988407 [PubMed - as supplied by publisher] (Source: Expert Opinion on Pharmacotherapy)

Managing Infusion-Related Reactions for Patients With Chronic Lymphocytic Leukemia Receiving Obinutuzumab.

Sun, 20 Mar 2016 05:19:02 +0100

Authors: Dawson K, Moran M, Guindon K, Wan H Abstract BACKGROUND: In patients with previously untreated chronic lymphocytic leukemia (CLL) and comorbidities, treatment with the glycoengineered, type II anti-CD20 monoclonal antibody obinutuzumab (Gazyva®) (GA101) plus chlorambucil (Leukeran®) was associated with superior outcomes to rituximab (Rituxan®) plus chlorambucil, with a similar safety profile. However, a higher occurrence of infusion-related reactions (IRRs) was reported with obinutuzumab. These reactions typically require additional management. OBJECTIVES: The focus of this article is to provide oncology nurses and physicians with advice for obinutuzumab IRR management based on clinical trial data and nursing experience. METHODS: The authors reviewed the publish...

Critical involvement of the α(1,2)-fucosyltransferase in multidrug resistance of human chronic myeloid leukemia.

Sat, 19 Mar 2016 17:53:03 +0100

This study indicated that α(1,2)-fucosyltransferase involved in the development of MDR of CML cells probably through FUT1 regulated the activity of EGFR/MAPK signaling pathway and the expression of P-gp. PMID: 26986216 [PubMed - as supplied by publisher] (Source: Oncology Reports)

To treat or not to treat: metabolomics reveals biomarkers for treatment indication in chronic lymphocytic leukaemia patients.

Sat, 19 Mar 2016 17:51:03 +0100

Authors: Piszcz J, Armitage EG, Ferrarini A, Rupérez FJ, Kulczynska A, Bolkun L, Kloczko J, Kretowski A, Urbanowicz A, Ciborowski M, Barbas C Abstract In chronic lymphocytic leukaemia (CLL), the clinical course of patients is heterogeneous. Some present an aggressive disease onset and require immediate therapy, while others remain without treatment for years. Current disease staging systems developed by Rai and Binet may be useful in forecasting patient survival time, but do not discriminate between stable and progressive forms of the disease in the early stages. Recently ample attention has been directed towards identifying new disease prognostic markers capable of predicting clinical aggressiveness at diagnosis. In the present study serum samples from stable (n = 51) and progres...

Paclitaxel induces apoptosis in leukemia cells through a JNK activation-dependent pathway.

Sat, 19 Mar 2016 03:01:03 +0100

Authors: Peng ZG, Liu DC, Yao YB, Feng XL, Huang X, Tang YL, Yang J, Wang XX Abstract Paclitaxel (PTX) is a mitotic inhibitor widely used in chemotherapy for many types of cancers, including solid tumors and hematological malignancies. However, the molecular basis of the anti-proliferation activity of PTX is not fully understood. In this paper, we focused on the role of c-Jun N-terminal kinase (JNK) pathways in PTX-induced apoptosis and proliferation inhibition. The effects of PTX were examined in human leukemia cell lines and patients' chronic lymphocytic leukemia (CLL) cells in relation to mitochondrial events, apoptosis, and perturbation of JNK activation using flow cytometry, siRNA, mitochondrial membrane potential determination, and western blotting. Exposure of cells to PTX a...

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Secondary non-Hodgkin’s lymphoma a concern for CML patients using TKIs

Sat, 19 Mar 2016 00:07:49 +0100

Patients with chronic myeloid leukaemia who use the tyrosine kinase inhibitor imatinib may be three to four times more likely to develop non-Hodgkin’s lymphoma than the general population, study findings indicate. (Source: MedWire News)

Vascular events in CML may not be linked to TKI therapy

Sat, 19 Mar 2016 00:07:49 +0100

The increased risk of vascular events observed among elderly patients with chronic myeloid leukaemia, compared with patients without cancer, may not be driven by tyrosine kinase inhibitor therapy, US researchers suggest. (Source: MedWire News)

Real-life data show feasibility of imatinib discontinuation in CML

Sat, 19 Mar 2016 00:07:49 +0100

Italian research shows that long-term imatinib discontinuation is feasible outside of a clinical trial setting for patients with chronic myeloid leukaemia who achieve stable undetectable molecular disease with front-line treatment. (Source: MedWire News)

Splenic irradiation before hematopoietic stem cell transplantation for chronic myeloid leukemia: long-term follow-up of a prospective randomized study

Sat, 19 Mar 2016 00:00:00 +0100

Abstract In the context of discussions on the reproducibility of clinical studies, we reanalyzed a prospective randomized study on the role of splenic irradiation as adjunct to the conditioning for hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML). Between 1986 and 1989, a total of 229 patients with CML were randomized; of these, 225 (98 %; 112 with, 113 without splenic irradiation) could be identified in the database and their survival updated. Results confirmed the early findings with no significant differences in all measured endpoints (overall survival at 25 years: 42.7 %, 32.0–52.4 % vs 52.9 %, 43.2–62.6 %; p = 0.355, log rank test). Additional splenic irradiation failed to reduce relapse incidence. It did not increase non-relapse...

Histiocytic Sarcoma as a Secondary Malignancy: Pathobiology, Diagnosis, and Treatment

Fri, 18 Mar 2016 21:34:17 +0100

This article is protected by copyright. All rights reserved. (Source: European Journal of Haematology)

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Nosocomial Co-Transmission of Avian Influenza A(H7N9) and A(H1N1)pdm09 Viruses between 2 Patients with Hematologic Disorders.

Fri, 18 Mar 2016 15:37:03 +0100

Authors: Chen H, Liu S, Liu J, Chai C, Mao H, Yu Z, Tang Y, Zhu G, Chen HX, Zhu C, Shao H, Tan S, Wang Q, Bi Y, Zou Z, Liu G, Jin T, Jiang C, Gao GF, Peiris M, Yu H, Chen E Abstract A nosocomial cluster induced by co-infections with avian influenza A(H7N9) and A(H1N1)pdm09 (pH1N1) viruses occurred in 2 patients at a hospital in Zhejiang Province, China, in January 2014. The index case-patient was a 57-year-old man with chronic lymphocytic leukemia who had been occupationally exposed to poultry. He had co-infection with H7N9 and pH1N1 viruses. A 71-year-old man with polycythemia vera who was in the same ward as the index case-patient for 6 days acquired infection with H7N9 and pH1N1 viruses. The incubation period for the second case-patient was estimated to be <4 days. Both case-...

Safety of combination treatment with imatinib mesylate, carboplatin, and cetuximab in a patient with multiple cancers: a case report.

Fri, 18 Mar 2016 12:25:02 +0100

CONCLUSIONS: Our report indicates the feasibility of combination imatinib and cetuximab plus carboplatin in a case of multiple cancer diagnoses, provided that the treatment with imatinib is modulated according to the expected bone marrow depression. PMID: 26979243 [PubMed - as supplied by publisher] (Source: Tumori)

Next-generation sequencing for sensitive detection of BCR-ABL1 mutations relevant to tyrosine kinase inhibitor choice in imatinib-resistant patients.

Fri, 18 Mar 2016 05:56:02 +0100

Authors: Soverini S, De Benedittis C, Machova Polakova KM, Linhartova J, Castagnetti F, Gugliotta G, Papayannidis C, Mancini M, Klamova H, Salvucci M, Crugnola M, Iurlo A, Albano F, Russo D, Rosti G, Cavo M, Baccarani M, Martinelli G Abstract In chronic myeloid leukemia (CML) and Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) patients who fail imatinib treatment, BCR-ABL1 mutation profiling by Sanger sequencing (SS) is recommended before changing therapy since detection of specific mutations influences second-generation tyrosine kinase inhibitor (2GTKI) choice. We aimed to assess i) in how many patients who relapse on second-line 2GTKI therapy next generation sequencing (NGS) may track resistant mutations back to the sample collected at the time of imatinib resistan...

Management of psychiatric adverse events with immunotherapy with interferon-alfa.

Fri, 18 Mar 2016 04:28:02 +0100

Authors: Van Gool AR, Kruit WH, Cornelissen JJ, Berk L, Eggermont AM, Bannink M Abstract Immunotherapy with interferon-alfa has become standard therapy in selected patients with viral hepatitis and chronic myelogenous leukemia. In addition, it is used in a variety of other diseases, both as standard therapy and in clinical trials. Its use is expected to expand in the following decade. Interferon can cause (severe) neuropsychiatric side effects. These side effects are discussed. Adequate management of these side effects is important, as is close collaboration between the oncologist and the psychiatrist. The cornerstone of management is patient education: this prevents interruption of therapy by patients who were not warned for neuropsychiatric side effects. Furthermore, patients sho...

High CIP2A levels correlate with an antiapoptotic phenotype that can be overcome by targeting BCL-XL in chronic myeloid leukemia

Fri, 18 Mar 2016 00:00:00 +0100

Authors: C M Lucas, M Milani, M Butterworth, N Carmell, L J Scott, R E Clark, G M Cohen & S Varadarajan (Source: Leukemia)

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Glyphosate: Claims against Monsanto for 'Farmer's Cancer'

Thu, 17 Mar 2016 21:53:47 +0100

Studies of occupational exposure to Glyphosate report increased risks for non-Hodgkin Lymphoma, Multiple Myeloma, Hairy Cell Leukemia, and Chronic Lymphocytic Leukemia (Source: Disabled World)

Estimating the Population Benefits and Costs of Rituximab Therapy in the United States from 1998 to 2013 Using Real-World Data

Thu, 17 Mar 2016 19:19:34 +0100

Conclusions: These analyses, based on real-world evidence, show that the introduction of rituximab into clinical practice has produced a substantial number of incremental life-years. Importantly, the economic benefit of the life-years gained greatly exceeds the added costs of treatment. (Source: Medical Care)

Linking Costs and Survival in the Treatment of Older Adults With Chronic Myeloid Leukemia: An Analysis of SEER-Medicare Data From 1995 to 2007

Thu, 17 Mar 2016 19:19:34 +0100

Conclusions: Our findings showed that, despite high costs, CML care may provide reasonable value for money among older patients between 1995–2007. Our study sheds light on the value of health care spending on CML by considering both the costs and the benefits. Future research should investigate strategies to improve treatment adherence to maximize the value of CML care. (Source: Medical Care)

In Vivo Cytochrome P450 3A Isoenzyme Activity and Pharmacokinetics of Imatinib in Relation to Therapeutic Outcome in Patients With Chronic Myeloid Leukemia

Thu, 17 Mar 2016 06:34:58 +0100

Conclusions: The CYP3A activity does not influence imatinib plasma concentrations or the therapeutic outcome. These results indicate that although imatinib is metabolized by CYP3A enzymes, this activity is not the rate-limiting step in imatinib metabolism and excretion. Future studies should focus on other pharmacokinetic processes so as to identify the major contributor to patient variability in imatinib plasma concentrations. (Source: Therapeutic Drug Monitoring)

Estimation of the prevalence and direct medical costs of chronic myeloid leukemia in the I.R. of Iran in the era of tyrosine kinase inhibitors

Thu, 17 Mar 2016 00:00:00 +0100

ConclusionsThe increased survival of CML patients and a possible increase in incidence of CML in Iran will most likely lead to a considerable rise in its prevalence and economic burden. (Source: Asia-Pacific Journal of Clinical Oncology)

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Characterization of a Novel Variant BCR–ABL1 Fusion Transcript in a Patient with Chronic Myeloid Leukemia: Implications for Molecular Monitoring

Thu, 17 Mar 2016 00:00:00 +0100

Publication date: Available online 17 March 2016 Source:Hematology/Oncology and Stem Cell Therapy Author(s): Mireille Crampe, Karl Haslam, Johanna Kelly, Eibhlin Conneally, Stephen E. Langabeer Molecular monitoring of BCR–ABL1 transcript levels using quantitative polymerase chain reaction is an essential part of the modern management of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. Establishing the diagnostic BCR–ABL1 fusion transcript is necessary in order to select appropriate primers and probes for such monitoring. A case is described in which quantitative polymerase chain reaction failed to detect the presence of BCR–ABL1 fusion transcript in a Philadelphia chromosome-positive chronic myeloid leukemia patient. Further investigation demonstrated...

Immunovirotherapy with vesicular stomatitis virus and PD-L1 blockade enhances therapeutic outcome in murine acute myeloid leukemia

Thu, 17 Mar 2016 00:00:00 +0100

Patients with relapsed acute myeloid leukemia (AML) have limited therapeutic options. Vesicular stomatitis virus (VSV)–interferon β (IFNβ)–sodium iodide symporter (NIS) is an oncolytic VSV encoding IFNβ and the NIS reporter. Syngeneic AML C1498 tumors responded to IV therapy with VSV-murine IFNβ (mIFNβ)-NIS in a dose-dependent manner. Imaging for NIS expression showed robust virus infection within the tumors. Virus infection did not increase programmed death ligand 1 (PD-L1) on tumor cells. Combining VSV-mIFNβ-NIS with anti-PD-L1 antibody (Ab) therapy enhanced antitumor activity compared with treatment with virus alone or Ab alone; this enhancement was not significant at higher VSV-mIFNβ-NIS doses. Systemic VSV therapy reduced systemic C1498&n...

Application of cell sorting for enhancing the performance of the cytokinesis-block micronucleus assay

Thu, 17 Mar 2016 00:00:00 +0100

Among the numerous methods available to assess genotoxicity, the cytokinesis-block micronucleus (CBMN) assay is very popular due its relative simplicity and power to detect both clastogenic and aneugenic compounds. A problem with the CBMN assay is that all DNA damaging agents also inhibit the ability of cells to progress through mitosis, leading to a low number of binucleated cells (BNCs). One method to resolve this issue is to ensure a sufficient proportion of BNCs in the samples. In the current study, the applicability of a cell sorting system capable of isolating cell fractions containing abundant BNCs was investigated. Furthermore, to investigate the relationship between the cell division delay due to radiation exposure and the generation of BNCs and micronuclei (MN), we assessed a ser...

Novel TNF-related Apoptotic-inducing Ligand-based Immunotoxin for Therapeutic Targeting of CD25 Positive Leukemia

Wed, 16 Mar 2016 23:00:00 +0100

Abstract Background Human TNF-related apoptotic-inducing ligand (TRAIL) has been used successfully for targeted therapy of almost all cancers. Leukemia is the most common type of cancer in children, and despite the advances in therapeutic strategies, the survival rate in leukemia cases is very low. Overexpression of interleukin 2 receptor (IL2R) in hematological malignancies has been utilized to target leukemia. Here, we report an immunotoxin fusion construct of human IL2α and TRAIL for targeting leukemia. Aim Our aim was to develop an immunotoxin to target CD25+ leukemic cells. Methods Recombinant fusion construct comprising human IL2α and TRAIL114–281 was cloned, expressed an...

Cancer incidence in France over the 1980-2012 period: Hematological malignancies.

Wed, 16 Mar 2016 14:18:02 +0100

CONCLUSION: The striking differences in the incidence patterns by histologic subtype strongly suggest a certain level of etiologic heterogeneity among hematological malignancies and support the pursuit of epidemiologic analysis by subtype for HMs in international studies. Age-standardized incidence rates are essential to analyze trends in risk, whereas the number of incident cases is necessary to make provisions for healthcare resources and to evaluate the overall burden of HM. PMID: 26973179 [PubMed - as supplied by publisher] (Source: Revue d Epidemiologie et de Sante Publique)

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Subtype-specific incidence rates of lymphoid malignancies in Hong Kong compared to the United States, 2001–2010

Wed, 16 Mar 2016 00:00:00 +0100

Publication date: June 2016 Source:Cancer Epidemiology, Volume 42 Author(s): Bryan A. Bassig, Wing-Yan Au, Oscar Mang, Roger Ngan, Lindsay M. Morton, Dennis K.M. Ip, Wei Hu, Tongzhang Zheng, Wei Jie Seow, Jun Xu, Qing Lan, Nathaniel Rothman Clinical studies of lymphoid malignancies (LMs) have suggested that the descriptive patterns of LMs differ in East Asia compared to Western populations. However, there are very limited available data on population-based, subtype-specific incidence rates of LMs in the East Asian population, particularly in Chinese. Using data from the Hong Kong (HK) Cancer Registry and United States (U.S.) SEER Program, we calculated and compared age-adjusted incidence rates of LM subtypes in HK to those in Whites and Asians living in the U.S. Overall and s...

Hair and Nail Effects of Ibrutinib Use in Chronic Lymphocytic Leukemia

Wed, 16 Mar 2016 00:00:00 +0100

This observational study assessed the incidence of brittle nails and hair changes in 66 patients with chronic lymphocytic leukemia (CLL) enrolled in a single-arm phase 2 clinical trial of ibrutinib for CLL. (Source: JAMA Dermatology)

Allogeneic Stem Cell Transplantation for Patients with T315I BCR-ABL Mutated Chronic Myeloid Leukemia

Wed, 16 Mar 2016 00:00:00 +0100

Allogeneic stem cell transplantation (Allo-SCT) is currently the only curative treatment option for chronic myeloid leukemia (CML) patients with BCR-ABL T315I mutations. We now report the outcome of SCT in 22 patients with T315I+ CML patients, the majority of which (n=16) from haploidentical family donors (HID-SCT). At the time the mutation was detected, 8 patients were in the chronic phase (CP), 7 in the accelerated phase (AP), and 7 in the blast phase (BP). At the time of SCT, 7 were in the CP, 8 in the AP or returning to the CP post-AP (AP/AP-CPn), and 7 in the BP or returning to CP post-BP (BP/BP-CPn). (Source: Biology of Blood and Marrow Transplantation)

Clinical Challenge: An Orbital Hickam’s Dictum

Wed, 16 Mar 2016 00:00:00 +0100

A 53-year old man with hyperthyroidism presented with asymmetric proptosis and diplopia. Thyroid stimulating immunoglobulin was elevated, suggesting active thyroid eye disease (TED). Imaging of the orbits revealed enlargement of the extraocular muscles including irregular enlargement of the left lateral rectus muscle. Biopsy of the lateral rectus muscle demonstrated infiltration of the muscle with Bcl-2 positive B lymphocytes, consistent with chronic lymphocytic leukemia (CLL). Evaluation for systemic lymphoproliferative disease was negative. (Source: Survey of Ophthalmology)

Using generic cancer drug could save many millions of dollars

Tue, 15 Mar 2016 11:00:00 +0100

With the expiration in January of the patent on Gleevec, the drug that 15 years ago changed chronic myeloid leukemia (CML) from a death sentence to a treatable illness, insurance companies and patients have the opportunity to realize huge cost savings, new Johns Hopkins Bloomberg School of Public Health research suggests. (Source: World Pharma News)

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Patient‐related factors independently impact overall survival in patients with myelodysplastic syndromes: an MDS‐CAN prospective study

Tue, 15 Mar 2016 00:00:00 +0100

Summary Little is known about the effects of frailty, disability and physical functioning on the clinical outcomes for myelodysplastic syndromes (MDS). We investigated the predictive value of these factors on overall survival (OS) in 445 consecutive patients with MDS and chronic monomyelocytic leukaemia (CMML) enrolled in a multi‐centre prospective national registry. Frailty, comorbidity, instrumental activities of daily living, disability, quality of life, fatigue and physical performance measures were evaluated at baseline and were added as covariates to conventional MDS‐related factors as predictors of OS in Cox proportional hazards models. The median age was 73 years, and 79% had revised International Prognostic Scoring System (IPSS‐R) risk scores of intermediate or lower. Frail...

Characterization and automatic screening of reactive and abnormal neoplastic B lymphoid cells from peripheral blood

Tue, 15 Mar 2016 00:00:00 +0100

ConclusionThe excellent automatic screening of the three groups of normal, reactive, and abnormal lymphocytes is useful as it discriminates between malignancy and not malignancy. The discrimination of the five groups of abnormal lymphoid cells is encouraging toward the idea that the system could be an automated image‐based screening method to identify blood involvement by a variety of B lymphomas. (Source: Clinical and Laboratory Haematology)

Bloodstream infections in patients with chronic lymphocytic leukemia: a longitudinal single-center study

Tue, 15 Mar 2016 00:00:00 +0100

Abstract Infectious complications in chronic lymphocytic leukemia (CLL) represent a major cause of morbidity and mortality. The aim of the study was to investigate temporal trends in bloodstream infections (BSIs) among patients with CLL. Individuals with blood cultures were linked to Swedish Cancer Registry and divided into three time periods (1988–1993, 1994–1999, and 2000–2006) according to year of CLL diagnosis. CLL patients (n = 275) with 1092 blood culture episodes were identified and linked to the nationwide Cause of Death Registry and Swedish Patient Registry (to retrieve information on splenectomies). The most common causes of BSI among CLL patients were Escherichia coli (11/43, 15/78, and 9/33), Streptococcus pneumoniae (7/43, 13/78, and 6/33), Pseudomonas aerug...

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Mimicking the tumour microenvironment of chronic lymphocytic leukaemia in vitro critically depends on the type of B-cell receptor stimulation

Tue, 15 Mar 2016 00:00:00 +0100

Authors: Ans Rombout, Sofie Lust, Fritz Offner, Evelien Naessens, Bruno Verhasselt & Jan Philippé (Source: British Journal of Cancer)

Is Wilms’ tumor gene 1 a useful biomarker for detecting minimal residual disease in chronic myeloid leukemia (BCR-ABL1-p210-positive) patients?

Tue, 15 Mar 2016 00:00:00 +0100

Abstract Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder characterized by the presence of Philadelphia (Ph) chromosome. Wilms’ tumor gene 1 (WT1) plays an important role in leukemogenesis and can be useful as a molecular marker to detect minimal residual disease (MRD). The goal of this study was to evaluate WT1 expression and compare it with BCR-ABL1 expression in peripheral blood (PB) of CML patients, in order to explore the utility of WT1 as an alternative marker for MRD detection. Eighteen newly diagnosed CML patients (BCR-ABL1-p210-positive), 16 chronic CML patients with a history of imatinib therapy, and 18 normal individuals (BCR-ABL1-p210-negative) as controls were enrolled in this study. WT1 and BCR-ABL1 expression was evaluated by quantitativ...

Poly(ADP-Ribose) Polymerase Inhibitor Hypersensitivity in Aggressive Myeloproliferative Neoplasms.

Tue, 15 Mar 2016 00:00:00 +0100

CONCLUSIONS: Like other neoplasms with HR defects, MPNs exhibit PARP inhibitor hypersensitivity compared to normal marrow. These results suggest that further preclinical and possibly clinical study of PARP inhibitors in MPNs is warranted. PMID: 26979391 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Unplugging JAK/STAT in Chronic Myelomonocytic Leukemia.

Tue, 15 Mar 2016 00:00:00 +0100

Authors: Solary E Abstract The proliferative component of chronic myelomonocytic leukemia, related to an increased sensitivity of myeloid progenitors to granulocyte macrophage-colony stimulating factor, suggests dedicated therapeutic approaches. In this issue, ruxolitinib, a janus activated kinase (JAK)-1 and -2 inhibitory drug, is shown to induce objective responses in chronic myelomonocytic leukemia patients. PMID: 26979390 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

[Leukemia research in Germany: the Competence Network Acute and Chronic Leukemias].

Tue, 15 Mar 2016 00:00:00 +0100

Authors: Kossak-Roth U, Saußele S, Aul C, Büchner T, Döhner H, Dugas M, Ehninger G, Ganser A, Giagounidis A, Gökbuget N, Griesshammer M, Hasford J, Heuser M, Hiddemann W, Hochhaus A, Hoelzer D, Niederwieser D, Reiter A, Röllig C, Hehlmann R Abstract The Competence Network "Acute and Chronic Leukemias" was founded in 1997 by the consolidation of the leading leukemia study groups in Germany. Key results are the development of new trials and cooperative studies, the setup of patient registries and biobanking facilities, as well as the improvement of study infrastructure. In 2003, the concept of the competence network contributed to the foundation of the European LeukemiaNet (ELN). Synergy with the ELN resulted in cooperation on a European and international level, standardization...

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Activity of the oral mitogen‐activated protein kinase kinase inhibitor trametinib in RAS‐mutant relapsed or refractory myeloid malignancies

Tue, 15 Mar 2016 00:00:00 +0100

CONCLUSIONSThe selective, single‐agent activity of trametinib against RAS‐mutated myeloid malignancies validates its therapeutic potential. Combination strategies based on a better understanding of the hierarchical role of mutations and signaling in myeloid malignancies are likely to improve the response rate and duration. Cancer 2016. © 2016 American Cancer Society. (Source: Cancer)

Viruses, Vol. 8, Pages 80: Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo

Mon, 14 Mar 2016 00:00:00 +0100

Clonal expansion of human T-lymphotropic virus type-1 (HTLV-1) infected cells in vivo is well documented. Unlike human immunodeficiency virus type 1 (HIV-1), HTLV-1 plasma RNA is sparse. The contribution of the “mitotic” spread of HTLV-1 compared with infectious spread of the virus to HTLV-1 viral burden in established infection is uncertain. Since extrachromosomal long terminal repeat (LTR) DNA circles are indicators of viral replication in HIV-1 carriers with undetectable plasma HIV RNA, we hypothesised that HTLV-1 LTR circles could indicate reverse transcriptase (RT) usage and infectious activity. 1LTR and 2LTR DNA circles were measured in HTLV-1 cell lines and peripheral blood mononuclear cells (PBMC) of asymptomatic carriers (ACs) and patients with HTLV-1-associated myelopathy/tro...

CYP3A7 Variation and Cancer Outcome

Mon, 14 Mar 2016 00:00:00 +0100

CYP3A enzymes metabolize endogenous hormones and chemotherapeutic agents used to treat cancer, thereby potentially affecting drug effectiveness. Here, we refined the genetic basis underlying the functional effects of a CYP3A haplotype on urinary estrone glucuronide (E1G) levels and tested for an association between CYP3A genotype and outcome in patients with chronic lymphocytic leukemia (CLL), breast, or lung cancers. The most significantly associated SNP was rs45446698, an SNP that tags the CYP3A7*1C allele; this SNP was associated with a 54% decrease in urinary E1G levels. Genotyping this SNP in 1,008 breast cancer, 1,128 lung cancer, and 347 CLL patients, we found that rs45446698 was associated with breast cancer mortality (HR, 1.74; P = 0.03), all-cause mortality in lung cancer patient...

Performance of Sokal and Eutos Scores for Predicting Cytogenetic and Molecular Response in Newly Diagnosed Chronic Myeloid Leukemia-Chronic Phase Patients on Imatinib

Mon, 14 Mar 2016 00:00:00 +0100

Abstract Sokal index was developed in the pre-imatinib era to predict and prognosticate the outcome of Chronic myeloid leukemia (CML) patients. In the Imatinib era, a new scoring system called EUTOS scoring system has been validated as a predictive marker in CML. The scores have shown variable correlation with complete cytogenetic response (CCyR) and major molecular response (MMR). To assess the performance of Sokal score and EUTOS score as a predictive marker for CCyR and MMR for newly diagnosed CML-CP patients treated with TKIs. 273 patients with newly diagnosed CML were included in the study. They were treated with upfront imatinib. They were followed up for a median period of 3 years. Cytogenetic and Molecular response to the treatment were monitored regularly. Out of 273 pat...

Dendrimer-based nanoparticles for potential personalized therapy in chronic lymphocytic leukemia: targeting the BCR-Signaling Pathway.

Mon, 14 Mar 2016 00:00:00 +0100

Authors: Franiak-Pietryga I, Maciejewski H, Ostrowska K, Appelhans D, Voit B, Misiewicz M, Kowalczyk P, Bryszewska M, Borowiec M Abstract Chronic lymphocytic leukemia (CLL) is one of the most prevalent forms of leukemia in western society. Although classic chemoimmune therapy is still the gold standard of care for leukemic patients, effective therapy of CLL is yet to be achieved. The present study examines the influence of poly(propylene)imine (PPI) dendrimers with primary amino surface groups modified with maltotriose residues in approximately 90% (PPI-G4-DS-Mal-III) or 30% (PPI-G4-OS-Mal-III) of cases on CLL cells (MEC-1 cell line with del(17p)), and confirms that the main trigger in this interaction is the induction of the apoptotic mechanism. The efficacy of each dendrimer was ...

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

RalA, a GTPase targeted by miR‑181a, promotes transformation and progression by activating the Ras‑related signaling pathway in chronic myelogenous leukemia.

Sun, 13 Mar 2016 18:08:02 +0100

Authors: Gu C, Feng M, Yin Z, Luo X, Yang J, Li Y, Li T, Wang R, Fei J Abstract BCR/ABL is a well-known activator of multiple signaling pathways. RalA, a Ras downstream signaling molecule and a small GTPase, plays an important role in Bcr-Abl-induced leukemogenesis but the exact mechanism remains elusive. Here, we show that RalA GTPase activity is commonly high in chronic myelogenous leukemia (CML) cell lines and patient samples. Overexpression of RalA results in malignant transformation and progression, and induces resistance to imatinib (IM) in BaF3 and K562 cell lines. RalA reduced survival and led to IM resistance in a xenografted mouse model. Ablation of RalA by either siRNA or miR-181a, a RalA targeting microRNA, attenuated the malignant phenotypes in K562 cells. RBC8, a sele...

MicroRNAs mediated regulation of MAPK signaling pathways in chronic myeloid leukemia.

Sun, 13 Mar 2016 18:08:02 +0100

Authors: Chakraborty C, Sharma AR, Patra BC, Bhattacharya M, Sharma G, Lee SS Abstract Chronic myeloid leukemia (CML) is a severe problem throughout the world and requires identification of novel targets for its treatment. This multifactorial disease accounts for about 15% of the all diagnosed leukemia cases. Mitogen-activated protein kinase (MAPK) signaling pathway is crucial for the cell survival and its dysregulation is being implicated in various types of cancers. In here, we have discussed the potential role of various miRNAs that are found involved in regulating the proteins cascades of MAPK signaling pathway associated with CML. An emphasis has been paid to summarize the influence of various miRNAs in elevating or suppressing the expression level of significant proteins such...

A Canadian perspective on the use of immunoglobulin therapy to reduce infectious complications in chronic lymphocytic leukemia.

Sun, 13 Mar 2016 18:01:02 +0100

Authors: Lachance S, Christofides AL, Lee JK, Sehn LH, Ritchie BC, Shustik C, Stewart DA, Toze CL, Haddad E, Vinh DC Abstract Infections are a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (cll), who typically have increased susceptibility because of hypogammaglobulinemia (hgg) related to their disease and its treatment. Immunoglobulin replacement therapy (igrt) has been shown to reduce the frequency of bacterial infections and associated hospitalizations in patients with hgg or a history of infection, or both. However, use of igrt in cll is contentious. Studies examining such treatment were conducted largely before the use of newer chemoimmunotherapies, which can extend lifespan, but do not correct the hgg inherent to the disease. Thus, the u...

Treating chronic lymphocytic leukemia with obinutuzumab: safety and efficacy considerations.

Sun, 13 Mar 2016 10:27:01 +0100

This article evaluates the safety of obinutuzumab in CLL patients, also addressing pharmacokinetics/pharmacodynamics (PK/PD), clinical use and efficacy. Moreover, a comparison with other anti-CD20 MoAb is performed. The principal available studies on obinutuzumab are reviewed, focusing on CLL. A PubMed literature search (August 2002 to September 2015) was conducted using the terms obinutuzumab, GA101, anti-CD20 antibody, and CLL. Expert opinion: Obinutuzumab, a third-generation anti-CD20 MoAb, is a safe and effective treatment for elderly patients who are un-fit for fludarabine-based regimen. Its use, proven in the CLL11 study and the results of many ongoing trials evaluating other obinutuzumab-based regimen can lead obinutuzumab to be a candidate to replace rituximab as the first-line tre...

Epstein-Barr Virus-positive T-cell Lymphoproliferative Disease Following Umbilical Cord Blood Transplantation for Acute Myeloid Leukemia.

Sat, 12 Mar 2016 22:12:02 +0100

We report a case of the extremely rare condition Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease (LPD) which occurred after umbilical cord blood transplantation. A 25-year-old Japanese man underwent cord blood transplantation from a male human leukocyte antigen 4/6-matched donor due to acute myeloid leukemia with trisomy 8. Bone marrow examination on day 30 showed chimerism with at least 90% donor cells and complete hematological response. Chronic symptoms of graft-versus-host disease appeared only on the skin and were successfully treated with cyclosporine alone. Three years later, however, the patient experienced repeated cold-like symptoms and was hospitalized with liver dysfunction. A high fever developed and was followed by significant edema of the right side of t...

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Serum Angiopoietin Levels are Different in Acute and Chronic Myeloid Neoplasms: Angiopoietins do not only Regulate Tumor Angiogenesis

Sat, 12 Mar 2016 18:35:07 +0100

Abstract Molecular balance between Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) has important effects in tumor angiogenesis. Ang-2 was shown to be elevated and proved to be a prognostic factor in acute myeloid leukemia (AML). To date studies revealed increased angiogenesis in bone marrows (BMs) of both myeloproliferative neoplasm (MPN) and AML patients. We conducted this study to demonstrate circulating levels of Ang-1 and Ang-2 in MPN patients since no data exists in literature. Thirty-three newly diagnosed MPN, 27 newly diagnosed AML patients and 25 controls (HC) were enrolled and Angiopoietin levels were determined with ELISA. We found that Ang-1 levels were higher whereas Ang-2 levels were lower in MPN and HC when compared to AML. Our results suggest that though angiogen...

UCLA faculty voice: When it comes to breastfeeding, a mother’s health and happiness matter too

Fri, 11 Mar 2016 09:06:19 +0100

Vivien Burt Robin Berman Dr. Vivien Burt is a professor emeritus of psychiatry and biobehavioral sciences and the co-director of the Women’s Life Center at the Resnick Neuropsychiatric Hospital at UCLA. Dr. Sonya Rasminsky is an associate clinical professor of psychiatry at UC Irvine. Dr. Robin Berman is an associate professor of psychiatry at UCLA. This column appeared March 3 in the Washington Post’s “On Parenting” blog. Whoever said, “Don’t cry over spilled milk” couldn’t possibly have been talking about breast milk. As reproductive psychiatrists who specialize in treating women who suffer from depression and anxiety during pregnancy and the postpartum, we see far too many tearful new mothers for whom breastfeeding is a source of self-recrimination. Doggedly determine...

Ibrutinib for treatment of chronic lymphocytic leukemia.

Fri, 11 Mar 2016 02:05:02 +0100

CONCLUSION: Ibrutinib is a first-in-class, orally active, irreversible BTK inhibitor with a novel mechanism of action. This unique mechanism of action and high overall response rates observed in clinical trials make ibrutinib an attractive second-line option in patients who have disease progression while receiving monoclonal antibody therapy or chemoimmunotherapy. PMID: 26953281 [PubMed - in process] (Source: American Journal of Health-System Pharmacy : AJHP)

A clinically relevant pharmacokinetic interaction between cyclosporine and imatinib

Fri, 11 Mar 2016 00:00:00 +0100

Conclusions Imatinib significantly increases CsA concentrations in HSCT patients, putting these patients at increased risk of CsA toxicity. We recommend intensive monitoring of CsA concentrations after initiation of imatinib; a pre-emptive CsA dose reduction of 25 % might be considered. (Source: European Journal of Clinical Pharmacology)

A high rate of telomeric sister chromatid exchange occurs in chronic lymphocytic leukaemia B‐cells

Fri, 11 Mar 2016 00:00:00 +0100

Summary Cancer cells protect their telomere ends from erosion through reactivation of telomerase or by using the Alternative Lengthening of Telomere (ALT) mechanism that depends on homologous recombination. Chronic lymphocytic leukaemia (CLL) B cells are characterized by almost no telomerase activity, shelterin deregulation and telomere fusions. To characterize telomeric maintenance mechanisms in B‐CLL patients, we measured their telomere length, telomerase expression and the main hallmarks of the ALT activity i.e. C‐circle concentration, an extra‐chromosomal telomere repeat (ECTR), and the level of telomeric sister chromatid exchange (T‐SCE) rate. Patients showed relative homogenous telomere length although almost no TERT transcript and nearly no C‐circle were evidenced. Neverth...

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Long‐Term Evaluation of Cardiac and Vascular Toxicity in Patients With Philadelphia Chromosome–Positive Leukemias Treated With Bosutinib

Fri, 11 Mar 2016 00:00:00 +0100

This article is protected by copyright. All rights reserved. (Source: American Journal of Hematology)

Lenalidomide treatment and prognostic markers in relapsed or refractory chronic lymphocytic leukemia: data from the prospective, multicenter phase-II CLL-009 trial

Fri, 11 Mar 2016 00:00:00 +0100

Authors: A Bühler, C-M Wendtner, T J Kipps, L Rassenti, G A M Fraser, A-S Michallet, P Hillmen, J Dürig, S A Gregory, M Kalaycio, T Aurran-Schleinitz, L Trentin, J G Gribben, A Chanan-Khan, B Purse, J Zhang, S De Bedout, J Mei, M Hallek & S Stilgenbauer (Source: Blood Cancer Journal)

Expression of activated molecules on CD5(+)B lymphocytes in autoimmune hemolytic anemia.

Fri, 11 Mar 2016 00:00:00 +0100

Authors: Zhu H, Xu W, Liu H, Wang H, Fu R, Wu Y, Qu W, Wang G, Guan J, Song J, Xing L, Shao Z Abstract To investigate the expression of activation molecules on CD5(+)B lymphocytes in peripheral blood of autoimmune hemolytic anemia (AIHA)/Evans patients. The expression of CD80, CD86, and CD69 on CD5(+)B lymphocytes was detected using flow cytometry in 30 AIHA/Evans patients, 18 normal controls (NC) and nine chronic lymphocytic leukemia (CLL) patients. CD80 on CD5(+)B lymphocytes in untreated patients was higher than that in remission patients (P < 0.05), NC (P < 0.01) and CLL patients (P < 0.01). CD80 on CD5(+)B lymphocytes was higher than that on CD5(-)B lymphocytes in untreated patients (P > 0.05), but lower than those of CD5(-)B lymphocytes in remission patien...

Expanding transplant options to patients over 50 years- Improved outcome after reduced intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: A report from the Acute Leukemia Working Party of the EBMT.

Fri, 11 Mar 2016 00:00:00 +0100

Authors: Savani BN, Labopin M, Kröger N, Finke J, Ehninger G, Niederwieser D, Schwerdtfeger R, Bunjes D, Glass B, Socie' G, Ljungman P, Craddock C, Baron F, Ciceri F, Gorin NC, Esteve J, Schmid C, Giebel S, Mohty M, Nagler A Abstract The outcome of patients undergoing HLA-matched unrelated donor allogeneic hematopoietic cell transplantation following reduced-intensity conditioning or myeloablative regimens is reported to be equivalent; however, it is not known if the intensity of the conditioning impacts outcomes after mismatched-unrelated donor transplantation for acute myeloid leukemia. Eight hundred eighty three patients receiving reduced-intensity conditioning were compared with 1041 myeloablative conditioning regimen recipients in the setting of mismatched-unrelated donor tra...

New class of drugs specifically induces cell death in B cell blood cancers

Thu, 10 Mar 2016 19:14:53 +0100

New research shows how one protein found on the endoplasmic reticulum can serve as a target for stimulating the immune system and a more direct target for cellular death in B cell malignancies. B cell malignancies include illnesses like chronic lymphocytic leukemia and multiple myeloma. (Source: ScienceDaily Headlines)

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

Metformin combined with sodium dichloroacetate promotes B leukemic cell death by suppressing anti-apoptotic protein Mcl-1.

Thu, 10 Mar 2016 18:18:02 +0100

Authors: Voltan R, Rimondi E, Melloni E, Gilli P, Bertolasi V, Casciano F, Rigolin GM, Zauli G, Secchiero P Abstract Metformin and the mitochondrial targeting dichloroacetate (DCA) have recently received attention due to their ability to inhibit anaerobic glycolysis, which renders most cancer cells resistant to apoptosis induction. We observed that Metformin alone exhibited a dose-dependent anti-leukemic activity in both B leukemic cell lines and primary B-chronic lymphocytic leukemia (B-CLL) patients' cells and its anti-leukemic activity was enhanced when used in combination with DCA. In order to overcome the problems of poor bioavailability and cellular uptake, which limit DCA efficacy, we have designed and synthetized cocrystals consisting of Metformin and DCA (Met-DCA) at diffe...

Impact of BCR-ABL transcript type on outcome in patients with chronic-phase CML treated with tyrosine kinase inhibitors

Thu, 10 Mar 2016 00:00:00 +0100

This study involved 481 patients with chronic phase CML expressing various BCR-ABL transcripts. Two hundred patients expressed e13a2 (42%), 196 (41%) expressed e14a2, and 85 (18%) expressed both transcripts. The proportion of patients with e13a2, e14a2, and both achieving complete cytogenetic response at 3 and 6 months was 59%, 67%, and 63% and 73%, 81%, and 82%, respectively, whereas major molecular response rates were 27%, 49%, and 50% at 3 months, 42%, 67%, and 70% at 6 months, and 55%, 83%, and 76% at 12 months, respectively. Median (international scale) levels of transcripts e13a2, e14a2, and both at 3 months were 0.2004, 0.056, and 0.0612 and at 6 months were 0.091, 0.0109, and 0.0130, respectively. In multivariate analysis, e14a2 and both predicted for optimal responses at 3, 6, and...

Simplifying procedure for prediction of resistance risk in CML patients – test of sensitivity to TKI ex vivo

Thu, 10 Mar 2016 00:00:00 +0100

Publication date: Available online 10 March 2016 Source:Blood Cells, Molecules, and Diseases Author(s): Markéta Žáčková, Tereza Macháčková Lopotová, Zuzana Ondráčková, Kateřina Kuželová, Hana Klamová, Jana Moravcová Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have dramatically improved chronic myeloid leukemia therapy. While imatinib remains to be the first line therapy, about 30% of patients develop resistance or intolerance to this drug and are recommended to switch to other TKIs. Nilotinib and dasatinib are currently implemented into the first line therapy and other inhibitors have already entered the clinical practice. This opens further questions on how to select the best TKI for each patient not only during the therapy but also at diagnosis. The indiv...

Dasatinib induces severe hemorrhagic colitis in a patient with accelerated phase of chronic myelogenous leukemia.

Thu, 10 Mar 2016 00:00:00 +0100

Authors: Yim E, Choi YG, Nam YJ, Lee J, Kim JA PMID: 26961484 [PubMed - as supplied by publisher] (Source: The Korean Journal of Internal Medicine)

Molecules, Vol. 21, Pages 331: Review on a Traditional Herbal Medicine, Eurycoma longifolia Jack (Tongkat Ali): Its Traditional Uses, Chemistry, Evidence-Based Pharmacology and Toxicology

Thu, 10 Mar 2016 00:00:00 +0100

Eurycoma longifolia Jack (known as tongkat ali), a popular traditional herbal medicine, is a flowering plant of the family Simaroubaceae, native to Indonesia, Malaysia, Vietnam and also Cambodia, Myanmar, Laos and Thailand. E. longifolia, is one of the well-known folk medicines for aphrodisiac effects as well as intermittent fever (malaria) in Asia. Decoctions of E. longifolia leaves are used for washing itches, while its fruits are used in curing dysentery. Its bark is mostly used as a vermifuge, while the taproots are used to treat high blood pressure, and the root bark is used for the treatment of diarrhea and fever. Mostly, the roots extract of E. longifolia are used as folk medicine for sexual dysfunction, aging, malaria, cancer, diabetes, anxiety, aches, constipation, exercise recove...

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

High LEF1 expression predicts adverse prognosis in chronic lymphocytic leukemia and may be targeted by ethacrynic acid.

Wed, 09 Mar 2016 06:24:02 +0100

In this study, we determined LEF1 gene expression levels in CLL (n = 197) and monoclonal B-cell lymphocytosis (MBL) (n = 6) patients through real-time RT-PCR. LEF1 was significantly up-regulated in both MBL and CLL patients compared with normal B cells. Treatment-free survival (TFS) time and overall survival (OS) time were much longer in CLL patients with low LEF1 expression than in those with high LEF1 levels. Furthermore, Wnt inhibitor ethacrynic acid (EA) induced both apoptosis and necroptosis in primary CLL cells. EA also enhanced the cytotoxicity of both fludarabine and cyclophosphamide against CLL cells in vitro. Finally, we demonstrated that EA functions by inhibiting the recruitment of LEF1 to DNA promoters and restoring cylindromatosis (CYLD) expression in CLL cells. Our results s...

Effects of tamoxifen on traumatic brain injury-induced depression in male rats

Wed, 09 Mar 2016 00:00:00 +0100

Conclusion Our results suggest that intraperitoneal injection of TMX may ameliorate TBI-induced depression-like behavior in rats by increasing neuronal p-ERK1/2 expression, which may be associated with neuronal Bcl2 and BDNF expression and decreased neuronal apoptosis. This effect might represent a mechanism underlying the recovery from depression-like behavior. (Source: Formosan Journal of Surgery)

Cyclin dependent kinase inhibitors for the treatment of chronic lymphocytic leukemia

Wed, 09 Mar 2016 00:00:00 +0100

In the last 10 years, oncology has been transformed by the development and broad availability of small molecule therapies for cancer. Compounds have been and are being developed to target nearly every known relevant component of the cell’s machinery. One class of compounds, the cyclin-dependent kinase (CDK) inhibitors, was originally conceived as an anticancer therapeutic based on the premise that as cancer is (in part) defined by loss of cell-cycle control, the interruption of cell cycle could arrest cancer growth. (Source: Seminars in Oncology)

Management of Elderly Patients with Newly Diagnosed Chronic Myeloid Leukemia in the Accelerated or Blastic Phase

Wed, 09 Mar 2016 00:00:00 +0100

Abstract In the elderly population, the accelerated and blastic phases of chronic myeloid leukemia (CML) are difficult to treat, not just because of the higher chance of acquired mutations than in younger individuals, but because of additional associated co-morbidities. Tyrosine kinase inhibitors are well-established in the treatment of the chronic phase of CML, and their use in advanced phases is ever-increasing. Elderly patients who are still eligible candidates for transplant can undergo reduced-intensity transplants from related or unrelated donors after reverting to chronic phase. Post-transplantation, these patients require adequate monitoring and therapy to prevent relapses. Newer modalities of treatment or interventions are urgently required in this complex group of patien...

Bortezomib-mediated downregulation of S-phase kinase protein-2 (SKP2) causes apoptotic cell death in chronic myelogenous leukemia cells

Wed, 09 Mar 2016 00:00:00 +0100

Proteasome inhibitors are attractive cancer therapeutic agents because they can regulate apoptosis-related proteins. Bortezomib also known as Velcade®, a proteasome inhibitor that has been approved by the food an... (Source: Journal of Translational Medicine)

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.