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British Journal of Haematology

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https://www.readbyqxmd.com/read/28342200/telomere-length-is-a-critical-determinant-for-survival-in-multiple-myeloma
#1
Sam Hyatt, Rhiannon E Jones, Nicole H Heppel, Julia W Grimstead, Chris Fegan, Graham H Jackson, Robert Hills, James M Allan, Guy Pratt, Chris Pepper, Duncan M Baird
The variable clinical outcomes of Multiple Myeloma (MM) patients are incompletely defined by current prognostication tools. We examined the clinical utility of high-resolution telomere length analysis as a prognostic marker in MM. Cohort stratification, using a previously determined length threshold for telomere dysfunction, revealed that patients with short telomeres had a significantly shorter overall survival (P < 0·0001; HR = 3·4). Multivariate modelling using forward selection identified International Staging System (ISS) stage as the most important prognostic factor, followed by age and telomere length...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28342183/results-of-a-multicentre-uk-wide-compassionate-use-programme-evaluating-the-efficacy-of-idelalisib-monotherapy-in-relapsed-refractory-follicular-lymphoma
#2
LETTER
Toby A Eyre, Wendy L Osborne, Eve Gallop-Evans, Kirit M Ardeshna, Shireen Kassam, Shalal Sadullah, Gamal Sidra, Dominic Culligan, Arvind Arumainathan, Paneesha Shankara, Kristian M Bowles, David W Eyre, Ying Y Peng, Ruth Pettengell, Adrian Bloor, Elisabeth Vandenberghe, Graham P Collins
No abstract text is available yet for this article.
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28340285/the-six-minute-walk-test-in-patients-with-al-amyloidosis-a-single-centre-case-series
#3
Vina Pulido, Gheorghe Doros, John L Berk, Vaishali Sanchorawala
The six-minute walk test (6MWT) has been widely used as an objective evaluation of functional exercise capacity and response to medical intervention in cardiopulmonary diseases. However, little is known about the 6MWT in evaluating patients with AL amyloidosis. We performed a retrospective study of 120 adults with systemic AL amyloidosis (60 with cardiac involvement and 60 without cardiac involvement) who had their initial evaluation at the Amyloidosis Center between 2013 and 2015 and had undergone 6MWT as a measure of functional exercise capacity...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28340283/comparative-analysis-of-pulmonary-hypertension-in-patients-treated-with-imatinib-nilotinib-and-dasatinib
#4
Mariko Minami, Takeshi Arita, Hiromi Iwasaki, Tsuyoshi Muta, Takatoshi Aoki, Kenichi Aoki, Satoshi Yamasaki, Takamitsu Matsushima, Koji Kato, Katsuto Takenaka, Kazuki Tanimoto, Tomohiko Kamimura, Ryosuke Ogawa, Koichi Akashi, Toshihiro Miyamoto
Pulmonary hypertension (PH) is a rare, but life-threatening, adverse event in patients treated with tyrosine kinase inhibitors (TKIs), such as dasatinib, but has not been fully evaluated in patients treated with imatinib or nilotinib. We used echocardiography to noninvasively assess the incidence of PH in 105 patients with chronic myeloid leukaemia (CML) treated with imatinib (n = 37), nilotinib (n = 30) or dasatinib (n = 38). The mean triscupid regurgitation peak gradient (TRPG), which reflects pulmonary arterial pressure, was 22·7 mmHg in the imatinib group, 23·1 mmHg in the nilotinib group and 23·4 mmHg for dasatinib group...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28340282/carfilzomib-induces-leukaemia-cell-apoptosis-via-inhibiting-elk1-kiaa1524-elk-1-cip2a-and-activating-pp2a-not-related-to-proteasome-inhibition
#5
Chun-Yu Liu, Feng-Shu Hsieh, Pei-Yi Chu, Wen-Chun Tsai, Chun-Teng Huang, Yuan-Bin Yu, Tzu-Ting Huang, Po-Shen Ko, Man-Hsin Hung, Wan-Lun Wang, Chung-Wai Shiau, Kuen-Feng Chen
Enhancing the tumour suppressive activity of protein phosphatase 2A (PP2A) has been suggested to be an anti-leukaemic strategy. KIAA1524 (also termed CIP2A), an oncoprotein inhibiting PP2A, is associated with disease progression in chronic myeloid leukaemia and may be prognostic in cytogenetically normal acute myeloid leukaemia. Here we demonstrated that the selective proteasome inhibitor, carfilzomib, induced apoptosis in sensitive primary leukaemia cells and in sensitive leukaemia cell lines, associated with KIAA1524 protein downregulation, increased PP2A activity and decreased p-Akt, but not with the proteasome inhibition effect of carfilzomib...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28340281/high-ten-year-remission-rates-following-rituximab-fludarabine-mitoxantrone-and-dexamethasone-r-fnd-with-interferon-maintenance-in-indolent-lymphoma-results-of-a-randomized-study
#6
Loretta J Nastoupil, Peter McLaughlin, Lei Feng, Sattva S Neelapu, Felipe Samaniego, Fredrick B Hagemeister, Ana Ayala, Jorge E Romaguera, Andre H Goy, Eleanor Neal, Michael Wang, Luis Fayad, Michelle A Fanale, Yasuhiro Oki, Jason R Westin, Maria A Rodriguez, Fernando Cabanillas, Nathan H Fowler
We report a single-centre, randomized study evaluating the efficacy and safety of concurrent fludarabine, mitoxantrone, dexamethasone (FND) and rituximab versus sequential FND followed by rituximab in 158 patients with advanced stage, previously untreated indolent lymphoma, enrolled between 1997 and 2002. Patients were randomized to 6-8 cycles of FND followed by 6 monthly doses of rituximab or 6 doses of rituximab given concurrently with FND. All patients who achieved at least a partial response received 12 months of interferon (IFN) maintenance...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28339096/pathogenesis-and-management-of-antiphospholipid-syndrome
#7
REVIEW
Deepa R J Arachchillage, Mike Laffan
Antiphospholipid antibodies are a heterogeneous group of autoantibodies that have clear associations with thrombosis and pregnancy morbidity, and which together constitute the 'antiphospholipid syndrome' (APS). However, the pathophysiology of these complications is not well understood and their heterogeneity suggests that more than one pathogenic process may be involved. Diagnosis remains a combination of laboratory analysis and clinical observation but there have been significant advances in identifying specific pathogenic features, such as domain I-specific anti-β2-glycoprotein-I antibodies...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28318026/bone-marrow-fibrosis-at-diagnosis-is-associated-with-tp53-overexpression-and-adverse-prognosis-in-low-risk-myelodysplastic-syndrome
#8
LETTER
Fernando B Duarte, Maritza C Barbosa, Talyta E Jesus Dos Santos, Romélia P G Lemes, João P Vasconcelos, Paulo R L de Vasconcelos, Francisco D Rocha, Ilana Zalcberg, Diego F Coutinho
No abstract text is available yet for this article.
March 20, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28317092/serpinc1-gene-mutations-in-antithrombin-deficiency
#9
René Mulder, F Nanne Croles, André B Mulder, James A Huntington, Karina Meijer, Michaël V Lukens
Existing evidence suggests that in most cases antithrombin deficiency can be explained by mutations in its gene, SERPINC1. We investigated the molecular background of antithrombin deficiency in a single centre family cohort study. We included a total of 21 families comprising 15 original probands and sixty-six relatives, 6 of who were surrogate probands for the genetic analysis. Antithrombin activity and antigen levels were measured. The heparin-antithrombin binding ratio assay was used to distinguish between the different subtypes of type II antithrombin deficiency...
March 20, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28300275/iron-chelation-therapy-in-low-risk-myelodysplastic-syndrome
#10
REVIEW
Sally B Killick
Anaemia is the commonest cytopenia seen in patients with myelodysplastic syndrome (MDS), and the majority of patients will require transfusion support at some point. Blood transfusions are rich in iron, which leads to the accumulation of body iron over time. It is accepted that this ultimately causes end organ damage and may impact on both morbidity and mortality. In addition, recent data has increased our interest in the subject with regard to the potential impact on stem cell transplant outcome and an anti-leukaemic effect of iron chelation therapy...
March 16, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28295224/sickle-cell-disease-in-africa-an-overview-of-the-integrated-approach-to-health-research-education-and-advocacy-in-tanzania-2004-2016
#11
REVIEW
Furahini Tluway, Julie Makani
Sickle cell disease (SCD) is the single most important genetic cause of childhood mortality globally. Tanzania has one of the highest annual births of SCD individuals in the world, estimated to reach 11 000 births a year. Without intervention, 50-90% of children will die in childhood. However, cost-effective interventions have the potential to reduce childhood mortality by up to 70%. The effects of SCD are multi-dimensional, ranging from causing high morbidity and mortality, and reducing the quality of life, to imposing a high socio-economic burden on individuals, families and health systems...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28295201/thrombopoetin-receptor-agonist-therapy-in-thrombocytopenia-itp-and-beyond
#12
Alice Taylor, John Paul Westwood, Faidra Laskou, Siobhan McGuckin, Marie Scully
Eltrombopag is well established in treatment of severe immune thrombocytopenia (ITP) and is increasingly commonplace in second-line management. A role is also suggested for both bridging therapy for surgery, as well as treating thrombocytopenia due to non-immune aetiologies. We present the largest single-centre experience with eltrombopag, with our cohort of 62 patients. Patients with severe ITP (n = 34) had 91·2% response, which was sustained over a median of 18·5 months. In 41·4% of ITP cases (n = 14), complete response (CR- platelet count >100 × 10(9) /l) was achieved and in 2 cases, therapy was stopped and CR maintained...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28295199/measurement-of-bcr-abl1-by-rt-qpcr-in-chronic-myeloid-leukaemia-findings-from-an-international-eqa-programme
#13
Stuart Scott, Debbie Travis, Liam Whitby, John Bainbridge, Nicholas C P Cross, David Barnett
Sequential measurement of BCR-ABL1 mRNA levels by reverse transcription quantitative polymerase chain reaction (RT-qPCR) is embedded in the management of patients with chronic myeloid leukaemia (CML), and has played an important role in the remarkable improvement in patient outcomes seen in this disease. As a provider of external quality assessment (EQA) in this area, UK NEQAS for Leucocyte Immunophenotyping (UKNEQAS LI) has a unique perspective on the changing face of BCR-ABL1 testing in CML. To assess the impact of technical standardisation and the development of the International Scale (IS) upon the accuracy of BCR-ABL1 testing, we reviewed EQA trial data from 2007 to 2015...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28295194/anti-leukaemic-activity-of-the-tyk2-selective-inhibitor-ndi-031301-in-t-cell-acute-lymphoblastic-leukaemia
#14
Koshi Akahane, Zhaodong Li, Julia Etchin, Alla Berezovskaya, Evisa Gjini, Craig E Masse, Wenyan Miao, Jennifer Rocnik, Rosana Kapeller, Jeremy R Greenwood, Hong Tiv, Takaomi Sanda, David M Weinstock, A Thomas Look
Activation of tyrosine kinase 2 (TYK2) contributes to the aberrant survival of T-cell acute lymphoblastic leukaemia (T-ALL) cells. Here we demonstrate the anti-leukaemic activity of a novel TYK2 inhibitor, NDI-031301. NDI-031301 is a potent and selective inhibitor of TYK2 that induced robust growth inhibition of human T-ALL cell lines. NDI-031301 treatment of human T-ALL cell lines resulted in induction of apoptosis that was not observed with the JAK inhibitors tofacitinib and baricitinib. Further investigation revealed that NDI-031301 treatment uniquely leads to activation of three mitogen-activated protein kinases (MAPKs), resulting in phosphorylation of ERK, SAPK/JNK and p38 MAPK coincident with PARP cleavage...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28295193/guidelines-in-lower-middle-income-countries
#15
REVIEW
Edeghonghon Olayemi, Eugenia V Asare, Amma A Benneh-Akwasi Kuma
Guidelines include recommendations intended to optimize patient care; used appropriately, they make healthcare consistent and efficient. In most lower-middle income countries (LMICs), there is a paucity of well-designed guidelines; as a result, healthcare workers depend on guidelines developed in Higher Income Countries (HICs). However, local guidelines are more likely to be implemented because they are applicable to the specific environment; and consider factors such as availability of resources, specialized skills and local culture...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28295191/clonal-dominance-of-pnh-another-piece-to-the-jigsaw
#16
Austin G Kulasekararaj
No abstract text is available yet for this article.
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28295190/phase-i-study-of-cord-blood-derived-natural-killer-cells-combined-with-autologous-stem-cell-transplantation-in-multiple-myeloma
#17
Nina Shah, Li Li, Jessica McCarty, Indreshpal Kaur, Eric Yvon, Hila Shaim, Muharrem Muftuoglu, Enli Liu, Robert Z Orlowski, Laurence Cooper, Dean Lee, Simrit Parmar, Kai Cao, Catherine Sobieiski, Rima Saliba, Chitra Hosing, Sairah Ahmed, Yago Nieto, Qaiser Bashir, Krina Patel, Catherine Bollard, Muzaffar Qazilbash, Richard Champlin, Katy Rezvani, Elizabeth J Shpall
Multiple myeloma (MM) is a disease with known immune dysregulation. Natural killer (NK) cells have shown preclinical activity in MM. We conducted a first-in-human study of umbilical cord blood-derived (CB) NK cells for MM patients undergoing high dose chemotherapy and autologous haematopoietic stem cell transplantation (auto-HCT). Patients received lenalidomide (10 mg) on days -8 to -2, melphalan 200 mg/m(2) on day -7, CB-NK cells on day -5 and auto-HCT on day 0. Twelve patients were enrolled, three on each of four CB-NK cell dose levels: 5 × 10(6) , 1 × 10(7) , 5 × 10(7) and 1 × 10(8) CB-NK cells/kg...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28295188/how-we-manage-iron-overload-in-sickle-cell-patients
#18
REVIEW
Thomas D Coates, John C Wood
Blood transfusion plays a prominent role in the management of patients with sickle cell disease (SCD), but causes significant iron overload. As transfusions are used to treat the severe complications of SCD, it remains difficult to distinguish whether organ damage is a consequence of iron overload or is due to the complications treated by transfusion. Better management has resulted in increased survival, but prolonged exposure to iron puts SCD patients at greater risk for iron-related complications that should be treated...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28295186/skin-lesions-and-cytological-features-in-htlv-1-associated-adult-t-cell-leukaemia-lymphoma
#19
Juan Marquet, Miguel Piris-Villaespesa, Eulalia Rodriguez, Sandra López, Jesús Villarrubia, Jose Antonio García-Vela
No abstract text is available yet for this article.
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28295185/dual-targeting-of-mcl1-and-noxa-as-effective-strategy-for-treatment-of-mantle-cell-lymphoma
#20
Elisabeth Höring, Arnau Montraveta, Simon Heine, Markus Kleih, Lea Schaaf, Matthias C Vöhringer, Anna Esteve-Arenys, Gael Roué, Dolors Colomer, Elias Campo, German Ott, Walter E Aulitzky, Heiko van der Kuip
Imbalances in the composition of BCL2 family proteins contribute to tumourigenesis and therapy resistance of mantle cell lymphoma (MCL), making these proteins attractive therapy targets. We studied the efficiency of dual targeting the NOXA/MCL1 axis by combining fatty acid synthase inhibitors (NOXA stabilization) with the CDK inhibitor Dinaciclib (MCL1 reduction). This combination synergistically induced apoptosis in cell lines and primary MCL cells and led to almost complete inhibition of tumour progression in a mouse model...
March 14, 2017: British Journal of Haematology
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