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Acute myeloid leukaemia

Haiyan Liu, Yuanmei Zhai, Wenli Zhao, Yun Wan, Wei Lu, Shaoxin Yang, Yehua Yu, Yanyu Wei, Zhiqiang Li, Jun Shi
BACKGROUND/AIMS: Chemotherapy is still the main strategy used to prevent the relapse of acute myeloid leukaemia (AML). As the most abundant stromal component in bone marrow (BM), marrow adipocytes have been previously shown to promote leukaemogenesis. The present study was designed to further validate whether marrow adipocytes exert synergistic effects on strengthening chemotherapeutic efficacy and evaluate the underlying mechanism. METHODS: A retrospective study of BM biopsies from 80 patients with AML in remission and 71 control subjects was applied to quantitatively analyse the marrow adipocyte volume...
March 13, 2018: Cellular Physiology and Biochemistry
Frederick Fasslrinner, Johannes Schetelig, Andreas Burchert, Michael Kramer, Rudolf Trenschel, Ute Hegenbart, Michael Stadler, Kerstin Schäfer-Eckart, Michael Bätzel, Hans Eich, Martin Stuschke, Rita Engenhart-Cabillic, Mechthild Krause, Peter Dreger, Andreas Neubauer, Gerhard Ehninger, Dietrich Beelen, Wolfgang E Berdel, Timo Siepmann, Matthias Stelljes, Martin Bornhäuser
BACKGROUND: The impact of the intensity of conditioning before allogeneic haemopoietic cell transplantation (HCT) has been studied in a randomised phase 3 trial comparing reduced-intensity conditioning with myeloablative conditioning in patients with acute myeloid leukaemia in first complete remission. Because of the short follow-up of the original trial, whether reduced-intensity conditioning increases the risk of late relapse compared with myeloablative conditioning remained unclear...
March 14, 2018: Lancet Haematology
Maro Ohanian, Ana Tari Ashizawa, Guillermo Garcia-Manero, Naveen Pemmaraju, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gautam Borthakur, Michael Andreeff, Marina Konopleva, Miranda Lim, Sherry Pierce, Susan O'Brien, Yesid Alvarado, Srdan Verstovsek, William Wierda, Hagop Kantarjian, Jorge Cortes
BACKGROUND: Activating mutations of tyrosine kinases are common in leukaemias. Oncogenic tyrosine kinases use the growth factor receptor-bound protein 2 (Grb2) for signal transduction, leading to activation of mitogen-activated protein kinase (MAPK) 1 and MAPK3 (ERK2 and ERK1). We hypothesised that inhibition of Grb2 would suppress ERK1 and ERK2 activation and inhibit leukaemia progression. To inhibit Grb2, a liposome-incorporated antisense oligodeoxynucleotide that blocks Grb2 protein expression, BP1001, was developed...
March 14, 2018: Lancet Haematology
Adam Gassas, Ponni Sivaprakasam, Michelle Cummins, Patricia Breslin, Katharine Patrick, Mary Slatter, Roderick Skinner, Geof Shenton, Brenda Gibson, Sarah Lawson, Toni Petterson, Michael Potter, Beki James, Rachael Hough, Prashant Hiwarkar, Ajay Vora, Paul Veys, Josu De La Fuente, Robert Wynn, Persis Amrolia
Paediatric therapy-related acute myeloid leukaemia (t-AML) is rare and the outcome is poor. While allogeneic haematopoietic stem cell transplantation (HSCT) is generally the accepted modality of treatment, data regarding salvage chemotherapy, remission induction, conditioning regimens, transplant-related mortality and outcome is scarce. Between 2000 and2016, 36 children with t-AML were treated in seven UK paediatric HSCT centres. The most common salvage protocol for remission induction was FLAG with or without idarubicin and 28 patients were in complete morphological remission prior to BMT...
March 15, 2018: Bone Marrow Transplantation
Inna M Yasinska, Giacomo Ceccone, Isaac Ojea-Jimenez, Jessica Ponti, Rohanah Hussain, Giuliano Siligardi, Steffen M Berger, Elizaveta Fasler-Kan, Marco Bardelli, Luca Varani, Walter Fiedler, Jasmin Wellbrock, Ulrike Raap, Bernhard F Gibbs, Luigi Calzolai, Vadim V Sumbayev
In this study we used 5 nm gold nanoparticles as delivery platforms to target cancer cells expressing the immune receptor Tim-3 using single chain antibodies. Gold surfaces were also covered with the cytotoxic drug rapamycin which was immobilised using a glutathione linker. These nanoconjugates allowed highly specific and efficient delivery of cytotoxic rapamycin into human malignant blood cells.
March 14, 2018: Nanoscale
Federica Vezzali, Silvia Grassilli, Elisabetta Lambertini, Federica Brugnoli, Simone Patergnani, Ervin Nika, Roberta Piva, Paolo Pinton, Silvano Capitani, Valeria Bertagnolo
It has been recently demonstrated that high pre-treatment levels of miR-29b positively correlated with the response of patients with acute myeloid leukaemia (AML) to hypomethylating agents. Upmodulation of miR-29b by restoring its transcriptional machinery appears indeed a tool to improve therapeutic response in AML. In cells from acute promyelocytic leukaemia (APL), miR-29b is regulated by PU.1, in turn upmodulated by agonists currently used to treat APL. We explored here the ability of PU.1 to also regulate miR-29b in non-APL cells, in order to identify agonists that, upmodulating PU...
March 13, 2018: Journal of Cellular and Molecular Medicine
Xiu Fen Chen, Joe Yeong, Kenneth Tou En Chang, Alvin Soon Tiong Lim, Chik Hong Kuick, Tse Hui Lim, Jain Sudhanshi, Sathiyamoorthy Selvarajan, Valerie Huei Li Gan, Li Yan Khor
Perivascular epithelioid cell tumor (PEComa) is an uncommon tumor which presents with epithelioid and spindled cell morphology and is immunoreactive for myogenic and melanocytic markers. Recently, a subset of PEComas has been reported to harbor TFE3 gene rearrangement.In this case report, we describe a TFE3 -expressing primary bladder PEComa in a 27-year-old male patient with acute myeloid leukaemia in remission. The tumor displayed epithelioid morphology with surrounding delicate blood vessels and was devoid of a prominent spindle cell component...
January 2018: Annals of Clinical and Laboratory Science
Andreas K Øvlisen, Anders Oest, Mette D Bendtsen, John Bæch, Preben Johansen, Line S Lynggaard, Ingolf Mølle, Thomas B Mortensen, Duruta Weber, Gideon Ertner, Claudia Schöllkopf, Jesper Q Thomassen, Ove Juul Nielsen, Lene Sofie Granfeldt Østgård, Martin Bøgsted, Karen Dybkær, Hans E Johnsen, Marianne T Severinsen
Stringent complete remission (sCR) of acute myeloid leukemia is defined as normal hematopoiesis after therapy. Less sCR, including non-sCR, was introduced as insufficient blood platelet, neutrophil, or erythrocyte recovery. These latter characteristics were defined retrospectively as postremission transfusion dependency and were suggested to be of prognostic value. In the present report, we evaluated the prognostic impact of achieving sCR and non-sCR in the Danish National Acute Leukaemia Registry, including 769 patients registered with classical CR (ie, <5% blasts in the postinduction bone marrow analysis)...
March 13, 2018: Blood Advances
Joanna Drozd-Sokołowska, Krzysztof Mądry, Anna Waszczuk-Gajda, Przemysław Biecek, Paweł Szwedyk, Katarzyna Budziszewska, Magdalena Raźny, Magdalena Dutka, Agata Obara, Ewa Wasilewska, Krzysztof Lewandowski, Agnieszka Piekarska, Grażyna Bober, Helena Krzemień, Beata Stella-Hołowiecka, Katarzyna Kapelko-Słowik, Waldemar Sawicki, Małgorzata Paszkowska-Kowalewska, Rafał Machowicz, Jadwiga Dwilewicz-Trojaczek
Atypical chronic myeloid leukaemia (aCML) belongs to myelodysplastic/myeloproliferative neoplasms. Because of its rarity and changing diagnostic criteria throughout subsequent classifications, data on aCML are very scarce. Therefore, we at the Polish Adult Leukemia Group performed a nationwide survey on aCML. Eleven biggest Polish centres participated in the study. Altogether, 45 patients were reported, among whom only 18 patients (40%) fulfilled diagnostic criteria. Among misdiagnosed patients, myelodysplastic/myeloproliferative syndrome unclassifiable and chronic myelomonocytic leukaemia were the most frequent diagnoses...
March 7, 2018: Hematological Oncology
Lene S G Østgård, Mette Nørgaard, Lars Pedersen, René D Østgård, Bruno C Medeiros, Ulrik M Overgaard, Claudia Schöllkopf, Marianne Severinsen, Claus W Marcher, Morten K Jensen
Previous studies reported increased risk of acute myeloid leukaemia (AML) in individuals with inflammatory conditions. However, it is unclear whether this association is explained by preceding cytotoxic therapy or haematological diseases. We conducted a nationwide case-control study that included 3053 AML patients, diagnosed in Denmark between 2000 and 2013, and 30 530 sex- and age-matched population controls. We retrieved information on autoimmune disease, infections, and use of antibiotics and computed odds ratios for AML (conditional logistic regression)...
March 5, 2018: British Journal of Haematology
Matt Stevenson, Abdullah Pandor, Jean Hamilton, John Stevens, Clare Rowntree, Marrissa Martyn-St James, Andrew Rawdin, Ruth Wong
As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer (Incyte Corporation) of ponatinib (Inclusig® ) to submit evidence of its clinical and cost effectiveness for previously treated Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) and chronic myeloid leukaemia. This paper focusses on Ph+ ALL. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent evidence review group (ERG)...
March 3, 2018: PharmacoEconomics
Josefina Reyes-Sebastian, Laura Arcelia Montiel-Cervantes, Elba Reyes-Maldonado, Maria Lilia Dominguez-Lopez, Rocio Ortiz-Butron, Aida Castillo-Alvarez, Ruth Angélica Lezama
Receptor tyrosine kinase (RTK) activity may contribute to carcinogenesis. The c-Kit receptor, a member of the RTK family, is expressed in immature haematopoietic system cells. Acute lymphoblastic leukaemia (ALL) presents incompletely differentiated lymphoblasts, and consequently, c-Kit expression can be detected in these cells. The BCR-ABL kinase, which is usually present in both ALL and chronic myeloid leukaemia, can trigger signalling pathways with neoplastic effects. However, a certain number of ALL patients and chronic myeloid leukaemia patients do not express this kinase, raising the question of which other proteins that intervene in signalling pathways may be involved in the development of these diseases...
March 1, 2018: Hematology (Amsterdam, Netherlands)
Liang Ying, Lei Tian, Yuanyuan Xie, Qin Wang, Xiajing Che, Jiayi Yan, Lijing Shen, Honghui Huang, Fangyuan Chen, Ming Zhang, Zhaohui Ni, Shan Mou
BACKGROUND: Significant attention has been directed toward the high incidence of malignant tumours that occur post-transplantation. However, there are few reports of myeloid sarcomas (MSs) following renal transplantation. CASE PRESENTATION: This case report describes a 26-year-old male patient who presented with repeatedly high creatinine levels and hydronephrosis six months post-renal transplantation. Surgical pathology revealed ureteral MS; however, the tumour recurred following resection...
February 27, 2018: BMC Nephrology
Claudio Guarneri, Uwe Wollina, Torello Lotti, Georgi Konstantinov Maximov, Ilia Lozev, Serena Gianfaldoni, Ivan Pidakev, Jacopo Lotti, Georgi Tchernev
Firstly described by Robert Douglas Sweet in 1964, febrile neutrophilic dermatosis is a disabling, not only cutaneous disorder, clinically characterised by fever and painful erythematous nodules, with a typical background of neutrophilia. Sweet's syndrome (SS) is a chronic inflammatory reactive disorder of unknown cause and incompletely established pathogenesis, although an interplay between genetic and environmental factors, including infections, is likely to occur. A significant part of cases has been demonstrated to be linked with malignancies, especially in the hematologic setting...
January 25, 2018: Open Access Macedonian Journal of Medical Sciences
Abdullah Pandor, Matt Stevenson, John Stevens, Marrissa Martyn-St James, Jean Hamilton, Jenny Byrne, Claudius Rudin, Andrew Rawdin, Ruth Wong
As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures ponatinib (Inclusig® ; Incyte Corporation) to submit evidence for the clinical and cost effectiveness for previously treated chronic myeloid leukaemia (CML) and Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). This paper focusses on the three phases of CML: the chronic phase (CP), the accelerated phase (AP) and the blast crisis phase (BP)...
February 26, 2018: PharmacoEconomics
Jana Mihalyova, Tomas Jelinek, Katerina Growkova, Matous Hrdinka, Michal Simicek, Roman Hajek
Inhibitors of anti-apoptotic proteins of the BCL2 family can successfully restart the deregulated process of apoptosis in malignant cells. While non-selective agents have been limited by their affinity to different BCL2 members, and thus inducing excessive toxicity, the highly selective BCL2 inhibitor, venetoclax (ABT-199, Venclexta™), has an acceptable safety profile. To date, it has been approved in monotherapy for the treatment of relapsed or refractory chronic lymphocytic leukaemia (CLL) with 17p deletion...
February 22, 2018: Experimental Hematology
Vera A de Vries, Marcella C A Müller, M Sesmu Arbous, Bart J Biemond, Nicole M A Blijlevens, Nuray Kusadasi, Goda C W Choi, Alexander P J Vlaar, David J van Westerloo, Hanneke C Kluin-Nelemans, Walter M van den Bergh
A few decades ago, the chances of survival for patients with a haematological malignancy needing Intensive Care Unit (ICU) support were minimal. As a consequence, ICU admission policy was cautious. We hypothesized that the long-term outcome of patients with a haematological malignancy admitted to the ICU has improved in recent years. Furthermore, our objective was to evaluate the predictive value of the Acute Physiology and Chronic Health Evaluation (APACHE) II score. A total of 1095 patients from 5 Dutch university hospitals were included from 2003 until 2015...
February 22, 2018: British Journal of Haematology
Nina K Steckel, Christoph Groth, Jan-Henrik Mikesch, Rudolf Trenschel, Hellmut Ottinger, Lambros Kordelas, Carsten Mueller-Tidow, Christoph Schliemann, Christian Reicherts, Joern C Albring, Gerda Silling, Eva Schmidt, Wolfgang E Berdel, Georg Lenz, Markus Ditschkowski, Dietrich W Beelen, Matthias Stelljes
Considering the unsatisfactory results of salvage therapies for patients with relapsed/refractory acute myeloid leukaemia (R/R-AML), their value before allogeneic haematopoietic stem cell transplantation (HSCT) remains questionable. However, direct allogeneic HSCT following established conditioning regimens applied in patients with R/R-AML during active disease has been equally disappointing. In this retrospective observational study, high-dose melphalan, as part of a sequential preparative regimen, followed by a total body irradiation (4 × 2 Gy)-based or a treosulfan-based dose-adapted conditioning therapy for allogeneic HSCT was administered to 292 adult patients (median age 56 years, range 17-74) with primary refractory (144 patients), secondary refractory (97 patients) or relapsed AML (51 patients)...
February 21, 2018: British Journal of Haematology
Diana Oelofse, Ilse Truter
BACKGROUND: The incidence of haematological malignancies in Africa's rapidly urbanising populations is insufficiently explored. Reliable population-based cancer statistics, however, continues to be a scarce resource in Africa and tends to be urban biased with limited rural coverage. In addition, many haematological malignancies are regarded as rare cancers, a sub-group that often affects the young disproportionately and require advanced diagnostic services and facilities able to deliver costly sophisticated treatments...
February 17, 2018: Cancer Epidemiology
Chien-Yuan Chen, Wang-Huei Sheng, Feng-Ming Tien, Po-Chu Lee, Shang-Yi Huang, Jih-Luh Tang, Woei Tsay, Hwei-Fang Tien, Po-Ren Hsueh
BACKGROUND/PURPOSE: This study was aimed to investigate clinical characteristics and treatment outcomes of pulmonary invasive fungal infection (IFI) among patients with hematological malignancy. METHODS: All patients with hematological malignancy who were treated at a medical centre from 2008 to 2013 were evaluated. Pulmonary IFI was classified according to the European Organization for Research and Treatment of Cancer 2008 consensus. RESULTS: During the study period, 236 (11...
January 31, 2018: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
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