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Lymphoblastic leukaemia

David J Flavell, Suzanne E Holmes, Sarah L Warnes, Sopsamorn U Flavell
We have previously shown that antibody-dependent cellular cytotoxicity (ADCC) cooperates with immunotoxin (IT)-mediated killing of human leukaemia cells in an severe combined immunodeficient (SCID) mouse model of human T-cell acute lymphoblastic leukaemia (SCID-HSB-2 mice), but not in an equivalent non-obese diabetic (NOD)/SCID mouse model. In these earlier studies, we reasoned that diminished ADCC due to the functional deficit in natural killer (NK) cell activity in NOD/SCID mice resulted in a failure of effective perforin/granzyme-mediated cytotoxicity necessary for the delivery of the augmentative effect...
February 16, 2019: Biomedicines
Yunzu Michele Wang, Jun Qin Mo, Dennis John Kuo, Victor Wong
We describe an unusual case of pre-B lymphoblastic leukaemia presenting with a unilateral maxillary sinus mass in which biopsies of the primary mass and the bone marrow demonstrated conflicting immunophenotyping results. The extramedullary mass was consistent with a precursor B-cell malignancy, while the bone marrow was initially reported as a possible mature B-cell malignancy. The treatments for the two are fundamentally different, which necessitated a delay in the initiation of his chemotherapy until a clear diagnosis was made...
February 15, 2019: BMJ Case Reports
Giancarla Scalone, Luca Mariani, Alessandro Aimi, Pierfrancesco Grossi
No abstract text is available yet for this article.
February 12, 2019: European Heart Journal
Jessica A Timms, Caroline L Relton, Gemma C Sharp, Judith Rankin, Gordon Strathdee, Jill A McKay
The aetiology of childhood acute lymphoblastic leukaemia (ALL) is unclear. Genetic abnormalities have been identified in a number of ALL cases, although these alone are not sufficient for leukaemic transformation. Various in utero and post-natal environmental exposures have been suggested to alter risk of childhood ALL. DNA methylation patterns can be influenced by environmental exposures, and are reported to be altered in ALL, suggesting a potential mediating mechanism between environment and ALL disease risk...
February 10, 2019: International Journal of Cancer. Journal International du Cancer
Gerhard Zugmaier
No abstract text is available yet for this article.
February 5, 2019: British Journal of Haematology
Anup Ashok, Kruthi Doriya, Jyothi Vithal Rao, Asif Qureshi, Anoop Kumar Tiwari, Devarai Santhosh Kumar
L-Asparaginase (L-asparagine aminohydrolase, E.C. has been proven to be competent in treating Acute Lymphoblastic Leukaemia (ALL), which is widely observed in paediatric and adult groups. Currently, clinical L-Asparaginase formulations are derived from bacterial sources such as Escherichia coli and Erwinia chrysanthemi. These formulations when administered to ALL patients lead to several immunological and hypersensitive reactions. Hence, additional purification steps are required to remove toxicity induced by the amalgamation of other enzymes like glutaminase and urease...
February 5, 2019: Scientific Reports
Stefanie Groeneveld-Krentz, Michael P Schroeder, Michael Reiter, Malwine J Pogodzinski, Helia J Pimentel-Gutiérrez, Renia Vagkopoulou, Jana Hof, Christiane Chen-Santel, Karin Nebral, Jutta Bradtke, Seval Türkmen, Claudia D Baldus, Stefan Gattenlöhner, Oskar A Haas, Arend von Stackelberg, Leonid Karawajew, Cornelia Eckert, Renate Kirschner-Schwabe
Aneuploidy is common in paediatric B-cell precursor acute lymphoblastic leukaemia (ALL). Specific subgroups, such as high hyperdiploidy (>50 chromosomes or DNA Index ≥1·16) and hypodiploidy (<45 chromosomes), predict outcome of patients after primary treatment. Whether aneuploidy has a prognostic value for relapsed disease is yet to be determined. Using DNA index and centromere screening by multiplex ligation-dependent probe amplification, we investigated aneuploidy in 413 children treated for first relapse of B-cell precursor ALL according to the ALL-REZ BFM 2002 protocol...
February 3, 2019: British Journal of Haematology
Francesca Bonifazi, Carlos Solano, Christine Wolschke, Mariarosaria Sessa, Francesca Patriarca, Francesco Zallio, Arnon Nagler, Carmine Selleri, Antonio Maria Risitano, Giuseppe Messina, Wolfgang Bethge, Pilar Herrera, Anna Sureda, Angelo Michele Carella, Michele Cimminiello, Stefano Guidi, Jürgen Finke, Roberto Sorasio, Christelle Ferra, Jorge Sierra, Domenico Russo, Edoardo Benedetti, Giuseppe Milone, Fabio Benedetti, Marion Heinzelmann, Domenico Pastore, Manuel Jurado, Elisabetta Terruzzi, Franco Narni, Andreas Völp, Francis Ayuk, Tapani Ruutu, Nicolaus Kröger
BACKGROUND: We previously showed that human anti-T-lymphocyte globulin (ATLG) plus ciclosporin and methotrexate given to patients with acute leukaemia in remission, having allogeneic haemopoietic stem-cell transplantation with peripheral blood stem cells from an HLA-identical sibling donor after myeloablative conditioning, significantly reduced 2-year chronic graft-versus-host disease (cGVHD) incidence and severity, without increasing disease relapse and infections, and improves cGVHD-free and relapse-free survival (cGRFS)...
February 2019: Lancet Haematology
Guillermo Gervasini, Sonia Mota-Zamorano
In the past two decades, a great body of research has been published regarding the effects of genetic polymorphisms on methotrexate (MTX)-induced toxicity and efficacy. Of particular interest is the role of this compound in childhood acute lymphoblastic leukaemia (ALL), where it is a pivotal drug in the different treatment protocols, both at low and high doses. MTX acts on a variety of target enzymes in the folates cycle, as well as being transported out and into of the cell by several transmembrane proteins...
January 30, 2019: Current Drug Metabolism
Guoqiao Zheng, Subhayan Chattopadhyay, Amit Sud, Kristina Sundquist, Jan Sundquist, Asta Försti, Richard Houlston, Akseli Hemminki, Kari Hemminki
Improvement of survival in lymphocytic leukaemia has been accompanied by the occurrence of second primary cancer (SPCs). Based on Swedish Family Cancer Database, we applied bi-directional analyses in which relative risks (RRs) were calculated for any SPCs in patients with chronic lymphocytic leukaemia (CLL), acute lymphoblastic leukaemia (ALL) and hairy cell leukaemia (HCL) and the risks of these leukaemias as SPCs. After CLL, RRs were significant for 20 SPCs, and high for skin squamous cell cancer (24·58 for in situ and 7·63 for invasive), Merkel cell carcinoma (14·36), Hodgkin lymphoma (7·16) and Kaposi sarcoma (6·76)...
January 31, 2019: British Journal of Haematology
Jiaoyang Cai, Jie Yu, Xiaofan Zhu, Shaoyan Hu, Yiping Zhu, Hua Jiang, Chunfu Li, Yongjun Fang, Changda Liang, Xiuli Ju, Xin Tian, Xiaowen Zhai, Jinjin Hao, Qun Hu, Ningling Wang, Hui Jiang, Lirong Sun, Chi Kong Li, Kaili Pan, Minghua Yang, Shuhong Shen, Cheng Cheng, Raul C Ribeiro, Ching-Hon Pui, Jingyan Tang
OBJECTIVES: Before 2003, most children with acute lymphoblastic leukaemia (ALL) abandoned treatment, with only approximately 30% treated in China. With the development of national insurance for underprivileged patients, we assessed the current frequency and causes of treatment abandonment among patients with ALL who were enrolled in the Chinese Children's Cancer Group ALL protocol between 2015 and 2016. METHODS: Demographic, clinical and laboratory data on patients who abandoned treatment, as well as economic and sociocultural data of their families were collected and analysed...
January 31, 2019: Archives of Disease in Childhood
Linus Knips, Nils Bergenthal, Fiona Streckmann, Ina Monsef, Thomas Elter, Nicole Skoetz
BACKGROUND: Although people with haematological malignancies have to endure long phases of therapy and immobility, which is known to diminish their physical performance level, the advice to rest and avoid intensive exercises is still common practice. This recommendation is partly due to the severe anaemia and thrombocytopenia from which many patients suffer. The inability to perform activities of daily living restricts them, diminishes their quality of life and can influence medical therapy...
January 31, 2019: Cochrane Database of Systematic Reviews
Benjamin J Shields, Christopher I Slape, Ngoc Vo, Jacob T Jackson, Adriana Pliego-Zamora, Hansini Ranasinghe, Wei Shi, David J Curtis, Matthew P McCormack
T cell acute lymphoblastic leukaemia (T-ALL) cases include subfamilies that overexpress the TAL1/LMO, TLX1/3 and HOXA transcription factor oncogenes. While it has been shown that TAL1/LMO transcription factors induce self-renewal of thymocytes, whether this is true for other transcription factor oncogenes is unknown. To address this, we have studied NUP98-HOXD13-transgenic (NHD13-Tg) mice, which overexpress HOXA transcription factors throughout haematopoiesis and develop both myelodysplastic syndrome (MDS) progressing to acute myeloid leukaemia (AML) as well as T-ALL...
January 30, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
T G Cristo, G Biezus, L F Noronha, L H H S Pereira, J A Withoeft, L V Furlan, L S Costa, S D Traverso, R A Casagrande
Lymphoma is the most important haemopoietic tumour in cats and has been associated with feline leukaemia virus (FeLV) infection. In Brazil, no studies have established a correlation between FeLV infection and lymphoma. The aim of this study was to characterize lymphomas arising in cats in Brazil anatomically and microscopically, and to correlate these data with FeLV infection as determined by immunohistochemistry for the FeLV gp70 antigen. Fifty-three cats with lymphoma were evaluated. The mean age of junior, prime, mature, senior and geriatric cats was 1...
January 2019: Journal of Comparative Pathology
Marianne Ifversen, Dominik Turkiewicz, Hanne V Marquart, Jacek Winiarski, Jochen Buechner, Karin Mellgren, Johan Arvidson, Jelena Rascon, Lenne-Triin Körgvee, Hans O Madsen, Jonas Abrahamsson, Bendik Lund, Olafur G Jonsson, Carsten Heilmann, Mats Heyman, Kjeld Schmiegelow, Kim Vettenranta
The population-based Nordic/Baltic acute lymphoblastic leukaemia (ALL) Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol combined minimal residual disease (MRD)-driven treatment stratification with very intense first line chemotherapy for patients with high risk ALL. Patients with MRD ≥5% at end of induction or ≥10-3 at end of consolidation or following two high risk blocks were eligible for haematopoietic cell transplantation (HCT) in first remission. After at least three high risk blocks a total of 71 children received HCT, of which 46 had MRD ≥5% at end of induction...
January 24, 2019: British Journal of Haematology
Jim H Hughes, Mitch A Phelps, Richard N Upton, Stephanie E Reuter, Yue Gao, John C Byrd, Michael R Grever, Craig C Hofmeister, Guido Marcucci, William Blum, Kristie A Blum, David J R Foster
AIMS: Lenalidomide is an immunomodulatory imide drug (IMiD) used broadly in the treatment of multiple myeloma and lymphoma. It continues to be evaluated in chronic lymphocytic leukaemia (CLL) at lower doses due to dose-related toxicities including tumour flare and tumour lysis syndrome. This study aimed to develop a population pharmacokinetic model for lenalidomide in multiple cancers, including CLL, to identify any disease-related differences in disposition. METHODS: Lenalidomide concentrations from four clinical trials were collated (1999 samples, 125 subjects), covering four cancers (multiple myeloma, CLL, acute myeloid leukaemia and acute lymphoblastic leukaemia) and a large dose range (2...
January 22, 2019: British Journal of Clinical Pharmacology
Elizabeth C Matheson, Huw Thomas, Marian Case, Helen Blair, Rosanna K Jackson, Dino Masic, Gareth Veal, Chris Halsey, David R Newell, Josef Vormoor, Julie A E Irving
New drugs are needed for relapsed acute lymphoblastic leukemia and preclinical evaluation of the MEK inhibitor, selumetinib, has shown excellent activity in those with RAS pathway mutations. The proapoptotic protein, BIM is pivotal in the induction of cell death by both selumetinib and glucocorticoids, suggesting the potential for synergy. Thus, combination indices for dexamethasone and selumetinib were determined in RAS pathway mutated acute lymphoblastic leukemia primagraft cells in vitro and were indicative of strong synergism (CI <0...
January 17, 2019: Haematologica
Sang-Nee Tan, Sai-Peng Sim
BACKGROUND: It has been found that chronic rhinosinusitis (CRS) increases the risk of developing nasopharyngeal carcinoma (NPC). CRS can be caused by gastro-oesophageal reflux (GOR) that may reach nasopharynx. The major component of refluxate, bile acid (BA) has been found to be carcinogenic and genotoxic. BA-induced apoptosis has been associated with various cancers. We have previously demonstrated that BA induced apoptosis and gene cleavages in nasopharyngeal epithelial cells. Chromosomal cleavage occurs at the early stage of both apoptosis and chromosome rearrangement...
January 15, 2019: BMC Medical Genomics
Mita Kuchimanchi, Min Zhu, John D Clements, Sameer Doshi
AIMS: The relationship between blinatumomab exposure and efficacy endpoints (occurrence of complete remission [CR] and duration of overall survival [OS]) or adverse events (occurrence of cytokine release syndrome [CRS] and neurologic events) were investigated in adult patients with relapsed/refractory acute lymphoblastic leukaemia (r/r ALL) receiving blinatumomab or standard of care (SOC) chemotherapy to evaluate appropriateness of the blinatumomab dosing regimen. METHODS: Exposure, efficacy, and safety data from adult patients (n=646) with r/r ALL receiving stepwise (9 then 28 μg day-1 , 4-week cycle) continuous intravenous infusion (n=537) of blinatumomab or SOC (n=109) chemotherapy were pooled from phase 2 and 3 studies...
January 15, 2019: British Journal of Clinical Pharmacology
Waseem Qasim
Allogeneic chimeric antigen receptor T (CAR T) cells can offer advantages over autologous T cell therapies, including the availability of 'fit' cells for production, and elimination of risks associated with inadvertent transduction of leukemic blasts. However, allogeneic T cell therapies must address HLA barriers and conventionally rely on the availability of a suitable HLA-matched donor if graft-versus-host-disease and rejection effects are to be avoided. More recently, the incorporation of additional genome editing manipulations, to disrupt T cell receptor expression and address other critical pathways have been explored...
January 11, 2019: American Journal of Hematology
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