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Lymphoblastic leukaemia

Jennifer E Hibma, Hagop M Kantarjian, Daniel J DeAngelo, Joseph P Boni
AIM: To characterize the effect of inotuzumab ozogamicin on QT interval in patients with B-cell malignancies. METHODS: Data were pooled from three clinical studies including 250 patients (N=2743) who received inotuzumab ozogamicin monotherapy. Patients with relapsed/refractory acute lymphoblastic leukaemia (NCT01564784 and NCT01363297) received 1.8 mg m-2 per cycle in divided doses (mean Cmax 371 ng ml-1 ; considered therapeutic) and patients with relapsed/refractory non-Hodgkin lymphoma (NCT00868608) received 1...
December 8, 2018: British Journal of Clinical Pharmacology
Sebastian Giebel, Myriam Labopin, Tomasz Czerw, Gérard Socié, Didier Blaise, Ardeshir Ghavamzadeh, Jacob Passweg, Per Ljungman, Xavier Poiré, Patrice Chevallier, Péter Reményi, Alessandro Rambaldi, Boris Anafasyev, Nathalie Fegueux, Montserrat Rovira, Maija Itälä-Remes, Martin Bornhäuser, Mohamad Mohty, Arnon Nagler
BACKGROUND: Anti-thymocyte globulin (ATG) is widely used to prevent graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (alloPBSCT). The goal of this study was to retrospectively assess the effect of ATG on outcomes in the setting of Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). METHODS: In the analysis, 1170 adult patients undergoing alloPBSCT from human leucocyte antigen-matched sibling or unrelated donors in the first complete remission between 2007 and 2016 were included...
December 5, 2018: European Journal of Cancer
Sang-Nee Tan, Sai-Peng Sim, Alan S B Khoo
BACKGROUND: Oxidative stress is known to be involved in most of the aetiological factors of nasopharyngeal carcinoma (NPC). Cells that are under oxidative stress may undergo apoptosis. We have previously demonstrated that oxidative stress-induced apoptosis could be a potential mechanism mediating chromosome breakages in nasopharyngeal epithelial cells. Additionally, caspase-activated DNase (CAD) may be the vital player in mediating the chromosomal breakages during oxidative stress-induced apoptosis...
December 4, 2018: BMC Molecular Biology
Achour Chergui, Mouloud Kecha, Abderrahmane Tighrine, Nabil Adrar, Samira Bouzida, Yacine Titouche, Lhadi Boughani, Nabil Kadri, Karim Houali
L-Asparaginase is an enzyme that hydrolyses the amino acid L-Asparagine into aspartic acid and ammonia. As a medication, L-Asparaginase is used in chemotherapy to treat acute lymphoblastic leukaemia by depleting circulating Asparagine and depriving tumor cells. Interest in Actinomycetes as potential producers of antibiotics and enzymes encouraged us to investigate an isolated strain (CA01) from soft wheat bran.The Actinomycete strain was characterized based on its morphological and biochemical characteristics and selected due to a proved promising ability to produce L-Asparaginase optimized in both solid and liquid media cultures...
November 30, 2018: Cellular and Molecular Biology
Refaat I ElFayoumi, Magda M Hagras, Adel Abozenadaha, Mamdouh Gari, Ibrahim Abosoudah, Thoraia Shinawi, Talaat Mirza, Waleed Bawazir
BACKGROUND: Glucocorticoids play essential roles in the treatment of childhood acute lymphoblastic leukaemia (ALL); however, treatment with these agents can result in severe side-effects. This study, the first of its kind in a Saudi population, investigates associations of ABCB1 gene polymorphisms (pharmacodynamics and pharmacokinetic) with the development of toxicity and side effects (glucose abnormality, liver toxicity and infection) in a small population of Saudi children with ALL...
September 28, 2018: Pharmacological Reports: PR
Andrea Biondi, Virginie Gandemer, Paola De Lorenzo, Gunnar Cario, Myriam Campbell, Anders Castor, Rob Pieters, André Baruchel, Ajay Vora, Veronica Leoni, Jan Stary, Gabriele Escherich, Chi-Kong Li, Giovanni Cazzaniga, Hélène Cavé, Jutta Bradtke, Valentino Conter, Vaskar Saha, Martin Schrappe, Maria Grazia Valsecchi
BACKGROUND: The EsPhALL2004 randomised trial showed a 10% advantage in disease-free survival for short, discontinuous use of imatinib after induction compared with no use of imatinib in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia receiving Berlin-Frankfurt-Münster chemotherapy and haemopoietic stem-cell transplantation (HSCT). Other contemporary studies showed an advantage from continuous protracted exposure to imatinib, challenging the indications to transplant...
December 2018: Lancet Haematology
Elias Jabbour, Nicholas J Short, Farhad Ravandi, Xuelin Huang, Naval Daver, Courtney D DiNardo, Marina Konopleva, Naveen Pemmaraju, William Wierda, Guillermo Garcia-Manero, Koji Sasaki, Jorge Cortes, Rebecca Garris, Joseph D Khoury, Jeffrey Jorgensen, Nitin Jain, Joie Alvarez, Susan O'Brien, Hagop Kantarjian
BACKGROUND: The combination of chemotherapy and ponatinib in Philadelphia chromosome-positive acute lymphoblastic leukaemia has the potential to be a new standard of care for the disease; however, long-term efficacy and safety data are needed. Our aim was to evaluate the long-term efficacy and safety of this regimen in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukaemia in this ongoing phase 2 trial. METHODS: In our single-centre, phase 2, single-arm trial in the USA, adult patients with previously untreated Philadelphia chromosome-positive acute lymphoblastic leukaemia were sequentially enrolled...
December 2018: Lancet Haematology
Josep-Maria Ribera
No abstract text is available yet for this article.
December 2018: Lancet Haematology
Yuefang Wang, Ge Zhang, Lei Ye, Qingkai Dai, Luyun Peng, Lan Chen, Qi Chen, Yongmei Jiang, Ju Gao
The time to platelet recovery (TPR) is becoming a predicting factor during the treatment of childhood acute leukaemia. However, the initial pre-treatment platelet count (PPC) could interfere with TPR. Here, we integrated both TPR and PPC as the average daily platelet amount increase (Ap) to predict the prognosis in childhood B-ALL during the recovery period.148 patients were enrolled. The relationship between the Ap and MRD was evaluated, and Multivariate analysis was performed to evaluate whether Ap was independently associated with a better EFS...
November 29, 2018: Platelets
Areesha Alam, Archana Kumar
OBJECTIVES: Efforts are being made worldwide to prevent abandonment in children with leukaemia. The study aimed to determine changes in treatment refusal, treatment abandonment rates and its reasons in response to financial support and focussed group counselling. METHODS: A retrospective cohort study conducted at paediatric haematology-oncology unit, King George's Medical University, Lucknow among children <18 years admitted with acute lymphoblastic leukaemia from 1995 to 2017...
November 29, 2018: Psycho-oncology
N Potter, L Jones, H Blair, S Strehl, C J Harrison, M Greaves, L Kearney, L J Russell
Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5-15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We have previously reported the genomic landscape of patients with CRLF2 rearrangements (CRLF2-r) using both whole genome and exome sequencing, which identified a number of potential clonal and sub-clonal genomic alterations. In this study, we aimed to assess when the CRLF2-r; IGH-CRLF2 or P2RY8-CRLF2, arose during the evolution of both Down syndrome-ALL (DS-ALL) and non-DS-ALL...
November 28, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Dongfeng Chen, Alessandro Camponeschi, Qingqing Wu, Natalija Gerasimcik, Huiqi Li, Xue Shen, Yujie Tan, Helene Sjögren, Jessica Nordlund, Gudmar Lönnerholm, Jonas Abrahamsson, Linda Fogelstrand, Inga-Lill Mårtensson
Our study aimed to determine the expression pattern and clinical relevance of CD99 in paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). Our findings demonstrate that high expression levels of CD99 are mainly found in high-risk BCP-ALL, e.g. BCR-ABL1 and CRLF2Re/Hi , and that high CD99 mRNA levels are strongly associated with a high frequency of relapse, high proportion of positive for minimal residual disease at day 29 and poor overall survival in paediatric cohorts, which indicate that CD99 is a potential biomarker for BCP-ALL...
November 28, 2018: British Journal of Haematology
Maria Sakarou, Lewin Eisele, Ulrich Dührsen, Andreas Hüttmann
OBJECTIVES: The GMALL-B-ALL/NHL2002 protocol is effective in Burkitt-lymphoma/leukaemia (BL). Its role in other aggressive lymphomas and in patients with simultaneous central nervous system (CNS) and peripheral involvement is unclear. METHODS: This is a retrospective outcome analysis in 76 patients with BL (n=26), B-lymphoblastic lymphoma (B-LBL; n=3), diffuse large B-cell lymphoma (DLBCL; n=31), mantle-cell lymphoma (MCL; n=6), transformed B-cell non-Hodgkin lymphomas (tB-NHL; n=7) and T-cell NHL (T-NHL; n=3) treated with the GMALL-B-ALL/NHL2002 protocol...
November 24, 2018: European Journal of Haematology
Prajwal Boddu, Beenu Thakral, Ahmed Alhuraiji, Naveen Pemmaraju, Tapan Kadia, Maro Ohanian, Farhad Ravandi, Elias Jabbour, William Wierda, Joseph D Khoury, Nitin Jain
T-lymphoblastic lymphoma and thymoma are distinct primary mediastinal neoplasms that can have similar clinical presentations and overlapping histological features. Microscopic distinction is occasionally difficult because the immature lymphocytes associated with thymoma may resemble T-lymphoblastic leukaemia/lymphoma cells, morphologically and immunohistochemically. An accurate diagnosis assumes particular importance since the treatment approaches for these two entities differ considerably. Multimodality diagnostic approaches incorporating histological, flow cytometry immunophenotypic' and molecular approaches are required...
November 22, 2018: Journal of Clinical Pathology
Sofie G Højfeldt, Benjamin O Wolthers, Morten Tulstrup, Jonas Abrahamsson, Ramneek Gupta, Arja Harila-Saari, Mats Heyman, Louise T Henriksen, Òlafur G Jónsson, Päivi M Lähteenmäki, Bendik Lund, Kaie Pruunsild, Goda Vaitkeviciene, Kjeld Schmiegelow, Birgitte K Albertsen
Asparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG-asparaginase) hampers anti-neoplastic efficacy. Patients with PEG-asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG-asparaginase hypersensitivity in a genome-wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol...
November 18, 2018: British Journal of Haematology
Juan Zhang, Mingyong Li, Yuan He
No abstract text is available yet for this article.
November 8, 2018: British Journal of Haematology
Kevin A Hay
Chimeric antigen receptor-modified (CAR)-T cells have demonstrated impressive results in the treatment of haematological malignancies. However, cytokine release syndrome (CRS) and neurotoxicity are common toxicities which are potentially life-threatening in severe cases. Risk factors for CRS and neurotoxicity identified so far include disease burden, lymphodepletion intensity and CAR-T cell dose administered. Risk-adapted dosing, with lower CAR-T cell doses administered to B-cell acute lymphoblastic leukaemia patients with high marrow blast counts, has been successful at decreasing severe CRS rates in this population...
November 2018: British Journal of Haematology
Chen Tian, Yong Yu, Yizhuo Zhang
No abstract text is available yet for this article.
November 8, 2018: British Journal of Haematology
Yuki Okuhashi, Mai Itoh, Shuji Tohda
BACKGROUND: Hedgehog (HH), WNT, NOTCH, and mechanistic target of rapamycin (mTOR) signalling pathways are known to regulate the progression of cancer; however, their interaction in leukaemia cells is not fully clarified. MATERIALS AND METHODS: Myeloid and T-lymphoblastic leukaemia cell lines (NB4, THP-1, Jurkat, and DND-41) were transfected with small interfering RNAs targeting the glioma-associated oncogene homolog 1 (GLI1) and catenin beta-1 (CTNNB1) genes involved in the regulation of HH and WNT pathways, respectively, and we examined cell proliferation and gene expression...
November 2018: Anticancer Research
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