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Lymphoblastic leukaemia

Natthapon Angsubhakorn, Attaya Suvannasankha
A previously healthy 37-year-old man presented with a 10-month history of intractable back pain. On examination, there was tenderness to palpation along lower thoracic and lumbar spine. Complete blood count showed mild anaemia but was otherwise unremarkable. Imaging studies revealed compression deformities with multiple osteolytic lesions involving multiple levels of the thoracic and lumbar spine. Bone marrow aspiration and biopsy were performed and demonstrated blast cells involving 80% of the bone marrow cellularity...
August 11, 2018: BMJ Case Reports
Narges Kalantari, Javad Rezanejad, Ahmad Tamadoni, Salman Ghaffari, Jaber Alipour, Masomeh Bayani
The possible association between Toxoplasma gondii infection and paediatric haematological malignancies in a group of patients and control subjects was evaluated in the present study. We performed an age-, gender- and residence frequency-matched case-control study of 101 blood cancer patients under 18 years of age, all of which were treated in Amirkola Pediatric Hospital. One hundred and thirty-eight control samples were gathered from the outpatient clinic in the hospital. All cases and controls were tested for the presence of anti-Toxoplasma IgG antibodies and then IgG-positive subjects were evaluated for IgM antibodies by enzyme-linked immunoassays...
August 10, 2018: Epidemiology and Infection
Zaina T Al-Salama
The intravenous CD22-directed antibody drug conjugate inotuzumab ozogamicin (Besponsa® ) is approved in several countries including in the USA, EU and Japan, as monotherapy for the treatment of adults with relapsed/refractory B-cell acute lymphoblastic leukaemia (ALL). In adults with relapsed/refractory B-cell ALL who had received one or two prior treatment regimens, inotuzumab ozogamicin was associated with significantly higher rates of complete remission (including complete remission with incomplete haematological recovery) [CR/CRi] than standard therapy in the pivotal INO-VATE ALL trial...
August 9, 2018: Targeted Oncology
Kris M Mahadeo, Sajad J Khazal, Hisham Abdel-Azim, Julie C Fitzgerald, Agne Taraseviciute, Catherine M Bollard, Priti Tewari, Christine Duncan, Chani Traube, David McCall, Marie E Steiner, Ira M Cheifetz, Leslie E Lehmann, Rodrigo Mejia, John M Slopis, Rajinder Bajwa, Partow Kebriaei, Paul L Martin, Jerelyn Moffet, Jennifer McArthur, Demetrios Petropoulos, Joan O'Hanlon Curry, Sarah Featherston, Jessica Foglesong, Basirat Shoberu, Alison Gulbis, Maria E Mireles, Lisa Hafemeister, Cathy Nguyen, Neena Kapoor, Katayoun Rezvani, Sattva S Neelapu, Elizabeth J Shpall
In 2017, an autologous chimeric antigen receptor (CAR) T cell therapy indicated for children and young adults with relapsed and/or refractory CD19+ acute lymphoblastic leukaemia became the first gene therapy to be approved in the USA. This innovative form of cellular immunotherapy has been associated with remarkable response rates but is also associated with unique and often severe toxicities, which can lead to rapid cardiorespiratory and/or neurological deterioration. Multidisciplinary medical vigilance and the requisite health-care infrastructure are imperative to ensuring optimal patient outcomes, especially as these therapies transition from research protocols to standard care...
August 6, 2018: Nature Reviews. Clinical Oncology
Anna Lin, Frankie W T Cheng, Alan K S Chiang, Chung-Wing Luk, Rever C H Li, Alvin S C Ling, Daniel K L Cheuk, Kai-On Chang, Dennis Ku, Vincent Lee, Shau-Yin Ha, Chi-Kong Li
OBJECTIVE: The aim of this study was to review clinical outcomes and prognosis of paediatric patients with acute lymphoblastic leukaemia (ALL) with TCF3-PBX1 rearrangement. PATIENTS: All children in Hong Kong diagnosed with ALL with TCF3-PBX1 rearrangement over the past two decades were included. METHODS: Six hundred and twenty-four newly diagnosed patients with ALL from four consecutive studies were enrolled from 1997 to 2016. Patients carrying TCF3-PBX1 rearrangement and patients at intermediate risk without the gene expression were compared for clinical characteristics, overall survival and event-free survival (EFS)...
July 26, 2018: Pediatric Blood & Cancer
Xiaowei Gong, Yuliia Didan, John G Lock, Staffan Strömblad
Membrane blebbing-dependent (blebby) amoeboid migration can be employed by lymphoid and cancer cells to invade 3D-environments. Here, we reveal a mechanism by which the small GTPase RhoB controls membrane blebbing and blebby amoeboid migration. Interestingly, while all three Rho isoforms (RhoA, RhoB and RhoC) regulated amoeboid migration, each controlled motility in a distinct manner. In particular, RhoB depletion blocked membrane blebbing in ALL (acute lymphoblastic leukaemia), melanoma and lung cancer cells as well as ALL cell amoeboid migration in 3D-collagen, while RhoB overexpression enhanced blebbing and 3D-collagen migration in a manner dependent on its plasma membrane localization and down-stream effectors ROCK and Myosin II RhoB localization was controlled by endosomal trafficking, being internalized via Rab5 vesicles and then trafficked either to late endosomes/lysosomes or to Rab11-positive recycling endosomes, as regulated by KIF13A...
July 26, 2018: EMBO Journal
Anna Pomorska, Anna Malecka, Radoslaw Jaworski, Julia Radon-Proskura, Rasmus Krøger Hare, Henrik Vedel Nielsen, Lee O'Brian Andersen, Henrik Elvang Jensen, Maiken Cavling Arendrup, Ninela Irga-Jaworska
Invasive mucormycosis in immunocompromised children is a life-threatening fungal infection. We report a case of a 7-year-old girl treated for acute lymphoblastic leukaemia complicated by disseminated mucormycosis during induction therapy. Microscopic examination of surgically removed lung tissue revealed wide, pauci-septate hyphae suggesting a Mucorales infection. This diagnosis was confirmed immunohistochemically and by PCR analysis followed by a final identification of Cunninghamella sp. The patient was treated successfully with surgical debridement and antifungal combination therapy with amphotericin B, caspofungin and isavuconazole...
July 23, 2018: Mycopathologia
Sara Ghorashian, Persis Amrolia, Paul Veys
T cells that are genetically modified to express chimeric antigen receptors (CARs) specific for CD19 show great promise for the treatment of relapsed/refractory acute lymphoblastic leukemia (ALL). The first U.S. Food and Drug Administration approval of a cellular cancer therapy in 2017, Novartis's CD19-targeting CAR T-cell product Kymriah within the context of relapsed/refractory pediatric ALL, followed rapidly by approval of Kite's Yescarta and, more recently, Kymriah for diffuse large B-cell indications in adults, highlights the pace of progress made in this field...
July 20, 2018: Experimental Hematology
Stephan Fuhrmann, Richard Schabath, Anja Möricke, Martin Zimmermann, Joachim B Kunz, Andreas E Kulozik, Wolf-Dieter Ludwig, Martin Schrappe, Leonid Karawajew, Richard Ratei
This study reports the prognostic impact of the expression of the natural killer cell marker CD56 in a large series of risk-adapted paediatric patients with T cell acute lymphoblastic leukaemia (T-ALL; n = 493) treated within the ALL-Berlin-Frankfurt-Münster (BFM) 2000 protocol. The immunophenotype was analysed centrally at diagnosis using flow cytometry and correlated with clinical parameters and outcome. CD56 expression was detected in 7·1% and early T-cell precursor (ETP) phenotype in 6·7% of all T-ALL patients...
July 20, 2018: British Journal of Haematology
Michaela Kuhlen, Peter Bader, Martin Sauer, Michael H Albert, Bernd Gruhn, Tayfun Güngör, Gabriele Kropshofer, Peter Lang, Anita Lawitschka, Markus Metzler, Falk Pentek, Claudia Rossig, Paul G Schlegel, Martin Schrappe, Johanna Schrum, Ansgar Schulz, Wolfgang Schwinger, Arend von Stackelberg, Brigitte Strahm, Meinolf Suttorp, Irene Teichert-von Luettichau, Wilhelm Wößmann, Arndt Borkhardt, Roland Meisel, Ulrike Poetschger, Evgenia Glogova, Christina Peters
Osteonecrosis (ON) was prospectively assessed in 557 children and adolescents in the Berlin-Frankfurt-Münster Stem Cell Transplantation in children with acute lymphoblastic leukaemia 2003 trial. Median age at haematopoietic stem cell transplantation (HSCT) was 10·3 years (range 0·5-26). Cumulative incidence of symptomatic ON (sON) was 9% at 5 years (standard deviation 1%), median time from HSCT to diagnosis of sON was 12·4 months (range 1-126). Multivariate analysis identified age at HSCT [10-15 years vs...
July 20, 2018: British Journal of Haematology
Mark P Little, Richard Wakeford, David Borrego, Benjamin French, Lydia B Zablotska, M Jacob Adams, Rodrigue Allodji, Florent de Vathaire, Choonsik Lee, Alina V Brenner, Jeremy S Miller, David Campbell, Mark S Pearce, Michele M Doody, Erik Holmberg, Marie Lundell, Siegal Sadetzki, Martha S Linet, Amy Berrington de González
BACKGROUND: Substantial evidence links exposure to moderate or high doses of ionising radiation, particularly in childhood, with increased risk of leukaemia. The association of leukaemia with exposure to low-dose (<100 mSv) radiation is less certain, although this is the dose range most relevant to the general population. We aimed to estimate the risk of leukaemia associated with low-dose radiation exposure in childhood (age <21 years). METHODS: In this analysis of historical cohort studies, we pooled eligible cohorts reported up to June 30, 2014...
August 2018: Lancet Haematology
Hisayuki Yao, Trevor T Price, Gaia Cantelli, Brandon Ngo, Matthew J Warner, Lindsey Olivere, Sarah M Ridge, Elizabeth M Jablonski, Joseph Therrien, Stacey Tannheimer, Chad M McCall, Anjen Chenn, Dorothy A Sipkins
Acute lymphoblastic leukaemia (ALL) has a marked propensity to metastasize to the central nervous system (CNS). In contrast to brain metastases from solid tumours, metastases of ALL seldom involve the parenchyma but are isolated to the leptomeninges, which is an infrequent site for carcinomatous invasion. Although metastasis to the CNS occurs across all subtypes of ALL, a unifying mechanism for invasion has not yet been determined. Here we show that ALL cells in the circulation are unable to breach the blood-brain barrier in mice; instead, they migrate into the CNS along vessels that pass directly between vertebral or calvarial bone marrow and the subarachnoid space...
August 2018: Nature
Elena Guadalupe Corella Aznar, Ariadna Ayerza Casas, Ana Carboné Bañeres, María Ángeles Carlota Calvo Escribano, José Ignacio Labarta Aizpún, Pilar Samper Villagrasa
BACKGROUND: Survival of childhood acute lymphoblastic leukaemia involves an increasing risk of long-term morbidities. Due to the impact of cancer treatment and comorbidities, AL survivors may experience a decrease in their health-related quality of life. OBJECTIVE: We aimed to describe the long-term comorbidities, related quality of life and their development predictors in these survivors. METHODS: cross-sectional study of 54 survivors aged ≥18 and who have a survival rate of more than 10 years...
July 12, 2018: Medicina Clínica
Joanna Zawitkowska, Monika Lejman, Agnieszka Zaucha-Prażmo, Katarzyna Drabko, Marcin Płonowski, Joanna Bulsa, Michał Romiszewski, Agnieszka Mizia-Malarz, Andrzej Kołtan, Katarzyna Derwich, Grażyna Karolczyk, Tomasz Ociepa, Magdalena Ćwiklińska, Joanna Trelińska, Joanna Owoc-Lempach, Maciej Niedźwiecki, Aleksandra Kiermasz, Jerzy Kowalczyk
OBJECTIVE: The aim of this study was to analyse the clinical characteristics and outcome of children diagnosed with Ph+ ALL. MATERIAL AND METHODS: A total of 2591 newly diagnosed ALL children were treated in Poland between the years 2005-2017. Of those, 44 were diagnosed with Ph(+) ALL. The patients were treated according to protocols: ALL IC - BFM 2002 and 2009 (26 patients), EsPhALL (12 patients), initially ALL IC - BFM and then EsPhALL (6 patients). RESULTS: The median of follow up in the observed group was 3 years...
July 14, 2018: European Journal of Haematology
Breon M Schmidt, Nadia M Davidson, Anthony D K Hawkins, Ray Bartolo, Ian J Majewski, Paul G Ekert, Alicia Oshlack
Background: Genomic profiling efforts have revealed a rich diversity of oncogenic fusion genes. While there are many methods for identifying fusion genes from RNA-sequencing (RNA-seq) data, visualizing these transcripts and their supporting reads remains challenging. Findings: Clinker is a bioinformatics tool written in Python, R, and Bpipe that leverages the superTranscript method to visualize fusion genes. We demonstrate the use of Clinker to obtain interpretable visualizations of the RNA-seq data that lead to fusion calls...
July 1, 2018: GigaScience
James B Studd, Minjun Yang, Zhenhua Li, Jayaram Vijayakrishnan, Yi Lu, Allen Eng-Juh Yeoh, Kajsa Paulsson, Richard S Houlston
Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy. Genome-wide association studies have shown variation at 14q11.2 influences ALL risk. We sought to decipher causal variant(s) at 14q11.2 and the mechanism of tumorigenesis. We show rs2239630 G>A resides in the promoter of the CCAT enhancer-binding protein epsilon (CEBPE) gene. The rs2239630-A risk allele is associated with increased promotor activity and CEBPE expression. Depletion of CEBPE in ALL cells reduces cell growth, correspondingly CEBPE binds to the promoters of electron transport and energy generation genes...
July 6, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Britt M Gustafsson, Kristin Mattsson, Gordana Bogdanovic, Gustaf Leijonhufvud, Emma Honkaniemi, Kim Ramme, Anthony M Ford
SCL/TAL1 interrupting locus (STIL)-T-cell acute leukaemia (TAL1) fusion genes are present in approximately 11-27% of children with paediatric T-cell acute lymphoblastic leukaemia (T-ALL), but the developmental timing of the rearrangement is still unknown. To investigate whether the fusion gene can be detected in neonatal blood spots (NBSs) from paediatric patients diagnosed with T-cell ALL, we analysed DNA from 38 paediatric patients with T-ALL by nested polymerase chain reaction and electrophoresis. The STIL-TAL1 fusion gene was not detected in NBSs from any of the 38 patients with T-ALL, suggesting that STIL-TAL1 fusion genes are most probably postnatal events in paediatric T-ALL...
July 3, 2018: Pediatric Blood & Cancer
Maddalena Paganin, Maria Francesca Grillo, Daniela Silvestri, Greta Scapinello, Barbara Buldini, Giovanni Cazzaniga, Andrea Biondi, Maria Grazia Valsecchi, Valentino Conter, Geertruij Te Kronnie, Giuseppe Basso
Notwithstanding the improvement in treatment results for paediatric T cell acute lymphoblastic leukaemia (T-ALL) it remains important to understand if genetic aberrations influence therapy response. PTEN tumour suppressor gene inactivation is a frequent event in T-ALL but its effect on patient therapy response is debatable. We analysed the effect of the presence of mutated PTEN on outcome in 257 children with T-ALL treated with Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP)-Berlin-Frankfürt-Münster (BFM) protocols...
June 25, 2018: British Journal of Haematology
Salma Ladhani, Brianna Empringham, Kuan-Wen Wang, Carol Portwine, Laura Banfield, Russell J de Souza, Lehana Thabane, M Constantine Samaan
INTRODUCTION: Acute lymphoblastic leukaemia is the most common paediatric cancer. Survivors of childhood acute lymphoblastic leukaemia (SALL) are at risk of obesity and related cardiometabolic diseases including type 2 diabetes, hypertension, stroke and cardiovascular events. Therefore, it is important to address obesity in this population as this may help mitigate future cardiometabolic comorbidities. In this systematic review, we aim to assess current treatment strategies including lifestyle interventions, pharmacotherapy and bariatric surgery to manage overweight and obesity in SALL...
June 22, 2018: BMJ Open
Ankita Singh, Prateek Bhatia, Amita Trehan, Deepak Bansal, Ajit Singh, Alka Bhatia
Background & objectives: Significance of apoptosis as a prognostic marker is less well studied in paediatric acute lymphoblastic leukaemia (ALL) cases. Hence, a prospective study, involving 30 paediatric ALL cases, was done to assess the clinical relevance of in vivo apoptosis. Methods: Peripheral blood mononuclear cells from all patients were subjected to annexin V/propidium iodide staining to detect the degree of apoptosis [apoptotic index (AI)] at day 0 and day 35 post-induction chemotherapy...
March 2018: Indian Journal of Medical Research
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