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Acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/29790971/brain-activity-associated-with-attention-deficits-following-chemotherapy-for-childhood-acute-lymphoblastic-leukemia
#1
Slim Fellah, Yin T Cheung, Matthew A Scoggins, Ping Zou, Noah D Sabin, Ching-Hon Pui, Leslie L Robison, Melissa M Hudson, Robert J Ogg, Kevin R Krull
Background: The impact of contemporary chemotherapy treatment for childhood acute lymphoblastic leukemia on central nervous system activity is not fully appreciated. Methods: Neurocognitive testing and functional magnetic resonance imaging (fMRI) were obtained in 165 survivors five or more years postdiagnosis (average age = 14.4 years, 7.7 years from diagnosis, 51.5% males). Chemotherapy exposure was measured as serum concentration of methotrexate following high-dose intravenous injection...
May 21, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29789639/fludarabine-and-neurotoxicity-in-engineered-t-cell-therapy
#2
Kate L Lowe, Crystal L Mackall, Elliot Norry, Rafael Amado, Bent K Jakobsen, Gwendolyn Binder
Adoptive T-cell therapy, incorporating engineered T cell receptors (TCRs) or chimeric antigen receptors (CARs), target tumor antigens with high affinity and specificity. To increase the potency of adoptively transferred T cells, patients are conditioned with lymphodepleting chemotherapy regimens prior to adoptive T-cell transfer (ACT), and data suggest that fludarabine is an important component of an effective regimen. In a recent clinical trial using CAR-T cells engineered to target the CD19 B-cell antigen to treat acute lymphoblastic leukemia, JCAR-015 (NCT02535364), two patient deaths due to cerebral edema led to trial suspension...
May 7, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29789603/vorinostat-and-quinacrine-have-synergistic-effects-in-t-cell-acute-lymphoblastic-leukemia-through-reactive-oxygen-species-increase-and-mitophagy-inhibition
#3
Bo Jing, Jin Jin, Rufang Xiang, Meng Liu, Li Yang, Yin Tong, Xinhua Xiao, Hu Lei, Wei Liu, Hanzhang Xu, Jiong Deng, Li Zhou, Yingli Wu
Despite recent progress in the treatment, the outcome of adult acute T-cell lymphoblastic leukemia (T-ALL) is poor. Development of novel approach to combat this disease is urgently required. Vorinostat, a pan-histone deacetylase (HDAC) inhibitor, exerts promising anticancer activity in a variety of solid and hematologic malignancies. However, the efficacy of vorinostat monotherapy is unsatisfactory. Here, we show that quinacrine (QC), an anti-malaria drug with potent autophagy inhibitory activity, could synergistically enhance vorinostat-induced cell death at a non-toxic concentration...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29786884/bone-morbidity-and-recovery-in-children-with-acute-lymphoblastic-leukemia-results-of-a-six-year-prospective-cohort-study
#4
Leanne M Ward, Jinhui Ma, Bianca Lang, Josephine Ho, Nathalie Alos, Mary Ann Matzinger, Nazih Shenouda, Brian Lentle, Jacob L Jaremko, Beverly Wilson, David Stephure, Robert Stein, Anne Marie Sbrocchi, Celia Rodd, Victor Lewis, Sara Israels, Ronald M Grant, Conrad V Fernandez, David B Dix, Elizabeth A Cummings, Robert Couch, Elizabeth Cairney, Ronald Barr, Sharon Abish, Stephanie A Atkinson, John Hay, Frank Rauch, David Moher, Kerry Siminoski, Jacqueline Halton
Osteoporotic fractures are a significant cause of morbidity in acute lymphoblastic leukemia (ALL). Our objective was to determine the incidence and predictors of fractures and recovery from osteoporosis in pediatric ALL over 6 years following glucocorticoid initiation. Vertebral fractures (VF) and vertebral body reshaping were assessed on annual spine radiographs, low-trauma non-VF were recorded at regular intervals and spine bone mineral density (BMD) was captured every 6 months for 4 years and then annually...
May 22, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29786757/copy-number-abnormality-of-acute-lymphoblastic-leukemia-cell-lines-based-on-their-genetic-subtypes
#5
Chihiro Tomoyasu, Toshihiko Imamura, Toshihiro Tomii, Mio Yano, Daisuke Asai, Hiroaki Goto, Akira Shimada, Masashi Sanada, Shotaro Iwamoto, Junko Takita, Masayoshi Minegishi, Takeshi Inukai, Kanji Sugita, Hajime Hosoi
In this study, we performed genetic analysis of 83 B cell precursor acute lymphoblastic leukemia (B-ALL) cell lines. First, we performed multiplex ligation-dependent probe amplification analysis to identify copy number abnormalities (CNAs) in eight genes associated with B-ALL according to genetic subtype. In Ph+ B-ALL cell lines, the frequencies of IKZF1, CDKN2A/2B, BTG1, and PAX5 deletion were significantly higher than those in Ph- B-ALL cell lines. The frequency of CDKN2A/2B deletion in KMT2A rearranged cell lines was significantly lower than that in non-KMT2A rearranged cell lines...
May 21, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29785311/acute-lymphoblastic-leukemia-following-lenalidomide-maintenance-for-multiple-myeloma-two-cases-with-unexpected-presentation-and-good-prognostic-features
#6
Abdullah M Khan, Jameel Muzaffar, Hermant Murthy, John R Wingard, Jan S Moreb
Lenalidomide maintenance following autologous stem cell transplant (ASCT) is considered the standard of care for eligible patients with multiple myeloma (MM). A recent meta-analysis has provided additional evidence that lenalidomide maintenance is associated with a higher incidence of second primary malignancies, including both hematologic and solid malignancies. Acute lymphoblastic leukemia (ALL) as a second primary malignancy is rarely described in the literature. Herein, we describe two patients with MM treated with induction therapy, ASCT, and lenalidomide maintenance that experienced cytopenias while on maintenance...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29784748/emerging-treatment-options-for-acute-lymphoblastic-leukemia-focus-on-car-t-cell-therapy
#7
Patrick A Brown, Bijal Shah
Acute lymphoblastic leukemia (ALL) comprises a heterogeneous group of diseases with different morphologic, cytogenetic, and molecular subgroups, some of which have significant therapeutic implications. It typically presents with an aggressive clinical course, and among adults, responds poorly to standard chemotherapy, and carries a high risk for relapse. Despite the significant progress made in inducing remission, frequent relapses remain a challenge. Novel drugs, such as potent later-generation tyrosine kinase inhibitors, antibody-drug conjugates, bispecific monoclonal antibodies, and chimeric antigen receptor (CAR) T-cell therapies, are being investigated in patients with ALL...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29783736/revisiting-cd28-superagonist-tgn1412-as-potential-therapeutic-for-pediatric-b-cell-leukemia-a-review
#8
REVIEW
Katelyn E Brown
Pediatric acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer diagnosis, with numbers rising gradually every year. This paper proposes a novel therapeutic agent for pediatric ALL on the basis of a failed clinical drug trial in 2006. TGN1412 was a promising therapeutic agent that yielded outstanding results in both in vitro studies and animal trials. It is a CD28 superagonist monoclonal antibody that activates T regulatory (TReg ) cells in the absence of costimulation of the T cell receptor (TCR) by an antigen-presenting cell...
May 19, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29781813/the-notch1-cd44-axis-drives-pathogenesis-in-a-t-cell-acute-lymphoblastic-leukemia-model
#9
Marina García-Peydró, Patricia Fuentes, Marta Mosquera, María J García-León, Juan Alcain, Antonio Rodríguez, Purificación García de Miguel, Pablo Menéndez, Kees Weijer, Hergen Spits, David T Scadden, Carlos Cuesta-Mateos, Cecilia Muñoz-Calleja, Francisco Sánchez-Madrid, María L Toribio
NOTCH1 is a prevalent signaling pathway in T cell acute lymphoblastic leukemia (T-ALL), but crucial NOTCH1 downstream signals and target genes contributing to T-ALL pathogenesis cannot be retrospectively analyzed in patients and thus remain ill defined. This information is clinically relevant, as initiating lesions that lead to cell transformation and leukemia-initiating cell (LIC) activity are promising therapeutic targets against the major hurdle of T-ALL relapse. Here, we describe the generation in vivo of a human T cell leukemia that recapitulates T-ALL in patients, which arises de novo in immunodeficient mice reconstituted with human hematopoietic progenitors ectopically expressing active NOTCH1...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29781717/white-matter-microstructure-and-information-processing-at-the-completion-of-chemotherapy-only-treatment-for-pediatric-acute-lymphoblastic-leukemia
#10
Simone J Darling, Cinzia De Luca, Vicki Anderson, Maria McCarthy, Stephen Hearps, Marc L Seal
Little is known about white matter microstructure and its role in information processing abilities of children treated for acute lymphoblastic leukemia (ALL) early posttreatment. Twenty-one survivors of ALL and 18 controls (7-16 years) underwent neurocognitive assessment. A subsample underwent diffusion-weighted magnetic resonance imaging. The ALL group performed poorer on measures of processing capacity, and had widespread areas of decreased fractional anisotropy and increased radial diffusivity. Significant group by white matter microstructure interactions was found when predicting processing speed...
May 21, 2018: Developmental Neuropsychology
https://www.readbyqxmd.com/read/29779335/-the-investigation-of-cag-regimen-in-relapsed-and-refractory-adult-acute-lymphoblastic-leukemia
#11
Y Wang, Y Chen, Y B Chen, Z Y Yan, Z Y Liu, J M Li, H M Sun, S J Zhang
No abstract text is available yet for this article.
April 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29779326/-clinical-study-on-the-chimeric-antigen-receptor-t-cells-for-the-treatment-of-t315i-mutated-central-relapsed-refractory-acute-lymphoblast-leukemia-a-case-report
#12
Y R Jiang, J X He, L Y Zhang, M X Zhao, S J Pang, Y Q Fang, Z K Li, S M Li, M J Wang
No abstract text is available yet for this article.
April 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29778230/etv6-runx1-positive-childhood-acute-lymphoblastic-leukemia-all-the-spectrum-of-clonal-heterogeneity-and-its-impact-on-prognosis
#13
Μ Αmpatzidou, S I Papadhimitriou, G Paterakis, D Pavlidis, Κ Tsitsikas, I V Kostopoulos, V Papadakis, G Vassilopoulos, S Polychronopoulou
The prognostic significance of the ETV6/RUNX1-fusion and of the accompanying aberrations is disputable; whether co-existing sub-clones are responsible for delayed MRD-clearance and thus, moderate outcome, remains to be clarified. We studied, in a paediatric cohort of 119 B-ALLs, the relation between the ETV6/RUNX1 aberration and the co-existing subclones with (a) presenting clinical/biological features, (b) early response to treatment(MRD) and (c) long-term outcome over a 12-year period. Patients were homogeneously treated according to BFM-based-protocols...
August 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29773604/transcriptional-activities-of-dux4-fusions-in-b-cell-acute-lymphoblastic-leukemia
#14
Yosuke Tanaka, Masahito Kawazu, Takahiko Yasuda, Miki Tamura, Fumihiko Hayakawa, Shinya Kojima, Toshihide Ueno, Hitoshi Kiyoi, Tomoki Naoe, Hiroyuki Mano
No abstract text is available yet for this article.
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773603/clinical-efficacy-of-ruxolitinib-and-chemotherapy-in-a-child-with-philadelphia-chromosome-like-acute-lymphoblastic-leukemia-with-golga5-jak2-fusion-and-induction-failure
#15
Yang Y Ding, Julie W Stern, Tracey F Jubelirer, Gerald B Wertheim, Fumin Li, Fengqi Chang, Zhaohui Gu, Charles G Mullighan, Yong Li, Richard C Harvey, I-Ming Chen, Cheryl L Willman, Stephen P Hunger, Marilyn M Li, Sarah K Tasian
No abstract text is available yet for this article.
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773592/investigating-chemoresistance-to-improve-sensitivity-of-childhood-t-cell-acute-lymphoblastic-leukemia-to-parthenolide
#16
Benjamin C Ede, Rafal R Asmaro, John P Moppett, Paraskevi Diamanti, Allison Blair
Current therapies for childhood T cell acute lymphoblastic leukemia have increased survival rates to above 85% in developed countries. Unfortunately, some patients fail to respond to therapy and many suffer from serious side effects, highlighting the need to investigate other agents to treat this disease. Parthenolide, a nuclear factor kappa B inhibitor and reactive oxygen species inducer, has been shown to have excellent anti-cancer activity in pediatric leukemia xenografts, with minimal effects on normal hemopoietic cells...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773429/real-life-experience-with-ponatinib-in-chronic-myeloid-leukemia-a-multicenter-observational-study
#17
Adi Shacham-Abulafia, Pia Raanani, David Lavie, Yulia Volchek, Ron Ram, Ilana Helman, Liat Shargian, Anna Gourevitch, Evgeni Chubar, Roy Ratzon, Uri Rozovski
BACKGROUND: The strict recruitment criteria of patients for clinical trials often lead to reduced generalizability of the findings. We studied how ponatinib is used outside clinical trials in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: The present retrospective study included all patients with a diagnosis of CML who had received ponatinib in 7 medical centers in Israel. RESULTS: From 2011 to 2016, we identified 37 patients with CML who had received ponatinib, 21 in the chronic phase and 16 in the advanced phase...
May 7, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29772458/phenotyping-and-target-expression-profiling-of-cd34-cd38-and-cd34-cd38-stem-and-progenitor-cells-in-acute-lymphoblastic-leukemia
#18
Katharina Blatt, Ingeborg Menzl, Gregor Eisenwort, Sabine Cerny-Reiterer, Harald Herrmann, Susanne Herndlhofer, Gabriele Stefanzl, Irina Sadovnik, Daniela Berger, Alexandra Keller, Alexander Hauswirth, Gregor Hoermann, Michael Willmann, Thomas Rülicke, Heinz Sill, Wolfgang R Sperr, Christine Mannhalter, Junia V Melo, Ulrich Jäger, Veronika Sexl, Peter Valent
Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+ /CD38- LSCs in patients with Ph+ ALL (n = 22) and Ph- ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested...
May 14, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29772353/cardiac-profile-of-chimeric-antigen-receptor-car-t-cell-therapy-in-children-a-single-institution-experience
#19
Danielle Burstein, Shannon Maude, Stephen Grupp, Heather Griffis, Joseph Rossano, Kimberly Lin
BACKGROUND: Immunotherapy with chimeric antigen receptor (CAR)-modified T-cells targeting CD19 for pediatric acute lymphoblastic leukemia (ALL) has demonstrated significant efficacy. The principle toxicity is cytokine release syndrome with resultant hypotension. However, the spectrum of cardiovascular effects associated with CAR T-cell therapy has not been systematically evaluated. METHODS: We reviewed all patients who received CD19-directed CAR T-cells at the Children's Hospital of Philadelphia between April 2012 and September 2016...
May 14, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29772352/allogeneic-stem-cell-transplantation-from-hla-mismatched-donors-for-pediatric-patients-with-acute-lymphoblastic-leukemia-treated-according-to-the-2003-bfm-and-2007-international-bfm-studies-impact-of-disease-risk-on-outcomes
#20
Jean-Hugues Dalle, Adriana Balduzzi, Peter Bader, Arjan Lankester, Isaac Yaniv, Jacek Wachowiak, Anna Pieczonka, Marc Bierings, Akif Yesilipek, Petr Sedlacek, Marianne Ifversen, Sabina Sufliarska, Jacek Toporski, Evgenia Glogova, Ulrike Poetschger, Christina Peters
RATIONAL: Allogeneic HSCT is beneficial for pediatric patients with relapsed or (very) high-risk ALL in remission. A total of 1115 consecutive patients were included in the ALL SCT 2003 BFM study and the ALL SCT 2007-International study and were stratified according to relapse risk (Standard vs. High vs. Very High Risk of Relapse) and donor type (Matched Sibling vs. Matched Donor vs. Mismatched Donor). PATIENTS AND METHODS: A total of 148 patients (60% male, median age 8...
May 14, 2018: Biology of Blood and Marrow Transplantation
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