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https://www.readbyqxmd.com/read/29910179/autologous-cd19-targeted-car-t-cells-in-patients-with-residual-cll-following-initial-purine-analog-based-therapy
#1
Mark B Geyer, Isabelle Rivière, Brigitte Sénéchal, Xiuyan Wang, Yongzeng Wang, Terence J Purdon, Meier Hsu, Sean M Devlin, Elizabeth Halton, Nicole Lamanna, Jurgen Rademaker, Michel Sadelain, Renier J Brentjens, Jae H Park
Patients with residual chronic lymphocytic leukemia (CLL) following initial purine analog-based chemoimmunotherapy exhibit a shorter duration of response and may benefit from novel therapeutic strategies. We and others have previously described the safety and efficacy of autologous T cells modified to express anti-CD19 chimeric antigen receptors (CARs) in patients with relapsed or refractory B cell acute lymphoblastic leukemia and CLL. Here we report the use of CD19-targeted CAR T cells incorporating the intracellular signaling domain of CD28 (19-28z) as a consolidative therapy in 8 patients with residual CLL following first-line chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab...
June 14, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29883054/genetic-compensation-of-runx-family-transcription-factors-in-leukemia
#2
REVIEW
Yasuhiko Kamikubo
RUNX1 is a transcription factor belonging to the Core Binding Factor (CBF) family. It is considered to be a master regulator of hematopoiesis and has been regarded as a tumor suppressor because it is essential for definitive hematopoiesis in vertebrates. It is one of the most frequent target genes of chromosomal translocation in leukemia, and germ line mutation of RUNX1 causes familial platelet disorder with associated myeloid malignancies (FPDMM). Somatic cell mutations and chromosomal abnormalities, including those of RUNX1, are observed in myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myelomonocytic leukemia (CMML) at a high frequency...
June 8, 2018: Cancer Science
https://www.readbyqxmd.com/read/29872609/l-asparaginase-a-feasible-therapeutic-molecule-for-multiple-diseases
#3
Archana Vimal, Awanish Kumar
This note highlights our understanding and thinking about the feasibility of l-asparaginase as therapeutics for multiple diseases. l-asparaginase enzyme (l-asparagine amidohydrolase, EC 3.5.1.1) is prominently known for its chemotherapeutic application. It is primarily used in the treatment of acute lymphoblastic leukemia in children. It is also used in the treatment of other forms of cancer Hodgkin disease, lymphosarcoma, acute myelomonocytic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, reticulosarcoma and melanosarcoma (Lopes et al...
June 2018: 3 Biotech
https://www.readbyqxmd.com/read/29869673/long-term-outcomes-of-total-body-irradiation-plus-cyclophosphamide-versus-busulfan-plus-cyclophosphamide-as-conditioning-regimen-for-acute-lymphoblastic-leukemia-a-comparative-study
#4
Ioanna Sakellari, Eleni Gavriilaki, Konstantinos Chatziioannou, Maria Papathanasiou, Despina Mallouri, Ioannis Batsis, Zoi Bousiou, Stella Bouziana, Varnavas Constantinou, Vassiliki Douka, Chrysa Apostolou, Michalis Iskas, Chrysavgi Lalayanni, Anastasia Athanasiadou, Damianos Sotiropoulos, Evangelia Yannaki, Vasilis Gianouzakos, Achilles Anagnostopoulos
The role of total body irradiation (TBI) in allogeneic hematopoietic stem cell transplantation (HCT) for adult acute lymphoblastic leukemia (ALL) remains controversial. Therefore, we investigated long-term treatment outcomes of transplanted ALL patients aiming to identify prognostic factors and the impact of conditioning. We enrolled consecutive ALL patients transplanted from 1990 to 2016, following TBI- or busulfan (Bu)-based conditioning regimen. We studied 151 ALL patients transplanted in first complete remission (CR) (60), other CR (33), or relapsed/refractory disease (58) from sibling (87), and HLA-matched (42) or mismatched (17) unrelated and alternative donors (5)...
June 5, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29861776/cytotoxic-activity-of-extracts-from-plants-of-central-argentina-on-sensitive-and-multidrug-resistant-leukemia-cells-isolation-of-an-active-principle-from-gaillardia-megapotamica
#5
María Laura González, Mariana Belén Joray, Jerónimo Laiolo, María Inés Crespo, Sara María Palacios, Gustavo Miguel Ruiz, María Cecilia Carpinella
Plants are a significant reservoir of cytotoxic agents, including compounds with the ability to interfere with multidrug-resistant (MDR) cells. With the aim of finding promising candidates for chemotherapy, 91 native and naturalized plants collected from the central region of Argentina were screened for their cytotoxic effect toward sensitive and MDR P-glycoprotein (P-gp) overexpressing human leukemia cells by means of MTT assays. The ethanol extracts obtained from Aldama tucumanensis , Ambrosia elatior , Baccharis artemisioides , Baccharis coridifolia , Dimerostemma aspilioides , Gaillardia megapotamica , and Vernonanthura nudiflora presented outstanding antiproliferative activity at 50  μ g/mL, with inhibitory values from 93 to 100%, when tested on the acute lymphoblastic leukemia (ALL) cell line CCRF-CEM and the resistant derivative CEM-ADR5000, while 70-90% inhibition was observed against the chronic myelogenous leukemia (CML) cell K562 and its corresponding resistant subline, Lucena 1...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29859988/taxodione-induces-apoptosis-in-bcr-abl-positive-cells-through-ros-generation
#6
Yuki Uchihara, Kenji Tago, Hidetoshi Taguchi, Yuji Narukawa, Fumiyuki Kiuchi, Hiroomi Tamura, Megumi Funakoshi-Tago
Chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) are hematopoietic malignancies caused by the constitutive activation of BCR-ABL tyrosine kinase. Although direct BCR-ABL inhibitors, such as imatinib, were initially successful in the treatment of leukemia, many patients developed drug resistance over time due to the gatekeeper mutation of BCR-ABL T315I. In the present study, we found that taxodione, a quinone methide diterpene isolated from Taxodium distichum, significantly induced apoptosis in human myelogenous leukemia-derived K562 cells, which were transformed by BCR-ABL...
May 31, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29849118/maintenance-and-pharmacologic-targeting-of-ror1-protein-levels-via-uhrf1-in-t-1-19-pre-b-all
#7
Marilynn Chow, Lina Gao, Jason D MacManiman, Vincent T Bicocca, Bill H Chang, Joshi J Alumkal, Jeffrey W Tyner
Expression of the transmembrane pseudokinase ROR1 is required for survival of t(1;19)-pre-B-cell acute lymphoblastic leukemia (t(1;19) pre-B-ALL), chronic lymphocytic leukemia, and many solid tumors. However, targeting ROR1 with small-molecules has been challenging due to the absence of ROR1 kinase activity. To identify genes that regulate ROR1 expression and may, therefore, serve as surrogate drug targets, we employed an siRNA screening approach and determined that the epigenetic regulator and E3 ubiquitin ligase, UHRF1, is required for t(1;19) pre-B-ALL cell viability in a ROR1-dependent manner...
May 30, 2018: Oncogene
https://www.readbyqxmd.com/read/29805426/expression-of-aberrant-antigens-in-hematological-malignancies-a-single-center-experience
#8
Aneeta Shahni, Madiha Saud, Saima Siddiqui, Samina Naz Mukry
Background and Objective: Aberrant phenotype is a phenomenon of abnormal expression or loss of expression of cell specific lineage marker not associated with specific cell type. Aberrant phenotype expression due to genetic defects may be associated with unfavorable outcome. It can be used to determine minimal residual disease status. The purpose of the study was to find out the occurrence of aberrant phenotypes in leukemia/lymphoma patients. Methods: One milliliter peripheral blood or bone marrow samples were analyzed on FACS Calibur flowcytometer...
March 2018: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/29803841/the-second-generation-tyrosine-kinase-inhibitor-dasatinib-induced-eryptosis-in-human-erythrocytes-an-in-vitro-study
#9
Wai Yin Chan, Pui Man Lau, Ka Wing Yeung, Siu Kai Kong
Dasatinib, a new tyrosine kinase inhibitor, is used clinically to kill chronic myelogenous leukemia and acute lymphoblastic leukemia through apoptosis. Obviously, anemia is developed in many patients receiving dasatinib for treatment. Until now, the mechanism for the cytotoxic effects of dasatinib in human erythrocytes is not fully understood. As many tyrosine kinases are found in human erythrocytes, it is therefore logical to hypothesize that dasatinib is able to induce apoptosis (or eryptosis) in human erythrocytes...
May 24, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29795428/impact-of-graft-versus-host-disease-on-relapse-and-survival-after-allogeneic-stem-cell-transplantation-for-pediatric-leukemia
#10
Motohiro Kato, Mio Kurata, Junya Kanda, Koji Kato, Daisuke Tomizawa, Kazuko Kudo, Nao Yoshida, Kenichiro Watanabe, Hiroyuki Shimada, Jiro Inagaki, Katsuyoshi Koh, Hiroaki Goto, Keisuke Kato, Yuko Cho, Yuki Yuza, Atsushi Ogawa, Keiko Okada, Masami Inoue, Yoshiko Hashii, Takanori Teshima, Makoto Murata, Yoshiko Atsuta
Graft-versus-host disease (GVHD) occasionally leads to morbidity and mortality but is thought to reduce the risk of relapses in patients with a hematological malignancy. However, information on the effect of GVHD in pediatric leukemia is limited. Using a nationwide registry, we retrospectively analyzed 1526 children who underwent allogeneic stem cell transplantation for leukemia. Grades 0-I acute GVHD were associated with a higher relapse rate at three years after transplantation, at 25.4 and 24.3%, respectively, than grades II, III, or IV acute GVHD at 18...
May 24, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29794073/related-donor-transplants-has-posttransplantation-cyclophosphamide-nullified-the-detrimental-effect-of-hla-mismatch
#11
Tara M Robinson, Ephraim J Fuchs, Mei-Jie Zhang, Andrew St Martin, Myriam Labopin, Daniel A Keesler, Didier Blaise, Asad Bashey, Jean-Henri Bourhis, Fabio Ciceri, Stefan O Ciurea, Steven M Devine, Mohamad Mohty, Shannon R McCurdy, Noel Milpied, Ian K McNiece, Vanderson Rocha, Rizwan Romee, Gerard Socie, Ibrahim Yakoub-Agha, Robert J Soiffer, Mary Eapen, Arnon Nagler
We sought to identify whether posttransplantation cyclophosphamide (PT-Cy) reduces or eliminates the detrimental impact of HLA mismatching on outcomes of HLA-haploidentical related donor transplantation for acute leukemia. Data from 2143 donor-recipient pairs (n = 218 haploidentical sibling; n = 218 offspring; n = 1707 HLA-matched sibling) with acute myeloid or lymphoblastic leukemia were studied. All received a calcineurin inhibitor for graft-versus-host disease (GVHD) prophylaxis while high-dose PT-Cy was also given to recipients of haploidentical transplant...
June 12, 2018: Blood Advances
https://www.readbyqxmd.com/read/29773429/real-life-experience-with-ponatinib-in-chronic-myeloid-leukemia-a-multicenter-observational-study
#12
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
#13
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/29766234/the-severe-cytokine-release-syndrome-in-phase-i-trials-of-cd19-car-t-cell-therapy-a-systematic-review
#14
REVIEW
Zhen Jin, Rufang Xiang, Kai Qing, Xiaoyang Li, Yunxiang Zhang, Lining Wang, Hongming Zhu, Yuanfei Mao, Zizhen Xu, Junmin Li
CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive results in treating acute lymphoblastic leukemia (B-ALL), chronic lymphoblastic leukemia (B-CLL), and B-cell non-Hodgkin lymphoma (B-NHL) over the past few years. Meanwhile, the cytokine release syndrome (CRS), which could be moderate or even life-threatening, has emerged as the most significant adverse effect in the clinical course of this novel targeting immunotherapy. In this systematic review, we analyzed the incidence of severe CRS in 19 clinical trials selected from studies published between 2010 and 2017...
May 15, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29743179/a-cd19-cd3-bispecific-antibody-for-effective-immunotherapy-of-chronic-lymphocytic-leukemia-in-the-ibrutinib-era
#15
Hannah R Robinson, Junpeng Qi, Erika M Cook, Cydney Nichols, Eman L Dadashian, Chingiz Underbayev, Sarah E M Herman, Nakhle S Saba, Keyvan Keyvanfar, Clare Sun, Inhye E Ahn, Sivasubramanian Baskar, Christoph Rader, Adrian Wiestner
The Bruton's tyrosine kinase inhibitor ibrutinib induces high rates of clinical response in chronic lymphocytic leukemia (CLL). However, there remains a need for adjunct treatments to deepen response and to overcome drug resistance. Blinatumomab, a CD19/CD3 bispecific antibody (bsAb) designed in the BiTE® format, is FDA approved for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Due to its short half-life of 2.1 hours, blinatumomab requires continuous intravenous dosing for efficacy...
May 9, 2018: Blood
https://www.readbyqxmd.com/read/29739773/graft-versus-host-disease-in-recipients-of-male-unrelated-donor-compared-with-parous-female-sibling-donor-transplants
#16
Anita J Kumar, Soyoung Kim, Michael T Hemmer, Mukta Arora, Stephen R Spellman, Joseph A Pidala, Daniel R Couriel, Amin M Alousi, Mahmoud D Aljurf, Jean-Yves Cahn, Mitchell S Cairo, Corey S Cutler, Shatha Farhan, Usama Gergis, Gregory A Hale, Shahrukh K Hashmi, Yoshihiro Inamoto, Rammurti T Kamble, Mohamed A Kharfan-Dabaja, Margaret L MacMillan, David I Marks, Hideki Nakasone, Maxim Norkin, Muna Qayed, Olle Ringden, Harry C Schouten, Kirk R Schultz, Melhem M Solh, Takanori Teshima, Alvaro Urbano-Ispizua, Leo F Verdonck, Robert Peter Gale, Betty K Hamilton, Navneet S Majhail, Alison W Loren
Optimal donor selection is critical for successful allogeneic hematopoietic cell transplantation (HCT). Donor sex and parity are well-established risk factors for graft-versus-host disease (GVHD), with male donors typically associated with lower rates of GVHD. Well-matched unrelated donors (URDs) have also been associated with increased risks of GVHD as compared with matched sibling donors. These observations raise the question of whether male URDs would lead to more (or less) favorable transplant outcomes as compared with parous female sibling donors...
May 8, 2018: Blood Advances
https://www.readbyqxmd.com/read/29730053/functional-vision-and-quality-of-life-in-children-with-microphthalmia-anophthalmia-coloboma-a-cross-sectional-study
#17
Annegret Dahlmann-Noor, Vijay Tailor, Yassir Abou-Rayyah, Gillian Adams, John Brookes, Sir Peng T Khaw, Catey Bunce, Maria Papadopoulos
PURPOSE: To determine the child's and parental perception of functional visual ability (FVA), vision-related and health-related quality of life (VR-QoL, HR-QoL) in children with microphthalmia/anophthalmia/coloboma (MAC). METHODS: Between June 25, 2014, and June 3, 2015, we carried out a cross-sectional observational study at Moorfields Eye Hospital, London, UK, enrolling 45 children 2-16 years of age with MAC attending our clinics, and their parents. To assess FVA, VR-QoL, and HR-QoL we asked participants to complete three validated tools, the Cardiff Visual Ability Questionnaire for Children (CVAQC), the Impact of Vision Impairment for Children (IVI-C) instrument, and the PedsQL V 4...
May 3, 2018: Journal of AAPOS: the Official Publication of the American Association for Pediatric Ophthalmology and Strabismus
https://www.readbyqxmd.com/read/29697355/genetic-variation-of-costimulatory-molecules-including-cytotoxic-t-lymphocyte-antigen-4-inducible-t-cell-costimulator-cluster-differentiation-28-and-programmed-cell-death-1-genes-in-iranian-patients-with-leukemia
#18
Mani Ramzi, Nargess Arandi, Mahdiyar Iravani Saadi, Ramin Yaghobi, Bita Geramizadeh
OBJECTIVES: There are limited studies about the possible relationship between genetic variations of costimulatory genes and susceptibility to hematologic malignancies like leukemia and lymphoma. MATERIALS AND METHODS: This cross-sectional study included 59 leukemia patients. The polymorphisms of costimulatory molecules, including the CTLA-4 gene (-318 C/T, -1722 T/C, -1661 A/G, +49 A/G), PD-1 gene (1.3 A/G, 1.9 C/T), ICOS gene (1720 C/T), and CD28 gene (17 C/T), were analyzed by polymerase chain reaction-restriction fragment length polymorphism methods...
April 26, 2018: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29692582/institutional-based-tumor-registry-of-hematopoietic-malignancies-a-4-years-preliminary-report-from-karachi
#19
Sadia Sultan, Syed Mohammed Irfan, Navaira Ali, Neesha Nawaz
BACKGROUND: Pakistan has a population of over 198 million making it the world's sixth populous country. However, operational population-based cancer registries in Pakistan are lacking. Limited data are available based on institutional or Karachi Cancer Registry from Karachi; however, no exclusive registry for hematological malignancies is established till date. Hence, we decided to conduct a database analysis to determine the frequencies of various hematological cancers in our tertiary care center in Karachi...
April 2018: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/29666622/chemotactic-cues-for-notch1-dependent-leukemia
#20
REVIEW
Erich Piovan, Valeria Tosello, Alberto Amadori, Paola Zanovello
The NOTCH signaling pathway is a conserved signaling cascade that regulates many aspects of development and homeostasis in multiple organ systems. Aberrant activity of this signaling pathway is linked to the initiation and progression of several hematological malignancies, exemplified by T-cell acute lymphoblastic leukemia (T-ALL). Interestingly, frequent non-mutational activation of NOTCH1 signaling has recently been demonstrated in B-cell chronic lymphocytic leukemia (B-CLL), significantly extending the pathogenic significance of this pathway in B-CLL...
2018: Frontiers in Immunology
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