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Adult Acute Leukemia

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https://www.readbyqxmd.com/read/29770900/insights-into-mutation-effect-in-three-poikiloderma-with-neutropenia-patients-by-transcript-analysis-and-disease-evolution-of-reported-patients-with-the-same-pathogenic-variants
#1
Elisa A Colombo, Nursel H Elcioglu, Claudio Graziano, Pamela Farinelli, Elisabetta Di Fede, Iria Neri, Elena Facchini, Mariangela Greco, Cristina Gervasini, Lidia Larizza
PURPOSE: Poikiloderma with neutropenia (PN) is a genodermatosis currently described in 77 patients, all presenting with early-onset poikiloderma, neutropenia, and several additional signs. Biallelic loss-of-function mutations in USB1 gene are detected in all molecularly tested patients but genotype-phenotype correlation remains elusive. Cancer predisposition is recognized among PN features and pathogenic variants found in patients who developed early in life myelodysplasia (n = 12), acute myeloid leukemia (n = 2), and squamous cell carcinoma (n = 2) should be kept into account in management and follow-up of novel patients...
May 16, 2018: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29770715/enasidenib-for-the-treatment-of-acute-myeloid-leukemia
#2
James Dugan, Daniel Pollyea
In August 2017 the United States Federal Drug Administration (FDA) approved enasidenib (Idhifa, Celgene/Agios) for adults with relapsed and refractory acute myelogenous leukemia (AML) with an IDH2 mutation. Enasidenib targets cells with mutant copies of isocitrate dehydrogenase-2 (IDH2), inhibiting the oncometabolite 2-hydroxyglutarte (2-HG) formed by the mutant IDH2. Areas covered: We review the studies leading to enasidenib's approval, as well as common side effects and safety issues experienced during the clinical trials...
May 17, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29764005/identification-of-novel-functional-variants-of-sin3a-and-srsf1-among-somatic-variants-in-acute-myeloid-leukemia-patients
#3
Jae-Woong Min, Youngil Koh, Dae-Yoon Kim, Hyung-Lae Kim, Jeong A Han, Yu-Jin Jung, Sung-Soo Yoon, Sun Shim Choi
The advent of massively parallel sequencing, also called nextgeneration sequencing (NGS), has dramatically influenced cancer genomics by accelerating the identification of novel molecular alterations. Using a whole genome sequencing (WGS) approach, we identified somatic coding and noncoding variants that may contribute to leukemogenesis in 11 adult Korean acute myeloid leukemia (AML) patients, with serial tumor samples (primary and relapse) available for 5 of them; somatic variants were identified in 187 AML-related genes, including both novel (SIN3A, C10orf53, PTPRR, and RERGL) and well-known (NPM1, RUNX1, and CEPBA) AMLrelated genes...
May 15, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29763550/selective-inhibition-of-the-myeloid-src-family-kinase-fgr-potently-suppresses-aml-cell-growth-in-vitro-and-in-vivo
#4
Mark C Weir, Sherry T Shu, Ravi K Patel, Sabine Hellwig, Li Chen, Li Tan, Nathanael S Gray, Thomas E Smithgall
Acute myelogenous leukemia (AML) is the most common hematologic malignancy in adults, and is often associated with constitutive tyrosine kinase signaling. These pathways involve the non-receptor tyrosine kinases Fes, Syk and the three Src-family kinases expressed in myeloid cells (Fgr, Hck, and Lyn). In this study, we report remarkable anti-AML efficacy of an N-phenylbenzamide kinase inhibitor, TL02-59. This compound potently suppressed the proliferation of bone marrow samples from twenty of twenty-six AML patients, with a striking correlation between inhibitor sensitivity and expression levels of the myeloid Src family kinases Fgr, Hck, and Lyn...
May 15, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29755998/application-of-a-pharmacokinetic-model-of-metformin-clearance-in-a-population-with-acute-myeloid-leukemia
#5
Alice C Ceacareanu, Geoffrey W Brown, Hoda A Moussa, Zachary A P Wintrob
Objective: We aimed to estimate the metformin-associated lactic acidosis (MALA) risk by assessing retrospectively the renal clearance variability and applying a pharmacokinetic (PK) model of metformin clearance in a population diagnosed with acute myeloid leukemia (AML) and diabetes mellitus (DM). Methods: All adults with preexisting DM and newly diagnosed AML at Roswell Park Cancer Institute were reviewed (January 2003-December 2010, n = 78). Creatinine clearance (CrCl) and total body weight distributions were used in a two-compartment PK model adapted for multiple dosing and modified to account for actual intra- and inter-individual variability...
January 2018: Journal of Research in Pharmacy Practice
https://www.readbyqxmd.com/read/29755706/infectious-risks-and-complications-in-adult-leukemic-patients-receiving-blinatumomab
#6
Wonhee So, Shuchi Pandya, Rod Quilitz, Bijal Shah, John N Greene
Background: Blinatumomab is an anti-CD19 immunotherapy approved for relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) with significantly increased survival rate. While blinatumomab showed lower rates of infection, neutropenia and mucosal barrier injury versus chemotherapy, its infection risks are not well described. Methods: All patients who received blinatumomab for ≥ seven days at an academic cancer center from May 2015 to April 2017 were included...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29753157/treosulfan-fludarabine-and-low-dose-total-body-irradiation-for-children-and-young-adults-with-acute-myeloid-leukemia-or-myelodysplastic-syndrome-undergoing-allogeneic-hematopoietic-cell-transplantation-a-prospective-phase-ii-trial-of-the-pediatric-blood-and
#7
Eneida R Nemecek, Ralf A Hilger, Alexia Adams, Bronwen E Shaw, Deidre Kiefer, Jennifer Le-Rademacher, John E Levine, Gregory Yanik, Wing Leung, Julie-An Talano, Paul Haut, David Delgado, Neena Kapoor, Aleksandra Petrovic, Roberta Adams, Rabi Hanna, Hemalatha Rangarajan, Jignesh Dalal, Joseph Chewning, Michael R Verneris, Stacy Epstein, Lauri Burroughs, Evelio D Perez-Albuerne, Michael A Pulsipher, Colleen Delaney
This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (1-19) underwent allogeneic HCT for AML in first (n=18), second (n=11), third or greater remission (n=3); or MDS (n=8) using bone marrow (n=25), peripheral blood stem cells (n=5) or cord blood (n=9). The regimen consisted of body surface area (BSA)-based treosulfan 10 g/m2 /day (BSA ≤ 0...
May 9, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29750898/mebendazole-exhibits-potent-anti-leukemia-activity-on-acute-myeloid-leukemia
#8
Licai He, Liuzhi Shi, Zhuanyun Du, He Huang, Rui Gong, Lan Ma, Lianjuan Chen, Shenmeng Gao, Jianxin Lyu, Haihua Gu
Acute myeloid leukemia (AML) is one of the most common types of acute leukemia in adults with the lowest survival rate of all leukemia. Resistance to cytarabine and anthracycline-based chemotherapy is a major cause of treatment failure. Thus, finding new drugs with anti-leukemia activities and minimal side effect is urgently needed. Here through screening more than 1000 drugs approved by the Food and Drug Administration (FDA) of United States, the antihelmintic drug mebendazole (MBZ) was found to inhibit the growth of AML cell lines (THP-1, U937, NB4 and K562) and bone marrow mononuclear cells (BM-MNCs) from AML patients at pharmacologically achievable concentrations...
May 8, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29749397/recurrent-somatic-mutations-are-rare-in-patients-with-cryptic-dyskeratosis-congenita
#9
Martin Kirschner, Angela Maurer, Marcin W Wlodarski, Monica S Ventura Ferreira, Anne-Sophie Bouillon, Insa Halfmeyer, Wolfgang Blau, Michael Kreuter, Martin Rosewich, Selim Corbacioglu, Joachim Beck, Michaela Schwarz, Jörg Bittenbring, Markus P Radsak, Christian Matthias Wilk, Steffen Koschmieder, Matthias Begemann, Ingo Kurth, Mirle Schemionek, Tim H Brümmendorf, Fabian Beier
Dyskeratosis congenita (DKC) is a paradigmatic telomere disorder characterized by substantial and premature telomere shortening, bone marrow failure, and a dramatically increased risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). DKC can occur as a late-onset, so-called cryptic form, with first manifestation in adults. Somatic MDS-related mutations are found in up to 35% of patients with acquired aplastic anemia (AA), especially in patients with short telomeres. The aim of our study was to investigate whether cryptic DKC is associated with an increased incidence of MDS-related somatic mutations, thereby linking the accelerated telomere shortening with the increased risk of MDS/AML...
April 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29743722/management-of-patients-with-acute-promyelocytic-leukemia
#10
REVIEW
Sabine Kayser, Richard F Schlenk, Uwe Platzbecker
With the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) acute promyelocytic leukemia (APL) has become from a detrimental to one of the most curable malignant diseases in humans. In particular, the chemotherapy-free regimen with ATO/ATRA has been proven to be highly effective in de novo APL and has become standard first-line therapy in younger adult, non-high-risk patients. Nevertheless, early death is still a major issue in APL, particularly in older patients, emphasizing the need of rapid diagnostics and supportive care together with immediate access to ATRA-based therapy...
April 24, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29743403/-role-of-anti-ccr4-antibody-in-the-treatment-of-transplant-eligible-patients-with-aggressive-adult-t-cell-leukemia-lymphoma
#11
Shigeo Fuji
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell lymphoma caused by the human T-cell lymphotropic virus type I. Patients with aggressive ATL show dismal prognoses, even with intensive dose-dense chemotherapy. Such patients often show chemo-refractoriness. Mogamulizumab (Moga) is a potent treatment option for patients with relapsed or refractory ATL. However, use of Moga before allo-HSCT could theoretically increase the risk of post-transplant complications like graft-versus-host disease (GVHD) as Moga depletes regulatory T-cells (Tregs)...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29742077/philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-in-adults-current-treatments-and-future-perspectives
#12
Musa Yilmaz, Hagop Kantarjian, Farhad Ravandi-Kashani, Nicholas J Short, Elias Jabbour
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) accounts for approximately one-fourth of cases of adult ALL. It typically presents with an aggressive clinical course, responds poorly to standard chemotherapy, and carries a high risk for relapse. The landscape of Ph+ ALL therapy has changed favorably since the development of tyrosine kinase inhibitors (TKIs). With the successful incorporation of TKIs into chemotherapy regimens, remissions occur more frequently and patients live longer...
March 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29741514/management-of-acute-lymphoblastic-leukemia-in-young-adults
#13
Lori S Muffly, Natalie Reizine, Wendy Stock
Substantial interest in acute lymphoblastic leukemia (ALL) in young adults (YAs) and investigations focused on this patient population have resulted in therapeutic advancements that are changing the management paradigm and improving outcomes. The pediatric ALL approach is feasible and effective when administered by medical oncologists. Advanced diagnostics and minimal residual disease measurements aid in prognostication and have resulted in shifting recommendations regarding allogeneic hematopoietic cell transplant in first remission...
February 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29739773/graft-versus-host-disease-in-recipients-of-male-unrelated-donor-compared-with-parous-female-sibling-donor-transplants
#14
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/29739753/health-related-quality-of-life-in-adults-with-relapsed-refractory-acute-lymphoblastic-leukemia-treated-with-blinatumomab
#15
Max S Topp, Zachary Zimmerman, Paul Cannell, Hervé Dombret, Johan Maertens, Anthony Stein, Janet Franklin, Qui Tran, Ze Cong, Andre C Schuh
In the phase 3 TOWER study, blinatumomab significantly improved overall survival in adults with relapsed or refractory (R/R) Philadelphia chromosome-negative (Ph-) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) relative to standard-of-care chemotherapy. A secondary objective of this study was to assess the impact of blinatumomab on health-related quality of life (HRQL) as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). This analysis included the 342 of 405 randomized patients for whom baseline and ≥1 post-baseline result were available in any EORTC multi-item scale or single-item measure...
May 8, 2018: Blood
https://www.readbyqxmd.com/read/29737901/chromogranin-a-and-neuron-specific-enolase-in-neuroblastoma-correlation-to-stage-and-prognostic-factors
#16
Kleopatra Georgantzi, Erik G Sköldenberg, Mats Stridsberg, Per Kogner, Åke Jakobson, Eva Tiensuu Janson, Rolf H B Christofferson
Chromogranin A (CgA) and neuron specific enolase (NSE) are important markers in adult neuroendocrine tumors (NET). Neuroblastoma (NB) has certain neuroendocrine properties. The aim of this study was to correlate blood concentrations of CgA, chromogranin B (CgB), and NSE to prognostic factors and outcome in children with NB. Blood samples from 92 patients with NB, 12 patients with benign ganglioneuroma (GN), 21 patients with non-NB solid tumors, 10 patients with acute leukemias, and 69 healthy children, were analyzed...
May 8, 2018: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29737460/association-between-ogg1-s326c-cc-genotype-and-elevated-relapse-risk-in-acute-myeloid-leukemia
#17
Nanami Gotoh, Takayuki Saitoh, Noriyuki Takahashi, Tetsuhiro Kasamatsu, Yusuke Minato, Alkebsi Lobna, Tsukasa Oda, Takumi Hoshino, Toru Sakura, Hiroaki Shimizu, Makiko Takizawa, Hiroshi Handa, Akihiko Yokohama, Norifumi Tsukamoto, Hirokazu Murakami
Recent studies have shown that tumors of relapsed acute myeloid leukemia (AML) present additional genetic mutations compared to the primary tumors. The base excision repair (BER) pathway corrects oxidatively damaged mutagenic bases and plays an important role in maintaining genetic stability. The purpose of the present study was to investigate the relationship between BER functional polymorphisms and AML relapse. We focused on five major polymorphisms: OGG1 S326C, MUTYH Q324H, APE1 D148E, XRCC1 R194W, and XRCC1 R399Q...
May 8, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29734215/impact-of-a-vitamin-d-replacement-algorithm-in-children-and-young-adults-with-acute-lymphoblastic-leukemia
#18
Jennifer Young, Elizabeth Welin, Carina Braeutigam, Elizabeth Gilger, Adam Lane, Ralph Salloum
BACKGROUND: Pediatric cancer patients have a high prevalence of vitamin D deficiency. Children and young adults with acute lymphoblastic leukemia are at high risk for associated poor bone outcomes due to contributing effects of chemotherapy and supportive care. Evidence-based vitamin D guidelines are lacking in this population. MATERIALS AND METHODS: This is a retrospective study following the implementation of an institutional guideline for standardized monitoring and supplementing vitamin D based on 25-hydroxyvitamin D levels and patient age...
May 4, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29733512/survival-analysis-of-adult-patients-with-all-in-mexico-city-first-report-from-the-acute-leukemia-workgroup-alwg-gtla
#19
Erick Crespo-Solis, Karla Espinosa-Bautista, Martha Alvarado-Ibarra, Etta Rozen-Fuller, Fernando Pérez-Rocha, Chantal Nava-Gómez, Maricela Ortiz-Zepeda, José Luis Álvarez-Vera, Christian Omar Ramos-Peñafiel, Luis Antonio Meillón-García, Sergio Rodríguez-Rodríguez, Alan Pomerantz-Okon, Francisco Javier Turrubiates-Hernández, Roberta Demichelis-Gómez
Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the clonal expansion of hematopoietic lymphoid progenitors. With new target therapies, the survival of adults with ALL has improved in the past few decades. Unfortunately, there are no large ALL patient series in many Latin American countries. Data from the Acute Leukemia Workgroup that includes five Mexico City referral centers were used. Survival was estimated for adult patients with ALL during 2009-2015. In total, 559 adults with ALL were included...
May 7, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29724899/the-dot1l-inhibitor-pinometostat-reduces-h3k79-methylation-and-has-modest-clinical-activity-in-adult-acute-leukemia
#20
Eytan M Stein, Guillermo Garcia-Manero, David A Rizzieri, Raoul Tibes, Jesus G Berdeja, Michael R Savona, Mojca Jongen-Lavrenic, Jessica K Altman, Blythe Thomson, Stephen J Blakemore, Scott R Daigle, Nigel J Waters, A Benjamin Suttle, Alicia Clawson, Roy Pollock, Andrei Krivtsov, Scott A Armstrong, Jorge DiMartino, Eric Hedrick, Bob Löwenberg, Martin S Tallman
Pinometostat (EPZ-5676) is a first-in-class, small-molecule inhibitor of the histone methyltransferase DOT1L. In this phase 1 study, pinometostat was evaluated for safety and efficacy in adult patients with advanced acute leukemias, particularly those involving MLL rearrangements ( MLL-r ) resulting from 11q23 translocations. Fifty-one patients were enrolled into 6 dose escalation cohorts (n=26) and 2 expansion cohorts (n=25) at pinometostat doses of 54 and 90 mg/m2 /day by continuous intravenous infusion in 28-day cycles...
May 3, 2018: Blood
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