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Adult Acute Leukemia

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https://www.readbyqxmd.com/read/29330049/the-histone-demethylase-phf8-promotes-adult-acute-lymphoblastic-leukemia-through-interaction-with-the-mek-erk-signaling-pathway
#1
Yue Fu, Yaling Yang, Xiaoming Wang, Xiaolin Yin, Minran Zhou, Siqi Wang, Lin Yang, Tao Huang, Man Xu, Chunyan Chen
Adult acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells that is associated with a high risk of relapse and poor prognosis. Thus, novel pathogenic mechanisms and therapeutic targets need to be explored. Histone methylation is one of the most significant chromatin post-translational modifications. Here, we show that the histone demethylase PHF8 is highly expressed in a large number of ALL clinical specimens and that PHF8 expression is associated with ALL progression. PHF8 knockdown inhibits proliferation and promotes the apoptosis of ALL cells in vitro as well as attenuates tumor growth in vivo...
January 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29327715/de-novo-pure-erythroid-leukemia-refining-the-clinicopathologic-and-cytogenetic-characteristics-of-a-rare-entity
#2
Erica F Reinig, Patricia T Greipp, April Chiu, Matthew T Howard, Kaaren K Reichard
Per the revised fourth edition World Health Organization classification of acute myeloid leukemia, pure erythroid leukemia is now the sole type of acute erythroid leukemia. The diagnosis of this rare entity is often challenging and the cytologic overlap with non-neoplastic (eg, megaloblastic anemia) and neoplastic entities (eg, other types of acute leukemia and non-hematopoietic malignancies) warrants a significant degree of clinical, laboratory, immunophenotypic, and genetic investigation. Given the limited number of reports of this rare and diagnostically challenging entity, we report detailed clinicopathologic characteristics from 15 patients, the largest series thus far, of primary de novo pure erythroid leukemia to provide further diagnostic insights into this entity and reveal strategies for making the diagnosis...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29327534/gastric-angioinvasive-mucormycosis-in-immunocompetent-adult-a-rare-occurrence
#3
Mukesh Nasa, Zubin Sharma, Lipika Lipi, Randhir Sud
Mucormycosis is a rare, opportunistic fungal infection that occurs almost exclusively in immunocompromised hosts such as patients with diabetes mellitus, leukemia, lymphoma, renal disease, septicemia, burns, malnutrition, and following long-term treatment with steroids and antibiotics. Based on the clinical presentation and involvement, mucormycosis is classified as six major forms, namely, rhinocerebral, pulmonary, cutaneous, gastrointestinal (GI), disseminated and miscellaneous, with rhinocerebral and pulmonary being the common forms...
December 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/29318644/description-and-prognostic-significance-of-the-kinetics-of-minimal-residual-disease-status-in-adults-with-acute-lymphoblastic-leukemia-treated-with-hypercvad
#4
Ryan D Cassaday, Philip A Stevenson, Brent L Wood, Pamela S Becker, Paul C Hendrie, Brenda M Sandmaier, Jerald L Radich, Andrei R Shustov
HyperCVAD is a commonly-used regimen for adults with newly-diagnosed acute lymphoblastic leukemia (ALL). However, relatively little is known about the application of minimal residual disease (MRD) detection with this treatment. To address this, we studied 142 adults with ALL treated with hyperCVAD over a 10-year period who had MRD assessed by either multi-parameter flow cytometry or (for patients with Philadelphia chromosome positive ALL) reverse transcriptase polymerase chain reaction for the BCR-ABL1 translocation...
January 10, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29316944/car-t-cells-targeting-cll-1-as-an-approach-to-treat-acute-myeloid-leukemia
#5
Jinghua Wang, Siyu Chen, Wei Xiao, Wende Li, Liang Wang, Shuo Yang, Weida Wang, Liping Xu, Shuangye Liao, Wenjian Liu, Yang Wang, Nawei Liu, Jianeng Zhang, Xiaojun Xia, Tiebang Kang, Gong Chen, Xiuyu Cai, Han Yang, Xing Zhang, Yue Lu, Penghui Zhou
BACKGROUND: Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts...
January 10, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29310512/moxifloxacin-versus-levofloxacin-for-antibacterial-prophylaxis-in-acute-leukemia-patients
#6
Pauline Lee, Randall W Knoebel, Jennifer Pisano, Natasha N Pettit
Objective The primary endpoint of this study was to determine the incidence of febrile neutropenia among patients receiving either moxifloxacin or levofloxacin for antibacterial prophylaxis. Secondary endpoints were number of documented infections and in-hospital mortality in patients who develop febrile neutropenia. Methods A single-center retrospective cohort analysis at a large tertiary care academic medical center was conducted. This study included adult acute leukemia patients (age ≥18 years old) who received inpatient antibacterial prophylaxis (moxifloxacin or levofloxacin) from 1 July 2012 to 1 October 2014...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29310477/rituximab-in-the-management-of-acute-lymphoblastic-leukemia
#7
Luciano Levato, Stefano Molica
The anti-CD20 chimeric monoclonal antibody rituximab has revolutionized the treatment of B-cell malignancies, significantly improving patient clinical outcome. Recently, some single-group studies have suggested that adding rituximab to chemotherapy can improve the outcome of CD20-positive B-cell acute lymphoblastic leukemia (ALL) patients. Areas covered: An overview of the current insights of rituximab in adult ALL patients is presented here. In particular, we focused on results of multicenter randomized phase III trial (GRAALL-2005- Group for Research on Adult Acute Lymphoblastic Leukemia) that evaluated the benefit of associating rituximab to chemotherapy in Ph-negative, B-lineage ALL expressing the CD20 antigen...
January 9, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29305723/image-guided-ommaya-reservoir-insertion-for-intraventricular-chemotherapy-a-retrospective-series
#8
Jonathan C Lau, Suzanne E Kosteniuk, David R Macdonald, Joseph F Megyesi
BACKGROUND: Ayub Ommaya proposed a surgical technique for subcutaneous reservoir and pump placement in 1963 to allow access to intraventricular cerebrospinal fluid (CSF). Currently, the most common indication for Ommaya reservoir insertion (ORI) in adults is for patients with hematologic or leptomeningeal disorders requiring repeated injection of chemotherapy into the CSF space. Historically, the intraventricular catheter has been inserted blindly based on anatomical landmarks. The purpose of this study was to examine short-term complication rates with ORI with image guidance (IG) and without image guidance (non-IG)...
January 5, 2018: Acta Neurochirurgica
https://www.readbyqxmd.com/read/29304724/treatment-patterns-healthcare-resource-utilization-and-costs-in-patients-with-acute-myeloid-leukemia-in-commercially-insured-and-medicare-populations
#9
Eytan M Stein, Gaetano Bonifacio, Dominick Latremouille-Viau, Annie Guerin, Sherry Shi, Patrick Gagnon-Sanschagrin, Owanate Briggs, George J Joseph
OBJECTIVE: To describe the setting, duration, and costs of induction and consolidation chemotherapy for adults with newly diagnosed acute myeloid leukemia (AML), who are candidates for standard induction chemotherapy, in the United States. METHODS: Adults newly diagnosed with AML who received standard induction chemotherapy in an inpatient setting were identified from the Truven Health Analytics MarketScan (2006-2015) and SEER-Medicare (2007-2011) databases. Patients were observed from induction therapy start to the first of hematopoietic stem cell transplant, 180 days after induction discharge, health plan enrollment/data availability end, or death...
January 5, 2018: Journal of Medical Economics
https://www.readbyqxmd.com/read/29303026/risk-factors-for-impaired-pulmonary-function-and-cardiorespiratory-fitness-in-very-long-term-adult-survivors-of-childhood-acute-lymphoblastic-leukemia-after-treatment-with-chemotherapy-only
#10
Ole Henrik Myrdal, Adriani Kanellopoulos, Jon R Christensen, Ellen Ruud, Elisabeth Edvardsen, Johny Kongerud, Liv Ingunn Sikkeland, May B Lund
BACKGROUND: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk of late treatment-related side-effects. Data regarding prevalence and risk factors for impairments in pulmonary function and cardiorespiratory fitness are limited, and reported findings are inconsistent and inconclusive. MATERIAL AND METHODS: In a cross-sectional study, 116 ALL survivors (median 5 years at diagnosis, 29 years at follow-up, 53% females) were examined, median 23 years after treatment with chemotherapy only...
January 5, 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29302561/low-backache-in-adults-as-an-initial-presentation-of-acute-lymphoblastic-leukemia
#11
Gunjan Garg, Naveen Chawla, Atul Gogia, Atul Kakar
Low backache as an initial manifestation of acute lymphoblastic leukemia (ALL) in adults has been rarely reported. In this hematological disorder, although bone marrow is replaced by malignant cells, not many cases of low backache as an initial presentation of ALL are reported. We present a series of clinical cases with low backache, which on evaluation found to have ALL.
April 2017: Journal of Family Medicine and Primary Care
https://www.readbyqxmd.com/read/29301374/why-differentiation-therapy-sometimes-fails-molecular-mechanisms-of-resistance-to-retinoids
#12
REVIEW
Petr Chlapek, Viera Slavikova, Pavel Mazanek, Jaroslav Sterba, Renata Veselska
Retinoids represent a popular group of differentiation inducers that are successfully used in oncology for treatment of acute promyelocytic leukemia in adults and of neuroblastoma in children. The therapeutic potential of retinoids is based on their key role in the regulation of cell differentiation, growth, and apoptosis, which provides a basis for their use both in cancer therapy and chemoprevention. Nevertheless, patients treated with retinoids often exhibit or develop resistance to this therapy. Although resistance to retinoids is commonly categorized as either acquired or intrinsic, resistance as a single phenotypic feature is usually based on the same mechanisms that are closely related or combined in both of these types...
January 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29300724/a-novel-prospective-isolation-of-murine-fetal-liver-progenitors-to-study-in-utero-hematopoietic-defects
#13
Julia E Draper, Patrycja Sroczynska, Muhammad Z H Fadlullah, Rahima Patel, Gillian Newton, Wolfgang Breitwieser, Valerie Kouskoff, Georges Lacaud
In recent years, highly detailed characterization of adult bone marrow (BM) myeloid progenitors has been achieved and, as a result, the impact of somatic defects on different hematopoietic lineage fate decisions can be precisely determined. Fetal liver (FL) hematopoietic progenitor cells (HPCs) are poorly characterized in comparison, potentially hindering the study of the impact of genetic alterations on midgestation hematopoiesis. Numerous disorders, for example infant acute leukemias, have in utero origins and their study would therefore benefit from the ability to isolate highly purified progenitor subsets...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29296964/alternative-donors-for-allogeneic-hematopoietic-stem-cell-transplantation-in-poor-risk-aml-in-cr1
#14
Jurjen Versluis, Myriam Labopin, Annalisa Ruggeri, Gerard Socie, Depei Wu, Liisa Volin, Didier Blaise, Noel Milpied, Charles Craddock, Ibrahim Yakoub-Agha, Johan Maertens, Per Ljungman, Anne Huynh, Mauricette Michallet, Eric Deconinck, Patrice Chevallier, Jakob Passweg, Fabio Ciceri, Mohamad Mohty, Jan J Cornelissen, Arnon Nagler
Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the treatment of choice to consolidate remission in patients with poor-risk acute myeloid leukemia (AML). With increasing alternative donors available, the preferred donor or stem cell source is debated. We set out to study outcome in recipients of alloHSCT with poor-risk AML in first complete remission (CR1) by donor type. A total of 6545 adult patients with poor-risk AML in CR1 receiving an alloHSCT using matched related donor (MRD, n = 3511) or alternative donors, including 10/10 (n = 1959) or 9/10 matched unrelated donors (MUDs, n = 549), umbilical cord blood (UCB) grafts (n = 333), or haplo-identical (haplo) donors (n = 193) were compared...
February 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296959/somatic-mutations-in-children-with-gata2-associated-myelodysplastic-syndrome-who-lack-other-features-of-gata2-deficiency
#15
Kevin E Fisher, Amy P Hsu, Christopher L Williams, Hadi Sayeed, Brian Y Merritt, M Tarek Elghetany, Steven M Holland, Alison A Bertuch, Maria Monica Gramatges
Approximately 10% of children with primary myelodysplastic syndrome (MDS) have germ line GATA2 mutations, leading to the proposal that all children with primary MDS and certain cytogenetic findings, including monosomy 7, be tested for germ line GATA2 mutations regardless of family history or other clinical features associated with GATA2 deficiency. In adults with familial GATA2-MDS, those with somatic mutations in ASXL1 experience rapid disease progression to acute myeloid leukemia (AML) and poor prognosis after stem cell transplantation; however, the prevalence of somatic mutations in primary pediatric GATA2-MDS is unclear...
February 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296895/minimal-residual-disease-in-adult-all-technical-aspects-and-implications-for-correct-clinical-interpretation
#16
REVIEW
Monika Brüggemann, Michaela Kotrova
Nowadays, minimal residual disease (MRD) is accepted as the strongest independent prognostic factor in acute lymphoblastic leukemia (ALL). It can be detected by molecular methods that use leukemia-specific or patient-specific molecular markers (fusion gene transcripts, or immunoglobulin/T-cell receptor [IG/TR] gene rearrangements), and by multi-parametric flow cytometry. The sensitivity and specificity of these methods can vary across treatment time points and therapeutic settings. Thus, knowledge of the principles and limitations of each technology is of the utmost importance for correct interpretation of MRD results...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296818/genetic-association-with-b-cell-acute-lymphoblastic-leukemia-in-allogeneic-transplant-patients-differs-by-age-and-sex
#17
Alyssa I Clay-Gilmour, Theresa Hahn, Leah M Preus, Kenan Onel, Andrew Skol, Eric Hungate, Qianqian Zhu, Christopher A Haiman, Daniel O Stram, Loreall Pooler, Xin Sheng, Li Yan, Qian Liu, Qiang Hu, Song Liu, Sebastiano Battaglia, Xiaochun Zhu, AnneMarie W Block, Sheila N J Sait, Ezgi Karaesmen, Abbas Rizvi, Daniel J Weisdorf, Christine B Ambrosone, David Tritchler, Eva Ellinghaus, David Ellinghaus, Martin Stanulla, Jacqueline Clavel, Laurent Orsi, Stephen Spellman, Marcelo C Pasquini, Philip L McCarthy, Lara E Sucheston-Campbell
The incidence and mortality rates of B-cell acute lymphoblastic leukemia (B-ALL) differ by age and sex. To determine if inherited genetic susceptibility contributes to these differences we performed 2 genome-wide association studies (GWAS) by age, sex, and subtype and subsequent meta-analyses. The GWAS included 446 B-ALL cases, and 3027 healthy unrelated blood and marrow transplant (BMT) donors as controls from the Determining the Influence of Susceptibility Conveying Variants Related to One-Year Mortality after BMT (DISCOVeRY-BMT) study...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296792/a-4-lncrna-scoring-system-for-prognostication-of-adult-myelodysplastic-syndromes
#18
Chi-Yuan Yao, Ching-Hsuan Chen, Huai-Hsuan Huang, Hsin-An Hou, Chien-Chin Lin, Mei-Hsuan Tseng, Chein-Jun Kao, Tzu-Pin Lu, Wen-Chien Chou, Hwei-Fang Tien
Long noncoding RNAs (lncRNAs) not only participate in normal hematopoiesis but also contribute to the pathogenesis of acute leukemia. However, their clinical and prognostic relevance in myelodysplastic syndromes (MDSs) remains unclear to date. In this study, we profiled lncRNA expressions in 176 adult patients with primary MDS, and identified 4 lncRNAs whose expression levels were significantly associated with overall survival (OS). We then constructed a risk-scoring system with the weighted sum of these 4 lncRNAs...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296760/clonality-of-htlv-1-infected-t-cells-as-a-risk-indicator-for-development-and-progression-of-adult-t-cell-leukemia
#19
Sanaz Firouzi, Amir Farmanbar, Kenta Nakai, Masako Iwanaga, Kaoru Uchimaru, Atae Utsunomiya, Yutaka Suzuki, Toshiki Watanabe
Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) that develops along a carcinogenic process involving 5 or more genetic events in infected cells. The lifetime incidence of ATL among HTLV-1-infected individuals is approximately 5%. Although epidemiologic studies have revealed risk factors for ATL, the molecular mechanisms that determine the fates of carriers remain unclear. A better understanding of clonal composition and related longitudinal dynamics would clarify the process of ATL leukemogenesis and provide insights into the mechanisms underlying the proliferation of a malignant clone...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296758/inotuzumab-ozogamicin-in-adults-with-relapsed-or-refractory-cd22-positive-acute-lymphoblastic-leukemia-a-phase-1-2-study
#20
Daniel J DeAngelo, Wendy Stock, Anthony S Stein, Andrei Shustov, Michaela Liedtke, Charles A Schiffer, Erik Vandendries, Katherine Liau, Revathi Ananthakrishnan, Joseph Boni, A Douglas Laird, Luke Fostvedt, Hagop M Kantarjian, Anjali S Advani
This study evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of inotuzumab ozogamicin (InO) for CD22-positive relapsed/refractory acute lymphoblastic leukemia. In phase 1, patients received InO 1.2 (n = 3), 1.6 (n = 12), or 1.8 (n = 9) mg/m2 per cycle on days 1, 8, and 15 over a 28-day cycle (≤6 cycles). The recommended phase 2 dose (RP2D) was confirmed (expansion cohort; n = 13); safety and activity of InO were assessed in patients receiving the RP2D in phase 2 (n = 35) and in all treated patients (n = 72)...
June 27, 2017: Blood Advances
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