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Adult Acute Leukemia

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https://www.readbyqxmd.com/read/28318489/deletion-of-the-mad2l1-spindle-assembly-checkpoint-gene-is-tolerated-in-mouse-models-of-acute-t-cell-lymphoma-and-hepatocellular-carcinoma
#1
Floris Foijer, Lee A Albacker, Bjorn Bakker, Diana C Spierings, Ying Yue, Stephanie Z Xie, Stephanie H Davis, Annegret Lutum-Jehle, Darin Takemoto, Brian Hare, Brinley Furey, Roderick T Bronson, Peter M Lansdorp, Allan Bradley, Peter K Sorger
Chromosome instability (CIN) is deleterious to normal cells because of the burden of aneuploidy. However, most human solid tumors have an abnormal karyotype implying that gain and loss of chromosomes by cancer cells confers a selective advantage. CIN can be induced in the mouse by inactivating the spindle assembly checkpoint. This is lethal in the germline but we show here that adult T cells and hepatocytes can survive conditional inactivation of the Mad2l1 SAC gene and resulting CIN. This causes rapid onset of acute lymphoblastic leukemia (T-ALL) and progressive development of hepatocellular carcinoma (HCC), both lethal diseases...
March 20, 2017: ELife
https://www.readbyqxmd.com/read/28318150/expression-of-cd4-is-correlated-with-an-unfavorable-prognosis-in-wild-type-npm1-flt3-itd-negative-cytogenetically-normal-adult-acute-myeloid-leukemia
#2
R J Guo, E G Atenafu, A D Schimmer, M D Minden, H Chang
INTRODUCTION: In the cytogenetically normal population of AML (CN-AML), FLT3-ITD-positive and wild-type NPM1 is correlated with a worse outcome, and FLT3-ITD-negative with NPM1-mut is correlated with a better outcome. This leaves a large subpopulation of CN-AML patients without NPM1 or FLT3-ITD mutations with heterogeneous outcomes with overall survivals (OS) ranging from several weeks to years. Therefore, new prognostic markers are needed to better risk stratify this subset of patients...
March 20, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28315529/self-reported-distress-adult-acute-leukemia-survivors-during-and-after-induction-therapy
#3
Joanne L Lester, Robin Stout, Kara Crosthwaite, Barbara L Andersen
BACKGROUND: Data suggest that acute leukemia survivors experience moderate to severe distress that does not significantly decline from diagnosis through survivorship.
. OBJECTIVES: The purpose of this study is to assess acute leukemia survivors' level and source of self-reported distress from active cancer treatment through six months post-treatment.
. METHODS: A cross-sectional group-comparison design was used. Male (n = 60) and female (n = 40) survivors aged 19-84 years were accrued from a National Cancer Institute-designated cancer center...
April 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28302711/precision-and-prognostic-value-of-clone-specific-minimal-residual-disease-in-acute-myeloid-leukemia
#4
Pierre Hirsch, Ruoping Tang, Nassera Abermil, Pascale Flandrin, Hannah Moatti, Fabrizia Favale, Ludovic Suner, Florence Lorre, Christophe Marzac, Fanny Fava, Anne-Claire Mamez, Simona Lapusan, Françoise Isnard, Mohamad Mohty, Ollivier Legrand, Luc Douay, Chrystele Bilhou-Nabera, François Delhommeau
The genetic landscape of adult acute myeloid leukemias has been recently unraveled. However, due to their genetic heterogeneity, only a handful of markers are currently used for the evaluation of minimal residual disease. Recent studies using multi-target strategies indicate that detection of residual mutations in less than 5% of cells in complete remission is associated with a better survival. Here, in a series of 69 acute myeloid leukemias with known clonal architecture, we design a clone-specific strategy based on fluorescent in situ hybridization and high-sensitivity next generation sequencing to detect chromosomal aberrations and mutations, respectively, in follow-up samples...
March 16, 2017: Haematologica
https://www.readbyqxmd.com/read/28297628/genetic-basis-of-acute-lymphoblastic-leukemia
#5
Ilaria Iacobucci, Charles G Mullighan
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and despite cure rates exceeding 90% in children, it remains an important cause of morbidity and mortality in children and adults. The past decade has been marked by extraordinary advances into the genetic basis of leukemogenesis and treatment responsiveness in ALL. Both B-cell and T-cell ALL comprise multiple subtypes harboring distinct constellations of somatic structural DNA rearrangements and sequence mutations that commonly perturb lymphoid development, cytokine receptors, kinase and Ras signaling, tumor suppression, and chromatin modification...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28295989/pharmacokinetics-of-two-6-mercaptopurine-liquid-formulations-in-children-with-acute-lymphoblastic-leukemia
#6
Jaszianne A Tolbert, Shasha Bai, Susan M Abdel-Rahman, Keith J August, Scott J Weir, Gregory L Kearns, Kathleen A Neville
BACKGROUND: A liquid formulation of 6-mercaptopurine (6-MP) was recently approved by the Food and Drug Administration (Purixan®) based on bioavailability (BA) data from healthy adults. We examined the pharmacokinetics (PK) and BA of 6-MP in children with acute lymphoblastic leukemia (ALL) comparing a marketed tablet, two extemporaneously prepared liquid formulations, and data from the approved liquid formulation. METHODS: Twenty-two children (6-17 years) participated in a randomized two-way, crossover study of two cohorts...
March 10, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28294102/fms-like-tyrosine-kinase-3-flt3-and-nucleophosmin-1-npm1-in-iranian-adult-acute-myeloid-leukemia-aml-patients-with-normal-karyotype-mutation-status-and-clinical-and-laboratory-characteristics
#7
Narges Rezaei, Nargess Arandi, Behnaz Valibeigi, Sezaneh Haghpanah, Mehdi Khansalar, Mani Ramzi
No abstract text is available yet for this article.
March 15, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28293819/characteristics-features-and-factors-influencing-early-death-in-acute-promyelocytic-leukemia-experience-from-united-arab-emirates-uae
#8
Inaam Bashir Hassan, Mariam R Al Zaabi, Arif Alam, Mohammed Jawad Hashim, Martin S Tallman, Jorgen Kristensen
Although acute promyelocytic leukemia (APL) is a curable hematologic malignancy, early death (ED) remains a significant cause of treatment failure especially in developing countries. In a retrospective data analysis of 67 adult APL patients diagnosed in United Arab Emirates we report an ED rate of 11.9% which is comparable to that reported from more developed countries. We identified the following parameters at presentation as significant predictor of increased ED: Age >40 years (P = 0.015), fever (P = 0...
March 14, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28293403/hydroxycarbamine-from-an-old-drug-used-in-malignant-hemopathies-to-a-current-standard-in-sickle-cell-disease
#9
REVIEW
Giovanna Cannas, Solène Poutrel, Xavier Thomas
While hydroxycarbamide (hydroxyurea, HU) has less and fewer indications in malignant hemopathies, it represents the only widely used drug which modifies sickle cell disease pathogenesis. Clinical experience with HU for patients with sickle cell disease has been accumulated over the past 25 years in Western countries. The review of the literature provides increasing support for safety and efficacy in both children and adults for reducing acute vaso-occlusive events including pain episodes and acute chest syndrome...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28286924/treatment-of-relapsed-refractory-acute-myeloid-leukemia
#10
REVIEW
Prithviraj Bose, Pankit Vachhani, Jorge E Cortes
Approximately 40-45% of younger and 10-20% of older adults with acute myeloid leukemia (AML) will be cured with current standard chemotherapy. The outlook is particularly gloomy for patients with relapsed and/or refractory disease (cure rates no higher than 10%). Allogeneic hematopoietic stem cell transplantation (HSCT), the only realistic hope of cure for these patients, is an option for only a minority. In recent years, much has been learned about the genomic and epigenomic landscapes of AML, and the clonal architecture of both de novo and secondary AML has begun to be unraveled...
March 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28286907/hypomethylating-agents-as-a-therapy-for-aml
#11
REVIEW
Claude Gardin, Hervé Dombret
Acute myeloid leukemia (AML) is predominantly a disease of older adults associated with poor long-term outcomes with available therapies. Used as single agents, hypomethylating agents (HMAs) induce only 15 to 25% complete remissions, but current data suggest that median OS observed after HMAs is comparable to that observed after more intensive therapies. Whether long-term cure may be obtained in some patients treated with HMAs is unknown. Combinations of HMAs to novel agents are now extensively investigated and attractive response rates have been reported when combining HMAs to different drug classes...
March 13, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28286617/allogeneic-hematopoietic-stem-cell-transplantation-for-adult-acute-lymphoblastic-leukemia-results-from-a-single-center-1993-2011
#12
Ipek Yonal-Hindilerden, Sevgi Kalayoglu-Besisik, Nuray Gurses-Koc, Fehmi Hindilerden, Deniz Sargin
Background: For adult ALL patients, the indications and appropriate timing of allogeneic hematopoietic stem cell transplantation (AHSCT) continue to be debated. The primary aim of this single-institution study was to compare the results of our adult ALL patients that had been allografted with those reported in the current literature. Subjects and Methods: This study included 53 consecutive adults with acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic stem cell transplantation (AHSCT) with myeloablative (92%) and reduced-intensity (8%) conditioning between 1993 and 2011...
January 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28282510/cxcr4-cd184-expression-on-stem-cell-harvest-and-cd34-cells-post-transplant
#13
Inas Asfour, Hanaa Afify, Shaza Elkourashy, Maryse Ayoub, Gihan Kamal, Mary Gamal, Ghada Elgohary
OBJECTIVES/BACKGROUND: CXCR4 is a receptor for stromal-derived factor-1 (SDF-1), a molecule that has a chemotactic activity for lymphocytes and is important in homing of hematopoietic stem cells to their adult marrow. We evaluated the CXCR4 (CD184) expression in the harvest cells and in the post-transplant bone marrow (BM) and its relation to engraftment, as determined by the consensus criteria and chimerism. METHODS: This is a prospective study which included 30 patients undergoing hematopoietic stem cell transplantation; 15 patients received autograft and 15 patients received allograft on dates between January 2012 and May 2014...
March 2, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28282218/immunotoxins-in-cancer-therapy-review-and-update
#14
Bahman Akbari, Safar Farajnia, Shiva Ahdi Khosroshahi, Fatemeh Safari, Mohammadreza Yousefi, Hassan Dariushnejad, Leila Rahbarnia
Immunotoxins are a novel class of cancer therapeutics that contains a cytotoxic agent fused to a targeting moiety. Various toxic agents from different sources are used in immunotoxin development, including bacterial, plant and human origin cytotoxic elements. Although bacterial and plant-derived toxins are highly toxic and commonly used in immunotoxins, their immunogenicity for human restricted their application in cancer therapy. Here, we discuss the advantages and limitations of bacterial toxins such as Pseudomonas and Diphtheria toxins, plant toxins such as ricin and gelonin, and some endogenous protein of human origin such as RNases and Granzymes...
March 1, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28274393/low-dose-cranial-boost-in-high-risk-adult-acute-lymphoblastic-leukemia-patients-undergoing-bone-marrow-transplant
#15
William Su, Marcher Thompson, Ren-Dih Sheu, Amir Steinberg, Luis Isola, Richard Stock, Richard L Bakst
PURPOSE: Acute lymphoblastic leukemia (ALL) has a predilection for CNS involvement. Patients with high-risk ALL are often managed with transplant using a radiation-based conditioning regimen. Historically, a high-dose prophylactic cranial boost (CB) of ≥12 Gy was given to reduce risk of central nervous system (CNS) recurrence. However, the use of CB has fallen out of favor because of toxicity concerns. In high-risk adults undergoing transplant at our institution, we have used a low-dose 6 Gy CB to reduce toxicity while conditioning adults with fully developed brains...
March 2017: Practical Radiation Oncology
https://www.readbyqxmd.com/read/28272704/a-minicircuitry-comprised-of-microrna-9-and-sirt1-contributes-to-leukemogenesis-in-t-8-21-acute-myeloid-leukemia
#16
L Zhou, L Fu, N Lv, X-S Chen, J Liu, Y Li, Q-Y Xu, S Huang, X-D Zhang, L-P Dou, L L Wang, Y-H Li, L Yu
OBJECTIVE: The AML1-ETO fusion protein (AE) resulting from the t(8;21) translocation is highly related to the pathogenesis and development of leukemia. microRNA-9 (miR-9) acts as a tumor suppressor gene in AE-positive acute myeloid leukemia (AML). Silent mating type information regulation 2 homolog-1 (SIRT1) is overexpressed in most cancer cells by increasing proliferation as a tumorigenic gene. The present study was performed to investigate the underlying interaction between miR-9 and SIRT1 in AE-positive AML...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28270734/successful-treatment-of-gastrointestinal-mucormycosis-in-an-adult-with-acute-leukemia-case-report-and-literature-review
#17
A Alghamdi, A Lutynski, M Minden, C Rotstein
Mucormycosis has emerged as an important cause of invasive fungal infection in patients with hematologic malignancies. Gastrointestinal mucormycosis is an unusual presentation of this invasive fungal infection, and it causes considerable morbidity and mortality. Such outcomes are due in part to a nonspecific presentation that results in delays in diagnosis and treatment. Successful treatment of gastrointestinal mucormycosis involves surgical debridement and appropriate antifungal therapy.
February 2017: Current Oncology
https://www.readbyqxmd.com/read/28270453/activation-of-the-lmo2-oncogene-through-a-somatically-acquired-neomorphic-promoter-in-t-cell-acute-lymphoblastic-leukemia
#18
Sunniyat Rahman, Michael Magnussen, Theresa E León, Nadine Farah, Zhaodong Li, Brian J Abraham, Krisztina Z Alapi, Rachel J Mitchell, Tom Naughton, Adele K Fielding, Arnold Pizzey, Sophia Bustraan, Christopher Allen, Teodora Popa, Karin Pike-Overzet, Laura Garcia-Perez, Rosemary E Gale, David C Linch, Frank J T Staal, Richard A Young, A Thomas Look, Marc R Mansour
Somatic mutations within non-coding genomic regions that aberrantly activate oncogenes have remained poorly characterized. Here we describe recurrent activating intronic mutations of LMO2, a prominent oncogene in T-cell acute lymphoblastic leukemia (T-ALL). Heterozygous mutations were identified in PF-382 and DU.528 T-ALL cell lines, in addition to 3.7% (6/160) of pediatric and 5.5% (9/163) of adult T-ALL patient samples. The majority of indels harbour putative de novo MYB, ETS1 or RUNX1 consensus binding sites...
March 7, 2017: Blood
https://www.readbyqxmd.com/read/28270346/molecular-and-hematologic-relapses-in-adult-patients-with-acute-promyelocytic-leukemia-a-cohort-study
#19
Ilana de França Azevedo, Michelline Gomes Magalhães, Fernanda Ribeiro Souto, Washington Batista das Neves, Fárida Coeli de Barros Correia Melo, Eduardo Magalhães Rego, Raul Antônio Morais Melo
OBJECTIVE: To evaluate factors predictive for relapse in a cohort of adult patients with acute promyelocytic leukemia monitored by molecular methods during consolidation and during at least one month of maintenance therapy. METHODS: The charts and laboratory data of 65 adult patients with acute promyelocytic leukemia treated according to the International Consortium on Acute Promyelocytic Leukemia 2006 protocol were reviewed. The identification of the promyelocytic leukemia-retinoic acid receptor-alpha gene rearrangement at diagnosis, post-induction, post-consolidation and during maintenance treatment was performed by qualitative and quantitative reverse transcription polymerase chain reaction...
January 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/28270340/adult-t-cell-leukemia-lymphoma-treatment-in-bahia-brazil
#20
Pedro Dantas Oliveira, Ítala Gomes, Victor Hugo Gomes Souza, Ernesto Cunha Pires, Glória Bomfim Arruda, Achiléa Bittencourt
BACKGROUND: Adult T-cell leukemia/lymphoma is a peripheral disease associated with human T-cell lymphotropic virus type 1. Treatment is carried out according to clinical type with watchful waiting being recommended for less aggressive types. Aggressive adult T-cell leukemia/lymphoma is generally treated with chemotherapy and/or antivirals. The objective of this study was to correlate the survival of patients diagnosed in Bahia, Brazil, with the therapeutic approaches employed and to evaluate what issues existed in their treatment processes...
January 2017: Revista Brasileira de Hematologia e Hemoterapia
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