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Adult Acute Leukemia

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https://www.readbyqxmd.com/read/29149251/parental-age-and-risk-of-lymphoid-neoplasms
#1
Gunnar Larfors, Ingrid Glimelius, Sandra Eloranta, Karin E Smedby
High parental age at childbirth has repeatedly been linked to childhood malignancies, while few studies have focused on the offspring's risk of adult cancer. In this population-based case-control study, we identified 32,000 patients with lymphoid neoplasms, diagnosed at ages 0-79 years during the period 1987-2011, and 160,000 matched controls in Sweden. Using prospectively registered data on their first-degree relatives, we evaluated the impact of parental age on the risk of lymphoid neoplasms by subtype. Overall, each 5-year increment in maternal age was associated with a 3% increase in incidence of offspring lymphoid neoplasms (hazard ratio = 1...
November 15, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/29132164/mutational-spectrum-of-fanconi-anemia-associated-myeloid-neoplasms
#2
Mwe Mwe Chao, Kathrin Thomay, Gudrun Goehring, Marcin Wlodarski, Victor Pastor, Brigitte Schlegelberger, Detlev Schindler, Christian Peter Kratz, Charlotte Niemeyer
Individuals with Fanconi anemia (FA) have a high risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), yet the secondary somatic mutations lending to these malignancies remain to be further elucidated. We employed a next-generation sequencing myeloid neoplasia gene panel to determine the mutational spectrum of FA-related MDS/AML. Ten of 16 patients showed missense, nonsense, insertion or duplication mutations in 13 genes. In contrast to findings in MDS in the general population, mutations in genes involved in RNA splicing were rarely affected...
November 2017: Klinische Pädiatrie
https://www.readbyqxmd.com/read/29129488/dna-hypomethylating-agents-as-epigenetic-therapy-before-and-after-allogeneic-hematopoietic-stem-cell-transplantation-in-myelodysplastic-syndromes-and-juvenile-myelomonocytic-leukemia
#3
REVIEW
Christian Flotho, Sebastian Sommer, Michael Lübbert
Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents 5-azacytidine (azacitidine) or decitabine...
November 9, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29121606/pattern-of-hematological-malignancies-in-adolescents-and-young-adults-in-bangladesh
#4
Md Mahbub Hasan, Enayetur Raheem, Tanvira Afroze Sultana, Mohammad Sorowar Hossain
INTRODUCTION: The adolescent and young adult (AYA) age group (15-39 years) bears distinct characteristics in terms of cancer biology, long-term health and treatment-related complications and psychosocial aspects. The overall scenario of cancer including hematological malignancies (HMs) is largely unknown in Bangladesh, where a significant proportion of people (44% of total population) belong to AYA age group. This study aims to describe the patterns of HM among AYA in the context of Bangladesh METHODS: Two previously published datasets (on hematological malignancies and childhood and adolescent cancer) were merged to construct a comprehensive dataset focusing exclusively on HMs in AYA age group...
November 6, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/29119643/a-phase-i-study-of-lenalidomide-plus-chemotherapy-with-mitoxantrone-etoposide-and-cytarabine-for-the-reinduction-of-patients-with-acute-myeloid-leukemia
#5
Daniel J DeAngelo, Andrew M Brunner, Lillian Werner, David Avigan, Amir T Fathi, Adam S Sperling, Abigail Washington, Dina Stroopinsky, Jacalyn Rosenblatt, Malgorzata McMasters, Katarina Luptakova, Martha Wadleigh, David P Steensma, Gabriela S Hobbs, Eyal C Attar, Philip C Amrein, Benjamin L Ebert, Richard M Stone, Karen K Ballen
Patients with relapsed AML have a poor prognosis and limited responses to standard chemotherapy. Lenalidomide is an immunomodulatory drug that may modulate anti-tumor immunity. We performed a study to evaluate the safety and tolerability of lenalidomide with mitoxantrone, etoposide and cytarabine (MEC) in relapsed/refractory AML. Adult patients with relapsed/refractory AML were eligible for this phase I dose-escalation study. We enrolled 35 patients using a '3 + 3' design, with a 10 patient expansion cohort at the maximum tolerated dose (MTD)...
November 9, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29119293/asparaginase-erwinia-chrysanthemi-effectively-depletes-plasma-glutamine-in-adult-patients-with-relapsed-refractory-acute-myeloid-leukemia
#6
Ashkan Emadi, Jennie Y Law, Erin T Strovel, Rena G Lapidus, Linda J B Jeng, Myounghee Lee, Miriam G Blitzer, Brandon A Carter-Cooper, Danielle Sewell, Isabella Van Der Merwe, Sunita Philip, Mohammad Imran, Stephen L Yu, Hongxia Li, Philip C Amrein, Vu H Duong, Edward A Sausville, Maria R Baer, Amir T Fathi, Zeba Singh, Søren M Bentzen
Depletion of glutamine (Gln) has emerged as a potential therapeutic approach in the treatment of acute myeloid leukemia (AML), as neoplastic cells require Gln for synthesis of cellular components essential for survival. Asparaginases deplete Gln, and asparaginase derived from Erwinia chrysanthemi (Erwinaze) appears to have the greatest glutaminase activity of the available asparaginases. In this Phase I study, we sought to determine the dose of Erwinaze that safely and effectively depletes plasma Gln levels to ≤ 120 μmol/L in patients with relapsed or refractory (R/R) AML...
November 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29114972/frontline-therapy-of-acute-promyelocytic-leukemia-randomized-comparison-of-atra-and-intensified-chemotherapy-versus-atra-and-anthracyclines
#7
Eva Lengfelder, Dennis Görlich, Daniel Nowak, Karsten Spiekermann, Claudia Haferlach, Utz Krug, Karl-Anton Kreuzer, Jan Braess, Christoph Schliemann, Hans-Walter Lindemann, Heinz A Horst, Xaver Schiel, Michael Flasshove, Anna Hecht, Susanne Schnittger, Stephanie Schneider, Bernhard Wörmann, Wolf-Karsten Hofmann, Wolfgang E Berdel, Eike Bormann, Cristina Sauerland, Thomas Büchner, Wolfgang Hiddemann
OBJECTIVES: Randomized comparison of two treatment strategies in frontline therapy of acute promyelocytic leukemia (APL): all-trans retinoic acid (ATRA) and double induction intensified by high dose cytosine arabinoside (HD ara-C) (German AMLCG) and therapy with ATRA and anthracyclines (Spanish PETHEMA, LPA99). PATIENTS AND RESULTS: Eighty of 87 adult patients with genetically confirmed APL of all risk groups were eligible. The outcome of both arms was similar: AMLCG vs PETHEMA: hematological complete remission 87% vs 83%, early death 13% vs 17% (p=0...
November 7, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29113330/flow-cytometric-analysis-of-cd64-expression-pattern-and-density-in-the-diagnosis-of-acute-promyelocytic-leukemia-a-multi-center-study-in-shanghai-china
#8
Min Liu, Xiangqin Weng, Shenglan Gong, Hui Chen, Jing Ding, Mengqiao Guo, Xiaoxia Hu, Jianmin Wang, Jianmin Yang, Gusheng Tang
No unified immunophenotypic profiles and corresponding analytic strategies have been established for the rapid diagnosis of acute promyelocytic leukemia (APL) using flow cytometry (FCM). Here we describe a characteristic immunophenotypic panel that can rapidly and accurately distinguish APL from other types of adult acute myeloid leukemia (AML) using only FCM. By comparing APL cells and non-APL AML cells that share APL common immunophenotypes (CD34(-)CD117(+)HLA(-)DR(-)) we found that CD64 was a significant factor that differentiated APL from other AMLs...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29108368/phase-i-clinical-trial-of-the-base-excision-repair-inhibitor-methoxyamine-in-combination-with-fludarabine-for-patients-with-advanced-hematologic-malignancies
#9
Paolo F Caimi, Brenda W Cooper, Basem M William, Afshin Dowlati, Paul M Barr, Pingfu Fu, John Pink, Yan Xu, Hillard M Lazarus, Marcos de Lima, Stanton L Gerson
Purpose: We determined the safety, pharmacokinetics, pharmacodynamics and recommended phase II dose of the base excision repair blocker methoxyamine combined with fludarabine. Materials and Methods: This was a phase I study with intravenous fludarabine (25 mg/m(2), days 1-5), and methoxyamine (15 mg/m(2)-120 mg/m(2), once). A maximum of six cycles were given. Adult patients with relapsed/refractory hematologic malignancies, excluding acute myeloid leukemia, were eligible...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29102597/predictors-for-requiring-re-induction-chemotherapy-in-acute-myeloid-leukemia-patients-with-residual-disease-on-day-14-bone-marrow-assessment
#10
Victoria R Nachar, Anthony J Perissinotti, Gianni B Scappaticci, Dale L Bixby, Bernard L Marini
PURPOSE: Day 14 bone marrow (BM) biopsies following standard induction in acute myeloid leukemia (AML) have a suboptimal ability to predict complete remission (CR). The decision to administer re-induction chemotherapy with residual disease on day 14 is variable and lacks clear guidance. METHODS: We retrospectively compared clinical and laboratory characteristics of adult patients with newly diagnosed, previously untreated AML who underwent 3+7 induction chemotherapy from January 2004 until February 2017...
November 2, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29100287/nedd9-an-independent-good-prognostic-factor-in-intermediate-risk-acute-myeloid-leukemia-patients
#11
Victor Pallarès, Montserrat Hoyos, M Carmen Chillón, Eva Barragán, M Isabel Prieto Conde, Marta Llop, María Virtudes Céspedes, Josep F Nomdedeu, Salut Brunet, Miguel Ángel Sanz, Marcos González-Díaz, Jorge Sierra, Isolda Casanova, Ramon Mangues
Intermediate-risk acute myeloid leukemia (IR-AML) is the largest subgroup of AML patients and is highly heterogeneous. Whereas adverse and favourable risk patients have well-established treatment protocols, IR-AML patients have not. It is, therefore, crucial to find novel factors that stratify this subgroup to implement risk-adapted strategies. The CAS (Crk-associated substrate) adaptor protein family regulates cell proliferation, survival, migration and adhesion. Despite its association with metastatic dissemination and prognosis of different solid tumors, the role of these proteins in hematological malignancies has been scarcely evaluated...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29098619/the-positive-effects-of-exercise-in-chemotherapy-related-cardiomyopathy
#12
Cavarretta Elena, Mastroiacovo Giorgio, Lupieri Annik, Frati Giacomo, Peruzzi Mariangela
Anthracyclines such as doxorubicin, daunorubicin, epirubicin, mitoxantrone and idarubicin, are powerful chemotherapeutic drugs used both in children and adult populations. Their properties made them particularly suitable for a large variety of neoplasms including breast adenocarcinoma, small cell lung cancer and acute leukemia. Early and late anthracycline-induced cardiotoxicity is a well-known phenomenon, and the incidence of heart failure in patients receiving doxorubicin is 2.2%, with a mortality rate over 60% at 2 years...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29092647/inotuzumab-ozogamicin-for-the-treatment-of-acute-lymphoblastic-leukemia
#13
Ariella Tvito, Jacob M Rowe
Acute lymphoblastic leukemia (ALL) is an uncommon disorder that affects about 20% of adults with acute leukemia. Historically, those who relapse from this condition have a dismal prognosis. Recent developments in immunoconjugate usage has changed the landscape of lymphoid B-cell malignancy therapy. One recent development is the FDA approved therapy inotuzumab ozogamicin which has the potential to reduce the overall toxicity of intensive regimens for ALL, as well as to possibly increase the number of patients who may achieve a state of minimal residual disease...
November 1, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29090417/long-term-clinical-remission-maintained-after-cessation-of-zidovudine-and-interferon-%C3%AE-therapy-in-chronic-adult-t-cell-leukemia-lymphoma
#14
Lucy B Cook, Aileen G Rowan, Maria A Demontis, Sophie Sagawe, Nicolas A Gillet, Anat Melamed, Claire Greiller, Aviva Witkover, Charles R M Bangham, Graham P Taylor
Globally, > 5-10 million people are estimated to be infected with Human T-lymphotropic virus type 1 (HTLV-1), of whom ~ 5% develop adult T-cell leukemia/lymphoma (ATL). Despite advances in chemotherapy, overall survival (OS) has not improved in the 35 years since HTLV-1 was first described. In Europe/USA, combination treatment with zidovudine and interferon-α (ZDV/IFN-α) has substantially changed the management of patients with the leukemic subtypes of ATL (acute or unfavorable chronic ATL) and is under clinical trial evaluation in Japan...
October 31, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29090343/epidemiological-genetic-and-clinical-characterization-by-age-of-newly-diagnosed-acute-myeloid-leukemia-based-on-an-academic-population-based-registry-study-amlsg-bio
#15
Gabriele Nagel, D Weber, E Fromm, S Erhardt, M Lübbert, W Fiedler, T Kindler, J Krauter, P Brossart, A Kündgen, H R Salih, J Westermann, G Wulf, B Hertenstein, M Wattad, K Götze, D Kraemer, T Heinicke, M Girschikofsky, H G Derigs, H A Horst, C Rudolph, M Heuser, G Göhring, V Teleanu, L Bullinger, F Thol, V I Gaidzik, P Paschka, K Döhner, A Ganser, Hartmut Döhner, R F Schlenk
We describe genetic and clinical characteristics of acute myeloid leukemia (AML) patients according to age from an academic population-based registry. Adult patients with newly diagnosed AML at 63 centers in Germany and Austria were followed within the AMLSG BiO registry (NCT01252485). Between January 1, 2012, and December 31, 2014, data of 3525 patients with AML (45% women) were collected. The median age was 65 years (range 18-94). The comparison of age-specific AML incidence rates with epidemiological cancer registries revealed excellent coverage in patients < 70 years old and good coverage up to the age of 80...
October 31, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29089774/adult-acute-megakaryoblastic-leukemia-rare-association-with-cytopenias-of-undetermined-significance-and-p210-and-p190-bcr-abl-transcripts
#16
Delia Dima, Liana Oprita, Ana-Maria Rosu, Adrian Trifa, Cristina Selicean, Vlad Moisoiu, Ioana Frinc, Mihnea Zdrenghea, Ciprian Tomuleasa
Acute megakaryocytic leukemia (M7-AML) is a rare form of acute myeloid leukemia (AML), which is associated with poor prognosis. The case presented in the current report is a statement for the difficult diagnosis and clinical management of M7-AML in the context of a previous hematologic disorder of undetermined significance and associated genetic abnormalities. Probably, following the complete hematologic remission and further with induction chemotherapy plus tyrosine kinase inhibitor therapy, the clinical management of this case will be followed by a allogeneic bone marrow transplantation, the only proven therapy to improve overall survival...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29089643/targeting-acute-myeloid-leukemia-by-drug-induced-c-myb-degradation
#17
V Walf-Vorderwülbecke, K Pearce, T Brooks, M Hubank, M M van den Heuvel-Eibrink, C M Zwaan, S Adams, D Edwards, J Bartram, S Samarasinghe, P Ancliff, A Khwaja, N Goulden, G Williams, J de Boer, O Williams
Despite advances in our understanding of the molecular basis for particular subtypes of acute myeloid leukemia (AML), effective therapy remains a challenge for many individuals suffering from this disease. A significant proportion of both pediatric and adult AML patients cannot be cured and since the upper limits of chemotherapy intensification have been reached, there is an urgent need for novel therapeutic approaches. The transcription factor c-MYB has been shown to play a central role in the development and progression of AML driven by several different oncogenes, including mixed lineage leukemia (MLL)-fusion genes...
November 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29082835/efficacy-and-safety-of-bispecific-t-cell-engager-blinatumomab-and-the-potential-to-improve-leukemia-free-survival-in-b-cell-acute-lymphoblastic-leukemia
#18
Josep-Maria Ribera
Immunotherapy is a promising modality of treatment of neoplastic diseases, including acute lymphoblastic leukemia (ALL). The CD19/CD3-bispecific T cell-engaging (BiTE®) monoclonal antibody blinatumomab can transiently bind cytotoxic T cells to CD19(+) target B cells of ALL inducing their serial lysis. Areas covered: This review focuses on the efficacy and safety of blinatumomab used for the treatment of relapsed/refractory (R/R) ALL and minimal residual disease (MRD)-positive B-cell precursor (BCP) ALL in adults and children, as well as the future prospects of this drug in the treatment of ALL...
October 30, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/29079128/dnmt3a-r882-mutation-features-and-prognostic-effect-in-acute-myeloid-leukemia-in-coexistent-with-npm1-and-flt3-mutations
#19
Dushyant Kumar, Anurag Mehta, Manoj Kumar Panigrahi, Sukanta Nath, Kandarpa Kumar Saikia
OBJECTIVE/BACKGROUND: In the absence of high-risk cytogenetic, DNMT3A mutation status has an impact on outcome in the presence of FLT3 and/or NPM1. In this study, we focus on the features and effect of DNMT3A (R882) mutation in acute myeloid leukemia (AML) in the presence or absence of NPM1 and FLT3 mutations. METHODS: A total of 174 cytogenetically normal (CN)-AML cases were analyzed for NPM1, FLT3, and DNMT3A mutations. For NPM1 mutation detection, we used the pyrosequencing technique; for FLT3 mutations, polymerase chain reaction and RFLP with ECO-RV techniques were used, and for DNMT3A mutation analysis, we used Sanger sequencing and RFLP techniques...
October 18, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/29076004/high-mtor-expression-independently-prognosticates-poor-clinical-outcome-to-induction-chemotherapy-in-acute-lymphoblastic-leukemia
#20
Asheema Khanna, Bharat Bhushan, Pradeep Singh Chauhan, Sunita Saxena, Dipendra Kumar Gupta, Fouzia Siraj
In acute lymphoblastic leukemia (ALL), limited data are available on mTOR gene expression in clinical samples and its role in predicting response to induction chemotherapy. mRNA expression of mTOR gene was determined quantitatively by real-time PCR in 50 ALL patients (30 B-ALL and 20 T-ALL) and correlated with clinical outcome after induction chemotherapy. Expression level of mTOR was upregulated in more than 50% of cases of ALL. In T-ALL, high expression of mTOR was commonly seen, more in adults than children (82 vs...
October 26, 2017: Clinical and Experimental Medicine
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