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https://www.readbyqxmd.com/read/27916512/impact-of-conditioning-regimen-on-outcomes-for-children-with-acute-myeloid-leukemia-transplanted-in-first-complete-remission-an-analysis-on-behalf-of-the-pediatric-disease-working-party-of-the-ebmt
#1
G Lucchini, M Labopin, E Beohou, A Dalissier, J H Dalle, J Cornish, M Zecca, S Samarasinghe, B Gibson, F Locatelli, Y Bertrand, F Abdel-Rahman, G Socie', M Sundin, A Lankester, P Sedlacek, R M Hamladji, C Heilmann, B Afanasyev, R Hough, C Peters, P Bader, P Veys
HSCT represents the cornerstone of treatment in pediatric high risk and relapsed AML. The aim of the present study was to compare outcomes of pediatric AML patients undergoing HSCT using three different conditioning regimens: TBI and cyclophosphamide (TBI-Cy), Busulfan and Cyclophosphamide (BuCy) or Busulfan, Cyclophosphamide and Melphalan (BuCyMel). In this retrospective study, registry data for pts>2 and <18 yrs age undergoing matched allogeneic HSCT for AML in CR1 in 204 EBMT Centres between 2000 and 2010 were analyzed...
December 1, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27915304/invasive-aspergillosis-in-acute-myeloid-leukemia-are-we-making-progress-in-reducing-mortality
#2
Giulia Dragonetti, Marianna Criscuolo, Luana Fianchi, Livio Pagano
The incidence of invasive fungal disease (IFD) has varied during the last decades. However, over the years, we have observed a progressive reduction of mortality, mainly due to wider use of prophylactic antifungal therapy (i.e., new azoles, such as posaconazole), the development of new and more effective antifungal drugs (lipid compounds of amphotericin B, candins, and azoles of the previous generation) and improvement of diagnostic tools. Based on a number of international studies across three decades, the attributable mortality rate for IFD and invasive aspergillosis (IA) among patients with acute myeloid leukemia (AML) has progressively declined...
December 2, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/27914967/survival-advantage-and-comparable-toxicity-in-reduced-toxicity-treosulfan-based-vs-reduced-intensity-busulfan-based-conditioning-regimen-in-mds-and-aml-patients-post-allogeneic-hematopoietic-cell-transplantation
#3
Ioanna Sakellari, Despina Mallouri, Eleni Gavriilaki, Ioannis Batsis, Maria Kaliou, Varnavas Constantinou, Apostolia Papalexandri, Chrysavgi Lalayanni, Chrysanthi Vadikolia, Anastasia Athanasiadou, Evangelia Yannaki, Damianos Sotiropoulos, Christos Smias, Achilles Anagnostopoulos
Treosulfan has been incorporated in conditioning regimens for sustained remissions without substantial toxicity and treatment related mortality (TRM). We aimed to analyze the safety and efficacy of FluTreo conditioning regimen (fludarabine 150mg/m(2), treosulfan 42g/m(2)) in medically infirm patients. Patients' outcome was compared with a similar historical group treated with FluBuATG (fludarabine 150-180mg/m(2), busulfex 6.4mg/Kg, thymoglobulin-ATG 5-7.5mg/kg). Thirty one consecutive patients suffering from AML (21), MDS (6) or treatment-related AML (4) received FluTreo conditioning...
November 30, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27911138/phase-1-dose-escalation-study-of-oral-abexinostat-for-the-treatment-of-patients-with-relapsed-refractory-higher-risk-myelodysplastic-syndromes-acute-myeloid-leukemia-or-acute-lymphoblastic-leukemia
#4
Norbert Vey, Thomas Prebet, Claire Thalamas, Aude Charbonnier, Jerome Rey, Ioana Kloos, Emily Liu, Ying Luan, Remus Vezan, Thorsten Graef, Christian Recher
Histone deacetylase (HDAC) inhibitor abexinostat is under investigation for the treatment of various cancers. Epigenetic changes including aberrant HDAC activity are associated with cancers, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). In this phase 1 dose-escalation study, 17 patients with relapsed/refractory higher-risk MDS, AML, or ALL received oral abexinostat (60, 80 [starting dose], 100, or 120 mg) twice daily (bid) on Days 1-14 of 21-day cycles...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27908880/an-anti-cd3-anti-cll-1-bispecific-antibody-for-the-treatment-of-acute-myeloid-leukemia
#5
Steven R Leong, Siddharth Sukumaran, Maria Hristopoulos, Klara Totpal, Shannon Stainton, Elizabeth Lu, Alfred Wong, Lucinda Tam, Robert Newman, Brian R Vuillemenot, Diego Ellerman, Chen Gu, Mary Mathieu, Mark S Dennis, Allen Nguyen, Bing Zheng, Crystal Zhang, Genee Lee, Yu-Waye Chu, Rodney A Prell, Kedan Lin, Steven T Laing, Andrew G Polson
Acute myeloid leukemia (AML) is major unmet medical need. Most patients have poor long-term survival and treatment has not significantly changed in 40 years. Recently, bispecific antibodies that redirect the cytotoxic activity of effector T-cells by binding to CD3, the signaling component of the T-cell receptor, and a tumor target have shown clinical activity. Notably, blinatumomab is approved to treat relapsed/refractory acute lymphoid leukemia. Here we describe the design, discovery, pharmacological activity, pharmacokinetics, and safety of a CD3 T-cell-dependent bispecific (TDB) full-length human IgG1 therapeutic antibody targeting CLL-1 that could potentially be used in humans to treat AML...
December 1, 2016: Blood
https://www.readbyqxmd.com/read/27904446/somatic-mutations-of-isocitrate-dehydrogenases-1-and-2-are-prognostic-and-follow-up-markers-in-patients-with-acute-myeloid-leukaemia-with-normal-karyotype
#6
Marijana Virijevic, Teodora Karan-Djurasevic, Irena Marjanovic, Natasa Tosic, Mirjana Mitrovic, Irena Djunic, Natasa Colovic, Ana Vidovic, Nada Suvajdzic-Vukovic, Dragica Tomin, Sonja Pavlovic
BACKGROUND: Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up. PATIENTS AND METHODS: In our study samples from 110 adult de novo AML-NK were studied for the presence of IDH1 and IDH2 mutations, their associations with other prognostic markers and disease outcome...
December 1, 2016: Radiology and Oncology
https://www.readbyqxmd.com/read/27893163/sorafenib-and-azacitidine-as-salvage-therapy-for-relapse-of-flt3-itd-mutated-aml-after-allo-sct
#7
Christina Rautenberg, Kathrin Nachtkamp, Ariane Dienst, Pia Verena Schmidt, Claudia Heyn, Mustafa Kondakci, Ulrich Germing, Rainer Haas, Guido Kobbe, Thomas Schroeder
OBJECTIVE: Patients with acute myeloid leukemia (AML) carrying FLT3-ITD mutations (FLT3-ITD+) who relapse after allogeneic 3transplantation (allo-SCT) have a very dismal prognosis with the currently available treatment options. METHODS: We treated 8 patients with FLT3-ITD+ AML who had relapsed in median 91 days (range, 28 - 249) following allo-SCT with a combination of the multikinase inhibitor Sorafenib and the DNA methyltransferase inhibitor Azacitidine (Aza)...
November 28, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27881579/a-mirnas-dnmt1-axis-is-involved-in-azacitidine-resistance-and-predicts-survival-in-higher-risk-myelodysplastic-syndrome-and-low-blast-count-acute-myeloid-leukemia
#8
Françoise Solly, Catherine Koering, Aminetou Mint-Mohamed, Delphinne Maucort-Boulch, Guillaume Robert, Patrick Auberger, Pascale Flandrin-Gresta, Lionel Ades, Pierre Fenaux, Olivier Kosmider, Emmanuelle Tavernier-Tardy, Jerome Cornillon, Denis Guyotat, Lydia Lydia Campos, Franck Mortreux, Eric Wattel
PURPOSE: Azacitidine (AZA) inhibits DNA methyltransferases, including DNMT1, and is currently the standard of care for patients with higher risk myelodysplastic syndrome (HRMDS) or low blast count AML (AML). EXPERIMENTAL DESIGN: The expression of 754 microRNAs (miRNAs) was compared in AZA-resistant and AZA-sensitive MDS cells. We investigated the role of differentially expressed miRNAs on DNMT1 expression and AZA-resistance in vitro. We next evaluated anti-DNMT1 miRNAs expression in pretreatment bone marrow samples deriving from 75 patients treated with AZA for HRMDS or AML...
November 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27879990/sequential-chemotherapy-followed-by-reduced-intensity-conditioning-and-allogeneic-haematopoietic-stem-cell-transplantation-in-adult-patients-with-relapse-or-refractory-acute-myeloid-leukaemia-a-survey-from-the-acute-leukaemia-working-party-of-ebmt
#9
Olle Ringdén, Myriam Labopin, Christoph Schmid, Behnam Sadeghi, Emmanuelle Polge, Johanna Tischer, Arnold Ganser, Mauricette Michallet, Lothar Kanz, Rainer Schwerdtfeger, Arnon Nagler, Mohamad Mohty
This study analysed the outcome of 267 patients with relapse/refractory acute myeloid leukaemia (AML) who received sequential chemotherapy including fludarabine, cytarabine and amsacrine followed by reduced-intensity conditioning (RIC) and allogeneic haematopoietic stem cell transplantation (HSCT). The transplants in 77 patients were from matched sibling donors (MSDs) and those in 190 patients were from matched unrelated donors. Most patients (94·3%) were given anti-T-cell antibodies. The incidence of acute graft-versus-host disease (GVHD) of grades II-IV was 32·1% and that of chronic GVHD was 30·2%...
November 23, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27872732/minimal-residual-disease-in-acute-myeloid-leukemia-of-adults-determination-prognostic-impact-and-clinical-applications
#10
REVIEW
Maria Ilaria Del Principe, Francesco Buccisano, Luca Maurillo, Giuseppe Sconocchia, Mariagiovanna Cefalo, Maria Irno Consalvo, Chiara Sarlo, Consuelo Conti, Giovanna De Santis, Eleonora De Bellis, Ambra Di Veroli, Patrizia Palomba, Cristina Attrotto, Annagiulia Zizzari, Giovangiacinto Paterno, Maria Teresa Voso, Giovanni Del Poeta, Francesco Lo-Coco, William Arcese, Sergio Amadori, Adriano Venditti
Pretreatment assessment of cytogenetic/genetic signature of acute myeloid leukemia (AML) has been consistently shown to play a major prognostic role but also to fail at predicting outcome on individual basis, even in low-risk AML. Therefore, we are in need of further accurate methods to refine the patients' risk allocation process, distinguishing more adequately those who are likely to recur from those who are not. In this view, there is now evidence that the submicroscopic amounts of leukemic cells (called minimal residual disease, MRD), measured during the course of treatment, indicate the quality of response to therapy...
2016: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/27872058/a-randomised-assessment-of-adding-the-kinase-inhibitor-lestaurtinib-to-1st-line-chemotherapy-for-flt3-mutated-aml
#11
Steven Knapper, Nigel Russell, Amanda Gilkes, Robert K Hills, Rosemary E Gale, James D Cavenagh, Gail Jones, Lars Kjeldsen, Michael R Grunwald, Ian Thomas, Heiko Konig, Mark J Levis, Alan K Burnett
The clinical benefit of adding FLT3-directed small molecule therapy to standard first-line treatment of acute myeloid leukemia (AML) has not yet been established. As part of the UK AML15 and 17 trials, patients with previously-untreated AML and confirmed FLT3-activating mutations, mostly aged <60 years, were randomised to receive oral Lestaurtinib (CEP701), or not, following each of four cycles of induction and consolidation chemotherapy. Lestaurtinib was commenced 2 days after completing chemotherapy and administered in cycles of up to 28 days...
November 21, 2016: Blood
https://www.readbyqxmd.com/read/27865463/molecular-changes-during-acute-myeloid-leukemia-aml-evolution-and-identification-of-novel-treatment-strategies-through-molecular-stratification
#12
E Karjalainen, G A Repasky
Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by impaired differentiation and uncontrollable proliferation of myeloid progenitor cells. Due to high relapse rates, overall survival for this rapidly progressing disease is poor. The significant challenge in AML treatment is disease heterogeneity stemming from variability in maturation state of leukemic cells of origin, genetic aberrations among patients, and existence of multiple disease clones within a single patient. Disease heterogeneity and the lack of biomarkers for drug sensitivity lie at the root of treatment failure as well as selective efficacy of AML chemotherapies and the emergence of drug resistance...
2016: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/27860411/secondary-primary-malignancies-during-the-lenalidomide-dexamethasone-regimen-in-relapsed-refractory-multiple-myeloma-patients
#13
Rouslan Kotchetkov, Esther Masih-Khan, Chia-Min Chu, Eshetu G Atenafu, Christine Chen, Vishal Kukreti, Suzanne Trudel, Rodger Tiedemann, Donna E Reece
Lenalidomide in combination with dexamethasone (Len-dex) represents a highly effective treatment in relapsed/refractory multiple myeloma (RRMM) patients. However, an increased risk of secondary primary malignancies (SPMs), including myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) has been described in patients receiving lenalidomide. In order to assess the incidence and features of this complication, we reviewed 195 patients with RRMM treated with Len-dex at our institution. The median follow-up time from diagnosis of MM was 73 months (10-234 months) and from initiation of Len-dex was 19 months (1-104 months)...
November 18, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27835920/-acute-myeloid-leukemia
#14
Jan Braess
Acute myeloid leukemia (AML) has been genetically characterized extensively and can now be subdivided into 9 to 11 pathogenetically different subtypes according to their profile of driver mutations. In clinical practice karyotyping and molecular analysis of NPM1, cEBPa and FLT3-ITD are required for treatment stratification and potentially genotype specific treatment. Some markers such as NPM1 not only offer prognostic information but can also serve as markers of minimal residual disease and thus have the potential to guide therapy in the future...
November 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27833171/serum-levels-of-soluble-adhesion-molecules-in-newly-diagnosed-acute-myeloid-leukemia-and-in-complete-remission-suggest-endothelial-cell-activation-by-myeloblasts
#15
Tomas Kupsa, Jan Vanek, Zak Pavel, Ladislav Jebavy, Jan M Horacek
BACKGROUND AND AIMS: Despite high-dose multi-agent chemotherapy and allogeneic stem cell transplantation, the relapse rate of acute myeloid leukemia (AML) is high. Further, the disease is highly resistent to drugs. We speculated that deeper understanding of AML-endothelial cell interactions might provide new targets for selective modulation of the AML microenvironment and form the basis for novel treatment approaches. In this study, we evaluated levels of endothelium derived soluble adhesion molecules in active disease and in complete remission (CR) and their relationship with inflammatory cytokines...
November 10, 2016: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/27833094/enhanced-sensitivity-to-glucocorticoids-in-cytarabine-resistant-aml
#16
D Malani, A Murumägi, B Yadav, M Kontro, S Eldfors, A Kumar, R Karjalainen, M M Majumder, P Ojamies, T Pemovska, K Wennerberg, C Heckman, K Porkka, M Wolf, T Aittokallio, O Kallioniemi
We sought to identify drugs that could counteract cytarabine resistance in acute myeloid leukemia (AML) by generating eight resistant variants from MOLM-13 and SHI-1 AML cell lines by long-term drug treatment. These cells were compared with 66 ex vivo chemorefractory samples from cytarabine-treated AML patients. The models and patient cells were subjected to genomic and transcriptomic profiling and high-throughput testing with 250 emerging and clinical oncology compounds. Genomic profiling uncovered deletion of the deoxycytidine kinase (DCK) gene in both MOLM-13- and SHI-1-derived cytarabine-resistant variants and in an AML patient sample...
December 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27816650/sequential-intensified-conditioning-regimen-allogeneic-hematopoietic-stem-cell-transplantation-in-adult-patients-with-intermediate-or-high-risk-acute-myeloid-leukemia-in-complete-remission-a-study-from-the-acute-leukemia-working-party-of-the-european-group
#17
Florent Malard, Myriam Labopin, Gernot Stuhler, Jörg Bittenbring, Arnold Ganser, Johanna Tischer, Mauricette Michallet, Nicolaus Kröger, Christoph Schmid, Anne Huynh, Michael Hallek, Bipin N Savani, Mohamad Mohty, Arnon Nagler
Post-transplant relapse is the leading cause of treatment failure in acute myeloid leukemia (AML) patients after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT). To improve their outcome, we evaluated the outcome of a sequential intermediate-intensity conditioning regimen combining fludarabine, cytosine arabinoside, amsacrine, cyclophosphamide, and either total body irradiation or busulfan (FLAMSA) in patients with intermediate or high-risk AML in first or second complete remission (CR)...
November 2, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27805558/-granulocytic-sarcoma-two-cases-with-lymph-node-presentation
#18
Maria Paula Russo, Diego Andresik, M Agustina Perusini
Two cases of granulocytic sarcoma (GS) with lymph node presentation without marrow involvement are presented because it is a rare presentation of acute myeloid leukemia (AML) that can coexist with or precede it and as initial symptom (case 1) or disease relapse (case 2). The most common differential diagnoses are lymphoma or solid tumor. Biopsy is essential for definitive diagnosis. Imaging studies such as positron emission tomography (PET) are very useful for staging and monitoring. The prognosis and treatment according to the literature is not different from AML...
2016: Revista de la Facultad de Ciencias Médicas
https://www.readbyqxmd.com/read/27802968/calreticulin-exposure-by-malignant-blasts-correlates-with-robust-anticancer-immunity-and-improved-clinical-outcome-in-aml-patients
#19
Jitka Fucikova, Iva Truxova, Michal Hensler, Etienne Becht, Lenka Kasikova, Irena Moserova, Sarka Vosahlikova, Jana Klouckova, Sarah E Church, Isabelle Cremer, Oliver Kepp, Guido Kroemer, Lorenzo Galluzzi, Cyril Salek, Radek Spisek
Cancer cell death can be perceived as immunogenic by the host only when malignant cells emit immunostimulatory signals (so-called "damage-associated molecular patterns", DAMPs), as they die in the context of failing adaptive responses to stress. Accumulating preclinical and clinical evidence indicates that the capacity of immunogenic cell death (ICD) to (re-)activate an anticancer immune response is key to the success of various chemo- and radiotherapeutic regimens. Malignant blasts from acute myeloid leukemia (AML) patients exposed multiple DAMPs including calreticulin (CRT), heat-shock protein 70 (HSP70) and HSP90 on their plasma membrane irrespective of treatment...
November 1, 2016: Blood
https://www.readbyqxmd.com/read/27801668/upregulation-of-mir-99a-is-associated-with-poor-prognosis-of-acute-myeloid-leukemia-and-promotes-myeloid-leukemia-cell-expansion
#20
Xiaohui Si, Xiaoyun Zhang, Xing Hao, Yunan Li, Zizhen Chen, Yahui Ding, Hui Shi, Jie Bai, Yingdai Gao, Tao Cheng, Feng-Chun Yang, Yuan Zhou
Leukemia stem cells (LSCs) can resist available treatments that results in disease progression and/or relapse. To dissect the microRNA (miRNA) expression signature of relapse in acute myeloid leukemia (AML), miRNA array analysis was performed using enriched LSCs from paired bone marrow samples of an AML patient at different disease stages. We identified that miR-99a was significantly upregulated in the LSCs obtained at relapse compared to the LSCs collected at the time of initial diagnosis. We also found that miR-99a was upregulated in LSCs compared to non-LSCs in a larger cohort of AML patients, and higher expression levels of miR-99a were significantly correlated with worse overall survival and event-free survival in these AML patients...
October 27, 2016: Oncotarget
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