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Remission, recovery, relapse

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https://www.readbyqxmd.com/read/29685952/hypomethylating-agents-in-relapsed-and-refractory-aml-outcomes-and-their-predictors-in-a-large-international-patient-cohort
#1
Maximilian Stahl, Michelle DeVeaux, Pau Montesinos, Raphael Itzykson, Ellen K Ritchie, Mikkael A Sekeres, John D Barnard, Nikolai A Podoltsev, Andrew M Brunner, Rami S Komrokji, Vijaya R Bhatt, Aref Al-Kali, Thomas Cluzeau, Valeria Santini, Amir T Fathi, Gail J Roboz, Pierre Fenaux, Mark R Litzow, Sarah Perreault, Tae Kon Kim, Thomas Prebet, Norbert Vey, Vivek Verma, Ulrich Germing, Juan Miguel Bergua, Josefina Serrano, Steven D Gore, Amer M Zeidan
Although hypomethylating agents (HMAs) are frequently used in the frontline treatment of older acute myeloid leukemia (AML) patients, little is known about their effectiveness in relapsed or primary treatment-refractory (RR)-AML. Using an international multicenter retrospective database, we studied the effectiveness of HMAs in RR-AML and evaluated for predictors of response and overall survival (OS). A total of 655 patients from 12 centers received azacitidine (57%) or decitabine (43%), including 290 refractory (44%) and 365 relapsed (56%) patients...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29676440/an-effective-modestly-intensive-re-induction-regimen-with-bortezomib-in-relapsed-or-refractory-paediatric-acute-lymphoblastic-leukaemia
#2
Gertjan J L Kaspers, Denise Niewerth, Bram A J Wilhelm, Peggy Scholte-van Houtem, Marta Lopez-Yurda, Johannes Berkhof, Jacqueline Cloos, Valerie de Haas, Ron A Mathôt, Andishe Attarbaschi, André Baruchel, Eveline S de Bont, Franca Fagioli, Claudia Rössig, Thomas Klingebiel, Barbara De Moerloose, Brigitte Nelken, Giuseppe Palumbo, Dirk Reinhardt, Pierre-Simon Rohrlich, Pauline Simon, Arend von Stackelberg, Michel M Zwaan
This trial explored the efficacy of re-induction chemotherapy including bortezomib in paediatric relapsed/refractory acute lymphoblastic leukaemia. Patients were randomized 1:1 to bortezomib (1.3 mg/m2 /dose) administered early or late to a dexamethasone and vincristine backbone. Both groups did not differ regarding peripheral blast count on day 8, the primary endpoint. After cycle 1, 8 of 25 (32%) patients achieved complete remission with incomplete blood count recovery, 7 (28%) a partial remission and 10 had treatment failure...
April 20, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29625762/effectiveness-of-preventive-cognitive-therapy-while-tapering-antidepressants-versus-maintenance-antidepressant-treatment-versus-their-combination-in-prevention-of-depressive-relapse-or-recurrence-drd-study-a-three-group-multicentre-randomised-controlled-trial
#3
Claudi L H Bockting, Nicola S Klein, Hermien J Elgersma, Gerard D van Rijsbergen, Christien Slofstra, Johan Ormel, Erik Buskens, Jack Dekker, Peter J de Jong, Willem A Nolen, Aart H Schene, Steven D Hollon, Huibert Burger
BACKGROUND: Keeping individuals on antidepressants after remission or recovery of major depressive disorder is a common strategy to prevent relapse or recurrence. Preventive cognitive therapy (PCT) has been proposed as an alternative to maintenance antidepressant treatment, but whether its addition would allow tapering of antidepressants or enhance the efficacy of maintenance antidepressant treatment is unclear. We aimed to compare the effectiveness of antidepressants alone, with PCT while tapering off antidepressants, or PCT added to antidepressants in the prevention of relapse and recurrence...
April 3, 2018: Lancet Psychiatry
https://www.readbyqxmd.com/read/29616840/decitabine-in-combination-with-g-csf-low-dose-cytarabine-and-aclarubicin-is-as-effective-as-standard-dose-chemotherapy-in-the-induction-treatment-for-patients-aged-from-55-to-69-years-old-with-newly-diagnosed-acute-myeloid-leukemia
#4
Jiayu Huang, Ming Hong, Yu Zhu, Huihui Zhao, Xiaoyan Zhang, Yujie Wu, Yun Lian, Xiaoli Zhao, Jianyong Li, Sixuan Qian
We retrospectively studied 87 patients aged from 55 to 69 years old with acute myeloid leukemia (AML) who received decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin (DCAG) or standard dose chemotherapy as induction therapy. Patients receiving DCAG had a similar overall response rate (ORR) (p = .6105) and complete remission (CR) rate (p = .3615) compared to those undergoing standard induction. The median overall survival (OS) and relapse-free survival (RFS) was also similar between the two groups although more 'older' (aged from 60 to 69 years old) and 'unfit' patients underwent DCAG regimen...
April 4, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29572158/a-phase-i-ii-trial-of-the-combination-of-azacitidine-and-gemtuzumab-ozogamicin-for-treatment-of-relapsed-acute-myeloid-leukemia
#5
Bruno C Medeiros, Tiffany N Tanaka, Larisa Balaian, Asad Bashey, Amy Guzdar, Hongying Li, Karen Messer, Edward D Ball
INTRODUCTION: Treatment with hypomethylating agent therapy might enhance anti-CD33 monoclonal antibody-mediated cytotoxicity against acute myeloid leukemia (AML) blasts through epigenetic effects on Syk and SHP-1 expression. PATIENTS AND METHODS: In the present phase I/II study, we treated patients with relapsed or refractory AML with azacitidine, followed by 2 doses of gemtuzumab ozogamicin (GO) at 6 mg/m2 , the Food and Drug Administration-approved dose and schedule at study initiation...
March 2, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29551027/-outcomes-of-adult-patients-with-de-novo-acute-myeloid-leukemia-received-idarubicin-plus-cytarabine-regimen-as-induction-chemotherapy
#6
X Ren, T Zhao, J Wang, H H Zhu, H Jiang, J S Jia, S M Yang, B Jiang, D B Wang, X J Huang, Q Jiang
Objective: To explore outcomes in adult with de novo acute myeloid leukemia (AML) received IA10 (10 mg/m(2) d1-3 idarubicin plus cytarabine 100 mg/m(2) d1-7) regimen as induction chemotherapy. Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed AML (non-M(3)) adults treated with IA10 who achieved morphologic leukemia-free state (MLFS) but not accepted allogeneic hematopoietic stem cell transplantation (allo-HSCT) were assessed retrospectively. Results: A total of 198 patients were included in this study with 96 (48...
January 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29550383/liposomal-grb2-antisense-oligodeoxynucleotide-bp1001-in-patients-with-refractory-or-relapsed-haematological-malignancies-a-single-centre-open-label-dose-escalation-phase-1-1b-trial
#7
Maro Ohanian, Ana Tari Ashizawa, Guillermo Garcia-Manero, Naveen Pemmaraju, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gautam Borthakur, Michael Andreeff, Marina Konopleva, Miranda Lim, Sherry Pierce, Susan O'Brien, Yesid Alvarado, Srdan Verstovsek, William Wierda, Hagop Kantarjian, Jorge Cortes
BACKGROUND: Activating mutations of tyrosine kinases are common in leukaemias. Oncogenic tyrosine kinases use the growth factor receptor-bound protein 2 (Grb2) for signal transduction, leading to activation of mitogen-activated protein kinase (MAPK) 1 and MAPK3 (ERK2 and ERK1). We hypothesised that inhibition of Grb2 would suppress ERK1 and ERK2 activation and inhibit leukaemia progression. To inhibit Grb2, a liposome-incorporated antisense oligodeoxynucleotide that blocks Grb2 protein expression, BP1001, was developed...
April 2018: Lancet Haematology
https://www.readbyqxmd.com/read/29540132/royal-australian-and-new-zealand-college-of-psychiatrists-clinical-practice-guidelines-for-mood-disorders-bipolar-disorder-summary
#8
Gin S Malhi, Tim Outhred, Grace Morris, Philip M Boyce, Richard Bryant, Paul B Fitzgerald, Malcolm J Hopwood, Bill Lyndon, Roger Mulder, Greg Murray, Richard J Porter, Ajeet B Singh, Kristina Fritz
In December 2015, the Royal Australian and New Zealand College of Psychiatrists published a comprehensive set of mood disorder clinical practice guidelines for psychiatrists, psychologists and mental health professionals. This guideline summary, directed broadly at primary care physicians, is an abridged version that focuses on bipolar disorder. It is intended as an aid to the management of this complex disorder for primary care physicians working in collaboration with psychiatrists to implement successful long term management...
March 19, 2018: Medical Journal of Australia
https://www.readbyqxmd.com/read/29529523/cortisol-increases-the-return-of-fear-by-strengthening-amygdala-signaling-in-men
#9
Valerie L Kinner, Oliver T Wolf, Christian J Merz
Relapses represent a major limitation to the long-term remission of pathological fear and anxiety. Stress modulates the acquisition and expression of fear memories and appears to promote fear recovery in patients with anxiety disorders. However, the neural correlates underlying stress hormone effects on the return of fear in humans remain unexplored. Likewise, little is known about the interactions between sex and stress hormones on return of fear phenomena. In this functional magnetic resonance imaging study, 32 men and 32 women were exposed to a fear renewal paradigm with fear acquisition in context A and extinction in context B...
February 21, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29523528/stringent-or-nonstringent-complete-remission-and-prognosis-in-acute-myeloid-leukemia-a-danish-population-based-study
#10
Andreas K Øvlisen, Anders Oest, Mette D Bendtsen, John Bæch, Preben Johansen, Line S Lynggaard, Ingolf Mølle, Thomas B Mortensen, Duruta Weber, Gideon Ertner, Claudia Schöllkopf, Jesper Q Thomassen, Ove Juul Nielsen, Lene Sofie Granfeldt Østgård, Martin Bøgsted, Karen Dybkær, Hans E Johnsen, Marianne T Severinsen
Stringent complete remission (sCR) of acute myeloid leukemia is defined as normal hematopoiesis after therapy. Less sCR, including non-sCR, was introduced as insufficient blood platelet, neutrophil, or erythrocyte recovery. These latter characteristics were defined retrospectively as postremission transfusion dependency and were suggested to be of prognostic value. In the present report, we evaluated the prognostic impact of achieving sCR and non-sCR in the Danish National Acute Leukaemia Registry, including 769 patients registered with classical CR (ie, <5% blasts in the postinduction bone marrow analysis)...
March 13, 2018: Blood Advances
https://www.readbyqxmd.com/read/29467192/combination-of-the-low-anticoagulant-heparin-cx-01-with-chemotherapy-for-the-treatment-of-acute-myeloid-leukemia
#11
Tibor J Kovacsovics, Alice Mims, Mohamed E Salama, Jeremy Pantin, Narayanam Rao, Ken M Kosak, Peter Ahorukomeye, Martha J Glenn, Michael W N Deininger, Kenneth M Boucher, Linda M Bavisotto, Gerardo Gutierrez-Sanchez, Thomas P Kennedy, Stephen G Marcus, Paul J Shami
Relapses in acute myelogenous leukemia (AML) are a result of quiescent leukemic stem cells (LSCs) in marrow stromal niches, where they resist chemotherapy. LSCs employ CXCL12/CXCR4 to home toward protective marrow niches. Heparin disrupts CXCL12-mediated sequestration of cells in the marrow. CX-01 is a low-anticoagulant heparin derivative. In this pilot study, we combined CX-01 with chemotherapy for the treatment of AML. Induction consisted of cytarabine and idarubicin (7 + 3) with CX-01. Twelve patients were enrolled (median age, 56 years; 3 women)...
February 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29463457/clinical-trajectories-in-the-ultra-high-risk-for-psychosis-population
#12
Andrea Polari, Suzie Lavoie, Hok-Pan Yuen, Paul Amminger, Gregor Berger, Eric Chen, Lieuwe deHaan, Jessica Hartmann, Connie Markulev, Fritha Melville, Dorien Nieman, Merete Nordentoft, Anita Riecher-Rössler, Stefan Smesny, John Stratford, Swapna Verma, Alison Yung, Patrick McGorry, Barnaby Nelson
BACKGROUND: Traditionally, research in the ultra-high risk (UHR) for psychosis population has focused on the treatment of existing symptomatology and prevention of transition to psychosis. Recently, there has been an increase in focus on outcomes in individuals who do not transition to psychosis. However, there is a lack of standardised definitions of remission, recovery, recurrence and relapse in UHR, resulting in the inability to generalise and replicate outcomes. METHOD: The aims of the current study were to develop definitions for remission, recovery, recurrence and relapse, and apply them to a UHR cohort allowing the identification of longitudinal clinical trajectories...
February 18, 2018: Schizophrenia Research
https://www.readbyqxmd.com/read/29407182/report-of-the-relapsed-refractory-cohort-of-swog-s0919-a-phase-2-study-of-idarubicin-and-cytarabine-in-combination-with-pravastatin-for-acute-myelogenous-leukemia-aml
#13
Anjali S Advani, Hongli Li, Laura C Michaelis, Bruno C Medeiros, Michaela Liedtke, Alan F List, Kristen O'Dwyer, Megan Othus, Harry P Erba, Frederick R Appelbaum
Inhibition of cholesterol synthesis and uptake sensitizes acute myeloid leukemia (AML) blasts to chemotherapy. A Phase 2 study of high dose pravastatin given in combination with idarubicin and cytarabine demonstrated an impressive response rate [75% complete remission (CR), CR with incomplete count recovery (CRi)]. However, this population was a favorable risk group as eligible patients had to have a CR/CRi lasting ≥3 months following their most recent chemotherapy. Therefore, the study was amended to treat patients with poor risk disease including those with CR/CRi <6 months following their last induction regimen or with refractory disease...
April 2018: Leukemia Research
https://www.readbyqxmd.com/read/29385370/tisagenlecleucel-in-children-and-young-adults-with-b-cell-lymphoblastic-leukemia
#14
MULTICENTER STUDY
Shannon L Maude, Theodore W Laetsch, Jochen Buechner, Susana Rives, Michael Boyer, Henrique Bittencourt, Peter Bader, Michael R Verneris, Heather E Stefanski, Gary D Myers, Muna Qayed, Barbara De Moerloose, Hidefumi Hiramatsu, Krysta Schlis, Kara L Davis, Paul L Martin, Eneida R Nemecek, Gregory A Yanik, Christina Peters, Andre Baruchel, Nicolas Boissel, Francoise Mechinaud, Adriana Balduzzi, Joerg Krueger, Carl H June, Bruce L Levine, Patricia Wood, Tetiana Taran, Mimi Leung, Karen T Mueller, Yiyun Zhang, Kapildeb Sen, David Lebwohl, Michael A Pulsipher, Stephan A Grupp
BACKGROUND: In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). METHODS: We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL...
February 1, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29343033/-clinical-features-and-prognosis-of-18-cases-of-primary-lymphocytic-hypophysitis
#15
Q Wei, G Q Yang, Y J Li, L Zang, Y Pei, J Du, W J Gu, J M Ba, Z H Lü, J T Dou, Y M Mu, J M Lu
Objective: To analyze clinical features, prognosis and treatment of lymphocytic hypophysitis (LYH). Methods: The clinical data, treatments and outcomes of 18 cases diagnosed as LYH at Chinese PLA General Hospital between January 2001 and July 2017 was respectively reviewed. Results: Eighteen patients with histology-proven LYH (13 females and 5 males ) were identified. All lymphocytic adenohypophysitis (LAH) were females(n=6), two of whom were associated with pregnancy. Eleven patients (6 females and 5 males) had lymphocytic panhypophysitis (LPH) and one(female) had hypothalamitis...
January 9, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29339097/safety-and-preliminary-efficacy-of-venetoclax-with-decitabine-or-azacitidine-in-elderly-patients-with-previously-untreated-acute-myeloid-leukaemia-a-non-randomised-open-label-phase-1b-study
#16
Courtney D DiNardo, Keith W Pratz, Anthony Letai, Brian A Jonas, Andrew H Wei, Michael Thirman, Martha Arellano, Mark G Frattini, Hagop Kantarjian, Relja Popovic, Brenda Chyla, Tu Xu, Martin Dunbar, Suresh K Agarwal, Rod Humerickhouse, Mack Mabry, Jalaja Potluri, Marina Konopleva, Daniel A Pollyea
BACKGROUND: Elderly patients (aged ≥65 years) with acute myeloid leukaemia have poor outcomes and no effective standard-of-care therapy exists. Treatment with hypomethylating agents such as azacitidine and decitabine is common, but responses are modest and typically short-lived. The oral anti-apoptotic B-cell lymphoma 2 protein inhibitor, venetoclax, has shown promising single-agent activity in patients with relapsed or refractory acute myeloid leukaemia and preclinical data suggested synergy between hypomethylating agents and venetoclax, which led to this combination phase 1b study...
February 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29305552/venetoclax-for-patients-with-chronic-lymphocytic-leukemia-who-progressed-during-or-after-idelalisib-therapy
#17
Steven Coutre, Michael Choi, Richard R Furman, Herbert Eradat, Leonard Heffner, Jeffrey A Jones, Brenda Chyla, Lang Zhou, Suresh Agarwal, Tina Waskiewicz, Maria Verdugo, Rod A Humerickhouse, Jalaja Potluri, William G Wierda, Matthew S Davids
B-cell receptor pathway inhibitors (BCRi) have transformed treatment for chronic lymphocytic leukemia (CLL); however, efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRi is unknown. Venetoclax is a selective, orally bioavailable BCL-2 inhibitor with activity in patients with CLL, including those who are heavily pretreated or have 17p deletion. This phase 2 study prospectively evaluated venetoclax in patients with R/R CLL after ibrutinib or idelalisib; here we report on patients who received idelalisib as the last BCRi prior to enrollment...
January 5, 2018: Blood
https://www.readbyqxmd.com/read/29304833/a-phase-i-study-of-selinexor-in-combination-with-high-dose-cytarabine-and-mitoxantrone-for-remission-induction-in-patients-with-acute-myeloid-leukemia
#18
Amy Y Wang, Howard Weiner, Margaret Green, Hua Chang, Noreen Fulton, Richard A Larson, Olatoyosi Odenike, Andrew S Artz, Michael R Bishop, Lucy A Godley, Michael J Thirman, Satyajit Kosuri, Jane E Churpek, Emily Curran, Kristen Pettit, Wendy Stock, Hongtao Liu
BACKGROUND: Novel therapies for patients with acute myeloid leukemia (AML) are imperative, particularly for those with high-risk features. Selinexor, an exportin 1 (XPO1/CRM1) inhibitor, has demonstrated anti-leukemia activity as a single agent, as well as in combination with anthracyclines and/or DNA-damaging agents. METHODS: We report the findings of a phase I dose escalation trial with cohort expansion in 20 patients with newly diagnosed or relapsed/refractory AML that combined selinexor with age-adjusted high-dose cytarabine and mitoxantrone (HiDAC/Mito)...
January 5, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29296758/inotuzumab-ozogamicin-in-adults-with-relapsed-or-refractory-cd22-positive-acute-lymphoblastic-leukemia-a-phase-1-2-study
#19
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
https://www.readbyqxmd.com/read/29288821/reduced-intensity-allogeneic-transplant-for-acute-myeloid-leukemia-and-myelodysplastic-syndrome-using-combined-cd34-selected-haploidentical-graft-and-a-single-umbilical-cord-unit-compared-with-matched-unrelated-donor-stem-cells-in-older-adults
#20
Stephanie B Tsai, Joanna Rhodes, Hongtao Liu, Tsiporah Shore, Michael Bishop, Melissa M Cushing, Usama Gergis, Lucy Godley, Justin Kline, Richard A Larson, Sebastian Mayer, Olatoyosi Odenike, Wendy Stock, Amittha Wickrema, Koen van Besien, Andrew S Artz
Haplo/cord transplantation combines an umbilical cord blood (UCB) graft with CD34-selected haploidentical cells and results in rapid hematopoietic recovery followed by durable UCB engraftment. We compared outcomes of transplants in older patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS) who received either HLA-matched unrelated donor (MUD) cells or haplo/cord grafts. Between 2007 and 2013, 109 adults ages 50 and older underwent similar reduced-intensity conditioning with fludarabine and melphalan and antibody-mediated T cell depletion for AML (n = 83) or high-risk MDS (n = 26) followed by either a MUD (n = 68) or haplo/cord (n = 41) graft...
December 27, 2017: Biology of Blood and Marrow Transplantation
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