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acute refractory myeloid leukemia

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https://www.readbyqxmd.com/read/28718728/a-phase-i-ii-randomized-trial-of-clofarabine-or-fludarabine-added-to-idarubicin-and-cytarabine-for-adults-with-relapsed-or-refractory-acute-myeloid-leukemia
#1
Nicholas J Short, Hagop Kantarjian, Farhad Ravandi, Xuelin Huang, Lianchun Xiao, Guillermo Garcia-Manero, William Plunkett, Varsha Gandhi, Koji Sasaki, Naveen Pemmaraju, Naval G Daver, Gautam Borthakur, Nitin Jain, Marina Konopleva, Zeev Estrov, Tapan M Kadia, William G Wierda, Courtney D DiNardo, Mark Brandt, Susan M O'Brien, Jorge E Cortes, Elias Jabbour
The purine nucleoside analogues clofarabine and fludarabine are active in acute myeloid leukemia (AML). We conducted a phase I/II randomized study of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) for relapsed or refractory AML. Clofarabine 15 mg/m(2) was identified as the recommended phase II dose. Eighty-one patients were assigned using adaptive randomization to CIA (n = 48) or FIA (n = 33). The complete response (CR)/CR without platelet recovery rate did not differ between CIA and FIA (38% versus 30%, respectively; p = ...
July 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28711727/a-chemotherapy-only-regimen-of-busulfan-melphalan-and-fludarabine-and-rabbit-atg-followed-by-allogeneic-t-cell-depleted-hematopoietic-stem-cell-transplants-for-the-treatment-of-myeloid-malignancies
#2
Barbara Spitzer, Ann A Jakubowski, Esperanza B Papadopoulos, Kirsten Fuller, Patrick D Hilden, James W Young, Juliet Barker, Guenther Koehne, Miguel-Angel Perales, Katharine C Hsu, Marcel R M van den Brink, Nancy A Kernan, Susan E Prockop, Andromachi Scaradavou, Hugo Castro-Malaspina, Richard J O'Reilly, Farid Boulad
We sought to develop a myeloablative chemotherapeutic regimen to secure consistent engraftment of T-cell depleted (TCD) hematopoietic stem cell transplants (HSCT) without the need for total body irradiation, thereby reducing toxicity, while maintaining low rates of GvHD and without increasing relapse. We investigated the myeloablative combination of busulfan and melphalan, with the immunosuppressive agents fludarabine and rabbit anti-thymocyte gloubin (r-ATG) as cytoreduction prior to a T-cell depleted HSCT...
July 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28711227/oncogenic-activities-of-idh1-2-mutations-from-epigenetics-to-cellular-signaling
#3
REVIEW
Laurence M Gagné, Karine Boulay, Ivan Topisirovic, Marc-Étienne Huot, Frédérick A Mallette
Gliomas and leukemias remain highly refractory to treatment, thus highlighting the need for new and improved therapeutic strategies. Mutations in genes encoding enzymes involved in the tricarboxylic acid (TCA) cycle, such as the isocitrate dehydrogenases 1 and 2 (IDH1/2), are frequently encountered in astrocytomas and secondary glioblastomas, as well as in acute myeloid leukemias; however, the precise molecular mechanisms by which these mutations promote tumorigenesis remain to be fully characterized. Gain-of-function mutations in IDH1/2 have been shown to stimulate production of the oncogenic metabolite R-2-hydroxyglutarate (R-2HG), which inhibits α-ketoglutarate (αKG)-dependent enzymes...
July 12, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28710745/the-pan-bcl2-inhibitor-at101-activates-the-intrinsic-apoptotic-pathway-and-causes-dna-damage-in-acute-myeloid-leukemia-stem-like-cells
#4
Leisi Zhang, Yong Zhou, Kai Chen, Pengcheng Shi, Yin Li, Manman Deng, Zhiwu Jiang, Xiangmeng Wang, Peng Li, Bing Xu
BACKGROUND: Leukemia stem cells (LSCs) are considered to be the cause of treatment failure and relapse in acute myeloid leukemia (AML). Overexpression of the Bcl-2 family of anti-apoptotic proteins such as Bcl-2, Bcl-xl, and Mcl-1 accounts for survival and self-renewal of LSCs. AT101 binds to the BH3 motif of all Bcl-2 family anti-apoptotic proteins and demonstrates anti-tumor activity in multiple types of tumor. Thus, we hypothesized that this agent might have the potential to deplete LSCs...
July 14, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28702160/bk-virus-associated-hemorrhagic-cystitis-in-patients-with-allogeneic-hematopoietic-cell-transplantation-report-of-three-cases
#5
Duygu Mert, Hikmetullah Batgi, Alparslan Merdin, Sabahat Çeken, Mehmet Sinan Dal, Emre Tekgündüz, Fevzi Altuntaş, Mustafa Ertek
BK viras is a human polyoma viras. It is acquired in early childhood and remains life-long latent in the genitourinary system. BK virus replication is more common in receiving immunosuppressive therapy receiving patients and transplant patients. BK virus could cause hemorrhagic cystitis in patients with allogeneic stem cell transplantation. Hemorrhagic cystitis is a serious complication of hematopoietic stem cell transplantation. Hemorrhagic cystitis could cause morbidity and long stay in the hospital. Diagnosis is more frequently determined by the presence of BK virus DNA detected with quantitative or real-time PCR testing in serum or plasma and less often in urine...
June 1, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28687223/how-to-prevent-relapse-after-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-acute-leukemia-and-myelodysplastic-syndrome
#6
REVIEW
N Yafour, F Beckerich, C E Bulabois, P Chevallier, E Daguindau, C Dumesnil, T Guillaume, A Huynh, S Masouridi Levrat, A L Menard, C Pautas, X Poiré, A Ravinet, M Michallet, A Bazarbachi
Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT). The risk of recurrence is elevated in acute myeloid leukemia (AML) patients with high-risk cytogenetic or molecular abnormalities, as well as when allo-HCT is performed in patients with refractory hematological malignancies or with persistent molecular or radiological (PET-CT scan) residual disease. For high risk AML and myelodysplasia (MDS), a post transplant maintenance strategy is possible, using hypomethylating agents or tyrosine kinase inhibitors (TKI) anti-FLT3 when the target is present...
July 4, 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28680951/health-related-quality-of-life-of-patients-with-acute-myeloid-leukemia-a-systematic-literature-review
#7
REVIEW
Ellen E Korol, Sisi Wang, Karissa Johnston, Farhad Ravandi-Kashani, Mark Levis, Floortje van Nooten
INTRODUCTION: Patients with acute myeloid leukemia (AML), especially those with relapsed or refractory AML, have poor clinical prognosis and outcomes. Health-related quality of life (HRQoL) assessments have become increasingly important in oncology, aiding in identifying and informing supportive therapy needs during treatment and beyond; however, HRQoL in hematology, and AML in particular, has received relatively minor attention. The aim was to identify and summarize estimates of HRQoL in patients with AML, including patients with relapsed or refractory AML...
2017: Oncology and Therapy
https://www.readbyqxmd.com/read/28680340/successful-treatment-of-pulmonary-candidiasis-and-aspergillosis-in-patient-with-refractory-hodgkin-lymphoma-using-micafungin-case-study-and-brief-literature-review
#8
Marta Barańska, Renata Kroll-Balcerzak, Lidia Gil, Joanna Rupa-Matysek, Mieczysław Komarnicki
The number of patients with hematological malignancies who develop invasive fungal disease (IFD) has increased dramatically in recent decades. This increase is attributed to impairment of the host immune system due to intensive cytotoxic chemotherapies, use of corticosteroids and profound immunosuppression after hematopoietic stem cell transplantation (HSCT). Additionally, the increasing prevalence of fungal infections caused by emerging and rare pathogens, IFD of mixed etiology or of atypical localization is observed...
2017: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/28674830/evidence-for-a-pre-existing-telomere-deficit-in-non-clonal-hematopoietic-stem-cells-in-patients-with-acute-myeloid-leukemia
#9
Mónica S Ventura Ferreira, Martina Crysandt, Patrick Ziegler, Sebastian Hummel, Stefan Wilop, Martin Kirschner, Mirle Schemionek, Edgar Jost, Wolfgang Wagner, Tim H Brümmendorf, Fabian Beier
Telomere shortening represents an established mechanism connecting aging and cancer development. We sequentially analyzed telomere length (TL) of 49 acute myeloid leukemia (AML) patients at diagnosis (n = 24), once they achieved complete cytological remission (CCR) and/or during refractory disease or relapse and after 1-year follow-up, with all patients having at least two sequential samples. TL was analyzed by monochrome multiplex quantitative polymerase chain reaction. We have observed substantially shortened TL in the cells of patients at diagnosis compared to age-adjusted controls...
July 3, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28671056/protein-kinase-inhibitors-as-therapeutic-drugs-in-aml-advances-and-challenges
#10
Yuan Ling, Zikang Zhang, Hua Zhang, Zunnan Huang
Acute myeloid leukemia (AML) is a malignant blood disorder and the cure rate has been remarkably improved over the past decade. However, recurrent or refractory leukemia remains the major problem of the AML and no clearly effective therapy has been established so far. Traditional treatments such as chemotherapy and hematopoietic stem cell transplantation are both far dissatisfying the patients partly for their individual variety. Besides, conventional treatments usually have many side effects to result in poor prognosis...
July 3, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28659444/positive-first-trial-of-enasidenib-for-aml
#11
(no author information available yet)
The first clinical trial of the investigational drug enasidenib, which targets IDH2 mutations, suggests that it is safe and may improve survival in patients with relapsed or refractory acute myeloid leukemia. It induced responses in 40.3% of patients, yielding a median overall survival of 9.3 months.
June 28, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28655096/-a-retrospective-analysis-of-prognosis-in-favorable-risk-acute-myeloid-leukemia-patients-with-different-consolidation-regimens
#12
H Y Wang, X B Bao, X W Tang, A N Sun, D P Wu, H X Zhou, H Y Qiu
Objective: To explore the impact on prognosis in favorable-risk acute myeloid leukemia (AML) patients with different consolidation regimens after first complete remission (CR(1)). Methods: A total of 107 cases of non-refractory adult AML from January 2010 to June 2015 in single center were enrolled in the study. HD-Ara-C group (38 cases) as the control group, we explore the prognosis in three consolidation regimens, including micro-transplantation (16 cases) , autologous transplantation (auto-PBSCT, 14 cases) , allogeneic transplantation (allo-HSCT, 39 cases)...
June 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28646908/comparison-of-matched-sibling-donors-versus-unrelated-donors-in-allogeneic-stem-cell-transplantation-for-primary-refractory-acute-myeloid-leukemia-a-study-on-behalf-of-the-acute-leukemia-working-party-of-the-ebmt
#13
Eolia Brissot, Myriam Labopin, Matthias Stelljes, Gerhard Ehninger, Rainer Schwerdtfeger, Jürgen Finke, Hans-Jochem Kolb, Arnold Ganser, Kerstin Schäfer-Eckart, Axel R Zander, Donald Bunjes, Stephan Mielke, Wolfgang A Bethge, Noël Milpied, Peter Kalhs, Igor-Woflgang Blau, Nicolaus Kröger, Antonin Vitek, Martin Gramatzki, Ernst Holler, Christoph Schmid, Jordi Esteve, Mohamad Mohty, Arnon Nagler
BACKGROUND: Primary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT) in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML...
June 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28645776/selective-inhibition-of-flt3-by-gilteritinib-in-relapsed-or-refractory-acute-myeloid-leukaemia-a-multicentre-first-in-human-open-label-phase-1-2-study
#14
Alexander E Perl, Jessica K Altman, Jorge Cortes, Catherine Smith, Mark Litzow, Maria R Baer, David Claxton, Harry P Erba, Stan Gill, Stuart Goldberg, Joseph G Jurcic, Richard A Larson, Chaofeng Liu, Ellen Ritchie, Gary Schiller, Alexander I Spira, Stephen A Strickland, Raoul Tibes, Celalettin Ustun, Eunice S Wang, Robert Stuart, Christoph Röllig, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark Levis
BACKGROUND: Internal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia. METHODS: In this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment...
June 20, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28643044/pd-1-signaling-and-inhibition-in-aml-and-mds
#15
REVIEW
Faysal Haroun, Sade A Solola, Samah Nassereddine, Imad Tabbara
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies...
June 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28625976/a-genome-wide-crispr-screen-identifies-genes-critical-for-resistance-to-flt3-inhibitor-ac220
#16
Panpan Hou, Chao Wu, Yuchen Wang, Rui Qi, Dheeraj Bhavanasi, Zhixiang Zuo, Cedric Dos Santos, Shuliang Chen, Yu Chen, Hong Zheng, Hong Wang, Alexander E Perl, Deyin Guo, Jian Huang
Acute myeloid leukemia (AML) is a malignant hematopoietic disease and the most common type of acute leukemia in adults. The mechanisms underlying drug resistance in AML are poorly understood. Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are the most common molecular abnormality in AML. Quizartinib (AC220) is a potent and selective second-generation inhibitor of FLT3. It is in clinical trials for the treatment of relapsed or refractory FLT3-ITD-positive and -negative AML patients and as maintenance therapy...
June 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28592755/acute-myeloid-leukemia-developing-secondary-immune-thrombocytopenia-after-umbilical-cord-blood-transplantation
#17
Rena Matsumoto, Kazuhiro Ito, Naoko Hosono, Yasufumi Matsuda, Katsunori Tai, Ippei Sakamaki, Goh Aoki, Hirohito Yamazaki, Shinji Nakao, Takahiro Yamauchi
A 64-year-old man was diagnosed with acute myeloid leukemia M2 (FLT3-ITD-positive). After induction chemotherapy and four courses of consolidation therapy, he underwent umbilical cord blood transplantation (CBT) in his first remission. He developed acute graft-versus-host disease (skin stage 2) after successful engraftment. On post-transplantation day 147, he was admitted to the hospital suffering from pneumonia. During the treatment, drastic thrombocytopenia was observed on day 251. Both platelet-associated immunoglobulin G and platelet antibody producing B cells were detected, and he was diagnosed with immune thrombocytopenia (ITP)...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28588617/outcomes-of-six-dose-high-dose-cytarabine-as-a-salvage-regimen-for-patients-with-relapsed-refractory-acute-myeloid-leukemia
#18
Brandi Anders, Lauren Veltri, Abraham S Kanate, Alexandra Shillingburg, Nilay Shah, Michael Craig, Aaron Cumpston
Relapsed/refractory acute myeloid leukemia (RR-AML) is associated with poor prognosis and long-term disease-free survival requires allogeneic hematopoietic cell transplantation (allo-HCT). Limited data exists, regarding the optimal regimen to obtain remission prior to allo-HCT. Single agent high-dose cytarabine (10-12 doses administered every 12 hours) has been previously used as induction therapy. Six-dose high-dose cytarabine (HiDAC-6), commonly used as a consolidation regimen, has never been evaluated as induction therapy...
2017: Advances in Hematology
https://www.readbyqxmd.com/read/28588020/enasidenib-in-mutant-idh2-relapsed-or-refractory-acute-myeloid-leukemia
#19
Eytan M Stein, Courtney D DiNardo, Daniel A Pollyea, Amir T Fathi, Gail J Roboz, Jessica K Altman, Richard M Stone, Daniel J DeAngelo, Ross L Levine, Ian W Flinn, Hagop M Kantarjian, Robert Collins, Manish R Patel, Arthur E Frankel, Anthony Stein, Mikkael A Sekeres, Ronan T Swords, Bruno C Medeiros, Christophe Willekens, Paresh Vyas, Alessandra Tosolini, Qiang Xu, Robert D Knight, Katharine E Yen, Sam Agresta, Stéphane de Botton, Martin S Tallman
Recurrent mutations in isocitrate dehydrogenase 2 (IDH2) occur in ~12% of patients with acute myeloid leukemia (AML). Mutated IDH2 proteins neomorphically synthesize 2-hydroxyglutarate resulting in DNA and histone hypermethylation, leading to blocked cellular differentiation. Enasidenib (AG-221/CC-90007) is a first-in-class, oral, selective inhibitor of mutant-IDH2 enzymes. This first-in-human, phase 1/2 study assessed the maximum tolerated dose (MTD), pharmacokinetic and pharmacodynamic profiles, safety, and clinical activity of enasidenib in patients with mutant-IDH2 advanced myeloid malignancies...
June 6, 2017: Blood
https://www.readbyqxmd.com/read/28588019/enasidenib-induces-acute-myeloid-leukemia-cell-differentiation-to-promote-clinical-response
#20
Michael D Amatangelo, Lynn Quek, Alan Shih, Eytan M Stein, Mikhail Roshal, Muriel D David, Benoit Marteyn, Noushin Rahnamay Farnoud, Stephane de Botton, Olivier A Bernard, Bin Wu, Katharine E Yen, Martin S Tallman, Elli Papaemmanuil, Virginie Penard-Lacronique, Anjan Thakurta, Paresh Vyas, Ross L Levine
Recurrent mutations at R140 and R172 in isocitrate dehydrogenase 2 (IDH2) occur in many cancers, including ~12% of acute myeloid leukemia (AML). In preclinical models these mutations cause accumulation of the oncogenic metabolite R-2-hydroxyglutarate (2-HG) and induce hematopoietic differentiation block. Single-agent enasidenib (AG-221/CC-90007), a selective mutant IDH2 (mIDH2) inhibitor, produced an overall response rate of 40.3% in relapsed/refractory AML patients with mIDH2 in a phase 1 trial. However, its mechanism of action and biomarkers associated with response remain unclear...
June 6, 2017: Blood
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