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acute refractory myeloid leukemia

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https://www.readbyqxmd.com/read/28088971/-eltrombopag-for-refractory-thrombocytopenia-in-patients-with-allogeneic-hematopoietic-stem-cell-transplantation
#1
Y R Ma, X J Huang, X D Mo, W Han, C H Yan, Y Chen, Y Ji, Y Y Chen, Y Wang, X H Zhang, K Y Liu, L P Xu
Objective: To evaluate the efficacy and safety of eltrombopag in post-HSCT thrombocytopenia. Methods: A total of 10 patients who underwent post-HSCT thrombocytopenia at Peking University center, who had been treated with eltrombopag, were retrospectively evaluated. Results: Of the 10 cases, 5 males and 5 females with a median of 34 years old (range, 17-54 years), 5 patients were acute myeloid leukemia, 3 with acute lymphoid leukemia and 2 with severe aplastic anemia. Nine patients had undergone haplo-identical donor transplantation, and one patient was a matched related recipient...
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28088962/-efficacy-and-safety-of-sorafenib-as-monotherapy-to-flt3-itd-positive-acute-myeloid-leukemia
#2
J S Jia, H H Zhu, H X Fu, L Z Gong, J Kong, X J Huang, H Jiang
Objective: To explore the efficacy and safety of Sorafenib as monotherapy to FLT3 positive acute myeloid leukemia (AML). Methods: From April 2014 to December 2015, fourteen AML patients with FLT3 positive, 7 males and 7 females with a median age of 42 (range: 14-81) years old, were enrolled in this study. Of the 14 cases, 4 were de novo cases, 9 refractory cases and 1 relapsed case, including 78.6% patients with severe complications and 57.1% patients with KPS score less than 60 [the median KPS score was 45 (20-70) ]...
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28088961/-the-clinical-and-prognostic-significance-of-acute-myeloid-leukemia-with-flt3-itd
#3
D Lin, H Wei, Y Wang, C L Zhou, B C Liu, K Q Liu, B F Gong, S N Wei, G J Zhang, Y T Liu, X Y Gong, S W Qiu, Y C Mi, J X Wang
Objective: To investigate the clinical significance and prognosis factors of acute myeloid leukemia (AML) with FLT3 mutation-internal tandem duplication (FLT3-ITD) and provide more evidence for prognosis evaluation in AML with FLT3-ITD. Methods: The clinical characteristics and outcomes of 98 AML with FLT3-ITD were analyzed. Results: In patients with FLT3-ITD positive AML, the median of WBC and peripheral blood blast at initial diagnosis were 58.2 (0.3-461.8) ×10(9)/L and 42.2 (0-397.1) ×10(9)/L, respectively...
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28067875/factors-predicting-outcome-after-allogeneic-transplant-in-refractory-acute-myeloid-leukemia-a-retrospective-analysis-of-gruppo-italiano-trapianto-di-midollo-osseo-gitmo
#4
E Todisco, F Ciceri, C Boschini, F Giglio, A Bacigalupo, F Patriarca, I Donnini, E P Alessandrino, W Arcese, A P Iori, P Marenco, I Cavattoni, P Chiusolo, E Terruzzi, L Castagna, A Santoro, A Bosi, E Oldani, B Bruno, F Bonifazi, A Rambaldi
The clinical outcome of primary refractory (PRF) AML patients is poor and only a minor proportion of patients is rescued by allogenic hematopoietic stem cell transplantation (HSCT). The identification of pre-HSCT variables may help to determine PRF AML patients who can most likely benefit from HSCT. We analyzed PRF AML patients transplanted between 1999 and 2012 from a sibling, unrelated donor or a cord blood unit. Overall, 227 patients from 26 Gruppo Italiano Trapianto di Midollo Osseo e Terapia cellulare centers were included in the analysis...
January 9, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28058490/second-line-azacitidine-for-elderly-or-infirmed-patients-with-acute-myeloid-leukemia-aml-not-eligible-for-allogeneic-hematopoietic-cell-transplantation-a-retrospective-national-multicenter-study
#5
Ron Ram, Moshe Gatt, Drorit Merkel, Ilana Helman, Tsofia Inbar, Arnon Nagler, Irit Avivi, Yishai Ofran
Elderly and infirm patients with acute myeloid leukemia (AML) with either induction refractory or relapse disease may benefit from treatment with azacitidine. We retrospectively reviewed the data from five tertiary centers in Israel, treated between 2009 and 2015. Thirty-four patients (median age 74 years) were identified. Sixty-two percent of the patients had relapsed disease and 38% had refractory disease. Median time of follow-up was 12.1 months. Out of a total of 327 courses, incidence of infectious episodes was 6%...
January 5, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28024959/clinicopathologic-immunophenotyping-and-cytogenetic-analysis-of-sweet-syndrome-in-egyptian-patients-with-acute-myeloid-leukemia
#6
Mohamed El-Khalawany, Soha Aboeldahab, Al-Sadat Mosbeh, Aida Thabet
BACKGROUND: Sweet syndrome (SS) is an uncommon dermatologic disorder that could be associated with hematologic malignancies. OBJECTIVE: To describe the clinicopathologic, immunophenotyping and cytogenetic characteristics of SS in Egyptian patients with acute myeloid leukemia (AML). METHODS: The study was conducted during the period from April 2011 to March 2015. For each patient, a clinical evaluation and histological assessment of cutaneous lesions were recorded...
October 26, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28013105/the-effects-of-azacitidine-on-the-response-and-prognosis-of-myelodysplastic-syndrome-and-acute-myeloid-leukemia-involving-a-bone-marrow-erythroblast-frequency-of-50
#7
Tomoyuki Uchida, Masao Hagihara, Jian Hua, Morihiro Inoue
We reviewed the cases of 68 consecutive patients who were diagnosed with myelodysplastic syndrome (MDS, n=61) or acute erythroleukemia (AEL, n=7) according to the World Health Organization (WHO) 2008 criteria and had previously been treated with azacitidine, a hypomethylating agent. Fifteen MDS patients had bone marrow erythroblast frequencies of ≥50%, and 6 out of the 7 AEL patients were reclassified as MDS (refractory anemia with excess blasts [RAEB]-1: 1, RAEB-2: 5) according to the revised WHO 2016 criteria...
November 25, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28011984/fractionated-gemtuzumab-ozogamicin-combined-with-intermediate-dose-cytarabine-and-daunorubicin-as-salvage-therapy-in-very-high-risk-aml-patients-a-bridge-to-reduced-intensity-conditioning-transplant
#8
Etienne Paubelle, Sophie Ducastelle-Leprêtre, Hélène Labussière-Wallet, Franck Emmanuel Nicolini, Fiorenza Barraco, Adriana Plesa, Gilles Salles, Eric Wattel, Xavier Thomas
Outcome of patients with primary refractory/relapsed (R/R) acute myeloid leukemia (AML) remains dismal. Herein, we present a retrospective monocentric study of 24 very high-risk AML patients who received a combination of fractionated gemtuzumab ozogamicin (GO) with intermediate-dose cytarabine and daunorubicin as salvage therapy. Median age was 55.3 years. Diagnostic was secondary AML for 33% of them. Seven patients had favorable risk, 8 had intermediate-1 or intermediate-2, and 6 had unfavorable risk of AML according to the European LeukemiaNet prognostic index...
December 23, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27991919/samhd1-is-a-biomarker-for-cytarabine-response-and-a-therapeutic-target-in-acute-myeloid-leukemia
#9
Constanze Schneider, Thomas Oellerich, Hanna-Mari Baldauf, Sarah-Marie Schwarz, Dominique Thomas, Robert Flick, Hanibal Bohnenberger, Lars Kaderali, Lena Stegmann, Anjali Cremer, Margarethe Martin, Julian Lohmeyer, Martin Michaelis, Veit Hornung, Christoph Schliemann, Wolfgang E Berdel, Wolfgang Hartmann, Eva Wardelmann, Federico Comoglio, Martin-Leo Hansmann, Alexander F Yakunin, Gerd Geisslinger, Philipp Ströbel, Nerea Ferreirós, Hubert Serve, Oliver T Keppler, Jindrich Cinatl
The nucleoside analog cytarabine (Ara-C) is an essential component of primary and salvage chemotherapy regimens for acute myeloid leukemia (AML). After cellular uptake, Ara-C is converted into its therapeutically active triphosphate metabolite, Ara-CTP, which exerts antileukemic effects, primarily by inhibiting DNA synthesis in proliferating cells. Currently, a substantial fraction of patients with AML fail to respond effectively to Ara-C therapy, and reliable biomarkers for predicting the therapeutic response to Ara-C are lacking...
December 19, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27976488/azacitidine-as-a-bridge-to-allogeneic-hematopoietic-cell-transplantation-in-a-pediatric-patient-with-fanconi-anemia-and-acute-myeloid-leukemia
#10
Hilda Ding, Hasan Hashem, Linda Cabral, Hemalatha Rangarajan, Ghada Abusin, Hillard M Lazarus, Rolla Abu-Arja
HCT is the definitive therapy for patients with FA and AML. Conventional cytotoxic agents cause potential DNA damage, and currently, there is no established regimen for these patients prior to HCT. A 13-year-old male with FA and refractory AML was given azacitidine, achieved morphologic remission and underwent HCT. At 95 days after HCT, he relapsed. Azacitidine along with DLI was used as first salvage therapy. Azacitidine was overall well tolerated with minimal side effects. In patients with AML and FA, azacitidine can be considered an alternative to conventional chemotherapy...
December 15, 2016: Pediatric Transplantation
https://www.readbyqxmd.com/read/27941286/adoptive-immunotherapy-utilizing-cancer-antigen-specific-t-cell-receptors
#11
Kazushi Tanimoto, Hiroshi Fujiwara
Synthetic immunology based on rapidly-advancing gene-engineering and immunobiology has made novel anticancer adoptive immunotherapies, using gene-modified T lymphocytes to express cancer antigen-specific receptors, a reality. Various technological innovations have overcome recent difficulties and achieved clear and long-lasting clinical efficacy against tumors, while seeking more powerful effector gene-modified T cells has yielded serious treatment-related adverse events. In this article, along with introducing our clinical trial for a novel anti-leukemia adoptive immunotherapy regimen using gene-modified autologous lymphocytes to express leukemia antigen Wilms Tumor 1(WT1)-specific T cell receptor (TCR) against refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), we provide an overview of the current status of this emerging treatment option and discuss its future form in the context of neoantigens encoded by mutated genes in cancer cells and immune checkpoint inhibitors...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27927766/phase-1-dose-finding-study-of-rebastinib-dcc-2036-in-patients-with-relapsed-chronic-myeloid-leukemia-and-acute-myeloid-leukemia
#12
Jorge Cortes, Moshe Talpaz, Hedy P Smith, David S Snyder, Jean Khoury, Kapil N Bhalla, Javier Pinilla-Ibarz, Richard Larson, David Mitchell, Scott C Wise, Thomas J Rutkoski, Bryan D Smith, Daniel L Flynn, Hagop M Kantarjian, Oliver Rosen, Richard A Van Etten
Available tyrosine kinase inhibitors for chronic myeloid leukemia bind in an ATP-binding pocket and are affected by evolving mutations that confer resistance. Rebastinib was identified as a switch control inhibitor of BCR-ABL1 and FLT3 and may be active against resistant mutations. A Phase 1, first in human, single-agent study investigated rebastinib in relapsed or refractory chronic or acute myeloid leukemia. Primary objectives were to investigate the safety of rebastinib and establish the maximum tolerated dose (MTD) and recommended Phase 2 dose...
December 7, 2016: Haematologica
https://www.readbyqxmd.com/read/27925043/outcomes-of-allogeneic-stem-cell-transplantation-among-patients-with-acute-myeloid-leukemia-presenting-active-disease-experience-of-a-single-european-comprehensive-cancer-center
#13
Ramon Andrade Bezerra De-Mello, Carlos Pinho-Vaz, Rosa Branca, Fernando Campilho, Maria Rosales, Susana Roncon, António Campos-Júnior
Introduction: Allogeneic hematopoietic stem cell transplantation (ASCT) representes a potentially curative approach for patients with relapsed or refractory acute myeloid leukemia (AML). We report the outcome of relapsed/refractory AML patients treated with ASCT. Method: A retrospective cohort from 1994 to 2013 that included 61 patients with diagnosis of relapsed/refractory AML. Outcomes of interest were transplant-related mortality (TRM), incidence of acute and chronic graft-versus-host disease (GVHD), relapse incidence, progression-free survival (PFS) and overall survival (OS)...
October 2016: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/27915304/invasive-aspergillosis-in-acute-myeloid-leukemia-are-we-making-progress-in-reducing-mortality
#14
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...
January 1, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/27913457/treatment-of-blastic-plasmacytoid-dendritic-cell-neoplasm
#15
Jill M Sullivan, David A Rizzieri
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy with no defined standard of care. BPDCN presents most commonly with skin lesions with or without extramedullary organ involvement before leukemic dissemination. As a result of its clinical ambiguity, differentiating BPDCN from benign skin lesions or those of acute myeloid leukemia with leukemia cutis is challenging. BPDCN is most easily defined by the phenotype CD4(+)CD56(+)CD123(+)lineage(-)MPO(-), although many patients will present with variable expression of CD4, CD56, or alternate plasmacytoid markers, which compounds the difficulty in differentiating BPDCN from other myeloid or lymphoid malignancies...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27911276/the-mtor-inhibitor-everolimus-in-combination-with-azacitidine-in-patients-with-relapsed-refractory-acute-myeloid-leukemia-a-phase-ib-ii-study
#16
Peter Tan, Ing Soo Tiong, Shaun Fleming, Giovanna Pomilio, Nik Cummings, Mark Droogleever, Julie McManus, Anthony Schwarer, John Catalano, Sushrut Patil, Sharon Avery, Andrew Spencer, Andrew Wei
Therapeutic options are limited in relapsed/refractory acute myeloid leukemia (AML). We evaluated the maximum tolerated dose (MTD) and preliminary efficacy of mammalian target of rapamycin (mTOR) inhibitor, everolimus (days 5-21) in combination with azacitidine 75 mg/m2 subcutaneously (days 1-5 and 8-9 every 28 days) in 40 patients with relapsed (n = 27), primary refractory (n = 11) or elderly patients unfit for intensive chemotherapy (n = 2). MTD was not reached following everolimus dose escalation (2.5, 5 or 10 mg; n = 19) to the 10 mg dose level which was expanded (n = 21)...
November 29, 2016: Oncotarget
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
#17
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
#18
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/27893466/cd30-expression-is-rare-in-myeloid-leukemia-cutis-a-study-of-55-cases-and-implications-for-routine-diagnostic-algorithms
#19
Olakunle Ogunrinade, David Terrano, April Chiu, Melissa Pulitzer
Expression of CD30 in blastoid cutaneous infiltrates typically signifies a CD30 lymphoproliferative disorder, often requiring minimal immunohistochemical workup, if clinically consonant. However, myeloid and other hematologic malignancies often express CD30. We retrospectively examined the prevalence of CD30 expression in 41 patients (median age 59) and 55 biopsies with the diagnosis of leukemia cutis (LC) to determine whether an extensive immunohistochemical workup is warranted in all large, round cell CD30 cutaneous infiltrates...
November 22, 2016: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/27890254/why-are-there-so-few-randomized-trials-for-patients-with-primary-refractory-acute-myeloid-leukemia
#20
REVIEW
Elihu Estey
Fewer patients with primary refractory AML ("PREF") are entered into phase 3 trials than are patients with relapsed AML. This is particularly noteworthy because data from phase 3 trials for newly diagnosed AML indicated PREF and relapse are equally common. Here I discuss three possible reasons for this discrepancy. First, there is disagreement whether the criterion for PREF AML should be failure of one or two courses of initial induction therapy. Second, there may be an impression that PREF AML is qualitatively worse than relapsed AML...
December 2016: Best Practice & Research. Clinical Haematology
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