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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
#1
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
#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/27913530/cytokine-release-syndrome-with-novel-therapeutics-for-acute-lymphoblastic-leukemia
#3
Noelle V Frey, David L Porter
T-cell-engaging immunotherapies are exciting new approaches to treat patients with acute lymphoblastic leukemia (ALL). These unique agents, which include blinatumomab, a CD3/CD19 bispecific antibody, and chimeric antigen receptor (CAR) modified T cells targeted to CD19 have shown unprecedented remission rates in the relapsed, refractory ALL setting. Cytokine release syndrome (CRS), resulting from the high magnitude of immune activation by these therapies, is the most significant treatment-related toxicity. CRS manifests with fever and malaise and can progress to life-threatening capillary leak with hypoxia and hypotension...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913457/treatment-of-blastic-plasmacytoid-dendritic-cell-neoplasm
#4
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
#5
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
#6
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/27909887/similar-outcome-after-allogeneic-stem-cell-transplantation-with-a-modified-flamsa-conditioning-protocol-substituting-4%C3%A2-gy-tbi-with-treosulfan-in-an-elderly-population-with-high-risk-aml
#7
Udo Holtick, Marco Herling, Natali Pflug, Geothy Chakupurakal, Silke Leitzke, Dominik Wolf, Michael Hallek, Christof Scheid, Jens M Chemnitz
The fludarabine, amsacrine, and cytarabine (FLAMSA)-reduced-intensity conditioning (RIC) protocol has been described to be effective in patients with high-risk and refractory acute myeloic leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (aSCT). To increase safety and tolerability of the conditioning, we previously reported the feasibility to substitute the TBI component by treosulfan in elderly AML patients. We now present long-term follow-up data on patients treated with FLAMSA/treosulfan compared to the original FLAMSA/4Gy TBI protocol...
December 1, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27908880/an-anti-cd3-anti-cll-1-bispecific-antibody-for-the-treatment-of-acute-myeloid-leukemia
#8
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/27905678/a-phase-i-ii-trial-of-at9283-a-selective-inhibitor-of-aurora-kinase-in-children-with-relapsed-or-refractory-acute-leukemia-challenges-to-run-early-phase-clinical-trials-for-children-with-leukemia
#9
B Vormoor, G J Veal, M J Griffin, A V Boddy, J Irving, L Minto, M Case, U Banerji, K E Swales, J R Tall, A S Moore, M Toguchi, G Acton, K Dyer, C Schwab, C J Harrison, J D Grainger, D Lancaster, P Kearns, D Hargrave, J Vormoor
Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies...
December 1, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27894958/poly-adp-ribose-polymerase-inhibitors-selectively-induce-cytotoxicity-in-tcf3-hlf-positive-leukemic-cells
#10
Jinhua Piao, Shiori Takai, Takahiro Kamiya, Takeshi Inukai, Kanji Sugita, Kazuma Ohyashiki, Domenico Delia, Mitsuko Masutani, Shuki Mizutani, Masatoshi Takagi
Poly (ADP-ribose) polymerase (PARP) is an indispensable component of the DNA repair machinery. PARP inhibitors are used as cutting-edge treatments for patients with homologous recombination repair (HRR)-defective breast cancers harboring mutations in BRCA1 or BRCA2. Other tumors defective in HRR, including some hematological malignancies, are predicted to be good candidates for treatment with PARP inhibitors. Screening of leukemia-derived cell lines revealed that lymphoid lineage-derived leukemia cell lines, except for those derived from mature B cells and KMT2A (MLL)-rearranged B-cell precursors, were relatively sensitive to PARP inhibitors...
November 25, 2016: Cancer Letters
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27888802/low-dose-triptolide-reverses-chemoresistance-in-adult-acute-lymphoblastic-leukemia-cells-via-reactive-oxygen-species-generation-and-dna-damage-response-disruption
#13
Haijun Zhao, Pengcheng Shi, Manman Deng, Zhiwu Jiang, Yin Li, Vinodh Kannappan, Weiguang Wang, Peng Li, Bing Xu
Chemoresistance represents a major challenge for treatment of acute lymphoblastic leukemia (ALL). Thus, new drugs to overcome chemoresistance in ALL are urgently needed. To this end, we established a cytarabine (araC)-resistant ALL cell line (NALM-6/R), which interestingly displayed cross-resistance towards doxorubicin (ADM). Here we report that low dose of triptolide (TPL), a natural product used for treating inflammatory diseases such as arthritis, could reverse araC and ADM resistance and in NALM-6/R cells as well as primary cells from patients with relapsed or refractory (R/R) ALL, reflected by inhibition of cell proliferation and induction of apoptosis in vitro, and repression of tumor growth in vivo in a mouse xenograft model...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27887660/co-infusion-of-haplo-identical-cd19-chimeric-antigen-receptor-t-cells-and-stem-cells-achieved-full-donor-engraftment-in-refractory-acute-lymphoblastic-leukemia
#14
Bo Cai, Mei Guo, Yao Wang, Yajing Zhang, Jun Yang, Yelei Guo, Hanren Dai, Changlin Yu, Qiyun Sun, Jianhui Qiao, Kaixun Hu, Hongli Zuo, Zheng Dong, Zechuan Zhang, Mingxing Feng, Bingxia Li, Yujing Sun, Tieqiang Liu, Zhiqing Liu, Yi Wang, Yajing Huang, Bo Yao, Weidong Han, Huisheng Ai
BACKGROUND: Elderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T) cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined. CASE PRESENTATION: We treated a 71-year-old female with relapsed and refractory ALL who received co-infusion of haplo-identical donor-derived CD19-directed CAR-T cells and mobilized peripheral blood stem cells (PBSC) following induction chemotherapy...
November 25, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27883945/recent-advances-in-the-treatment-of-lower-risk-non-del-5q-myelodysplastic-syndromes-mds
#15
REVIEW
Antonio Almeida, Pierre Fenaux, Alan F List, Azra Raza, Uwe Platzbecker, Valeria Santini
Patients with lower-risk myelodysplastic syndromes (MDS) are affected primarily by symptoms of chronic anemia and fatigue rather than progression to acute myeloid leukemia. Severe thrombocytopenia, although less common in lower-risk MDS, is associated with increased risk of bleeding. For anemic patients, the principal aim of treatment is to improve anemia and decrease red blood cell transfusions. For transfusion-dependent patients with lower-risk MDS without chromosome 5q deletion [non-del(5q) MDS], there are limited effective treatments...
November 13, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27881874/acute-myeloid-leukemia-derived-from-lympho-myeloid-clonal-hematopoiesis
#16
F Thol, S Klesse, L Köhler, R Gabdoulline, A Kloos, A Liebich, M Wichman, A Chaturvedi, J Fabisch, V I Gaidzik, P Paschka, L Bullinger, G Bug, H Serve, G Göhring, B Schlegelberger, M Lübbert, H Kirchner, M Wattad, D Kraemer, B Hertenstein, G Heil, W Fiedler, J Krauter, R Schlenk, K Döhner, H Döhner, A Ganser, M Heuser
We studied acute myeloid leukemia (AML) patients with lympho-myeloid clonal hematopoiesis (LM-CH), defined by the presence of DNA methyltransferase 3A (DNMT3A) mutations in both the myeloid and lymphoid T-cell compartment. Diagnostic, CR and relapse samples were sequenced for 34 leukemia-related genes in 171 DNMT3A mutated adult AML patients. AML with LM-CH was found in 40 patients (23%) and was associated with clonal haematopoiesis of indeterminate potential (CHIP) years prior to AML, older age, secondary AML, and more frequent MDS-type co-mutations (TET2, RUNX1 and EZH2)...
November 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27873237/estimating-long-term-survival-of-adults-with-philadelphia-chromosome-negative-relapsed-refractory-b-precursor-acute-lymphoblastic-leukemia-treated-with-blinatumomab-using-historical-data
#17
Arie Barlev, Vincent W Lin, Aaron Katz, Kuolung Hu, Ze Cong, Beth Barber
INTRODUCTION: Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(-) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years. METHODS: The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset...
November 21, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27870570/activating-notch1-mutations-define-a-distinct-subgroup-of-patients-with-adenoid-cystic-carcinoma-who-have-poor-prognosis-propensity-to-bone-and-liver-metastasis-and-potential-responsiveness-to-notch1-inhibitors
#18
Renata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N William, Bonnie S Glisson, Michael J Wick, Ann M Kapoun, Amita Patnaik, Gail Eckhardt, Pamela Munster, Leonardo Faoro, Jakob Dupont, J Jack Lee, Andrew Futreal, Adel K El-Naggar, John V Heymach
Purpose Adenoid cystic carcinomas (ACCs) represent a heterogeneous group of chemotherapy refractory tumors, with a subset demonstrating an aggressive phenotype. We investigated the molecular underpinnings of this phenotype and assessed the Notch1 pathway as a potential therapeutic target. Methods We genotyped 102 ACCs that had available pathologic and clinical data. Notch1 activation was assessed by immunohistochemistry for Notch1 intracellular domain. Luciferase reporter assays were used to confirm Notch1 target gene expression in vitro...
November 21, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27869523/nelarabine-in-the-treatment-of-pediatric-and-adult-patients-with-t-cell-acute-lymphoblastic-leukemia-and-lymphoma
#19
Tapan M Kadia, Varsha Gandhi
Introduction T-cell acute lymphoblastic leukemia (ALL) and lymphoma (LBL) are aggressive hematologic neoplasms that are treated with combination chemotherapy in the frontline, but have limited options in the relapsed or refractory setting. Based on observations in patients with purine nucleoside phosphorylase (PNP) deficiency, a guanosine nucleoside analogue, arabinosylguanine (ara-G) was developed that provided T-cell specificity. Nelarabine was developed as the water-soluble, clinically useful-prodrug of ara-G and based on its activity was approved for the treatment of relapsed or refractory T-ALL/LBL...
November 21, 2016: Expert Review of Hematology
https://www.readbyqxmd.com/read/27860411/secondary-primary-malignancies-during-the-lenalidomide-dexamethasone-regimen-in-relapsed-refractory-multiple-myeloma-patients
#20
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
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