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refractory acute leukemia

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https://www.readbyqxmd.com/read/28087456/phase-i-trial-of-total-marrow-and-lymphoid-irradiation-transplant-conditioning-in-patients-with-relapsed-refractory-acute-leukemia
#1
Anthony Stein, Joycelynne Palmer, Ni-Chun Tsai, Monzr M Al Malki, Ibrahim Aldoss, Haris Ali, Ahmed Aribi, Len Farol, Chatchada Karanes, Samer Khaled, An Liu, Margaret O'Donnell, Pablo Parker, Anna Pawlowska, Vinod Pullarkat, Eric Radany, Joseph Rosenthal, Firoozeh Sahebi, Amandeep Salhotra, James F Sanchez, Tim Schultheiss, Ricardo Spielberger, Sandra H Thomas, David Snyder, Ryotaro Nakamura, Guido Marcucci, Stephen J Forman, Jeffrey Wong
Current conditioning regimens provide insufficient disease control in relapsed/refractory acute leukemia (AL) patients undergoing hematopoietic stem cell transplantation (HSCT) with active disease. Intensification of chemotherapy and/or total body irradiation (TBI) is not feasible because of excessive toxicity. Total marrow and lymphoid irradiation (TMLI) allows for precise delivery and increased intensity treatment via sculpting radiation to sites with high disease burden or high risk for disease involvement, while sparing normal tissue...
January 10, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28069570/anti-cd22-car-therapy-leads-to-all-remissions
#2
(no author information available yet)
In a first-in-human trial of an anti-CD22 chimeric antigen receptor T-cell therapy in children and young adults with relapsed and refractory acute lymphocytic leukemia, researchers found that the immunotherapeutic approach was not only feasible and safe, but also effective, leading to remissions in most patients. Infusions of higher numbers of T cells correlated with improved responses.
January 9, 2017: Cancer Discovery
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
#3
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
#4
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/28039267/potent-anti-leukemia-activities-of-chimeric-antigen-receptor-modified-t-cells-against-cd19-in-chinese-patients-with-relapsed-refractory-acute-lymphocytic-leukemia
#5
Yongxian Hu, Zhao Wu, Yi Luo, Jimin Shi, Jian Yu, Chengfei Pu, Zhuyu Liang, Guoqing Wei, Qu Cui, Jie Sun, Jing Jiang, Jue Xie, Yamin Tan, Wanmao Ni, Jifang Tu, Jinping Wang, Aiyun Jin, Hao Zhang, Zhen Cai, Lei Xiao, He Huang
PURPOSE: Patients with relapsed/refractory acute lymphocytic leukemia (R/R ALL) have a poor prognosis. Chimeric antigen receptor modified T cells against CD19 (CART19s) have displayed anti-leukemia activities. However, data from systemic trials in Chinese patients are limited. STUDY DESIGN: T cells transduced with CD19-directed CAR lentiviral vectors were infused in patients with R/R ALL under fludarabine- and cyclophosphamide-based lymphodepletion. The post-infusion responses, toxicities, expansion and persistence of CART19s in enrolled patients were observed and monitored...
December 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28028314/redirecting-t-cells-to-eradicate-b-cell-acute-lymphoblastic-leukemia-bispecific-t-cell-engagers-and-chimeric-antigen-receptors
#6
REVIEW
I Aldoss, R C Bargou, D Nagorsen, G R Friberg, P A Baeuerle, S J Forman
Recent advances in antibody technology to harness T-cells for cancer immunotherapy, particularly in the difficult-to-treat setting of relapsed or refractory acute lymphoblastic leukemia (r/r ALL), has led to innovative methods for directing cytotoxic T-cells to specific surface antigens on cancer cells. One approach involves administration of soluble bispecific (or dual-affinity) antibody-based constructs that temporarily bridge T-cells and cancer cells. Another approach infuses ex vivo-engineered T-cells that express a surface plasma membrane-inserted antibody construct called a chimeric antigen receptor (CAR)...
December 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28024959/clinicopathologic-immunophenotyping-and-cytogenetic-analysis-of-sweet-syndrome-in-egyptian-patients-with-acute-myeloid-leukemia
#7
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/28024518/-role-of-autophagy-in-acute-lymphoblastic-leukemia-review
#8
Qiong Liao, Xia Ren, Guo-Sheng Jiang
Autophagy is an evolutionarily highly conservative lysosomal degradative process and closely associates with pathogenesis, process, treatment, drug resistance and relapse of acute lymphoblastic leukemia (ALL). Whether the autophagy displays resistance to chemotherapy or a tumor suppressor in ALL, it mainly depends on the context of autophagy in the cells. Understanding the different role of autophagy in different conditions for ALL, determing the autophagy signaling pathways and targeting combination with autophagy revulsants or inhibitors were significant for the therapy of ALL, particularly for the treatment of refractory/relapsed ALL patients...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
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
#9
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
#10
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/27998223/phase-i-phase-ii-study-of-blinatumomab-in-pediatric-patients-with-relapsed-refractory-acute-lymphoblastic-leukemia
#11
Arend von Stackelberg, Franco Locatelli, Gerhard Zugmaier, Rupert Handgretinger, Tanya M Trippett, Carmelo Rizzari, Peter Bader, Maureen M O'Brien, Benoît Brethon, Deepa Bhojwani, Paul Gerhardt Schlegel, Arndt Borkhardt, Susan R Rheingold, Todd Michael Cooper, Christian M Zwaan, Phillip Barnette, Chiara Messina, Gérard Michel, Steven G DuBois, Kuolung Hu, Min Zhu, James A Whitlock, Lia Gore
Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children < 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II)...
December 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27991919/samhd1-is-a-biomarker-for-cytarabine-response-and-a-therapeutic-target-in-acute-myeloid-leukemia
#12
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/27987201/treatment-of-acute-lymphoblastic-leukemia-in-adults-applying-lessons-learned-in-children
#13
REVIEW
Ibrahim T Aldoss, Guido Marcucci, Vinod Pullarkat
Although pediatric acute lymphoblastic leukemia (ALL) has cure rates of over 90%, adult ALL remains a challenging disease to treat, with cure rates roughly half those seen in children. The inferior outcomes in adults can be attributed mainly to adverse genetic features, as well as the inability-particularly of older adults-to tolerate chemotherapy. Modest improvements have been seen in outcomes for adolescents and young adults; these can largely be attributed to the use of pediatric-type combination chemotherapy regimens in patients aged 50 years or younger...
December 15, 2016: Oncology (Williston Park, NY)
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
#14
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/27941287/adoptive-immunotherapy-utilizing-anti-cd19-chimeric-antigen-receptor-t-cells-for-b-cell-malignancies
#15
Iekuni Oh, Yukiko Oh, Ken Ohmine
Genetically modified T-cells with forced expression of anti-CD19 chimeric antigen receptor (CD19 CAR) have demonstrated promising clinical results for relapsed and refractory B cell malignancies in early clinical trial settings. The first beneficial tumor regressions were identified among approximately half of CLL patients in 2011. Similarly, CD19 CAR T-cells achieved remissions in about 80% of aggressive B-cell lymphomas in 2012. Furthermore, in 2013 this cellular therapy showed an extremely high rate of efficacy against refractory CD19 positive acute lymphoid leukemia, which had been regarded as the most difficult to treat hematologic disease...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27941286/adoptive-immunotherapy-utilizing-cancer-antigen-specific-t-cell-receptors
#16
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/27935578/comment-on-blinatumomab-vs-historical-standard-therapy-of-adult-relapsed-refractory-acute-lymphoblastic-leukemia
#17
W H Tong
No abstract text is available yet for this article.
December 9, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27930631/cd19-targeted-car-t-cells-as-novel-cancer-immunotherapy-for-relapsed-or-refractory-b-cell-acute-lymphoblastic-leukemia
#18
Marco L Davila, Renier J Brentjens
Immunotherapy has demonstrated significant potential for the treatment of patients with chemotherapy-resistant hematologic malignancies and solid tumors. One type of immunotherapy involves the adoptive transfer of T cells that have been genetically modified with a chimeric antigen receptor (CAR) to target a tumor. These hybrid proteins are composed of the antigen-binding domains of an antibody fused to T-cell receptor signaling machinery. CAR T cells that target CD19 recently have made the jump from the laboratory to the clinic, and the results have been remarkable...
October 2016: Clinical Advances in Hematology & Oncology: H&O
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
#19
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/27927646/bcr-abl-specific-t-cell-therapy-in-ph-all-patients-on-tyrosine-kinase-inhibitors
#20
Patrizia Comoli, Sabrina Basso, Giovanni Riva, Patrizia Barozzi, Ilaria Guido, Antonella Gurrado, Giuseppe Quartuccio, Laura Rubert, Ivana Lagreca, Daniela Vallerini, Fabio Forghieri, Monica Morselli, Paola Bresciani, Angela Cuoghi, Ambra Paolini, Elisabetta Colaci, Roberto Marasca, Antonio Cuneo, Lorenzo Iughetti, Tommaso Trenti, Franco Narni, Robin Foà, Marco Zecca, Mario Luppi, Leonardo Potenza
While the emergence of bone marrow-resident (p190)BCR-ABL-specific T lymphocytes has been correlated with hematologic and cytogenetic remissions in patients with Philadelphia chromosome positive, acute lymphoblastic leukemia (Ph+ ALL) undergoing maintenance tyrosine-kinase inhibitor treatment, little is known about the possibility of culturing these cells ex vivo and employing them in T-cell therapy strategies. We investigated the feasibility of expanding/priming (p190)BCR-ABL-specific T cells in vitro by stimulation with dendritic cells pulsed with (p190)BCR-ABL peptides derived from the BCR-ABL junctional region and alternative splicing, and of adoptively administering them to patients with relapsed disease...
December 7, 2016: Blood
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