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Leukemia Research

Eun-Ji Choi, Je-Hwan Lee, Jung-Hee Lee, Han-Seung Park, Sun-Hye Ko, Eun-Hye Hur, Juhyun Moon, Bon-Kwan Goo, Yeonhee Kim, Miee Seol, Young-Shin Lee, Young-Ah Kang, Mijin Jeon, Ji Min Woo, Kyoo-Hyung Lee
This retrospective analysis compared anthracyclines (as part of an induction regimen) in 128 newly diagnosed FLT3-ITD-mutated AML patients. Induction regimens comprised high-dose daunorubicin (HD-DN; 90 mg/m2 /d × 3d; n = 44), standard-dose daunorubicin (SD-DN; 45 mg/m2 /d × 3d; n = 51), or idarubicin (IDA; 12 mg/m2 /d × 3d; n = 33) in combination with cytarabine (100-200 mg/m2 /d × 7d). Fifty-three patients showing persistent leukemia on interim bone marrow examination received a second course of induction chemotherapy comprising 2 days of daunorubicin (45 mg/m2 /d) or IDA (8 or 12 mg/m2 /d) in addition to 5 days of cytarabine...
March 8, 2018: Leukemia Research
Amanda N Seddon, Joshua Chaim, Oguz Akin, Esther Drill, Angela G Michael, Nelly Adel, Martin S Tallman
BACKGROUND: The current standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) is an anthracycline plus cytarabine. Both anthracyclines and cytarabine have been associated with the development of typhlitis, a serious adverse event characterized by inflammation of the bowel wall in patients with profound neutropenia, diagnosed by abdominal CT imaging and clinical symptoms. Given the paucity of available data, the aim of our study was to determine the incidence of typhlitis among AML patients receiving induction chemotherapy with idarubicin 12 mg/m2 (IDA), daunorubicin 60 mg/m2 (DNA60), or daunorubicin 90 mg/m2 (DNA90)...
March 8, 2018: Leukemia Research
Qingkai Dai, Xiaojuan Liu, Hui Yang, Siqi Guo, Yuefang Wang, Luyun Peng, Lei Ye, Lan Chen, Chunqi Lai, Qi Chen, Ge Zhang, Yongmei Jiang
Detection of aberrant antigen expression in acute lymphoblastic leukemia (ALL) by flow cytometric is proposed for the quantification of minimal residual disease (MRD). There are few studies that investigate the stability of the antigen expression in children with B lineage ALL at the end of remission induction therapy and determine its prognostic impact. Between 2010 and 2015, 691 bone marrow specimens of childhood ALL were sent at diagnosis for immunophenotypic characterization, and follow-up samples for MRD were analyzed on day 33...
March 2, 2018: Leukemia Research
Fang Zhu, Ismat Khatri, David Spaner, Reginald M Gorczynski
Chronic Lymphocytic Leukemia B cells (CLL) are malignant cells which retain at least some functions of normal B cells. Paramount amongst the latter is that when such cells are appropriately stimulated, they are able to present antigens, including any potential tumor antigens, making them excellent choices as a candidate tumor vaccine. We show that following stimulation of CLL cells with Phorbol myristic acetate, IL-2, the TLR7 agonist imiquimod (P2I) and ionomycin (P2Iio), markedly increased expression of CD54 and CD83 was seen, indicative of B cell activation and a transition to antigen-presenting cells...
March 2, 2018: Leukemia Research
Chezi Ganzel, Ory Rouvio, Irit Avivi, Hila Magen, Osnat Jarchowsky, Katrin Herzog, Yossi Cohen, Tamar Tadmor, Netanel Horwitz, Merav Leiba, Arnon Nagler, Yael Cohen, Shlomo Bulvik, Aaron Polliack, Jacob M Rowe, Moshe E Gatt
Primary plasma cell leukemia (PPCL) is a rare form of multiple myeloma with a dismal prognosis. This retrospective multi-center study examines the national experience of PPCL in the era of novel agents. During 2002-2016, thirty-nine patients with PPCL were identified in 11 Israeli centers. One-fifth of them died in the first 2 months after diagnosis. The overall survival (OS) of those who survived the first 3 months was 22.5 months. About 70% of patients received at least one type of immunomodulatory drug (IMiD) and similarly proteasome inhibitor (PI) during treatment...
March 1, 2018: Leukemia Research
Colombe Saillard, Elodie Elkaim, Jerome Rey, Evelyne d'Incan, Aude Charbonnier, Anne Etienne, Antoine Sannini, Laurent Chow-Chine, Magali Bisbal, Norbert Vey, Djamel Mokart
No abstract text is available yet for this article.
February 28, 2018: Leukemia Research
Jia Liu, Wenting Lu, Shuang Liu, Ying Wang, Saisai Li, Yingxi Xu, Haiyan Xing, Kejing Tang, Zheng Tian, Qing Rao, Min Wang, Jianxiang Wang
The t(8;21)(q22;q22) translocation generated the fusion protein AML1-ETO. AML1-ETO recruits histone deacetylase (HDAC) complex via its ETO part to repress AML1-mediated transactivation. Our previous study demonstrated that HDAC inhibitor phenylbutyrate (PB) could induce AML1-ETO positive leukemia cell line Kasumi-1 cells to undergo differentiation and apoptosis accompanied by significant changes in gene expression profile. ZFP36L2 was one of the up-regulated genes in Kasumi-1 cells induced by PB treatment. In this study, ZFP36L2 was found to express at a lower level in acute myeloid leukemia (AML) patients with t(8;21) compared to AML patients without t(8;21)...
February 27, 2018: Leukemia Research
Noriyoshi Iriyama, Hiromichi Takahashi, Katsuhiro Miura, Yoshihito Uchino, Masaru Nakagawa, Yoshihiro Hatta, Masami Takei
We investigated the effects of dasatinib on natural killer (NK) cell-induced signaling protein and perforin expression as well as plasma cytokine levels by analyzing blood samples from patients with well-controlled chronic myeloid leukemia receiving tyrosine kinase inhibitor (TKI) therapy. Perforin expression and phosphorylation of signal transducer and activator of transcription (STAT) 1, STAT3, Janus kinase (JAK) 1, and JAK2 in NK cells were evaluated by flow cytometry, and the levels of plasma cytokines, including interferon (IFN)-γ and interleukin (IL)-2, were determined by enzyme-linked immunosorbent assays in 40 patients (dasatinib, n = 23; imatinib, n = 11; and nilotinib, n = 6)...
February 24, 2018: Leukemia Research
Devendra Hiwase, Peter Tan, James D'Rozario, John Taper, Anthony Powell, Ian Irving, Matthew Wright, Susan Branford, David T Yeung, Luke Anderson, Othon Gervasio, Carly Levetan, Will Roberts, Ann Solterbeck, Robert Traficante, Timothy Hughes
BACKGROUND: Some patients receiving a tyrosine kinase inhibitor (TKI) for the first-line treatment of chronic phase chronic myeloid leukemia (CML-CP) experience intolerable adverse events. Management strategies include dose adjustments, interrupting or discontinuing therapy, or switching to an alternative TKI. METHODS: This multicenter, single-arm, Phase IIIb study included CML-CP patients intolerant of, but responsive to, first-line treatment with imatinib or dasatinib...
February 21, 2018: Leukemia Research
Simon Kavanagh, Emily Heath, Rose Hurren, Marcela Gronda, Samir H Barghout, Sanduni U Liyanage, Thirushi P Siriwardena, Jaime Claudio, Tong Zhang, Mahadeo Sukhai, Tracy L Stockley, Suzanne Kamel-Reid, Amr Rostom, Andrzej Lutynski, Dina Khalaf, Anna Rydlewski, Steven M Chan, Vikas Gupta, Dawn Maze, Hassan Sibai, Andre C Schuh, Karen Yee, Mark D Minden, Aaron D Schimmer
We evaluated outcomes of 100 patients with high risk AML treated with Ida-FLAG induction as first-line therapy. 72 achieved remission with one cycle; 19 did not. High risk cytogenetics and TP53 mutations were associated with failure to achieve remission. In those reaching remission, allogeneic bone marrow transplantation was associated with better relapse-free and overall survival. Those not achieving remission with induction therapy were extremely unlikely to reach remission with further therapy and had a dismal prognosis...
February 20, 2018: Leukemia Research
Brady E Beltrán, Sally Paredes, Esther Cotrina, Eduardo M Sotomayor, Jorge J Castillo
The neutrophil:lymphocyte ratio (NLR) has emerged as prognostic in patients with hematological malignancies. We aimed at evaluating the NLR as predictive for complete response (CR) and prognostic for progression-free (PFS) and overall survival (OS) in a study cohort of 121 Peruvian patients with diffuse large B-cell lymphoma (DLCBL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Patients with an NLR ≥6 (n = 28) were more likely to have a performance status ECOG ≥2 (74% vs...
February 19, 2018: Leukemia Research
Amy L Deckert, Galina Gheihman, Rinat Nissim, Cynthia Chung, Aaron D Schimmer, Camilla Zimmermann, Gary Rodin
PURPOSE: The symptom burden of acute myeloid leukemia (AML) and its treatment can accelerate physical deconditioning and impair mobility and quality of life. In the present study, we explore the subjective experience of functional capacity in people living with AML. METHODS: A secondary qualitative analysis was performed on a subset of interviews (n = 21) obtained from an observational cohort study of people with acute leukemia. Conventional content analysis was employed to identify key themes and concepts...
February 15, 2018: Leukemia Research
Tariq I Mughal, Jason Gotlib, Ruben Mesa, Steffen Koschmieder, H Jean Khoury, Jorge E Cortes, Tiziano Barbui, Rüdiger Hehlmann, Michael Mauro, Susanne Saussele, Jerald P Radich, Richard A Van Etten, Giuseppe Saglio, Srdnan Verstovek, Robert Peter Gale, Omar Abdel-Wahab
This review is based on the presentations and deliberations at the 7th John Goldman Chronic Myeloid Leukemia (CML) and Myeloproliferative Neoplasms (MPN) Colloquium which took place in Estoril, Portugal on the 15th October 2017, and the 11th post-ASH International Workshop on CML and MPN which took place on the 6th-7th December 2016, immediately after the 58th American Society of Hematology Annual Meeting. Rather than present a resume of the proceedings, we have elected to address some of the topical translational research and clinically relevant topics in greater detail...
February 14, 2018: Leukemia Research
Xue Li, Dong Li, Xiaoyang Huang, Panpan Zhou, Qing Shi, Bing Zhang, Xiuli Ju
Regulatory T cells (Tregs) characterized by the transcription factor forkhead box P3 (FoxP3) are crucial for maintaining immune tolerance and preventing autoimmunity. However, FoxP3 does not function alone and Helios is considered a potential candidate for defining Treg subsets. In this study, we investigated the expression and function of Helios for identifying Tregs in childhood precursor B-cell acute lymphoblastic leukemia (pre-B ALL). Our results demonstrated that patients with pre-B ALL had a higher percentage of Helios+ FoxP3+ CD4+ Tregs...
February 14, 2018: Leukemia Research
Zachary D Epstein-Peterson, Sean M Devlin, Eytan M Stein, Elihu Estey, Martin S Tallman
PURPOSE: Measurable residual disease (MRD) has prognostic importance for patients with acute myeloid leukemia (AML). How leukemia providers incorporate MRD into routine practice remains undefined. PATIENTS AND METHODS: A survey was developed and distributed to a large sample of leukemia physicians. Demographic information was collected along with details concerning MRD practices. A multivariable logistic regression model evaluated provider characteristics predictive of MRD utilization...
February 13, 2018: Leukemia Research
Colleen A C Wong, Shannon A Y Wong, Heather A Leitch
BACKGROUND: An increased incidence of infections and infectious mortality has been reported in myelodysplastic syndromes (MDS) patients receiving red blood cell (RBC) transfusions. METHODS: We examined incidence of infections requiring antibiotics, antifungal or antiviral medications in transfused lower International Prognostic Scoring System (IPSS) risk MDS patients and whether this differed with iron chelation therapy (ICT). RESULTS: 138 transfused MDS patients were lower IPSS risk...
February 10, 2018: Leukemia Research
Bruno C Medeiros
Treatment regimens for acute myeloid leukemia (AML) have remained largely unchanged until recently. Molecular advances have opened the door to targeted therapies, many of which are in late-phase clinical trials. As new therapeutic opportunities arise, it is appropriate to review key aspects of clinical trial design, statistical interpretation of outcomes, and methods of data reporting. Complete remission and overall survival (OS) are common primary endpoints in early-phase AML clinical trials. OS and event-free survival are frequent primary endpoints in phase 3 trials...
February 7, 2018: Leukemia Research
Yuta Baba, Bungo Saito, Shotaro Shimada, Yohei Sasaki, So Murai, Maasa Abe, Shun Fujiwara, Nana Arai, Yukiko Kawaguchi, Nobuyuki Kabasawa, Hiroyuki Tsukamoto, Yui Uto, Hirotsugu Ariizumi, Kouji Yanagisawa, Norimichi Hattori, Hiroshi Harada, Tsuyoshi Nakamaki
Studies showed red cell distribution width (RDW) can improve the detection of morphological changes in red blood cells and the understanding of their contribution to dyserythropoiesis in myelodysplastic syndrome (MDS). The purpose of the study was to evaluate dyserythropoiesis in MDS by RDW analysis and to explore the utility of RDW in clinical practice. We retrospectively analyzed laboratory and clinical data of 101 patients (59 patients was refractory anemia (RA) according to the French-American-British (FAB) classification)...
February 7, 2018: Leukemia Research
Natasa Tosic, Isidora Petrovic, Natasa Kovacevic Grujicic, Slobodan Davidovic, Marijana Virijevic, Nada Suvajdzic Vukovic, Sonja Pavlovic, Milena Stevanovic
Aberrant expression of different SOX (SRY-related high mobility group (HMG) box) genes has been observed in number of tumors but, little is known about their expression patterns in hematological malignancies, especially in acute myeloid leukemia (AML). In this study we investigated SOX2, SOX3, SOX11, SOX14 and SOX18 gene expression in 50 de novo adult AML patients and correlated our findings with known clinical and molecular prognostic markers of the disease. We have found that these genes are overexpressed in 10-22% of patients and preliminary findings suggest that high expression level of these genes may have prognostic significance in AML patients...
February 6, 2018: Leukemia Research
Matthew P Blakley, Janice P Dutcher, Peter H Wiernik
BACKGROUND: There is mounting evidence that Langerhans cell histiocytosis (LCH) and acute myeloid leukemia (AML) are hematopoietic neoplasms that arise from the same myeloid precursor cell. In addition, studies suggest a relationship between LCH and primary idiopathic myelofibrosis (MF). Furthermore familial LCH, AML, and MF have each been reported. METHODS: We examined more than 750 pedigrees of familial hematologic malignancies for evidence of familial LCH, AML, and/or MF and identified one family with all three neoplasms, which is presented here...
February 2, 2018: Leukemia Research
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