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acute myeloide leukemia relapse

Hanna Grauers Wiktorin, Malin S Nilsson, Roberta Kiffin, Frida Ewald Sander, Brianna Lenox, Anna Rydström, Kristoffer Hellstrand, Anna Martner
Myeloid-derived suppressor cells (MDSCs) are immature monocytes and granulocytes that impede immune-mediated clearance of malignant cells by multiple mechanisms, including the formation of immunosuppressive reactive oxygen species (ROS) via the myeloid cell NADPH oxidase (NOX2). Histamine dihydrochloride (HDC), a NOX2 inhibitor, exerts anti-cancer efficacy in experimental tumor models but the detailed mechanisms are insufficiently understood. To determine effects of HDC on the MDSC compartment we utilized three murine cancer models known to entail accumulation of MDSC, i...
October 12, 2018: Cancer Immunology, Immunotherapy: CII
Yumi Park, Jinsook Lim, Seonyoung Kim, Ikchan Song, Kyechul Kwon, Sunhoe Koo, Jimyung Kim
Background: Tumor-infiltrating lymphocytes, which form a part of the host immune system, affect the development and progression of cancer. This study investigated whether subsets of lymphocytes reflecting host-tumor immunologic interactions are related to the prognosis of patients with acute myeloid leukemia (AML). Methods: Lymphocyte subsets in the peripheral blood of 88 patients who were newly diagnosed with AML were analyzed by quantitative flow cytometry. The relationships of lymphocyte subsets with AML subtypes, genetic risk, and clinical courses were analyzed...
September 2018: Blood Research
Lauren Veltri, Katayoun Rezvani, Betul Oran, Rohtesh Mehta, Gabriela Rondon, Partow Kebriaei, Uday Popat, Yago Nieto, Chitra Hosing, Muzaffar Qazilbash, Issa Khouri, Elizabeth Shpall, Richard Champlin, David Marin
Outcome of persons >65 years with acute myeloid leukemia (AML) is poor. A transplant from an HLA-identical sibling or an HLA-matched unrelated donor can cure some of these patients but is associated with a substantial transplant-related mortality and a high relapse risk. We analyzed 185 subjects >65 years with high-risk AML receiving conventional (n=42) or reduced-intensity (n=143) pre-transplant conditioning and a transplant from an HLA-identical sibling (n=66) or a 10/10 loci HLA-matched unrelated donor (n=119)...
October 8, 2018: Biology of Blood and Marrow Transplantation
Yuichi Ishikawa
Core binding factor-acute myeloid leukemia (CBF-AML) comprises AML with t (8;21) (p22;q22) and inv16 (q16q16) /t (16;16) (q16;q16) and accounts for 20% of AML cases. The 2016 WHO classification categorized CBF-AML under AML with recurrent genetic abnormalities and considered it as a favorable risk group with a higher remission rate and better overall survival with high-dose cytarabine post-remission therapy. However, relapse occurs in approximately 40% of patients, thereby necessitating the establishment of risk stratification and risk-adapted therapy in CBF-AML...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Lijun Jiang, Taoran Deng, Di Wang, Yi Xiao
BACKGROUND: The prognostic significance of miR-125b in intermediate-risk acute myeloid leukemia has not been well investigated. The aim of the study was to reveal the relationship between the elevated exosomal miR-125b level and the poor prognosis in adult patients with this disease. METHODS: A total of 154 consecutive patients with intermediate-risk acute myeloid leukemia were enrolled. Exosomes were isolated from blood specimens. The exosomal miR-125b level was determined using quantitative real-time polymerase chain reaction...
October 10, 2018: Acta Haematologica
Run-Hui Zheng, Bao-Dan Yu, Li-Xia Zheng, Chun-Yan Wang, Peng-Fei Qin, Xiao-Dan Luo, Jing-Ren Lin, Huo Tan, Jun Xu
OBJECTIVE: To analyze the relationship between T cell subsets and clinical data. METHODS: mononuclear cells were collected from 103 patients with acute leukemia (AL) and 28 healthy volunteers, and percentage changes of CD3+ CD4+ , CD3+ CD8+ and CD4+ CD25+ Foxp3+ cell subsets were assayed by flow cytometory. Relationship between the T subsets and clinical features of the patients was analyzed. RESULTS: Ratio of CD3+ T cells decreased more significantly in patients with >50% blast cells than that in patients with <50% blast cells, while the ratio of Treg between the 2 groups was not significantly different...
October 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
M Ruan, B Q Qi, F Liu, T F Liu, X M Liu, X J Chen, W Y Yang, Y Guo, L Zhang, Y Zou, Y M Chen, X F Zhu
Objective: To investigate the efficacy and the prognostic factors of Chinese Academy of Medical Sciences 2005 (CAMS-2005) regimen in the treatment of pediatric acute myeloid leukemia (AML). Methods: Eighty-eight cases of newly-diagnosed AML patients, who were treated with the CAMS-2005 regimen from April 2005 to July 2009, were enrolled in this case observational study. Clinical characteristics, long-term prognosis and prognostic factors were analyzed retrospectively. Overall survival (OS) and event free survival (EFS) rates were estimated by the Kaplan-Meier method...
October 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Amin Alousi, Tao Wang, Michael T Hemmer, Stephen R Spellman, Mukta Arora, Daniel R Couriel, Joseph Pidala, Paolo N Anderlini, Michael Boyiadzis, Christopher N Bredeson, Jean-Yves Cahn, Mitchell S Cairo, Shahinaz M Gadalla, Shahrukh K Hashmi, Robert Peter Gale, Junya Kanda, Rammurti T Kamble, Mohamed A Kharfan-Dabaja, Mark R Litzow, Olle Ringden, Ayman A Saad, Kirk R Schultz, Leo F Verdonck, Edmund K Waller, Jean A Yared, Shernan G Holtan, Daniel J Weisdorf
BACKGROUND: Peripheral Blood (PB) or Bone Marrow (BM) from unrelated donors can serve as a graft source for hematopoietic cell transplantation. Currently, PB is most commonly used in roughly 80% of adult recipients. Determining the long-term impact of graft source on outcomes would inform this decision. METHODS: Data collected by the Center for International Blood and Marrow Transplant Research (CIBMTR) from 5,200 adult recipients of a first transplant from a 8/8 or 7/8- human-leukocyte antigen matched unrelated donor for treatment of acute leukemia, chronic myeloid leukemia or myelodysplastic syndrome between the years of 2001-2011 were analyzed to determine the impact of graft source on Graft-versus-Host Disease (GVHD), Relapse-Free Survival (GRFS) defined as freedom from grade III/IV acute GVHD, chronic GVHD requiring immunosuppressive therapy, relapse, or death and overall survival...
October 3, 2018: Biology of Blood and Marrow Transplantation
Kaito Harada, Noritaka Sekiya, Shuntaro Ikegawa, Shugo Sasaki, Takeshi Kobayashi, Kazuteru Ohashi
Cytomegalovirus meningitis/meningoencephalitis is a potentially fatal complication following hematopoietic stem cell transplantation that causes significant morbidity and mortality. In the pre-transplant setting, a few cases involving lymphoid malignancies have been reported. However, there have been no reports of patients with myeloid malignancies. A 36-year-old man with relapsed acute myeloid leukemia received high-dose cytarabine-containing salvage chemotherapies and then developed grade 4 lymphopenia for more than one month...
October 5, 2018: International Journal of Hematology
Jieping Li, Li Yang, Rui Shen, Li Gong, Zhiqiang Tian, Huarong Qiu, Zhe Shi, Lichen Gao, Hongwu Sun, Guangsen Zhang
BACKGROUND: Recently, we found that berberine (BBR) exerts anti-acute myeloid leukemia activity, particularly toward high-risk and relapsed/refractory acute myeloid leukemia MV4-11 cells in vitro. However, the poor water solubility and low bioavailability observed with oral BBR administration has limited its clinical use. Therefore, we design and develop a novel oil-in-water self-nanoemulsifying system for BBR (BBR SNE) to improve oral bioavailability and enhance BBR efficacy against acute myeloid leukemia by greatly improving its solubility...
October 5, 2018: Journal of Nanobiotechnology
Maxim Norkin, Bronwen E Shaw, Ruta Brazauskas, Heather R Tecca, Helen L Leather, Juan Gea-Banacloche, Rammurti Kamble, Zachariah DeFilipp, David A Jacobsohn, Olle Ringden, Yoshihiro Inamoto, Kimberly Kasow, David Buchbinder, Peter Shaw, Peiman Hematti, Raquel Schears, Sherif M Badawy, Hillard M Lazarus, Neel Bhatt, Biljana Horn, Saurabh Chhabra, Kristin Page, Betty Hamilton, Gerhard C Hildebrandt, Jean A Yared, Vaibhav Agrawal, Amer Beitinjaneh, Navneet Majhail, Tamila Kindwall-Keller, Richard F Olsson, Helene Schoemans, Robert Peter Gale, Siddhartha Ganguly, Ibrahim Ahmed, Harry C Schouten, Jane Liesveld, Nandita Khera, Amir Steinberg, Ami J Shah, Melhem Solh, David I Marks, Witold Rybka, Mahmoud Aljurf, Andrew C Dietz, Usama Gergis, Biju George, Sachiko Seo, Mary E D Flowers, Minoo Battiwalla, Bipin N Savani, Marcie L Riches, John R Wingard
BACKGROUND: We analyzed late fatal infections (LFI) in allogeneic stem cell transplant (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. METHODS: We analyzed the incidence, infection types and risk factors contributing to LFI in 10336 adult and 5088 pediatric subjects surviving ≥2 years after first HCT without relapse. RESULTS: Among 2245 adult and 377 pediatric subjects who died, infections were a primary or contributory cause of death in 687(31%) and 110(29%) subjects, respectively...
October 1, 2018: Biology of Blood and Marrow Transplantation
Jun Xu, Ting-Ting Lv, Xiao-Fen Zhou, Ying Huang, Dong-Dong Liu, Guo-Lin Yuan
To assess treatment response and overall survival (OS) in refractory or relapsed acute myeloid leukemia (R/R AML) patients treated by different common salvage chemotherapy regimens.Medical records data from 142 R/R AML patients were reviewed in this retrospective study. Patients were treated with regimens based on the following drugs: cytarabine, granulocyte colony-stimulating factor (G-CSF), and fludarabine (FLAG) (n = 46); cytarabine and G-CSF in addition to aclarubicin or daunorubicin (CAG/DAG) (n = 30); cytarabine, G-CSF, and cladribine (CLAG) (n = 27); cytarabine, etoposide, and mitoxantrone (MEA) (n = 17); cytarabine plus idarubicin, daunorubicin, or mitoxantrone (IA/DA/MA) (n = 12); and homoharringtonine, cytarabine, and aclarubicin or daunorubicin (HAA/HAD) (n = 10)...
September 2018: Medicine (Baltimore)
Sarah A Buckley, Mary-Elizabeth Percival, Megan Othus, Anna B Halpern, Emily M Huebner, Pamela S Becker, Carole Shaw, Mazyar Shadman, Roland B Walter, Elihu H Estey
Patients with newly diagnosed (ND) and relapsed/refractory (RR) acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS, ≥10% blasts) often receive intensive chemotherapy at diagnosis and relapse. We retrospectively identified 365 patients and categorized the reasons for receiving treatment off study (medical, logistical, or unclear). The pretreatment characteristics of the on and off study groups were similar. Rates of the complete remission (CR) without measurable residual disease were significantly higher for ND patients treated on versus off study (61% versus 35%), but CR rates and survival were low for all RR patients regardless of study assignment...
October 2, 2018: Leukemia & Lymphoma
Jonas Westhus, Richard Noppeney, Ulrich Dührsen, Maher Hanoun
Acute myeloid leukemia (AML) is characterized by a high failure rate to achieve complete remission as well as high relapse rates that cause an emergent need for efficient and tolerable salvage therapies. The combination of FLAG with idarubicin (FLAG-Ida) is a widely used protocol. However, its efficacy has been analyzed in only a limited number of studies with majorly small patient cohorts. Here, we analyzed 132 patients with largely primary refractory or first-time relapsed AML treated according to the FLAG-Ida protocol...
October 2, 2018: Leukemia & Lymphoma
Vipul Sheth, Boaz Nachmias, Sigal Grisariu, Batia Avni, Reuven Or, Michael Shapira
Myeloablative doses of busulfan (Bu) with fludarabine (Flu) have reduced toxicity, however, limited by an increased relapse rate. We aimed to improve outcome of Flu-Bu regimen by augmentation with thiotepa (TT) (10 mg/kg). Eighty-nine patients with AML, 44 patients conditioned with Flu-Bu (group 1), and 45 patients augmented with TT (Flu-Bu-TT, group 2), were retrospectively analyzed. Primary objectives were toxicity and outcomes. Major toxicities were comparable: mucositis (p = 1.0), sepsis (p = ...
October 2, 2018: Leukemia & Lymphoma
Monika Herrmann, Christina Krupka, Katrin Deiser, Bettina Brauchle, Anetta Marcinek, Ana Ogrinc Wagner, Felicitas Rataj, Ralph Mocikat, Klaus H Metzeler, Karsten Spiekermann, Sebastian Kobold, Nadja C Fenn, Karl-Peter Hopfner, Marion Subklewe
The CD33-targeting bispecific T-cell engager (BiTE®) AMG 330 proved to be highly efficient in mediating cytolysis of acute myeloid leukemia (AML) cells in vitro and in mouse models. Yet, T-cell activation is correlated with upregulation of PD-L1 and other inhibitory checkpoints on AML cells that confer adaptive immune resistance. PD 1 and PD-L1 blocking agents may counteract T-cell dysfunction, however, at the expense of broadly distributed immune-related adverse events (irAEs). We developed a bifunctional checkpoint inhibitory T-cell-engaging (CiTE) antibody that combines T-cell redirection to CD33 on AML cells with locally restricted immune checkpoint blockade...
October 1, 2018: Blood
Christan M Thomas, Peter Campbell
FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase that is responsible for the proliferation and survival of hematopoietic stem cells in acute myeloid leukemia. Although patients with FLT3 mutations have similar rates of remission following induction chemotherapy, relapse rates are significantly higher and patients with FLT3 mutations have significantly worse outcomes for overall survival and disease-free survival. Early FLT3 inhibitors, such as sorafenib, were non-selective and inhibited several tyrosine kinase receptors resulting in significant toxicity...
September 30, 2018: Journal of Oncology Pharmacy Practice
Yoo Jin Lee, Dong Won Baek, Jae-Sook Ahn, Seo-Yeon Ahn, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Hyeoung Joon Kim, Ji Yeon Ham, Jang Soo Suh, Sang Kyun Sohn, Joon Ho Moon
BACKGROUND: The optimal number of high-dose cytarabine (HDAC) consolidation cycles before allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia is not fully standardized. PATIENTS AND METHODS: This study evaluated the impact of HDAC consolidation cycles before allogeneic HCT in 194 patients with acute myeloid leukemia in first complete remission between 1998 and 2014. The patients were reclassified into 3 groups-no consolidation (C0, n = 20), 1 consolidation (C1, n = 115), and ≥ 2 consolidations (C2, n = 59)-by pre-HCT consolidation cycle...
August 29, 2018: Clinical Lymphoma, Myeloma & Leukemia
Thibault Voeltzel, Mario Flores-Violante, Florence Zylbersztejn, Sylvain Lefort, Marion Billandon, Sandrine Jeanpierre, Stéphane Joly, Gaelle Fossard, Milen Milenkov, Frédéric Mazurier, Ali Nehme, Amine Belhabri, Etienne Paubelle, Xavier Thomas, Mauricette Michallet, Fawzia Louache, Franck-Emmanuel Nicolini, Claude Caron de Fromentel, Véronique Maguer-Satta
In a significant number of cases cancer therapy is followed by a resurgence of more aggressive tumors derived from immature cells. One example is acute myeloid leukemia (AML), where an accumulation of immature cells is responsible for relapse following treatment. We previously demonstrated in chronic myeloid leukemia that the bone morphogenetic proteins (BMP) pathway is involved in stem cell fate and contributes to transformation, expansion, and persistence of leukemic stem cells. Here, we have identified intrinsic and extrinsic dysregulations of the BMP pathway in AML patients at diagnosis...
September 27, 2018: Cell Death & Disease
Arnaud Pigneux, Marie C Béné, Louis-Rachid Salmi, Pierre-Yves Dumas, Jacques Delaunay, Caroline Bonmati, Romain Guièze, Isabelle Luquet, Pascale Cornillet-Lefebvre, Eric Delabesse, Jean-Christophe Ianotto, Mario Ojeda-Uribe, Mathilde Hunault, Anne Banos, Luc Matthieu Fornecker, Marc Bernard, Eric Jourdan, Norbert Vey, Hacene Zerazhi, Yosr Hishri, Ariane Mineur, Julien Asselineau, Roselyne Delepine, Jean-Yves Cahn, Norbert Ifrah, Christian Récher
PURPOSE: Acute myeloid leukemia (AML) in elderly patients has a poor prognosis. In an attempt to improve outcome for these patients, the prospective open-label phase III LAM-SA 2007 (Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old) trial randomly assigned patients to a standard induction regimen with lomustine added or to a consolidation regimen with cytarabine and idarubicin...
September 27, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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