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Hematologic malignancy

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https://www.readbyqxmd.com/read/28240607/downregulation-of-gata1-drives-impaired-hematopoiesis-in-primary-myelofibrosis
#1
Laure Gilles, Ahmet Dirim Arslan, Christian Marinaccio, Qiang Jeremy Wen, Priyanka Arya, Maureen McNulty, Qiong Yang, Jonathan C Zhao, Katerina Konstantinoff, Terra Lasho, Animesh Pardanani, Brady Stein, Isabelle Plo, Sriram Sundaravel, Amittha Wickrema, Annarita Migliaccio, Sandeep Gurbuxani, William Vainchenker, Leonidas C Platanias, Ayalew Tefferi, John D Crispino
Primary myelofibrosis (PMF) is a clonal hematologic malignancy characterized by BM fibrosis, extramedullary hematopoiesis, circulating CD34+ cells, splenomegaly, and a propensity to evolve to acute myeloid leukemia. Moreover, the spleen and BM of patients harbor atypical, clustered megakaryocytes, which contribute to the disease by secreting profibrotic cytokines. Here, we have revealed that megakaryocytes in PMF show impaired maturation that is associated with reduced GATA1 protein. In investigating the cause of GATA1 downregulation, our gene-expression study revealed the presence of the RPS14-deficient gene signature, which is associated with defective ribosomal protein function and linked to the erythroid lineage in 5q deletion myelodysplastic syndrome...
February 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28239468/immunotherapy-associated-autoimmune-hemolytic-anemia
#2
Uqba Khan, Farman Ali, Muhammad Siddique Khurram, Awais Zaka, Tarik Hadid
BACKGROUND: Immunotherapy has been widely used in the treatment of several solid and hematologic malignancies. Checkpoint inhibitors have been the forefront of cancer immunotherapy in recent years. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) pathway are the prototypic checkpoint targets for immunotherapy. When combined, CTLA-4 and PD-1 checkpoint inhibitors work synergistically, but with increased probability of toxicity. The following case represents an unusual adverse effect of combined treatment with ipilimumab and nivolumab used for treatment of metastatic melanoma...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28239465/pd-1-blockade-induces-remissions-in-relapsed-classical-hodgkin-lymphoma-following-allogeneic-hematopoietic-stem-cell-transplantation
#3
James Godfrey, Michael R Bishop, Sahr Syed, Elizabeth Hyjek, Justin Kline
BACKGROUND: Allogeneic hematopoietic stem cell transplantation and checkpoint blockade therapy are immune-based therapies that have activity in selected refractory hematologic malignancies. Interest has developed in combining these treatments for high-risk hematologic diseases. However, there is concern that checkpoint blockade could augment graft-versus-host disease, and very few studies have evaluated the safety of checkpoint blockade in the post-allogeneic setting. Here, we report the outcomes of three patients with relapsed classical Hodgkin's lymphoma following allogeneic transplant that were treated with the anti-PD-1 antibody, nivolumab...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28238096/clinical-impact-of-galectin-3-in-newly-diagnosed-t-15-17-q22-q21-pml-rara-acute-promyelocytic-leukemia-treated-with-all-trans-retinoic-acid-and-arsenic-trioxide-based-regimens
#4
Na Gao, Xue-Xia Wang, Jian-Rong Sun, Wen-Zheng Yu, Xi-Zhi Li
Increased galectin-3 expression has been currently showed to be associated with poor prognosis in some hematological malignancies, such as acute myeloid leukemia, diffuse large B cell lymphoma. However, little is known about the clinical significance of galectin-3 in patients with acute promyelocytic leukemia (APL). We investigated the concentration of serum galectin-3 and characterized the relationship between galectin-3 and outcome in patients with APL. Higher galectin-3 levels were detected in patients with APL compared with the healthy controls (p < 0...
February 25, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28237835/integration-of-a-cd19-car-into-the-tcr-alpha-chain-locus-streamlines-production-of-allogeneic-gene-edited-car-t-cells
#5
Daniel T MacLeod, Jeyaraj Antony, Aaron J Martin, Rachel J Moser, Armin Hekele, Keith J Wetzel, Audrey E Brown, Melissa A Triggiano, Jo Ann Hux, Christina D Pham, Victor V Bartsevich, Caitlin A Turner, Janel Lape, Samantha Kirkland, Clayton W Beard, Jeff Smith, Matthew L Hirsch, Michael G Nicholson, Derek Jantz, Bruce McCreedy
Adoptive cellular therapy using chimeric antigen receptor (CAR) T cell therapies have produced significant objective responses in patients with CD19(+) hematological malignancies, including durable complete responses. Although the majority of clinical trials to date have used autologous patient cells as the starting material to generate CAR T cells, this strategy poses significant manufacturing challenges and, for some patients, may not be feasible because of their advanced disease state or difficulty with manufacturing suitable numbers of CAR T cells...
February 22, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28236351/genomic-array-as-compared-to-karyotyping-in-myelodysplastic-syndromes-in-a-prospective-clinical-trial
#6
Marian J Stevens-Kroef, Daniel Olde Weghuis, Najat ElIdrissi-Zaynoun, Bert van der Reijden, Eline M P Cremers, Canan Alhan, Theresia M Westers, Heleen A Visser-Wisselaar, Dana A Chitu, Sonia M Cunha, Edo Vellenga, Saskia K Klein, Pierre Wijermans, Georgine E de Greef, M R Schaafsma, Petra Muus, Gert J Ossenkoppele, Arjan A van de Loosdrecht, Joop H Jansen
Karyotyping is considered as the gold standard in the genetic subclassification of myelodysplastic syndrome (MDS). Oligo/SNP-based genomic array profiling is a high-resolution tool that also enables genome wide analysis. We compared karyotyping with oligo/SNP-based array profiling in 104 MDS patients from the HOVON-89 study. Oligo/SNP-array identified all cytogenetically defined genomic lesions, except for subclones in two cases and balanced translocations in three cases. On the other hand oligo/SNP-based genomic array profiling had a higher success rate, showing 55 abnormal cases, while an abnormal karyotype was found in only 35 patients...
February 25, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28236299/development-of-the-platelet-efficacy-score-pescore-to-predict-the-efficacy-of-platelet-transfusion-in-oncohematologic-patients
#7
Anna Quaglietta, Maura Di Saverio, Giuseppe Lucisano, Patrizia Accorsi, Antonio Nicolucci
BACKGROUND: Despite the prophylactic use of platelet transfusion, hemorrhagic complications still represent an important cause of morbidity and mortality in patients with hematologic malignancies. Patient-related factors and characteristics of the transfused product can affect transfusion efficacy. STUDY DESIGN AND METHODS: The aim of this study was to develop and validate the Platelet Efficacy Score (PEscore), based on patient and product characteristics, to predict the likelihood of a satisfactory platelet transfusion (absolute increment ≥10...
February 24, 2017: Transfusion
https://www.readbyqxmd.com/read/28230830/several-aspects-of-descriptive-epidemiology-of-hematological-malignancies-in-adult-population-of-ukraine-belarus-and-russian-federation-after-chornobyl-accident
#8
N Guslitser, M P Zavelevich, S V Koval, D F Gluzman
Chornobyl impact on the health of adult population in Ukraine, Belarus and Russian Federation was a subject of several studies. However, the studies of the effects of Chornobyl on leukemia in adult populations in post-Soviet countries are scarce and the results are contradictory up to present. The results of the epidemiological studies of the oncohematological consequences of Chornobyl accident are briefly reviewed with particular focus on pre-Chornobyl and post-Chornobyl trends in leukemia incidence in Ukraine, Belarus and Russian Federation as well as in small territories of these countries with various levels of radionuclide contamination...
December 2016: Experimental Oncology
https://www.readbyqxmd.com/read/28230450/characteristics-and-medication-use-of-psoriasis-patients-who-may-or-may-not-qualify-for-randomized-controlled-trials
#9
William Malatestinic, Beth Nordstrom, Jashin J Wu, Orin Goldblum, Kathleen Solotkin, Chen-Yen Lin, Kristin Kistler, Kathy Fraeman, Joseph Johnston, Lcdr Lesley Hawley, Nicholas Sicignano, Andre Araujo
BACKGROUND: Clinical trials impose exclusion criteria that may limit the generalizability of results. OBJECTIVES: To (a) determine the percentage of real-world patients who would qualify for psoriasis randomized controlled trials; (b) ascertain differences between moderate-to-severe psoriasis patients who would be eligible, ineligible, or potentially eligible for clinical trials; and (c) compare their biologic treatment patterns. METHODS: Moderate-to-severe psoriasis patients were identified from the U...
March 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28226419/evaluation-of-risk-factors-for-clostridium-difficile-infection-in-hematopoietic-stem-cell-transplant-recipients
#10
Tonya L Scardina, Elena Kang Martinez, Neelam Balasubramanian, Mary Fox-Geiman, Scott E Smith, Jorge P Parada
STUDY OBJECTIVES: The primary objective was to determine the impact of hematologic malignancies and/or conditioning regimens on the risk of developing Clostridium difficile infection (CDI) in patients undergoing hematopoietic stem cell transplantation (HSCT). Secondary objectives were to determine if traditional CDI risk factors applied to patients undergoing HSCT and to determine the presence of CDI markers of severity of illness among this patient population. DESIGN: Single-center, retrospective, case-control study...
February 22, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28225458/prognostic-factors-and-outcome-of-patients-with-hematological-malignancies-in-phase-i-trials-the-gustave-roussy-scoring-system
#11
Lina Benajiba, Jean-Marie Michot, Capucine Baldini, Laura Faivre, Andrea Varga, Rastilav Balheda, Anas Gazzah, Ecaterina Ileana, Sophie Postel-Vinay, Christophe Massard, Stéphane de Botton, Jean-Charles Soria, Vincent Ribrag
Despite considerable progress in hematological malignancies (HM) biology during the last decades, translation into clinical benefit remains a major challenge. To improve patient selection and identify patients most likely to benefit from phase I trials, we designed and validated, in an independent cohort, a simple prognostic score. Treatment outcome, toxicity, and survival data from 82 consecutive patients enrolled in 14 phase I trials were reviewed (January 2008-February 2012). We validated these results on a prospectively collected cohort (17 phase I trials, February 2012-May 2014, 88 patients)...
February 20, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28224299/clinical-impact-of-sarcopenia-and-relevance-of-nutritional-intake-in-patients-before-and-after-allogeneic-hematopoietic-stem-cell-transplantation
#12
Shouichi Tanaka, Osamu Imataki, Atsuo Kitaoka, Shuji Fujioka, Etsuyo Hanabusa, Yumiko Ohbayashi, Makiko Uemura, Nobuo Arima, Tetsuji Yamamoto
PURPOSE: We conducted a retrospective study to evaluate the effect of rehabilitation on minimizing sarcopenia during hematopoietic stem cell transplantation (HSCT) therapy. METHODS: We developed a protocol to test for retention of physical function during HSCT. Muscle strength, muscle circumference, and muscle function before and after HSCT were measured. Consecutive patients with hematological malignancies who underwent HSCT treatment were recruited in this research...
February 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28222739/generation-of-donor-specific-tr1-cells-to-be-used-after-kidney-transplantation-and-definition-of-the-timing-of-their-in-vivo-infusion-in-the-presence-of-immunosuppression
#13
Bechara Mfarrej, Eleonora Tresoldi, Angela Stabilini, Alessia Paganelli, Rossana Caldara, Antonio Secchi, Manuela Battaglia
BACKGROUND: Operational tolerance is an alternative to lifelong immunosuppression after transplantation. One strategy to achieve tolerance is by T regulatory cells. Safety and feasibility of a T regulatory type 1 (Tr1)-cell-based therapy to prevent graft versus host disease in patients with hematological malignancies has been already proven. We are now planning to perform a Tr1-cell-based therapy after kidney transplantation. METHODS: Upon tailoring the lab-grade protocol to patients on dialysis, aims of the current work were to develop a clinical-grade compatible protocol to generate a donor-specific Tr1-cell-enriched medicinal product (named T10 cells) and to test the Tr1-cell sensitivity to standard immunosuppression in vivo to define the best timing of cell infusion...
February 21, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28222323/a-case-report-of-the-clear-cell-variant-of-gallbladder-carcinoma
#14
Ravi Maharaj, Christo Cave, Kevin Sarran, Nigel Bascombe, Dilip Dan, Wesley Greaves, Wayne A Warner
INTRODUCTION: Clear cell gallbladder carcinoma accounts for less than 1% of all gallbladder malignancies and demonstrates its unique histopathological characteristics in patients with no prior medical illness or familial predisposition. PRESENTATION OF CASE: Here we present a case of a 56-year-old female, with no prior medical conditions presented with a 2-month history of upper abdominal pain. Routine hematological and biochemical tests were unremarkable. An abdominal ultrasound revealed the presence of a gallbladder calculi, and a fundic mass while magnetic resonance cholangiopancreatography revealed a 8...
January 12, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28222220/meaningful-endpoints-for-therapies-approved-for-hematologic-malignancies
#15
B Douglas Smith, Amy E DeZern, Alex W Bastian, Brian G M Durie
BACKGROUND: Overall survival (OS) is considered the gold standard for determining treatment efficacy in oncology trials, but the relation between treatment and OS can be challenging to assess because of long study durations and the impact of subsequent therapies on outcome. Using OS can be particularly difficult for new therapies in hematologic malignancies (HMs). METHODS: This retrospective analysis was conducted to characterize the primary endpoints used to support US Food and Drug Administration (FDA) approvals for new drug or novel HM indications between January 2002 and July 2015...
February 21, 2017: Cancer
https://www.readbyqxmd.com/read/28222037/cancer-during-pregnancy-clinical-characteristics-treatment-outcomes-and-prognosis-for-mothers-and-infants
#16
Katarina Jeremic, Aleksandar Stefanovic, Jelena Dotlic, Sasa Kadija, Olivera Kontic, Miroslava Gojnic, Jelena Jeremic, Vesna Kesic
OBJECTIVE: To assess which obstetrical characteristics and treatment improved outcomes and prognosis of pregnant women with malignancy. METHODS: A prospective study, undertaken between 2005 and 2014, involving 35 pregnant women who were diagnosed with malignant tumors during pregnancy. Patients were followed-up for 1 year after delivery. The pregnancy course and outcome and parameters that could influence the condition of mother and fetus were evaluated. RESULTS: Most malignancies were hematological, diagnosed in the second trimester and treated with combined therapy (surgery/adjuvant) after pregnancy...
February 21, 2017: Journal of Perinatal Medicine
https://www.readbyqxmd.com/read/28220348/proteasome-inhibitor-mg132-induces-thyroid-cancer-cell-apoptosis-by-modulating-the-activity-of-transcription-factor-foxo3a
#17
Wei Qiang, Fang Sui, Jingjing Ma, Xinru Li, Xiaojuan Ren, Yuan Shao, Jiazhe Liu, Haixia Guan, Bingyin Shi, Peng Hou
Proteasome inhibitors are promising antitumor drugs with preferable cytotoxicity in malignant cells and have exhibited clinical efficiency in several hematologic malignancies. P53-dependent apoptosis has been reported to be a major mechanism underlying. However, apoptosis can also be found in cancer cells with mutant-type p53, suggesting the involvement of p53-independent mechanism. Tumor suppressor forkhead Box O3 is another substrate of proteasomal degradation, which also functions partially through inducing apoptosis...
February 20, 2017: Endocrine
https://www.readbyqxmd.com/read/28219836/donor-lymphocyte-infusion-for-relapsed-hematological-malignancies-after-unrelated-allogeneic-bone-marrow-transplantation-facilitated-by-the-japan-marrow-donor-program
#18
Toshihiro Miyamoto, Takahiro Fukuda, Marie Nakashima, Tomoko Henzan, Shinsuke Kusakabe, Naoki Kobayashi, Junichi Sugita, Takeshi Mori, Mineo Kurokawa, Shin-Ichiro Mori
To evaluate the safety and efficacy of donor lymphocyte infusion (DLI), we retrospectively analyzed 414 recipients who received unrelated DLI (UDLI) for the treatment of relapsed hematological malignancy after unrelated bone marrow transplantation (BMT). UDLI was administered for acute myelogenous leukemia (n=184), myelodysplastic syndrome (n=69), acute lymphocytic leukemia (n=57), chronic myelogenous leukemia (CML, n=36), lymphoid neoplasms (n=38), adult T-cell leukemia/lymphoma (n=18), and multiple myeloma (n=12)...
February 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28218826/synthesis-and-antiproliferative-effect-of-ethyl-4-4-substitutedpiperidin-1-yl-benzylpyrrolo-1-2-a-quinoxaline-carboxylate-derivatives-on-human-leukemic-cells
#19
Jean Guillon, Vanessa Desplat, Marian Vincenzi, Romain Lucas, Stéphane Moreau, Solène Savrimoutou, Noel Pinaud, David Bigat, Elodie Enriquez, Mathieu Marchivie, Sylvain Routier, Pascal Sonnet, Filomena Rossi, Luisa Ronga
Acute leukemia is a hematological malignancy with high incidence and recurrence rates, and is characterized by an accumulation of blasts in bone marrow due to proliferation of immature lymphoid or myeloid cells associated with a blockade of differentiation. The heterogeneity of leukemia led to look for new specific molecules for leukemia subtypes or even for therapy-resistant cases. Among heterocyclic derivatives that attracted attention due to their large spread biological activities, we have focused our interest towards the pyrrolo[1,2-a]quinoxaline heterocyclic framework that has been previously identified as an interesting scaffold for antiproliferative activities against various human cancer cell lines...
February 20, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28218709/pet-imaging-for-initial-staging-and-therapy-assessment-in-multiple-myeloma-patients
#20
REVIEW
Clément Bailly, Rodolphe Leforestier, Bastien Jamet, Thomas Carlier, Mickael Bourgeois, François Guérard, Cyrille Touzeau, Philippe Moreau, Michel Chérel, Françoise Kraeber-Bodéré, Caroline Bodet-Milin
Multiple myeloma (MM) is a hematological neoplasm characterized by the clonal proliferation of malignant plasma cells in the bone marrow. MM results in diffuse or focal bone infiltration and extramedullary lesions. Over the past two decades, advances have been made with regard to the diagnosis, staging, treatment, and imaging of MM. Computed tomography (CT) and magnetic resonance imaging (MRI) are currently recommended as the most effective imaging modalities at diagnostic. Yet, recent data from the literature suggest that positron emission tomography combined with computed tomography (PET/CT) using (18)F-deoxyglucose (FDG) is a promising technique for initial staging and therapeutic monitoring in this pathology...
February 18, 2017: International Journal of Molecular Sciences
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