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https://www.readbyqxmd.com/read/29222308/hemophilia-gene-therapy-comes-of-age
#1
REVIEW
Lindsey A George
Concurrent with the development of recombinant factor replacement products, the characterization of the F9 and F8 genes over 3 decades ago allowed for the development of recombinant factor products and made the hemophilias a target disease for gene transfer. The progress of hemophilia gene therapy has been announced in 3 American Society of Hematology scientific plenary sessions, including the first "cure" in a large animal model of hemophilia B in 1998, first in human sustained vector-derived factor IX activity in 2011, and our clinical trial results reporting sustained vector-derived factor IX activity well into the mild or normal range in 2016...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222298/management-of-multiple-myeloma-in-the-newly-diagnosed-patient
#2
REVIEW
María-Victoria Mateos, Jesús F San Miguel
Multiple myeloma is the second most frequent hematological disease. The introduction of melphalan as high-dose therapy followed by autologous hematopoietic cell transplantation (HDT/ASCT) for young patients and the availability of novel agents for young and elderly patients with multiple myeloma have dramatically changed the perspective of treatment. However, further research is necessary if we want definitively to cure the disease. Treatment goals for transplant-eligible and non-transplant-eligible patients should be to prolong survival by achieving the best possible response while ensuring quality of life...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222296/what-are-the-current-treatment-approaches-for-patients-with-polycythemia-vera-and-essential-thrombocythemia
#3
REVIEW
Alessandro M Vannucchi, Paola Guglielmelli
Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative neoplasms that are characterized by thrombohemorrhagic complications, symptom burden, and impaired survival mainly due to thrombosis, progression to myelofibrosis, and transformation to acute leukemia. In this manuscript, we will review the most recent changes in diagnostic criteria, the improvements in risk stratification, and the "state of the art" in the daily management of these disorders. The role of conventional therapies and novel agents, interferon α and the JAK2 inhibitor ruxolitinib, is critically discussed based on the results of a few basic randomized clinical studies...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29207115/current-status-and-future-prospects-of-the-strategy-of-combining-car%C3%A2-t-with-pd%C3%A2-1-blockade-for-antitumor-therapy-review
#4
Jinjing Xu, Qing Zhang, Kang Tian, Haiyu Wang, Hong Yin, Junnian Zheng
The immune system serves an important role in controlling and eradicating malignant cells. Immunotherapy for treating tumors has received much attention in recent years due to its marked effect. There are two approaches which currently lead this field: Chimeric antigen receptor‑modified T‑cell immunotherapy (CAR‑T) and programmed cell death protein-1 blockade (PD‑1 blockade). CAR‑T has emerged as a promising regimen for the treatment of a range of types of cancer, including chronic lymphoid leukemia and neuroblastoma, with studies of long term remission in certain patients...
November 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29203585/safety-and-efficacy-of-selinexor-in-relapsed-or-refractory-multiple-myeloma-and-waldenstrom-s-macroglobulinemia
#5
Christine Chen, David Siegel, Martin Gutierrez, Meagan Jacoby, Craig C Hofmeister, Nashat Gabrail, Rachid Baz, Morten Mau-Sorensen, Jesus G Berdeja, Michael Savona, Lynn Savoie, Suzanne Trudel, Nuchanan Areethamsirikul, T J Unger, Tami Rashal, Tim Hanke, Michael Kauffman, Sharon Shacham, Donna Reece
Novel therapies are needed for patients with relapsed or refractory multiple myeloma (MM). We conducted a multicenter, phase 1 study in advanced hematological malignancies to assess the safety, efficacy and recommended phase 2 dose (RP2D) of oral selinexor, a selective inhibitor of the nuclear export protein XPO1. In the dose-escalation phase, 25 patients with heavily pretreated MM (22) or Waldenstrom's macroglobulinemia (3) were administered selinexor (3-60 mg/m2) in 8 or 10 doses per 28-day cycle. In the dose-expansion phase, 59 patients with MM received selinexor at 45 or 60 mg/m2 with 20 mg dexamethasone, twice-weekly in 28-day cycles, or selinexor (40 or 60mg flat dose) without corticosteroids in 21 day cycles...
December 4, 2017: Blood
https://www.readbyqxmd.com/read/29200115/medical-complications-of-brain-tumors
#6
Nimish A Mohile
PURPOSE OF REVIEW: This article discusses common and emergent medical complications encountered in patients with primary brain tumors. RECENT FINDINGS: Clinical studies and systematic reviews published in recent years have improved knowledge regarding the incidence of neurologic and medical complications occurring in patients with primary brain tumors. Studies in tumor-related epilepsy and venous thromboembolism provide data for the clinician to make evidence-based decisions about perioperative management, prophylaxis, and therapy...
December 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/29195897/an-inflammatory-environment-containing-tnf%C3%AE-favors-tet2-mutant-clonal-hematopoiesis
#7
Samuel O Abegunde, Rena Buckstein, Richard A Wells, Michael J Rauh
Clonal hematopoiesis of aging and indeterminate potential (ARCH or CHIP), driven mainly by mutations in DNMT3A and TET2, is an emerging public health issue, affecting at least 10-15% of adults older than 65 years. CHIP is associated with increased risks of de novo and therapy-related hematological neoplasms and serves as a reservoir for leukemic relapse. CHIP is also associated with increased all-cause mortality and risk of cardio-metabolic disease. The latter association may be explained, at least in part, by the effects of inactivating mutations in TET2 on progeny macrophages...
November 28, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29195008/consensus-predictive-model-for-the-prediction-of-human-k562-cell-growth-inhibition-through-enalos-cloud-platform
#8
Antreas Afantitis, Georgios Leonis, Roberto Gambari, Georgia Melagraki
Beta thalassemia is an inherited hematologic disorder caused by various mutations of the β-globin gene, thus resulting in a significant decrease of adult hemoglobin (HbA) production. Since no other specific treatment exists to date, apart from blood transfusion and chelation therapy, the increase of fetal hemoglobin (HbF) levels by drug molecules is considered of great potential in β-thalassemia treatment, being expected to counterbalance the impaired production of HbA. Within this context, we have worked towards the development of a predictive model that will allow the identification of new possible HbF inducers...
December 1, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29189429/new-developments-in-immunotherapy-for-pediatric-solid-tumors
#9
Liora M Schultz, Robbie Majzner, Kara L Davis, Crystal Mackall
PURPOSE OF REVIEW: Building upon preclinical advances, we are uncovering immunotherapy strategies that are translating into improved outcomes in tumor subsets. Advanced pediatric solid tumors carry poor prognoses and resultant robust efforts to apply immunotherapy advances to pediatric solid tumors are in progress. Here, we discuss recent developments in the field using mAb and mAb-based therapies including checkpoint blockade and chimeric antigen receptors (CARs). RECENT FINDINGS: The pediatric solid tumor mAb experience targeting the diganglioside, GD2, for patients with neuroblastoma has been the most compelling to date...
November 20, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29184971/positioning-of-proteasome-inhibitors-in-therapy-of-solid-malignancies
#10
REVIEW
Margot S F Roeten, Jacqueline Cloos, Gerrit Jansen
Targeting of the protein degradation pathway, in particular, the ubiquitin-proteasome system, has emerged as an attractive novel cancer chemotherapeutic modality. Although proteasome inhibitors have been most successfully applied in the treatment of hematological malignancies, they also received continuing interest for the treatment of solid tumors. In this review, we summarize the current positioning of proteasome inhibitors in the treatment of common solid malignancies (e.g., lung, colon, pancreas, breast, and head and neck cancer), addressing topics of their mechanism(s) of action, predictive factors and molecular mechanisms of resistance...
November 28, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29179521/silibinin-an-old-drug-for-hematological-disorders
#11
REVIEW
Hai Zou, Xing-Xing Zhu, Guo-Bing Zhang, Yuan Ma, Yi Wu, Dong-Sheng Huang
Introduction: Silibinin (silybin), a non-toxic natural polyphenolic flavonoid, is the principal and the most biologically active component of silymarin. It is efficient in the treatment of acute and chronic liver disorders caused by toxins, drug, alcohol, hepatitis, and gall bladder disorders. Further, in our previous studies, we explored the anti-cancer efficacy in common cancers, such as lung, prostatic, colon, breast, bladder, as well as, hepatocellular carcinoma. Interestingly, silibinin is still not solely limited to the treatment of these diseases...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29167924/persistent-cytarabine-and-daunorubicin-exposure-after-administration-of-novel-liposomal-formulation-cpx-351-population-pharmacokinetic-assessment
#12
Mina Nikanjam, Edmund V Capparelli, Jeffrey E Lancet, Arthur Louie, Gary Schiller
PURPOSE: CPX-351 is a novel liposomal formulation of cytarabine and daunorubicin which has recently been FDA approved for treatment of acute myeloid leukemia (AML). The current study investigated the pharmacokinetics (PK) of this liposomal formulation. METHODS: CPX-351 PK data (cytarabine, daunorubicin, and metabolites) from a phase I study of relapsed and refractory AML were used for the analysis. Therapy was given days 1, 3, and 5 of induction (3-134 units/m(2))...
November 22, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29167672/novel-concept-of-cd4-mediated-activation-of-regulatory-t-cells-for-the-treatment-of-graft-versus-host-disease
#13
REVIEW
Janine Schlöder, Carsten Berges, Andrea Tuettenberg, Helmut Jonuleit
Allogeneic hematopoietic stem cell transplantation is the only curative treatment option for several hematological malignancies and immune deficiency syndromes. Nevertheless, the development of a graft-versus-host disease (GvHD) after transplantation is a high risk and a severe complication with high morbidity and mortality causing therapeutic challenges. Current pharmacological therapies of GvHD lead to generalized immunosuppression followed by severe adverse side effects including infections and relapse of leukemia...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163800/end-of-life-care-in-children-with-hematologic-malignancies
#14
Jessica I Hoell, Jens Warfsmann, Stefan Balzer, Arndt Borkhardt, Gisela Janssen, Michaela Kuhlen
Introduction: Hematologic malignancies (HM) represent the most common neoplasms in childhood. Despite improved overall survival rates, they are still a major contributor to cancer death in children. Aims: To determine the proportion of children with HM in pediatric palliative care (PPC) and to identify the clinical characteristics and symptoms in comparison to children with extracranial solid tumors (non HM patients). Patients and Methods: This study was conducted as a single-center retrospective cohort study of patients in the care of a large specialized PPC team...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156888/chimeric-antigen-receptor-car-t-and-other-t-cell-strategies-for-pancreas-adenocarcinoma
#15
Anna M Varghese
Treatments in metastatic pancreas cancer remain based in cytotoxic chemotherapy, and novel treatment strategies are needed. Building on the emerging role of T cell therapy in hematologic malignancies and our understanding of the underlying biology of pancreas cancer, research is growing in the role of T cell therapy for patients with solid tumors in general and more specifically patients with pancreas cancer. This review will focus on describing the biology of T cell therapy and its current applications in pancreas cancer...
October 24, 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29149783/hematological-improvement-of-patients-with-active-rheumatoid-arthritis-by-%C3%AE-d-mannuronic-acid-m2000-as-a-novel-nsaid-with-immunosuppressive-property
#16
Hossein Ahmadi, Ahmad Reza Jamshidi, Mahdi Mahmoudi, Farhad Gharibdoost, Mahdi Vojdanian, Mohammad Javad Fattahi, Noushin Rastkari, Zahra Aghazadeh, Abbas Mirshafiey
The aim of this study was to investigate the effect of β-D-mannuronic acid (M2000) on hematological parameters in patients with active rheumatoid arthritis. This study was conducted on 25 patients with active rheumatoid arthritis (RA) (identifier: IRCT2014011213739N2). M2000 was administered orally for anemic and non-anemic RA patients at a dose of 500 mg twice daily for 12 weeks. The patients were permitted to continue the conventional treatments excluding NSAIDs. Blood samples were collected at baseline, 4 and 12 weeks after drug administration and were tested for hematological parameters...
October 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29145997/correlation-of-graft-immune-composition-with-outcomes-after-allogeneic-stem-cell-transplantation-moving-towards-a-perfect-transplant
#17
REVIEW
Guang Gu, Jian-Zhu Yang, Li-Xia Sun
Allogeneic stem cell transplantation (allo-SCT) offers an important curative therapy for hematological malignancies and other diseases. A number of studies have demonstrated the association of immune compositions in allografts with outcomes after allo-SCT, which promote graft engineering to improve transplant prognosis. This review summarizes the advances in investigating the correlation of the graft immune compositions with transplant outcomes in different transplant modalities, focusing on the immune subsets likely to have the greatest impact on clinical outcomes...
November 7, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29133623/immu-140-a-novel-sn-38-antibody-drug-conjugate-targeting-hla-dr-mediates-dual-cytotoxic-effects-in-hematological-cancers-and-malignant-melanoma
#18
Thomas M Cardillo, Serengulam V Govindan, Maria B Zalath, Diane L Rossi, Yang Wang, Chien-Hsing Chang, David M Goldenberg
HLA-DR is a member of the MHC class II antigen family expressed on hematological and solid tumors.  Antibodies directed against HLA-DR have demonstrated some clinical success, but toxicities limited development.  IMMU-140 is an anti-HLA-DR antibody-drug conjugate comprised of the active metabolite of irinotecan, SN-38, conjugated to a humanized anti-HLA-DR IgG4 antibody (IMMU-114); the IgG4 naked antibody is devoid of immune functions. Our aim was to determine if SN-38, the metabolite of a drug not commonly used in hematopoietic cancers, would be effective and safe when targeted to HLA-DR-expressing tumors...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29120553/rituximab-maintenance-strategy-in-advanced-follicular-lymphoma-facts-and-controversies
#19
Vibor Milunović, Martina Bogeljić Patekar, Karla Mišura Jakubac, Inga Mandac Rogulj, Delfa Radić-Krišto, Ana Planinc-Peraica, Slobodanka Ostojić Kolonić
Rituximab is a chimeric monoclonal CD20 antibody used in the treatment of CD20 positive non-Hodgkin lymphomas and has revolutionized treatment approach to these hematologic malignancies in the last decade. The main aim of this review is to present data on the use of rituximab in the treatment of follicular lymphoma (FL). We will focus on rituximab maintenance strategies in the first and second line treatment. This approach has improved the outcome in FL patients with better progression-free survival in all patients and better overall survival in relapsed setting...
March 2017: Acta Clinica Croatica
https://www.readbyqxmd.com/read/29119551/chimeric-antigen-receptor-transduced-t-cells-tuning-up-for-the-next-generation
#20
REVIEW
Maria-Luisa Schubert, Jean-Marc Hoffmann, Peter Dreger, Carsten Müller-Tidow, Michael Schmitt
Chimeric antigen receptor (CAR) T cell therapy has recently achieved impressive clinical outcome in patients with CD19-positive hematologic malignancies. Extrapolation of CAR T cell treatment to solid tumors, however, has not yet yielded similar results. This might be due to intrinsic causes, e.g. insufficient CAR T cell activation or CAR toxicity as well as extrinsic factors displaying an unfavorable tumor environment for CAR T cells by raising physical and chemical barriers. In this review, we discuss the advantages as well as major obstacles of CAR T cell therapy, particularly in the context of solid tumors, and focus on efforts and novel strategies in CAR T cell development...
November 9, 2017: International Journal of Cancer. Journal International du Cancer
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