journal
MENU ▼
Read by QxMD icon Read
search

Blood

journal
https://www.readbyqxmd.com/read/29150421/final-analysis-of-survival-outcomes-in-the-randomized-phase-3-first-trial
#1
Thierry Facon, Meletios A Dimopoulos, Angela Dispenzieri, John V Catalano, Andrew Belch, Michele Cavo, Antonello Pinto, Katja Weisel, Heinz Ludwig, Nizar J Bahlis, Anne Banos, Mourad Tiab, Michel Delforge, Jamie D Cavenagh, Catarina Geraldes, Je-Jung Lee, Christine Chen, Albert Oriol, Javier De La Rubia, Darell White, Daniel Binder, Jin Lu, Kenneth C Anderson, Philippe Moreau, Michel Attal, Aurore Perrot, Bertrand Arnulf, Lugui Qiu, Murielle Roussel, Eileen Boyle, Salomon Manier, Mohamad Mohty, Herve Avet-Loiseau, Xavier Leleu, Annette Ervin-Haynes, Guang Chen, Vanessa Houck, Lotfi Benboubker, Cyrille Hulin
This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥ 60 months' follow-up)...
November 17, 2017: Blood
https://www.readbyqxmd.com/read/29146883/a-landscape-of-germline-mutations-in-a-cohort-of-inherited-bone-marrow-failure-patients
#2
Olivier Bluteau, Marie Sebert, Thierry Leblanc, Régis Peffault de Latour, Samuel Quentin, Elodie Lainey, Lucie Hernandez, Jean-Hugues Dalle, Flore Sicre de Fontbrune, Etienne Lengline, Raphael Itzykson, Emmanuelle Clappier, Nicolas Boissel, Naddia Vasquez, Mélanie Da Costa, Julien Masliah-Planchon, Wendy Cuccuini, Anna Raimbault, Louis De Jaegere, Lionel Adès, Pierre Fenaux, Sébastien Maury, Claudine Schmitt, Marc Muller, Carine Domenech, Nicolas Blin, Bénédicte Bruno, Isabelle Pellier, Mathilde Hunault, Stéphane Blanche, Arnaud Petit, Guy Leverger, Gérard Michel, Yves Bertrand, André Baruchel, Gérard Socié, Jean Soulier
Bone marrow failure (BMF) in children and young adults is often suspected to be inherited, but in many cases diagnosis remains uncertain. We studied a cohort of 179 patients (from 173 families) with BMF of suspected inherited origin but unresolved diagnosis after medical evaluation and Fanconi anemia exclusion. All patients had cytopenias, and 12.0% presented ≥5% bone marrow blast cells. Median age at genetic evaluation was 11 years; 20.7% of patients were aged ≤2 years and 36.9% were ≥18 years. We analyzed genomic DNA from skin fibroblasts using whole-exome sequencing, and were able to assign a causal or likely causal germline mutation in 86 patients (48...
November 16, 2017: Blood
https://www.readbyqxmd.com/read/29146882/physiological-srsf2-p95h-expression-causes-impaired-hematopoietic-stem-cell-functions-and-aberrant-rna-splicing-in-mice
#3
Ayana Kon, Satoshi Yamazaki, Yasuhito Nannya, Keisuke Kataoka, Yasunori Ota, Masahiro Marshall Nakagawa, Kenichi Yoshida, Yusuke Shiozawa, Maiko Morita, Tetsuichi Yoshizato, Masashi Sanada, Manabu Nakayama, Haruhiko Koseki, Hiromitsu Nakauchi, Seishi Ogawa
Splicing factor (SF) mutations are characteristic of myelodysplastic syndromes (MDS) and related myeloid neoplasms and implicated in their pathogenesis, but their roles in the development of MDS have not fully been elucidated. Here, we investigated the consequence of mutant Srsf2 expression using newly generated Vav1-Cre-mediated conditional knock-in mice. Mice carrying a heterozygous Srsf2 P95H mutation showed significantly reduced numbers of hematopoietic stem and progenitor cells (HSPCs) and differentiation defects both in the steady-state condition and transplant settings...
November 16, 2017: Blood
https://www.readbyqxmd.com/read/29141948/a-phase-i-study-of-romidepsin-and-pralatrexate-reveals-marked-activity-in-relapsed-and-refractory-t-cell-lymphoma
#4
Jennifer E Amengual, Renee Lichtenstein, Jennifer Lue, Ahmed Sawas, Changchun Deng, Emily Lichtenstein, Karen Khan, Laine Atkins, Aishling Rada, Hye A Kim, Codruta Chiuzan, Matko Kalac, Enrica Marchi, Lorenzo Falchi, Mark A Francescone, Lawrence Schwartz, Serge Cremers, Owen A O'Connor
The peripheral T-cell lymphomas (PTCL) are a group of rare malignancies characterized by chemotherapy insensitivity and poor prognosis. Romidepsin and pralatrexate were approved by the U.S. FDA for patients with relapsed/refractory PTCL, exhibiting response rates of 25% and 29% respectively. Based on synergy of the combination in preclinical models of PTCL, we initiated a phase I study of pralatrexate plus romidepsin in patients with relapsed/refractory lymphoma (ClinicalTrials.gov (NCT01947140)). This was a single institution dose-escalation phase I study of pralatrexate plus romidepsin designed to determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetic profile and response rates...
November 15, 2017: Blood
https://www.readbyqxmd.com/read/29141947/aging-of-hematopoietic-stem-cells
#5
Gerald de Haan, Seka Lazare
Hematopoietic stem cells (HSCs) ensure a balanced production of all blood cells throughout life. As they age, HSCs gradually lose their self-renewal and regenerative potential, while the occurrence of cellular derailment strongly increases. Here we review our current understanding of the molecular mechanisms that contribute to HSC aging. We argue that most of the causes that underlie HSC aging result from cell-intrinsic pathways, and reflect on which aspects of the aging process may be reversible. As many hematological pathologies are strongly age-associated, strategies to intervene in aspects of the stem cell aging process may have significant clinical relevance...
November 15, 2017: Blood
https://www.readbyqxmd.com/read/29141946/age-related-clonal-hematopoiesis-arch
#6
Liran I Shlush
Age related alterations in the human blood system occur in B cells, T cells, cells of the innate system, as well as in hematopoietic stem and progenitor cells (HSPCs). Interestingly, age related, reduced genetic diversity can be identified both at the stem cell level, but also independently in B cells and T cells. This reduced diversity is most probably related to somatic mutations, or to changes in the micro-environmental niche. Either process can select for specific clones, or cause repeated evolutionary bottlenecks...
November 15, 2017: Blood
https://www.readbyqxmd.com/read/29141945/a-series-of-reviews-on-hematologic-disease-at-older-age
#7
Bob Lowenberg
No abstract text is available yet for this article.
November 15, 2017: Blood
https://www.readbyqxmd.com/read/29141944/dna-damage-responses-and-p53-in-the-aging-process
#8
Hui-Ling Ou, Björn Schumacher
The genome is constantly attacked by genotoxic insults. DNA damage has long been established to cause cancer development through its mutagenic consequences. Conversely, DNA damage is induced during radiation- and chemotherapy to drive cells into apoptosis or senescence as outcomes of the DNA damage response (DDR). More recently, DNA damage has been recognized as a causal factor for the aging process. The causal role of DNA damage in aging and age-related diseases is illustrated by numerous congenital progeroid syndromes that are caused by mutations in genome maintenance pathways...
November 15, 2017: Blood
https://www.readbyqxmd.com/read/29141943/anemia-at-older-age-etiologies-clinical-implications-and-management
#9
Reinhard Stauder, Peter Valent, Igor Theurl
Anemia is quite frequently diagnosed in older individuals and is a key indicator of various reactive and clonal conditions. Many underlying diseases, like the myelodysplastic syndromes (MDS), develop preferentially in elderly individuals. The prevalence of anemia at older age is increasing, and this is mainly due to more frequently applied diagnostics and demographic changes in our societies. The etiology of anemia at older age is complex and ranges from bone marrow failure syndromes to chronic kidney disease, and from nutritional deficiencies to inflammatory processes including inflammaging in immunosenescence...
November 15, 2017: Blood
https://www.readbyqxmd.com/read/29141942/frailty-and-the-management-of-hematologic-malignancies
#10
Gregory A Abel, Heidi D Klepin
The majority of blood cancers occur in the elderly. This fact conspires with an aging population in many countries to make rigorous assessment for frailty increasingly important for hematologic oncologists. In this review, we first define frailty and its relevance for patients with hematologic malignancy. Next, we review current data regarding the impact of domains of frailty on outcomes for blood cancers including myelodysplastic syndromes (MDS), acute leukemia, non-Hodgkin lymphomas such as chronic lymphocytic leukemia (CLL), and multiple myeloma...
November 15, 2017: Blood
https://www.readbyqxmd.com/read/29138222/decitabine-enhances-targeting-of-aml-cells-by-cd34-progenitor-derived-nk-cells-in-nod-scid-il2rg-null-mice
#11
Jeannette Cany, Mieke W H Roeven, Janneke S Hoogstad-van Evert, Willemijn Hobo, Frans Maas, Rosalia Franco Fernandez, Nicole M A Blijlevens, Walter J van der Velden, Gerwin Huls, Joop H Jansen, Nicolaas P M Schaap, Harry Dolstra
Combining NK cell adoptive transfer with hypomethylating agents (HMA) is an attractive therapeutic approach for patients with acute myeloid leukemia (AML). However, data regarding the impact of HMA on NK cell functionality are mostly derived from in vitro studies with high non-clinical relevant drug concentrations. Here, we report a comparative study of azacitidine and decitabine in combination with allogeneic NK cells generated from CD34(+) hematopoietic stem and progenitor cells (HSPC-NK cells) in in vitro and in vivo AML models...
November 14, 2017: Blood
https://www.readbyqxmd.com/read/29138221/immature-cml-cells-implement-a-bmp-autocrine-loop-to-escape-tki-treatment
#12
Elodie Grockowiak, Bastien Laperrousaz, Sandrine Jeanpierre, Thibault Voeltzel, Boris Guyot, Stéphanie Gobert, Franck E Nicolini, Véronique Maguer-Satta
The BCR-ABL specific Tyrosine Kinase Inhibitors (TKI) changed the outcome of Chronic Myeloid Leukemia (CML), turning a life-threatening disease into a chronic illness. However, TKI are not yet curative, since most patients retain leukemic stem cells (LSC) and their progenitors in bone marrow and relapse following treatment cessation. At diagnosis, deregulations of the Bone Morphogenetic Proteins (BMP) pathway are involved in LSC and progenitors expansion. Here, we report that BMP pathway alterations persist in TKI-resistant patients...
November 14, 2017: Blood
https://www.readbyqxmd.com/read/29138220/antibodies-targeting-surface-membrane-antigens-in-patients-with-chronic-graft-versus-host-disease
#13
Kathy S Wang, Haesook T Kim, Sarah Nikiforow, Alexander T Heubeck, Vincent T Ho, John Koreth, Edwin P Alyea, Philippe Armand, Bruce R Blazar, Robert J Soiffer, Joseph H Antin, Corey S Cutler, Jerome Ritz
Chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplant (HSCT) reflects a complex immune response resulting in chronic damage to multiple tissues. Previous studies indicated that donor B cells and the antibodies they produce play an important role in the development of cGVHD. To understand the pathogenic role of antibodies in cGVHD, we focused our studies on post-transplant production of IgG antibodies targeting cell surface antigens expressed in multiple cGVHD affected tissues, due to their potential functional impact on living cells in vivo...
November 14, 2017: Blood
https://www.readbyqxmd.com/read/29133350/extracellular-histones-induce-erythrocyte-fragility-and-anemia
#14
Farzaneh Kordbacheh, Connor H O'Meara, Lucy A Coupland, Patrick M Lelliott, Christopher R Parish
Extracellular histones have been shown to play an important pathogenic role in many diseases, primarily through their cytotoxicity towards nucleated cells and their ability to promote platelet activation with resultant thrombosis and thrombocytopenia. In contrast, little is known about the effect of extracellular histones on erythrocyte function. We demonstrate here that histones promote erythrocyte aggregation, sedimentation and, using a novel in vitro shear stress model, induce erythrocyte fragility and lysis in a concentration dependent manner...
November 13, 2017: Blood
https://www.readbyqxmd.com/read/29122757/crispr-mediated-tcr-replacement-generates-superior-anticancer-transgenic-t-cells
#15
Mateusz Legut, Garry Dolton, Afsar Ali Mian, Oliver Ottmann, Andrew Sewell
Adoptive transfer of T-cells genetically modified to express a cancer-specific T-cell receptor (TCR) has shown significant therapeutic potential for both hematological and solid tumors. However, a major issue of transducing T-cells with a transgenic TCR is the pre-existing expression of TCRs in the recipient cells. These endogenous TCRs compete with the transgenic TCR for surface expression and allow mixed dimer formation. Mixed dimers, formed by mispairing between the endogenous and transgenic TCRs, may harbor autoreactive specificities...
November 9, 2017: Blood
https://www.readbyqxmd.com/read/29122756/foxp1-expression-is-a-prognostic-biomarker-in-follicular-lymphoma-treated-with-rituximab-containing-regimens
#16
Anja Mottok, Vindi Jurinovic, Pedro Farinha, Andreas Rosenwald, Ellen Leich, German Ott, Heike Horn, Wolfram Klapper, Michael Boesl, Wolfgang Hiddemann, Christian Steidl, Joseph M Connors, Laurie H Sehn, Randy D Gascoyne, Eva Hoster, Oliver Weigert, Robert Kridel
Follicular lymphoma (FL) is a clinically and molecularly highly heterogeneous disease, yet prognostication relies predominantly on clinical tools. We recently demonstrated that integration of mutation status of seven genes, including EZH2 and MEF2B, improves risk stratification. We mined gene expression data to uncover genes that are differentially expressed in EZH2- and MEF2B-mutated cases. We focused on FOXP1 and assessed its protein expression by immunohistochemistry (IHC) in a total of 763 tissue biopsies...
November 9, 2017: Blood
https://www.readbyqxmd.com/read/29118010/cd38-antibodies-in-multiple-myeloma-back-to-the-future
#17
Niels W C J van de Donk, Paul G Richardson, Fabio Malavasi
CD38 is highly and uniformly expressed on MM cells, and at relatively low levels on normal lymphoid and myeloid cells, and in some tissues of non-hematopoietic origin. CD38 is a transmembrane glycoprotein with ectoenzymatic activity, and also functions as receptor and adhesion molecule. Altogether, this has triggered the development of several CD38 antibodies including daratumumab (fully human), isatuximab (chimeric), and MOR202 (fully human). CD38 antibodies have pleiotropic mechanisms of action including Fc-dependent immune effector mechanisms, direct apoptotic activity, and immunomodulatory effects by the elimination of CD38-positive immunesuppressor cells...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29118009/immunotherapy-targeting-4-1bb-mechanistic-rationale-clinical-results-and-future-strategies
#18
Cariad Chester, Miguel F Sanmamed, Jun Wang, Ignacio Melero
4-1BB (CD137, TNFRSF9) is an inducible costimulatory receptor expressed on activated T and natural killer (NK) cells. 4-1BB ligation on T cells triggers a signaling cascade that results in upregulation of antiapoptotic molecules, cytokine secretion, and enhanced effector function. In dysfunctional T cells that have a decreased cytotoxic capacity, 4-1BB ligation demonstrates a potent ability to restore effector functions. On NK cells, 4-1BB signaling can increase antibody-dependent cell-mediated cytotoxicity...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29118008/ctla-4-a-moving-target-in-immunotherapy
#19
Behzad Rowshanravan, Neil Halliday, David M Sansom
CD28 and CTLA-4 are members of a family of Immunoglobulin-related receptors that are responsible for various aspects of T cell immune regulation. The family includes CD28, CTLA-4 and ICOS as well as other proteins including PD-1, BTLA and TIGIT. These receptors have both stimulatory (CD28, ICOS) as well as inhibitory roles (CTLA-4, PD-1, BTLA and TIGIT) in T cell function. Increasingly these pathways are targeted as part of immune modulatory strategies to treat cancers, referred to generically as immune checkpoint blockade, and conversely to treat autoimmunity and CTLA-4 deficiency...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29118007/pd-1-expression-and-clinical-pd-1-blockade-in-b-cell-lymphomas
#20
Zijun Y Xu-Monette, Jianfeng Zhou, Ken H Young
PD-1 blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/PD-L1 expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1(+) tumor-infiltrating T cells, 9p24 genetic alteration and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORR) of 65-87% and durable disease control in phase I/II clinical trials...
November 8, 2017: Blood
journal
journal
20052
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"