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https://read.qxmd.com/read/30862646/a-phase-ib-study-of-isatuximab-plus-pomalidomide-dexamethasone-in-relapsed-refractory-multiple-myeloma
#1
Joseph Mikhael, Paul Richardson, Saad Z Usmani, Noopur Raje, William Bensinger, Chatchada Karanes, Frank Campana, Dheepak Kanagavel, Franck Dubin, Qianying Liu, Dorothée Semiond, Kenneth Anderson
This phase Ib dose-escalation study evaluated isatuximab plus pomalidomide/dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received ≥2 prior MM therapies, including lenalidomide and a proteasome inhibitor (PI), were enrolled and received isatuximab at 5, 10, or 20 mg/kg (weekly [QW] for 4 weeks, followed by every 2 weeks [Q2W]), pomalidomide 4 mg (Days 1-21), and dexamethasone 40 mg (QW) in 28-day cycles until progression/intolerable toxicity. The primary objective was to determine the safety and recommended dose of isatuximab with this combination...
March 12, 2019: Blood
https://read.qxmd.com/read/30862645/phase-1b-study-of-venetoclax-obinutuzumab-in-previously-untreated-and-relapsed-refractory-chronic-lymphocytic-leukemia
#2
Ian W Flinn, John G Gribben, Martin J S Dyer, William Wierda, Michael B Maris, Richard R Furman, Peter Hillmen, Kerry A Rogers, Swaminathan Padmanabhan Iyer, Anne Quillet-Mary, Loic Ysebaert, Harriet S Walter, Maria Verdugo, Christian Klein, Huang Huang, Yanwen Jiang, Gerard Lozanski, Daniela Soriano Pignataro, Kathryn Humphrey, Mehrdad Mobasher, Thomas J Kipps
This single-arm, open-label, phase 1b study evaluated the maximum tolerated dose (MTD) of venetoclax when given with obinutuzumab and its safety and tolerability in patients with relapsed/refractory (R/R) or previously untreated (1L) chronic lymphocytic leukemia. Venetoclax dose initially was escalated (100-400 mg) in a 3+3 design to define the MTD combined with standard-dose obinutuzumab. Patients received venetoclax (Schedule A) or obinutuzumab (Schedule B) first to compare safety and determine dose/schedule for expansion...
March 12, 2019: Blood
https://read.qxmd.com/read/30858233/retraction-nankanja-r-kiyaga-c-geisberg-m-serrao-e-and-balyegyusa-s-implementation-of-a-sickle-cell-disease-screening-initiative-in-uganda-with-hemotypesctm-blood-2018-132-suppl-1-lba-3
#3
https://read.qxmd.com/read/30858232/simplifying-the-diagnosis-of-inherited-platelet-disorders-the-new-tools-do-not-make-it-any-easier
#4
Andreas Greinacher, Julia J M Eekels
Molecular causes of many inherited platelet disorders have been unraveled. Next generation sequencing facilitates diagnosis in 30-50% of patients. However, interpretation of genetic variants is challenging and requires careful evaluation in the context of the patient's phenotype. Before detailed testing is initiated, the treating physician and the patient should be aware why testing is performed and should agree on the consequences it may have, especially before testing for variants in genes associated with an increased risk for hematologic malignancies...
March 11, 2019: Blood
https://read.qxmd.com/read/30858231/hydroxyurea-reduces-cerebral-metabolic-stress-in-patients-with-sickle-cell-anemia
#5
Melanie E Fields, Kristin P Guilliams, Dustin Ragan, Michael M Binkley, Amy Mirro, Slim Fellah, Monica L Hulbert, Morey Blinder, Cihat Eldeniz, Katie Vo, Joshua S Shimony, Yasheng Chen, Robert C McKinstry, Hongyu An, Jin-Moo Lee, Andria L Ford
Chronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs, and OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared to patients not receiving disease-modifying therapy, we prospectively obtained brain MRIs with voxel-wise measurements of CBF and OEF in 84 participants with SCA who were grouped by therapy: no disease-modifying therapy, HU, or CTT...
March 11, 2019: Blood
https://read.qxmd.com/read/30858230/low-vs-high-hemoglobin-trigger-for-transfusion-in-vascular-surgery-tv-a-randomized-clinical-feasibility-trial
#6
Anders Møller, Henning B Nielsen, Jørn Wetterslev, Ole B Pedersen, Dorthe Hellemann, Per Winkel, Klaus V Marcussen, Benedicte G U Ramsing, Anette Mortensen, Janus C Jakobsen, Saeid Shahidi
Current guidelines advocate to limit red-cell transfusion during surgery, but the feasibility and safety of such strategy remains unclear as the majority of evidence is based on postoperative stable patients. We assessed the effects of a protocol aiming to restrict red-cell transfusion throughout hospitalization for vascular surgery. Fifty-eight patients scheduled for lower limb-bypass or open abdominal aortic aneurysm repair were randomized upon hemoglobin drop below 9.7g/dL to a low-trigger (hemoglobin<8...
March 11, 2019: Blood
https://read.qxmd.com/read/30850381/venetoclax-plus-r-or-g-chop-in-non-hodgkin-lymphoma-results-from-the-cavalli-phase-1b-trial
#7
Andrew D Zelenetz, Gilles Salles, Kylie D Mason, Carla Casulo, Steven Le Gouill, Laurie H Sehn, Herve Tilly, Guillaume Cartron, Martine E D Chamuleau, Andre Goy, Constantine S Tam, Pieternella J Lugtenburg, Adam M Petrich, Arijit Sinha, Divya Samineni, Sylvia Herter, Ellen Ingalla, Edith Szafer-Glusman, Christian Klein, Deepak Sampath, Martin Kornacker, Mehrdad Mobasher, Franck Morschhauser
Novel strategies, such as chemosensitization with targeted agents, that build on the success of standard immunochemotherapy show promise for the treatment of non-Hodgkin lymphoma (NHL). Here, we report a phase 1b study investigating dose escalation of the BCL2 inhibitor, venetoclax, in combination with rituximab or obinutuzumab and cyclophosphamide, doxorubicin, vincristine, and prednisone (R-/G-CHOP) chemotherapy in B-cell NHL. Objectives included safety assessment and determination of a recommended phase 2 dose (RP2D)...
March 8, 2019: Blood
https://read.qxmd.com/read/30842083/long-term-follow-up-of-the-resonate%C3%A2-phase-3-trial-of-ibrutinib-versus-ofatumumab
#8
John C Byrd, Peter Hillmen, Susan O'Brien, Jacqueline C Barrientos, Nishitha M Reddy, Steven Coutre, Constantine S Tam, Stephen P Mulligan, Ulrich Jaeger, Paul M Barr, Richard R Furman, Thomas J Kipps, Patrick Thornton, Carol Moreno, Marco Montillo, John M Pagel, Jan A Burger, Jennifer A Woyach, Sandra Dai, Remus Vezan, Danelle F James, Jennifer R Brown
Ibrutinib, a once-daily oral inhibitor of Bruton's tyrosine kinase, has greatly improved outcomes for patients with chronic lymphocytic leukemia (CLL). The phase 3 RESONATE™, which compared single-agent ibrutinib to ofatumumab in high-risk, relapsed patients with CLL, provided support for approval of ibrutinib in the US and Europe. We describe long-term follow-up of patients treated in RESONATE, where continued superiority of progression-free survival (PFS) (hazard ratio [HR] 0.133; 95% CI, 0.099-0.178) was observed...
March 6, 2019: Blood
https://read.qxmd.com/read/30833414/a-cytosine-rich-splice-regulatory-determinant-enforces-functional-processing-of-the-human-%C3%AE-globin-gene-transcript
#9
Xinjun Ji, Jesse Humenik, Stephen A Liebhaber
The establishment of efficient and stable splicing patterns in terminally differentiated cells is critical to maintenance of specific functions throughout the lifespan of an organism. The human (h)α-globin gene contains three exons separated by two short introns. Naturally occurring α-thalassemia mutations that trigger aberrant splicing have revealed the presence of cryptic splice sites within the hα-globin gene transcript. How cognate (functional) splice sites are selectively utilized in lieu of these cryptic sites has remained unexplored...
March 4, 2019: Blood
https://read.qxmd.com/read/30833413/tumor-educated-platelets
#10
Sjors G J G In 't Veld, Thomas Wurdinger
Liquid biopsies have been considered the holy grail towards achieving effective cancer management, with blood tests offering a minimally invasive, safe, and sensitive alternative or complementary approach for tissue biopsies. Currently, blood-based liquid biopsy measurements focus on evaluation of biomarker types, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), extracellular vesicles (EVs; exosomes, oncosomes), and tumor-educated platelets (TEPs). Despite the potential of individual techniques, each has its own advantages and disadvantages...
March 4, 2019: Blood
https://read.qxmd.com/read/30819926/randomized-phase-3-study-of-carfilzomib-or-bortezomib-with-melphalan-prednisone-for-transplant-ineligible-ndmm-patients
#11
Thierry Facon, Jae Hoon Lee, Philippe Moreau, Ruben Niesvizky, Meletios Dimopoulos, Roman Hajek, Ludek Pour, Artur Jurczyszyn, Lugui Qiu, Zandra Klippel, Anita Zahlten-Kumeli, Muhtarjan Osman, Bruno Paiva, Jesus San-Miguel
The phase 3 CLARION study compared carfilzomib-melphalan-prednisone (KMP) with bortezomib-melphalan-prednisone (VMP) in transplant-ineligible newly-diagnosed multiple myeloma (NDMM) patients. Patients were randomized 1:1 to KMP or VMP for nine 42-day cycles (C). Patients received carfilzomib on days (D) 1, 2, 8, 9, 22, 23, 29, 30 (20 mg/m2: C1D1, C1D2; 36 mg/m2 thereafter) or bortezomib on D1, 4, 8, 11, 22, 25, 29, 32 (1.3 mg/m2; D4, 11, 25, 32 omitted for C5-9). Melphalan (9 mg/m2) and prednisone (60 mg/m2) were administered on D1-4...
February 28, 2019: Blood
https://read.qxmd.com/read/30819925/hap1-loss-confers-l-asparaginase-resistance-in-all-by-downregulating-the-calpain-1-bid-caspase-3-12-pathway
#12
JungKwon Lee, SungMyung Kang, Xidi Wang, Jesusa L Rosales, Xu Gao, Hee-Guk Byun, Yan Jin, Songbin Fu, Jinghua Wang, Ki-Young Lee
L-asparaginase is a strategic component of treatment protocols for acute lymphoblastic leukemia (ALL). It causes asparagine deficit, resulting in protein synthesis inhibition and subsequent leukemic cell death and ALL remission. However, patients often relapse due to the development of resistance, but the underlying mechanism of ALL cell resistance to L-asparaginase remains unknown. Through unbiased genome-wide RNAi screening, we identified huntingtin associated protein 1 ( HAP1 ) as an ALL biomarker for L-asparaginase resistance...
February 28, 2019: Blood
https://read.qxmd.com/read/30814063/a-gene-based-recessive-diplotype-exome-scan-discovers-fgf6-a-novel-hepcidin-regulating-iron-metabolism-gene
#13
Shicheng Guo, Shuai Jiang, Narendranath Epperla, Yanyun Ma, Mehdi Maadooliat, Zhan Ye, Brent Olson, Minghua Wang, Terrie Kitchner, Jeffrey Joyce, Robert Strenn, Joseph J Mazza, Jennifer K Meece, Wenyu Wu, Li Jin, Judith A Smith, Jiucun Wang, Steven J Schrodi
Standard analyses applied to genome-wide association data are well-designed to detect additive effects of moderate strength. However, the power for standard GWAS analyses to identify effects from recessive diplotypes is not typically high. We proposed and conducted a gene-based compound heterozygosity test to reveal additional genes underlying complex diseases. With this approach applied to iron overload, a strong association signal was identified between the fibroblast growth factor-encoding gene, FGF6 , and hemochromatosis in the central Wisconsin population...
February 27, 2019: Blood
https://read.qxmd.com/read/30814062/neural-cell-adhesion-molecule-1-ncam1-cd56-promotes-leukemogenesis-and-confers-drug-resistance-in-aml
#14
Daniel Sasca, Jakub Szybinski, Andrea Schüler, Viral Shah, Jan Heidelberger, Patricia S Haehnel, Anna Dolnik, Oliver Kriege, Eva-Marie Fehr, Wolf Henning Gebhardt, George Reid, Claudia Scholl, Matthias Theobald, Lars Bullinger, Petra Beli, Thomas Kindler
Neural cell adhesion molecule 1 (NCAM1; CD56) is expressed in up to 20% of acute myeloid leukemia (AML) patients. NCAM1 is widely used as a marker of minimal residual disease; however, the biological function of NCAM1 in AML remains elusive. In this study we investigated the impact of NCAM1 expression on leukemogenesis, drug resistance and its role as a biomarker to guide therapy. Beside t(8;21) leukemia, NCAM1 expression was found in most molecular AML subgroups at highly heterogeneous expression levels. Using complementary genetic strategies, we demonstrated an essential role of NCAM1 in the regulation of cell survival and stress resistance...
February 27, 2019: Blood
https://read.qxmd.com/read/30814061/ibrutinib-therapy-downregulates-aid-enzyme-and-proliferative-fractions-in-chronic-lymphocytic-leukemia
#15
Pablo Elías Morande, Mariela Sivina, Angimar Uriepero, Noé Seija, Catalina Berca, Pablo Fresia, Ana Inés Landoni, Javier Di Noia, Jan A Burger, Pablo Oppezzo
Activation-induced cytidine deaminase (AID) initiates somatic hypermutation and class switch recombination of the immunoglobulin genes. As a trade-off for its physiological function, AID also contributes to tumor development through its mutagenic activity. In chronic lymphocytic leukemia (CLL), AID is over-expressed in the proliferative fractions (PFs) of the malignant B lymphocytes and its anomalous expression has been associated with a clinical poor outcome. Recent preclinical data suggested that ibrutinib and idelalisib, two clinically approved kinase inhibitors, increase AID expression and genomic instability in normal and neoplastic B cells...
February 27, 2019: Blood
https://read.qxmd.com/read/30808640/introduction-to-a-review-series-on-transfusion-medicine
#16
Mario Cazzola
No abstract text is available yet for this article.
February 26, 2019: Blood
https://read.qxmd.com/read/30808639/blood-group-genotyping
#17
Connie M Westhoff
Genomics is impacting all areas of medicine. In transfusion medicine, DNA-based genotyping is being used as an alternative to serological antibody-based methods to determine blood groups for matching donor to recipient. Most antigenic polymorphisms are due to single nucleotide changes (SNP's) in the respective genes and DNA-arrays that target these changes have been validated by comparison with antibody-based typing. Importantly, the ability to test for antigens for which there are no serologic reagents is a major medical advance to identify antibodies and to find compatible donor units and can be life-saving...
February 26, 2019: Blood
https://read.qxmd.com/read/30808638/transfusion-associated-circulatory-overload-and-transfusion-related-acute-lung-injury
#18
John W Semple, Johan Rebetz, Rick Kapur
Transfusion-associated circulatory overload (TACO) and Transfusion-related acute lung injury (TRALI) are syndromes of acute respiratory distress which occur within 6 hours of blood transfusion. TACO and TRALI are the leading causes of transfusion-related fatalities and specific therapies are unavailable. Diagnostically, it remains very challenging to distinguish TACO and TRALI from underlying causes of lung injury and/or fluid overload as well as from each other. TACO is characterized by pulmonary hydrostatic (cardiogenic) edema, while TRALI presents as pulmonary permeability edema (noncardiogenic)...
February 26, 2019: Blood
https://read.qxmd.com/read/30808637/prevention-of-transfusion-transmitted-infections
#19
Michael P Busch, Evan M Bloch, Steven H Kleinman
Since the 1970s, introduction of serological assays targeting virus-specific antibodies and antigens has been effective in identifying blood donations infected with the classic transfusion-transmitted infectious (TTI) agents (HBV, HIV, HTLV-I/II, HCV). Subsequently, progressive implementation of nucleic acid-amplification technology (NAT) screening for HIV, HCV, and HBV has reduced the residual risk of infectious window period donations, such that per unit risks are <1 in 1,000,000 in the US, other high-income countries, and in high incidence regions performing NAT...
February 26, 2019: Blood
https://read.qxmd.com/read/30808636/transfusion-related-red-blood-cell-alloantibodies-induction-and-consequences
#20
Christopher A Tormey, Jeanne E Hendrickson
Blood transfusion is the most common procedure completed during a given hospitalization in the United States. Although often life-saving, transfusions are not risk-free. One sequelae that occurs in a subset of red blood cell (RBC) transfusion recipients is the development of alloantibodies. It is estimated that only 30% of induced RBC alloantibodies are detected, given alloantibody induction and evanescence patterns, missed opportunities for alloantibody detection, and record fragmentation. Alloantibodies may be clinically significant in future transfusion scenarios, potentially resulting in acute or delayed hemolytic transfusion reactions, or resulting in difficulty locating compatible RBC units for future transfusion...
February 26, 2019: Blood
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