865 results match your criteria Blood advances[Journal]


Nox2 NADPH oxidase is dispensable for platelet activation or arterial thrombosis in mice.

Blood Adv 2019 Apr;3(8):1272-1284

Department of Internal Medicine.

Deficiency of the Nox2 (gp91phox) catalytic subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a genetic cause of X-linked chronic granulomatous disease, a condition in which patients are prone to infection resulting from the loss of oxidant production by neutrophils. Some studies have suggested a role for superoxide derived from Nox2 NADPH oxidase in platelet activation and thrombosis, but data are conflicting. Using a rigorous and comprehensive approach, we tested the hypothesis that genetic deficiency of Nox2 attenuates platelet activation and arterial thrombosis. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018025569DOI Listing

CD34 cell content of 126 341 cord blood units in the US inventory: implications for transplantation and banking.

Blood Adv 2019 Apr;3(8):1267-1271

National Marrow Donor Program, Minneapolis, MN.

CD34 cell dose is critical for cord blood (CB) engraftment. However, the CD34 content of the CB inventory in the United States is unknown. We examined the CD34 cell content of 126 341 red blood cell-depleted US units banked from January 2007 to September 2017 with a total nucleated cell (TNC) count of ≥90 × 10 and a cryovolume of 24-55 mL. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018029157DOI Listing

Par-4 overexpression impedes leukemogenesis in the Eµ-TCL1 leukemia model through downregulation of NF-κB signaling.

Blood Adv 2019 Apr;3(8):1255-1266

The James Comprehensive Cancer Center and.

Prostate apoptosis response 4 (Par-4) is a tumor suppressor that prevents proliferation and induces cell death in several solid tumors. However, its role in B-cell malignancies has not been elucidated. To describe the role of Par-4 in chronic lymphocytic leukemia (CLL) pathogenesis, we developed a B-cell-specific human Par-4-overexpressing mouse model of CLL using the TCL1 leukemia model. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018025973DOI Listing
April 2019
1 Read

Mutations in the zebrafish gene reveal a novel function for isoprenoids during red blood cell development.

Blood Adv 2019 Apr;3(8):1244-1254

Department of Biological Sciences and Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX.

Erythropoiesis is the process by which new red blood cells (RBCs) are formed and defects in this process can lead to anemia or thalassemia. The GATA1 transcription factor is an established mediator of RBC development. However, the upstream mechanisms that regulate the expression of are not completely characterized. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018024539DOI Listing

Preclinical development of CD37CAR T-cell therapy for treatment of B-cell lymphoma.

Blood Adv 2019 Apr;3(8):1230-1243

Division of Cancer Medicine, Department of Cellular Therapy, and.

T cells modified to express chimeric antigen receptor (CAR) targeting CD19 (CD19CAR) have produced remarkable clinical responses in patients with relapsed/refractory B-cell acute lymphoblastic leukemia. CD19CAR T-cell therapy has also demonstrated prominent effects in B-cell non-Hodgkin lymphoma (B-NHL) patients. However, a subset of patients who relapse after CD19CAR T-cell therapy have outgrowth of CD19 tumor cells. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018029678DOI Listing
April 2019
3 Reads

Comparison of different techniques to identify cardiac involvement in immunoglobulin light chain (AL) amyloidosis.

Blood Adv 2019 Apr;3(8):1226-1229

Division of Hematology and.

We retrospectively reviewed the utility of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and transthoracic echocardiogram (TTE) in diagnosing cardiac involvement in patients with biopsy-proven systemic immunoglobulin light chain amyloidosis seen at the Mayo Clinic between 1 January 2006 and 30 December 2015. We analyzed 2 cohorts: patients undergoing endomyocardial biopsy for suspicion of cardiac involvement (cohort 1) and patients who had serum NT-proBNP and comprehensive echocardiographic evaluation at diagnosis (cohort 2). Of 179 patients undergoing endomyocardial biopsy (cohort 1), 173 (97%) had evidence of amyloid deposition, with 159 having NT-proBNP performed at the time of the procedure. Read More

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http://dx.doi.org/10.1182/bloodadvances.2019032458DOI Listing
April 2019
2 Reads

Glia maturation factor-γ regulates murine macrophage iron metabolism and M2 polarization through mitochondrial ROS.

Blood Adv 2019 Apr;3(8):1211-1225

Molecular and Clinical Hematology Branch, National Heart, Lung, and Blood Institute.

In macrophages, cellular iron metabolism status is tightly integrated with macrophage phenotype and associated with mitochondrial function. However, how molecular events regulate mitochondrial activity to integrate regulation of iron metabolism and macrophage phenotype remains unclear. Here, we explored the important role of the actin-regulatory protein glia maturation factor-γ (GMFG) in the regulation of cellular iron metabolism and macrophage phenotype. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018026070DOI Listing

Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update.

Blood Adv 2019 Apr;3(8):1197-1210

Western University, London, ON, Canada.

Purpose: To update the American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer.

Methods: PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs in patients with cancer published from January 31, 2010, through May 14, 2018. For biosimilar ESAs, the literature search was expanded to include meta-analyses and RCTs in patients with cancer or chronic kidney disease and cohort studies in patients with cancer due to limited RCT evidence in the cancer setting. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018030387DOI Listing
April 2019
2 Reads

MicroRNA-155 controls vincristine sensitivity and predicts superior clinical outcome in diffuse large B-cell lymphoma.

Blood Adv 2019 Apr;3(7):1185-1196

Department of Hematology, Aalborg University Hospital, Aalborg, Denmark.

A major clinical challenge of diffuse large B-cell lymphoma (DLBCL) is that up to 40% of patients have refractory disease or relapse after initial response to therapy as a result of drug-specific molecular resistance. The purpose of the present study was to investigate microRNA (miRNA) involvement in vincristine resistance in DLBCL, which was pursued by functional in vitro analysis in DLBCL cell lines and by outcome analysis of patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Differential miRNA expression analysis identified miR-155 as highly expressed in vincristine-sensitive DLBCL cell lines compared with resistant ones. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018029660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457225PMC
April 2019
2 Reads

Clonotypic heterogeneity in cutaneous T-cell lymphoma (mycosis fungoides) revealed by comprehensive whole-exome sequencing.

Blood Adv 2019 Apr;3(7):1175-1184

Division of Dermatology, Department of Medicine, and.

Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, is believed to represent a clonal expansion of a transformed skin-resident memory T cell. T-cell receptor (TCR) clonality (ie, identical sequences of rearranged TCRα, TCRβ, and TCRγ), the key premise of this hypothesis, has been difficult to document conclusively because malignant cells are not readily distinguishable from the tumor-infiltrating reactive lymphocytes that contribute to the TCR clonotypic repertoire of MF. Here, we have successfully adopted targeted whole-exome sequencing (WES) to identify the repertoire of rearranged TCR genes in tumor-enriched samples from patients with MF. Read More

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http://www.bloodadvances.org/lookup/doi/10.1182/bloodadvance
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http://dx.doi.org/10.1182/bloodadvances.2018027482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457216PMC
April 2019
7 Reads

Efficacy results of a phase 2 trial of first-line idelalisib plus ofatumumab in chronic lymphocytic leukemia.

Blood Adv 2019 Apr;3(7):1167-1174

Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.

PI3 kinase (PI3K) activity is critical for survival of neoplastic B cells in patients with chronic lymphocytic leukemia (CLL). Blockade of PI3K signaling with idelalisib is effective for the treatment of relapsed CLL in combination with the anti-CD20 antibody ofatumumab. In this single-arm, open-label, nonrandomized phase 2 study, we investigated the efficacy and safety of idelalisib with ofatumumab in 27 patients with treatment-naïve CLL in need of therapy. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018030221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457234PMC
April 2019
3 Reads

Diacylglycerol kinase ζ is a negative regulator of GPVI-mediated platelet activation.

Blood Adv 2019 Apr;3(7):1154-1166

Blood Research Institute, Versiti, Milwaukee, WI.

Diacylglycerol kinases (DGKs) are a family of enzymes that convert diacylglycerol (DAG) into phosphatidic acid (PA). The ζ isoform of DGK (DGKζ) has been reported to inhibit T-cell responsiveness by downregulating intracellular levels of DAG. However, its role in platelet function remains undefined. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018026328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457232PMC

Targeting CD47 in Sézary syndrome with SIRPαFc.

Blood Adv 2019 Apr;3(7):1145-1153

Department of Dermatology, University of Pittsburgh, Pittsburgh, PA.

Sézary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma, has limited treatment options and rare occurrences of long-term remission, thus warranting research into new treatment approaches. CD47 has emerged as a promising target for multiple tumor types, but its role in SS remains unknown. Here, we show that CD47 is highly expressed on Sézary cells in the peripheral blood and skin, and the high level of CD47 expression correlates with worse overall survival (OS) in patients with SS. Read More

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http://www.bloodadvances.org/lookup/doi/10.1182/bloodadvance
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http://dx.doi.org/10.1182/bloodadvances.2018030577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457236PMC
April 2019
8 Reads

Plasmacytoid dendritic cells respond to Epstein-Barr virus infection with a distinct type I interferon subtype profile.

Blood Adv 2019 Apr;3(7):1129-1144

Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.

Infectious mononucleosis, caused by infection with the human gamma-herpesvirus Epstein-Barr virus (EBV), manifests with one of the strongest CD8 T-cell responses described in humans. The resulting T-cell memory response controls EBV infection asymptomatically in the vast majority of persistently infected individuals. Whether and how dendritic cells (DCs) contribute to the priming of this near-perfect immune control remains unclear. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018025536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457222PMC
April 2019
3 Reads

The influence of stem cell source on transplant outcomes for pediatric patients with acute myeloid leukemia.

Blood Adv 2019 Apr;3(7):1118-1128

Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.

When hematopoietic stem cell transplant (HSCT) is necessary for children with acute myeloid leukemia (AML), there remains debate about the best stem cell source. Post-HSCT relapse is a common cause of mortality, and complications such as chronic graft versus host disease (cGVHD) are debilitating and life-threatening. To compare post-HSCT outcomes of different donor sources, we retrospectively analyzed consecutive transplants performed in several international centers from 2005 to 2015. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018025908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457227PMC
April 2019
2 Reads

Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML.

Blood Adv 2019 Apr;3(7):1103-1117

Azienda Socio-Sanitaria Territoriale (ASST) Ospedale Papa Giovanni XXIII, Bergamo, Italy.

Here we evaluated whether sequential high-dose chemotherapy (sHD) increased the early complete remission (CR) rate in acute myelogenous leukemia (AML) compared with standard-intensity idarubicin-cytarabine-etoposide (ICE) chemotherapy. This study enrolled 574 patients (age, 16-73 years; median, 52 years) who were randomly assigned to ICE (n = 286 evaluable) or sHD (2 weekly 3-day blocks with cytarabine 2 g/m twice a day for 2 days plus idarubicin; n = 286 evaluable). Responsive patients were risk-stratified for a second randomization. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018026625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457212PMC
April 2019
2 Reads

Intratumoral platelet aggregate formation in a murine preclinical glioma model depends on podoplanin expression on tumor cells.

Blood Adv 2019 Apr;3(7):1092-1102

Division of Signal Transduction and Growth Control, German Cancer Research Center (DKFZ)-Center for Molecular Biology of the University of Heidelberg (ZMBH) Alliance, DKFZ, Heidelberg, Germany.

Binding of the sialomucin-like transmembrane glycoprotein podoplanin (PDPN) to the platelet receptor C-type lectin-like receptor 2 induces platelet activation and aggregation. In human high-grade gliomas, PDPN is highly expressed both in tumor cells and in tumor-associated astrocytes. In glioma patients, high expression of PDPN is associated with worse prognosis and has been shown to correlate with intratumoral platelet aggregation and an increased risk of venous thromboembolism (VTE). Read More

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http://dx.doi.org/10.1182/bloodadvances.2018015966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457221PMC
April 2019
3 Reads

The natural history of vascular and other complications in patients treated with nilotinib for chronic myeloid leukemia.

Blood Adv 2019 Apr;3(7):1084-1091

Department of Clinical Haematology, Austin Hospital, Melbourne, Australia.

Although second-generation tyrosine kinase inhibitors (TKIs) show superiority in achieving deep molecular responses in chronic myeloid leukemia in chronic phase (CML-CP) compared with imatinib, the differing adverse effect (AE) profiles need consideration when deciding the best drug for individual patients. Long-term data from randomized trials of nilotinib demonstrate an increased risk of vascular AEs (VAEs) compared with other TKIs, although the natural history of these events in response to dose modifications or cessation has not been fully characterized. We retrospectively reviewed the incidence of nilotinib-associated AEs in 220 patients with CML-CP at 17 Australian institutions. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018028035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457217PMC

Morphine promotes neovascularizing retinopathy in sickle transgeneic mice.

Blood Adv 2019 Apr;3(7):1073-1083

Vascular Biology Center, and.

Neovascularizing retinopathy is a significant complication of sickle cell disease (SCD), occurring more frequently in HbSC than HbSS disease. This risk difference is concordant with a divergence of angiogenesis risk, as identified by levels of pro- vs anti-angiogenic factors in the sickle patient's blood. Because our prior studies documented that morphine promotes angiogenesis in both malignancy and wound healing, we tested whether chronic opioid treatment would promote retinopathy in NY1DD sickle transgenic mice. Read More

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http://www.bloodadvances.org/lookup/doi/10.1182/bloodadvance
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http://dx.doi.org/10.1182/bloodadvances.2018026898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457224PMC
April 2019
2 Reads

Hematopoietic cytokines mediate resistance to targeted therapy in FLT3-ITD acute myeloid leukemia.

Blood Adv 2019 Apr;3(7):1061-1072

Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, PA; and.

Activating mutations in Fms-like tyrosine kinase 3 (FLT3) occur in ∼30% of adult cases of acute myeloid leukemia (AML). Selective second- and third-generation FLT3 inhibitors have shown significant clinical activity in patients with relapsed FLT3-mutant AML. However, clearance of FLT3-mutant clones does not consistently occur, and disease will progress in most patients after an initial response. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018029850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457213PMC
April 2019
2 Reads

NUP98-HBO1-fusion generates phenotypically and genetically relevant chronic myelomonocytic leukemia pathogenesis.

Blood Adv 2019 Apr;3(7):1047-1060

Laboratory of Oncology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.

Chronic myelomonocytic leukemia (CMML) constitutes a hematopoietic stem cell (HSC) disorder characterized by prominent monocytosis and myelodysplasia. Although genome sequencing has revealed the CMML mutation profile, the mechanism of disease development remains unclear. Here we show that aberrant histone acetylation by nucleoporin-98 (NUP98)-HBO1, a newly identified fusion in a patient with CMML, is sufficient to generate clinically relevant CMML pathogenesis. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018025007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457235PMC
April 2019
4 Reads

Germline deletion of in familial acute lymphoblastic leukemia.

Blood Adv 2019 Apr;3(7):1039-1046

Department of Pathology, St. Jude Children's Research Hospital, Memphis TN.

Recent studies have identified germline mutations in , , , and in kindreds with familial acute lymphoblastic leukemia (ALL), but the genetic basis of ALL in many kindreds is unknown despite mutational analysis of the exome. Here, we report a germline deletion of identified by linkage and structural variant analysis of whole-genome sequencing data segregating in a kindred with thrombocytopenia, B-progenitor acute lymphoblastic leukemia, and diffuse large B-cell lymphoma. The 75-nt deletion removed the exon 7 splice acceptor, resulting in exon skipping and protein truncation. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018030635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457220PMC
April 2019
4 Reads

Impact of age on clinical risk scores in follicular lymphoma.

Blood Adv 2019 Apr;3(7):1033-1038

Department of Medicine III, University Hospital, and.

The Follicular Lymphoma (FL) International Prognostic Index (FLIPI) and FLIPI-2 are well-described clinical risk models. Age >60 years at diagnosis is a risk factor in both scores. Recently, we showed that older age is not associated with higher risk of disease progression or inferior treatment efficacy. Read More

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http://dx.doi.org/10.1182/bloodadvances.2019032136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457218PMC
April 2019
4 Reads

Decellularized Wharton jelly matrix: a biomimetic scaffold for ex vivo hematopoietic stem cell culture.

Blood Adv 2019 Apr;3(7):1011-1026

Hematology/Oncology and Bone Marrow Transplant Program, Department of Medicine, University of Rochester Medical Center, Rochester, NY.

Hematopoietic stem progenitor cells (HSPCs) reside in the bone marrow (BM) hematopoietic "niche," a special 3-dimensional (3D) microenvironment that regulates HSPC self-renewal and multipotency. In this study, we evaluated a novel 3D in vitro culture system that uses components of the BM hematopoietic niche to expand umbilical cord blood (UCB) CD34 cells. We developed this model using decellularized Wharton jelly matrix (DWJM) as an extracellular matrix (ECM) scaffold and human BM mesenchymal stromal cells (MSCs) as supporting niche cells. Read More

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http://www.bloodadvances.org/lookup/doi/10.1182/bloodadvance
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http://dx.doi.org/10.1182/bloodadvances.2018019315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457237PMC
April 2019
2 Reads

Ocular instillation of vitamin A-coupled liposomes containing HSP47 siRNA ameliorates dry eye syndrome in chronic GVHD.

Blood Adv 2019 Apr;3(7):1003-1010

Graduate School of Medicine, Faculty of Medicine, Hokkaido University, Sapporo, Japan.

Chronic graft-versus-host disease (GVHD) profoundly affects the quality of life of long-term survivors of allogeneic hematopoietic stem cell transplantation (SCT). The eyes are frequently involved, and dry eye syndrome is the most common manifestation of ocular chronic GVHD. We explored the role of heat shock protein 47 (HSP47) in ocular GVHD and developed a novel antifibrotic topical therapy using vitamin A-coupled liposomes containing HSP47 small interfering RNA (siRNA) against HSP47 (VA-lip HSP47). Read More

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http://dx.doi.org/10.1182/bloodadvances.2018028431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457226PMC
April 2019
2 Reads

Citron Rho-interacting kinase silencing causes cytokinesis failure and reduces tumor growth in multiple myeloma.

Blood Adv 2019 Apr;3(7):995-1002

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.

Citron Rho-interacting serine/threonine kinase (CIT) is a serine/threonine kinase that acts as a key component of the midbody and is essential for cytokinesis. CIT has been reported to be highly expressed in some tumor tissues and to play a role in cancer proliferation; however, the significance of CIT has not been investigated in multiple myeloma (MM). Here, we identified, by protein microarray and immunohistochemistry, that CIT is 1 of the upregulated proteins in the plasma cells of MM patients compared with healthy controls. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018028456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457230PMC
April 2019
1 Read

Functional analysis of clinical response to low-dose IL-2 in patients with refractory chronic graft-versus-host disease.

Blood Adv 2019 Apr;3(7):984-994

Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston MA.

Patients with chronic graft-versus-host disease (cGVHD) have a paucity of regulatory CD4 T cells (CD4Tregs) that mediate peripheral tolerance. In clinical trials, daily low-dose interleukin-2 (IL-2) has been administered safely for prolonged periods in patients with steroid-refractory cGVHD. Peripheral CD4Tregs expand dramatically in all patients during IL-2 therapy but clinical improvement was observed in ∼50% of patients. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018027474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457229PMC
April 2019
5 Reads

Efficacy and immunologic effects of extracorporeal photopheresis plus interleukin-2 in chronic graft-versus-host disease.

Blood Adv 2019 Apr;3(7):969-979

Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA; and.

Chronic graft-versus-host disease (cGVHD) affects >50% of hematopoietic stem cell transplant patients. Extracorporeal photopheresis (ECP), an immunomodulatory therapy, provides clinical benefit in steroid-refractory (SR) cGVHD, possibly via regulatory T (T) and natural killer (NK) cell expansion. We demonstrated that low-dose interleukin-2 (IL2) led to clinical improvement in SR-cGVHD and stimulated preferential T and NK-cell expansion with minimal effect on conventional T (T) cells. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018029124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457231PMC
April 2019
1 Read

von Willebrand factor self-association is regulated by the shear-dependent unfolding of the A2 domain.

Blood Adv 2019 Apr;3(7):957-968

Department of Chemical and Biological Engineering and.

von Willebrand factor (VWF) self-association results in the homotypic binding of VWF upon exposure to fluid shear. The molecular mechanism of this process is not established. In this study, we demonstrate that the shear-dependent unfolding of the VWF A2 domain in the multimeric protein is a major regulator of protein self-association. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018030122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457215PMC
April 2019
2 Reads

HLA-DRB3*01:01 exhibits a dose-dependent impact on HPA-1a antibody levels in HPA-1a-immunized women.

Blood Adv 2019 Apr;3(7):945-951

Department of Laboratory Medicine, Diagnostic Clinic, University Hospital of North Norway, Tromsø, Norway.

HLA-DRB3*01:01 is a predisposing factor for human platelet antigen 1a (HPA-1a) immunization, which is responsible for most cases of fetal and neonatal alloimmune thrombocytopenia. The aim of this study was to investigate if the HLA-DRB3*01:01 allele imposes a dose-dependent effect on anti-HPA-1a levels and neonatal platelet counts. One hundred and thirty HPA-1a-immunized women were divided into 3 groups: HLA-DRB3*01:01 negative, HLA-DRB3*01:01 hemizygous or heterozygous, and HLA-DRB3*01:01 homozygous. Read More

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http://dx.doi.org/10.1182/bloodadvances.2019032227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457228PMC

Racial disparities in access to HLA-matched unrelated donor transplants: a prospective 1312-patient analysis.

Blood Adv 2019 Apr;3(7):939-944

Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

Availability of 8/8 HLA-allele matched unrelated donors (URDs) is a barrier for ethnic and racial minorities. We prospectively evaluated receipt of 8/8 HLA-allele matched URD or either 7/8 URD or cord blood (CB) transplants by patient ancestry from 2005 to 2017. Matched URDs were given priority if they were available. Read More

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http://www.bloodadvances.org/lookup/doi/10.1182/bloodadvance
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http://dx.doi.org/10.1182/bloodadvances.2018028662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457223PMC
April 2019
3 Reads

A scale for patient-reported symptom assessment for patients with Erdheim-Chester disease.

Blood Adv 2019 Apr;3(7):934-938

Department of Epidemiology and Biostatistics.

Erdheim-Chester disease (ECD) is an ultra-rare hematologic neoplasm characterized by somatic mutations of the MAPK pathway and by accumulation of lesional histiocytes within tissues. Clinical phenotypes and sites of disease involvement are heterogenous in ECD, and no tool exists for systematic and comprehensive assessment of ECD symptomatology. We describe a collaborative effort among ECD specialists, patient-reported outcome (PRO) methodologists, and ECD patients to develop the Erdheim-Chester Disease Symptom Scale (ECD-SS): a symptom inventory for clinical ECD care and evaluation of ECD therapies. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018030502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457219PMC
April 2019
1 Read

mutations define a specific subgroup of MDS and MDS/MPN patients with favorable outcomes with intensive chemotherapy.

Blood Adv 2019 Mar;3(6):922-933

Department of Leukemia and.

Nucleophosmin () mutations are common in acute myeloid leukemia and are associated with high remission rates and prolonged survival with intensive chemotherapy. mutations are rare in myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN), and the clinical outcomes of these patients, when treated with intensive chemotherapy, are unknown. We retrospectively evaluated the clinicopathologic characteristics and the impact of therapy in 31 patients with MDS or MDS/MPN and mutations. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018026989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436014PMC
March 2019
1 Read

Subclonal STAT3 mutations solidify clonal dominance.

Blood Adv 2019 Mar;3(6):917-921

Department of Translational Hematology and Oncology Research and.

T large granular lymphocyte leukemia (T-LGLL) is a clonal lymphoproliferative disorder that can arise in the context of pathologic or physiologic cytotoxic T-cell (CTL) responses. mutations are often absent in typical T-LGLL, suggesting that in a significant fraction of patients, antigen-driven expansion alone can maintain LGL clone persistence. We set out to determine the relationship between activating hits and CTL clonal selection at presentation and in response to therapy. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018027862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436009PMC
March 2019
3 Reads

Role of CYP3A4 in bone marrow microenvironment-mediated protection of FLT3/ITD AML from tyrosine kinase inhibitors.

Blood Adv 2019 Mar;3(6):908-916

Sidney Kimmel Comprehensive Cancer Center and.

An intriguing aspect of the clinical activity of FMS-like tyrosine kinase 3 inhibitors (FLT3 TKIs) is their apparent higher activity against peripheral blasts from FLT3/internal tandem duplication (ITD) acute myeloid leukemia than marrow disease in the same patients. Accordingly, studies showed that the bone marrow microenvironment plays a role in FLT3 TKI resistance, although the underlying mechanisms are unclear. We recently identified a previously undescribed mechanism by which the bone marrow microenvironment can contribute to drug resistance: expression of cytochrome P450 enzymes (CYPs). Read More

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http://dx.doi.org/10.1182/bloodadvances.2018022921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436013PMC
March 2019
7 Reads

Novel CD19-targeted TriKE restores NK cell function and proliferative capacity in CLL.

Blood Adv 2019 Mar;3(6):897-907

Division of Hematology, Oncology, and Transplantation, Department of Medicine, and.

Chronic lymphocytic leukemia (CLL) is characterized by chronic clonal expansion of mature CD19-expressing B lymphocytes and global dysfunction of immune effectors, including natural killer (NK) cells. CLL remains incurable, and novel approaches to refractory CLL are needed. Our group has previously described trispecific killer engager (TriKE) molecules that redirect NK cell function against tumor cells. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018029371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436008PMC
March 2019
1 Read

Effects of aged stored autologous red blood cells on human plasma metabolome.

Blood Adv 2019 Mar;3(6):884-896

Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA.

Cold storage of blood for 5 to 6 weeks has been shown to impair endothelial function after transfusion and has been associated with measures of end-organ dysfunction. Although the products of hemolysis, such as cell-free plasma hemoglobin, arginase, heme, and iron, in part mediate these effects, a complete analysis of transfused metabolites that may affect organ function has not been evaluated to date. Blood stored for either 5 or 42 days was collected from 18 healthy autologous volunteers, prior to and after autologous transfusion into the forearm circulation, followed by metabolomics analyses. Read More

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http://www.bloodadvances.org/lookup/doi/10.1182/bloodadvance
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http://dx.doi.org/10.1182/bloodadvances.2018029629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436007PMC
March 2019
5 Reads

Plerixafor alone for the mobilization and transplantation of HLA-matched sibling donor hematopoietic stem cells.

Blood Adv 2019 Mar;3(6):875-883

Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match, Minneapolis, MN.

Plerixafor, a direct antagonist of CXCR4/stromal-derived factor 1, can safely and rapidly mobilize allografts without the use of granulocyte colony-stimulating factor (G-CSF). We conducted a phase 2, multicenter, prospective study of plerixafor-mobilized HLA-identical sibling allografts for allogeneic hematopoietic cell transplantation in recipients with hematological malignancies. Donors (n = 64) were treated with subcutaneous plerixafor (240 µg/kg) and started leukapheresis (LP) 4 hours later. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018027599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436017PMC
March 2019
3 Reads

Stem cell transplantation for osteopetrosis in patients beyond the age of 5 years.

Blood Adv 2019 Mar;3(6):862-868

Department of Pediatrics and Adolescent Medicine.

Osteopetrosis (OP) is a rare disease caused by defective osteoclast differentiation or function. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment available in the infantile "malignant" form of OP. Improved clinical and genetic diagnosis of OP has seen the emergence of a cohort of patients with less severe and heterogeneous clinical presentations. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018025890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436016PMC
March 2019
2 Reads

Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs.

Blood Adv 2019 Mar;3(6):851-861

Department of Leukemia.

Cardiovascular or arteriothrombotic adverse events (CV- or AT-AEs) are reported in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs). The incidence and characteristics across different TKI have not been systematically analyzed. We analyzed 531 patients treated with frontline TKIs in different prospective trials: imatinib 400 mg (n = 71) and 800 mg (n = 203), nilotinib (n = 108), dasatinib (n = 106), and ponatinib (n = 43). Read More

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http://dx.doi.org/10.1182/bloodadvances.2018025874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436011PMC

Modulation of TAP-dependent antigen compartmentalization during human monocyte-to-DC differentiation.

Blood Adv 2019 Mar;3(6):839-850

Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany.

Dendritic cells (DCs) take up antigen in the periphery, migrate to secondary lymphoid organs, and present processed antigen fragments to adaptive immune cells and thus prime antigen-specific immunity. During local inflammation, recirculating monocytes are recruited from blood to the inflamed tissue, where they differentiate to macrophages and DCs. In this study, we found that monocytes showed high transporter associated with antigen processing (TAP)-dependent peptide compartmentalization and that after antigen pulsing, they were not able to efficiently stimulate antigen-specific T lymphocytes. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018027268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436010PMC
March 2019
4 Reads

FVIII expression by its native promoter sustains long-term correction avoiding immune response in hemophilic mice.

Blood Adv 2019 Mar;3(5):825-838

Department of Health Sciences, Università del Piemonte Orientale "Amedeo Avogadro," Novara, Italy; and.

Here we describe a successful gene therapy approach for hemophilia A (HA), using the natural F8 promoter (pF8) to direct gene replacement to factor VIII (FVIII)-secreting cells. The promoter sequence and the regulatory elements involved in the modulation of F8 expression are still poorly characterized and biased by the historical assumption that FVIII expression is mainly in hepatocytes. Bioinformatic analyses have highlighted an underestimated complexity in gene expression at this locus, suggesting an activation of pF8 in more cell types than those previously expected. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018027979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418497PMC
March 2019
2 Reads

Enhancing the antitumor functions of invariant natural killer T cells using a soluble CD1d-CD19 fusion protein.

Blood Adv 2019 Mar;3(5):813-824

Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN.

Invariant natural killer T (iNKT) cells comprise a unique lineage of CD1d-restricted lipid-reactive T lymphocytes that potently kill tumor cells and exhibit robust immunostimulatory functions. Optimal tumor-directed iNKT cell responses often require expression of the antigen-presenting molecule CD1d on tumors; however, many tumor cells downregulate CD1d and thus evade iNKT cell recognition. We generated a soluble bispecific fusion protein designed to direct iNKT cells to the site of B-cell cancers in a tumor antigen-specific but CD1d-independent manner. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018028886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418505PMC
March 2019
1 Read

Oncolytic immunotherapy and bortezomib synergy improves survival of refractory multiple myeloma in a preclinical model.

Blood Adv 2019 Mar;3(5):797-812

Division of Medical Oncology, Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; and.

The oncolytic reovirus (RV) has demonstrated clinical efficacy and minimal toxicity in a variety of cancers, including multiple myeloma (MM). MM is a malignancy of plasma cells that is considered treatable but incurable because of the 90% relapse rate that is primarily from drug resistance. The systemic nature of MM and the antitumor immunosuppression by its tumor microenvironment presents an ongoing therapeutic challenge. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018025593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418503PMC
March 2019
5 Reads