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https://www.readbyqxmd.com/read/29352515/principles-of-alemtuzumab-immunoablation-in-hematopoietic-cell-transplantation-for-non-malignant-diseases-in-children-a-review
#1
REVIEW
Gregory M T Guilcher, Ravi Shah, Shalini Shenoy
Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell lines). A growing understanding of the PKs, dosing, and timing of administration of alemtuzumab has allowed for the study of its use as a conditioning agent for allogeneic HCT. The highly immunosuppressive properties of the drug are particularly appealing in the setting of non-malignant HCT, where GVHD provides no clinical benefit and relapse of malignancy is not applicable...
January 19, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29351987/cd83-is-a-new-potential-biomarker-and-therapeutic-target-for-hodgkin-lymphoma
#2
Ziduo Li, Xinsheng Ju, Kenneth Lee, Candice Clarke, Jennifer L Hsu, Edward Abadir, Christian E Bryant, Suzanne Pears, Neroli Sunderland, Scott Heffernan, Annemarie Hennessy, Tsun-Ho Lo, Geoffrey A Pietersz, Fiona Kupresanin, Phillip D Fromm, Pablo A Silveira, Con Tsonis, Wendy A Cooper, Ilona Cunningham, Christina Brown, Georgina J Clark, Derek N J Hart
Chemotherapy and hematopoietic stem cell transplantation are effective treatments for most Hodgkin lymphoma patients, however there remains a need for better tumor-specific target therapy in Hodgkin lymphoma patients with refractory or relapsed disease. We demonstrate that membrane CD83 is a diagnostic and therapeutic target, highly expressed in Hodgkin lymphoma cell lines and Hodgkin and Reed-Sternberg cells in 29/35 (82.9%) Hodgkin lymphoma patient lymph node biopsies. CD83 from Hodgkin lymphoma tumor cells was able to trogocytose to surrounding T cells and interestingly, the trogocytosing CD83+T cells expressed significantly more PD-1 compared to CD83- T cells...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351985/tocilizumab-tacrolimus-and-methotrexate-for-the-prevention-of-acute-graft-versus-host-disease-low-incidence-of-lower-gastrointestinal-tract-disease
#3
William R Drobyski, Aniko Szabo, Fenlu Zhu, Carolyn Keever-Taylor, Kyle M Hebert, Renee Dunn, Sharon Yim, Bryon Johnson, Anita D'Souza, Mary Eapen, Timothy S Fenske, Parameswaran Hari, Mehdi Hamadani, Mary M Horowitz, J Douglas Rizzo, Wael Saber, Nirav Shah, Bronwen Shaw, Marcelo Pasquini
We conducted a phase 2 study in which patients undergoing allogeneic hematopoietic stem cell transplantation received Tocilizumab in addition to standard immune suppression with tacrolimus and methotrexate for graft versus host disease prophylaxis. Thirty-five patients were enrolled between January 2015 and June 2016. The median age of the cohort was 66 (range 22-76). All patients received busulfan-based conditioning, and were transplanted with HLA-matched related or matched unrelated bone marrow or peripheral stem cell grafts...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351753/mesenchymal-stem-cells-show-functional-defect-and-decreased-anti-cancer-effect-after-exposure-to-chemotherapeutic-drugs
#4
Chinnapaka Somaiah, Atul Kumar, Renu Sharma, Amit Sharma, Trishna Anand, Jina Bhattacharyya, Damodar Das, Sewali Deka Talukdar, Bithiah Grace Jaganathan
BACKGROUND: Mesenchymal stem cells (MSC) are used for several therapeutic applications to improve the functions of bone, cardiac, nervous tissue as well as to facilitate the repopulation of hematopoietic stem cells. MSC give rise to the non-hematopoietic stromal cells of the bone marrow and are important for the maintenance of normal hematopoiesis. Chemotherapeutic drugs used for treatment of leukemia extensively damage the stromal cells and alter their gene expression profiles. METHODS: We determined the changes in adipogenic, osteogenic differentiation, phenotypic and gene expression in MSC during treatment with chemotherapeutic drugs cytarabine, daunorubicin and vincristine...
January 19, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29350698/identification-and-management-sinusoidal-obstruction-syndrome-veno-occlusive-disease-eelated-to-hematopoietic-stem-cell-transplantation%C3%A2
#5
Mairéad Ní Chonghaile, Karen Wolownik
BACKGROUND: Sinusoidal obstruction syndrome (SOS), also called hepatic veno-occlusive disease (VOD), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT) that affects about 1 in 7 patients undergoing this procedure. SOS/VOD is caused by the conditioning regimens administered prior to HSCT; in some cases, SOS/VOD results from chemotherapy alone. SOS/VOD usually develops within three weeks following HSCT; however, it can have later onset. 
...
February 1, 2018: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/29350425/the-impact-of-preapheresis-white-blood-cell-count-on-autologous-peripheral-blood-stem-cell-collection-efficiency-and-hsc-infusion-side-effect-rate
#6
Araci M Sakashita, Andrea T Kondo, Ana Paula H Yokoyama, Sanny M C Lira, Carolina B Bub, Aline M Souza, Andrea N F Cipolletta, Kelen C Alvarez, Nelson Hamerschlak, Jose M Kutner, Carlos S Chiattone
BACKGROUND: Autologous peripheral blood hematopoietic stem cell (PBSC) collection efficiency (CE) is reportedly affected by the patient's blood properties; however, studies to identify factors correlated with CE have shown inconsistent results. Additionally, variables such as stem cell graft granulocyte content and patient age, sex, and underlying disease, may be associated with hematopietic stem cell (HSC) infusion-related adverse reactions. In this study, we evaluated the correlation of preleukapheresis PB granulocyte count and PBSC harvest variables with CD34+ collection yield and efficiency, and thawed HSC infusion side effect occurrence...
January 19, 2018: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/29349879/a-novel-pklr-gene-mutation-identified-using-advanced-molecular-techniques
#7
Yunyan He, Jianming Luo, Yonghong Lei, Siyuan Jia, Ning Liao
This study's purposes were to diagnose intractable hemolytic anemia and to provide guiding treatment for the affected family members. We performed NGS in a panel of 600 genes for blood diseases on a patient with obscure hemolytic anemia and her parents. We confirmed the diagnosis of pyruvate kinase deficiency, identified a novel homozygous mutation of the PKLR gene (NM_000298: exon 6: c.T941C: p.I314T), and ruled out other blood diseases in the Chinese family. Furthermore, amniotic fluid was taken from the mother during the second trimester, and DNA was extracted to analyze the type of PKLR gene mutation...
January 18, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29348881/allogeneic-stem-cell-transplantation-in-acute-lymphoblastic-leukemia-patients-older-than-60-years-a-survey-from-the-acute-leukemia-working-party-of-ebmt
#8
Gabrielle Roth-Guepin, Jonathan Canaani, Annalisa Ruggeri, Myriam Labopin, Juergen Finke, Jan J Cornelissen, Jeremy Delage, Gernot Stuhler, Monserrat Rovira, Mike Potter, Michael Stadler, Hendrik Veelken, Jean Yves Cahn, Matthew Collin, Yves Beguin, Sebastian Giebel, Arnon Nagler, Mohamad Mohty
Hematopoietic stem cell transplantation (HSCT) is being increasingly explored as a treatment modality for older patients with acute lymphoblastic leukemia (ALL). Yet, concerns regarding the long term outcome of transplantation in older patients limit the wide spread applicability of this approach. In this analysis we set out to determine the outcome of ALL patients over the age of 60 who underwent reduced intensity HSCT. Herein, we present the experience of the acute leukemia working party (ALWP) of the EBMT in this age group...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348574/full-body-physical-therapy-evaluation-for-pre-and-post-hematopoietic-cell-transplant-patients-and-the-need-for-a-modified-rehabilitation-musculoskeletal-specific-grading-system-for-chronic-graft-versus-host-disease
#9
Jaleel Mohammed, Ahmed AlGhamdi, Shahrukh K Hashmi
No abstract text is available yet for this article.
January 18, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29348127/murine-chronic-graft-versus-host-disease-proteome-profiling-discovers-ccl15-as-a-novel-biomarker-in-patients
#10
Jing Du, Ryan Flynn, Katelyn Paz, Hong-Gang Ren, Yuko Ogata, Qing Zhang, Philip R Gafken, Barry E Storer, Nathan H Roy, Janis K Burkhardt, Wendy Mathews, Jakub Tolar, Stephanie J Lee, Bruce R Blazar, Sophie Paczesny
Improved diagnostic and treatment methods are needed for chronic graft-versus-host disease (cGVHD), the leading cause of late non-relapse mortality (NRM) in long-term survivors of allogenic hematopoietic cell transplantation (allo-HCT). Validated biomarkers that facilitate disease diagnosis, and classification generally are lacking in cGVHD. Here, we conducted whole serum proteomics analysis of a well-established murine multi-organ system cGVHD model. We discovered 4 up-regulated proteins during cGVHD that are targetable by genetic ablation or blocking antibodies, including the RAS and JUN kinase activator, CRKL, and CXCL7, CCL8 and CCL9 chemokines...
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29348122/macrophage-transitions-in-heart-valve-development-and-myxomatous-valve-disease
#11
Alexia Hulin, Lindsey J Anstine, Andrew J Kim, Sarah J Potter, Tony DeFalco, Joy Lincoln, Katherine E Yutzey
OBJECTIVE: Hematopoietic-derived cells have been reported in heart valves but remain poorly characterized. Interestingly, recent studies reveal infiltration of leukocytes and increased macrophages in human myxomatous mitral valves. Nevertheless, timing and contribution of macrophages in normal valves and myxomatous valve disease are still unknown. The objective is to characterize leukocytes during postnatal heart valve maturation and identify macrophage subsets in myxomatous valve disease...
January 18, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29346409/prediction-of-absolute-risk-of-acute-graft-versus-host-disease-following-hematopoietic-cell-transplantation
#12
Catherine Lee, Sebastien Haneuse, Hai-Lin Wang, Sherri Rose, Stephen R Spellman, Michael Verneris, Katharine C Hsu, Katharina Fleischhauer, Stephanie J Lee, Reza Abdi
Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for a variety of hematologic malignancies and disorders. Unfortunately, acute graft-versus-host disease (GVHD) is a frequent complication of HCT. While substantial research has identified clinical, genetic and proteomic risk factors for acute GVHD, few studies have sought to develop risk prediction tools that quantify absolute risk. Such tools would be useful for: optimizing donor selection; guiding GVHD prophylaxis, post-transplant treatment and monitoring strategies; and, recruitment of patients into clinical trials...
2018: PloS One
https://www.readbyqxmd.com/read/29345374/ship-negatively-regulates-type-ii-immune-responses-in-mast-cells-and-macrophages
#13
REVIEW
Peter Dobranowski, Laura M Sly
SHIP is a hematopoietic-specific lipid phosphatase that dephosphorylates PI3K-generated PI(3,4,5)-trisphosphate. SHIP removes this second messenger from the cell membrane blunting PI3K activity in immune cells. Thus, SHIP negatively regulates mast cell activation downstream of multiple receptors. SHIP has been referred to as the "gatekeeper" of mast cell degranulation as loss of SHIP dramatically increases degranulation or permits degranulation in response to normally inert stimuli. SHIP also negatively regulates Mϕ activation, including both pro-inflammatory cytokine production downstream of pattern recognition receptors, and alternative Mϕ activation by the type II cytokines, IL-4, and IL-13...
January 17, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344584/early-and-late-outcomes-after-cord-blood-transplantation-for-pediatric-patients-with-inherited-leukodystrophies
#14
Brigitte T A van den Broek, Kristin Page, Annalisa Paviglianiti, Janna Hol, Heather Allewelt, Fernanda Volt, Gerard Michel, Miguel Angel Diaz, Victoria Bordon, Tracey O'Brien, Peter J Shaw, Chantal Kenzey, Amal Al-Seraihy, Peter M van Hasselt, Andrew R Gennery, Eliane Gluckman, Vanderson Rocha, Annalisa Ruggeri, Joanne Kurtzberg, Jaap Jan Boelens
Leukodystrophies (LD) are devastating inherited disorders leading to rapid neurological deterioration and premature death. Hematopoietic stem cell transplantation (HSCT) can halt disease progression for selected LD. Cord blood is a common donor source for transplantation of these patients because it is rapidly available and can be used without full HLA matching. However, precise recommendations allowing care providers to identify patients who benefit from HSCT are lacking. In this study, we define risk factors and describe the early and late outcomes of 169 patients with globoid cell leukodystrophy, X-linked adrenoleukodystrophy, and metachromatic leukodystrophy undergoing cord blood transplantation (CBT) at an European Society for Blood and Marrow Transplantation center or at Duke University Medical Center from 1996 to 2013...
January 9, 2018: Blood Advances
https://www.readbyqxmd.com/read/29343837/neurocognitive-dysfunction-in-hematopoietic-cell-transplant-recipients-expert-review-from-the-late-effects-and-quality-of-life-working-committee-of-the-cibmtr-and-complications-and-quality-of-life-working-party-of-the-ebmt
#15
REVIEW
David Buchbinder, Debra Lynch Kelly, Rafael F Duarte, Jeffery J Auletta, Neel Bhatt, Michael Byrne, Zachariah DeFilipp, Melissa Gabriel, Anuj Mahindra, Maxim Norkin, Helene Schoemans, Ami J Shah, Ibrahim Ahmed, Yoshiko Atsuta, Grzegorz W Basak, Sara Beattie, Sita Bhella, Christopher Bredeson, Nancy Bunin, Jignesh Dalal, Andrew Daly, James Gajewski, Robert Peter Gale, John Galvin, Mehdi Hamadani, Robert J Hayashi, Kehinde Adekola, Jason Law, Catherine J Lee, Jane Liesveld, Adriana K Malone, Arnon Nagler, Seema Naik, Taiga Nishihori, Susan K Parsons, Angela Scherwath, Hannah-Lise Schofield, Robert Soiffer, Jeff Szer, Ida Twist, Anne B Warwick, Baldeep M Wirk, Jean Yi, Minoo Battiwalla, Mary D E Flowers, Bipin Savani, Bronwen E Shaw
Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and non-malignant diseases. Despite increasing survival rates, long-term morbidity following HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction following HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction following HCT...
January 17, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29343826/mammalian-sterile-20-kinase-1-and-2-are-important-regulators-of-hematopoietic-stem-cells-in-stress-condition
#16
Da-Hye Lee, Tae-Shin Kim, Dongjun Lee, Dae-Sik Lim
The mammalian Hippo signaling pathway has been implicated in the self-renewal and differentiation of stem and progenitor cells. MST1 and MST2 (MST1/2) are core serine-threonine kinases in the Hippo signaling pathway, one of which, MST1, has been extensively investigated for its role in T cell and myeloid cell function. These studies have identified MST1 as a promising therapeutic target in immunological disease. However, the roles of MST1/2 in hematopoietic stem cell (HSC) function in vivo are not fully understood...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343764/genome-wide-association-study-in-79-366-european-ancestry-individuals-informs-the-genetic-architecture-of-25-hydroxyvitamin-d-levels
#17
Xia Jiang, Paul F O'Reilly, Hugues Aschard, Yi-Hsiang Hsu, J Brent Richards, Josée Dupuis, Erik Ingelsson, David Karasik, Stefan Pilz, Diane Berry, Bryan Kestenbaum, Jusheng Zheng, Jianan Luan, Eleni Sofianopoulou, Elizabeth A Streeten, Demetrius Albanes, Pamela L Lutsey, Lu Yao, Weihong Tang, Michael J Econs, Henri Wallaschofski, Henry Völzke, Ang Zhou, Chris Power, Mark I McCarthy, Erin D Michos, Eric Boerwinkle, Stephanie J Weinstein, Neal D Freedman, Wen-Yi Huang, Natasja M Van Schoor, Nathalie van der Velde, Lisette C P G M de Groot, Anke Enneman, L Adrienne Cupples, Sarah L Booth, Ramachandran S Vasan, Ching-Ti Liu, Yanhua Zhou, Samuli Ripatti, Claes Ohlsson, Liesbeth Vandenput, Mattias Lorentzon, Johan G Eriksson, M Kyla Shea, Denise K Houston, Stephen B Kritchevsky, Yongmei Liu, Kurt K Lohman, Luigi Ferrucci, Munro Peacock, Christian Gieger, Marian Beekman, Eline Slagboom, Joris Deelen, Diana van Heemst, Marcus E Kleber, Winfried März, Ian H de Boer, Alexis C Wood, Jerome I Rotter, Stephen S Rich, Cassianne Robinson-Cohen, Martin den Heijer, Marjo-Riitta Jarvelin, Alana Cavadino, Peter K Joshi, James F Wilson, Caroline Hayward, Lars Lind, Karl Michaëlsson, Stella Trompet, M Carola Zillikens, Andre G Uitterlinden, Fernando Rivadeneira, Linda Broer, Lina Zgaga, Harry Campbell, Evropi Theodoratou, Susan M Farrington, Maria Timofeeva, Malcolm G Dunlop, Ana M Valdes, Emmi Tikkanen, Terho Lehtimäki, Leo-Pekka Lyytikäinen, Mika Kähönen, Olli T Raitakari, Vera Mikkilä, M Arfan Ikram, Naveed Sattar, J Wouter Jukema, Nicholas J Wareham, Claudia Langenberg, Nita G Forouhi, Thomas E Gundersen, Kay-Tee Khaw, Adam S Butterworth, John Danesh, Timothy Spector, Thomas J Wang, Elina Hyppönen, Peter Kraft, Douglas P Kiel
Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29343653/establishment-of-a-screening-system-to-identify-novel-gata-2-transcriptional-regulators
#18
Keiichi Ohashi, Tohru Fujiwara, Koichi Onodera, Yo Saito, Satoshi Ichikawa, Masahiro Kobayashi, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Hideo Harigae
Hematopoietic stem cells can self-renew and differentiate into all blood cell types. The transcription factor GATA-2 is expressed in hematopoietic stem and progenitor cells and is essential for cell proliferation and differentiation. Heterozygous germline GATA2 mutations induce GATA-2 deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia and acute myeloid leukemia, and a profoundly reduced dendritic cell (DC) population, which is associated with increased susceptibility to viral infections...
2018: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29343582/hiv-replication-and-latency-in-a-humanized-nsg-mouse-model-during-suppressive-oral-combinational-art
#19
Sangeetha Satheesan, Haitang Li, John C Burnett, Mayumi Takahashi, Shasha Li, Shiny Xiaqin Wu, Timothy W Synold, John J Rossi, Jiehua Zhou
Although current combinatorial antiretroviral therapy (cART) is therapeutically effective in the majority of HIV patients, interruption of therapy can cause a rapid rebound in viremia, demonstrating the existence of a stable reservoir of latently infected cells. HIV latency is therefore considered a primary barrier to HIV eradication. Identifying, quantifying, and purging the HIV reservoir is crucial to effectively curing patients and relieving them from the lifelong requirement for therapy. Latently infected transformed cell models have been used to investigate HIV latency; however, they cannot accurately represent the quiescent cellular environment of primary latently infected cells in vivo...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343274/coexistent-sickle-cell-anemia-and-autoimmune-disease-in-eight-children-pitfalls-and-challenges
#20
Valerie Li-Thiao-Te, Florence Uettwiller, Pierre Quartier, Florence Lacaille, Brigitte Bader-Meunier, Valentine Brousse, Mariane de Montalembert
BACKGROUND: Patients with sickle cell disease (SCD) present a defective activation of the alternate complement pathway that increases the risk of infection and is thought to predispose to autoimmune disease (AID). However, coexisting AID and SCD is rarely reported, suggesting possible underdiagnosis due to an overlapping of the symptoms. STUDY DESIGN: Among 603 patients with SCD followed between 1999 and June 2016, we retrospectively searched for patients with coexisting SCD and AID...
January 17, 2018: Pediatric Rheumatology Online Journal
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