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https://www.readbyqxmd.com/read/28067165/gene-therapy-in-fanconi-anemia-a-matter-of-time-safety-and-gene-transfer-tool-efficiency
#1
Verhoeyen Els, Francisco José Román Rodríguez, François-Loïc Cosset, Camille Lévy, Paula Rio
Fanconi anemia (FA) is a rare genetic syndrome characterized by progressive marrow failure. Gene therapy by infusion of FA-corrected autologous hematopoietic stem cells (HSCs) may offer a potential cure since it is a monogenetic disease with mutations in the FANC genes, coding for DNA repair enzymes (See review[1]). However, the collection of hCD34 +-cells in FA patients implies particular challenges because of the reduced numbers of progenitor cells present in their bone marrow (BM)[2] or mobilized peripheral blood[3-5]...
January 9, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/27989932/allele-level-hla-matching-impacts-key-outcomes-following-umbilical-cord-blood-transplantation-for-inherited-metabolic-disorders
#2
Kanwaldeep K Mallhi, Angela R Smith, Todd E DeFor, Troy C Lund, Paul J Orchard, Weston P Miller
Allogeneic hematopoietic stem cell transplantation has demonstrated efficacy for numerous inherited metabolic disorders (IMDs). Umbilical cord blood transplant (UCBT) is increasingly used as a graft source in IMDs, but little is known of the impact of cord blood unit (CBU)/recipient HLA allelic disparity on key outcomes following UCBT for IMD. We reviewed outcomes of 106 consecutive first, single UCBTs for IMD at the University of Minnesota with regard to CBU/recipient HLA allelic matching (HLA-A, -B, -C, and -DRB1)...
January 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27932186/late-graft-rejection-in-association-with-t-large-granular-lymphocyte-expansion-of-recipient-origin-after-human-leukocyte-antigen-haploidentical-stem-cell-transplantation-a-case-report
#3
N Nakagawa, H Yamazaki, G Aoki, Y Kondo, S Nakao
BACKGROUND: Large granular lymphocyte (LGL) expansion occasionally occurs after allogeneic stem cell transplantation (allo-SCT), and is thought to be a good prognostic sign that is associated with a lower relapse rate. However, there have been no reports of late graft failure (LGF) due to graft rejection in association with oligoclonal LGL expansion. We herein report a case of LGF associated with the transient expansion of recipient-derived T-LGL after allo-SCT. CASE REPORT: A 65-year-old man underwent peripheral blood stem cell transplantation (PBSCT) from his human leukocyte antigen (HLA)-haploidentical son for the treatment of acute myeloid leukemia, which had evolved from a myelodysplastic syndrome (MDS)...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27921235/transplantation-of-collagen-scaffold-with-autologous-bone-marrow-mononuclear-cells-promotes-functional-endometrium-reconstruction-via-downregulating-%C3%AE-np63-expression-in-asherman-s-syndrome
#4
Guangfeng Zhao, Yun Cao, Xianghong Zhu, Xiaoqiu Tang, Lijun Ding, Haixiang Sun, Juan Li, Xinan Li, Chenyan Dai, Tong Ru, Hui Zhu, Jingjie Lu, Caimei Lin, Jingmei Wang, Guijun Yan, Huiyan Wang, Lei Wang, Yimin Dai, Bin Wang, Ruotian Li, Jianwu Dai, Yan Zhou, Yali Hu
Asherman's syndrome (AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells (BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration...
December 1, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27907031/in-vitro-pre-clinical-validation-of-suicide-gene-modified-anti-cd33-redirected-chimeric-antigen-receptor-t-cells-for-acute-myeloid-leukemia
#5
Kentaro Minagawa, Muhammad O Jamil, Mustafa Al-Obaidi, Larisa Pereboeva, Donna Salzman, Harry P Erba, Lawrence S Lamb, Ravi Bhatia, Shin Mineishi, Antonio Di Stasi
BACKGROUND: Approximately fifty percent of patients with acute myeloid leukemia can be cured with current therapeutic strategies which include, standard dose chemotherapy for patients at standard risk of relapse as assessed by cytogenetic and molecular analysis, or high-dose chemotherapy with allogeneic hematopoietic stem cell transplant for high-risk patients. Despite allogeneic hematopoietic stem cell transplant about 25% of patients still succumb to disease relapse, therefore, novel strategies are needed to improve the outcome of patients with acute myeloid leukemia...
2016: PloS One
https://www.readbyqxmd.com/read/27901481/human-pancreatic-cancer-xenografts-recapitulate-key-aspects-of-cancer-cachexia
#6
Daniel Delitto, Sarah M Judge, Andrea E Delitto, Rachel L Nosacka, Fernanda G Rocha, Bayli B DiVita, Michael H Gerber, Thomas J George, Kevin E Behrns, Steven J Hughes, Shannon M Wallet, Andrew R Judge, Jose G Trevino
Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27890707/novel-mutation-in-dock8-hies-with-severe-phenotype-and-successful-transplantation
#7
Latifa Al Shekaili, Farrukh Sheikh, Sulaiman Al Gazlan, Hasan Al Dhekri, Hamoud Al Mousa, Abdulaziz Al Ghonaium, Bander Al Saud, Saleh Al Mohsen, Agha M Rehan Khaliq, Safiah Al Sumayli, Mufarreh Al Zahrani, Anas Dababo, Ammar AlKawi, Abbas Hawwari, Rand Arnaout
BACKGROUND: Hyper-IgE syndrome (HIES) due to DOCK8 deficiency is an autosomal recessive (AR) primary combined immunodeficiency which results in significant morbidity and mortality at a young age. Different mutations in the DOCK8 gene can lead to variable severity of the disease. OBJECTIVE: We evaluated the genetic mutations in three related patients with severe clinical manifestations suggestive of AR HIES. We also explored whether treatment with stem cell transplantation could lead to complete disease resolution...
November 23, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27888540/higher-dose-of-cd34-peripheral-blood-stem-cells-is-associated-with-better-survival-after-haploidentical-stem-cell-transplantation-in-pediatric-patients
#8
Yao Chen, Lan-Ping Xu, Kai-Yan Liu, Huan Chen, Yu-Hong Chen, Xiao-Hui Zhang, Yu Wang, Feng-Rong Wang, Wei Han, Jing-Zhi Wang, Chen-Hua Yan, Xiao-Jun Huang
Haploidentical stem cell transplantation (SCT) is increasingly used to treat pediatric patients with malignant or non-malignant hematological disorders. The CD34+ dose of bone marrow or peripheral blood stem cells (PBSCs) has been shown to be an important determinant of the transplant outcome in adults under various preparative regimens. However, knowledge of the effect of the CD34+ dose in pediatric haploidentical SCT is limited. We analyzed the data of 348 pediatric patients (aged 2-18 years) with acute or chronic leukemia, myelodysplastic syndrome (MDS), and other hematological disorders that received a transplant between 2002 and 2012...
November 26, 2016: Clinical Transplantation
https://www.readbyqxmd.com/read/27853082/early-improvement-in-marrow-fibrosis-following-haploidentical-stem-cell-transplantation-for-a-patient-with-myelodysplastic-syndrome-with-bone-marrow-fibrosis
#9
Shuichiro Takahashi, Riko Tsumanuma, Keiko Aizawa, Mitsumasa Osakabe, Kunihiko Maeda, Ejiro Omoto
The prognosis for myelodysplastic syndrome with bone marrow fibrosis (MDS-F) is worse than the prognosis of MDS without fibrosis. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy; however, the indications and the procedures involved in HSCT remain unclear. We herein describe a 69-year-old Japanese man with MDS-F who received haploidentical HSCT and post-transplantation cyclophosphamide. Although the first HSCT resulted in secondary graft failure, the second HSCT using PTCy led to successful engraftment after early improvement in fibrosis...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27829721/successful-engraftment-after-hematopoietic-stem-cell-transplantation-with-infusion-of-donor-stem-cells-through-the-extracorporeal-membrane-oxygenation-circuit
#10
Pilar Anton-Martin, Cindy Darnell-Bowens, Victor M Aquino, Teresa Jones, Lakshmi Raman
Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency due to mutations in the WAS gene expressed in hematopoietic cells. Hematopoietic stem cell transplantation (HSCT) is the treatment of choice when an appropriate human leukocyte antigen-matched donor is available. The use of the extracorporeal membrane oxygenation (ECMO) circuit to infuse donor cells for HSCT has not been previously published in the literature. We describe a case of a child who had successful engraftment after HSCT with infusion of the donor stem cells through the ECMO circuit...
October 2016: Indian Journal of Critical Care Medicine
https://www.readbyqxmd.com/read/27816481/nk-cell-effector-functions-in-a-ch%C3%A3-diak-higashi-patient-undergoing-cord-blood-transplantation-effects-of-in-vitro-treatment-with-il-2
#11
Loredana Cifaldi, Rita Maria Pinto, Ippolita Rana, Maurizio Caniglia, Adriano Angioni, Stefano Petrocchi, Caterina Cancrini, Laura Cursi, Giuseppe Palumbo, Alessandra Zingoni, Angela Gismondi, Paolo Rossi, Angela Santoni, Cristina Cerboni
NK cell cytotoxicity in Chédiak-Higashi syndrome (CHS) is strongly impaired as lytic granules are not released upon NK-target cell contact, contributing to several defects typical of this severe immunodeficiency. Correction of NK cell defects in CHS should improve the outcome of hematopoietic stem-cell transplantation, proposed as therapy. We investigated NK cell functions in a CHS patient before and after cord-blood transplantation, and the ability of in vitro IL-2 treatment to restore them. Before the transplant, the strong defect in NK cell-mediated natural and antibody-dependent cytotoxicity, as well as in IFN-γ production, could be restored up to normal levels by in vitro IL-2 treatment...
November 2, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27803295/strong-antineoplastic-effects-of-metformin-in-preclinical-models-of-liver-carcinogenesis
#12
François Cauchy, Mouniya Mebarki, Benjamin Leporq, Samira Laouirem, Miguel Albuquerque, Simon Lambert, Pierre Bourgoin, Olivier Soubrane, Bernard E Van Beers, Sandrine Faivre, Pierre Bedossa, Valérie Paradis
Studies suggest that metformin, widely used for treating Type 2 diabetes, possesses innate antineoplastic properties. For metabolic syndrome patients with hepatocellular carcinoma (HCC), metformin may provide antitumoral effects. We evaluated the impact of metformin on tumour growth and visceral fat composition using relevant preclinical models of metabolic syndrome. Studies were performed in three hepatoma cell lines, in HepG2 xenograft mice fed with standard chow (SC) diet, 60% high-fat diet (HFD) or 30% fructose diet (FR), and an ex vivo model of human cultured HCC slices...
January 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27762068/procalcitonin-and-cytokine-profiles-in-engraftment-syndrome-in-pediatric-stem-cell-transplantation
#13
Nirali N Shah, Theresa M Watson, Bonnie Yates, David J Liewehr, Seth M Steinberg, David Jacobsohn, Terry J Fry
BACKGROUND: Diagnosis of engraftment syndrome (ES) following allogeneic hematopoietic stem cell transplantation (HSCT) can be a challenge due to the systemic presentation and alternative etiologies. With a goal of establishing biomarkers to more accurately distinguish ES, we prospectively analyzed levels of cytokines during HSCT. PROCEDURES: We performed a prospective study of children ≤21 years who underwent allogeneic HSCT. Blood samples for interleukin (IL)-6, IL-8, IL-10, IL-1b, IL-12p70, interferon-γ, tumor necrosis factor alpha (TNF-α) and procalcitonin were obtained from each subject prior to conditioning, at day 0, and then biweekly through engraftment and at days 30, 60 and 100...
October 20, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27722122/pre-engraftment-syndrome-clinical-significance-and-pathophysiology
#14
REVIEW
Young-Ho Lee, Wee-Jin Rah
No abstract text is available yet for this article.
September 2016: Blood Research
https://www.readbyqxmd.com/read/27715384/allogeneic-hematopoietic-stem-cell-transplantation-for-nonmalignant-hematologic-disorders-using-chemotherapy-only-cytoreductive-regimens-and-t-cell-depleted-grafts-from-human-leukocyte-antigen-matched-or-mismatched-donors
#15
Alberto Mussetti, Nancy A Kernan, Susan E Prockop, Andromachi Scaradavou, Rachel Lehrman, Julianne M Ruggiero, Kevin Curran, Rachel Kobos, Richard O'Reilly, Farid Boulad
Nonmalignant hematologic disorders (NMHD) of childhood comprise a variety of disorders, including acquired severe aplastic anemia and inherited marrow failure syndromes. Patients with high-risk NMHD without matched related donors fare poorly with allogeneic hematopoietic alternative donor stem cell transplantation (allo-HSCT) and are at high risk for developing graft-versus-host disease following unmodified grafts. The authors retrospectively analyzed data on 18 patients affected by NMHD, lacking a human leukocyte antigen (HLA)-identical sibling donor, who underwent an alternative donor allo-HSCT at their institution between April 2005 and May 2013...
September 2016: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/27699249/a-xenograft-model-of-macrophage-activation-syndrome-amenable-to-anti-cd33-and-anti-il-6r-treatment
#16
Mark Wunderlich, Courtney Stockman, Mahima Devarajan, Navin Ravishankar, Christina Sexton, Ashish R Kumar, Benjamin Mizukawa, James C Mulloy
Transgenic expression of key myelosupportive human cytokines in immune-deficient mice corrects for the lack of cross-species activities of stem cell factor (SCF), IL-3, and GM-CSF. When engrafted with human umbilical cord blood (UCB), these triple-transgenic mice produce BM and spleen grafts with much higher myeloid composition, relative to nontransgenic controls. Shortly after engraftment with UCB, these mice develop a severe, fatal macrophage activation syndrome (MAS) characterized by a progressive drop in rbc numbers, increased reticulocyte counts, decreased rbc half-life, progressive cytopenias, and evidence of chronic inflammation, including elevated human IL-6...
September 22, 2016: JCI Insight
https://www.readbyqxmd.com/read/27687869/allogeneic-hematopoietic-stem-cell-transplant-in-adult-patients-with-myelodysplastic-syndrome-myeloproliferative-neoplasm-mds-mpn-overlap-syndromes
#17
Prashant Sharma, Shivani S Shinde, Moussab Damlaj, Mehrdad Hefazi Rorghabeh, Shahrukh K Hashmi, Mark R Litzow, William J Hogan, Naseema Gangat, Michelle A Elliott, Aref Al-Kali, Ayalew Tefferi, Mrinal M Patnaik
MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasm) overlap syndromes are myeloid malignancies for which allogeneic hematopoietic stem cell transplant (allo-HSCT) is potentially curative. We describe transplant outcomes of 43 patients - 35 with chronic myelomonocytic leukemia, CMML (of which 17 had blast transformation, BT) and eight with MDS/MPN-unclassifiable (MDS/MPN,U). At median follow-up of 21 months, overall survival (OS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 55%, 29%, and 25% respectively in CMML without BT and 47%, 40%, and 34% respectively in CMML with BT...
August 11, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27662232/haematopoietic-stem-cell-transplantation-in-inborn-errors-of-metabolism
#18
Robert Chiesa, Robert F Wynn, Paul Veys
PURPOSE OF REVIEW: This review summarizes the main results of haematopoietic stem cell transplantation (HSCT) in selected inborn errors of metabolism (IEMs). RECENT FINDINGS: Early diagnosis and immediate referral to an IEM specialist is of paramount importance to improve clinical outcome: patients who are transplanted early or in their presymptomatic phase generally achieve better correction of their somatic symptoms and neurocognitive development. Long-term outcome in children with Hurler syndrome is influenced by age at HSCT, baseline clinical status and post-HSCT enzyme levels...
November 2016: Current Opinion in Hematology
https://www.readbyqxmd.com/read/27643869/thrombomodulin-blocks-calcineurin-inhibitor-induced-vascular-permeability-via-inhibition-of-src-ve-cadherin-axis
#19
T Ikezoe, J Yang, C Nishioka, K Umezawa, A Yokoyama
Recombinant human soluble thrombomodulin (rTM) counteracted capillary leakage and alleviated edema in individuals with sinusoidal obstruction syndrome and engraftment syndrome after hematopoietic stem cell transplantation. We previously showed that rTM increased levels of antiapoptotic protein Mcl-1 and protected endothelial cells from calcineurin inhibitor cyclosporine A (CsA)-induced apoptosis. However, the molecular mechanisms by which rTM enhances barrier function in vascular endothelial cells remain unknown...
September 19, 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27634201/high-dose-therapy-and-autologous-stem-cell-transplantation-in-patients-with-poems-syndrome-a-retrospective-study-of-the-plasma-cell-disorder-sub-committee-of-the-chronic-malignancy-working-party-of-the-european-society-for-blood-marrow-transplantation
#20
Gordon Cook, Simona Iacobelli, Anja van Biezen, Dimitris Ziagkos, Veronique LeBlond, Julie Abraham, Grant McQuaker, Stefan Schoenland, Alessandro Rambaldi, Kazimierz Halaburda, Maria Rovira, Simona Sica, Jenny Byrne, Ramon Garcia Sanz, Arnon Nagler, Niels W C J van de Donk, Marjatta Sinisalo, Mark Cook, Nicolaus Kröger, Theo De Witte, Curly Morris, Laurant Garderet
POEMS syndrome is a rare para-neoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment can control the disease-related symptom complex. We describe the clinical outcome of autologous stem cell transplantation for patients with POEMS syndrome, determining the impact of patient- and disease-specific factors on prognosis. One hundred and twenty-seven patients underwent an autologous stem cell transplantation between 1997-2010 with a median age of 50 years (range 26-69 years). Median time from diagnosis to autologous stem cell transplantation was 7...
January 2017: Haematologica
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