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haematopoietic stem cell transplant

Lei Dong, Wen-Mei Yu, Hong Zheng, Mignon L Loh, Silvia T Bunting, Melinda Pauly, Gang Huang, Muxiang Zhou, Hal E Broxmeyer, David T Scadden, Cheng-Kui Qu
Germline activating mutations of the protein tyrosine phosphatase SHP2 (encoded by PTPN11), a positive regulator of the RAS signalling pathway, are found in 50% of patients with Noonan syndrome. These patients have an increased risk of developing leukaemia, especially juvenile myelomonocytic leukaemia (JMML), a childhood myeloproliferative neoplasm (MPN). Previous studies have demonstrated that mutations in Ptpn11 induce a JMML-like MPN through cell-autonomous mechanisms that are dependent on Shp2 catalytic activity...
October 26, 2016: Nature
Ghady Haidar, Christa S Zerbe, Michelle Cheng, Adrian M Zelazny, Steven M Holland, Kathleen R Sheridan
Aspergillus spp. are a leading cause of mortality in chronic granulomatous disease (CGD), but other fungi have emerged in the era of mould prophylaxis. Of these, Phellinus spp. are an under-recognised cause of invasive fungal infections (IFIs) in CGD, and data on their presentation and management are scarce. We present a patient with CGD who developed disseminated IFI involving the lungs and brain. Surgical specimens grew a basidiomycete which was disregarded as a contaminant. After three months of progressive disease despite antifungals, he was diagnosed with Phellinus tropicalis by internal transcribed spacer (ITS) sequencing...
October 26, 2016: Mycoses
Mark R Schleiss
Congenital cytomegalovirus (CMV) infection is the most common infectious cause of disability in newborn infants. CMV also causes serious disease in solid organ (SOT) and haematopoietic stem cell transplant (HSCT) recipients. In otherwise healthy children and adults, primary CMV infection rarely causes illness. However, even asymptomatic CMV infections may predispose an individual towards an increased risk of atherosclerosis, cancer and immune senescence over the life course, although such associations remain controversial...
October 5, 2016: Journal of Virus Eradication
M T Cardoso, A O Pinheiro, A S Vidane, J B Casals, V C de Oliveira, Njn Gonçalves, D S Martins, C E Ambrósio
The biosafety of innovative procedures that utilize stem cells in regenerative medicine has been addressed in several studies. Previous work has showed no tumour formation following the use of feline and human amniotic membrane-derived stem cells (AMSCs). In contrast, tumour formation was observed when canine AMSCs were utilized. These findings suggested that feline and human, but not canine, AMSCs are suitable for cell transplantation trials. This study aimed to further evaluate the feasibility of utilizing canine AMSCs for transplantation purposes as well as for felines...
October 23, 2016: Reproduction in Domestic Animals, Zuchthygiene
Adewumi Adediran, Modu Baba Kagu, Tamunomieibi Wakama, Aliyu Ahmadu Babadoko, Dapus Obadiah Damulak, Sunday Ocheni, Marcus Inyama Asuquo
Background. Sickle cell anaemia (SCA) is an inherited condition whose clinical manifestations arise from the tendency of haemoglobin to polymerize and deform red blood cells into characteristic sickle shape. Allogeneic bone marrow transplantation offers a cure. The aim of this study was to determine the level of awareness, knowledge, and acceptance of this beneficial procedure in Nigeria. Materials and Methods. This multicentre cross-sectional study was conducted in 7 tertiary hospitals in Nigeria in 2015. Approval was obtained from each institution's research and ethics committee...
2016: Bone Marrow Research
Janette Kwok, Mengbiao Guo, Wanling Yang, C K Lee, Jenny Ho, W H Tang, Y S Chan, Derek Middleton, L W Lu, Godfrey C F Chan
HLA-A, -B, -C and -DRB1 gene and haplotype frequencies have been calculated from 7595 southern Chinese unrelated donors in a Hong Kong Bone Marrow Donor Registry. This is the first large-scale paper to report the distribution of A-C-B-DRB1 alleles in Hong Kong Chinese. This information is important for phylogenetic, comparative studies and estimating the optimal and cost-effective donor size and likelihood of obtaining appropriately matched donors for Chinese patients awaiting haematopoietic stem cell transplantation...
October 18, 2016: Human Immunology
Janette Kwok, Mengbiao Guo, Wanling Yang, C K Lee, N K Chan, Jenny Ho, W H Tang, Y S Chan, Derek Middleton, L W Lu, Godfrey C F Chan
HLA-A, -B and -DRB1 gene and haplotype frequencies have been calculated from 3892 southern Chinese unrelated cord blood units in a Hong Kong Cord Blood Registry. This is the first large-scale paper to report the distribution of A-B-DRB1 alleles in Hong Kong Chinese Cord Blood Units. This information is important for estimating the optimal and economically cost-effective donor size and likelihood of obtaining appropriately matched cord blood units for Chinese patients awaiting haematopoietic stem cell transplantation...
October 18, 2016: Human Immunology
Jennifer E Adair, Timothy Waters, Kevin G Haworth, Sara P Kubek, Grant D Trobridge, Jonah D Hocum, Shelly Heimfeld, Hans-Peter Kiem
Haematopoietic stem cell (HSC) gene therapy has demonstrated potential to treat many diseases. However, current state of the art requires sophisticated ex vivo gene transfer in a dedicated Good Manufacturing Practices facility, limiting availability. An automated process would improve the availability and standardized manufacture of HSC gene therapy. Here, we develop a novel program for semi-automated cell isolation and culture equipment to permit complete benchtop generation of gene-modified CD34(+) blood cell products for transplantation...
October 20, 2016: Nature Communications
B P C Hoppe, E de Jongh, A Griffioen-Keijzer, J M Zijlstra-Baalbergen, E P F IJzerman, F Baboe
Human metapneumovirus (hMPV) is a paramyxovirus that causes respiratory tract infections ranging from mild upper airway infection to severe pneumonia. Patients with haematological disease, especially haematopoietic stem cell transplantation (HSCT) recipients, are more likely to develop more severe infections. We describe three cases of hMPV infection in HSCT patients. The most reliable diagnostic procedure for hMPV is multiplex ligation-dependent probe amplification (MLPA) on a nasopharyngeal swab. Sensitivity and specificity of MLPA to detect hMPV is high and time to diagnosis is short...
October 2016: Netherlands Journal of Medicine
Lokesh Shahani
Liver failure is a frequent and serious complication that causes morbidity and mortality in haematopoietic stem cell transplantation (HCT) recipients. Liver dysfunction in these patients can be related to infectious causes, most common viral hepatitis. We report a case of disseminated acyclovir-resistant herpes simplex virus (HSV) infection following HCT that led to acute liver failure and death. Although rare, HSV hepatitis leads to high morbidity and mortality and should be considered in the differential diagnosis of HCT recipients with marked elevation of hepatic transaminase...
October 17, 2016: BMJ Case Reports
Irina A Tikhonova, Martin W Hoyle, Tristan M Snowsill, Chris Cooper, Joanna L Varley-Campbell, Claudius E Rudin, Ruben E Mujica Mota
The National Institute for Health and Care Excellence (NICE) invited the manufacturer of azacitidine (Celgene) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of acute myeloid leukaemia with more than 30 % bone marrow blasts in adults who are not eligible for haematopoietic stem cell transplantation, as part of the NICE's Single Technology Appraisal process. The Peninsula Technology Assessment Group was commissioned to act as the Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE...
October 17, 2016: PharmacoEconomics
Michael J Watts, David C Linch
Clinical practice and the technology of cell processing for autologous stem cell transplantation has continued to evolve over the last two decades and merits review of current quality control expectations. The external regulatory era has improved quality and safety standards but there is still variable practice, with specific risks illuminated by a number of clinical incidents. Viable CD34(+) cell assays may fail to indicate significant losses in progenitor function during storage, particularly after cryopreservation, and there is a need to develop an alternative, real time functional assay to replace colony assays...
October 17, 2016: British Journal of Haematology
Mark W Lowdell, Amy Thomas
Advanced therapy medicinal products (ATMPs) represent the current pinnacle of 'patient-specific medicines' and will change the nature of medicine in the near future. They fall into three categories; somatic cell-therapy products, gene therapy products and cells or tissues for regenerative medicine, which are termed 'tissue engineered' products. The term also incorporates 'combination products' where a human cell or tissue is combined with a medical device. Plainly, many of these new medicines share similarities with conventional haematological stem cell transplant products and donor lymphocyte infusions as well as solid organ grafts and yet ATMPs are regulated as medicines and their development has remained predominantly in academic settings and within specialist centres...
October 17, 2016: British Journal of Haematology
Ali Tafazoli
A 26-year-old woman developed symptoms of acute toxicity during cyclosporine (CsA) therapy for graft-versus-host disease prophylaxis. The standard regimen included CsA in a dose of 1.5 mg/kg (120 mg) every 12 h, but, as a medication error, she received a high dose of 500 mg of oral CsA. After 2 h, she developed nausea and vomiting and, subsequently, flushing, chest tightness, tremor and vertigo. Laboratory and clinical examinations revealed high blood CsA concentrations (1000 ng/mL after 12 h) with a mild increase in blood pressure...
December 2015: Drug Saf Case Rep
Benedetta Mazzanti, Serena Urbani, Simone Dal Pozzo, Paola Bufano, Lara Ballerini, Alessia Gelli, Irene Sodi, Irene Donnini, Massimo Di Gioia, Stefano Guidi, Julien Camisani, Riccardo Saccardi
BACKGROUND: Clinical grade processing of harvested bone marrow is required in various clinical situations, particularly in the management of ABO mismatching in allogeneic haematopoietic stem cell transplantation (HSCT) and in regenerative medicine. MATERIAL AND METHODS: We report a single-centre experience using a fully automated, clinical grade, closed system (Sepax, Biosafe, Switzerland). From 2003 to 2015, 125 procedures were performed in our laboratory, including buffy-coat production for HSCT (n=58), regenerative medicine in an orthopaedic setting (n=54) and density-gradient separation in a trial for treatment of critical limb ischaemia (n=13)...
September 27, 2016: Blood Transfusion, Trasfusione del Sangue
Xingbin Hu, Mayra Garcia, Lihong Weng, Xiaoman Jung, Jodi L Murakami, Bijender Kumar, Charles D Warden, Ivan Todorov, Ching-Cheng Chen
Microenvironment cues received by haematopoietic stem cells (HSC) are important in regulating the choice between self-renewal and differentiation. On the basis of the differential expression of cell-surface markers, here we identify a mesenchymal stromal progenitor hierarchy, where CD45(-)Ter119(-)CD31(-)CD166(-)CD146(-)Sca1(+)(Sca1(+)) progenitors give rise to CD45(-)Ter119(-)CD31(-)CD166(-)CD146(+)(CD146(+)) intermediate and CD45(-)Ter119(-)CD31(-)CD166(+)CD146(-)(CD166(+)) mature osteo-progenitors. All three progenitors preserve HSC long-term multi-lineage reconstitution capability in vitro; however, their in vivo fates are different...
October 10, 2016: Nature Communications
Mildred C Embree, Mo Chen, Serhiy Pylawka, Danielle Kong, George M Iwaoka, Ivo Kalajzic, Hai Yao, Chancheng Shi, Dongming Sun, Tzong-Jen Sheu, David A Koslovsky, Alia Koch, Jeremy J Mao
Tissue regeneration using stem cell-based transplantation faces many hurdles. Alternatively, therapeutically exploiting endogenous stem cells to regenerate injured or diseased tissue may circumvent these challenges. Here we show resident fibrocartilage stem cells (FCSCs) can be used to regenerate and repair cartilage. We identify FCSCs residing within the superficial zone niche in the temporomandibular joint (TMJ) condyle. A single FCSC spontaneously generates a cartilage anlage, remodels into bone and organizes a haematopoietic microenvironment...
October 10, 2016: Nature Communications
William Nigel Patton, Ian Nivison-Smith, Peter Bardy, Anthony Dodds, David Ma, Peter John Shaw, John Kwan, Leonie Wilcox, Andrew Butler, John M Carter, Hilary Blacklock, Jeffrey Szer
A previous study found that platelet recovery and mortality were worse in recipients of myeloablative bone marrow transplants where graft transit times were longer than 20 hours. This retrospective study of unrelated myeloablative allogeneic transplantation performed within Australia and NZ analysed transplant outcomes according to graft transit times. Of evaluable cases (n=233), 76 (33%) grafts were sourced from bone marrow (BM) and 157 (67%) from peripheral blood. Grafts sourced from Australia and NZ (47% of total) were associated with a median transit time of 6 hours versus 32 hours for overseas sourced grafts (53% of total)...
October 4, 2016: Biology of Blood and Marrow Transplantation
Thomas Altmann, Andrew R Gennery
DNA ligase IV deficiency is a rare primary immunodeficiency, LIG4 syndrome, often associated with other systemic features. DNA ligase IV is part of the non-homologous end joining mechanism, required to repair DNA double stranded breaks. Ubiquitously expressed, it is required to prevent mutagenesis and apoptosis, which can result from DNA double strand breakage caused by intracellular events such as DNA replication and meiosis or extracellular events including damage by reactive oxygen species and ionising radiation...
October 7, 2016: Orphanet Journal of Rare Diseases
Alex F Herrera, Haesook T Kim, Katherine A Kong, Malek Faham, Heather Sun, Aliyah R Sohani, Edwin P Alyea, Victoria E Carlton, Yi-Bin Chen, Corey S Cutler, Vincent T Ho, John Koreth, Chitra Kotwaliwale, Sarah Nikiforow, Jerome Ritz, Scott J Rodig, Robert J Soiffer, Joseph H Antin, Philippe Armand
Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ctDNA was associated with outcome after allogeneic haematopoietic stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in lymphoma. Conventional restaging and collection of peripheral blood samples occurred at pre-specified time points before and after HSCT and were assayed for ctDNA by sequencing of the immunoglobulin or T-cell receptor genes...
October 6, 2016: British Journal of Haematology
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