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https://www.readbyqxmd.com/read/28807770/gsta1-genetic-variants-and-conditioning-regimen-missing-key-factors-in-dosing-guidelines-of-busulfan-in-pediatric-hematopoietic-stem-cell-transplantation
#1
T Nava, M A Rezgui, Crs Uppugunduri, P Huezo-Diaz Curtis, Y Théoret, M Duval, L E Daudt, M Ansari, M Krajinovic, H Bittencourt
Busulfan (Bu) is a key component of conditioning regimens used prior to hematopoietic stem cell transplantation (SCT) in children. Different predictive methods have been used to calculate the Bu first-dose. To evaluate the necessity of further improvements, we retrospectively analyzed the currently available weight- and age-based guidelines to calculate the first doses in 101 children who underwent allogenic SCT in CHU Sainte-Justine, Montreal, following an intravenous Bu-containing conditioning regimen according to genetic and clinical factors...
August 11, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28799202/immune-tolerance-induced-by%C3%A2-platelet-targeted-factor-viii-gene-therapy-in-hemophilia-a-mice-is-cd4%C3%A2-t-cell-mediated
#2
Y Chen, X Luo, J A Schroeder, J Chen, C K Baumgartner, J Hu, Q Shi
BACKGROUND: Immune responses are a major concern in gene therapy. Our previous studies demonstrated that platelet-targeted FVIII (2bF8) gene therapy together with in vivo drug-selection of transduced cells can rescue the bleeding diathesis and induce immune tolerance in FVIII(null) mice. OBJECTIVE: To investigate whether non-selectable 2bF8 lentiviral vector (LV) for the induction of platelet-FVIII expression is sufficient to induce immune tolerance and how immune tolerance is induced after 2bF8LV gene therapy...
August 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28798776/protective-effects-of-chronic-intermittent-hypobaric-hypoxia-pretreatment-against-aplastic-anemia-through-improving-the-adhesiveness-and-stress-of-mesenchymal-stem-cells-in-rats
#3
Jing Yang, Li Zhang, Handong Wang, Zan Guo, Yixian Liu, Yi Zhang, Chuan Wang, Quanhai Li
Aplastic anemia (AA) is a common malignant blood disease, and chronic intermittent hypobaric hypoxia (CIHH) has a beneficial effect against different diseases. The aim of the present study was to investigate the protective effect of CIHH against AA and underlying mechanisms. 5-Fluorouracil and busulfan treatment induced AA model in rats with reduction of hematological parameters and bone marrow tissue injury and decrease of the colony numbers of progenitor cells. CIHH pretreatment significantly reduced the incidence rate of AA and alleviated above symptoms in AA model...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28782395/myeloablative-busulfan-cytoxan-conditioning-versus-reduced-intensity-fludarabine-melphalan-conditioning-for-allogeneic-hematopoietic-stem-cell-transplant-in-patients-with-acute-myelogenous-leukemia
#4
Vishal Dhere, Scott Edelman, Edmund K Waller, Amelia Langston, Michael Graiser, Erin C Connolly, Jeffrey M Switchenko, Natia Esiashvili, Mohammad K Khan
Fludarabine and melphalan (Flu/Mel) has emerged as a more tolerable chemotherapy-based conditioning regimen compared with busulfan and cyclophosphamide (Bu/Cy) for allogeneic stem cell transplant (allo-hematopoietic stem cell transplantation (HSCT)) patients with acute myelogenous leukemia (AML). We conducted a retrospective review of a single-institution database including patients with AML who received allo-HSCT following conditioning with Mel/Flu or Bu/Cy-based regimens. We performed descriptive statistical analysis to examine patient demographics and clinical outcomes...
August 7, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28780238/tcr%C3%AE-%C3%AE-and-cd19-cell-depleted-haploidentical-and-mismatched-hematopoietic-stem-cell-transplantation-in-primary-immune-deficiency
#5
Ravi M Shah, Reem Elfeky, Zohreh Nademi, Waseem Qasim, Persis Amrolia, Robert Chiesa, Kanchan Rao, Giovanna Lucchini, Juliana M F Silva, Austen Worth, Dawn Barge, David Ryan, Jane Conn, Andrew J Cant, Roderick Skinner, Intan Juliana Abd Hamid, Terence Flood, Mario Abinun, Sophie Hambleton, Andrew R Gennery, Paul Veys, Mary Slatter
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is used as a therapeutic approach for primary immunodeficiencies (PIDs). The best outcomes have been achieved using HLA-matched donors, but when a matched donor is not available, a haploidentical or mismatched unrelated donor (mMUD) can be useful. Various strategies are used to mitigate the risk of graft versus host disease (GvHD) and rejection associated with such transplants. OBJECTIVE: We sought to evaluate the outcomes of haploidentical or mMUD HSCT after depleting GvHD causing TCRαβCD3+ cells from the graft...
August 2, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28777437/double-sex-and-mab-3-related-transcription-factor-1-regulates-differentiation-and-proliferation-in-dairy-goat-male-germline-stem-cells
#6
Yudong Wei, Shufang Cai, Fanglin Ma, Ying Zhang, Zhe Zhou, Shuanshuan Xu, Mengfei Zhang, Sha Peng, Jinlian Hua
The protein encoded by double sex and mab-3 related transcription factor 1 (Dmrt1)gene contains a double sex/mab-3 domain, which was considered as one of the most conservative structures in sex determination. However, its effect on spermatogenesis of dairy goat spermatogonial stem cells (SSCs) remains to be clarified. For the first time, the roles of Dmrt1 in spermatogenesis of livestock are highlighted. Here, we investigated the expression pattern of Dmrt1 in the testes of dairy goats. Dmrt1 primarily located in undifferentiated SSCs...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28771045/expression-patterns-and-changes-of-the-lcn2-gene-in-the-testes-of-induced-cryptorchidism-and-busulfan-treated-mice
#7
Zhenlong Kang, Na Qiao, Zhigang Tan, Zhaoxin Tang, Ying Li
Lipocalin-2 (LCN2) was known to play various roles in different type cells; however, little was known about the effect of LCN2 in male fertility. In this study, we aimed to explore the expression pattern of LCN2 with increasing age in mice, and to obtain insight into the role of LCN2 in mice testes by induced cryptorchidism and busulfan-treated infertility. In situ hybridization showed that LCN2 was localized primarily in Leydig cells, but was absent in Sertoli and germ cells. Its expression in testes exhibited an age-related increase from day 1 to 8 months, then reduced by the twelth month...
August 3, 2017: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/28768794/embryonic-stem-cell-derived-germ-cells-induce-spermatogenesis-following-transplantation-to-testis-of-adult-mouse-azoospermia-model
#8
Zohreh Makoolati, Mansoureh Movahedin, Mehdi Forouzandeh-Moghadam, Majid Naghdi, Morteza Koruji
This study aimed to (a) identify the exogenous factors that allow in vitro differentiation of mouse SSCs from embryonic stem cells (ESCs); (b) evaluate the effects of Sertoli cells on SSCs enrichment; and (c) to assess the success of transplantation using in vitro differentiated SSCs in mouse busulfan-treated azoospermia model. One-day-old embryoid body (EB) received 5 ng/ml BMP4 for 4 days, 3 µM retinoic acid (RA) in STO co-culture (Co-C) system for 7 days and subsequently co-cultured for 2 days with Sertoli cell in the presence or absence of LIF, bFGF and RA composition and in the presence of these factors in the simple culture media...
August 2, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28766962/clarifying-busulfan-metabolism-and-drug-interactions-to-support-new-therapeutic-drug-monitoring-strategies-a-comprehensive-review
#9
Alan L Myers, Jitesh D Kawedia, Richard E Champlin, Mark A Kramer, Yago Nieto, Romi Ghose, Borje S Andersson
Busulfan (Bu) is an alkylating agent with a limited therapeutic margin and exhibits inter-patient variability in pharmacokinetics (PK). Despite decades of use, mechanisms of Bu PK-based drug-drug interactions (DDIs), as well as the negative downstream effects of these DDIs, have not been fully characterized. Areas covered: This article provides an overview of Bu PK, with a primary focus on how known and potentially unknown drug metabolism pathways influence Bu-associated DDIs. In addition, pharmacogenomics of Bu chemotherapy and Bu-related DDIs observed in the stem cell transplant clinic (SCT) are summarized...
August 2, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28752258/allogeneic-reduced-intensity-hematopoietic-stem-cell-transplantation-for-chronic-granulomatous-disease-a-single-center-prospective-trial
#10
Mark Parta, Corin Kelly, Nana Kwatemaa, Narda Theobald, Diane Hilligoss, Jing Qin, Douglas B Kuhns, Christa Zerbe, Steven M Holland, Harry Malech, Elizabeth M Kang
PURPOSE: The purpose of this study was to evaluate engraftment and adverse events with a conditioning and prophylactic regimen intended to achieve high rates of engraftment with minimal graft-versus-host disease (GVHD) in allogeneic transplantation for chronic granulomatous disease in a single center. METHODS: Forty patients, 37 male, with chronic granulomatous disease were transplanted. Transplant products were matched sibling peripheral blood stem cells (PBSCs) in four and matched unrelated donor (MUD) bone marrow in three, and one patient received mismatched unrelated PBSCs...
July 28, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28744217/the-association-of-combined-gstm1-and-cyp2c9-genotype-status-with-the-occurrence-of-hemorrhagic-cystitis-in-pediatric-patients-receiving-myeloablative-conditioning-regimen-prior-to-allogeneic-hematopoietic-stem-cell-transplantation
#11
Chakradhara Rao S Uppugunduri, Flavia Storelli, Vid Mlakar, Patricia Huezo-Diaz Curtis, Aziz Rezgui, Yves Théorêt, Denis Marino, Fabienne Doffey-Lazeyras, Yves Chalandon, Peter Bader, Youssef Daali, Henrique Bittencourt, Maja Krajinovic, Marc Ansari
Hemorrhagic cystitis (HC) is one of the complications of busulfan-cyclophosphamide (BU-CY) conditioning regimen during allogeneic hematopoietic stem cell transplantation (HSCT) in children. Identifying children at high risk of developing HC in a HSCT setting could facilitate the evaluation and implementation of effective prophylactic measures. In this retrospective analysis genotyping of selected candidate gene variants was performed in 72 children and plasma Sulfolane (Su, water soluble metabolite of BU) levels were measured in 39 children following treatment with BU-CY regimen...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28737776/therapeutic-salivary-monitoring-of-iv-busulfan-in-patients-undergoing-hematopoietic-stem-cell-transplantation-a-pilot-study
#12
L M Bezinelli, F P Eduardo, D L C de Carvalho, C E Dos Santos Ferreira, E V de Almeida, L R Sanches, I Esteves, P V Campregher, N Hamerschlak, L Corrêa
Individual therapeutic monitoring of busulfan (BU) minimizes its toxicity and improves the therapeutic outcomes during hematopoietic stem cell transplantation (HSCT). For individual dose adjustment, several blood collections are performed that are uncomfortable for patients. The aim of this pilot study was to validate a laboratory method for quantification of BU in saliva and to present the results obtained using this protocol in HSCT patients. We performed analyses of selectivity, precision and accuracy of saliva with standard concentrations of BU using ultra-high-performance liquid chromatography with diode array detection...
July 24, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28733264/the-impact-of-toxicities-on-first-year-outcomes-after-ex-vivo-cd34-selected-allogeneic-hematopoietic-cell-transplantation-in-adults-with-hematologic-malignancies
#13
Satyajit Kosuri, Diego Adrianzen Herrera, Michael Scordo, Gunjan L Shah, Christina Cho, Sean M Devlin, Molly A Maloy, Jimmy Nieves, Taylor Borrill, Dean C Carlow, Scott T Avecilla, Richard C Meagher, Richard J O'Reilly, Esperanza B Papadopoulos, Ann A Jakubowski, Guenther Koehne, Boglarka Gyurkocza, Hugo Castro-Malaspina, Brian C Shaffer, Roni Tamari, Sergio A Giralt, Miguel-Angel Perales
Factors that impact first-year morbidity and mortality in adults undergoing myeloablative allogeneic hematopoietic cell transplantation with ex vivo CD34(+) selection have not been previously reported. We assessed all toxicities ≥ grade 3 from the start of conditioning to date of death, relapse, or last contact in 200 patients during the first year after transplantation, identifying 1885 individual toxicities among 17 organ-based toxicity groups. The most prevalent toxicities in the first year were of infectious, metabolic, hematologic, oral/gastrointestinal, hepatic, cardiac, and pulmonary etiologies...
July 18, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28733263/consolidation-therapy-for-newly-diagnosed-pediatric-patients-with-high-risk-neuroblastoma-using-busulfan-melphalan-autologous-hematopoietic-cell-transplantation-anti-gd2-antibody-granulocyte-macrophage-colony-stimulating-factor-interleukin-2-and-haploidentical
#14
Aimee C Talleur, Brandon M Triplett, Sara Federico, Ewelina Mamcarz, William Janssen, Jianrong Wu, David Shook, Wing Leung, Wayne L Furman
The treatment of pediatric high-risk neuroblastoma is intensive and multimodal. Despite the introduction of immunotherapy for minimal residual disease, survival rates remain suboptimal and new therapies are needed. As part of a phase 2 trial, we are using a consolidation therapy regimen that combines a busulfan/melphalan conditioning schema, autologous hematopoietic cell transplantation (AHCT), and experimental immunotherapy with hu14.18K322A (a humanized anti-GD2 monoclonal antibody), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-2, with or without the adoptive transfer of haploidentical natural killer cells (NKs)...
July 18, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28726193/regenerative-potential-of-spermatogonial-stem-cells-endothelial-progenitor-cells-and-epithelial-progenitor-cells-of-c57bl-6-male-mice-with-metabolic-disorders
#15
E G Skurikhin, A V Pakhomova, O V Pershina, L A Ermolaeva, V A Krupin, N N Ermakova, E S Pan, A I Kudryashova, O Yu Rybalkina, T B Pavlovskaya, N V Litvyakov, V E Goldberg, A M Dygai
The properties of spermatogonial stem cells, endothelial progenitor cells, and the epithelial progenitors of C57Bl/6 mice under conditions of metabolic disorders were studied using the model of busulfan-induced suppression of spermatogenesis and in vitro culture technique. Spermatogonial stem cells CD117-CD90(+) and epithelial progenitors CD45-CD31-Sca-1(+)CD49f(+) derived from the testes of mice with metabolic disturbances demonstrated 17- and 28-fold increase in the respective cell mass and generated cell colonies in vitro...
June 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28711727/a-chemotherapy-only-regimen-of-busulfan-melphalan-and-fludarabine-and-rabbit-antithymocyte-globulin-followed-by-allogeneic-t-cell-depleted-hematopoietic-stem-cell-transplantations-for-the-treatment-of-myeloid-malignancies
#16
Barbara Spitzer, Ann A Jakubowski, Esperanza B Papadopoulos, Kirsten Fuller, Patrick D Hilden, James W Young, Juliet Barker, Guenther Koehne, Miguel-Angel Perales, Katharine C Hsu, Marcel R M van den Brink, Nancy A Kernan, Susan E Prockop, Andromachi Scaradavou, Hugo Castro-Malaspina, Richard J O'Reilly, Farid Boulad
We sought to develop a myeloablative chemotherapeutic regimen to secure consistent engraftment of T cell-depleted (TCD) hematopoietic stem cell transplantations (HSCT) without the need for total body irradiation, thereby reducing toxicity while maintaining low rates of graft-versus-host disease (GVHD) and without increasing relapse. We investigated the myeloablative combination of busulfan (Bu) and melphalan (Mel), with the immunosuppressive agents fludarabine (Flu) and rabbit antithymocyte globulin (r-ATG) as cytoreduction before a TCD HSCT...
July 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28707754/non-sibling-hematopoietic-stem-cell-transplantation-using-myeloablative-conditioning-regimen-in-children-with-maroteaux-lamy-syndrome-a-brief-report
#17
Maryam Behfar, S Sharareh Dehghani, Tahereh Rostami, Ardeshir Ghavamzadeh, Amir Ali Hamidieh
Maroteaux-Lamy syndrome is a rare inherited lysosomal storage disorder with a progressive course. HSCT is a curable option for treatment in these patients. The following report describes our experience in HSCT for three patients with Maroteaux-Lamy syndrome using non-sibling donors. All of the patients received the same myeloablative regimen consisting of intravenous busulfan, cyclophosphamide, and rabbit antithymocyte globulin. Patients underwent HSCT from haploidentical other-related (n=1), full-matched other-related (n=1), and one-locus-mismatched unrelated donor...
August 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28691152/reduced-bucy-2-and-g-csf-primed-bone-marrow-associates-with-low-graft-versus-host-disease-and-transplant-related-mortality-in-allogeneic-hsct
#18
Eucario Leon Rodriguez, Monica M Rivera Franco, Sandra I Perez Alvarez
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the ideal treatment for several diseases. However, the morbidity and mortality associated with the procedure might limit its widespread use; therefore, we implemented reduced BUCY2 as conditioning method along with the use of G-CSF-primed bone marrow (G-BM) in order to reduce complications, including graft-versus-host-disease (GVHD), and to improve survival in these patients. An analysis of transplant characteristics, complications, and survival of patients undergoing an allo-HSCT using this conditioning regimen (busulfan 12 mg/kg and cyclophosphamide 80 mg/kg) plus G-BM was performed...
September 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28687222/tp53-and-idh2-somatic-mutations-are-associated-with-inferior-overall-survival-after-allogeneic-hematopoietic-cell-transplantation-for-myelodysplastic-syndrome
#19
Mohamed A Kharfan-Dabaja, Rami S Komrokji, Qing Zhang, Ambuj Kumar, Athanasios Tsalatsanis, Janelle Perkins, Taiga Nishihori, Teresa Field, Najla Al Ali, Asmita Mishra, David Sallman, Karma Z Salem, Ling Zhang, Lynn Moscinski, Hugo F Fernandez, Jeffrey Lancet, Alan List, Claudio Anasetti, Eric Padron
BACKGROUND: Next-generation sequencing has identified somatic mutations that are prognostic of cancer. PATIENTS AND METHODS: We evaluated the incidence and prognostic significance of somatic mutations in 89 myelodysplastic syndrome (MDS) patients who received an allogeneic hematopoietic cell transplantation. Next-generation sequencing was performed on paraffin embedded bone marrow, which was obtained at a median of 31 days before initiating the preparative regimen...
June 16, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28684379/pharmacokinetics-directed-intravenous-busulfan-combined-with-high-dose-melphalan-and-bortezomib-as-a-conditioning-regimen-for-patients-with-multiple-myeloma
#20
Stefan K Barta, Rishi Jain, Amithaba Mazumder, Jason Carter, Lawrence Almanzar, Roy Browne, Samira Shahnaz, Richard Elkind, David Kaminetzky, Ramakrishna Battini, Olga Derman, Noah Kornblum, Amit Verma, Ira Braunschweig
BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has a well-established role in the treatment of patients with multiple myeloma. Melphalan 200 mg/m(2) (Mel200) is the most commonly used preparative regimen. Several studies have provided evidence for potential synergism and safety when combining bortezomib (Btz) or busulfan (Bu) with melphalan (Mel). PATIENTS AND METHODS: We conducted a prospective phase II study to investigate the safety and efficacy of conditioning with pharmacokinetics (PK)-directed intravenous (IV) Bu with Btz and Mel...
June 17, 2017: Clinical Lymphoma, Myeloma & Leukemia
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