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Fertility challenges for women with sickle cell disease.
Ghafuri DL, Stimpson SJ, Day ME, James A, DeBaun MR, Sharma D
(2017) Expert Rev Hematol 10: 891-901
MeSH Terms: Anemia, Sickle Cell, Blood Transfusion, Chronic Pain, Female, Fertility, Fertility Preservation, Genetic Therapy, Hematopoietic Stem Cell Transplantation, Humans, Hydroxyurea, Infertility, Pregnancy, Primary Ovarian Insufficiency, Reproductive Health, Transplantation Conditioning
Show Abstract · Added November 9, 2018
INTRODUCTION - Sickle cell disease (SCD) represents one of the most common monogenic blood disorders worldwide, with an incidence of over 300,000 newborns affected per year. Reproductive challenges for men and women with SCD have been previously reviewed; however, evidence-based strategies to prevent and manage infertility and increase fecundity are lacking in women with SCD, which is one of the most important factors for quality of life. Areas covered: This review article summarizes the known risk factors for infertility, low fecundity, and premature menopause related to SCD. Expert commentary: Women with SCD have unique risk factors that may impact their ability to conceive, including chronic inflammation, oxidative stress, transfusion-related hemochromatosis, and ovarian sickling, causing ischemia and reperfusion injury to the ovary. Contraception is strongly recommended while on hydroxyurea therapy during reproductive years and discontinuing hydroxyurea for family planning and during pregnancy based on teratogenicity in animal studies. Hematopoietic stem cell transplantation (HSCT), the only curative therapy, sometimes involves conditioning regimens containing alkylating agents and total body irradiation that contribute to infertility and premature ovarian failure. Prior to HSCT or gene therapy, we strongly recommend referral to a reproductive endocrinologist to discuss fertility preservation and surrogacy options for all women with SCD.
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MeSH Terms
Reactive Oxygen Species Shielding Hydrogel for the Delivery of Adherent and Nonadherent Therapeutic Cell Types.
Dollinger BR, Gupta MK, Martin JR, Duvall CL
(2017) Tissue Eng Part A 23: 1120-1131
MeSH Terms: Animals, Cell Adhesion, Cell Count, Cell Death, Cytoprotection, Humans, Hydrogels, Hydrogen Peroxide, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Mice, Polymers, Reactive Oxygen Species, Rheology
Show Abstract · Added March 14, 2018
Cell therapies suffer from poor survival post-transplant due to placement into hostile implant sites characterized by host immune response and innate production of high levels of reactive oxygen species (ROS). We hypothesized that cellular encapsulation within an injectable, antioxidant hydrogel would improve viability of cells exposed to high oxidative stress. To test this hypothesis, we applied a dual thermo- and ROS-responsive hydrogel comprising the ABC triblock polymer poly[(propylene sulfide)-block-(N,N-dimethyl acrylamide)-block-(N-isopropylacrylamide)] (PPS-b-PDMA-b-PNIPAAM, PDN). The PPS chemistry reacts irreversibly with ROS such as hydrogen peroxide (HO), imparting inherent antioxidant properties to the system. Here, PDN hydrogels were successfully integrated with type 1 collagen to form ROS-protective, composite hydrogels amenable to spreading and growth of adherent cell types such as mesenchymal stem cells (MSCs). It was also shown that, using a control hydrogel substituting nonreactive polycaprolactone in place of PPS, the ROS-reactive PPS chemistry is directly responsible for PDN hydrogel cytoprotection of both MSCs and insulin-producing β-cell pseudo-islets against HO toxicity. In sum, these results establish the potential of cytoprotective, thermogelling PDN biomaterials for injectable delivery of cell therapies.
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14 MeSH Terms
Cardiac repair in a mouse model of acute myocardial infarction with trophoblast stem cells.
Li G, Chen J, Zhang X, He G, Tan W, Wu H, Li R, Chen Y, Gu R, Xie J, Xu B
(2017) Sci Rep 7: 44376
MeSH Terms: Animals, Cardiac Surgical Procedures, Cell Differentiation, Disease Models, Animal, Humans, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Mice, Myocardial Infarction, Myocardium, Myocytes, Cardiac, Trophoblasts
Show Abstract · Added September 11, 2017
Various stem cells have been explored for the purpose of cardiac repair. However, any individual stem cell population has not been considered as the ideal source. Recently, trophoblast stem cells (TSCs), a newly described stem cell type, have demonstrated extensive plasticity. The present study evaluated the therapeutic effect of TSCs transplantation for heart regeneration in a mouse model of myocardial infarction (MI) and made a direct comparison with the most commonly used mesenchymal stem cells (MSCs). Transplantation of TSCs and MSCs led to a remarkably improved cardiac function in contrast with the PBS control, but only the TSCs exhibited the potential of differentiation into cardiomyocytes in vivo. In addition, a significantly high proliferation level of both transplanted stem cells and resident cardiomyocytes was observed in the TSCs group. These findings primary revealed the therapeutic potential of TSCs in transplantation therapy for MI.
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12 MeSH Terms
Current Management of Refractory Germ Cell Tumors and Future Directions.
Allen JC, Kirschner A, Scarpato KR, Morgans AK
(2017) Curr Oncol Rep 19: 8
MeSH Terms: Antineoplastic Combined Chemotherapy Protocols, Cisplatin, Disease Management, Hematopoietic Stem Cell Transplantation, Humans, Male, Neoplasms, Germ Cell and Embryonal
Show Abstract · Added April 2, 2019
PURPOSE OF REVIEW - We review current management strategies for patients with relapsed and refractory germ cell tumors (GCTs), defined as relapsed or persistent disease following at least one line of cisplatin-based chemotherapy. Additionally, we discuss future directions in the management of these patients.
RECENT FINDINGS - Recent studies involving targeted therapies have been disappointing. Nevertheless, studies of the management of refractory germ cell cancer are ongoing, with a focus on optimal utilization of high-dose chemotherapy and autologous stem cell transplant, as well as the role of immune checkpoint inhibitors in refractory germ cell tumors. Studies aiming to identify those patients who may benefit from more intensive treatment up front to prevent the development of refractory disease are also in progress. Testicular germ cell tumors are among the most curable of all solid tumor malignancies, with cure being possible even in the refractory, metastatic setting. Treatment of refractory disease remains a challenging clinical scenario, but potentially practice changing studies are ongoing.
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Hematopoietic Stem Cell Mobilization Is Necessary but Not Sufficient for Tolerance in Islet Transplantation.
Stocks BT, Thomas AB, Elizer SK, Zhu Y, Marshall AF, Wilson CS, Moore DJ
(2017) Diabetes 66: 127-133
MeSH Terms: Allografts, Animals, Female, Flow Cytometry, Hematopoietic Stem Cell Mobilization, Hematopoietic Stem Cell Transplantation, Islets of Langerhans Transplantation, Leukocyte Common Antigens, Mice, Mice, Inbred NOD, Osteoblasts
Show Abstract · Added November 1, 2016
Overcoming the immune response to establish durable immune tolerance in type 1 diabetes remains a substantial challenge. The ongoing effector immune response involves numerous immune cell types but is ultimately orchestrated and sustained by the hematopoietic stem cell (HSC) niche. We therefore hypothesized that tolerance induction also requires these pluripotent precursors. In this study, we determined that the tolerance-inducing agent anti-CD45RB induces HSC mobilization in nonautoimmune B6 mice but not in diabetes-prone NOD mice. Ablation of HSCs impaired tolerance to allogeneic islet transplants in B6 recipients. Mobilization of HSCs resulted in part from decreasing osteoblast expression of HSC retention factors. Furthermore, HSC mobilization required a functioning sympathetic nervous system; sympathectomy prevented HSC mobilization and completely abrogated tolerance induction. NOD HSCs were held in their niche by excess expression of CXCR4, which, when blocked, led to HSC mobilization and prolonged islet allograft survival. Overall, these findings indicate that the HSC compartment plays an underrecognized role in the establishment and maintenance of immune tolerance, and this role is disrupted in diabetes-prone NOD mice. Understanding the stem cell response to immune therapies in ongoing human clinical studies may help identify and maximize the effect of immune interventions for type 1 diabetes.
© 2017 by the American Diabetes Association.
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11 MeSH Terms
Reduced-Intensity Conditioning with Fludarabine, Cyclophosphamide, and Rituximab Is Associated with Improved Outcomes Compared with Fludarabine and Busulfan after Allogeneic Stem Cell Transplantation for B Cell Malignancies.
Kennedy VE, Savani BN, Greer JP, Kassim AA, Engelhardt BG, Goodman SA, Sengsayadeth S, Chinratanalab W, Jagasia M
(2016) Biol Blood Marrow Transplant 22: 1801-1807
MeSH Terms: Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Busulfan, Calcineurin Inhibitors, Cyclophosphamide, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, B-Cell, Methotrexate, Middle Aged, Prognosis, Retrospective Studies, Rituximab, Survival Analysis, Transplantation Conditioning, Transplantation, Homologous, Vidarabine
Show Abstract · Added July 28, 2016
Reduced-intensity conditioning (RIC) has been used increasingly for allogeneic hematopoietic cell transplantation to minimize transplant-related mortality while maintaining the graft-versus-tumor effect. In B cell lymphoid malignancies, reduced-intensity regimens containing rituximab, an antiCD20 antibody, have been associated with favorable survival; however, the long-term outcomes of rituximab-containing versus nonrituximab-containing regimens for allogeneic hematopoietic cell transplantation in B cell lymphoid malignancies remain to be determined. We retrospectively analyzed 94 patients who received an allogeneic transplant for a B cell lymphoid malignancy. Of these, 33 received RIC with fludarabine, cyclophosphamide, and rituximab (FCR) and graft-versus-host disease (GVHD) prophylaxis with a calcineurin inhibitor and mini-methotrexate, and 61 received RIC with fludarabine and busulfan (FluBu) and GVHD prophylaxis with a calcineurin inhibitor and mycophenolate mofetil. The 2-year overall survival was superior in patients who received FCR versus FluBu (72.7% versus 54.1%, P = .031), and in multivariable analysis adjusted for Disease Risk Index and donor type, only the conditioning regimen (FluBu versus FCR: HR, 2.06; 95% CI, 1.04 to 4.08; P = .037) and Disease Risk Index (low versus intermediate/high: HR, .38; 95% CI, .17 to .86; P = .02) were independent predictors of overall survival. The 2-year cumulative incidence of chronic GVHD was lower in patients who received FCR versus FluBu (24.2% versus 51.7%, P = .01). There was no difference in rate of relapse/progression or acute GVHD. Our results demonstrate that the use of RIC with FCR and GVHD prophylaxis with a calcineurin inhibitor and mini-methotrexate is associated with decreased chronic GVHD and improved overall survival.
Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
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19 MeSH Terms
How do I manage hyperglycemia/post-transplant diabetes mellitus after allogeneic HSCT.
Fuji S, Rovó A, Ohashi K, Griffith M, Einsele H, Kapp M, Mohty M, Majhail NS, Engelhardt BG, Tichelli A, Savani BN
(2016) Bone Marrow Transplant 51: 1041-9
MeSH Terms: Diabetes Mellitus, Disease Management, Forecasting, Hematopoietic Stem Cell Transplantation, Humans, Hyperglycemia, Transplantation, Homologous
Show Abstract · Added July 28, 2016
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients frequently develop glucose intolerance and post-transplant diabetes mellitus (PTDM). The clinical importance of PTDM and its detrimental impact on HSCT outcomes are under-recognized. After allo-HSCT, various mechanisms can contribute to the development of PTDM. Here we review information about hyperglycemia and PTDM after allo-HSCT as well as PTDM after solid organ transplantation and describe ways to manage hyperglycemia/PTDM after allogeneic HSCT. Taking into consideration a lack of well-established evidence in the field of allo-HSCT, more studies should be conducted in the future, which will require closer multidisciplinary collaboration between hematologists, endocrinologists and nutritionists.
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7 MeSH Terms
Early Th1 immunity promotes immune tolerance and may impair graft-versus-leukemia effect after allogeneic hematopoietic cell transplantation.
Engelhardt BG, Paczesny S, Jung DK, Daguindau E, Jagasia M, Savani BN, Chinratanalab W, Cornell RF, Goodman S, Greer JP, Kassim AA, Sengsayadeth S, Yoder SM, Rock MT, Crowe JE
(2016) Haematologica 101: e204-8
MeSH Terms: Adult, Aged, Allografts, Female, Graft vs Leukemia Effect, Hematopoietic Stem Cell Transplantation, Humans, Immune Tolerance, Immunity, Cellular, Leukemia, Male, Middle Aged, Th1 Cells
Added February 4, 2016
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13 MeSH Terms
Venous thromboembolism in hematopoietic stem cell transplant recipients.
Chaturvedi S, Neff A, Nagler A, Savani U, Mohty M, Savani BN
(2016) Bone Marrow Transplant 51: 473-8
MeSH Terms: Allografts, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Lenalidomide, Multiple Myeloma, Postoperative Complications, Thalidomide, Venous Thromboembolism
Show Abstract · Added April 25, 2016
Venous thromboembolism (VTE) is an increasingly recognized problem in the post-hematopoietic stem cell transplantation (HSCT) setting, with a lack of high-quality evidence-based data to recommend best practices. Few patients with hematologic malignancies and even fewer post-HSCT patients were included in randomized trials of VTE prophylaxis and treatment. Prior VTE, GVHD, infections and indwelling venous catheters are risk factors for thrombosis. The increasing use of post-transplant maintenance therapy with lenalidomide in patients with multiple myeloma adds to this risk after autologous HSCT. These patients are also at high risk of bleeding complications because of prolonged thrombocytopenia and managing the competing risks of bleeding and thrombosis can be challenging. This review aims to provide a practical, clinician-focused approach to the prevention and treatment of VTE in the post-HSCT setting.
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9 MeSH Terms
Cardiovascular disease following hematopoietic stem cell transplantation: Pathogenesis, detection, and the cardioprotective role of aerobic training.
Scott JM, Armenian S, Giralt S, Moslehi J, Wang T, Jones LW
(2016) Crit Rev Oncol Hematol 98: 222-34
MeSH Terms: Cardiovascular Diseases, Coronary Artery Disease, Exercise, Heart Failure, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Life Style
Show Abstract · Added March 6, 2016
Advances in hematopoietic cell transplantation (HCT) techniques and supportive care strategies have led to dramatic improvements in relapse mortality in patients with high-risk hematological malignancies. These improvements, however, conversely increase the risk of late-occurring non-cancer competing causes, mostly cardiovascular disease (CVD). HCT recipients have a significantly increased risk of CVD-specific mortality, including elevated incidence of coronary artery disease (CAD), cerebrovascular disease, and heart failure (HF) compared to age-matched counterparts. Accordingly, there is an urgent need to identify techniques for the detection of early CVD in HCT patients to inform early prevention strategies. Aerobic training (AT) is established as the cornerstone of primary and secondary disease prevention in multiple clinical settings, and may confer similar benefits in HCT patients at high-risk of CVD. The potential benefits of AT either before, immediately after, or in the months/years following HCT have received limited attention. Here, we discuss the risk and extent of CVD in adult HCT patients, highlight novel tools for early detection of CVD, and review existing evidence in oncology and non-oncology populations supporting the efficacy of AT to attenuate HCT-induced CVD. This knowledge can be utilized to optimize treatment, while minimizing CVD risk in individuals with hematological malignancies undergoing HCT.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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8 MeSH Terms