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https://www.readbyqxmd.com/read/28067870/a-single-center-s-experience-using-four-different-front-line-mobilization-strategies-in-lymphoma-patients-planned-to-undergo-autologous-hematopoietic-cell-transplantation
#1
B M Haverkos, Y Huang, P Elder, L O'Donnell, D Scholl, B Whittaker, S Vasu, S Penza, L A Andritsos, S M Devine, S M Jaglowski
In an otherwise eligible patient with relapsed lymphoma, inadequate mobilization of hematopoietic stem cells (HSCs) is a limiting factor to proceeding with an autologous hematopoietic cell transplantation (auto-HCT). Multiple strategies have been used to mobilize an adequate number of HSCs with no obvious front-line strategy. We report a single institutional experience mobilizing HSCs using four different approaches in lymphoma patients. We prospectively collected mobilization outcomes on patients planned to undergo auto-HCT at Ohio State University...
January 9, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28040478/cathepsin-k-cleavage-of-sdf-1%C3%AE-inhibits-its-chemotactic-activity-towards-glioblastoma-stem-like-cells
#2
Vashendriya V V Hira, Urška Verbovšek, Barbara Breznik, Matic Srdič, Marko Novinec, Hala Kakar, Jill Wormer, Britt Van der Swaan, Brigita Lenarčič, Luiz Juliano, Shwetal Mehta, Cornelis J F Van Noorden, Tamara T Lah
Glioblastoma (GBM) is the most aggressive primary brain tumor with poor patient survival that is at least partly caused by malignant and therapy-resistant glioma stem-like cells (GSLCs) that are protected in GSLC niches. Previously, we have shown that the chemo-attractant stromal-derived factor-1α (SDF-1α), its C-X-C receptor type 4 (CXCR4) and the cysteine protease cathepsin K (CatK) are localized in GSLC niches in glioblastoma. Here, we investigated whether SDF-1α is a niche factor that through its interactions with CXCR4 and/or its second receptor CXCR7 on GSLCs facilitates their homing to niches...
December 28, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28034992/plerixafor-and-g-csf-combination-mobilizes-hematopoietic-stem-and-progenitors-cells-with-a-distinct-transcriptional-profile-and-a-reduced-in-vivo-homing-capacity-compared-to-plerixafor-alone
#3
Maria Rosa Lidonnici, Annamaria Aprile, Marta Claudia Frittoli, Giacomo Mandelli, Ylenia Paleari, Antonello Spinelli, Bernhard Gentner, Matilde Zambelli, Cristina Parisi, Laura Bellio, Elena Cassinerio, Laura Zanaboni, Maria Domenica Cappellini, Fabio Ciceri, Sarah Marktel, Giuliana Ferrari
No abstract text is available yet for this article.
December 29, 2016: Haematologica
https://www.readbyqxmd.com/read/28034547/how-to-manage-poor-mobilizers-for-high-dose-chemotherapy-and-autologous-stem-cell-transplantation
#4
REVIEW
Pinar Ataca Atilla, Sule Mine Bakanay Ozturk, Taner Demirer
Today, peripheral blood stem cells are the preferred source of stem cells over bone marrow. Therefore, mobilization plays a crutial role in successful autologous stem cell transplantation. Poor mobilization is generally defined as failure to achieve the target level of at least 2×10(6) CD34(+) cells/kg body weight. There are several strategies to overcome poor mobilization: 1) Larger volume Leukapheresis (LVL) 2) Re-mobilization 3) Plerixafor 4) CM+Plerixafor (P)+G-CSF and 5) Bone Marrow Harvest. In this review, the definitions of successful and poor mobilization are discussed...
December 26, 2016: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/27987208/poor-stem-cell-harvest-may-not-always-be-related-to-poor-mobilization-lessons-gained-from-a-mobilization-study-in-patients-with-%C3%AE-thalassemia-major
#5
Varnavas C Constantinou, Asimina Bouinta, Garyfalia Karponi, Fani Zervou, Penelope-Georgia Papayanni, George Stamatoyannopoulos, Achilles Anagnostopoulos, Evangelia Yannaki
BACKGROUND: Hematopoietic stem cell mobilization and leukapheresis in adult patients with β-thalassemia have recently been optimized in the context of clinical trials for obtaining hematopoietic stem cells for thalassemia gene therapy. In some patients, however, the yield of cluster of differentiation 34-positive (CD34+) cells was poor despite successful mobilization, and a modification of apheresis settings was mandatory for harvest rescue. STUDY DESIGN AND METHODS: Data were analyzed from 20 adult patients with β-thalassemia who were enrolled in a clinical trial of optimizing mobilization strategies for stem cell gene therapy...
December 17, 2016: Transfusion
https://www.readbyqxmd.com/read/27982313/hodgkin-s-lymphoma-evaluation-of-patients-submitted-to-autologous-transplantation-of-hematopoietic-cells-in-the-hematology-service-of-the-hospital-walter-cant%C3%A3-dio-fortaleza-brazil
#6
Fernando Barroso Duarte, Mabel Gomes de Brito Fernandes, Jacques Kaufmann, Karine Sampaio Nunes Barroso, João Paulo de Vasconcelos Leitão, Beatriz Stela Gomes de Souza Pitombeira Araujo, Clara Maria Bastos Eloy da Costa, Acy Teles Quixadá-Medica, Jacqueline de Souza Holanda, Samuel Vasconcelos Landim, Maria Helena Pitombeira
The Autologous HSCT is an important alternative for refractory or recurrent HL patients in terms of survival and improved quality of life. This study analyzes the results of autologous BMT performed in HL patients in the Transplant Unit of the HUWC/ HEMOCE (Fortaleza - CE, Brazil). Fifty-two transplanted patients were studied from January 2009 to October 2015, among them, 30 men and 22 women, mean age of 28.2 years. All of them received GCS-F during the mobilization, in some cases associated with Vinorelbine or Plerixafor, with CD34 collection averaging 4...
October 2016: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/27965305/bone-marrow-cell-trafficking-analyzed-by-89zr-oxine-positron-emission-tomography-in-a-murine-transplantation-model
#7
Kingsley O Asiedu, Sho Koyasu, Lawrence P Szajek, Peter L Choyke, Noriko Sato
PURPOSE: The success of hematopoietic stem cell transplantation (HSCT) depends on donor cell homing to the bone marrow (BM). However, there is no reliable method of noninvasively monitoring the kinetics and distribution of transferred cells. Using Zirconium-89 ((89)Zr)-oxine cell labeling combined with positron emission tomography (PET) imaging, we sought to visualize and quantify donor cell homing in a mouse BM transplantation model. EXPERIMENTAL DESIGN: The effect of (89)Zr-oxine labeling on BM cell viability and differentiation was evaluated in vitro...
December 13, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27926729/intracellular-allosteric-antagonism-of-the-ccr9-receptor
#8
Christine Oswald, Mathieu Rappas, James Kean, Andrew S Doré, James C Errey, Kirstie Bennett, Francesca Deflorian, John A Christopher, Ali Jazayeri, Jonathan S Mason, Miles Congreve, Robert M Cooke, Fiona H Marshall
Chemokines and their G-protein-coupled receptors play a diverse role in immune defence by controlling the migration, activation and survival of immune cells. They are also involved in viral entry, tumour growth and metastasis and hence are important drug targets in a wide range of diseases. Despite very significant efforts by the pharmaceutical industry to develop drugs, with over 50 small-molecule drugs directed at the family entering clinical development, only two compounds have reached the market: maraviroc (CCR5) for HIV infection and plerixafor (CXCR4) for stem-cell mobilization...
December 15, 2016: Nature
https://www.readbyqxmd.com/read/27905003/new-agents-in-hsc-mobilization
#9
REVIEW
Mélanie J Domingues, Susan K Nilsson, Benjamin Cao
Mobilized peripheral blood (PB) is the most common source of hematopoietic stem cells (HSC) for autologous transplantation. Granulocyte colony stimulating factor (G-CSF) is the most commonly used mobilization agent, yet despite its widespread use, a considerable number of patients still fail to mobilize. Recently, a greater understanding of the interactions that regulate HSC homeostasis in the bone marrow (BM) microenvironment has enabled the development of new molecules that mobilize HSC through specific inhibition, modulation or perturbation of these interactions...
November 30, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27896627/n-11-c-methyl-amd3465-pet-as-a-tool-for-in-vivo-measurement-of-chemokine-receptor-4-cxcr4-occupancy-by-therapeutic-drugs
#10
S V Hartimath, M A Khayum, A van Waarde, R A J O Dierckx, E F J de Vries
PURPOSE: Chemokine receptor 4 (CXCR4) is overexpressed in many cancers and a potential drug target. We have recently developed the tracer N-[(11)C]methyl-AMD3465 for imaging of CXCR4 expression by positron emission tomography (PET). We investigated the pharmacokinetics of N-[(11)C]methyl-AMD3465 in rats bearing a C6 tumor and assessed whether the CXCR4 occupancy by the drug Plerixafor® can be measured with this PET tracer. PROCEDURE: A subcutaneous C6 tumor was grown in Wistar rats...
November 28, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/27859332/patients-outcome-after-rescue-plerixafor-administration-for-autologous-stem-cell-mobilization-a-single-center-retrospective-analysis
#11
Silvia Spoerl, Robert Peter, Dagmar Wäscher, Katharina Götze, Mareike Verbeek, Christian Peschel, Angela M Krackhardt
BACKGROUND: Plerixafor is predominantly used for patients mobilizing inadequate stem cell numbers for autologous transplantation after stimulation with granulocyte-colony-stimulating factor (G-CSF). STUDY DESIGN AND METHODS: We here report on 300 patients undergoing stem cell mobilization with G-CSF, among them 36 poor mobilizers (CD34+ cell counts < 50 × 10(6) /L blood) receiving G-CSF alone and 49 receiving G-CSF in combination with plerixafor for rescue intervention...
November 18, 2016: Transfusion
https://www.readbyqxmd.com/read/27846612/effect-of-high-dose-plerixafor-on-cd34-cells-mobilization-in-healthy-stem-cell-donors-results-of-a-randomized-crossover-trial
#12
Jeremy Pantin, Enkhtsetseg Purev, Xin Tian, Lisa Cook, Theresa Donohue-Jerussi, Elena Cho, Robert Reger, Matthew Hsieh, Hanh Khuu, Gary Calandra, Nancy L Geller, Richard W Childs
Hematopoietic stem cells can be mobilized from healthy donors using single-agent plerixafor without G-CSF, and following allogeneic transplantation, can result in sustained donor derived hematopoiesis. However, when a single dose of plerixafor is administered at a conventional 240 mg/kg dose, approximately one third of donors will fail to mobilize the minimally acceptable dose of CD34+ cells needed for allogeneic transplantation. We conducted an open-label, randomized trial to assess the safety and activity of high-dose (480 mg/kg) plerixafor in CD34+ cell mobilization in healthy donors...
October 20, 2016: Haematologica
https://www.readbyqxmd.com/read/27826715/extracellular-molecules-in-hematopoietic-stem-cell-mobilisation
#13
REVIEW
Linda Bendall
Hematopoietic stem cells are a remarkable resource currently used for the life saving treatment, hematopoietic stem cell transplantation. Today, hematopoietic stem cells are primarily obtained from mobilized peripheral blood following treatment of the donor with the cytokine G-CSF, and in some settings, chemotherapy and/or the CXCR4 antagonist plerixafor. The collection of hematopoietic stem cells is contingent on adequate and timely mobilization of these cells into the peripheral blood. The use of healthy donors, particularly when unrelated to the patient, requires mobilization strategies be safe for the donor...
November 8, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27809841/pharmacological-targeting-of-cxcl12-cxcr4-signaling-in-prostate-cancer-bone-metastasis
#14
M Katie Conley-LaComb, Louie Semaan, Rajareddy Singareddy, Yanfeng Li, Elisabeth I Heath, Seongho Kim, Michael L Cher, Sreenivasa R Chinni
BACKGROUND: The CXCL12/CXCR4 axis transactivates HER2 and promotes intraosseous tumor growth. To further explore the transactivation of HER2 by CXCL12, we investigated the role of small GTP protein Gαi2 in Src and HER2 phosphorylation in lipid raft membrane microdomains and the significance of CXCR4 in prostate cancer bone tumor growth. METHODS: We used a variety of methods such as lipid raft isolation, invasion assays, an in vivo model of intratibial tumor growth, bone histomorphometry, and immunohistochemistry to determine the role of CXCR4 signaling in lipid raft membrane microdomains and effects of targeting of CXCR4 for bone tumor growth...
November 3, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27749622/plerixafor-mobilization-of-peripheral-blood-hematopoietic-progenitors-to-support-further-high-dose-chemotherapy-cycles-in-a-patient-with-germ-cell-tumor-relapsing-after-previous-tandem-high-dose-chemotherapy-and-hematopoietic-cell-transplantation-report-of
#15
Constantinos Miltiadous, Georgios K Dimitriadis, Pavlos Roditis, Christos Kosmas
Salvage high-dose chemotherapy (HDC) and autologous hematopoietic stem cell (HSC) transplantation represents a curative treatment option for patients with relapsed/refractory germ-cell tumors (GCTs). However, an appreciable proportion of these fail to mobilize adequate numbers of hematopoietic progenitors; thus, plerixafor is applied for that purpose. Limited data exist on remobilization of HSCs after previous autografting. Here, we report a unique case that had undergone successful previous tandem HDC for relapsed GCT, and 1 year later required remobilization of HSCs to support two further cycles of HDC after subsequent multiple relapses and refractoriness requiring various salvage regimens...
February 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27735212/upfront-use-of-plerixafor-and-granulocyte-colony-stimulating-factor-gcsf-for-stem-cell-mobilization-in-patients-with-multiple-myeloma-efficacy-and-analysis-of-risk-factors-associated-with-poor-stem-cell-collection-efficiency
#16
Adebayo Ogunniyi, Mabel Rodriguez, Sean Devlin, Nelly Adel, Heather Landau, David J Chung, Nikoletta Lendvai, Alexander Lesokhin, Guenther Koehne, Sham Mailankody, Neha Korde, Lilian Reich, Ola Landgren, Sergio Giralt, Hani Hassoun
Plerixafor (P), an agent that selectively and reversibly binds to the chemokine receptor CXCR4, has been approved in combination with G-CSF (P + G-CSF) for stem cell (SC) mobilization in patients with multiple myeloma (MM). The goal of this study was to determine the SC collection success rate of P + G-CSF using a clinically relevant outcome defined as the ability to collect at least 5 × 10(6) CD34(+) cells/kg to allow safely two transplants, and identify risk factors impacting SC mobilization...
October 13, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27731496/how-do-we-mobilize-and-collect-autologous-peripheral-blood-stem-cells
#17
Shan Yuan, Shirong Wang
Autologous stem cell transplantation (ASCT) with mobilized peripheral blood stem cells (PBSCs) has become a widely applied therapeutic approach for many hematologic and nonhematologic diseases. Adequate PBSC mobilization is critical to the success of ASCT. However, many factors can contribute to poor mobilization. Plerixafor is an effective yet costly adjunct agent that has been increasingly used to improve mobilization in a variety of diagnoses and clinical settings. However, to achieve both optimal cell collection yields and cost-effectiveness, the role of plerixafor in PBSC mobilization needs to be well defined in terms of triggers for initiating its use and criteria for monitoring response...
October 12, 2016: Transfusion
https://www.readbyqxmd.com/read/27697997/plerixafor-improves-primary-tumor-response-and-reduces-metastases-in-cervical-cancer-treated-with-radio-chemotherapy
#18
Naz Chaudary, Melania Pintilie, Salomeh Jelveh, Patricia Lindsay, Richard P Hill, Michael Milosevic
PURPOSE: There is an important need to improve the effectiveness of radio-chemotherapy (RTCT) for cervical cancer. The CXCL12/CXCR4 pathway can influence RT response by recruiting normal myeloid cells to the tumor microenvironment that in turn can exert radioprotective effects, and may promote metastases. The objective of this study was to explore the efficacy and toxicity of combining RTCT with CXCL12/CXCR4 inhibition in cervical cancer. EXPERIMENTAL DESIGN: CXCR4 expression was measured in 115 patients with cervical cancer...
October 3, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27634446/stem-cell-mobilizers-novel-therapeutics-for-acute-kidney-injury
#19
Yue Xu, Qiang Zhang, Song Zeng, Zijiang Zhang, Xiaopeng Hu
In the past decade, rapid developments in stem cell studies have occurred. Researchers have confirmed the plasticity of bone marrow stem cells and the repair and regeneration effects of bone marrow hematopoietic stem cells on solid organs. These findings have suggested the possibility of using bone marrow to repair and regenerate injured organs. Recent studies on the effects of granulocyte colony-stimulating factor (G-CSF) and Plerixafor (AMD3100) on mouse acute kidney injury models have confirmed that the use of bone marrow may be an effective therapeutic measure...
September 9, 2016: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/27617863/abc-transporters-and-nr4a1-identify-a-quiescent-subset-of-tissue-resident-memory-t-cells
#20
Chandra Sekhar Boddupalli, Shiny Nair, Simon M Gray, Heba N Nowyhed, Rakesh Verma, Joanna A Gibson, Clara Abraham, Deepak Narayan, Juan Vasquez, Catherine C Hedrick, Richard A Flavell, Kavita M Dhodapkar, Susan M Kaech, Madhav V Dhodapkar
Immune surveillance in tissues is mediated by a long-lived subset of tissue-resident memory T cells (Trm cells). A putative subset of tissue-resident long-lived stem cells is characterized by the ability to efflux Hoechst dyes and is referred to as side population (SP) cells. Here, we have characterized a subset of SP T cells (Tsp cells) that exhibit a quiescent (G0) phenotype in humans and mice. Human Trm cells in the gut and BM were enriched in Tsp cells that were predominantly in the G0 stage of the cell cycle...
October 3, 2016: Journal of Clinical Investigation
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