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Chong Chyn Chua, Hui Yin Lim, Khai Li Chai, Jeremy Ong, Shirlene Sim, Colin Wood, Michael Dickinson, Philip Campbell, Jennifer Hempton, Hayley King, Claire Dowsing, Krystal Bergin, Sharon Muir, Simon Gibbs, Andrew Grigg
Bortezomib-based induction is often used in transplant-eligible patients with myeloma. The optimal peripheral blood stem cell (PBSC) mobilisation strategy in this context is unclear. We reviewed the efficacy of G-CSF alone (G-alone) vs. G-CSF and cyclophosphamide (G-cyclo: standard dose: 1.5-2 g/m2 ; high dose: 3-4 g/m2 ) PBSC mobilisation strategies in 288 patients who only received bortezomib, cyclophosphamide and dexamethasone (VCD) induction prior to autograft across six apheresis centres from November 2012 to June 2017...
March 9, 2018: Bone Marrow Transplantation
Binghao Li, Yang Zeng, Patrick M Reeves, Chongzhao Ran, Qiuyan Liu, Xiying Qu, Yingying Liang, Zhao Liu, Jianping Yuan, Pierre R Leblanc, Zhaoming Ye, Ann E Sluder, Jeffrey A Gelfand, Timothy A Brauns, Huabiao Chen, Mark C Poznansky
AMD3100 (plerixafor), a CXCR4 antagonist, has been demonstrated to suppress tumor growth and modulate intratumoral T-cell trafficking. However, the effect of AMD3100 on immunomodulation remains elusive. Here, we explored immunomodulation and antitumor efficacy of AMD3100 in combination with a previously developed mesothelin-targeted, immune-activating fusion protein, VIC-008, in two syngeneic, orthotopic models of malignant mesothelioma (MM) in immunocompetent mice. We showed that combination therapy significantly suppressed tumor growth and prolonged animal survival in two mouse models...
March 6, 2018: Cancer Immunology Research
David Martínez-Cuadrón, Blanca Boluda, Pilar Martínez, Juan Bergua, Rebeca Rodríguez-Veiga, Jordi Esteve, Susana Vives, Josefina Serrano, Belen Vidriales, Olga Salamero, Lourdes Cordón, Amparo Sempere, Ana Jiménez-Ubieto, Julio Prieto-Delgado, Marina Díaz-Beyá, Ana Garrido, Celina Benavente, José Antonio Pérez-Simón, Federico Moscardó, Miguel A Sanz, Pau Montesinos
The name of Pau Montesinos was inadvertently presented as Pau Montesinos Fernández in the original article.The original version of this article was revised: The name of Pau Montesinos was inadvertently presented as Pau Montesinos Fernández.
February 23, 2018: Annals of Hematology
Chantal Lagresle-Peyrou, François Lefrère, Elisa Magrin, Jean-Antoine Ribeil, Oriana Romano, Leslie Weber, Alessandra Magnani, Hanem Sadek, Clémence Plantier, Aurélie Gabrion, Brigitte Ternaux, Tristan Félix, Chloé Couzin, Aurélie Stanislas, Jean-Marc Tréluyer, Lionel Lamhaut, Laure Joseph, Marianne Delville, Annarita Miccio, Isabelle André-Schmutz, Marina Cavazzana
Sickle cell disease is characterized by chronic anaemia and vaso-occlusive crises, which eventually lead to multi-organ damage and premature death. Haematopoietic stem cell transplantation is the only curative treatment but it is limited by toxicity and poor availability of HLA-compatible donors. A gene therapy approach based on the autologous transplantation of lentiviral-corrected haematopoietic stem and progenitor cells was shown to be efficacious in one patient. However, alterations of the bone marrow environment and the red blood cells' properties hamper the harvesting and immunoselection of patient stem cells from bone marrow...
February 22, 2018: Haematologica
Christian Berg, Viktorija Daugvilaite, Anne Steen, Astrid Sissel Jørgensen, Jon Våbenø, Mette Marie Rosenkilde
CXC chemokine receptor 4 (CXCR4) is involved in multiple physiological and pathological processes, notably as a co-receptor for human immunodeficiency virus (HIV) cell entry. Its broad expression pattern and vital biological importance make CXCR4 a troublesome drug target, as disruption of the interaction with its endogenous ligand, CXC chemokine ligand 12 (CXCL12), has severe consequences. In fact, only one CXCR4 drug, the bicyclam antagonist and HIV entry inhibitor AMD3100 (Plerixafor/Mozobil), has been approved for clinical use, however only for stem cell mobilization-a consequence of CXCR4 antagonism...
February 20, 2018: ACS Chemical Biology
Farid Boulad, Tsiporah Shore, Koen van Besien, Caterina Minniti, Mihaela Barbu-Stevanovic, Sylvie Wiener Fedus, Fabiana Perna, June Greenberg, Danielle Guarneri, Vijay Nandi, Audrey Mauguen, Karina Yazdanbakhsh, Michel Sadelain, Patricia A Shi
Gene therapy for sickle cell disease is limited by the yield of hematopoietic progenitor cell harvest for transduction or gene editing. We therefore performed a Phase I dose-escalation study of the hematopoietic progenitor cell mobilizing agent plerixafor to evaluate the efficacy and safety of standard dosing on peripheral blood CD34+ cell mobilization. Of 15 patients enrolled to date, only one was chronically transfused and 10 were on hydroxyurea. Of 8 patients achieving a CD34+ cell concentration >30 cells/μl, 6 were on hydroxyurea...
February 1, 2018: Haematologica
Magali Lecavalier-Barsoum, Naz Chaudary, Kathy Han, Marianne Koritzinsky, Richard Hill, Michael Milosevic
Cervical cancer is the fourth most commonly diagnosed cancer and the fourth leading cause of cancer death in women worldwide. Approximately half of cervical cancer patients present with locally advanced disease, for which surgery is not an option. These cases are nonetheless potentially curable with radiotherapy and cisplatin chemotherapy. Unfortunately, some tumours are resistant to treatment, and lymph node and distant recurrences are major problems in patients with advanced disease at diagnosis. New targeted treatments that can overcome treatment resistance and reduce metastases are urgently needed...
February 8, 2018: International Journal of Cancer. Journal International du Cancer
Ivana N Micallef, Patrick J Stiff, Auayporn P Nademanee, Richard T Maziarz, Mitchell E Horwitz, Edward A Stadtmauer, Jonathan L Kaufman, John M McCarty, Rita Vargo, Peter D Cheverton, Martin Struijs, Brian Bolwell, John F DiPersio
The purpose of this report is to analyze long-term clinical outcomes of patients exposed to plerixafor plus granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization. This was a study of patients with non-Hodgkin's lymphoma (NHL, n = 167) and multiple myeloma (MM, n = 163) who were enrolled in the long-term follow-up of 2 pivotal phase III studies (NCT00741325 and NCT00741780) of 240 µg/kg plerixafor plus 10 µg/kg G-CSF, or placebo plus 10 µg/kg G-CSF to mobilize and collect CD34+ cells for auto-HSCT...
February 1, 2018: Biology of Blood and Marrow Transplantation
David Martínez-Cuadrón, Blanca Boluda, Pilar Martínez, Juan Bergua, Rebeca Rodríguez-Veiga, Jordi Esteve, Susana Vives, Josefina Serrano, Belen Vidriales, Olga Salamero, Lourdes Cordón, Amparo Sempere, Ana Jiménez-Ubieto, Julio Prieto-Delgado, Marina Díaz-Beyá, Ana Garrido, Celina Benavente, José Antonio Pérez-Simón, Federico Moscardó, Miguel A Sanz, Pau Montesinos Fernández
Clinical outcomes of patients with acute myeloid leukemia (AML) showing the first primary refractory or early-relapsed disease remain very poor. The Programa Español de Tratamientos en Hematología (PETHEMA) group designed a phase I-II trial using FLAG-Ida (fludarabine, idarubicin, cytarabine, and G-CSF) plus high-dose intravenous plerixafor, a molecule inducing mobilization of blasts through the SDF-1α-CXCR4 axis blockade and potentially leading to chemosensitization of the leukemic cells. We aimed to establish a recommended phase 2 dose (RP2D) of plerixafor plus FLAG-Ida, as well as the efficacy and safety of this combination for early-relapsed (first complete remission (CR/CRi) < 12 months) or primary refractory AML...
February 2, 2018: Annals of Hematology
Mahmut Yeral, Pelin Aytan, Can Boğa
No abstract text is available yet for this article.
February 2, 2018: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Cornelia Monzel, Alexandra S Becker, Rainer Saffrich, Patrick Wuchter, Volker Eckstein, Anthony D Ho, Motomu Tanaka
Efficient mobilization of hematopoietic stem and progenitor cells (HSPC) is one of the most crucial issues for harvesting an adequate amount of peripheral HSPC for successful clinical transplantation. Applying well-defined surrogate models for the bone marrow niche, live cell imaging techniques, and novel tools in statistical physics, we have quantified the functionality of two mobilization agents that have been applied in the clinic, NOX-A12 and AMD3100 (plerixafor), as compared to a naturally occurring chemokine in the bone marrow, SDF1α...
January 30, 2018: Scientific Reports
Firoozeh Sahebi, Simona Iacobelli, Giulia Sbianchi, Linda Koster, Didier Blaise, Péter Reményi, Nigel H Russell, Per Ljungman, Guido Kobbe, Jane Apperley, Marek Trneny, Marta Krejci, Wieslaw Wiktor-Jedrzejczak, James F Sanchez, Nicolaas Schaap, Cecilia Isaksson, Stig Lenhoff, Paul Browne, Christof Scheid, Keith M O Wilson, Ibrahim Yakoub-Agha, Soledad González Muñiz, Stefan Schönland, Curly Morris, Laurent Garderet, Nicolaus Kröger
The advent of novel agents for multiple myeloma (MM) is cause for a re-examination of the incidence of second primary malignancies (SPM). We examined the SPM rate in MM patients who were enrolled in the prospective observational Collaboration to Collect Autologous Transplant outcome in Lymphoma and Myeloma (CALM) study. Between 2008 and 2012, 3204 patients with MM underwent a first autologous hematopoietic stem cell transplantation (auto-HSCT). Plerixafor was used as a mobilizing agent for patients with poor (or potentially poor) stem cell mobilization as defined by the respective centers...
January 12, 2018: Biology of Blood and Marrow Transplantation
Jacopo Olivieri, Immacolata Attolico, Roberta Nuccorini, Sara Pasquina Pascale, Martina Chiarucci, Monica Poiani, Paolo Corradini, Lucia Farina, Gianluca Gaidano, Luca Nassi, Simona Sica, Nicola Piccirillo, Pietro Enrico Pioltelli, Massimo Martino, Tiziana Moscato, Massimo Pini, Francesco Zallio, Fabio Ciceri, Sarah Marktel, Andrea Mengarelli, Pellegrino Musto, Saveria Capria, Francesco Merli, Katia Codeluppi, Giuseppe Mele, Francesco Lanza, Giorgina Specchia, Domenico Pastore, Giuseppe Milone, Francesco Saraceni, Elvira Di Nardo, Paolo Perseghin, Attilio Olivieri
Predicting mobilization failure before it starts may enable patient-tailored strategies. Although consensus criteria for predicted PM (pPM) are available, their predictive performance has never been measured on real data. We retrospectively collected and analyzed 1318 mobilization procedures performed for MM and lymphoma patients in the plerixafor era. In our sample, 180/1318 (13.7%) were PM. The score resulting from published pPM criteria had sufficient performance for predicting PM, as measured by AUC (0...
January 12, 2018: Bone Marrow Transplantation
Jun Zhu, Huiqiang Huang, Huan Chen, Xi Zhang, Zengjun Li, Depei Wu, Daobin Zhou, Yongping Song, Yu Hu, Yingmin Liang, Hanyun Ren, He Huang, Nainong Li, Hu Chen, Jiong Hu, Jianyong Li, Robin Meng, Junlong Wu, Dong Yu, Xiaojun Huang
BACKGROUND: This Phase 3 randomized, double-blind study evaluated the efficacy and safety of plerixafor plus granulocyte-colony-stimulating factor for the mobilization of hematopoietic stem cells in Chinese patients with non-Hodgkin's lymphoma. STUDY DESIGN AND METHODS: Adults (ages 18-75 years) with non-Hodgkin's lymphoma in first or second complete or partial remission, without previous hematopoietic stem cell mobilization or autologous transplant, were included...
December 13, 2017: Transfusion
Carlos H Villa, Thomas Porturas, Mary Sell, Mark Wall, Gene DeLeo, Jenna Fetters, Sam Mignono, Leah Irwin, Wei-Ting Hwang, Una O'Doherty
BACKGROUND: Rapid analytics to predict circulating hematopoietic stem cells are valuable for optimal management of mobilization, particularly for the use of newer and costly mobilization agents such as plerixafor. STUDY DESIGN AND METHODS: We used stepwise, linear multiple regression modeling applied to cell population data collected by routine hematology analyzers (Beckman Coulter DxH 800) on patients undergoing autologous stem cell collection (n = 131). Beta coefficients were used to derive a formula for a stem cell index (SCI)...
February 2018: Transfusion
Sarita Rani Jaiswal, Prakash Bhakuni, Aby Joy, Nisha Murli, Priyanka Bharadwaj, Shamsur Zaman, Murugayan Nedunchezian, Suparno Chakrabarti
We conducted a prospective study on T and natural killer (NK) cell subset composition of graft and transplant outcomes in T cell-replete haploidentical transplantation with a single dose of subcutaneous plerixafor (Px) added to granulocyte colony-stimulating factor (G-CSF)-based mobilization in allogeneic donors to collect 10 × 106 /kg CD34+ hematopoietic stem cells (HSCs) at single apheresis. Twnety-six donors received G-CSF + Px and 25 G-CSF alone for mobilization. Despite significantly lower peripheral blood (PB) CD34+ HSCs on day 4 in the G-CSF + Px group (33 [range, 6-47] cells/µL versus 81 [range, 50-168] cells/µL in the G-CSF group; P = ...
March 2018: Biology of Blood and Marrow Transplantation
Omur Gokmen Sevindik, Serdal Korkmaz, Fevzi Altuntas
Multiple myeloma is the leading indication of autologous hematopoietic cell transplantation (AHCT) worldwide. Hematopoietic progenitor cell mobilization (HPCM) is the first step of a successful AHCT. A minimum of 2×106 CD34+ cells/kg are needed for successful engraftment. Growth factors have been used both alone or in combination with chemotherapy for HPCM of patients with myeloma. Mobilization failures result in delays in AHCT and increased cost and resource utility. Strategies to mobilize progenitor cells were mainly chemotherapy and growth factor or growth factor-only mobilization until the advent of plerixafor...
December 2017: Transfusion and Apheresis Science
Sinem Namdaroglu, Serdal Korkmaz, Fevzi Altuntas
In contemporary clinical practice, almost all allogeneic transplantations and autologous transplantations now capitalize on peripheral blood stem cells (PBSCs) as opposed to bone marrow (BM) for the source of stem cells. In this context, granulocyte colony-stimulating factor (G-CSF) plays a pivotal role as the most frequently applied frontline agent for stem cell mobilization. For patients classified as high-risk, chemotherapy based mobilization regimens can be preferred as a first choice and it is notable that this also used for remobilization...
November 8, 2017: Transfusion and Apheresis Science
Roland Christian Schelker, Sabine Iberl, Gunnar Müller, Christina Hart, Wolfgang Herr, Jochen Grassinger
OBJECTIVES: Multipotent mesenchymal stromal cells (MSCs) play a central role within the bone marrow (BM) niche, supporting hematopoiesis via soluble factors like cytokines and chemokines. In our study, we sought to investigate the effect of blocking transforming growth factor beta 1 (TGF-β1) and C-X-C motif chemokine 12 (CXCL12) receptor CXCR4 on acute myeloid leukemia (AML) cells in an MSC co-culture system. METHODS: Human MSCs were obtained by BM aspirates and their phenotype and functional properties were confirmed in vitro...
November 15, 2017: Hematology (Amsterdam, Netherlands)
Gabriel Park, Sepideh Shayani, Tracey Stiller, Shirong Wang, Shan Yuan
BACKGROUND: Plerixafor is frequently used as an adjunct agent to improve mobilization of peripheral blood stem cells in many clinical settings. However, its high cost (>$8000 per single-use 24-mg vial) is a significant concern. The manufacturer-recommended dose is 0.24 mg/kg. Therefore, patients weighing more than 100 kg would require a second vial, thus doubling the drug cost per dose. We implemented a policy of capping the dose of plerixafor at 24 mg, or one vial, for patients weighing more than 100 kg...
November 13, 2017: Transfusion
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