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Plerixafor

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https://www.readbyqxmd.com/read/29339268/incidence-of-second-primary-malignancies-after-autologous-transplantion-for-multiple-myeloma-in-the-era-of-novel-agents
#1
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
https://www.readbyqxmd.com/read/29330395/predicting-failure-of-hematopoietic-stem-cell-mobilization-before-it-starts-the-predicted-poor-mobilizer-ppm-score
#2
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
https://www.readbyqxmd.com/read/29238988/plerixafor-and-granulocyte-colony-stimulating-factor-for-mobilization-of-hematopoietic-stem-cells-for-autologous-transplantation-in-chinese-patients-with-non-hodgkin-s-lymphoma-a-randomized-phase-3-study
#3
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
https://www.readbyqxmd.com/read/29230822/rapid-prediction-of-stem-cell-mobilization-using-volume-and-conductivity-data-from-automated-hematology-analyzers
#4
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)...
December 11, 2017: Transfusion
https://www.readbyqxmd.com/read/29191663/the-impact-of-single-dose-plerixafor-as-an-adjunct-to-g-csf-based-peripheral-blood-stem-cell-mobilisation-on-the-graft-composition-and-outcome-for-t-replete-haploidentical-pbsc-transplantation-with-post-transplantation-cyclophosphamide-a-comparative-study
#5
Sarita Rani Jaiswal, Prakash Bhakuni, Aby Joy, Nisha Murli, Priyanka Bharadwaj, Shamsur Zaman, Nedunchezian Murugayan, Suparno Chakrabarti
We conducted a prospective study on T and NK cell subset composition of the graft and the transplant outcomes inT-replete haploidentical transplantationwithsingle dose of subcutaneous Plerixafor(Px)added to G-CSF based mobilisation in allogeneic donors to collect 10 x 106/kg CD34+HSC at single apheresis. 26 donors received G-CSF+Px and 25 donors received G-CSF alone for mobilisation. Despite a significantly lower peripheral blood (PB) CD34+HSC on day 4 in the G-CSF+Px group [33(6-47) cells/µl vs 81(50-168) cells/µl in G-CSF group, p=0...
November 27, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29174798/current-status-of-art-mobilization-in-myeloma
#6
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
https://www.readbyqxmd.com/read/29153350/management-of-mobilization-failure-in-2017
#7
REVIEW
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
https://www.readbyqxmd.com/read/29140182/tgf-%C3%AE-1-and-cxcl12-modulate-proliferation-and-chemotherapy-sensitivity-of-acute-myeloid-leukemia-cells-co-cultured-with-multipotent-mesenchymal-stromal-cells
#8
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)
https://www.readbyqxmd.com/read/29134662/dose-capping-of-plerixafor-in-patients-weighing%C3%A2-more-than-100%C3%A2-kg-at-one-vial-led-to-successful-mobilization-outcomes-and-significant-cost-savings
#9
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
https://www.readbyqxmd.com/read/29132746/diabetes-mellitus-as-a-poor-mobilizer-condition
#10
REVIEW
Gian Paolo Fadini, John F DiPersio
Hematopoietic stem cell (HSC) transplantation in an effective and curative therapy for numerous hematological malignancies. Mobilization of HSCs from bone marrow (BM) to peripheral blood (PB) followed by apheresis is the gold standard for obtaining HSCs for both autologous and allogeneic stem cell transplantation. After administration of granulocyte-colony stimulating factor (G-CSF), up to 30% of patients fail to mobilize "optimal" numbers of HSCs required for engraftment. This review summarizes the current experimental and clinical evidence that diabetes mellitus is a risk factor for poor mobilization...
November 8, 2017: Blood Reviews
https://www.readbyqxmd.com/read/29125295/structure-activity-relationships-and-biological-characterization-of-a-novel-potent-and-serum-stable-c-x-c-chemokine-receptor-type-4-cxcr4-antagonist
#11
Salvatore Di Maro, Francesco Saverio Di Leva, Anna Maria Trotta, Diego Brancaccio, Luigi Portella, Michela Aurilio, Stefano Tomassi, Anna Messere, Deborah Sementa, Secondo Lastoria, Alfonso Carotenuto, Ettore Novellino, Stefania Scala, Luciana Marinelli
In our ongoing pursuit of CXCR4 antagonists as potential anticancer agents, we recently developed a potent, selective and plasma stable peptide, Ac-Arg-Ala-[D-Cys-Arg-Phe-Phe-Cys]-COOH (3). Nevertheless, this compound was still not enough potent (IC50 ≈ 53 nM) to enter preclinical studies. Thus, a lead-optimization campaign was here undertaken to further improve the binding affinity of 3 while preserving its selectivity and proteolytic stability. Specifically, extensive structure-activity relationships (SARs) investigations were carried out on both its aromatic and disulfide forming amino acids...
November 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29081261/stem-cell-mobilization-in-poor-mobilizers-with-multiple-myeloma-or-lymphoma-before-and-after-introduction-of-plerixafor-a-single-center-comparative-analysis-using-a-cost-efficient-single-fixed-dose-schedule
#12
Christine Greil, Gabriele Ihorst, Chrissoula Kiote-Schmidt, Steffi Hildenbeutel, Katja Kühbach, Roland Bosse, Justus Duyster, Monika Engelhardt, Ralph Wäsch
No abstract text is available yet for this article.
October 30, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29075055/single-dose-preemptive-plerixafor-for-stem-cell-mobilization-for-asct-after-lenalidomide-based-therapy-in-multiple-myeloma-impact-in-resource-limited-setting
#13
Rajiv Kumar, Rajan Kapoor, Bhushan Asthana, Jasjit Singh, Tarun Verma, Rajesh Chilaka, N K Singh, Ajay Sharma, S Das, Velu Nair
Peripheral blood stem cell mobilization with cytokines for autologous stem cell transplant in multiple myeloma is adversely affected by initial induction therapy consisting of either Lenalidomide or cytotoxic drugs, with failure rates of up to 45%. The use of Plerixafor with G-CSF for PBSC mobilisation significantly improves the chances of a successful mobilization. Plerixafor is a costly therapy and increases the overall costs of ASCT which can affect the number of patients being taken up for ASCT in resource limited settings...
December 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/29066537/how-i-treat-warts-hypogammaglobulinemia-infections-and-myelokathexis-syndrome
#14
REVIEW
Raffaele Badolato, Jean Donadieu
Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a genetic disease characterized by neutropenia, lymphopenia, susceptibility to infections, and myelokathexis, which describes degenerative changes of mature neutrophils and hyperplasia of bone marrow myeloid cells. Some patients present with hypogammaglobulinemia and/or refractory warts of skin and genitalia. Congenital cardiac defects constitute uncommon manifestations of the disease. The disorder, which is inherited as an autosomal dominant trait, is caused by heterozygous mutations of the chemokine receptor CXCR4...
December 7, 2017: Blood
https://www.readbyqxmd.com/read/29058701/nsaid-treatment-with-meloxicam-enhances-peripheral-stem-cell-mobilization-in-myeloma
#15
B Jeker, U Novak, B Mansouri Taleghani, G M Baerlocher, K Seipel, B U Mueller, M Bigler, D Betticher, J-M Luethi, S Farese, A Ruefer, T Pabst
Chemotherapy with G-CSF is used to mobilize peripheral stem cells in multiple myeloma (MM) patients, with plerixafor as a rescue strategy for poorly mobilizing patients. Preclinical studies suggested that the nonsteroidal anti-inflammatory drug meloxicam enhances the mobilization of CD34(+) cells. In this single-center study, we evaluated whether adding meloxicam to chemotherapy/G-CSF mobilization increases peripheral hematopoietic CD34(+) cell levels and reduces the need of using plerixafor. We prospectively compared two consecutive cohorts of MM patients in first remission mobilized with G-CSF and non-myelosuppressive chemotherapy with vinorelbine or gemcitabine...
October 23, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29057173/pathogenesis-diagnosis-and-therapeutic-strategies-in-whim-syndrome-immunodeficiency
#16
Lauren E Heusinkveld, Erin Yim, Alexander Yang, Ari B Azani, Qian Liu, Ji-Liang Gao, David H McDermott, Philip M Murphy
21 INTRODUCTION: WHIM syndrome is a rare combined primary immunodeficiency disorder caused by autosomal dominant gain-of-function mutations in the chemokine receptor CXCR4. It is the only Mendelian condition known to be caused by mutation of a chemokine or chemokine receptor. As such, it provides a scientific opportunity to understand chemokine-dependent immunoregulation in humans and a medical opportunity to develop mechanism-based treatment and cure strategies. 22 AREAS COVERED: This review covers the clinical features, genetics, immunopathogenesis and clinical management of WHIM syndrome...
2017: Expert Opinion on Orphan Drugs
https://www.readbyqxmd.com/read/28916148/chemokine-receptor-directed-imaging-and-therapy
#17
REVIEW
Andreas K Buck, Antje Stolzenburg, Heribert Hänscheid, Andreas Schirbel, Katharina Lückerath, Margret Schottelius, Hans-Jürgen Wester, Constantin Lapa
The C-X-C chemokine receptor 4 (CXCR4) and its natural ligand CXCL12 are key factors in the process of cell migration, homing of hematopoietic stem cells to the bone marrow, and represent important mediators of angiogenesis and cell proliferation. The CXCR4/CXCL12 interplay can be disrupted by CXCR4 antagonists such as Plerixafor which are already in daily clinical use, i.e. for mobilization and subsequent harvesting of hematopoietic progenitor cells and stem cell transplantation. In a pathological condition, involvement in the process of metastasis and homing of cancer cells to a protective niche has been described, making CXCR4 an attractive target for imaging and treatment of malignant diseases...
November 1, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28894310/chemical-stability-of-plerixafor-after-opening-of-single-use-vial
#18
Jack T Seki, Andrea Bozovic, Roy Lee, Rita Kwong, Eshetu G Atenafu, Anna Xu, Jin-Hyeun Huh
BACKGROUND: The addition of the immunostimulant plerixafor to the current standard-of-care regimens of granulocyte colony-stimulating growth factor with or without chemotherapy has improved clinical results in terms of successful stem cell mobilization and the outcomes of stem cell transplant in various settings. With this medical innovation has come an added financial cost for institutions where stem cell transplants are routinely performed, and there may be a further financial burden when the contents of partial vials of the drug are wasted, given that plerixafor vials (Mozobil, Sanofi-Aventis Canada Inc) are currently deemed suitable only for single use...
July 2017: Canadian Journal of Hospital Pharmacy
https://www.readbyqxmd.com/read/28879595/preemptive-plerixafor-injection-added-to-pegfilgrastim-after-chemotherapy-in-non-hodgkin-lymphoma-patients-mobilizing-poorly
#19
A Partanen, J Valtola, A Ropponen, K Vasala, K Penttilä, L Ågren, M Pyörälä, T Nousiainen, T Selander, P Mäntymaa, J Pelkonen, V Varmavuo, E Jantunen
Filgrastim is usually combined with chemotherapy to mobilize hematopoietic progenitor cells in non-Hodgkin lymphoma (NHL) patients. Limited information is available on the efficacy of a preemptive plerixafor (PLER) injection in poor mobilizers after chemotherapy and pegfilgrastim. In this prospective study, 72 patients with NHL received chemotherapy plus pegfilgrastim, and 25 hard-to-mobilize patients received also PLER. The usefulness and efficacy of our previously developed algorithm for PLER use in pegfilgrastim-containing mobilization regimen were evaluated as well as the graft cellular composition, hematological recovery, and outcome after autologous stem cell transplantation (auto-SCT) according to the PLER use...
November 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28817386/cxcr4-blockade-with-amd3100-enhances-taxol-chemotherapy-to-limit-ovarian-cancer-cell-growth
#20
Patrick M Reeves, Mojgan A Abbaslou, Farah R W Kools, Mark C Poznansky
The standard of care for ovarian cancer includes initial treatment with chemotherapy. Despite initial efficacy, over 70% of patients develop recurrence; thus, there is a need to identify novel approaches that can improve therapeutic outcomes. We evaluated AMD3100 (Plerixafor), an FDA-approved CXCR4 inhibitor, as a potential adjunctive therapy for low-dose Taxol (Paclitaxel) by assessing the impact on in-vitro ovarian cancer cell proliferation. Proliferation was a measure for both human TOV-112D and murine ID8 ovarian cancer cells incubated with AMD3100 and Taxol, either individually or in combination...
August 16, 2017: Anti-cancer Drugs
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