DOCSLIB.ORG

Mobilization of Hematopoietic Stem Cells for Use in Autologous Transplantation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mobilization of Hematopoietic Stem Cells for Use in Autologous Transplantation Mobilization of Hematopoietic Stem Cells for Use in Autologous Transplantation Hollie Devine, MSN, RN, CNP, D. Kathryn Tierney, RN, PhD, Kim Schmit-Pokorny, RN, MSN, OCN®, and Kathleen McDermott, RN, BSN, OCN® Autologous hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach for various malignant hematologic and lymphoid diseases. Hematopoietic stem cells (HSCs) may be collected from the blood or the bone marrow. HSCs are capable of self-renewal and give rise to progenitor cells, multipotent cells that differentiate and proliferate into the mature cells of the blood and immune system. HSCs and progenitor cells are released from the bone marrow into the peripheral blood through a process called mobilization. HSCs then are collected from the blood in a process called apheresis and cryopreserved for administration following the high-dose preparative regimen. This article reviews stem cell biology, current mobilization strategies, use of novel mobilization agents, and nursing care of patients during the mobilization phase of autologous HSCT. Understanding the biology and process of HSC mobilization is critical for transplantation nurses to deliver and coordinate care during this complex phase of autologous HSCT. utologous hematopoietic stem cell transplantation (HSCT) is a therapeutic approach that is potentially At a Glance curative for a number of malignant hematologic Mobilization of hematopoietic stem cells (HSCs) from the bone and lymphoid diseases. The three types of HSCT marrow into the peripheral blood is a multistep process involv- are allogeneic, autologous, and syngeneic. In allo- ing the interplay among chemokines, cytokines, cell adhesion Ageneic transplantation, the hematopoietic stem cells (HSCs) molecules, and the bone marrow microenvironment. are obtained from a human leukocyte antigen–matched sibling, The goal of stem cell collection is to mobilize a sufficient an unrelated volunteer donor, or cyropreserved umbilical cord number of HSCs that are capable of regenerating the full blood. In autologous HSCT, the HSCs are collected from the hematopoietic lineages and to achieve adequate engraftment bone marrow or the blood of the patient when the cancer is following autologous HSC transplantation. in remission or a state of minimal residual disease. The third type of HCT is a syngeneic transplantation, where the source Nurses need to understand stem cell biology and the mecha- of the graft is an identical twin. Peripheral blood HSCs have nisms of action of current mobilization strategies. largely replaced the use of bone marrow as the graft source for autologous HSCT. The benefits of using HSCs collected from mobilization techniques will be reviewed, including the use the blood compared to HSCs collected from the bone marrow of novel mobilization agents. The collection, processing, and include a shorter period of neutropenia, which translates into cryopreservation of HSCs will be outlined. reduced use of antibiotics, decreased risk of infection, shorter hospitalization, and reduced costs (Schmitz et al., 1996; Smith et al., 1997). Hollie Devine, MSN, RN, CNP, is an adult nurse practitioner and educator The focus of this article is the mobilization of HSCs for use for advanced practice nurses and physician assistants in the James Can- in autologous HSCT. The term mobilization is used to describe cer Hospital at the Ohio State University Medical Center in Columbus; the process by which HSCs are released from the bone marrow D. Kathryn Tierney, RN, PhD, is an oncology clinical nurse specialist at into the blood. The biology of HSCs and the mechanisms by Stanford University Medical Center in California; Kim Schmit-Pokorny, which HSCs remain in the bone marrow microenvironment or RN, MSN, OCN®, is a transplant manager at the University of Nebraska are released into the blood will be reviewed. To date, the two Medical Center in Omaha; and Kathleen McDermott, RN, BSN, OCN®, is principle means of mobilization are the use of cytokines alone a clinical research nurse at the Dana-Farber Cancer Institute in Boston, or the use of cytokines in combination with chemotherapy. MA. (First submission August 2009. Revision submitted September 2009. These mobilization strategies will be described. Strategies for Accepted for publication October 8, 2009.) individuals who do not collect a sufficient graft with current Digital Object Identifier: 10.1188/10.CJON.212-222 212 April 2010 • Volume 14, Number 2 • Clinical Journal of Oncology Nursing Stem Cell Biology As HSCs mature, they expresses specific combinations of cell surface proteins that serve as biochemical markers. These bio- The Hematopoietic System chemical markers identify the evolutionary stage of the blood cell, dictate the next steps in cell maturation, and serve as regulatory Hematopoiesis is a cell-renewal process that leads to the signals (Scholossman et al., 1997; Zola et al., 2005; Zola, Swart, constant manufacturing of functional differentiated blood cells Boumsell, & Mason, 2003; Zola, Swart, Nicholson, & Voss, 2007). from HSCs and progenitor cells (Lataillade, Domenech, & Le Flow cytometry through the use of fluorescent-labeled antibodies Bousse-Kerdiles, 2004). HSCs are cells that can differentiate into is a technique for analyzing multiple markers of individual cells. functional mature blood cells while maintaining an indefinite The cluster of differention or cluster of designation (CD) system capacity for self-renewal. HSCs have three general properties: is the nomenclature used to classify and analyze cell surface mol- they are capable of self-renewing, they are unspecialized, and ecules present on leukocytes. The CD marker is used to associate they give rise to specialized cells. HSCs are vital in that they as- cells with certain immune functions and properties (Scholoss- sist in regenerating cells damaged by disease, injury, and daily man et al., 1997; Zola et al., 2003, 2005, 2007). CD34 is a marker use (Stem Cell Information, 2006). A progenitor cell is a dividing of HSCs and is used clinically to separate HSCs from other types cell with capacity to differentiate. The developmental pathway of leukocytes (see Figure 2). As HSCs differentiate, they lose the of HSCs into functional blood cells involves loss of the poten- CD34 marker and acquire other biochemical markers specific to tial to proliferate, with progressive differentiation into specific a lineage. T cells will acquire CD4 or CD8 surface markers and B blood elements with defined functions. These fully differentiat- cells will acquire surface immunoglobulin markers and antigen- ed blood cells have finite life spans, requiring constant renewal specific receptors (Manz et al., 2004). Table 2 summarizes the from the HSC pool (Manz, Akashi, & Weissman, 2004). biochemical markers of the various blood cells. In the bone marrow microenvironment, stem cells may The biology of HSC mobilization is a complex process. For remain quiescent for long periods of time until they are acti- successful proliferation of later-stage myeloid and lymphoid vated for the purpose of homeostasis or tissue repair (Manz et cells to occur, the hematopoietic system needs several factors: a al., 2004). Inside the bone marrow reside long-term HSCs that consortium of HSCs, hematopoietic growth factors to stimulate have the capacity for self-renewal (see Figure 1). A subset of proliferation, and stromal cell interactions between HSCs and these long-term HSCs will differentiate into short-term HSCs, progenitor cells. which give rise to multipotent progenitors of either the myeloid or lymphoid cell lineages. The common lymphoid progenitor differentiates into precursors of the B and T lymphocyte and Bone Marrow Microenvironment natural killer lineages. The common myeloid progenitor gives Inside the bone marrow is a multifunctional network of cells rise to two types of progenitors; the granulocyte-monocyte and extracellular matrix that maintain HSC proliferation, differ- progenitor and a megakaryocyte-erythrocyte progenitor. The entiation, and survival. This network of cells and extracellular granulocyte-monocyte progenitor produces the granulocyte lin- matrix are known as the bone marrow microenvironment (see eages (which produce neutrophils, basophils, and eosinophils), Figure 3). Stromal cells are the layers of cells that support the the monocyte-macrophage lineages, and the dendritic cell lin- infrastructure of the bone marrow. Stromal cells assist in the eages. The megakaryocyte-erythrocyte progenitor produces the regulation of HSCs and are important cells for providing dif- erythroid-lineage cells and megakaryocytes (Manz et al., 2004). ferentiation signals to HSCs. Additionally, stromal cells direct Table 1 describes the function of each blood cell. the movement of HSCs out of the bone marrow and into the peripheral circulation (Lataillade et al., 2004). Stromal cells produce stromal-cell derived factor- CLP 1a (SDF-1a), a chemokine widely expressed by Pro-T T many tissues such as the ectoderm, endoderm, B Pro-B mesoderm, and mesenchymal cells (McGrath, NK LT-HSC ST-HSC MPP GMP Koniski, Maltby, McGann, & Palis, 1999). SDF-1a Granulocytes is a signaling molecule involved in the prolif- Monocytes eration, homing, and engraftment of HSCs and Dendritic cells CMP MEP leukocytes. Erythrocytes Platelets Mechanisms of Mobilization CLP—common lymphoid progenitor; CMP—common myeloid progenitor; GMP— In addition to HSCs and stromal cells, mobili- granulocyte-monocyte progenitor; LT-HSC—long-term hematopoietic
Load more

Recommended publications
  • The Act of Controlling Adult Stem Cell Dynamics: Insights from Animal Models
    biomolecules Review The Act of Controlling Adult Stem Cell Dynamics: Insights from Animal Models Meera Krishnan 1, Sahil Kumar 1, Luis Johnson Kangale 2,3 , Eric Ghigo 3,4 and Prasad Abnave 1,* 1 Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Gurgaon-Faridabad Ex-pressway, Faridabad 121001, India; [email protected] (M.K.); [email protected] (S.K.) 2 IRD, AP-HM, SSA, VITROME, Aix-Marseille University, 13385 Marseille, France; [email protected] 3 Institut Hospitalo Universitaire Méditerranée Infection, 13385 Marseille, France; [email protected] 4 TechnoJouvence, 13385 Marseille, France * Correspondence: [email protected] Abstract: Adult stem cells (ASCs) are the undifferentiated cells that possess self-renewal and differ- entiation abilities. They are present in all major organ systems of the body and are uniquely reserved there during development for tissue maintenance during homeostasis, injury, and infection. They do so by promptly modulating the dynamics of proliferation, differentiation, survival, and migration. Any imbalance in these processes may result in regeneration failure or developing cancer. Hence, the dynamics of these various behaviors of ASCs need to always be precisely controlled. Several genetic and epigenetic factors have been demonstrated to be involved in tightly regulating the proliferation, differentiation, and self-renewal of ASCs. Understanding these mechanisms is of great importance, given the role of stem cells in regenerative medicine. Investigations on various animal models have played a significant part in enriching our knowledge and giving In Vivo in-sight into such ASCs regulatory mechanisms. In this review, we have discussed the recent In Vivo studies demonstrating the role of various genetic factors in regulating dynamics of different ASCs viz.
    [Show full text]
  • Transforming Growth Factor-β in Stem Cells and Tissue Homeostasis
    Bone Research www.nature.com/boneres REVIEW ARTICLE OPEN Transforming growth factor-β in stem cells and tissue homeostasis Xin Xu1, Liwei Zheng2, Quan Yuan3, Gehua Zhen4, Janet L. Crane4,5, Xuedong Zhou1 and Xu Cao4 TGF-β 1–3 are unique multi-functional growth factors that are only expressed in mammals, and mainly secreted and stored as a latent complex in the extracellular matrix (ECM). The biological functions of TGF-β in adults can only be delivered after ligand activation, mostly in response to environmental perturbations. Although involved in multiple biological and pathological processes of the human body, the exact roles of TGF-β in maintaining stem cells and tissue homeostasis have not been well-documented until recent advances, which delineate their functions in a given context. Our recent findings, along with data reported by others, have clearly shown that temporal and spatial activation of TGF-β is involved in the recruitment of stem/progenitor cell participation in tissue regeneration/remodeling process, whereas sustained abnormalities in TGF-β ligand activation, regardless of genetic or environmental origin, will inevitably disrupt the normal physiology and lead to pathobiology of major diseases. Modulation of TGF- β signaling with different approaches has proven effective pre-clinically in the treatment of multiple pathologies such as sclerosis/ fibrosis, tumor metastasis, osteoarthritis, and immune disorders. Thus, further elucidation of the mechanisms by which TGF-β is activated in different tissues/organs and how targeted cells respond in a context-dependent way can likely be translated with clinical benefits in the management of a broad range of diseases with the involvement of TGF-β.
    [Show full text]
  • The Hepatocyte Growth Factor/Scatter Factor
    Cutting Edge: Identification of a Hybrid Cytokine Consisting of IL-7 and the β-Chain of the Hepatocyte Growth Factor/Scatter Factor This information is current as Laijun Lai and Irving Goldschneider of September 23, 2021. J Immunol 2001; 167:3550-3554; ; doi: 10.4049/jimmunol.167.7.3550 http://www.jimmunol.org/content/167/7/3550 Downloaded from References This article cites 30 articles, 13 of which you can access for free at: http://www.jimmunol.org/content/167/7/3550.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 23, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2001 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. ● Cutting Edge: Identification of a Hybrid Cytokine Consisting of IL-7 and the ␤-Chain of the Hepatocyte Growth Factor/Scatter Factor1 Laijun Lai and Irving Goldschneider2 initiate or up-regulate the expression of terminal deoxynucleotidyl Pre-pro-B cell growth-stimulating factor (PPBSF) is a het- transferase, cytoplasmic Ig␮ heavy chain, and IL-7R␣-chain (Ref.
    [Show full text]
  • Caspase-Activated ROCK-1 Allows Erythroblast Terminal Maturation Independently of Cytokine-Induced Rho Signaling
    Cell Death and Differentiation (2011) 18, 678–689 & 2011 Macmillan Publishers Limited All rights reserved 1350-9047/11 www.nature.com/cdd Caspase-activated ROCK-1 allows erythroblast terminal maturation independently of cytokine-induced Rho signaling A-S Gabet1, S Coulon1, A Fricot1, J Vandekerckhove1, Y Chang2,3, J-A Ribeil1, L Lordier2,3, Y Zermati4, V Asnafi1, Z Belaid1, N Debili2,3, W Vainchenker2,3, B Varet1,5, O Hermine*,1,5 and G Courtois*,1 Stem cell factor (SCF) and erythropoietin are strictly required for preventing apoptosis and stimulating proliferation, allowing the differentiation of erythroid precursors from colony-forming unit-E to the polychromatophilic stage. In contrast, terminal maturation to generate reticulocytes occurs independently of cytokine signaling by a mechanism not fully understood. Terminal differentiation is characterized by a sequence of morphological changes including a progressive decrease in cell size, chromatin condensation in the nucleus and disappearance of organelles, which requires transient caspase activation. These events are followed by nucleus extrusion as a consequence of plasma membrane and cytoskeleton reorganization. Here, we show that in early step, SCF stimulates the Rho/ROCK pathway until the basophilic stage. Thereafter, ROCK-1 is activated independently of Rho signaling by caspase-3-mediated cleavage, allowing terminal maturation at least in part through phosphorylation of the light chain of myosin II. Therefore, in this differentiation system, final maturation occurs independently
    [Show full text]
  • Transmembrane Stem Cell Factor Protein Therapeutics Enhance Revascularization in Ischemia Without Mast Cell Activation
    bioRxiv preprint doi: https://doi.org/10.1101/2020.04.06.028563; this version posted April 7, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Transmembrane Stem Cell Factor Protein Therapeutics Enhance Revascularization in Ischemia without Mast Cell Activation Eri Takematsu1, Jeff Auster1, Po-Chih Chen1, Sanjana Srinath1, Sophia Canga1, Aditya Singh1, Marjan Majid1, Michael Sherman2, Andrew Dunn1, Annette Graham3, Patricia Martin3 and Aaron B. Baker1,4,5,6 1Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 2Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 3Department of Biological and Biomedical Sciences, School of Health and Life Sciences, Glasgow Caledonian University, G4 0BA, Scotland, UK 4Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 5The Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, TX 6Institute for Biomaterials, Drug Delivery and Regenerative Medicine, University of Texas at Austin, Austin, TX Total Figures: 6 + 7 Supplemental Figures Total Tables: 1 Main Manuscript Word Count: 5,485 Running Title: Transmembrane SCF Nanodiscs Enhance Revascularization Correspondence to: Aaron B. Baker University of Texas at Austin Department of Biomedical Engineering 1 University Station BME 5.202D, C0800 Austin, TX 78712 Phone: 512-232-7114 E-mail: [email protected] Page 1 of 41 bioRxiv preprint doi: https://doi.org/10.1101/2020.04.06.028563; this version posted April 7, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.
    [Show full text]
  • Mobilization Failure in Hematopoietic Stem Cell Transplantation
    MOBILIZATION FAILURE IN HEMATOPOIETIC STEM CELL TRANSPLANTATION Siret Ratip Department of Haematology, Acıbadem University School of Medicine, İstanbuy, Turkey G-CSF–based mobilization regimens have a plantations, G-CSF is given at 10 μg/kg per day 5%-30% failure rate among healthy donors and subcutaneously with apheresis beginning on the patients, but the rate can be up to 60% in high- fifth day until the yield target is reached. There is risk patients such as those exposed to fludarabine. no evidence that twice daily administration gives a Poor mobilization has significant consequences for higher yield than once-daily (4). the patient with potential loss of the transplant as a treatment option. Repeated attempts at mobiliza- Combining G-CSF with chemotherapy for tion increase resource use, morbidity, and patient/ mobilization donor inconvenience. Therefore, there is much Combining G-CSF with chemotherapy achieves interest in the prevention and salvage of mobiliza- both mobilization and antitumor activity and has tion failure with novel strategies. been shown to result in a higher CD34+ cell yield than G-CSF alone (5). Regimens such as cyclo- The role of CD34+ cell dose in phosphamide, doxorubicin, vincristine, and pred- haematopoeitic stem cell transplantation nisone/dexamethasone, high-dose cytarabine, and Benefits of rapid recovery in HSCT are reduced cisplatin or cyclophosphamide 1-5 g/m2 have been hospitalization, blood product usage, and infec- used with G-CSF which is commenced 1-3 days tions. Minimum threshold of CD34+ cell dose for following cyclophosphamide. Apheresis is usually autologous transplantation is currently 2 × 106 started when leukocyte count reaches > 2 × 109/L.
    [Show full text]
  • Cytokine Receptors and Hematopoietic Differentiation
    Oncogene (2007) 26, 6715–6723 & 2007 Nature Publishing Group All rights reserved 0950-9232/07 $30.00 www.nature.com/onc REVIEW Cytokine receptors and hematopoietic differentiation LRobb The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Colony-stimulating factors and other cytokines signal via finely tuned regulatory pathways that control both basal their cognate receptors to regulate hematopoiesis. In and emergency hematopoiesis are mediated largely by many developmental systems, inductive signalling deter- cytokines and their cognate receptors. Cytokines are a mines cell fate and, by analogy with this, it has been large family of specific extracellular ligands that can postulated that cytokines, signalling via their cognate stimulate biological responses in diverse cell types by receptors, may play an instructive role in lineage binding to, and activating, a family of structurally and specification in hematopoiesis. An alternative to this functionally conserved cytokine receptors. instructive hypothesis is the stochastic or permissive Cytokines of the hematopoietic system include inter- hypothesis. The latter proposes that commitment to a leukins (ILs), colony-stimulating factors (CSFs), inter- particular hematopoietic lineage is an event that occurs ferons, erythropoietin (EPO) and thrombopoietin independently of extrinsic signals. It predicts that the role (TPO). They bind to a family of cytokine receptors that of cytokines is to provide nonspecific survival and share a number of features. The receptors can be proliferation signals. In this review, we look at the role composed of dimers of a single receptor (granulocyte of cytokine receptor signalling in hematopoiesis and (G)-CSF receptor (R), EPO receptor (EPOR), TPO consider the evidence for both hypotheses.
    [Show full text]
  • Peripheral Blood Progenitor Cells Mobilization in Patients with Multiple Myeloma
    ell Res C ea m rc te h S & f o T h l Journal of e a Ria and Vacca, J Stem Cell Res Ther 2014, 4:8 r n a r p u DOI: 10.4172/2157-7633.1000226 y o J ISSN: 2157-7633 Stem Cell Research & Therapy Review Article Open Access Peripheral Blood Progenitor Cells Mobilization in Patients with Multiple Myeloma Roberto Ria* and Angelo Vacca Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy Abstract Autologous stem cell transplantation (ASCT) is considered the standard therapy for younger patients with newly diagnosed symptomatic multiple myeloma (MM). The introduction into clinical practice of novel agents (i.e.: proteasome inhibitors and immunomodulatory derivatives [IMiDs]) has significantly contributed to major advances in MM therapy and prognosis. These novel agents are incorporated into induction regimens to enhance the depth of response before ASCT and further improve post-ASCT outcomes. Collection of adequate hematopoietic stem cells (HSCs) is necessary for successful autologous transplantation. The mobilizing regimen usually consists of cyclophosphamide or disease-specific agents, in combination with a hematopoietic cytokine, usually G-CSF, which mobilizes HPSCs into the bloodstream, in particular when administered after myelosuppressive chemotherapy. In some patients, the number of mobilized CD34+ cells is not sufficient to perform successful stem cell transplantation due to bone marrow damage by neoplastic proliferation and/or chemoradiotherapy. To improve the collection of CD34+ cells, the mobilization procedure can be repeated or an alternative chemotherapy regimen can be chosen. Recently, the new drug plerixafor (Mozobil®) has been introduced to increase the number of circulating CD34+ cells.
    [Show full text]
  • Kit Transduced Signals Counteract Erythroid Maturation by MAPK-Dependent Modulation of Erythropoietin Signaling and Apoptosis Induction in Mouse Fetal Liver
    Cell Death and Differentiation (2015) 22, 790–800 & 2015 Macmillan Publishers Limited All rights reserved 1350-9047/15 www.nature.com/cdd Kit transduced signals counteract erythroid maturation by MAPK-dependent modulation of erythropoietin signaling and apoptosis induction in mouse fetal liver N Haas1, T Riedt2, Z Labbaf1, K Baßler1, D Gergis3, H Fröhlich3, I Gütgemann1, V Janzen2 and H Schorle*,1 Signaling by the stem cell factor receptor Kit in hematopoietic stem and progenitor cells is functionally associated with the regulation of cellular proliferation, differentiation and survival. Expression of the receptor is downregulated upon terminal differentiation in most lineages, including red blood cell terminal maturation, suggesting that omission of Kit transduced signals is a prerequisite for the differentiation process to occur. However, the molecular mechanisms by which Kit signaling preserves the undifferentiated state of progenitor cells are not yet characterized in detail. In this study, we generated a mouse model for inducible expression of a Kit receptor carrying an activating mutation and studied its effects on fetal liver hematopoiesis. We found that sustained Kit signaling leads to expansion of erythroid precursors and interferes with terminal maturation beyond the erythroblast stage. Primary KITD816V erythroblasts stimulated to differentiate fail to exit cell cycle and show elevated rates of apoptosis because of insufficient induction of survival factors. They further retain expression of progenitor cell associated factors c-Myc, c-Myb and GATA-2 and inefficiently upregulate erythroid transcription factors GATA-1, Klf1 and Tal1. In KITD816V erythroblasts we found constitutive activation of the mitogen-activated protein kinase (MAPK) pathway, elevated expression of the src kinase family member Lyn and impaired Akt activation in response to erythropoietin.
    [Show full text]
  • Systematic Review of Randomized Controlled Trials of Hematopoietic Stem Cell Mobilization Strategies for Autologous Transplantat
    CLINICAL RESEARCH Systematic Review of Randomized Controlled Trials of Hematopoietic Stem Cell Mobilization Strategies for Autologous Transplantation for Hematologic Malignancies Dawn Sheppard, Christopher Bredeson, David Allan, Jason Tay Collection of adequate hematopoietic stem cells (HSCs) is necessary for successful autologous transplanta- tion; however, a proportion of patients fail to collect the minimum number of cells required. We summarized the efficacy and safety of HSC mobilization strategies. We performed a systematic review of randomized controlled trials comparing HSC mobilization strategies before autologous transplantation for hematologic malignancies. The primary outcome was CD341 cell yield. Secondary outcomes included number of apher- eses, proportion of failures, rate of count recovery, and adverse events. We identified 28 articles within 3 broad strategies. Using a cyclophosphamide with growth factor strategy (10 articles), CD341 cell yield is improved by addition of molgramostim to cyclophosphamide (1.4 vs 0.5 Â 106/kg; P 5 .0165), addition of cyclophosphamide to filgrastim (7.2 vs 2.5 Â 106/kg; P 5.004), and addition of ancestim to cyclophosphamide and filgrastim (12.4 vs 8.3 Â 106/kg; P 5.007). Within a growth factor-based strategy (6 articles), addition of plerixafor improves CD341 cell yield over filgrastim alone in multiple myeloma (MM; 11.0 vs 6.2 Â 106/kg; P \ .001) and non-Hodgkin lymphoma (5.69 vs 1.98 Â 106/kg; P \ .01). With combination or noncyclophosphamide-based chemotherapy (12 articles), higher-dose filgrastim (8.2 vs 4.7 Â 106/kg for 16 vs 8/mcg/kg daily of filgrastim, respectively; P \.0001) and addition of rituximab to etoposide and filgras- tim (9.9 vs 5.6 Â 106/kg; P 5.021) improve CD341 cell yield.
    [Show full text]
  • Method of Production of Transgenic Avian Using Embryonic Stem Cells
    (19) TZZ ZZ__T (11) EP 2 500 417 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 19.09.2012 Bulletin 2012/38 C12N 5/0735 (2010.01) A01K 67/027 (2006.01) (21) Application number: 12167371.9 (22) Date of filing: 09.08.2007 (84) Designated Contracting States: (72) Inventors: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR • Valarche, Isabelle HU IE IS IT LI LT LU LV MC MT NL PL PT RO SE 44000 Nantes (FR) SI SK TR • Batard, Luc Designated Extension States: 44000 Nantes (FR) AL BA HR MK RS • Mehtali, Majid 44220 Coueron (FR) (30) Priority: 09.08.2006 US 836378 P (74) Representative: Flesselles, Bruno F.G. et al (62) Document number(s) of the earlier application(s) in BF IP accordance with Art. 76 EPC: 4, rue Ribera 07802553.3 / 2 054 507 75016 Paris (FR) (71) Applicant: Vivalis Remarks: 49450 Roussay (FR) This application was filed on 09-05-2012 as a divisional application to the application mentioned under INID code 62. (54) Method of production of transgenic avian using embryonic stem cells (57) The present invention concerns a method of cul- inhibitory factor (LIF), interleukin 11 (II-11), oncostatin turing embryonic stem (ES) cells of avian, comprising the and cardiotrophin; b) seeding the suspension of ES cells steps of: a) suspending ES cells originating from the blas- obtained in step a) on a layer of feeder cells and further toderm disk of fertilized un-incubated avian egg(s) in a culturing the ES cells for at least between 2 to 10 pas- basal culture medium supplemented with: insulin-like sages; c) optionally removing at least one growth factors growth factor-1 (IGF-1) and ciliary neurotrophic factor selected SCF, FGF, II-6, II-6R, LIF, oncostatin and car- (CNTF); and animal serum; and optionally, at least one diotrophin and II-11 from the culture medium; d) further growth factors selected in the group comprising inter- culturing the ES cells in the medium of step c) on a layer leukin 6 (II-6), interleukin 6 receptor (II-6R), stem cell of feeder cells.
    [Show full text]
  • Human Granulocyte-Colony Stimulating Factor (G-CSF)/Stem Cell Factor (SCF) Fusion Proteins: Design, Characterization and Activity
    Human granulocyte-colony stimulating factor (G-CSF)/stem cell factor (SCF) fusion proteins: design, characterization and activity Gitana Mickiene1,2, Indrė Dalgėdienė1, Gintautas Zvirblis1, Zilvinas Dapkunas1,2, Ieva Plikusiene3, Ernesta Buzavaite-Verteliene4, Zigmas Balevičius4, Audronė Rukšėnaitė1 and Milda Pleckaityte1 1 Institute of Biotechnology, Vilnius University, Vilnius, Lithuania 2 Profarma UAB, Vilnius, Lithuania 3 Department of Physical Chemistry, Faculty of Chemistry and Geosciences, Vilnius University, Vilnius, Lithuania 4 Plasmonics and Nanophotonics Laboratory, Department of Laser Technology, Center for Physical Sciences and Technology, Vilnius, Lithuania ABSTRACT Background: Stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) are well-characterized vital hematopoietic growth factors that regulate hematopoiesis. G-CSF and SCF synergistically exhibit a stimulatory effect on hematopoietic progenitors. The combination of G-CSF and SCF has been used for mobilization of peripheral blood progenitor cells in cancer and non-cancerous conditions. To overcome challenges connected with the administration of two cytokines, we developed two fusion proteins composed of human SCF and human G-CSF interspaced by an alpha-helix-forming peptide linker. Methods: The recombinant proteins SCF-La-GCSF and GCSF-La-SCF were purified in three steps using an ion-exchange and mixed-mode chromatography. The purity and quantity of the proteins after each stage of purification was assessed using RP-HPLC, SDS-PAGE, and the Bradford assays. Purified proteins were Submitted 22 April 2020 identified using high-performance liquid chromatography/electrospray ionization Accepted 31 July 2020 mass spectrometry (HPLC/ESI-MS) and the Western blot analyses. The molecular Published 21 August 2020 weight was determined by size exclusion HPLC (SE-HPLC).
    [Show full text]