New agents in HSC mobilization

Domingues, Mélanie J.; Nilsson, Susan K.; Cao, Benjamin

doi:10.1007/s12185-016-2156-2

Cited by 46 publications

(32 citation statements)

References 108 publications

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“…Other ␣4 antagonists, such as the orally bioavailable drug called firategrast, are being developed but are not yet commercially available. 132 The development of integrin antagonists for blocking the ␣ 9 ␤ 1 integrin, whose expression is restricted to HSPCs, is promising. The small molecule N-(benzenesulfonyl)-l-prolyl-l-O-(1-pyrrolidinylcarbonyl)tyrosine (BOP), which is a dual ␣ 9 ␤ 1 /␣ 4 ␤ 1 integrin antagonist, mobilizes multilineage reconstituting HSPCs after a single dose in mice.…”

Section: Nonsteroidal Anti-inflammatory Drugsmentioning

confidence: 99%

Cytokine‐induced hematopoietic stem and progenitor cell mobilization: unraveling interactions between stem cells and their niche

Kruijf

Fibbe

Pel

2019

Annals of the New York Academy of Sciences

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Peripheral blood hematopoietic stem and progenitor cells (HSPCs), mobilized by granulocyte colony-stimulating factor, are widely used as a source for both autologous and allogeneic stem cell transplantation. The use of mobilized HSPCs has several advantages over traditional bone marrow-derived HSPCs, including a less invasive harvesting process for the donor, higher HSPC yields, and faster hematopoietic reconstitution in the recipient. For years, the mechanisms by which cytokines and other agents mobilize HSPCs from the bone marrow were not fully understood. The field of stem cell mobilization research has advanced significantly over the past decade, with major breakthroughs in the elucidation of the complex mechanisms that underlie stem cell mobilization. In this review, we provide an overview of the events that underlie HSPC mobilization and address the relevant cellular and molecular components of the bone marrow niche. Furthermore, current and future mobilizing agents will be discussed.

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Section: Nonsteroidal Anti-inflammatory Drugsmentioning

confidence: 99%

Cytokine‐induced hematopoietic stem and progenitor cell mobilization: unraveling interactions between stem cells and their niche

Kruijf

Fibbe

Pel

2019

Annals of the New York Academy of Sciences

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“…Another CXCR4 inhibitor, T-140, mobilizes HSPCs and also erythroblasts in murine models and displays synergy with G-CSF [96]. To date, more chemical inhibitors have been developed as a means to mobilize HSPCs from bone marrow into blood and are in part clinically tested [97]. Another way, which is also followed clinically, is mobilization of HSPCs by functionblocking antibodies or chemicals directed against integrins, mediating HSPC adhesion to niche cells.…”

Section: Pharmacological Inhibition Of Hspc-niche Interactions Leadinmentioning

confidence: 99%

Current Developments in Mobilization of Hematopoietic Stem and Progenitor Cells and Their Interaction with Niches in Bone Marrow

Richter

Forssmann

Henschler

2017

Transfus Med Hemother

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The clinical application of hematopoietic stem and progenitor cells (HSPCs) has evolved from a highly experimental stage in the 1980s to a currently clinically established treatment for more than 20,000 patients annually who suffer from hematological malignancies and other severe diseases. Studies in numerous murine models have demonstrated that HSPCs reside in distinct niches within the bone marrow environment. Whereas transplanted HSPCs travel through the bloodstream and home to sites of hematopoiesis, HSPCs can be mobilized from these niches into the blood either physiologically or induced by pharmaceutical drugs. Firstly, this review aims to give a synopsis of milestones defining niches and mobilization pathways for HSPCs, including the identification of several cell types involved such as osteoblasts, adventitial reticular cells, endothelial cells, monocytic cells, and granulocytic cells. The main factors that anchor HSPCs in the niche, and/or induce their quiescence are vascular cell adhesion molecule(VCAM)-1, CD44, hematopoietic growth factors, e.g. stem cell factor (SCF) and FLT3 Ligand, chemokines including CXCL12, growth-regulated protein beta and IL-8, proteases, peptides, and other chemical transmitters such as nucleotides. In the second part of the review, we revise the current understanding of HSPC mobilization. Here, we discuss which mechanisms found to be active in HSPC mobilization correspond to the mechanisms relevant for HSPC interaction with niche cells, but also deal with other mediators and signals that target individual cell types and receptors to mobilize HSPCs. A multitude of questions remain to be addressed for a better understanding of HSPC biology and its implications for therapy, including more comprehensive concepts for regulatory circuits such as calcium homeostasis and parathormone, metabolic regulation such as by leptin, the significance of autonomic nervous system, the consequences of alteration of niches in aged patients, or the identification of more easily accessible markers to better predict the efficiency of HSPC mobilization.

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“…Approximately 20% of the MM patients undergoing mobilization of peripheral blood stem cells (PBSC) with granulocyte colony stimulating factor (G‐CSF) alone, or G‐CSF plus chemotherapy are not able to mobilize the minimum number of CD‐34+ stem cells (2 × 10 6 CD34 cells/kg) recommended for transplant . Plerixafor (P) is a reversible direct antagonist of CXCR4/SDF‐1, which prevents binding of its ligand CXCL12 and induces mobilization of cells expressing this receptor, including hematopoietic stem and progenitor cells (HSPCs) . Based on a pivotal randomized phase‐3 study comparing G‐CSF vs G‐CSF plus plerixafor, plerixafor has been approved for mobilization of PBSCs in MM by the Food and Drug Administration .…”

Section: Introductionmentioning

confidence: 99%

Clinical outcomes of multiple myeloma patients who undergo autologous hematopoietic stem cell transplant with G‐CSF or G‐CSF and plerixafor mobilized grafts

et al. 2019

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Impact of Plerixafor (P) mobilized stem cells on immune reconstitution, such as absolute lymphocyte count at day 30 (ALC30), and on long-term outcomes of Multiple Myeloma (MM) patients undergoing autologous stem cell transplant (ASCT) has not been well established. We evaluated total of 469 patients mobilized with G-CSF (G) alone, and 141 patients mobilized with G-CSF plus plerixafor (G+ P). Patients only received plerixafor if they had peripheral blood CD34 + blood count <20/μL on first planned day of collection. Primary endpoint, ALC30, was 1.3 K/μL (range, 0.1-4.5) and 1.2 K/μL (range, 0.1-5.1) for G and G + P, respectively (P =. 61). The median PFS was 2.5 years (95% CI, 2.1-3.2) and 2.8 years (95% CI, 2.0-3.3) for G and G + P, respectively (HR: 1.13; 95% CI, 0.84-1.50; P = .42). The median OS was 6.1 years (95% CI, 4.6-NR) for G group compared to 3.7 years (95% CI, 3.2-NR) for the G + P group (HR: 1.64; 95% CI, 1.12-2.40; P = .01). The median follow-up time for OS was 2.53 years (95% CI, 2.13-2.99) and 1.59 years (95% CI, 1.17-2.02) for G and G+ P group, respectively. In this large retrospective analysis of MM patients mobilized with G-CSF vs G-CSF + P, there was no significant difference in lymphocyte recovery or PFS. There was an overall survival difference in patients who were poor mobilizers and could not be mobilized with G-CSF alone.

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New agents in HSC mobilization

Cited by 46 publications

References 108 publications

Cytokine‐induced hematopoietic stem and progenitor cell mobilization: unraveling interactions between stem cells and their niche

Cytokine‐induced hematopoietic stem and progenitor cell mobilization: unraveling interactions between stem cells and their niche

Current Developments in Mobilization of Hematopoietic Stem and Progenitor Cells and Their Interaction with Niches in Bone Marrow

Clinical outcomes of multiple myeloma patients who undergo autologous hematopoietic stem cell transplant with G‐CSF or G‐CSF and plerixafor mobilized grafts

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