The Mobilization Effects of G-CSF, GM-CSF and Darbepoetin-α for Allogeneic Peripheral Blood Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4932-4932
Author(s):  
Shi Nae Kim ◽  
Sang Kyun Sohn ◽  
Jong Gwang Kim ◽  
Yee Soo Kim ◽  
Yoon Young Cho ◽  
...  
Keyword(s):  
Stem Cells ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Red Blood Cell Transfusion ◽  
Combination Group ◽  
Combination Regimen ◽  
Cell Recovery ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Cell Counts

Abstract Background: Granulocyte colony-stimulating-factor (G-CSF) is widely used for the mobilization of hematopoietic stem cells from normal donors. It has been reported that the addition of granulocyte-macrophage CSF (GM-CSF) to G-CSF mobilized more primitive CD34+ subsets than did G-CSF alone. We investigated the effects of combination regimen (GM-CSF + G-CSF + darbepoetin-α) for mobilization in normal healthy donors and compared its efficacy in mobilizing stem cells with G-CSF alone. Methods: Thirty donors were randomly assigned to one of the following regimens for mobilization: G-CSF group (G-CSF 5ug/kg/day for 5 to 7 days) and combination group (GM-CSF 10ug/kg/day on 1st and 2nd days, G-CSF 5ug/kg/day for 5 to 7 days and 40mg of dalbepoetin-α on day 1) Results: The counts of MNC and CD34+ cells/kg were not significantly different between two groups (p=0.129 and p=0.651). The CD3+ cell counts per kilogram were 3.48±1.45×108/kg and 2.54±0.94×108/kg in a G-CSF group and a combination group, respectively (p=0.04). Red blood cell transfusion requirement was not different between two groups (p=0.469). The median time to neutrophil and platelet engraftment was 12.5 vs. 12.0 days (p=0.443) and 11.5 vs. 11.0 days (p=0.752). Red blood cell recovery was 7.5 days and 7 days in G-CSF group and combination group, respectively (p=0.231). Grade II–IV acute graft-versus-host disease (GVHD) was observed in 20% in G-CSF group and 13% in combination group (p=0.50). Conclusion: The combination regimen was not superior to G-CSF alone in terms of acute GVHD and CD34+ cell dose. But CD3+ cell count was significantly lower in combination regimen group. The role of lower CD3+ cells in the graft need to be elucidated in the future.

Telomere Elongation In Vivo and Clinical Response Upon Androgen Treatment in a Patient with Aplastic Anemia and a Heterozygous hTERT Gene Mutation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3427-3427
Author(s):  
Tim H Brümmendorf ◽  
Patrick Ziegler ◽  
Jamil Akkad ◽  
Ute Brassat ◽  
Lucia Vankann ◽  
...  
Keyword(s):  
Blood Cell ◽  
Aplastic Anemia ◽  
Telomere Length ◽  
Red Blood Cell ◽  
Red Blood Cell Transfusion ◽  
Hematopoietic Stem ◽  
Telomere Elongation ◽  
Htert Gene ◽  
Androgen Treatment

Abstract Abstract 3427 Telomere length both reflects and limits the replicative life-span of normal somatic cells and critically shortened telomeres are associated with a variety of disease states. In patients with aplastic anemia telomere lengths in granulocytes and lymphocytes can be found to be significantly shorter as compared to age-adjusted controls. Telomere shortening in peripheral blood cells therby mirrors telomere shortening in the underlying hematopoietic stem cell reserve, which can be severely diminished in acquired bone marrow failure syndromes. Genetic aberrations such as mutations in the gene for dyskerin or in subunits of the telomerase-complex such as the RNA subunit hTERC or mutations in the human telomerase gene (hTERT) have been described and linked to critically short telomeres found in blood cells. We report here on a 51 year old male patient with moderate aplastic anemia (AA) and a non-synonymous variation of codon 1062 of the hTERT gene (pAla1062Thr). Cells with deficient expression of glycosylphosphatidylinositol-anchored proteins (GPI-AP), i.e. cells with a PNH phenotype, were detected (1.2% of erythrocytes, 8% of reticulocytes and 15% of neutrophils). The patient was found to have dramatically shortened telomere length below 1% percentile of normal individuals both in lymphocytes (4.28 +/− 0.02 kbp) and granulocytes (4.14 +/−0.1 kbp). Based on the clinical presentation (i.e. predominance of red blood cell transfusion dependence and thrombocytopenia, but absence of immediate risk e.g. of infections or bleeding) we decided to initiate androgen treatment rather than to initiate standard immunosuppression. The initially red blood cell transfusion dependent and thrombocytopenic patient became completely red blood cell transfusion independent after twelve months of ongoing androgen treatment. A significant proportion of GPI-AP deficient red cells and reticulocytes could no longer be detected and only a very small proportion of GPI-AP deficient granulocytes (<1%) persisted. The clinical and hematological improvement during androgen therapy was mirrored by a continuous and persistent lengthening of telomere length in total peripheral blood mononuclear cells (MNCs) measured by qPCR as well as in both leukocyte subpopulations measured by Flow-FISH. To our knowledge, this represents the first case of sustained telomere elongation in hematopoietic stem cells induced by a pharmacological approach in vivo. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Megakaryocyte TGFβ1 Partitions Hematopoiesis into Immature Progenitor/Stem Cells and Maturing Precursors

2019 ◽  
Author(s):  
Silvana Di Giandomenico ◽  
Pouneh Kermani ◽  
Nicole Molle ◽  
Maria Mia Yabut ◽  
Ghaith Abu Zeinah ◽  
...  
Keyword(s):  
Stem Cells ◽  
Blood Cell ◽  
Progenitor Cells ◽  
Peripheral Blood Cell ◽  
Erythroid Progenitors ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Erythroid Precursors ◽  
New Strategy ◽  
Stem And Progenitor Cells

SummaryErythropoiesis is a multiweek program coupling massive proliferation with progressive cellular differentiation ultimately enabling a limited number of hematopoietic stem cells (HSCs) to yield millions of erythrocytes per second1. Erythropoietin (Epo) is essential for red blood cell (RBC) production but this cytokine acts well after irreversible commitment of hematopoietic progenitor cells (HPCs) to an erythroid fate. It is not known if terminal erythropoiesis is tethered to the pool of available immature hematopoietic stem and progenitor cells (HSPCs). We now report that megakaryocyte-derived TGFβ1 compartmentalizes hematopoiesis by coupling HPC numbers to production of mature erythrocytes. Genetic deletion of TGFβ1 specifically in megakaryocytes (TGFβ1ΔMk/ΔMk) increased functional HSPCs including committed erythroid progenitors, yet total bone marrow and spleen cellularity and peripheral blood cell counts were entirely normal. Instead, excess erythroid precursors underwent apoptosis, predominantly those erythroblasts expressing the Epo receptor (Epor) but not Kit. Despite there being no deficiency of plasma Epo inTGFβ1ΔMk/ΔMkmice, exogenous Epo rescued survival of excess erythroid precursors and triggered exuberant erythropoiesis. In contrast, exogenous TGFβ1 caused anemia and failed to rescue erythroid apoptosis despite its ability to restore downstream TGFβ-mediated Smad2/3 phosphorylation in HSPCs. Thus, megakaryocytic TGFβ1 regulates the size of the pool of immature HSPCs and in so doing, improves the efficiency of erythropoiesis by governing the feed of lineage-committed erythroid progenitors whose fate is decided by extramedullary renal Epo-producing cells sensing the need for new RBCs. Independent manipulation of distinct immature Epo-unresponsive HSPCs within the hematopoietic compartments offers a new strategy to overcome chronic anemias or possibly other cytopenias.

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