Treatment of Clozapine- and Molindone-Induced Agranulocytosis with Granulocyte Colony-Stimulating Factor

1993 ◽  
Vol 27 (10) ◽  
pp. 1190-1192 ◽  
Author(s):  
Charles B. Geibig ◽  
Louis W. Marks
Keyword(s):  
Bone Marrow ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Short Term ◽  
Drug Induced ◽  
Clozapine Therapy ◽  
Case Summary ◽  
Wbc Count ◽  
Stimulating Factor

OBJECTIVE: To report a case of clozapine- and molindone-induced agranulocytosis and to discuss treatment using filgrastim, a granulocyte colony-stimulating factor. CASE SUMMARY: A 64-year-old woman who had been on long-term clozapine therapy for schizophrenia was hospitalized with presumed drug-induced agranulocytosis. She had also been on short-term molindone therapy. A bone marrow biopsy and the initial white blood cell (WBC) count were consistent with drug-induced agranulocytosis. Following seven days of treatment with subcutaneous filgrastim 300 μg/d, her absolute neutrophil count was above 500 × 106/L. DISCUSSION: Reports in the literature discussing antipsychotic drug-induced agranulocytosis are reviewed. A relationship between treatment with filgrastim and WBC response is postulated. CONCLUSIONS: Filgrastim may be useful in ameliorating the effects of clozapine- and molindone-induced agranulocytosis.

scholarly journals Effects of recombinant human granulocyte colony-stimulating factor (CSF), human granulocyte macrophage-CSF, and gibbon interleukin-3 on hematopoiesis in human long-term bone marrow culture

Blood ◽  
1990 ◽  
Vol 75 (11) ◽  
pp. 2118-2129 ◽  
Author(s):  
LH Coutinho ◽  
A Will ◽  
J Radford ◽  
R Schiro ◽  
NG Testa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factors ◽  
Bone Marrow Culture ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Nonadherent Cells ◽  
Stimulating Factor

We have studied the effects of recombinant human granulocyte colony- stimulating factor (rhG-CSF), hG macrophage-CSF (hGM-CSF), and gibbon interleukin-3 (gIL-3) on cell proliferation and differentiation in human long-term bone marrow culture (LTBMC). hG-CSF induced a maximal increase of 2.3-fold in both total nonadherent cells and GM cluster- forming cells, but only an increase of 1.7-fold in GM-colony-forming cell (GM-CFC) numbers, influencing mainly neutrophil differentiation. Cultures treated with hGM-CSF demonstrated a peak of 12.8-, 21- and 3.2- fold elevations in total nonadherent cells, cluster, and GM-CFC, respectively, and influenced differentiation of neutrophils, monocytes, eosinophils, and lymphocytes. Cultures treated with gIL-3 demonstrated the largest expansion in the GM-CFC population, reaching a maximum of 5.3-fold in relation to that of unstimulated controls. IL-3 treatment also increased the numbers of GM clusters and mature cells (including all myeloid cells and lymphocytes) 7.8- and 4.8-fold, respectively. Similar quantitative and qualitative changes were induced by G-CSF, GM- CSF, and IL-3 in LTBMCs of patients in remission after treatment for acute lymphoblastic leukemia or Hodgkin's lymphoma. Overall, the expansion of GM progenitor cells in cultures treated with growth factors was larger in the adherent cell layer than in the nonadherent cell fraction. In addition, hGM-CSF, gIL-3, and hG-CSF to a less extent, increased the cycling rates of GM-CFC progenitors located in the adherent layer. These results indicate that hG-CSF is a much less potent stimulus of hematopoiesis in LTBMC than the other CSFs assayed, and that the increases in cell production after treatment with G-CSF, GM-CSF, or IL-3 may be achieved by primary expansion of different cell populations within the hierarchy of the hematopoietic system. The effects of the growth factors were transient and the longevity of hematopoiesis in the cultures was not altered, suggesting that treatment with IL-3, GM-CSF, or G-CSF had not compromised the ability of primitive cells to give rise to mature cells. This indicates that the stromal microenvironment in LTBMC can override potential differentiation-inducing activities of the CSFs.

scholarly journals Effects of recombinant human granulocyte colony-stimulating factor (CSF), human granulocyte macrophage-CSF, and gibbon interleukin-3 on hematopoiesis in human long-term bone marrow culture

Blood ◽  
1990 ◽  
Vol 75 (11) ◽  
pp. 2118-2129 ◽  
Author(s):  
LH Coutinho ◽  
A Will ◽  
J Radford ◽  
R Schiro ◽  
NG Testa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factors ◽  
Bone Marrow Culture ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Nonadherent Cells ◽  
Stimulating Factor

Abstract We have studied the effects of recombinant human granulocyte colony- stimulating factor (rhG-CSF), hG macrophage-CSF (hGM-CSF), and gibbon interleukin-3 (gIL-3) on cell proliferation and differentiation in human long-term bone marrow culture (LTBMC). hG-CSF induced a maximal increase of 2.3-fold in both total nonadherent cells and GM cluster- forming cells, but only an increase of 1.7-fold in GM-colony-forming cell (GM-CFC) numbers, influencing mainly neutrophil differentiation. Cultures treated with hGM-CSF demonstrated a peak of 12.8-, 21- and 3.2- fold elevations in total nonadherent cells, cluster, and GM-CFC, respectively, and influenced differentiation of neutrophils, monocytes, eosinophils, and lymphocytes. Cultures treated with gIL-3 demonstrated the largest expansion in the GM-CFC population, reaching a maximum of 5.3-fold in relation to that of unstimulated controls. IL-3 treatment also increased the numbers of GM clusters and mature cells (including all myeloid cells and lymphocytes) 7.8- and 4.8-fold, respectively. Similar quantitative and qualitative changes were induced by G-CSF, GM- CSF, and IL-3 in LTBMCs of patients in remission after treatment for acute lymphoblastic leukemia or Hodgkin's lymphoma. Overall, the expansion of GM progenitor cells in cultures treated with growth factors was larger in the adherent cell layer than in the nonadherent cell fraction. In addition, hGM-CSF, gIL-3, and hG-CSF to a less extent, increased the cycling rates of GM-CFC progenitors located in the adherent layer. These results indicate that hG-CSF is a much less potent stimulus of hematopoiesis in LTBMC than the other CSFs assayed, and that the increases in cell production after treatment with G-CSF, GM-CSF, or IL-3 may be achieved by primary expansion of different cell populations within the hierarchy of the hematopoietic system. The effects of the growth factors were transient and the longevity of hematopoiesis in the cultures was not altered, suggesting that treatment with IL-3, GM-CSF, or G-CSF had not compromised the ability of primitive cells to give rise to mature cells. This indicates that the stromal microenvironment in LTBMC can override potential differentiation-inducing activities of the CSFs.

Use of Granulocyte Colony-Stimulating Factor in the Treatment of Pancytopenia Secondary to Colchicine Overdose

1992 ◽  
Vol 26 (9) ◽  
pp. 1087-1088 ◽  
Author(s):  
Roya Katz ◽  
Linda C. Chuang ◽  
Jacqueline D. Sutton
Keyword(s):  
Bone Marrow ◽  
Suicide Attempt ◽  
Elevated Liver Enzyme ◽  
Subcutaneous Administration ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Bone Marrow Depression ◽  
Case Summary ◽  
Colchicine Overdose ◽  
Stimulating Factor

OBJECTIVE: To report a case of pancytopenia following colchicine overdose and to discuss the use of granulocyte colony-stimulating factor (G-CSF) for treating this severe complication. CASE SUMMARY: A 19-year-old man developed pancytopenia four days after ingestion of approximately 50–60 0.6-mg colchicine tablets in a suicide attempt. His pancytopenia resolved after subcutaneous administration of one 300-μg dose of G-CSF. The patient recovered from his other multiorgan disturbances during his hospitalization and was discharged from the hospital with elevated liver enzyme concentrations. CONCLUSIONS: Colchicine overdose is rare, but can be fatal. The use of G-CSF appears to be beneficial in alleviating bone marrow depression in colchicine overdose situations.

scholarly journals Mobilization of long-term hematopoietic reconstituting cells in mice by the combination of stem cell factor plus granulocyte colony-stimulating factor

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 795-799 ◽  
Author(s):  
XQ Yan ◽  
R Briddell ◽  
C Hartley ◽  
G Stoney ◽  
B Samal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Short Term ◽  
Term Survival ◽  
Group A ◽  
Group B ◽  
Stimulating Factor

Abstract In this study, we have compared the ability of recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone and the combination of low doses of recombinant rat pegylated stem cell factor (rrSCF-PEG) plus rhG-CSF to mobilize peripheral blood progenitor cells (PBPCs) with long-term engrafting potential. Female recipient irradiated mice were transplanted with PBPCs from male mice that were mobilized with rhG-CSF alone (group A) or rrSCF-PEG plus rhG-CSF (group B). As previously shown, greater short-term survival resulted in group B compared with group A, with 80% and 40% survival at 30 days posttransplant, respectively. Both groups of animals showed long-term donor-derived engraftment in greater than 95% of animals, as determined by quantitative specific polymerase chain reaction amplification of a Y chromosome sequence from whole blood of the mice at 6 to 12 months posttransplantation. Analysis of individual granulocyte-macrophage colonies, picked up from semisolid methylcellulose culture of bone marrow cells from transplanted mice, resulted in detection of donor- derived DNA in 98% of colonies from group B mice compared with 81% from group A mice. These data show that cells with long-term potential are mobilized by rhG-CSF alone and the combination of rrSCF-PEG plus rhG- CSF. Furthermore, an increased number of cells with short-term and long- term engraftment potential was obtained with rrSCF-PEG plus rhG-CSF compared with rhG-CSF alone.

scholarly journals Pure White Cell Aplasia and Necrotizing Myositis

2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
Peter Geon Kim ◽  
Joome Suh ◽  
Max W. Adelman ◽  
Kwadwo Oduro ◽  
Erik Williams ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Liver Injury ◽  
White Cell ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Drug Induced ◽  
Hematologic Disorder ◽  
Necrotizing Myositis ◽  
Stimulating Factor ◽  
Pure White

Pure white cell aplasia (PWCA) is a rare hematologic disorder characterized by the absence of neutrophil lineages in the bone marrow with intact megakaryopoiesis and erythropoiesis. PWCA has been associated with autoimmune, drug-induced, and viral exposures. Here, we report a case of a 74-year-old female who presented with severe proximal weakness without pain and was found to have PWCA with nonspecific inflammatory necrotizing myositis and acute liver injury on biopsies. These findings were associated with a recent course of azithromycin and her daily use of a statin. Myositis improved on prednisone but PWCA persisted. With intravenous immunoglobulin and granulocyte-colony stimulating factor therapies, her symptoms and neutrophil counts improved and were sustained for months.

scholarly journals G-CSF–mediated thrombopoietin release triggers neutrophil motility and mobilization from bone marrow via induction of Cxcr2 ligands

Blood ◽  
2011 ◽  
Vol 117 (16) ◽  
pp. 4349-4357 ◽  
Author(s):  
Anja Köhler ◽  
Katia De Filippo ◽  
Mike Hasenberg ◽  
Cindy van den Brandt ◽  
Emma Nye ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Single Injection ◽  
Neutrophil Granulocytes ◽  
Clinical Grade ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Short Term ◽  
Stimulating Factor

Abstract Emergency mobilization of neutrophil granulocytes (neutrophils) from the bone marrow (BM) is a key event of early cellular immunity. The hematopoietic cytokine granulocyte-colony stimulating factor (G-CSF) stimulates this process, but it is unknown how individual neutrophils respond in situ. We show by intravital 2-photon microscopy that a systemic dose of human clinical-grade G-CSF rapidly induces the motility and entry of neutrophils into blood vessels within the tibial BM of mice. Simultaneously, the neutrophil-attracting chemokine KC (Cxcl1) spikes in the blood. In mice lacking the KC receptor Cxcr2, G-CSF fails to mobilize neutrophils and antibody blockade of Cxcr2 inhibits the mobilization and induction of neutrophil motility in the BM. KC is expressed by megakaryocytes and endothelial cells in situ and is released in vitro by megakaryocytes isolated directly from BM. This production of KC is strongly increased by thrombopoietin (TPO). Systemic G-CSF rapidly induces the increased production of TPO in BM. Accordingly, a single injection of TPO mobilizes neutrophils with kinetics similar to G-CSF, and mice lacking the TPO receptor show impaired neutrophil mobilization after short-term G-CSF administration. Thus, a network of signaling molecules, chemokines, and cells controls neutrophil release from the BM, and their mobilization involves rapidly induced Cxcr2-mediated motility controlled by TPO as a pacemaker.

scholarly journals Mobilization of long-term hematopoietic reconstituting cells in mice by the combination of stem cell factor plus granulocyte colony-stimulating factor

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 795-799 ◽  
Author(s):  
XQ Yan ◽  
R Briddell ◽  
C Hartley ◽  
G Stoney ◽  
B Samal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Short Term ◽  
Term Survival ◽  
Group A ◽  
Group B ◽  
Stimulating Factor

In this study, we have compared the ability of recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone and the combination of low doses of recombinant rat pegylated stem cell factor (rrSCF-PEG) plus rhG-CSF to mobilize peripheral blood progenitor cells (PBPCs) with long-term engrafting potential. Female recipient irradiated mice were transplanted with PBPCs from male mice that were mobilized with rhG-CSF alone (group A) or rrSCF-PEG plus rhG-CSF (group B). As previously shown, greater short-term survival resulted in group B compared with group A, with 80% and 40% survival at 30 days posttransplant, respectively. Both groups of animals showed long-term donor-derived engraftment in greater than 95% of animals, as determined by quantitative specific polymerase chain reaction amplification of a Y chromosome sequence from whole blood of the mice at 6 to 12 months posttransplantation. Analysis of individual granulocyte-macrophage colonies, picked up from semisolid methylcellulose culture of bone marrow cells from transplanted mice, resulted in detection of donor- derived DNA in 98% of colonies from group B mice compared with 81% from group A mice. These data show that cells with long-term potential are mobilized by rhG-CSF alone and the combination of rrSCF-PEG plus rhG- CSF. Furthermore, an increased number of cells with short-term and long- term engraftment potential was obtained with rrSCF-PEG plus rhG-CSF compared with rhG-CSF alone.

scholarly journals Primitive Long-Term Culture Initiating Cells (LTC-ICs) in Granulocyte Colony-Stimulating Factor Mobilized Peripheral Blood Progenitor Cells Have Similar Potential for Ex Vivo Expansion as Primitive LTC-ICs in Steady State Bone Marrow

Blood ◽  
1997 ◽  
Vol 89 (11) ◽  
pp. 3991-3997 ◽  
Author(s):  
Felipe Prosper ◽  
Kirk Vanoverbeke ◽  
David Stroncek ◽  
Catherine M. Verfaillie
Keyword(s):  
Bone Marrow ◽  
Steady State ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hla Dr ◽  
Stimulating Factor

Abstract We have recently shown that more than 90% of long-term culture initiating cells (LTC-IC) mobilized in the peripheral blood (PB) of normal individuals express HLA-DR and CD38 antigens and can sustain hematopoiesis for only 5 weeks. However, 10% of LTC-IC in mobilized PB are CD34+HLA-DR− and CD34+CD38− and can sustain hematopoiesis for at least 8 weeks. We now examine the ex vivo expansion potential of CD34+HLA-DR+ cells (rich in mature LTC-IC) and CD34+HLA-DR− cells (rich in primitive LTC-IC) in granulocyte colony-stimulating factor (G-CSF ) mobilized PB progenitor cells (PBPC). Cells were cultured in contact with M2-10B4 cells (contact) or in transwells above M2-10B4 (noncontact) without and with interleukin-3 (IL-3) and macrophage inflammatory protein (MIP-1α) for 2 and 5 weeks. Progeny were evaluated for the presence of colony-forming cells (CFC) and LTC-IC. When CD34+HLA-DR+ PB cells were cultured in contact cultures without cytokines, a threefold expansion of CFC was seen at 2 weeks, but an 80% decrease in CFC was seen at week 5. Further, the recovery of LTC-IC at week 2 was only 17% and 1% at week 5. This confirms our previous observation that although CD34+HLA-DR+ mobilized PB cells can initiate long-term cultures, they are relatively mature and cannot sustain long-term hematopoiesis. In contrast, when CD34+HLA-DR− mobilized PB cells were cultured in contact cultures without cytokines, CFC expansion persisted until week 5 and 49% and 11% of LTC-IC were recovered at week 2 and 5, respectively. As we have shown for steady state bone marrow (BM) progenitors, recovery of LTC-IC was threefold higher when CD34+HLA-DR− PBPC were cultured in noncontact rather than contact cultures, and improved further when IL-3 and MIP-1α were added to noncontact cultures (96 ± 2% maintained at week 5). We conclude that although G-CSF mobilizes a large population of “mature” CD34+HLA-DR+ LTC-IC with a limited proliferative capacity, primitive CD34+HLA-DR− LTC-IC present in mobilized PB have similar characteristics as LTC-IC from steady state BM: (1) they can be maintained in noncontact cultures containing IL-3 and MIP-1α for at least 5 weeks; (2) they are subject to the same proliferation inhibitory influences of contact with stroma. Since the absolute number of primitive LTC-IC (week 8 LTC-IC) per mL of G-CSF mobilized PB is similar to that per mL of steady state BM, these studies further confirm that G-CSF mobilized PBPC may have similar long-term repopulating abilities as steady state BM.

scholarly journals PU.1 regulates the commitment of adult hematopoietic progenitors and restricts granulopoiesis

2005 ◽  
Vol 201 (9) ◽  
pp. 1487-1502 ◽  
Author(s):  
Aleksandar Dakic ◽  
Donald Metcalf ◽  
Ladina Di Rago ◽  
Sandra Mifsud ◽  
Li Wu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Progenitors ◽  
Adult Mice ◽  
Myeloid Progenitor ◽  
Myeloid Development ◽  
Stimulating Factor

Although the transcription factor PU.1 is essential for fetal lymphomyelopoiesis, we unexpectedly found that elimination of the gene in adult mice allowed disturbed hematopoiesis, dominated by granulocyte production. Impaired production of lymphocytes was evident in PU.1-deficient bone marrow (BM), but myelocytes and clonogenic granulocytic progenitors that are responsive to granulocyte colony-stimulating factor or interleukin-3 increased dramatically. No identifiable common lymphoid or myeloid progenitor populations were discernable by flow cytometry; however, clonogenic assays suggested an overall increased frequency of blast colony-forming cells and BM chimeras revealed existence of long-term self-renewing PU.1-deficient cells that required PU.1 for lymphoid, but not granulocyte, generation. PU.1 deletion in granulocyte-macrophage progenitors, but not in common myeloid progenitors, resulted in excess granulocyte production; this suggested specific roles of PU.1 at different stages of myeloid development. These findings emphasize the distinct nature of adult hematopoiesis and reveal that PU.1 regulates the specification of the multipotent lymphoid and myeloid compartments and restrains, rather than promotes, granulopoiesis.

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