Combination of Granulocyte Colony-Stimulating Factor and Low-Dose Cytosine Arabinoside Further Enhances Myeloid Differentiation in Leukemia Cells in Vitro

Abstract Objective To explore the efficiency and safety of Low-dose Cytosine arabinoside and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) for patients with refractory and relapsed adult acute lymphocytic leukemia (ALL). Methods We treated 10 patients of refractory and relapsed adult ALL with CAG regimen (median age 28 years, range 17–58, male 5, female 5). The regimen consisted of low-dose cytosine arabinoside (10mg/m2 q12h, day1to14), aclarubicin (10mg/day, day1to8), and granulocyte colony-stimulating factor (G-CSF) (200 μg/m2/day). Result 8/10 patients (80%) achieved complete remission (CR) after one course, including 4 out of 5 refractory and 4 out of 5 relapsed patients. 1 patient who relapsed after the first course, then achieved CR again after the second course. 6 of the 8 complete remission received consolidation therapy with the CAG regimen or other regimens. Toxic effects were very rare and mainly consisted of neutropenia and thrombocytopenia due to myelosuppression; 8 of all patients had neutropenia or thrombocytopenia that exceeded WHO grade II. However, severe non-hematologic toxicity included nausea and vomiting (WHO grade ≥III) was characteristically rare. Conclusion CAG regimen is an effective and safety in the treatment of refractory and relapsed ALL.

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Intermittent Exposure of Primitive Quiescent Chronic Myeloid Leukemia Cells to Granulocyte-Colony Stimulating Factor In vitro Promotes their Elimination by Imatinib Mesylate

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-05-0429 ◽

2006 ◽

Vol 12 (2) ◽

pp. 626-633 ◽

Cited By ~ 67

Author(s):

Heather G. Jørgensen ◽

Mhairi Copland ◽

Elaine K. Allan ◽

Xiaoyan Jiang ◽

Allen Eaves ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Imatinib Mesylate ◽

Myeloid Leukemia ◽

Leukemia Cells ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Intermittent Exposure ◽

Stimulating Factor

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Effect of human recombinant granulocyte colony-stimulating factor on induction of myeloid leukemias by X-irradiation in mice

Blood ◽

10.1182/blood.v82.7.2163.bloodjournal8272163 ◽

1993 ◽

Vol 82 (7) ◽

pp. 2163-2168 ◽

Cited By ~ 1

Author(s):

Y Kawase ◽

M Akashi ◽

H Ohtsu ◽

Y Aoki ◽

A Akanuma ◽

...

Keyword(s):

Myeloid Leukemia ◽

Whole Body ◽

Leukemia Cells ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Myeloid Leukemias ◽

Fab Classification ◽

Radiation Induced ◽

Stimulating Factor

Hematopoietic suppression is one of the serious problems induced by whole body irradiation. Granulocyte colony-stimulating factor (G-CSF) stimulates the progenitors of granulocytes and accelerates their recovery from bone marrow suppression induced by cytotoxic chemotherapy or radiation. On the other hand, G-CSF stimulates proliferation of myeloid leukemia cells as well as normal granulocytes in vitro. We designed a method to determine if G-CSF affects the incidence of myeloid leukemias induced by irradiation and the types of leukemias induced according to the French-American-British (FAB) classification in RFM/MsNrs mice. Administration of G-CSF (2 micrograms/d for 7 days) after a single 3-Gy irradiation significantly increased the number of peripheral blood neutrophils as compared with those in control mice. Even after discontinuation of G-CSF, both the total leukocyte and neutrophil counts increased to day 10, and their levels remained elevated until day 14. The incidence of myeloid leukemia in mice exposed to a single 3-Gy irradiation was 18.6% (38 of 204), and treatment with G-CSF did not increase the incidence (15.7% [32 of 204]). In the mice with radiation-induced leukemia, those receiving G- CSF had a mean survival time of 357 days, whereas those not receiving the factor survived for 349 days. There was no significant difference of survivals between the two groups. Most of the radiation-induced leukemias in the two groups were M1 or M2, according to the FAB classification; no characteristic difference was observed among the types of leukemias. Although G-CSF stimulated the leukemia cells in vitro, G-CSF administration after irradiation did not increase the occurrence of radiation-induced myeloid leukemias. Our results show that administration of G-CSF effectively accelerates neutrophil recovery from irradiation-induced hematopoietic injury and does not enhance the induction of myeloid leukemia in RFM/MsNrs mice by irradiation.

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Glucocorticoids Dose-Dependently Increase Plasma Levels of Granulocyte Colony Stimulating Factor in Man

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.3.4802 ◽

1998 ◽

Vol 83 (3) ◽

pp. 1037-1040 ◽

Cited By ~ 17

Author(s):

Bernd Jilma ◽

Petra Stohlawetz ◽

Thomas Pernerstorfer ◽

Hans-Georg Eichler ◽

Claudia Müllner ◽

...

Keyword(s):

Plasma Levels ◽

Low Dose ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Double Blind ◽

Healthy Men ◽

Gm Csf ◽

Csf Levels ◽

Stimulating Factor

Glucocorticoids increase neutrophil counts by decreasing the margination of neutrophils and mobilizing neutrophils from the bone marrow pool. The mechanisms for these effects however are not fully elucidated, but it has been demonstrated that dexamethasone enhances release of colony stimulating factor (G-CSF) in-vitro. We therefore hypothesized, that dexamethasone may increase plasma levels of G-CSF. A double blind, randomized, placebo-controlled, three-way cross-over trial was conducted in nine healthy men. Every subject received four identical infusions of saline, 0.04 mg/kg or 1.0 mg/kg dexamethasone during three observation periods of 48 hours each. The low dose of dexamethasone increased G-CSF levels from a baseline of 15.5 ng/L (CI: 10.6–20.4) by 240% (CI: 115–366%) at 24 hours. The high dexamethasone dose increased G-CSF levels from a baseline of 12.3 ng/L (CI: 9.7–14.9) by 871% (CI: 592–1149%) at 24 hours (P = 0.008 for all comparisons). No further increase was observed at 48 hours but the effect was less pronounced (P < 0.008 and P = 0.08 for the high and the low dose of dexamethasone, respectively). Granulocyte-macrophage-CSF (GM-CSF) levels were below the assay’s detection limit of 0.36 ng/L in all subjects. In conclusion, dexamethasone dose dependently increases G-CSF levels in healthy men, an effect which may account for some of its effects on neutrophils.

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Effect of human recombinant granulocyte colony-stimulating factor on induction of myeloid leukemias by X-irradiation in mice

Blood ◽

10.1182/blood.v82.7.2163.2163 ◽

1993 ◽

Vol 82 (7) ◽

pp. 2163-2168 ◽

Cited By ~ 3

Author(s):

Y Kawase ◽

M Akashi ◽

H Ohtsu ◽

Y Aoki ◽

A Akanuma ◽

...

Keyword(s):

Myeloid Leukemia ◽

Whole Body ◽

Leukemia Cells ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Myeloid Leukemias ◽

Fab Classification ◽

Radiation Induced ◽

Stimulating Factor

Abstract Hematopoietic suppression is one of the serious problems induced by whole body irradiation. Granulocyte colony-stimulating factor (G-CSF) stimulates the progenitors of granulocytes and accelerates their recovery from bone marrow suppression induced by cytotoxic chemotherapy or radiation. On the other hand, G-CSF stimulates proliferation of myeloid leukemia cells as well as normal granulocytes in vitro. We designed a method to determine if G-CSF affects the incidence of myeloid leukemias induced by irradiation and the types of leukemias induced according to the French-American-British (FAB) classification in RFM/MsNrs mice. Administration of G-CSF (2 micrograms/d for 7 days) after a single 3-Gy irradiation significantly increased the number of peripheral blood neutrophils as compared with those in control mice. Even after discontinuation of G-CSF, both the total leukocyte and neutrophil counts increased to day 10, and their levels remained elevated until day 14. The incidence of myeloid leukemia in mice exposed to a single 3-Gy irradiation was 18.6% (38 of 204), and treatment with G-CSF did not increase the incidence (15.7% [32 of 204]). In the mice with radiation-induced leukemia, those receiving G- CSF had a mean survival time of 357 days, whereas those not receiving the factor survived for 349 days. There was no significant difference of survivals between the two groups. Most of the radiation-induced leukemias in the two groups were M1 or M2, according to the FAB classification; no characteristic difference was observed among the types of leukemias. Although G-CSF stimulated the leukemia cells in vitro, G-CSF administration after irradiation did not increase the occurrence of radiation-induced myeloid leukemias. Our results show that administration of G-CSF effectively accelerates neutrophil recovery from irradiation-induced hematopoietic injury and does not enhance the induction of myeloid leukemia in RFM/MsNrs mice by irradiation.

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