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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/11/02 08:40:34」(JST)

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Sargramostim (marketed by Genzyme under the tradename Leukine) is a recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) that functions as an immunostimulator.^[1]

It is produced in yeast.^[2]

Therapeutic uses

Sargramostim is primarily used for myeloid reconstitution after autologous or allogeneic bone marrow transplantation. It is also used to treat neutropenia induced by chemotherapy during the treatment of acute myeloid leukemia. Sargramostim has recently shown promise in treating Crohn's disease and other GI inflammatory disorders. This medication is being investigated in trials to treat autoimmune pulmonary alveolar proteinosis (PAP).^[3] It is also being investigated in combination with oncolytic reovirus in brain cancer. ^[4]

Contraindications

Sargramostim should not be used in patients with excessive leukemic myeloid blasts in the bone marrow or peripheral blood (≥ 10%), in patients with known hypersensitivity to GM-CSF, yeast-derived products or any component of the product and for concomitant use with chemotherapy and radiotherapy.

History

The sequence of human GM-CSF was first identified in 1985 and soon three recominbant human GM-CSFs were produced, one in bacteria, one in mammalian cells, and one in yeast;^[5] Immunex developed GM-CSF manufactured in yeast into Leukine.^[6] Clinical trials of sargramostim were initiated in 1987;^[7] in that same year it was administered to six people as part of a compassionate-use protocol for the victims of cesium irradiation from the Goiânia accident.^[8]

It was approved by the FDA in March 1991 under the trade name Leukine for acceleration of white blood cell recovery following autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma, acute lymphocytic leukemia, or Hodgkin's disease.^[9] In November 1996, the FDA also approved sargramostim for treatment of fungal infections and replenishment of white blood cells following chemotherapy.^[10] A liquid formulation was approved in 1995.^[6] Immunex was acquired by Amgen in 2002.^[7] As part of the acquisition, Leukine was spun off to Berlex, which became Bayer HealthCare in 2007.^[6] In 2009, Genzyme acquired the rights to Leukine from Bayer, including the manufacturing facility in the Seattle area.^[7]^[11]^[12]

Liquid formulation - withdrawn

On January 23, 2008, Bayer informed healthcare professionals of the market withdrawal of the current liquid formulation of sargramostim. The liquid formulation was withdrawn because of an upward trend in spontaneous reports of adverse reactions, including syncope (fainting), which are temporally correlated with a change that was made to the formulation around April 2007 to include edetate disodium (EDTA).^[6] The upward trend in adverse reaction reporting rates had not been observed with the use of lyophilized sargramostim.^[13] The original liquid formulation without EDTA was returned to the market in the US in May 2008.^[14]

References

^ Kirman I, Belizon A, Balik E, et al. (2007). "Perioperative sargramostim (recombinant human GM-CSF) induces an increase in the level of soluble VEGFR1 in colon cancer patients undergoing minimally invasive surgery". European Journal of Surgical Oncology. 33 (10): 1169–1176. doi:10.1016/j.ejso.2007.03.014. PMID 17512160.
^ Beveridge RA, Miller JA, Kales AN, et al. (1998). "A comparison of efficacy of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in the therapeutic setting of chemotherapy-induced myelosuppression". Cancer Invest. 16 (6): 366–373. doi:10.3109/07357909809115775. PMID 9679526.
^ "Whole Lung Lavage (WLL)/Inhaled Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis (PAP). Phase II/III trial 2009-2013". Clinicaltrials.gov. Retrieved 2012-06-20.
^ "Wild-Type Reovirus in Combination With Sargramostim in Treating Younger Patients With High-Grade Recurrent or Refractory Brain Tumors.". Clinicaltrials.gov. Retrieved 2015-05-14.
^ Armitage, JO (15 December 1998). "Emerging applications of recombinant human granulocyte-macrophage colony-stimulating factor.". Blood. 92 (12): 4491–508. PMID 9845514.
^ ^a ^b ^c ^d Staff (May 2008). "Back to the Future: Original Liquid Leukine® Coming Soon" (PDF). Oncology Business Review.
^ ^a ^b ^c "Immunex Corporation". Company Histories & Profiles. FundingUniverse.com. Retrieved 12 November 2011.
^ Schmeck HM (1987-11-02). "Radiation Team Sent to Brazil Saves Two With a New Drug". New York Times. Retrieved 2012-06-20.
^ "Approval Summary for sargramostim". Oncology Tools. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. 1991-03-05. Archived from the original on 2007-09-29. Retrieved 20 September 2009.
^ "Newly Approved Drug Therapies (179): Leukine (sargramostim), Immunex". CenterWatch. Retrieved 2008-10-12.
^ "Bayer Healthcare Pharmaceuticals Plant, Snohomish County, Washington State". pharmaceutical-technology.com. Retrieved 12 November 2011.
^ "Genzyme and Bayer HealthCare Enter New Strategic Agreement". Genzyme. March 31, 2009. Retrieved 12 November 2011.
^ "MedWatch Safety Alerts for Human Medical Products" (PDF). Fda.gov. 2008-11-06. Retrieved 2012-07-07.
^ Chi, Judy (May 21, 2008). "Bayer launches Leukine without EDTA". Drug Topics.

External links

Leukine product website from Genzyme
Leukine prescribing information
Leukine Patient information
Leukine product information

UpToDate Contents

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1. 化学療法による好中球減少症を有する成人患者と、急性白血病、骨髄異形成症候群、造血細胞移植以外の病態を有する成人患者における顆粒球コロニー刺激因子の利用 use of granulocyte colony stimulating factors in adult patients with chemotherapy induced neutropenia and conditions other than acute leukemia myelodysplastic syndrome and hematopoietic cell transplantation
2. 成人の肺胞タンパク症の治療と予後 treatment and prognosis of pulmonary alveolar proteinosis in adults
3. 造血細胞移植後の造血の促進 hematopoietic support after hematopoietic cell transplantation
4. 敗血症に対する治験剤および無効剤 investigational and ineffective therapies for sepsis
5. クローン病の内科的マネージメントにおける試験研究治療 investigational therapies in the medical management of crohn disease

English Journal

Preexisting Levels of CD4 T Cells Expressing PD-1 Are Related to Overall Survival in Prostate Cancer Patients Treated with Ipilimumab.

Kwek SS1, Lewis J1, Zhang L2, Weinberg V3, Greaney SK1, Harzstark AL1, Lin AM1, Ryan CJ2, Small EJ2, Fong L4.
Cancer immunology research.Cancer Immunol Res.2015 Sep;3(9):1008-16. doi: 10.1158/2326-6066.CIR-14-0227. Epub 2015 May 12.
Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockade can induce tumor regression and improved survival in cancer patients. This treatment can enhance adaptive immune responses without an exogenous vaccine, but the immunologic biomarkers associated with improved clinical outcome in cancer pa
PMID 25968455

Single Institution Experience of Ipilimumab 3 mg/kg with Sargramostim (GM-CSF) in Metastatic Melanoma.

Luke JJ1, Donahue H2, Nishino M3, Giobbie-Hurder A4, Davis M2, Bailey N2, Ott PA5, Hodi FS5.
Cancer immunology research.Cancer Immunol Res.2015 Sep;3(9):986-91. doi: 10.1158/2326-6066.CIR-15-0066. Epub 2015 May 5.
Ipilimumab, 10 mg/kg with sargramostim (GM-CSF; GM), improved overall survival (OS) and safety of patients with advanced melanoma over ipilimumab in a randomized phase II trial. The FDA-approved dose of ipilimumab of 3 mg/kg has not been assessed with GM (IPI-GM). Consecutive patients treated with I
PMID 25943535

G-CSF and GM-CSF in Neutropenia.

Mehta HM1, Malandra M2, Corey SJ3.
Journal of immunology (Baltimore, Md. : 1950).J Immunol.2015 Aug 15;195(4):1341-9. doi: 10.4049/jimmunol.1500861.
G-CSF and GM-CSF are used widely to promote the production of granulocytes or APCs. The U.S. Food and Drug Administration approved G-CSF (filgrastim) for the treatment of congenital and acquired neutropenias and for mobilization of peripheral hematopoietic progenitor cells for stem cell transplantat
PMID 26254266

Japanese Journal

Sargramostim in patients with Crohn's disease : results of a phase 1-2 study

Journal of gastroenterology 44(6), 535-543, 2009-06-01
NAID 10025175442

Sargramostim for active Crohn's disease

N Engl J Med 352, 2193-2201, 2005
NAID 30022562670

Use of sargramostim (rh-GM-CSF) as adjunctive treatment of fluconazole-refractory oropharyngeal candidiasis in patients with AIDS : a pilot study

HIV Clin Trials 1, 23-29, 2000
NAID 30007778164

Related Pictures

★リンクテーブル★

リンク元	「サイトカイン」「サルグラモスチム」

「サイトカイン」

Sargramostim
Systematic (IUPAC) name
	Human granulocyte macrophage colony stimulating factor
Clinical data
AHFS/Drugs.com	Monograph
MedlinePlus	a693005
Legal status
Legal status	℞ (Prescription only);
Identifiers
CAS Number	83869-56-1
ATC code	L03AA09 (WHO)
DrugBank	DB00020
ChemSpider	none
UNII	5TAA004E22
ChEMBL	CHEMBL1201670
Chemical data
Formula	C639H1006N168O196S8
Molar mass	14434.5 g/mol
(what is this?) (verify)

　　[★]

cyto=cell kin(e)=small substance

ex. manikine

細胞が分泌する糖タンパク質で、生物活性(増殖・分化・タンパク産生誘導などを)を有するもの

英: cytokine, cytokines
関: サイトカイン受容体、インターロイキン、リンホカイン

生態情報伝達方式

傍分泌系、自己分泌系により情報を伝達する。局所ホルモンともいえる(ホルモンは血流を介して他臓器に働く)

産生細胞・機能による分類名

機能

機能	サブグループ	サイトカイン	標的	機能
炎症性サイトカイン	TNFファミリー	TNF-α	白血球、上皮細胞	活性化
	インターロイキン	IL-1	上皮細胞、リンパ球	活性化
		IL-6	種々の細胞	活性化
		IL-8	白血球	炎症部位遊走
T細胞の増殖・分化	インターロイキン	IL-2	T細胞	活性化。増殖
		IL-4	T細胞	増殖
		IL-4	Th2細胞	分化誘導
		IL-12	Th1細胞	分化誘導
	インターフェロン	IFN-γ	Th2細胞	分化抑制
B細胞の増殖・分化	インターロイキン	IL-2	B細胞	活性化
		IL-4	B細胞	活性化、増殖、分化
		IL-5	B細胞	活性化、増殖
		IL-6	B細胞	増殖、分化
		TGF-β	B細胞	分化(IgA分泌)
アレルギー調節サイトカイン	インターロイキン	IL-3	肥満細胞	増殖、分化促進
		IL-4	B細胞	IgEクラススイッチ促進
		IL-5	好酸球	増殖、分化促進
		IL-13	B細胞	IgEクラススイッチ促進
	インターフェロン	IFN-γ	B細胞	IgEクラススイッチ抑制
走化性サイトカイン(ケモカイン)	CCケモカイン	MIP-1	好中球	遊走
		MIP-2	好中球
		RANTES	単球
	CXCケモカイン	IL-8	好中球、リンパ球、好塩基球
	CXCケモカイン	SDF-1	好中球、リンパ球、好塩基球
造血系サイトカイン		SCF
	インターロイキン	IL-7
		erythropoietin
	コロニー刺激因子	GM-CSF
		G-CSF
		M-CSF