1.Efficacy, Prognosis and Safety of Decitabine Combined with Low-Dose Cytarabine in the Treatment of Elderly Patients with Relapsed/Refractory Acute Myeloid Leukemia.
Dong CHEN ; Ying LU ; Ren-Zh YAN ; Pei-Pei YE ; Yu-Sheng ZHANG ; Jun-Xia MA
Journal of Experimental Hematology 2019;27(2):390-395
		                        		
		                        			OBJECTIVE:
		                        			To investigate the efficacy, prognosis and safety of decitabine combined with low-dose CAG regimen in the treatment of elderly patients with acute myeloid leukemia (AML).
		                        		
		                        			METHODS:
		                        			The clinical data of 40 elderly patients with relapsed/refractory AML (69-85 years old) admitted to our hospital from January 2014 to August 2016 were analyzed retrospectively. 40 patients were divided into combination therapy group and CAG group according to different treatment methods. 20 patients of the combination therepy group were treated with decitabine combined with low-dose CAG (decitabine, 15 mg/m, d 1; aclarithromycin, 10 mg/m, d 3-6; Cytidine, 10 mg/m, d 1-14; recombinant human granulocyte macrophage colony-stimulating factor (G-CSF) for injection, 200 μg/(m·d), d 1-14). 20 patients of CAG group were treated by the standard CAG protocol (acralmycin 20 mg/m, d 1-4; cytarabine for injection, 15 mg/m, d 1-14; G-CSF 400 μg/(m·d), d 1-14). One course of treatment lasted for 2 weeks, after 2 courses of continuous medication, the complete remission rate (CR), overall remission rate (ORR), overall survival (OS), 1-year survival rate, hemoglobin, white blood cells, platelets improvement, and incidence of adverse reactions were compared.
		                        		
		                        			RESULTS:
		                        			In combination therapy group the CR was 55.00% (11/20), OR was 85.00% (17/20), but in the CAG group CR was 30.00% (6/20), and OR was 50.00% (10/20). Till to February 2018, out of 40 patients 17 survived, 20 died, and 3 failed to be followed-up. The median follow-up time was 12 (2 to 35) months; the median survival time in the comtination therapy group was 13 (2-35) months, and the 1-year OS rate was 70.00%, and the median survival time of the CAG group was 10 (2-31) months, and the 1-year OS rate was 50.00%, without staistical significance between the 2 groups (P>0.05). After treatment, the WBC and Plt counts in the combination therapy group were higher than those in the CAG group, but the Hb level was lower than that in the CAG group with statistically significant difference (P<0.05). In the combination therapy group, the incidence of lung infection, nausea and vomiting was higher than that of the CAG group (65.00% vs 25.00%, 50.00% vs 20.00%), with statistically significant difference (P<0.05).
		                        		
		                        			CONCLUSION
		                        			Decitabine combined with low-dose CAG regimen is effective for the treatment of relapsed/refractory AML in the elderly. Compared with the standard CAG regimen, the long-term efficacy of this regimen is not different significantly, but its adverse reactions are increase, thus the preventive treatment should be given in time.
		                        		
		                        		
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols
		                        			;
		                        		
		                        			Cytarabine
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Decitabine
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Granulocyte Colony-Stimulating Factor
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Leukemia, Myeloid, Acute
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
2.Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin in MDS-EB and AML-MRC.
Jing LIU ; Jin Song JIA ; Li Zhong GONG ; Shen Ye LU ; Hong Hu ZHU ; Xiao Jun HUANG ; Hao JIANG
Chinese Journal of Hematology 2018;39(9):734-738
		                        		
		                        			
		                        			Objective: To evaluate the clinical efficacy and safety of decitabine in combination with lower-dose CAG regimen (G-CSF, cytarabine and aclarubicin; D-CAG regimen) in the treatment of myelodysplastic syndromes with excess blasts (MDS-EB) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), compared to standard CAG regimen. Methods: A total of 42 patients with newly diagnosed MDS-EB and AML-MRC from May 2011 to March 2017 were included in the retrospective study. 21 cases were initially treated with G-CSF for priming, in combination with cytarabine of 10 mg/m(2) q12h for 14 days and aclarubicin of 20 mg/d for 4 days (CAG regimen) and the other 21 cases were initially treated with decitabine of 20 mg/m(2) for 5 days and lower-dose CAG regimen (cytarabine of 10 mg/m(2) q12h for 7 days, aclarubicin of 10 mg/d for 4 days, and G-CSF for priming (D-CAG regimen). After two cycles of induction chemotherapy, the patients who obtained complete remission(CR) received consolidation chemotherapy or hematopoietic stem cell transplantation (HSCT). Results: Among a total of 42 patients, the median age was 52.5 years (18-65 years) and 64.3% of them were male. Baseline characteristics of patients between D-CAG group and CAG group showed no significant differences. The CR for patients in D-CAG group was 81.0% (17/21), compared to 52.4% (11/21) in CAG group after 2 cycles of therapy (χ(2)=3.857, P=0.050). The overall response rate (ORR) for patients in D-CAG group and CAG group was 85.7% (18/21) and 76.2% (15/21) respectively, without significant difference (χ(2)=1.273, P=0.259). By December 2017, the median follow-up of D-CAG group and CAG group was 13(6-32) months and 15(2-36) months respectively. Finally, 10 patients in D-CAG group and 7 patients in CAG group received HSCT respectively. Except patients receiving HSCT, the median leukemia-free survival (LFS) time for patients in D-CAG group and CAG group was 18.0 (95%CI 6.6-29.4) months and 11.0 (95%CI 0-23.9) months respectively. Probabilities of 12 months LFS for D-CAG group and CAG group were (63.6±14.5)% and (50.0±13.4)% respectively, without difference (χ(2)=0.049, P=0.824). Except patients receiving HSCT, there were 2 deaths in D-CAG group and 7 deaths in CAG group respectively. The cumulative probabilities of 12 months OS for non-HSCT patients in D-CAG group and CAG group were (90.9±8.7)% and (61.5±13.5)% respectively, without significant difference (χ(2)=1.840, P=0.175). The incidences of side effects between D-CAG group and CAG group did not show significant differences (P=0.479), and the main side effects included cytopenias, pneumonia, infections of skin and soft tissues, neutropenic patients with fever, liver dysfunction. Conclusion: The decitabine in combination with lower-dose CAG regimen improved CR for patients with MDS-EB and AML-MRC, and was a promising choice.
		                        		
		                        		
		                        		
		                        			Aclarubicin
		                        			;
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
		                        			;
		                        		
		                        			Cytarabine/administration & dosage*
		                        			;
		                        		
		                        			Decitabine/administration & dosage*
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Granulocyte Colony-Stimulating Factor/administration & dosage*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Leukemia, Myeloid, Acute/drug therapy*
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Myelodysplastic Syndromes/drug therapy*
		                        			;
		                        		
		                        			Remission Induction
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Young Adult
		                        			
		                        		
		                        	
3.Tolerogenic Dendritic Cells Reduce Airway Inflammation in a Model of Dust Mite Triggered Allergic Inflammation.
Luciana S ARAGÃO-FRANÇA ; Viviane C J ROCHA ; Andre CRONEMBERGER-ANDRADE ; F H B COSTA ; José Fernandes VASCONCELOS ; Daniel Abensur ATHANAZIO ; Daniela Nascimento SILVA ; E S SANTOS ; Cássio Santana MEIRA ; C F ARAÚJO ; Jéssica Vieira CERQUEIRA ; Fabíola CARDILLO ; Neuza Maria ALCÂNTARA-NEVES ; Milena Botelho Pereira SOARES ; Lain C PONTES-DE-CARVALHO
Allergy, Asthma & Immunology Research 2018;10(4):406-419
		                        		
		                        			
		                        			PURPOSE: The use of tolerogenic dendritic cells (TolDCs) to control exacerbated immune responses may be a prophylactic and therapeutic option for application in autoimmune and allergic conditions. The objective of this work was to evaluate the effects of TolDC administration in a mouse model of allergic airway inflammation caused by mite extract. METHODS: Mouse bone marrow-derived TolDCs were induced by incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) and dexamethasone, and then characterized by flow cytometry and cytokine production by enzyme-linked immunosorbent assay (ELISA). For the in vivo model of Blomia tropicalis-induced allergy, mice transplanted with antigen-pulsed TolDCs were sensitized intraperitoneally with B. tropicalis mite extract (BtE) adsorbed to aluminium hydroxide. After challenge by nasal administration of BtE, bronchoalveolar lavage fluid (BALF), lungs, spleen and serum were collected for analysis. RESULTS: Induction of TolDCs was efficiently achieved as shown by low expression of major histocompatibility complex (MHC) II, programmed death-ligand (PD-L) 2 and pro-inflammatory cytokine production, and up-regulation of interleukin (IL)-10, upon LPS stimulation in vitro. Transplantation of 1 or 2 doses of BtE-pulsed TolDCs reduced the number of inflammatory cells in BALF and lungs as well as mucus deposition. Moreover, compared to saline-injected controls, TolDC-treated mice showed lower serum levels of anti-BtE immunoglobulin E (IgE) antibodies as well as reduced Gata3 and IL-4 gene expression in the lungs and decreased IFN-γ levels in the supernatant of splenocyte cultures Transplantation of TolDCs increased the percentage of the regulatory T cells in the spleen and the lungs. CONCLUSIONS: Preventive treatment with TolDCs protects against dust mite-induced allergy in a mouse model, reinforcing the use of tolerogenic dendritic cells for the management of allergic conditions.
		                        		
		                        		
		                        		
		                        			Administration, Intranasal
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		                        			Animals
		                        			;
		                        		
		                        			Antibodies
		                        			;
		                        		
		                        			Antigens, Dermatophagoides
		                        			;
		                        		
		                        			Asthma
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		                        			Bronchoalveolar Lavage Fluid
		                        			;
		                        		
		                        			Dendritic Cells*
		                        			;
		                        		
		                        			Dexamethasone
		                        			;
		                        		
		                        			Dust*
		                        			;
		                        		
		                        			Enzyme-Linked Immunosorbent Assay
		                        			;
		                        		
		                        			Flow Cytometry
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		                        			Gene Expression
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		                        			Granulocyte-Macrophage Colony-Stimulating Factor
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		                        			Hypersensitivity
		                        			;
		                        		
		                        			Immunoglobulin E
		                        			;
		                        		
		                        			Immunoglobulins
		                        			;
		                        		
		                        			In Vitro Techniques
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		                        			Inflammation*
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		                        			Interleukin-4
		                        			;
		                        		
		                        			Interleukins
		                        			;
		                        		
		                        			Lung
		                        			;
		                        		
		                        			Major Histocompatibility Complex
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		                        			Mice
		                        			;
		                        		
		                        			Mites*
		                        			;
		                        		
		                        			Mucus
		                        			;
		                        		
		                        			Spleen
		                        			;
		                        		
		                        			T-Lymphocytes, Regulatory
		                        			;
		                        		
		                        			Up-Regulation
		                        			
		                        		
		                        	
4.A Case of Therapy-Related Acute Leukemia With Mixed Phenotype With BCR-ABL1 After Treatment of Diffuse Large B-Cell Lymphoma.
Dahae YANG ; Sung Ran CHO ; Seri JUNG ; Woonhyoung LEE ; Hyun Yong HWANG ; Ho Seop LEE ; Yang Soo KIM ; Jong Rak CHOI ; Mi Hyang KIM
Annals of Laboratory Medicine 2017;37(2):166-168
		                        		
		                        			
		                        			No abstract available.
		                        		
		                        		
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/adverse effects
		                        			;
		                        		
		                        			Bone Marrow Cells/cytology/pathology
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Flow Cytometry
		                        			;
		                        		
		                        			Fusion Proteins, bcr-abl/*genetics
		                        			;
		                        		
		                        			Granulocyte Colony-Stimulating Factor/therapeutic use
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Immunophenotyping
		                        			;
		                        		
		                        			Leukemia/*diagnosis/etiology
		                        			;
		                        		
		                        			Lymphoma, Large B-Cell, Diffuse/*drug therapy
		                        			;
		                        		
		                        			Phenotype
		                        			;
		                        		
		                        			Rituximab/administration & dosage
		                        			
		                        		
		                        	
5.A multicenter, randomized, controlled, phase Ⅲ clinical study of PEG-rhG-CSF for preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer.
Binghe XU ; Fuguo TIAN ; Jingrui YU ; Yanqiu SONG ; Jianhua SHI ; Baihong ZHANG ; Yanjun ZHANG ; Zhiping YUAN ; Qiong WU ; Qingyuan ZHANG ; Kejun NAN ; Qiang SUN ; Weilian LI ; Jianbing HU ; Jingwang BI ; Chun MENG ; Hong DAI ; Hongchuan JIANG ; Shun YUE ; Bangwei CAO ; Yuping SUN ; Shu WANG ; Zhongsheng TONG ; Peng SHEN ; Gang WU ; Lili TANG ; Yongchuan DENG ; Liqun JIA ; Kunwei SHEN ; Wu ZHUANG ; Xiaodong XIE ; Youhua WU ; Lin CHEN
Chinese Journal of Oncology 2016;38(1):23-27
OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.
METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.
RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).
CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.
Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects
6.Vascular endothelial growth factor secreted by breast cancer cells plays a critical role in the formation of pre-metastatic niche in the mouse lung.
Ranran LI ; Bing YUAN ; Ying ZHANG ; Jianjian DAI ; Pengfei ZHANG ; Feifei FANG ; Mingyong HAN
Chinese Journal of Oncology 2016;38(1):17-22
OBJECTIVETo explore the formation of pre-metastatic niche in the mouse lung and to study the underlying molecular mechanisms whereby primary breast carcinoma-derived factors mediate recruitment of bone marrow-derived cells (BMDCs) and affect the formation of pre-metastatic lung environment before the arrival of tumor cells.
METHODSMammary carcinoma 4T1 cells were inoculated into the mammary gland to construct mouse model of breast cancer. Confocal microscopy was used to detect the recruitment of BMDCs in the pre-metastatic lungs. The expression of factors in the mouse sera and 4T1 cell culture media was assayed using RayBio Custom mouse cytokine antibody array kit. The mice were injected daily with recombinant VEGF for 7 consecutive days to observe the effect of VEGF on BMDCs recruitment in the mouse lung.
RESULTSNo BMDCs were observed in the lungs of control and 4T1-tumor-bearing mice on day 0. On day 7 and 14, clusters of BMDCs observed in the lungs of 4T1-tumor-bearing mice were 8.7±2.2/objective field and 48.8±3.2/objective field, respectively, significantly higher than those in the control mice (1.1±0.8/objective field and 3.1±1.7/objective field) (P<0.05 for both). Confocal microscopic observation found that metastatic breast cancer cells preferentially facilitate BMDCs recruitment sites in the pre-metastatic mouse lungs. The levels of VEGF, GM-CSF, and IL-6 in the serum of 4T1-tumor-bearing mice were significantly increased compared with those in the control group (P<0.05 for all). However, VEGF was detected only in the culture media of 4T1 cells. The amount of BMDCs in the mouse lung tissue was (22.8±3.6)/objective field in the VEGF group and (3.1±0.4)/objective field in the control group (P<0.05). There were 36.8±5.4 metastatic foci in the lung tissue of VEGF group and 12.6±2.2 in the control group (P<0.05).
CONCLUSIONSThe results of this study demonstrate that primary breast cancer cells can alter the lung microenvironment during the pre-metastatic phase and induce the formation of pre-metastatic niche. Primary tumor cell-derived VEGF may be a crucial factor responsible for the formation of pre-metastatic niche.
Animals ; Bone Marrow Cells ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; blood ; Humans ; Interleukin-6 ; blood ; Lung ; pathology ; Lung Neoplasms ; secondary ; Mice ; Recombinant Proteins ; administration & dosage ; Time Factors ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A ; administration & dosage ; physiology ; secretion
7.Protective effects of paeoniflorin and albiflorin on chemotherapy-induced myelosuppression in mice.
Ying-Li ZHU ; Lin-Yuan WANG ; Jing-Xia WANG ; Chun WANG ; Cheng-Long WANG ; Dan-Ping ZHAO ; Zi-Chen WANG ; Jian-Jun ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2016;14(8):599-606
		                        		
		                        			
		                        			Paeonia lactiflora root (baishao in Chinese) is a commonly used herb in traditional Chinese medicines (TCM). Two isomers, paeoniflorin (PF) and albiflorin (AF), are isolated from P. lactiflora. The present study aimed to investigate the protective effects of PF and AF on myelosuppression induced by chemotherapy in mice and to explore the underlying mechanisms. The mouse myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide (CP, 200 mg·kg(-1)). The blood cell counts were performed. The thymus index and spleen index were also determined and bone morrow histological examination was performed. The levels of tumor necrosis factor-α (TNF-α) in serum and colony-stimulating factor (G-CSF) in plasma were measured by Enzyme-Linked Immunosorbent Assays (ELISA) and the serum levels of interleukin-3 (IL-3), granulocyte-macrophagecolony-stimulatingfactor (GM-CSF), and interleukin-6 (IL-6) were measured by radioimmunoassay (RIA). The levels of mRNA expression protein of IL-3, GM-CSF and G-CSF in spleen and bone marrow cells were determined respectively. PF and AF significantly increased the white blood cell (WBC) counts and reversed the atrophy of thymus. They also increased the serum levels of GM-CSF and IL-3 and the plasma level of G-CSF and reduced the level of TNF-α in serum. PF enhanced the mRNA level of IL-3 and AF enhanced the mRNA levels of GM-CSF and G-CSF in the spleen. PF and AF both increased the protein levels of GM-CSF and G-CSF in bone marrow cells. In conclusion, our results demonstrated that PF and AF promoted the recovery of bone marrow hemopoietic function in the mouse myelosuppression model.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Antineoplastic Agents
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			Bridged-Ring Compounds
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Cyclophosphamide
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			Drugs, Chinese Herbal
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Glucosides
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Granulocyte Colony-Stimulating Factor
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Granulocyte-Macrophage Colony-Stimulating Factor
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Hematologic Diseases
		                        			;
		                        		
		                        			etiology
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			prevention & control
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Interleukin-3
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Interleukin-6
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Monoterpenes
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Paeonia
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			Tumor Necrosis Factor-alpha
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			metabolism
		                        			
		                        		
		                        	
8.Treatment of Chemotherapy Related Leukocytopenia by Oral Administration of Multiple Leucogenic Drugs Combined with G-CSF: an Experimental Study.
Xi-ping ZHANG ; Xiang ZHANG ; Hong-jian YANG ; De-hong ZOU ; Xiang-ming HE ; Xing-fei YU ; Yong-feng LI
Chinese Journal of Integrated Traditional and Western Medicine 2015;35(7):860-865
OBJECTIVETo evaluate efficacies of three commonly used oral drugs including Berbamine Hydrochloride Tablet (B), Qijiao Shengbai Capsule (Q), and Leucogen Tablet (L) (by single drug, two drugs or three drugs) combined with granulocyte colony-stimulating factor (G-CSF) for treat ment of chemotherapy related leukocytopenia in mice.
METHODSTotally 156 Kunming male mice were divided into the normal control group (A, n=24), the model group (B, n=24), the G-CSF group (C, n =24), the G-CSF+Q group (D, n=12), G-CSF+ B (E, n=12), the G-CSF+L group (F, n=12), the G-CSF + Q + B group (G, n=12), the G-CSF + Q + L group (H, n=12), the G-CSF + L + B group (I, n=12), and the G-CSF + L + Q + B (J, n=12). Mouse models of chemotherapy related leukocytopenia were established by intraperitoneal injection of cyclophosphamide (CTX). A G-CSF group was set up as a positive control. Mice were treated by a single oral drug, a single oral drug combined with G-CSF, and two or three drugs combined with G-CSF respectively, and the death rate calculated. Hemocytes [such as white blood cells (WBC) and its classification, red blood cells (RBC), platelet (PLT), hemoglobin (Hb)] were calculated by hematology analyzer. Mice were anatomized and important organs weighed. Organ indices were calculated.
RESULTSThere was no statistical difference in the mortality rate among all groups (P > 0.05). Compared with Group B, WBC was elevated in all other groups (P < 0.01). WBC and PLT were elevated most in Group J, Hb and RBC were also increased at the same time (P < 0.05, P < 0. 01). Compared with Group B, RBC increased in Group E, F, G, I, and J (P < 0.01); Hb obviously increased in Group C, E, F, H, I, and J (P<0.01). Compared with Group B and D, the promotion of erythroid hematopoiesis by G-CSF could be elevated in any group contained drug B and L (P < 0.05, P < 0.01). The spleen index of model mice could be significantly improved in Group C, D, and G (P < 0.01). The thymus index of model mice could be significantly improved in Group H (P < 0.05).
CONCLUSIONSThe best scheme to treat mice with chemotherapy related leukopenia or decreased three blood series was to administrate three commonly oral drugs combined with G-CSF. Authors speculated that G-CSF and Q might have a certain effect on CTX induced immune inhibition.
Administration, Oral ; Animals ; Blood Platelets ; Cyclophosphamide ; Drug-Related Side Effects and Adverse Reactions ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Erythrocyte Count ; Granulocyte Colony-Stimulating Factor ; metabolism ; Hematopoiesis ; Hemoglobins ; Leukocyte Count ; Leukocytes ; Leukopenia ; chemically induced ; drug therapy ; Male ; Mice ; Pharmaceutical Preparations
9.Clinical efficacy analysis of recombinant human erythropoietin in the treatment of lower-risk myelodysplastic syndromes.
Hongli ZHANG ; Tiejun QIN ; Zefeng XU ; Liwei FANG ; Lijuan PAN ; Naibo HU ; Shiqiang QU ; Yue ZHANG ; Zhijian XIAO
Chinese Journal of Hematology 2014;35(1):18-23
OBJECTIVETo investigate the efficacy and impact factors in lower-risk [International prognostic scoring system (IPSS) low or intermediate-1 risk] myelodysplastic syndrome (MDS) patients treated with recombinant human erythropoietin (rhEPO) alone or in combination with recombinant human granulocyte colony- stimulating factor (rhG-CSF).
METHODSA total of 52 consecutive lower-risk MDS patients received subcutaneous injection of rhEPO alone or in combination with rhG-CSF at least 8 weeks, the rhEPO dose would be reduced slowly to stop or kept at minimum to maintain the response when the best efficacy achieved and maintained for 4 weeks. Their clinical features, efficacy, survival and the predictors of efficacy were analyzed retrospectively.
RESULTSThe overall response rate was 51.9% (27/52) with 33.3%(9/27) achieving complete remission (CR) and 66.7%(18/27) achieving erythroid response (HI-E). In multivariate analysis, sEPO level (less than 500 U/L), BFU-E count (more than 25/10⁵ BMMNC), intermediate and high doses rhEPO±rhG-CSF therapy were independent predictors of better response. The median therapy period was 8(2-45) months and the median efficacy duration was 37(6-94) months (38 months for CR, 36 months for HI-E). Ten of the 27 responsive patients relapsed and 40% of them had disease progressions. Hemoglobin levels and karyotype affect response duration. Median overall survival was 47(6-114) months on a 37(6-114) months median follow-up. In multivariate analysis, ages (less than 60 years old), karyotype (good or intermediate) and response to rhEPO±rhG-CSF therapy may have a favorable survival impact on MDS.
CONCLUSIONrhEPO, alone or in combination with rhG-CSF, is a useful drug for the treatment of anemia in lower-risk MDS patients and has favorable impact on life expectancy.
Adult ; Aged ; Aged, 80 and over ; Drug Therapy, Combination ; Erythropoietin ; administration & dosage ; therapeutic use ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; therapy ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Retrospective Studies ; Treatment Outcome ; Young Adult
10.Immunosuppressive therapy using antithymocyte globulin and cyclosporin A with or without human granulocyte colony-stimulating factor in children with acquired severe aplastic anemia.
Xiaoming LIU ; Yao ZOU ; Shuchun WANG ; Li ZHANG ; Wenyu YANG ; Jiayuan ZHANG ; Fang LIU ; Tianfeng LIU ; Xiaojuan CHEN ; Min RUAN ; Jianfeng ZHOU ; Xiaojin CAI ; Benquan QI ; Lixian CHANG ; Wenbin AN ; Ye GUO ; Yumei CHEN ; Xiaofan ZHU
Chinese Journal of Pediatrics 2014;52(2):84-89
OBJECTIVETo compare the efficacy and safety of four different regimens for pediatric severe aplastic anemia (SAA) with immuno-suppressive therapy (IST) with or without combined human granulocyte colony-stimulating factor (G-CSF).
METHODThe authors retrospectively analyzed 105 children with SAA treated with IST with or without G-CSF in the hospital from February 2000 to September 2010. Regimen A, without G-CSF in the whole treatment, was used to treat Group A patients, n = 27; Regimen B, G-CSF, was initiated in Group B, n = 24, before the IST until hematologic recovery; Regimen C, G-CSF, was used together with the IST for Group C patients, n = 24, until hematologic recovery; Regimen D,G-CSF was used for Group D, n = 30, after the end of IST until hematologic recovery. The response rate, relapse rate, mortality, infection rate, infection-related death rate, risk of evolving into MDS/AML, survival rate, factors affecting the time of event-free survival and so on.
RESULT(1) The response (CR+PR) rates 4, 6, 12 and 24 months after IST of the whole series of 105 SAA children were 50.5% (7.6%+42.9%) , 60.0% (21.9%+38.1%) , 67.6% (38.1%+29.5%) and 69.5% (40.0%+29.5%) respectively. The 2-year survival rate was 90.5%; the follow-up of the patients for 13 years showed that the whole survival rate was 87.6%. (2) The differences of the response rates 4, 6, 12 and 24 months after IST of the 4 groups were not significant (P > 0.05). (3) No significant differences were found in the mortalities 4, 6, 12 and 24 months among the 4 groups (P > 0.05). (4) Of the 105 patients, 4 children had relapsed disease in the period of time from 6 to 24 months after IST. All the four patients belonged to the groups with G-CSF. (5) The use of G-CSF could not decrease the infection period before IST (day) (P = 0.273), and it had no impact on the infection rate after IST (P = 0.066). It did not reduce the rates of septicemia and infectious shock. And to the infection-related death rate no significant conclusion can be made. (6) Follow up of the patients for 13 years, showed that 2 had the evolution to MDS/AML in the 105 patients and the two children belonged to the groups with G-CSF. (7) Kaplan-meier curve analysis did not show any differences in the survival rates of the four groups. (8) Cox regression analysis showed that the use of G-CSF had no benefit to the patients' long term survival. While the age of diagnosis and the infection history before IST were significantly related to the patients' long term survival.
CONCLUSIONThe use of G-CSF did not contribute to the early response and could not reduce the infection rate, infection-related death rate and the patients' long term survival. There were no significant differences in the survival rates of the four groups. Attention should be paid to the risk of the evolution to MDS/AML.
Adolescent ; Anemia, Aplastic ; drug therapy ; immunology ; mortality ; Antilymphocyte Serum ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Cyclosporine ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; therapeutic use ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Infant ; Male ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Survival Rate ; Treatment Outcome
            
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