Mobilization of Peripheral Blood Stem Cells Using Regimen Combining Docetaxel with Granulocyte Colony-stimulating Factor in Breast Cancer Patients

Objective：To evaluate the effectiveness and safety of the mobilization of peripheral blood hematopoietic stem cells by combining docetaxel with granulocyte colony-stimulating factor（G-CSF） in breast cancer patients.Methods：A total of 57 breast cancer patients were treated with docetaxel 120 mg/m2.When the white blood cell（WBC） count decreased to 1.0×109/L,patients were given G-CSF 5-g/kg daily by subcutaneous injection until the end of apheresis.Peripheral blood mononuclear cells（MNC） were isolated by Cobe Spectra Apheresis System.The percentage of CD34＋ cell was assayed by flow cytometry.Results：At a median 6 of days（range 3-8） after the administration of docetaxel,the median WBC count decreased to 1.08×109/L（range 0.20-2.31）.The median duration of G-CSF mobilization was 3 days（range 2-7）.The MNC collection was conducted 8-12 days（median 10 days） after docetaxel treatment.The median MNC was 5.35×108/kg（range 0.59-14.07）,the median CD34＋ cell count was 2.43×106/kg（range 0.16-16.69）.The CD34＋ cell count was higher than 1.00×106/kg in 47 of 57 cases（82.46%） and higher than 2.00×106/kg in 36 cases（63.16%）.The CD34＋ cell count was higher than 2.00×106/kg in 27 collections（23.68%）.The MNC count and the CD34＋ cell count were correlated with the bottom of WBC after docetaxel chemotherapy（r=0.364,0.502,P=0.005,0.000）.The CD34＋ cell count was correlated with the MNC count（r=0.597,P=0.000）.The mobilization and apheresis were well tolerated in all patients.Mild perioral numbness and numbness of hand or feet were observed in 3 cases.No serious adverse events were reported.Conclusion：Mobilization of peripheral blood hematopoietic stem cell by combining docetaxel with G-CSF was effective and safety in breast cancer patients.

Mononuclear cells from the cord blood and granulocytecolony stimulating factor-mobilized peripheral blood:is there a potential for treatment of cerebral palsy?

To investigate a possible therapeutic mechanism of cell therapy in the field of cerebral palsy using granulocyte-colony stimulating factor（G-CSF）-mobilized peripheral blood mononuclear cells（m PBMCs）,we compared the expression of inflammatory cytokines and neurotrophic factors in PBMCs and m PBMCs from children with cerebral palsy to those from healthy adult donors and to cord blood mononuclear cells donated from healthy newborns.No significant differences in expression of neurotrophic factors were found between PBMCs and m PBMCs.However,in cerebral palsy children,the expression of interleukin-6 was significantly increased in m PBMCs as compared to PBMCs,and the expression of interleukin-3 was significantly decreased in m PBMCs as compared to PBMCs.In healthy adults,the expression levels of both interleukin-1βand interleukin-6 were significantly increased in m PBMCs as compared to PBMCs.The expression of brain-derived neurotrophic factors in m PBMC from cerebral palsy children was significantly higher than that in the cord blood or m PBMCs from healthy adults.The expression of G-CSF in m PBMCs from cerebral palsy children was comparable to that in the cord blood but significantly higher than that in m PBMCs from healthy adults.Lower expression of pro-inflammatory cytokines（interleukin-1β,interleukin-3,and-6）and higher expression of anti-inflammatory cytokines（interleukin-8 and interleukin-9）were observed from the cord blood and m PBMCs from cerebral palsy children rather than from healthy adults.These findings indicate that m PBMCs from cerebral palsy and cord blood mononuclear cells from healthy newborns have the potential to become seed cells for treatment of cerebral palsy.

The current G-CSF use in cancer patients with chemotherapy

Objective: The purpose of the study was to survey current G-CSF use in cancer patients, investigate whether the use of granulocyte colony-stimulating factor(G-CSF) is standardized. Methods: From July 2012 to October 2012, patients in a third-grade class-A hospital were investigated by self-designed questionnaires, according to ASCO's recommendations for white blood cell growth factors in 2006 and NCCN myeloid growth factors guideline in 2012. Results: Two hundred and twenty-two patients treated with 724 courses of chemotherapy were included. In prophylactic use, 259(35.8%) cases used G-CSF that the guideline doesn't recommend, which belonged to excessive use, the dose were 274 700 μg, accounting for 59.7% of the totle prophylactic use; 105(14.5%) didn't use while the guideline recommend, belonging to lack of use. 89.0% of the prophylactic use were 24–72 h after chemotherapy, only a few(5.4%) on the day of chemotherapy. In therapeutic use, only 3.1% were standardized, with the dose of 23 000 μg, accounting for 7.4% of the total. So 92.6% were excessive. 14.2% of the therapeutic use were 24–72 h after chemotherapy, 21.2% on the day of chemotherapy. Conclusion: More than 50% use of G-CSF weren't standardized, especially the excessive use.

Granulocyte Colony-Stimulating Factor Enhances the Anticancer Effects of Cisplatin against Lung Cancer by Promoting Angiogenesis

The G-CSF is used as a therapeutic drug of the febrile neutropenia in lung cancer chemotherapy, however, there were few reports that showed the effects of combination effects of G-CSF and anticancer drugs against lung cancer. In the present study, we investigated the effects of G-CSF and the combination effects of G-CSF and cisplatin on lung cancer growth. We investigated the effect of G-CSF against the LL-2 and KLN-205 cells by MTT assay and tried to detect the G-CSF receptor by RT-PCR. Next, to analyze the G-CSF effects in vivo, we transplanted the LL-2 into C57BL/6 mice, intraperitoneally administered G-CSF (30 micro/kg/day) with or without cisplatin (5 mg/kg), measured the tumor size and analyzed pathologically by HE and immunostaining. In vitro analyses, G-CSF showed no effects in LL-2 and KLN-205 cells, and RT-PCR revealed no G-CSF receptor mRNA. In vivo analyses, G-CSF alone did not significantly suppress tumor growth. However, concurrent G-CSF administration with cisplatin significantly enhanced the tumor suppressing effect of cisplatin in early stage of tumor growth. The analysis data of vWF immunostaining indicated that the neovascularization in the peripheral region of the tumors was more enhanced in G-CSF treatment mice. ELISA assay revealed that G-CSF did not influence the serum concentration of TNF-alpha and IL-12 in tumor-bearing mice. This study suggests that concurrent (combination) administration of cisplatin with G-CSF is a safe and effective method for enhancing anticancer effects and reducing chemotherapeutic agent-induced myelosuppression.

Current management of chemotherapy-induced neutropenia in adults:key points and new challenges

Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.

Efficacy of Azithromycin sequential therapy combined with Tanreqing injection for treatment of children with mycoplasma pneumonia

Objective:To study the effect of Azithromycin sequential therapy combined with Tanreqing injection on serum sTREM-1, CK, G-CSF, IL-10, CRP and TNF-α in children with mycoplasma pneumonia.Methods:A total of 80 children with mycoplasma pneumonia in our hospital from June 2014 to September 2016 were enrolled in this study. The subjects were divided into the control group (n=40) and the treatment group (n=40) randomly. The control group were treated with Azithromycin sequential therapy, the treatment group were treated with Azithromycin sequential therapy combined with Tanreqing injection. The two groups were treated for 2 periods. The serum sTREM-1, CK, G-CSF, IL-10, CRP and TNF-α levels of the two groups before and after treatment were compared.Results: There were no significantly differences of the serum sTREM-1, CK, G-CSF, IL-10, CRP and TNF-α levels of the two groups before treatment. The serum sTREM-1, CK, G-CSF, IL-10, CRP and TNF-α levels of the two groups after treatment were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group.Conclusion:Azithromycin sequential therapy combined with Tanreqing injection can significantly reduce the serum sTREM-1, CK, G-CSF, IL-10, CRP and TNF-α levels of children with mycoplasma pneumonia, have good clinical efficacy, and it was worthy clinical application.

Clinical practice guidelines for acute-on-chronic liver failure: are we ready for reaching global consensus?

The concept of acute-on-chronic liver failure(ACLF)has gained increasing awareness during the last decade.It considers liver cirrhosis as a systemic disease where precipitating events lead to a sudden deterioration,decompensation and extrahepatic organ failures.Disease severity is determined by the number and types of organ failures and patients with ACLF have a distinct and worse prognosis than patients with acute decompensation but not fulfilling ACLF criteria(1-3).