Granulocyte/macrophage-colony stimulating factor and interleukin-4 expand and activate type-1 dendritic cells (DC1) when administered in vivo to cancer patients

Two rare populations of cells with the features of dendritic cell precursors (preDC) can be identified in human peripheral blood. PreDC1 are HLA-DR+/CD11c+ cells which mature into DC1 capable of stimulating Th1 responses. In contrast, preDC2 are HLA-DR+/CD11c-/CD123+ cells that promote Th2 responses when matured into DC2. We hypothesized that administration of GM-CSF and IL-4, growth factors for DC1, would specifically augment the number and function of circulating DC1 in vivo. Patients with advanced metastatic cancer were treated with GM-CSF (2.5 microg/kg/day) and IL-4 (4 or 6 microg/kg/day) for 7 days. Cytokine administration at the highest IL-4 dose produced an average 2.3-fold increase in preDC2 number, but a 6.5-fold increase in preDC1, resulting in an increased ratio of circulating preDC1:preDC2 from 1.4:1 pre-treatment to 4.3:1 after cytokine therapy. DC1 precursors identified after in vivo therapy were larger, more complex and expressed higher levels of HLA-DR, CD11c and CD80 than pre-treatment cells. DC1 isolated from the peripheral blood of patients receiving GM-CSF/IL-4 therapy demonstrated MLR activity comparable to that of monocyte-derived DC generated in vitro from the patients' pre-treatment blood using GM-CSF and IL-4. We conclude that systemic administration of GM-CSF and IL-4 preferentially expands and matures the preDC1 population in vivo. These effects correlate with antigen-presenting activity, providing a mechanism by which systemic GM-CSF and IL-4 might stimulate anti-tumor immunity in vivo.     

Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma

K-RAS mutations are frequently found in adenocarcinomas of the pancreas, and induction of immunity against mutant ras can therefore be of possible clinical benefit in patients with pancreatic cancer. We present data from a clinical phase I/II trial involving patients with adenocarcinoma of the pancreas vaccinated by i.d. injection of synthetic mutant ras peptides in combination with granulocyte-macrophage colony-stimulating factor. Forty-eight patients (10 surgically resected and 38 with advanced disease) were treated on an outpatient basis. Peptide-specific immunity was induced in 25 of 43 (58%) evaluable patients, indicating that the protocol used is very potent and capable of eliciting immune responses even in patients with end-stage disease. Patients followed-up for longer periods showed evidence of induction of long-lived immunological memory against the ras mutations. CD4(+) T cells reactive with an Arg12 mutation also present in the tumor could be isolated from a tumor biopsy, demonstrating that activated, ras-specific T cells were able to selectively accumulate in the tumor. Vaccination was well tolerated in all patients. Patients with advanced cancer demonstrating an immune response to the peptide vaccine showed prolonged survival from the start of treatment compared to non-responders (median survival 148 days vs. 61 days, respectively; p = 0.0002). Although a limited number of patients were included in our study, the association between prolonged survival and an immune response against the vaccine suggests that a clinical benefit of ras peptide vaccination may be obtained for this group of patients.     

Physiopathological studies on granulocyte-macrophage colony stimulating factor and multi colony stimulating factor producing leukemia, L8313, induced by irradiation of C3H mice

Radiation-induced L8313 leukemia bearing mice (L8313 mice) had marked granulo-cytosis with splenomegaly. Hemopoietic stem cells and progenitors increased in the spleen but not in the bone marrow. Spleen conditioned-medium and serum from L8313 mice induced the formation of granulocyte-macrophage colonies (CFU-GM), erythroid bursts (BFU-E) and mixed colonies (CFU-Mix). Bone marrow conditioned medium did not show such activity. A cell line (STIL-3) was established from the spleen cells of L8313 mice. Surface marker analysis showed that the established cells were suppressor T cell. The cells produced IL-3 and GM-CSF in vitro, and induce essentially the same “leukemic” response in recipient mice. Inoculation of STIL-3 in diffusion chamber also induced leukemoid reaction, i.e. a marked granulocytosis with splenomegaly. Therefore, L8313 leukemia may be linked to an abnormality of growth and production of hemopoietic factors in hemopoetic regulatory cells.     

低剂量粒—巨噬细胞集落刺激因子在肺癌化疗中的应用

３１例肺癌患者大剂量化疗４０例次，采用配对法分成加用低剂量粒－巨噬细胞集落刺激因子（ＧＭ－ＣＳＦ）的治疗组及不加用的对照组（二组均为２０例次）。结果表明，低剂量ＧＭ－ＣＳＦ明显缩短化疗所致白细胞低下的时间：治疗组为１４．５±９．４９天，对照组为１９．４±８．８５天（Ｐ＝０．０２），同时提高白细胞下降最低值：治疗组为３．３５×１０９／Ｌ±１．３７×１０９／Ｌ，对照组为２．９×１０９／Ｌ±１．１８×１０９／Ｌ。低剂量ＧＭ－ＣＳＦ的主要不良反应为发热（８０％）及肌痛、骨痛（１０％）。结果提示：低剂量ＧＭ－ＣＳＦ能支持癌症患者的大剂量化疗及连续化疗     

The association between physician reimbursement in the US and use of hematopoietic colony stimulating factors as adjunct therapy for older patients with acute myeloid leukemia: Results from the 1997 American Society of Clinical Oncology survey

Background/objectives: Financial considerations play an important role in the delivery of medical care in the US. In 1996, revised guidelines from the American Society of Clinical Oncology (ASCO) indicated that granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF) were unlikely to be harmful for older acute myeloid leukemia (AML) patients and suggested that physicians could consider their use in this setting. In 1997, the ASCO health services research committee evaluated whether physician reimbursement was a primary determinant in the decision to use G-CSF and GM-CSF in this clinical situation.Patients and methods: A questionnaire describing clinical scenarios for a 67-year-old man with newly diagnosed de novo AML was mailed to 1500 ASCO members who practiced medical oncology and hematology. Physicians were queried about their preferences for adjunctive CSF use following induction and consolidation chemotherapy.Results: Of 1020 potentially eligible respondents, returned surveys were received from 672. Following induction chemotherapy, support for CSF use was 40%, similar in magnitude for that for non-use of these agents. The most important determinant of support for CSF use was being in a fee-for-service practice (P < 0.001).Conclusions: Physicians in the US are mixed in their support for CSFs for older AML patients. Support was high in settings where CSF use was accompanied by financial profit to the physician practice, and support was low otherwise.     

Antigen association of J6-1 cell membrane associated factor receptor with macrophage colony stimulating factor receptor

Macrophagecolonystimulatingfactor(M-CSF)orcolonystimulatingfactor--l(CSF-1)isalineagespecifichematopoieticregulatorwhichcanstimulatetheproliferationandsupportthesurvivalofmononuclearphagocyteseries.[]]A]thoughoriginallydefinedthroughitsactivitiesonhematopoieticcells,M-CSFmayhaveimportantfunctionsoutsidethecontextofhematopoiesis,suchasbreastcancersandfemalereproductivetracttumorsformationetc.[2]Inthehematopoieticsystem,M--CSFexertsitspleiotropiceffectsbybindingtoasingleclassofhigh-affinit…     

Expression of granulocyte-colony-stimulating factor and its receptor in human Ewing sarcoma cells and patient tumor specimens: potential consequences of granulocyte-colony-stimulating factor administration

BACKGROUND: Ewing sarcoma (ES) is a highly vascular malignancy. It has been demonstrated that both angiogenesis and vasculogenesis contribute to the growth of ES tumors. Granulocyte-colony-stimulating factor (G-CSF), a cytokine known to stimulate bone marrow (BM) stem cell production and angiogenesis, is routinely administered to ES patients after chemotherapy. Whether ES cells and patient tumor samples express G-CSF and its receptor (G-CSFR) and whether treatment with this factor enhances tumor growth was examined. METHODS: Human ES cell lines were analyzed for expression of G-CSF and G-CSFR in vitro and in vivo. Sixty-eight paraffin-embedded and 15 frozen tumor specimens from patients with ES were also evaluated for the presence of G-CSF and G-CSFR. The in vivo effect of G-CSF on angiogenesis and BM cell migration was determined. Using a TC/7-1 human ES mouse model, the effect of G-CSF administration on ES tumors was investigated. RESULTS: G-CSF and G-CSFR protein and RNA expression was identified in all ES cell lines and patient samples analyzed. In addition, G-CSF was found to stimulate angiogenesis and BM cell migration in vivo. Tumor growth was found to be significantly increased in mice treated with G-CSF. The average tumor volume for the group treated with G-CSF was 1218 mm(3) compared with 577 mm(3) for the control group (P = .006). CONCLUSIONS: The findings that ES cells and patient tumors expressed both G-CSF and its receptor in vitro and in vivo and that the administration of G-CSF promoted tumor growth in vivo suggest that the potential consequences of G-CSF administration should be investigated further.     

Modulation of colony stimulating factor release and apoptosis in human colon cancer cells by anticancer drugs

Modulation of the immune response against tumour cells is emerging as a valuable approach for cancer treatment. Some experimental studies have shown that secretion of colony stimulating factors by cancer cells reduces their tumorigenicity and increases their immunogenicity probably by promoting the cytolitic and antigen presenting activities of leukocytes. We have observed that human colon cancer cells (HT-29) are able to secrete granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor when stimulated with cytokines (IL-1beta and TNF-alpha). In this study we assessed, for the first time, the effects of several anticancer drugs on colony stimulating factor release or apoptosis in HT-29 cells. Cytokine-induced release of granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor was significantly increased by cisplatin and 6-mercaptopurine. Taxol only increased macrophage-colony stimulating factor release while reduced that of granulocyte-colony stimulating factor. No changes in colony stimulating factor secretion were observed after treatment with methotrexate. Only cisplatin and taxol induced apoptosis in these cells. Secretion of colony stimulating factors by colon cancer cells may contribute to the immune host response against them. Anticancer drugs such as cisplatin and 6-mercaptopurine increase colony stimulating factor secretion by cytokine stimulated cancer cells probably through mechanisms different to those leading to cell apoptosis, an effect that may contribute to their anti-neoplasic action.     

Phase 1/2 dose-escalation study of a GM-CSF-secreting, allogeneic, cellular immunotherapy for metastatic hormone-refractory prostate cancer

BACKGROUND: This open-label, multicenter, dose-escalation study evaluated multiple dose levels of immunotherapy in patients with metastatic hormone-refractory prostate cancer (HRPC). The immunotherapy, based on the GVAX platform, consisted of 2 allogeneic prostate-carcinoma cell lines modified to secrete granulocyte-macrophage-colony-stimulating factor (GM-CSF). METHODS: Dose levels ranged from 100 x 10(6) cells q28d x 6 to 500 x 10(6) cells prime/300 x 10(6) cells boost q14d x 11. Endpoints included safety, immunogenicity, overall survival, radiologic response, prostate-specific antigen (PSA) kinetics, and serum GM-CSF pharmacokinetics. RESULTS: Eighty men, median age 69 years (range, 49-90 years), were treated. The most common adverse effect was injection-site erythema. Overall, the immunotherapy was well tolerated. A maximal tolerated dose was not established. The median survival time was 35.0 months in the high-dose group, 20.0 months in the mid-dose, group, and 23.1 months in the low-dose group. PSA stabilization occurred in 15 (19%) patients, and a >50% decline in PSA was seen in 1 patient. The proportion of patients who generated an antibody response to 1 or both cell lines increased with dose and included 10 of 23 (43%) in the low-dose group, 13 of 18 (72%) in the mid-dose group, and 16 of 18 (89%) in the high-dose group (P = .002; Cochran-Armitage trend test). CONCLUSIONS: This immunotherapy was well tolerated. Immunogenicity and overall survival varied by dose. Two phase 3 trials in patients with metastatic HRPC are underway.     

Immune modulation of minimal residual disease in early chronic phase chronic myelogenous leukemia: a randomized trial of frontline high-dose imatinib mesylate with or without pegylated interferon alpha-2b and granulocyte-macrophage colony-stimulating factor

BACKGROUND:

Most patients with chronic myelogenous leukemia (CML) harbor residual disease, as evidenced by molecular techniques even after treatment with high‐dose imatinib (ie, 800 mg/d). Interferon alpha (IFN α) is efficacious in CML likely due to its immunomodulatory properties, and is synergistic in vitro with imatinib and granulocyte macrophage‐colony stimulating factor (GM‐CSF).

METHODS:

A study was undertaken to determine whether adding pegylated (PEG) IFN α‐2b and GM‐CSF to high‐dose imatinib may improve the complete molecular response rate in patients with CML in chronic phase. Ninety‐four patients were treated with imatinib 800 mg/d for the first 6 months, then randomly assigned to continue high‐dose imatinib alone (n = 49) or in combination with PEG IFN α‐2b 0.5 μg/kg/wk and GM‐CSF 125 mg/m² 3× weekly (n = 45).

RESULTS:

The median follow‐up for all patients was 54 months (range, 7‐70 months). There were no differences in the rates of complete cytogenetic response (87% vs 90%; P = 1.0), or of major (77% vs 77%; P = 1.0) or complete (11% vs 13%; P = 1.0) molecular response (on the international scale) at 12 months between the 2 arms, or at any time during the study. Adverse events led to PEG IFN α‐2b discontinuation in all patients.

CONCLUSIONS:

The addition of PEG IFN α‐2b and GM‐CSF to high‐dose imatinib therapy does not improve significantly the cytogenetic or molecular response rates compared with high‐dose imatinib alone. The high dropout rate in the PEG IFN α‐2b arm may have compromised its potential immunomodulatory benefit. Cancer 2011. © 2010 American Cancer Society.     

PEG-rhG-CSF对同步放化疗中性粒细胞缺乏挽救性治疗临床分析

目的 聚乙二醇化重组人粒细胞集落刺激因子(pegylated recombinant human granulocyte colony-stimulating factor,PEG-rhG-CSF)体内半衰期长,可有效防治同步放化疗所致的Ⅳ度中性粒细胞缺乏,与重组人粒细胞刺激因子(recombinant human granulocyte colony stimulating factor,rhG-CSF)相比疗效上更具优势.但由于PEG-rhG-CSF临床时间尚短,合并应用rhG-CSF是否能够进一步减轻重度骨髓抑制程度及缩短恢复时间等相关研究非常少见.本研究通过比较PEG-rhG-CSF联合rhG-CSF与单纯PEG-rhG-CSF治疗恶性肿瘤同步放化疗后Ⅲ/Ⅳ度中性粒细胞缺乏的有效性,为临床合理应用提供依据.方法 回顾性分析自2014-04-01-2016-06-31于河北医科大学第四医院放疗一病区就诊,共52例经同步放化疗所致Ⅲ/Ⅳ度中性粒细胞缺乏的恶性肿瘤患者.52例患者分为单药治疗组9例及联合治疗组43例.其中Ⅲ度中性粒细胞缺乏34例,给予单纯PEG-rhG-CSF 3 mg单次皮下注射患者4例,PEG-rhG-CSF 3 mg单次皮下注射联合rhG-CSF(1次/d)皮下注射患者30例.Ⅳ度中性粒细胞缺乏18例,给予单纯PEG-rhG-CSF 3 mg单次皮下注射患者5例,PEG-rhG-CSF 3 mg单次皮下注射联合rhG-CSF(1次/d)皮下注射患者13例.联合组至中性粒细胞恢复≥2.0×109L-1后停用rhG-CSF.分析各组患者挽救性治疗后不同时间段(用药后24～48和72～96 h)中性粒细胞绝对计数、中性粒细胞增殖率以及中性粒细胞恢复至≥2.0×109 L-1所需时间.结果 单药组及联合组在挽救性治疗后24～48 h中性粒细胞绝对计数分别为(5.86士8.31)×10 9及(4.99±5.80)×109 L-1,P=0.94;中性粒细胞增殖率分别为(969.94±1 125.30)×109及(635.70±908.99)×109 L-1,P=0.57.治疗后72～96 h 2治疗组的中性粒细胞绝对计数分别为(7.05±6.19)×109及(9.29±8.07)×109 L-1,P=0.52;中性粒细胞增殖率分别为(125.00±162.10)×109及(260.50±391.139)×109 L-1,P=0.42.单药组恢复时间[(69.33±51.54) h]与联用组[(63.07±42.88) h]相比差异无统计学意义,P=0.71.亚组分析显示,无论Ⅲ度还是Ⅳ度中性粒细胞缺乏患者,在挽救性治疗后不同时间段中性粒细胞绝对计数、中性粒细胞增殖率及恢复时间上均差异无统计学意义,P＞0.05.结论 单独应用PEGrhG-CS即可有效缓解同步放化疗所致的Ⅲ/Ⅳ度中性粒细胞缺乏,保证患者能够足量地按疗程进行抗肿瘤治疗,同时减少补充rhG-CSF剂量.     

Supplementary granulocyte macrophage colony‐stimulating factor to chemotherapy and programmed death‐ligand 1 blockade decreases local recurrence after surgery in bladder cancer

Despite advances and refinements in surgery and perioperative chemotherapy, there are still unmet medical needs with respect to radical cystectomy for muscle‐invasive bladder cancer (MIBC). We investigated the potential benefit of supplementary granulocyte macrophage colony‐stimulating factor (GM‐CSF) to chemoimmunotherapy with programmed cell death protein‐1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) axis blockade and standard neoadjuvant chemotherapy in bladder cancer. We inoculated 2 × 10⁵ MBT2 cells s.c. in C3H mice to create a syngeneic animal model of local recurrence (LR). When the tumor diameter reached 12 mm, the mice were allocated randomly as follows: (i) non‐treated control (vehicle only); (ii) anti‐mPD‐L1 monotherapy; (iii) mGM‐CSF monotherapy; (iv) anti‐mPD‐L1 plus mGM‐CSF; (v) gemcitabine and cisplatin (GC); (vi) GC plus anti‐mPD‐L1; (vii) GC plus mGM‐CSF; and (viii) GC plus anti‐mPD‐L1 plus mGM‐CSF. After completing 2‐week neoadjuvant therapy, tumors were resected for resection margin evaluation and immunohistochemical staining and blood was collected for flow cytometry and ELISA. Operative wounds were sutured, and the operative site was monitored to detect LR. Addition of anti‐mPD‐L1 and mGM‐CSF to neoadjuvant GC chemotherapy enhanced the antitumor effect and reduced positive resection margins (50% vs 12.5%). Combination of GC, anti‐mPD‐L1, and mGM‐CSF resulted in longer LR‐free survival and cancer‐specific survival compared to those in other groups. These effects involved an immunotherapy‐related decrease in oncological properties such as tumor invasion capacity and epithelial‐mesenchymal transition. mGM‐CSF significantly decreased the accumulation of myeloid‐derived suppressor cells in both the blood and tumor microenvironment and blood interleukin‐6 levels. Supplementary GM‐CSF to neoadjuvant GC plus PD‐L1 blockade could decrease LR after radical surgery by immune modulation in the blood and tumor microenvironment.     

基因重组人粒细胞集落刺激因子在肿瘤大剂量联合化疗中的临床应用研究

目的　观察基因重组人粒细胞集落刺激因子 (rhG CSF)在肿瘤大剂量联合化疗中预防白细胞减少症的疗效。方法　全组病人 16 7例 ,采用自身对照 ,以第一周期为对照周期 ,第二周期为治疗周期 ,在治疗周期末次给药后 48小时起 ,皮下注射rhG CSF 75 μg/d。 结果　化疗后白细胞降低恢复至正常水平以上所需的时间治疗周期显著缩短 (约 11天 ) ,白细胞的下降程度治疗周期显著优于对照周期 ,治疗周期感染的发生率亦显著低于对照周期。结论　rhG CSF的应用可有效预防白细胞减少症的发生及其程度 ,有力支持肿瘤大剂量联合化疗的进行。     

The safety of full-dose chemotherapy with secondary prophylactic granulocyte colony stimulating factor (G-CSF) following a prior cycle with febrile neutropenia

Secondary prophylactic administration of recombinant human granulocyte colony stimulating factor (G-CSF) following an episode of febrile neutropenia is recommended if maintenance of dose-intensity is desired. This policy was adopted in our center in patients treated with an intent for cure or durable complete response. The purpose of this study was to evaluate the safety and feasibility of this policy. Patients in whom neutropenia was associated with a life-threatening infection and those who developed prolonged myelosuppression were excluded. Fifty-one patients who developed febrile neutropenia that required intravenous antibiotics following moderately myelotoxic chemotherapy were included. These patients received the next cycle of the same chemotherapy regime without dose modification but with the support of filgrastim (300 or 480 mg/d sc for at least 10 consecutive days). Diagnoses included lymphoma (n=19), breast cancer (n=15), germ cell tumor (n=7), small-cell lung cancer (n=5), and other solid tumors (n=5). The incidence of febrile neutropenia during the first cycle given with filgrastim support (N1) was 8/51 (16%). Intravenous antibiotics were required for 3–7 d (median, 4.5 d). During the following cycle (N2), febrile neutropenia developed in 4/41 (10%) patients. Intravenous antibiotics were given for 2, 4, 5, and 7 d. Other dose-limiting toxicities developed in 1/51 patients who received N1 and in 1/41 patients who received N2. There was no drug-related death associated with either cycle. In conclusion, a policy of full-dose chemotherapy with secondary G-CSF support in patients who develop febrile neutropenia following moderately myelotoxic chemotherapy is relatively safe and feasible.     

重组人粒-巨噬细胞集落刺激因子联合R-CHOP方案治疗初治弥漫大B细胞淋巴瘤效果观察

目的:观察重组人粒-巨噬细胞集落刺激因子（rhGM-CSF）联合R-CHOP方案治疗初治弥漫大B细胞淋巴瘤的临床效果及安全性。方法:回顾性分析2017年2月至2019年11月海军军医大学（第二军医大学）长海医院39例接受rhGM-CSF联合R-CHOP方案及39例接受R-CHOP方案治疗的初治DLBCL患者的临床资料,比较两组患者的总反应率（ORR）、完全缓解（CR）率、总生存（OS）、无进展生存（PFS）及不良反应发生情况。结果:rhGM-CSF联合R-CHOP方案组及R-CHOP方案组的ORR分别为87.2%（34/39）、82.1%（32/39）,差异无统计学意义（ χ2=0.394, P=0.53）,CR率分别为71.8%（28/39）、56.4%（22/39）,差异亦无统计学意义（ χ2=2.006, P=0.157）。随访截至2020年9月19日,rhGM-CSF联合R-CHOP方案组生存32例,死亡7例,其中1例死于肠癌,原发病仍处于CR状态;R-CHOP方案组生存32例,死亡7例。rhGM-CSF联合R-CHOP方案组及R-CHOP方案组2年OS率分别为82.5%、73.9%（ χ2=0.038, P=0.845）,2年PFS率分别为67.1%、55.2%（ χ2=0.457, P=0.499）。亚组分析结果显示,rhGM-CSF联合R-CHOP方案组及R-CHOP方案组的生发中心B细胞型亚组间、非生发中心B细胞型亚组间、Lugano分期Ⅰ~Ⅱ期亚组间、Lugano分期Ⅲ~Ⅳ期亚组间、年龄<60岁亚组间、年龄≥60岁亚组间CR率分别比较,差异均无统计学意义（均 P>0.05）。主要不良反应为骨髓抑制及其所致感染,两组3~4级血液学不良反应及感染发生率比较,差异均无统计学意义（均 P>0.05）。予支持治疗后,所有患者均安全度过骨髓抑制期,无治疗相关死亡。 结论:rhGM-CSF联合R-CHOP方案用于初治DLBCL患者安全有效。     

An assessment of erythroid response to epoetin α as a single agent versus in combination with granulocyte– or granulocyte‐macrophage–colony‐stimulating factor in myelodysplastic syndromes using a meta‐analysis approach

BACKGROUND:

Epoetin α (EPO) continues to be the initial treatment of choice for most anemic patients with myelodysplastic syndromes (MDS). Over the years, different therapeutic strategies have been adopted to optimize the clinical benefits of EPO in this setting.

METHODS:

In the current meta‐analysis of published literature, erythroid response (ER) rates with EPO as a single agent versus its combination with granulocyte–colony‐stimulating factor (G‐CSF) or granulocyte‐macrophage–colony‐stimulating factor (GM‐CSF) were compared.

RESULTS:

The assessment indicated that the ER rates were comparable between the 2 EPO‐based therapeutic strategies. Furthermore, EPO monotherapy at a higher dose of 60,000 to 80,000 U weekly produced significantly higher ER rates (64.5%) compared with the standard oncology dose of 30,000 to 40,000 U weekly either as a single agent (49%; P < .001) or in combination with G‐CSF/GM‐CSF (50.6% P = .007). In addition, when transfusion‐dependent patients were assessed separately, both EPO monotherapy and its combination with G‐CSF/GM‐CSF produced comparable and appreciable levels of transfusion independence (28.8% and 24.8%, respectively).

CONCLUSIONS:

In the current meta‐analysis, higher doses of EPO demonstrated better ER rates compared with EPO at standard doses alone or in combination with G‐CSF/GM‐CSF. Furthermore, the authors concluded that prospective clinical studies are warranted to evaluate the use of higher doses of EPO in anemic patients with MDS. Cancer 2009. © 2009 American Cancer Society.     

Incidence of chemotherapy‐induced neutropenia and current practice of prophylaxis with granulocyte colony‐stimulating factors in cancer patients in Spain: a prospective,observational study

We aimed to describe the incidence of neutropenia in breast cancer and lymphoma patients and granulocyte colony‐stimulating factors (G‐CSF) use in clinical practice. We conducted a multicentre, prospective, observational study including breast cancer and lymphoma patients initiating chemotherapy (≥10% febrile neutropenia risk). We included 734 patients with breast cancer and 291 with lymphoma. Over the first four chemotherapy cycles, patients had an incidence of 11.0% grade 3–4 neutropenia (absolute neutrophil count <1.0 × 10⁹/L) and 4.3% febrile neutropenia (absolute neutrophil count <0.5 × 10⁹/L and fever ≥38°C) in the breast cancer cohort, and 40.5% and 14.8% in the lymphoma cohort. Full dose on schedule (>85% of planned chemotherapy dose and ≤3 days delay) was achieved by 85.6% of breast cancer and 68.9% of lymphoma patients. Hospitalisation due to febrile neutropenia was required in 2.0% and 12.0% of breast cancer and lymphoma patients respectively. G‐CSF was administered to 70.0% of breast cancer and 83.8% of lymphoma patients, and initiated from the first chemotherapy cycle (primary prophylaxis) in 60.6% and 64.2% of cases. Severe neutropenia affects approximately one in 10 breast cancer patients and one in two lymphoma patients receiving chemotherapy with moderate or greater risk of febrile neutropenia. Most patients received treatment with G‐CSF in Spanish clinical practice.     

重组人粒细胞巨噬细胞集落刺激因子联合传统药物保留灌肠治疗子宫颈癌、子宫内膜癌患者慢性放射性直肠炎效果观察

目的:观察重组人粒细胞巨噬细胞集落刺激因子（rhGM-CSF）联合传统药物保留灌肠治疗慢性放射性直肠炎的临床疗效及安全性。方法:选取2017年10月至2019年10月襄阳市中心医院肿瘤科收治的128例经病理证实为子宫颈癌、子宫内膜癌的1、2级慢性放射性直肠炎患者,进行随机、单盲、对照试验。患者按随机数字表法分为对照组、...     

Feasibility of a dose-intensive CMF regimen with granulocyte colony-stimulating factor as adjuvant therapy in premenopausal patients with node-positive breast cancer

Our aim was to study the feasibility of an intensified intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) schedule with the aim to escalate dose intensity (DI). Twenty-three premenopausal breast cancer patients received 6 cycles of adjuvant CMF intravenously on days 1 and 8 every 3 weeks and granulocyte colony-stimulating factor days 9-18. Endpoints were DI and toxicity. Twenty-one out of 23 patients (91%) received the projected total dose and reached > or =85% of the projected DI. Compared to 'classical' CMF, all patients reached > or = 111% DI. Nine patients received the planned schedule without delay. Thirteen patients (57%) were treated for infection and four patients (17%) were hospitalized for febrile neutropenia. Twelve patients received red blood cell transfusions (52%). Radiation therapy (n = 6) had no adverse impact on dose intensity or haematological toxicity. This dose-intensified CMF schedule was accompanied by enhanced haematological toxicity with clinical sequelae, namely fever, intravenous antibiotics and red blood cell transfusions, but allows a high dose intensity in a majority of patients.     

Carcinoembryonic antigen‐related cell adhesion molecule 1 negatively regulates granulocyte colony‐stimulating factor production by breast tumor‐associated macrophages that mediate tumor angiogenesis

Carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1), a cell adhesion molecule expressed on epithelial cells and activated immune cells, is downregulated in many cancers and plays a role in inhibition of inflammation in part by inhibition of granulocyte colony‐stimulating factor (G‐CSF) production by myeloid cells. As macrophages are associated with a poor prognosis in breast cancer, but play important roles in normal breast, we hypothesized that CEACAM1 downregulation would lead to tumor promotion under inflammatory conditions. Cocultures of proinflammatory M1 macrophages with CEACAM1 negative MCF7 breast cells produced high levels of G‐CSF (10 ng/mL) compared to CEACAM1‐transfected MCF7/4S cells (1 ng/mL) or anti‐inflammatory M2 macrophage cocultures (0.5 or 0.1 ng/mL, MCF7 or MCF7/4S, respectively). The expression of CEACAM1 on M1s was much greater than for M2s and was observed only in cocultures with either MCF7 or MCF7/4S cells. When M1 macrophages were mixed with MCF7 cells and implanted in murine mammary fat pads of nonobese diabetic/severe combined immunodeficient mice, tumor size and blood vessel density were significantly greater than MCF7 or MCF7/4S only tumors which were hardly detected after 8 weeks of growth. In contrast, M1 cells had a much reduced effect on MCF7/4S tumor growth and blood vessel density, indicating that the tumor inhibitory effect of CEACAM1 is most likely related to its anti‐inflammatory action on inflammatory macrophages. These results support our previous finding that CEACAM1 inhibits both G‐CSF production by myeloid cells and G‐CSF‐stimulated tumor angiogenesis.