西艾克联合化疗与G-CSF联用治疗难治复发性非霍奇金淋巴瘤临床观察

目的：观察西艾克（VDS）联合化疗与重组粒细胞集落刺激因子（G－CSF）联合治疗难治复发性非霍奇金淋巴瘤（NHL）的疗效。方法：采用VDS替代长春新碱（VCR）组成CHOP＋足叶乙苷（VP16）方案联合化疗,72h后加用G－CSF治疗难治复发性NHLⅢ－Ⅳ期12例,观察其临床疗效及毒副作用。结果：12例中完全缓解（CR）5例（41.66%),部分缓解（PR）3例（25％）,稳定（S）1例（8.3%),总有效率74.96%,主要副作用为骨髓抑制。结论：VDS联合化疗与G－CSF联用治疗难治复发性NHL是一种有效的挽救方案。     

Clinical evaluation of colony-stimulating factor 1 receptor inhibitors

Signaling through colony-stimulating factor 1 receptor (CSF1R) regulates the development, differentiation, and activation of mononuclear phagocytic cells. Inhibition of this pathway provides an opportunity for therapeutic intervention in diseases in which these cells play a pathogenic role, including cancers, inflammation, fibrosis, and others. Multiple monoclonal antibodies and small molecule inhibitors targeting CSF1R or its known ligands CSF1 and IL-34 have been clinically tested and are generally well tolerated with side effects associated with on-target macrophage inhibition or depletion. To date, clinical activity of CSF1R inhibitors has been primarily observed in diffuse-type tenosynovial giant cell tumors, a disease characterized by genetic alterations in CSF1 leading to dysregulated CSF1R signaling. Expanded development into novel indications such as chronic graft vs host disease may provide new opportunities to further explore areas where a role for CSF1R dependent monocytes and macrophages has been established. This review presents key findings from the clinical development of 12 CSF1/CSF1R targeted therapies as monotherapy or in combination with immune checkpoint inhibitors and chemotherapy.     

Functions of macrophage colony-stimulating factor (CSF1) in development,homeostasis, and tissue repair

Macrophage colony-stimulating factor (CSF1) is the primary growth factor required for the control of monocyte and macrophage differentiation, survival, proliferation and renewal. Although the cDNAs encoding multiple isoforms of human CSF1 were cloned in the 1980s, and recombinant proteins were available for testing in humans, CSF1 has not yet found substantial clinical application. Here we present an overview of CSF1 biology, including evolution, regulation and functions of cell surface and secreted isoforms. CSF1 is widely-expressed, primarily by cells of mesenchymal lineages, in all mouse tissues. Cell-specific deletion of a floxed Csf1 allele in mice indicates that local CSF1 production contributes to the maintenance of tissue-specific macrophage populations but is not saturating. CSF1 in the circulation is controlled primarily by receptor-mediated clearance by macrophages in liver and spleen. Administration of recombinant CSF1 to humans or animals leads to monocytosis and expansion of tissue macrophage populations and growth of the liver and spleen. In a wide variety of tissue injury models, CSF1 administration promotes monocyte infiltration, clearance of damaged cells and repair. We suggest that CSF1 has therapeutic potential in regenerative medicine.     

Predictors for successful PBSC collection on the fourth day of G‐CSF‐induced mobilization in allogeneic stem cell donors

Peripheral blood stem cells (PBSCs) used for allogeneic transplantation are collected by apheresis after pre‐treatment of donors with G‐CSF. Using modern apheresis devices stem cells can be collected more efficiently. It was studied whether collection on the 4th instead of the 5th day after initiation of G‐CSF treatment might be feasible. Stem cell yields that could have been collected on day 4 were calculated in two cohorts treated with 10 µg/kg G‐CSF once daily (n = 106, cohort I) or 5 µg/kg twice daily schedule (n = 85, cohort II). Harvests were predicted using the median collection efficiency (CE) of the apheresis machine and regarded successful when > 5.0 x10⁶ CD34^+/kg recipient body weight. Successful harvests at day 4 could have been obtained in only 22.6% and 41.2% of donors in cohort I and II respectively, while the expected successful collections on day 5 were 55.7% and 76.5%. Individual donor factors that correlated with a successful harvest on day 4 were weight, BMI, age, ratio donor/recipient weight and total G‐CSF dose in cohort I, whereas ratio donor/recipient weight was the only significant predictor in cohort II. Donor weight, BMI and total G‐CSF dose correlated positively with CD34⁺ values in the blood on day 4 in all donors. However, donor characteristics were not able to be used as strong predictors in daily practice. In conclusion, PBSC collection on day 4 will not result in a successful harvest in most stem cell donors, however using a twice daily G‐CSF scheme increases the yield.     

Rapid identification of nonblood sterile site broth cultures using the FilmArray blood culture identification panel

The FilmArray Blood Culture Identification Panel was validated for nonblood sterile site specimens with clinical impact of rapid identification compared to conventional diagnostics. The panel accurately identified target organisms from 98% of positive broth cultures a median 1.1?day faster than conventional techniques (P?<?0.0001) with potential clinical impact in 22% of cases.     

Direct Identification of Enteroviruses in Cerebrospinal Fluid of Patients with Suspected Meningitis by Nested PCR Amplification

Enteroviruses, the most common human viral pathogens worldwide, have been associated with serous meningitis, encephalitis, syndrome of acute flaccid paralysis, myocarditis and the onset of diabetes type 1. In the future, the rapid identification of the etiological agent would allow to adjust the therapy promptly and thereby improve the course of the disease and prognosis. We developed RT-nested PCR amplification of the genomic region coding viral structural protein VP1 for direct identification of enteroviruses in clinical specimens and compared it with the existing analogs. One-hundred-fifty-nine cerebrospinal fluids (CSF) from patients with suspected meningitis were studied. The amplification of VP1 genomic region using the new method was achieved for 86 (54.1%) patients compared with 75 (47.2%), 53 (33.3%) and 31 (19.5%) achieved with previously published methods. We identified 11 serotypes of the Enterovirus species B in 2012, including relatively rare echovirus 14 (E-14), E-15 and E-32, and eight serotypes of species B and 5 enteroviruses A71 (EV-A71) in 2013. The developed method can be useful for direct identification of enteroviruses in clinical material with the low virus loads such as CSF.