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Background: Epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancer (NSCLC) develops resistance to tyrosine kinase inhibitors (TKIs). Here, we evaluated the efficacy of radiotherapy and continuation of TKIs in patients with advanced NSCLC with oligoprogression after EGFR‐TKIs. Methods: From January 2011 to January 2019, 33 patients with EGFR‐mutated NSCLC on TKIs were treated by radiotherapy and continuation of TKIs for oligoprogressive disease. The primary endpoints were median progression‐free survival 1 (mPFS1), mPFS2, and median overall survival (mOS). PFS1 was measured from the start of EGFR‐TKIs therapy to the oligoprogression of the disease. PFS2 was measured from the date of oligoprogression to the further progression of the disease, while OS was calculated from oligoprogression to death from any cause or was censored at the last follow‐up date. Result: The mPFS1, mPFS2, and mOS were 11.0 (95% CI, 4.4–17.6), 6.5 (95% CI, 1.4–11.6) and 21.8 (95% CI, 14.8–28.8) months, respectively. Univariate analysis showed that EGFR mutation type (p = 0.024), radiotherapy method (p = 0.001), and performance status (p = 0.017) were significantly correlated with PFS2. Univariate analysis showed that sex (p = 0.038), smoking history (p = 0.031), EGFR mutation type (p = 0.012), and radiotherapy method (p = 0.009) were significantly correlated with OS. Multivariate analysis suggested that radiotherapy method (p = 0.001) and performance status (p = 0.048) were prognostic factors for PFS2, and radiotherapy method (p = 0.040) was a prognostic factor for OS. Conclusion: Radiotherapy with continued TKIs is effective for EGFR‐mutated NSCLC with oligoprogression, and it should be conducted as soon as possible. T790M+ patients have higher sensitivity to radiotherapy, and patients with good performance status and stereotactic body radiation therapy have better PFS2 and OS. Almost all EGFR mutation‐positive advanced NSCLC patients treated with TKI will progress. The definition of oligometastasis disease included ≤5 metastases with ≤3 organs involved, and all metastatic sites could be amenable to local radical treatment. Radiotherapy with continued TKIs is effective for EGFR‐mutated NSCLC with oligoprogression. [ABSTRACT FROM AUTHOR]

Background: Chronic lymphocytic leukemia (CLL) remains incurable with standard therapy, and is characterized by excessive expansion of monoclonal abnormal mature B cells and more regulatory immune properties of T cell compartment. Thus, developing novel strategies to enhance immune function merits further investigation as a possible therapy for CLL.Methods: We generated a fusion cytokine (fusokine) arising from the combination of human GM-CSF and IL-4 (named GIFT4). Primary CLL cells were treated with GIFT4 or GM-CSG and IL-4 in vitro. GIFT4-triggered STAT5 signaling in CLL cells was examined by Western blot. The phenotype and secretome of GIFT4-treated CLL cells (GIFT4-CLL cells), and the immune stimulatory function of GIFT4-CLL cells on autologous T cells were analyzed by flow cytometry and luminex assay.Results: GIFT4-CLL up-regulated the expression of co-stimulatory molecules CD40, CD80 and CD86 and adhesion molecule CD54. GIFT4-CLL cells secreted IL-1β, IL-6, ICAM-1 and substantial IL-2 relative to unstimulated CLL cells. GIFT4 treatment led to JAK1, JAK2 and JAK3-mediated hyper-phosphorylation of STAT5 in primary CLL cells, which is essential for GIFT4-triggered conversion of CLL cells. GIFT4-CLL cells directly propelled the expansion of autologous IFN-γ-producing CD314(+) cytotoxic T cells in vitro, and that these could lyse autologous CLL cells. Furthermore, administration of GIFT4 protein promoted the expansion of human T cells in NOD-scid IL2Rγ(null) immune deficient mice adoptively pre-transferred with peripheral blood mononuclear cells from subjects with CLL.Conclusion: GIFT4 has potent capability to converts primary CLL cells into APC-like immune helper cells that initiate a T cell driven anti-CLL immune response. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors, especially programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have made a breakthrough in the treatment of NSCLC and changed the treatment pattern for NSCLC. Immunological checkpoint inhibitors targeting PD-1/PD-L1 are beneficial to patients, both in the first-line and second-line treatment of advanced NSCLC, in the adjuvant treatment of locally-advanced NSCLC, and in the neoadjuvant therapy of early NSCLC, which show an important role in the comprehensive treatment of NSCLC. This article reviews the clinical research progress of immunological checkpoint inhibitors targeting PD-1/PD-L1 in NSCLC.
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The most important adverse effects of phenobarbital, an anticonvulsant drug, are behavior and cognitive alterations. Hypersensitivity syndrome caused by phenobarbital presenting with a leukemoid reaction is a rare side effect, which is rarely ever reported and needs to be known. We report on a 27-year-old Chinese woman who experienced hypersensitivity syndrome three weeks after the initiation of phenobarbital. The patient developed fever, skin rash, face swelling, lymphadenopathy, myalgia, hepatitis, eosinophilia, atypical lymphocytes and leukocytosis. Along with the pathological progress of the disease, the patient noticed a gradual exacerbation of her symptoms. And the highest leukocyte count was up to 127.2 x 10(9)/L. After discontinuing of phenobarbital and administration of methylprednisolone combined with the intravenous immunoglobulin shock therapy, all initial symptoms improved and the leukocyte count normalized. This case is reported because of its rarity of the leukemoid reaction secondary to hypersensitivity syndrome to phenobarbital.