To optimize the culture environment and protocol of hematopoietic cells' expansion, avoiding the fluctuation caused by medium changing in stirred culture and concentration gradient in static culture, the hematopoietic cells from cord blood (CB) were cultured in a stirred bioreactor connected with a cell retention system, which is a gravity sedimentation settler designed for hematopoietic cell. Total cells expanded 11.5 and 18.6 fold respectively in the twice perfusion stirred cultures, in which CFU-Mix was expanded 23.2 and 20.4 fold, CFU-GM 13.9 fold and 21.5 fold, BFU-E 8.0 fold and 6.9 fold, CD34+ cells 17.1 fold and 15.4 fold. After 12-day culture, it was obtained that 1082 x 10(6) total cells, 6.31 x 10(6) CFU-GM, 6.2 x 10(6) CFU-Mix and 23 x 10(6) CD34+ cells from 267 x 10(6) CB mononuclear cells (MNC) in the first culture, and 1080 x 10(6) total cells, 4.65 x 10(6) CFU-GM, 11.0 x 10(6) CFU-Mix, and 25.0 x 10(6) CD34+ cells from 180 x 10(6) CB MNC. These two cultures met to the clinical scale. Due to the optimized dissolved oxygen (DO) and stable culture environment, the rate of stem/progenitor cells to total cells in the perfusion culture was higher than that in T-flask cell-retention feeding culture. But the cell growth was inhibited in the later phase of perfusion culture, when the cell density is high. The inhibition should be attribute to the high cell density itself. The perfusion culture environment in bioreactor with optimal DO and pH controlling is more favorable for stem/progenitor cells' maintenance and expansion, and the expanded cells' number has reached a clinical scale. But the high cell density in the later phase of perfusion culture caused inhibition to mature hematopoietic cell's growth.
Objective
To explore the safety and efficacy of interventional sclerotherapy for mediastinal lymphatic malformations in children.
Methods
The clinical data of 23 children with mediastinal lymphatic malformations on sclerotherapy was retrospectively analyzed. There were 13 boys and 10 girls with an average age of (2.0±0.6) years. Preoperative computed tomography or magnetic resonance (CT/MR) was performed. and the diagnosis was further confirmed by fluid content in cyst. After general anesthesia, the lesions were punctured under the guidance of imaging. Liquid was extracted and bleomycin injected. A pigtail tube was inserted into large sac and rinsed daily until no more fluid runoff. The average follow-up period was (2.3±0.6) (0.6-6.0) years. Clinical symptoms, imaging findings, therapeutic efficacies and postoperative complications were evaluated.
Results
The clinical types were cervical-mediastinal (n=20) and mediastinal (n=3). And the histological types were macrocystic (n=14), microcystic (n=4) and combined (n=5). For a total of 56 treatment sessions, there were 1-6 sessions per case. And pigtail tube was inserted in 9 cases. The outcomes were cure (n=20), relief (n=1) and re-resection due to recurrent hemorrhage and respiratory oppression (n=2). There was no onset of nerve injury, chylothorax or cardiopulmonary accident.
Conclusions
Interventional sclerotherapy is both safe and efficacious for mediastinal lymphatic malformations.
Key words:
Mediastinum; Lymphatic vessel; Deformity; Sclerosis
Intravenous chemotherapy (IVC) and intra-arterial chemotherapy (IAC) have become the primary treatments for retinoblastoma; however, some controversy remains over which method is more effective. We conducted a meta-analysis to compare the clinical efficacy of IVC and IAC. We systematically searched literature published on PubMed, Embase, and Cochrane Library up to May 2017. Studies containing either IAC or IVC that reported on efficacy were included. The effects estimate was expressed as a pooled rate with 95% confidence interval (CI), using a fixed-effects or random-effects model. Twenty-six studies were identified which included 1541 eyes (IAC: 11 trials, 445 eyes; IVC: 16 trials, 1096 eyes). The mean follow-up times were 49.4 months (range, 13.0–105.3 months) for IVC and 21.7 months (range, 8.8–38.7 months) for IAC. For the International Classification of Intraocular Retinoblastoma (ICRB) grading, the overall success rate was higher with IAC than with IVC (75.7% [95%CI: 65.7%–83.6%] vs. 69.5% [95%CI: 51.9%–82.8%], P < 0.001). The globe salvage with IAC was higher than with IVC in group D eyes (79.5% [95%CI: 71.8%–85.4%] vs. 55.1% [95%CI: 45.6%–64.2%], P < 0.001), but not in groups B (95.8% [95%CI: 57.5%–99.7%] vs. 82.5% [95%CI: 58.9%–94.0%], P = 0.163), C (91.3% [95%CI: 65.9%–98.3%] vs. 89.0% [95%CI: 69.0%–96.7%], P = 0.212), and E eyes (51.2% [95%CI: 37.0%–65.2%] vs. 43.2% [95%CI: 18.3%–72.1%], P = 0.578). IAC and IVC were not significantly different regarding the recurrence and metastasis rates (15.0% vs. 15.4%, P = 0.148 and 2.7% vs. 0.6%, P = 0.194, respectively). For Reese-Ellsworth (RE) grading, IAC had a higher globe salvage in groups IV (90.9% [95%CI: 56.0%–98.7%] vs. 66.3% [95%CI: 32.4%–89.0%], P = 0.047) and V eyes (83.2% [95%CI: 72.0%–90.5%] vs. 59.9% [95%CI: 43.1%–74.6%], P = 0.003), but not in group I-III eyes (88.6% [95%CI: 58.3%–97.7%] vs. 88.1% [95%CI: 76.6%–94.4%], P = 0.244). The overall success rate was higher in IAC than in IVC (87.1% [95%CI: 78.1%–92.7%] vs. 77.3% [95%CI: 68.1%–84.4%], P = 0.033). IAC may be superior to IVC for the treatment of retinoblastoma, with a higher overall success rate and higher globe salvage in group D or groups IV and V eyes.
Abstract Lessons Learned Patients with metastatic colorectal cancer with good performance status or no liver metastasis could benefit from apatinib. Circulating tumor DNA abundance may be a predictor in serial monitoring of tumor load. Background Apatinib, an oral vascular endothelial growth factor (VEGF) receptor-2 inhibitor, has been approved as third-line treatment for metastatic gastric cancer in China. The aim of this study was to evaluate the efficacy and safety of apatinib, in the treatment of patients with refractory metastatic colorectal cancer after failure of two or more lines of chemotherapy. Methods In this open-label, single-arm, phase II study, patients with histological documentation of adenocarcinoma of the colon or rectum were eligible if they had received at least two prior regimens of standard therapies including fluoropyrimidine, oxaliplatin, and irinotecan. These patients were treated with apatinib in a daily dose of 500 mg, p.o., in the third-line or higher setting. Capture sequencing was dynamically performed to identify somatic variants in circulating tumor DNA (ctDNA) with a panel of 1,021 cancer-related genes. The primary endpoint was progression-free survival (PFS) and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Interim analysis was applied as predefined. Results From June 1, 2016 to December 31, 2017, 26 patients were enrolled. The median PFS of the whole group was 3.9 months (95% confidence interval [CI]: 2.1–5.9). The median overall survival (OS) was 7.9 months (95% CI: 4.6–10.1+). Patients with performance status (PS) 0–1 had longer PFS than those with PS 2 (4.17 months vs. 1.93 months, p = .0014). Patients without liver metastasis also had longer PFS than those who had live metastasis (5.87 months vs. 3.33 months, p = .0274). The common side effects of apatinib were hypertension, hand-foot syndrome, proteinuria, and diarrhea. The incidence of grade 3–4 hypertension, hand-foot syndrome, proteinuria, and diarrhea was 76.92%, 11.54%, 73.08%, and 23.08%, respectively. All of the patients received dose reduction because of adverse effect. Results of capture sequencing showed APC, TP53, and KRAS were most frequently mutant genes. c?tDNA abundance increased before the radiographic assessment in ten patients. Conclusion Apatinib monotherapy showed promising efficiency for patients with refractory colorectal cancer, especially in patients with PS 0–1 or no liver metastasis. ctDNA abundance may be a predictor in serial monitoring of tumor load.
e21066 Background: Lung cancer ranks first globally in morbidity and mortality rates among cancers. There are few studies focused on the different doses of chemotherapy drugs in combination with programmed cell death-1 (PD-1) inhibitors in non-small-cell lung cancer (NSCLC). Tislelizumab, a novel PD-1 monoclonal antibody, has been shown to improve antitumor activity when combined with chemotherapy as first-line treatment for patients with NSCLC. Elderly patients usually have poor physical conditions and many complications, resulted in higher risks of chemotherapy. This study aimed to preliminarily assess the efficacy and safety of low-dose chemotherapy plus tislelizumab for elderly patients with metastatic NSCLC. Methods: Eligible patients should be diagnosed as metastatic NSCLC, aged ≥65 years, and failed in one or more lines treatment. Patients with epidermal growth factor receptor (EGFR) / anaplastic lymphoma kinase (ALK) inhibitor resistance could be enrolled in the study. Participants received albumin-bound paclitaxel (130mg/m 2 ) plus tislelizumab (200mg) every 3 weeks. Chemotherapy lasted for no more than 6 cycles. Once chemotherapy intolerance occurred or at end of 6 cycles, patients with objective response or stable disease would continue to receive tislelizumab until confirmed disease progression, death, and unacceptable toxicity. Primary endpoints were progression free survival (PFS) and safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), as well as overall survival (OS). Results: Total 23 patients were enrolled from May 2019 to March 2020: 43.5% (10/23) male, 39.1% (9/23) smokers, 26.1% (6/23) with squamous cell carcinoma and 56.5% (13/23) with ECOG 2. Median age was 71 yr (range: 65, 82). Patients had received 1 (47.8%) or ≥2 (52.2%) lines of therapy. 13 (56.5%) patients with EGFR/ALK TKI resistance participated in the study. As of data cut-off on December 1, 2020, the median PFS was 9.5 months (95% CI: 5.7–13.3 months). Nine patients achieved partial response (PR). The ORR was 39.1% (9/23) and DCR was 87.0% (20/23). Only 4 participants died in the study and the mOS was not reached. Sixteen (69.6%) patients had a decrease in tumor size as compared with baseline and the median change from baseline was −22%. 13 (56.5%) participants suffered at least one adverse event (grade 3 in 3 (13.0%) patients). The main adverse events were fatigue (17.4%), fever (17.4%), abnormal liver function (17.4%), rash (13.0%) and numbness (13.0%). No grade 4 adverse event was reported. Conclusions: Low-dose albumin-bound paclitaxel plus tislelizumab might be an optional choice for elderly patients with metastatic NSCLC after the failure of platinum-based chemotherapy or targeted therapy. Perspective clinical studies with large sample size are needed to validate our results.
To evaluate the effectiveness and complications of intra-arterial chemotherapy (IAC) for treating advanced refractory retinoblastoma (RB) in a large single-center cohort.Eighty-four eyes of 62 consecutive patients with advanced refractory RB who received IAC were included in the study during January 2013 and April 2015. These patients failed to respond adequately to a standard systemic chemotherapy (i.e., carboplatin, vincristine, and etoposide) with or without local therapy. Clinical outcomes and complications of these patients were reviewed.All of these patients received IAC of melphalan combined with topotecan. The mean follow-up period was 14.2 months after final IAC (ranged from 3 to 28 months). The rate of eye preservation was 41.67% in Group D and 20.83% in Group E of this study. Short-term ocular adverse events included eyelid edema (n = 12, 14.29%), bulbar conjunctiva congestion (n = 25, 29.76%), and excessive tearing (n = 10, 11.90%). Long-term complications included vitreous hemorrhage (n = 7, 8%), subretinal hemorrhage (n = 9, 11%), retinal vasculopathy (n = 6, 7%), and ophthalmic artery spasm with reperfusion (n = 11, 13%). Fever was observed after IAC in 14 patients; transient vomiting was observed in 17 patients; there were 8 cases of transient myelosuppression.IAC can be an optional treatment to save eyes of Group D RB that failed in systemic chemotherapy and were destined for enucleation. However, it should be cautioned for Group E. Both the ocular and systemic toxicities of IAC were within tolerance.
To compare the effect of xinruibai (Pegfilgrastim) and filgrastim injections on white blood cell and platelet (PLT) recovery, adverse events, post-operative complications, and cost effectiveness after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Children who underwent allo-HSCT at our hospital from January 2014 to May 2017 due to thalassemia major, aplastic anemia, leukemia, and mucopolysaccharidosis were included. Among the children, 53 received xinruibai injections and 33 received filgrastim injections. There were no significant differences in the average time to neutrophil and platelet recovery, the incidence of post-operative complications after allo-HSCT, the number of red blood cell and PLT infusions, or the incidence of adverse events related to the injection between two groups (P > 0.05). The pain score was 3.06 (SD 0.41) for the xinruibai group and 25.18 (SD 6.22) for the filgrastim group, indicating significant differences between the two groups (P < 0.001). No difference was found in the hospitalization cost. The cost of the granulocyte-colony stimulating factor (G-CSF) was 257.11 ± 61.87 Euro in the xinruibai group and 214.79 ± 0.00 Euro in the filgrastim group, showing significant difference (P < 0.001). Xinruibai injection was more convenient, simple, effective, and safer than filgrastim.
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