Background
Glioblastoma multiforme (GBM) is associated with remarkably poor prognosis, and its treatment is challenging. This investigation aimed to evaluate the safety of suicide gene therapy using allogeneic adipose tissue-derived mesenchymal stem cells (ADSCs) carrying herpes simplex virus-thymidine kinase (HSV-TK) gene for the first time in patients with recurrent GBM.
Methods
This study was a first-in-human, open-label, single-arm, phase I clinical trial with a classic 3 + 3 dose escalation design. Patients who did not undergo surgery for their recurrence were included and received this gene therapy protocol. Patients received the intratumoral stereotactic injection of ADSCs according to the assigned dose followed by prodrug administration for 14 days. The first dosing cohort (n = 3) received 2.5 × 105 ADSCs; the second dosing cohort (n = 3) received 5 × 105 ADSCs; the third dosing cohort (n = 6) received 10 × 105 ADSCs. The primary outcome measure was the safety profile of the intervention.
Results
A total of 12 patients with recurrent GBM were recruited. The median follow-up was 16 (IQR, 14-18.5) months. This gene therapy protocol was safe and well tolerated. During the study period, eleven (91.7%) patients showed tumor progression, and nine (75.0%) died. The median overall survival (OS) was 16.0 months (95% CI 14.3–17.7) and the median progression-free survival (PFS) was 11.0 months (95% CI 8.3–13.7). A total of 8 and 4 patients showed partial response and stable disease, respectively. Moreover, significant changes were observed in volumetric analysis, peripheral blood cell counts, and cytokine profile.
Conclusions
The present clinical trial, for the first time, showed that suicide gene therapy using allogeneic ADSCs carrying the HSV-TK gene is safe in patients with recurrent GBM. Future phase II/III clinical trials with multiple arms are warranted to validate our findings and further investigate the efficacy of this protocol compared with standard therapy alone.
Trial registration: Iranian Registry of Clinical Trials (IRCT), IRCT20200502047277N2. Registered 8 October 2020, https://www.irct.ir/.
Background: The complexity of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) makes the clinical course of the disease develop rapidly, causing severe and deadly complications. Identifying effective laboratory biomarkers able to predicting patients based on their risk. This study aimed to look for those serobiomarkers in hospitalized patients with Coronavirus Disease 2019 (COVID‐19). Materials and Methods: In this retrospective observational study, 114 patients with COVID-19, admitted to Valian hospital in Aligudarz, City, Iran from October to December 2020 were examined. The disease outcome was followed along with the hospital course of every patient at the time of analysis. Laboratory investigations of all patients were monitored at the time of admission. A comparative analysis was done between the survivors (n=73) and non-survivors (n=41). Statistical analysis was conducted using SPSS. Results: Of the 114 patients, 40.4% (n=41) were non-survivor, and there were significant differences in Hemoglobin (Hb), Hematocrit (Hct), Platelet (PLT), Alkaline Phosphatase (ALP), Total Bilirubin, Fasting Blood Suger (FBS), Total Iron-Binding Capacity (TIBC), Lactate Dehydrogenase (LDH), Blood Urea Nitrogen (BUN), Creatinine (Cr), Albumin (ALB), and C-Reactive Protein (CRP) between survivors and non-survivors. Conclusion: The laboratory parameters have fundamental roles in poor prognosis and mortality prediction rated among patients with COVID-19 in the first admission. Thus, it is highly recommended to collaborate among hematologists, health managers, and clinical especialists.
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