RESUMEN
Primary mediastinal B-cell lymphoma (PMBCL) is an uncommon disease, consisting of 2-4% of non-Hodgkin lymphomas. Radiotherapy-free DA-EPOCH-R and R-CHOP plus radiotherapy (RT) have been the upfront standard regimens worldwide. However, performing DA-EPOCH-R in resource-constrained settings can be burdensome, especially in low/middle-income countries, where data on PMBCL are still largely unknown. We retrospectively analyzed 93 patients with PMBCL diagnosed between 2008 and 2018 with the intention of comparing the characteristics of the patients and the results obtained with each protocol and to verify if the use of less intensive chemotherapy is still possible to be used. The median age was 28 years, 59.1% were female, 42.3% were in advanced stages, and 92.1% were with bulky disease. DA-EPOCH-R (41.9%), R-CHOP (35.5%), and R-CHOEP (22.6%) were the regimens used, and no difference was observed in the characteristics of the patients. After four cycles of chemotherapy, complete response (CR), partial response (PR), and progressive disease (PD) rates were 40%, 55.7%, and 4.5%, respectively. At the end of treatment, metabolic CR and PD rates were 56.8% and 11.1%. RT was performed in 42.1% of DA-EPOCH-R, 75% of R-CHOP, and 83% of R-CHOEP, and switched PR to CR in 73.7%. Estimated 5-year PFS and OS were 77.2% and 77.4%, respectively. Only LDH levels remained independently associated with PFS, and type of treatment was not associated with OS, PFS, or relapse rate. Therefore, we conclude that in a resource-constrained setting, R-CHOP or R-CHOEP could be still safely adopted in upfront treatment for PMBCL.
RESUMEN
Tuberculosis (TB) is one of the most fatal diseases and is responsible for the infection of millions of people around the world. Most recently, scientific frontiers have been engaged to develop new drugs that can overcome drug-resistant TB. Following this direction, using a designed scaffold based on the combination of two separate pharmacophoric groups, a series of menadione-derived selenoesters was developed with good yields. All products were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv and attractive results were observed, especially for the compounds 8a, 8c and 8f (MICs 2.1, 8.0 and 8.1 µM, respectively). In addition, 8a, 8c and 8f demonstrated potent in vitro activity against multidrug-resistant clinical isolates (CDCT-16 and CDCT-27) with promising MIC values ranging from 0.8 to 3.1 µM. Importantly, compounds 8a and 8c were found to be non-toxic against the Vero cell line. The SI value of 8a (>23.8) was found to be comparable to that of isoniazid (>22.7), which suggests the possibility of carrying out advanced studies on this derivative. Therefore, these menadione-derived selenoesters obtained as hybrid compounds represent promising new anti-tubercular agents to overcome TB multidrug resistance.