ABSTRACT
Objective:To investigate the effectiveness and safety of bortezomib combined with conventional chemotherapy regimens for treatment of relapsed/refractory acute B lymphoblastic leukemia (B-ALL).Methods:Twenty patients with relapsed/refractory B-ALL treated with bortezomib combined with chemotherapy in Jiaozuo People's Hospital Affiliated to Xinxiang Medical College, Jiaozuo Coal Industry Group Central Hospital and the Second People's Hospital of Jiaozuo from September 2021 to June 2022 were collected, and their treatment response and prognosis were retrospectively analyzed.Results:The median age of the 20 patients was 49.5 years old (25.0-58.5 years old); 12 were male and 8 were female; 12 were relapsed and 8 were refractory. All patients completed 1 course of bortezomib (1.6 mg/m 2, subcutaneous injection on days 2 and 16) combined with chemotherapy. Before bortezomib treatment, there were 0 case of complete remission (CR), 7 cases of partial remission (PR) and 13 cases of non-remission (NR) in 20 patients, the objective remission rate (ORR) was 35% (7/20), and all were positive for minimal residual disease (MRD). After bortezomib treatment, there were 13 cases of CR, 3 cases of PR and 4 cases of NR, and the ORR was 80% (16/20); the MRD of all patients decreased, among which 13 cases (65%) turned to negative; the differences were statistically significant when comparing CR rate, ORR and MRD negative conversion rate before and after bortezomib treatment ( χ2 values were 65.41, 8.83 and 19.30, all P < 0.05). Four of the 20 patients developed central nervous system infiltration despite bone marrow remission, and one died from post-chemotherapy infection. Myelosuppression occurred in all patients, the incidence of infection was 90% (18/20), and the incidence of digestive system adverse effects was 75% (15/20). Conclusions:Bortezomib combined with conventional chemotherapy regimens is effective and well tolerated in the treatment of relapsed/refractory ALL, and has the potential to enable patients with multi-drug resistant relapse to overcome resistance and to achieve deep remission.
ABSTRACT
BACKGROUND:Burned rat serum has been reported as an inducer that can induce differentiation of mesenchymal stem cells into epidermal cells. OBJECTIVE:To induce in vitro differentiation of bone marrow mesenchymal stem cells into epidermal cells that were transplanted alone or combined with inducers for the repair of skin wound defect and epidermal reconstruction. METHODS:Under aseptic environment, rat bone marrow was harvested to culture adherent cells using low-glucose Dulbecco’s modified Eagle’s medium. Culture cells at passage 4 were confirmed as mesenchymal stem cells by flow cytometry. Bone marrow mesenchymal stem cells were induced by Dulbecco’s modified Eagle’s medium/Ham’s nutrient mixture F-12 containing 20%burned rat serum to differentiate into epidermal cells that were identified by immunohistochemistry. Wistar rat models of ful-thickness skin wounds were prepared and divided into three groups. The 5-bromo-2-deoxyuridine-labeled autologous bone marrow mesenchymal stem cells and induced bone marrow mesenchymal stem cells were coated singly onto a rat model of burn wounds, and rat models of burn wounds with no treatment served as controls. Wound contraction and regeneration of epidermal cells and skin appendages were observed. RESULTS AND CONCLUSION:After isolation and culture of cells for 24 hours, a few of adherent cells grew as fibroblast-like cells with fusiform shape. At 16 days, cells completely covered the bottom of bottle, exhibiting a fish or reticular arrangement. After detection by flow cytometry, cells were cultured in Dulbecco’s modified Eagle’s medium/Ham’s nutrient mixture F-12 containing 20%burned rat serum, and fusiform-shaped cells gradual y became round or oval cells. Flow cytometry analysis and immunocytochemistry results showed that cells expressed keratin, which were confirmed as epidermal cells. The results show that both the bone marrow mesenchymal stem cells transplantation alone or with necessary inductor is better for skin repair than natural healing, exhibiting a faster regeneration of skin and skin appendages. Bone marrow mesenchymal stem cells are deduced preliminarily to be involved in epidermis and hair fol icle regeneration, thereby improving skin healing.