ABSTRACT
Chronic lymphocytic leukemia (CLL) is a heterogeneous, mature B-cell clonal malignancy that mainly affects the senior. The immunotherapies such as chimeric antigen receptor T cell therapy, bi/tri-specific cell binding agent, immune check point therapy, etc., pave several new avenues for CLL treatment, especially the combined applications of new and existing therapies have shown improved efficacy and safety. This article attempts to review the immunotherapies and their combinatorial applications in CLL.
ABSTRACT
With continuous discovery of tumor immune targets and continuous changes in antibody research and development technology, antibody drugs are becoming more and more widely used in clinical practice. However, some targets are not only expressed on tumor cells, but also on red blood cells. Therefore, the clinical application of antibodies against the corresponding targets may interfere with the detection of blood transfusion compatibility, resulting in difficulty in blood matching or delay of blood transfusion. This consensus summarizes the current solutions for the interference of CD38 monoclonal antibody (CD38 mAb) in transfusion compatibility testing. After analyzing the advantages and disadvantages of different methods, polybrene and sulfhydryl reducing agents [dithiothreitol (DTT) or 2-mercaptoethanol (2-Me)], as a solution for CD38 mAb interference in blood compatibility testing, are recommended for Chinese patients, so as to eliminate blood transfusion interference produce by CD38 mAb and further provide a pre-transfusion workflow for clinicians and technicians in Department of Blood Transfusion.
ABSTRACT
Malignant cell transformation could be considered as a series of cell reprogramming events driven by oncogenic transcription factors and upstream signalling pathways. Chromatin plasticity and dynamics are critical determinants in the control of cell reprograming. An increase in chromatin dynamics could therefore constitute an essential step in driving oncogenesis and in generating tumour cell heterogeneity, which is indispensable for the selection of aggressive properties, including the ability of cells to disseminate and acquire resistance to treatments. Histone supply and dosage, as well as histone variants, are the best-known regulators of chromatin dynamics. By facilitating cell reprogramming, histone under-dosage and histone variants should also be crucial in cell transformation and tumour metastasis. Here we summarize and discuss our knowledge of the role of histone supply and histone variants in chromatin dynamics and their ability to enhance oncogenic cell reprogramming and tumour heterogeneity.
ABSTRACT
Autoimmune hemolytic anemia (AIHA) is a common complication of chronic lymphocytic leukemia (CLL) with a complicated pathogenesis. CLL tumor cells can trigger AIHA by directly secreting autoantibodies targeting red blood cells or by presenting erythrocyte antigens. According to the disease features of different patients, multiple treatment regimens, such as glucocorticoid, immunoglobulin, rituximab and chemotherapy containing rituximab and glucocorticoid, could be chosen. AIHA patients respond well to the treatment, but it is easy to relapse. Further studies are needed to optimize the treatment and improve the overall survival of the patients.
ABSTRACT
Objective To evaluate the efficacy of PAD regimen (bortezomib, doxorubicin, dexamethasone) and VAD-like T regimen (vincristine, doxorubicin/doxorubicin derivatives, dexamethasone combined with thalidomide) in the treatment of patients with newly diagnosed multiple myeloma (MM). Methods The efficacy of 54 patients with MM who received VAD like-T regimen and 72 patients with MM who were treated with PAD regimen, including complete remission (CR) rate, very good partial remission (VGPR) rate, overall response rate (ORR), overall survival (OS), progression-free survival (PFS) and adverse events, were retrospectively analyzed. Results The CR rate of PAD group was higher than that of VAD-like T group [31.5 % (23/72) vs. 9.3 % (5/54), χ2=0.30, P=0.002]. The VGPR rate and ORR of PAD group were not statistically higher than those of VAD-like T group [16.7 % (12/72) vs. 16.6 % (9/54), P=0.180; 82.2 %(65/72) vs. 81.5 % (44/54), P=0.190, respectively]. Median PFS of PAD group was significant longer than that of VAD-like T group [(38.2±2.2) months vs. (28.0±7.6) months, P=0.017]. The 3- and 5-year OS rates of PAD group were higher than those of VAD-like T group, but there were no significant differences between two groups (P>0.05). In terms of the adverse events, the incidence of peripheral neuropathy in PAD group was significantly higher than that of VAD-like T group [31.5 % (23/72) vs. 14.5 % (8/54), P=0.03]. Conclusions Compared with PAD protocol, the CR and median PFS of VAD-like T regimen are poor, however, VGPR,ORR, PFS and 5-year OS are similar between the two groups, and VAD-like T regimen is safer with low incidence of peripheral neuropathy. VAD-like T regimen as the first-line treatment is effective and well-tolerated, especially for newly diagnosed MM patients not suitable for transplantation and bortezomib.