Short-Term Efficacy and Safety Profile of Generic Bortezomib in the Treatment of Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the short-term efficacy and safety of generic bortezomib in the treatment of Chinese patients with multiple myeloma (MM).@*METHODS@#Clinical data of 62 MM patients (median age of 62 years) who had accepted at least 2 cycles of chemotherapy based on generic bortezomib in our center from December 2017 to July 2019 were retrospectively analyzed, including 47 newly diagnosed patients and 15 with disease recurrence or progression.@*RESULTS@#Anemia, renal dysfunction, hypoproteinemia and high level of β @*CONCLUSION@#The disease severity can be rapidly alleviated after generic bortezomib-based chemotherapy, and a favorable short-term efficacy and survival have been observed with a generally acceptable toxicity profile. However, the long-term outcomes will be examined through further follow-up.

Effect of High Dose Vitamin C on Proliferation and Apoptosis of Acute Myeloid Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of high dose vitamin C on proliferation and apoptosis of acute myeloid leukemia (AML) cell lines including HL-60, U937 and primary CD34 leukemia cells in AML.@*METHODS@#CD34 cells were sorted by using immunomagnetic cell sorting system, then the primary CD34 leukemia cells, including HL-60 and U937 cell lines were cultured in vitro. Cells in each group were treated with different concentrations of vitamin C, the survival rate of cells was determined by MTT assay, the apoptosis rate of cells was evaluated by Annexin V/PI double staining, the expression of apoptotic proteins-including cleaved caspase 3, cleaved caspase-9 and cleaved PARP were detected by Western blot.@*RESULTS@#The proliferation of HL-60 and U937 cells could be inhibited by high dose vitamin C, which showed a concentration-dependent manner (r=-0.9664; r=-0.9796). HL-60 and U937 cells were treated with different concentrations of vitamin C (8 and 20 mmol/L) for 24 hours, respectively, it was found that with the increasing of vitamin C concentration, cell apoptosis rate was significantly increased (r=0.9905; r=0.9971), and the expression of apoptosis related proteins including cleaved caspase 3, cleaved caspase-9 and cleaved PARP was aslo significantly increased with the increasing of concentration. In addition, it was found that with or without the mutation of TET2, high dose vitamin C could inhibit the proliferation (r=-0.9719; r=-0.9699) and promote the apoptosis (r=0.9998; r=0.9901) of primary CD34 leukemia cells in AML, which showed a dose-dependent manner, but it showed no effect on the proliferation (r=-0.2032) and apoptosis (r=0.1912) of normal CD34 cells.@*CONCLUSION@#High dose vitamin C can inhibit the proliferation and promote the apoptosis of acute myeloid leukemia cells, and selectively kill primary CD34 leukemia cells in AML.

Clinical observation of early re-induction with priming low dose regimen containing G-CSF in treating acute myeloid leukemia / 重庆医学

Objective To evaluate the remission situation of early re-induction with priming low dose regimen containing G-CSF in treating acute myeloid leukemia (AML).Methods Ninety-seven AML patients in our hospital from March 2015 to January 2017 were retrospectively analyzed.All cases adopted the standard DA regimen for conducting the induction chemotherapy,among them,38 cases had significant residual disease on 14 d of induction chemotherapy,21 cases adopted the low dose priming regimen for conducting the early re-induction chemotherapy,17 cases adopted the tandard DA gregimen for conducting the re-induction chemotherapy.The complete remission(CR) rate and and adverse reactions were compared between two groups.Results The total CR rate in all 97 cases was 60.8％;among 38 cases needing re-induction chemotherapy,the CR rate in the priming regimen re-induction group was 76.2 ％,which was significantly higher than 41.2 ％ in the DA regimen re-induction group,the difference was statistically significant (P=0.028);the occurrence rates of side effects such as infection and cytopenia during re-induction chemotherapy process had no difference between two groups(P＞0.05).Conclusion For AML patients with obvious residual disease on 14 d of induction chemotherapy,adopting low dose priming regimen in re-duction chemotherapy has higher CR,which is superior to the standard DA regimen.

Detection of imatinib in the plasma and its effect in the patient with chronic myeloid leukemia / 白血病·淋巴瘤

Objective To evaluate the relationship between plasma imatinib and its effect in the treatment of chronic myeloid leukemia(CML). Methods Fifty-one CML patients were included in this study,who began taking imatinib from July 2005 to February 2008, with 34 cases of male, and 17 cases of female.Nine patients took imatinib at dose of 300 mg/d, 37 patients took imatinib at dose of 400 mg/d, and 5 patients took imatinib at dose of 600 mg/d. High-performance liquid chromatography was used to test imatinib plasma levels. Results The imatinib plasma levels was imatinib dose-related, and the imatinib plasma trough levels significantly varied between individuals[(342-4688)ng/ml]. The imatinib plasma levels was significant lower in 300 mg/d dose group [(1037±514) ng/ml] than 400 mg/d dose group [(2123±1016) ng/ml] (t =2.34, P =0.032),and the effective rate was 66.7 % (6/9) in 300 mg/d dose group, which was lower than 400 mg/d dose group of 89.19 % (33/37) (χ2=7.14, P =0.008). In 300 mg/d and 400 mg/d dose groups, 39 patients achieved effective treatment, and their imatinib plasma levels was significant higher than that of 7 patients who did not achieved effective treatment (t =2.25, P =0.037). The ROC curve results suggested that clinical treatment may be poor when the imatinib plasma level was lower than 1050 ng/ml (sensitivity was 84.6 %, specificity was 71.1 %).Conclusion The imatinib plasma levels was dose-related, and significantly varied between individuals.Clinical treatment effect may be poor when the imatinib plasma level was lower than 1050 ng/ml.

Expression of B7-H1 molecule on human bone marrow mesenchymal stem cells and its effects on T lymphocyte proliferation / 中国实验血液学杂志

The mechanisms of human bone marrow mesenchymal stem cells (hBMMSCs)-mediated immunomodulation are still not be completely clarified. In order to investigate the expression of B7-H1 on hBMMSCs and to explore whether B7-H1 mediated signaling pathway (B7-H1/PD-1) involves in the mechanisms of hBMMSCs-mediated immunomodulation, the hBMMSCs were isolated, cultured and identified, the B7-H1 expression on hBMMSCs was detected by flow cytometry, RT-PCR, and Western blot. The inhibitory effect of hBMMSCs on proliferation of T lymphocytes was observed in mixed lymphocyte culture, and then the functional anti-B7-H1 monoclonal antibody (mcAb) was used to block B7-H1, the proliferation of T lymphocytes was detected by using CCK-8. The results indicated that hBMMSCs highly expressed B7-H1 molecule, hBMMSCs effectively inhibited the proliferation of T lymphocytes with a dose-dependent manner, and the inhibitory proliferation of T lymphocytes by hBMMSCs could be partially restored when the anti-B7-H1 mAb was used to block the B7-H1, the inhibitory rate of T lymphocyte proliferation decreased from 64.1% to 38.75%. It is concluded that B7-H1 highly expresses on hBMMSCs, the B7-H1 mediated signaling pathway (B7-H1/PD-1) involves in the mechanisms for hBMMSCs-mediated immunomodulation.

The clinical significance of Ig heavy chain and TCR gamma gene rearrangement detected in free DNA in plasma in patients with non-Hodgkin lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the clinical significance of IgH and TCR gamma gene rearrangement in plasma free DNA in patients with non-Hodgkin Lymphoma (NHL).</p><p><b>METHODS</b>Plasma free DNA in 74 patients with NHL were extracted and identified by Globin gene. IgH (FR3A/VLJH), TCR gamma (TVG/TJX) clonal rearrangements were amplified by PCR and compared with results of mononuclear cell DNA and pathological biopsy sample DNA.</p><p><b>RESULTS</b>Plasma free DNAs were successfully obtained from 58 cases (35 B-NHL and 23 T-NHL) of newly diagnostic, refractory and relapsed NHL out of total 74 patients (78.4%), but not found in the rest 16 patients in remission. Of 35 B-NHL cases, 31 showed IgH rearrangement (88.6%), and none with TCR gamma rearrangement; of 23 T-NHL cases, 8 showed TCR gamma rearrangement (34.8%), and 2 with IgH gene rearrangement synchronously. In comparison with the results of IgH and TCR gamma gene rearrangement in biopsy samples in 30 B-NHL cases, 26 cases in plasma free DNA (86.7%) and 24 in biopsy samples (80%) were positive (P > 0.05). In 20 T-NHL patients, 7 cases in plasma cell-free DNA (35%) and 6 cases in biopsy samples (30%) were positive (P >0.05).</p><p><b>CONCLUSIONS</b>Tumor-derived DNA could be detected in plasma from underlying cancer patients. For NHL patients, detecting IgH and TCR gamma gene rearrangement in plasma free DNA has the same clinical significance as in biopsy samples.</p>