Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience / 中华血液学杂志

Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.

Neuroprotective effect of Paeoniae Radix Rubra on hippocampal CA1 region of mice induced by transient focal cerebral ischemia via anti-gliosis and anti-oxidant activity / 中草药·英文版

Objective: Stroke is the second leading cause of death worldwide. This study aimed to investigate the neuroprotective effect of Paeoniae Radix Rubra (PRR) on ischemic stroke of mice. Methods: The focal ischemic stroke model was produced via middle cerebral artery occlusion. The experimental mice were divided into four groups: vehicle-sham group, PRR-sham group, vehicle-ischemia group, and PRR-treated ischemia group. The cerebral infarction volume was detected with TTC staining. The number of neurons in the hippocampal CA1 of the ischemic side, and the activation of astrocytes and microglia were observed via immunohistochemical staining. Western blotting was used to determine the expression changes of SOD1, SOD2, and Catalase protein levels in the hippocampus. Results: PRR significantly reduced the cerebral infarct volume induced by ischemic injury and inhibited the astrocytes and microglia activation in the hippocampal CA1 region. The decreased levels of SOD1, SOD2, and Catalase that was induced by ischemic reperfusion were simultaneously improved after PRR treatment. Conclusion: PRR improved neuronal injuries that were induced by transient cerebral ischemia via inhibiting gliosis and elevating anti-oxidants.

Pathogenesis and Prevention of Transfusion-Associated Graft-versus-Host Disease / 中国实验血液学杂志

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare complication of blood transfusion. The disease is fulminant and fatal in most patients. TA-GVHD is caused by transfused alloreactive donor T lymphocytes that attack host tissue, including skin, liver, gastrointestinal tract and bone marrow. Most patients are immunocompromised, but immunocompetent patients can also be involved. Irradiation of blood components is generally recommended to prevent the onset of TA-GVHD for susceptible recipients. This review focus on pathogenesis and prevention of TA-GVHD.

Construction of Lentivirus Vector Carrying HGF and Exploration of Transfection Condition of Rat Adipocyte-derived Mesenchymal Stem Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>This study was to construct the lentivirus vector carrying hepatocyte growth factor (HGF) gene and to explore the condition for transfecting the adipocyte-derived mesenchymal stem cells (ADSC) by HGF lentivirus.</p><p><b>METHODS</b>The target gene was obtained from plasmid carrying HGF gene by PCR and was cloned into GV287 vector. The recombinant GV287-HGF vector plasmid and lentivirus-packing plasmid were co-transfected into 293 T cells to generate HGF lentivirus, and the virus titer was assayed, then the ADSC were transfected by using recombinant HGF lentivirus, and the optimal multplicity of infection (MOI) was detected.</p><p><b>RESULTS</b>The PCR product of HGF gene was consistent with expectant sizes, suggesting that the electrophoretic result of recombinant GV287-HGF plasmid PCR product was correct. The sequencing analysis of cleaved product showed consistance of obtained results with the sequences of target gene, suggesting correct construction of recombinant lentivirus carrying HGF gene. The ELISA showed that the virus tilter was 5×10(8) TU/ml. The optimal MOI for transfecting ADSC with recombinant lentivirus carrying HGF gene was 50.</p><p><b>CONCLUSION</b>The lentivirus vector expressing human HGF gene has been constructed, and transfected the ADSC succesfully. This study lays a foundation for further stadying the ADSC over-expressioning HGF, treating the radiation damage of bone marrow and impartant internal organs.</p>

Research advances on ADAM28 expression and ADAM28-mediated tumor metastasis / 中国实验血液学杂志

A disintegrin-metalloproteinase 28 (ADAM28) is one of important members of ADAM family, that is involved in various biological events including cell adhesion, proteolysis, growth and metastasis of solid tumors and hematological malignancies. Studies have shown that ADAM28 is highly expressed in several human tumors, such as lung, breast and bladder cancers, and chronic lymphocytic leukemia, and its tissue expression levels correlate with cancer metastasis. ADAM28-mediated cancer cell metastasis may be related with the cleavage of von Willebrand's factor (vWF), insulin-like growth factor binding protein-3 (IGFBP-3) and connective tissue growth factor (CTGF), as well as the promoting PSGL-1/P-selectin-mediated cell adhesion. This review summarizes the basic and translational aspects of ADAM28 biology that might stimulate the interest in ADAM28 research and discovery of novel ADAM28 targets, providing potential novel therapies for metastatic cancers.