Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）.@*METHODS@#A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed.@*RESULTS@#A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients.@*CONCLUSION@#VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.

Research Progress of Allogeneic Hematopoietic Stem Sell Trans-plantation in the Treatment of Adult Hemophagocytic Lympho-histiocytosis --Review / 中国实验血液学杂志

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory clinical syndrome of uncontrolled immune response which results in hypercytokinemia due to underlying primary or secondary immune defect. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only cure therapy for primary HLH and recurrent/refractory hemophagocytic lymphohistiocytosis. Compared with children HLH, adult HLH is a much more heterogeneous syndrome requiring a more individualized protocol depending on the underlying trigger, disease severity and genetic background. At present, there remain controversies in various aspects including indications of haematopoietic cell transplantation (HCT), conditioning regimen, efficacy and prognosis. This article will review the recent advances of allo-HSCT in the treatment of adult HLH based on the above issues.

Establishment and Clinical Significance of Prognostic Nomogram Model for Diffuse Large B-Cell Lymphoma Based on Immunohistochemistry Markers and International Prognostic Index Scores / 中国实验血液学杂志

OBJECTIVE@#To retrospectively analyze clinical characteristics and survival time of patients with diffuse large B-cell lymphoma (DLBCL), detect prognosis-related markers, and establish a nomogram prognostic model of clinical factors combined with biomarkers.@*METHODS@#One hundred and thirty-seven patients with DLBCL were included in this study from January 2014 to March 2019 in the First Affiliated Hospital of Nanchang University. The expression of GCET1, LMO2, BCL-6, BCL-2 and MYC protein were detected by immunohistochemistry (IHC), then the influences of these proteins on the survival and prognosis of the patients were analyzed. Univariate and multivariate Cox regression analysis were used to gradually screen the prognostic factors in nomogram model. Finally, nomogram model was established according to the result of multivariate analysis.@*RESULTS@#The positive expression of GCET1 protein was more common in patients with Ann Arbor staging I/II (P =0.011). Compared with negative patients, patients with positive expression of LMO2 protein did not often show B symptoms (P =0.042), and could achieve better short-term curative effect (P =0.005). The overall survival (OS) time of patients with positive expression of LMO2 protein was significantly longer than those with negative expression of LMO2 protein (P =0.018), though the expression of LMO2 protein did not correlate with progression-free survival (PFS) (P >0.05). However, the expression of GCET1 protein had no significant correlation with OS and PFS. Multivariate Cox regression analysis showed that nomogram model consisted of 5 prognostic factors, including international prognostic index (IPI), LMO2 protein, BCL-2 protein, MYC protein and rituximab. The C-index applied to the nomogram model for predicting 4-year OS rate was 0.847. Moreover, the calibrated curve of 4-year OS showed that nomogram prediction had good agreement with actual prognosis.@*CONCLUSION@#The nomogram model incorporating clinical characteristics and IHC biomarkers has good discrimination and calibration, which provides a useful tool for the risk stratification of DLBCL.

Efficacy and Safety of Etoposide Combined with Cyclophosphamide for Autologous Peripheral Blood Stem Cell Mobilization in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of etoposide combined with cyclophosphamide (EC) regimen for mobilization of autologous peripheral blood stem cells (APBSCs) in patients with multiple myeloma (MM).@*METHODS@#The clinical data of 48 MM patients who received APBSC transplantation (APBSCT) in Department of Hematology of the First Affiliated Hospital of Nanchang University from January 2015 to October 2021 were retrospectively analyzed. The mobilization success rate and mobilization optimal rate of EC regimen were counted, and its effect on transplant efficacy, adverse reactions, hematopoietic reconstitution after transplantation, and survival time of MM patients were analyzed.@*RESULTS@#APBSCs were collected on day 14 (10-19) after EC administration. The median of collected CD34+ cells was 6.82 (1.27-22.57)×106/kg, and the median number of apheresis session was 2 (1-4). The mobilization success rate (collecting CD34+ cells≥2×106 cells/kg after completion of apheresis) was 98% (47/48), and mobilization optimal rate (collecting CD34+ cells≥5×106 cells/kg after completion of apheresis) was 71% (34/48). The depth of remission were improved after APBSCT, and the complete remission (CR) rate increased from 45.8% before transplantation to 87.5% after transplantation (P <0.01). There was no transplant-related death, no blood transfusion during mobilization, and no mucositis occurred in the patients. The most common complication was neutropenia, with an incidence of 75.0% (36/48). After transplantation, all the patients successfully achieved hematopoietic reconstitution. The median time to neutrophil engraftment was 10 (9-26) days, and median time to platelet engraftment was 10 (8-33) days. By the end of follow-up, both the median progression-free survival (PFS) and overall survival (OS) time were not reached. The 5-year estimated PFS rate and OS rate was 53.8% and 82.4%, respectively.@*CONCLUSION@#The EC regimen for mobilization of APBSC has a high acquisition success rate and controllable adverse reactions, which can be an effective and safe mobilization regimen in MM patients.

Association between platelet-derived growth factor-C single nucleotide polymorphisms and nonsyndromic cleft lip with or without cleft palate in Western Chinese population / 华西口腔医学杂志

OBJECTIVE@#To explore the association between two single nucleotide polymorphisms (SNPs), namely, rs4691383 and rs7667857, in the platelet-derived growth factor-C (PDGF-C) gene, the genotypes, environmental exposure factors, and nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Western Chinese population.@*METHODS@#A total of 268 case-parent trios were selected, and two SNPs (rs4691383 andrs7667857) were genotyped by using polymerase chain reaction and restriction enzyme fragment length polymorphic method and direct sequencing method. Hardy-Weinberg equilibrium, linkage disequilibrium test, transmission disequilibrium test, and haplotype analysis were conducted to analyze the data. Meanwhile, the questionnaires on the epidemiology of cleft lip and palate filled by the included samples were collected, and the interaction between the genotypes of the two SNPs and environmental exposure factors was assessed by conditional logistic regression.@*RESULTS@#The A allele at rs4691383 and the G allele at rs7667857 of PDGF-C gene were over-transmitted for NSCL/P (P0.05).@*CONCLUSIONS@#The rs4691383 and rs7667857 at PDGF-C gene are closely related to the occurrence of NSCL/P in Western Chinese population. However, the interaction between environmental exposure factors and PDGF-C genotypes is not obvious in the occurrence of NSCL/P.

Prognostic Impact of 1q21 Amplification in Newly Diagnosed Multiple Myeloma Patients Receiving Bortezomib-Based First-Line Treatment / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the amplification rate, clinical correlation and prognostic significance of 1q21 amplification in newly diagnosed patients with multiple myeloma (MM).</p><p><b>METHODS</b>I-FISH was performed on purified 138plasma cells from 72 newly diagnosed MM patients from February 2013 to February 2016 receiving bortezomib-based chemotherapy by using probe covered 1q21 region. Cut off value is 20%. Amplification rate, clinical relevance and prognostic significance were analysed in MM patients.</p><p><b>RESULTS</b>Among 72 patients, male 52, femail 20, the median age was 58(33-80).The amplification rate of 1q21 was 45.8%, the 1q21 amplification was positivly correlated with 13q14 deletion(P=0.041)and ISS III stage (P=0.002). With a median follow-up time of 17.0(3.0-40.0)months, the estimated median progression-free survival(PFS) time and overall survival(OS) time for patients with 1q21 amplification were 17.0 and 22.0 months, however, they did not reach in patients without 1q21 amplification(P=0.000, P=0.001). The multivariate analysis showed that del(17p13), 1q21 amplification and LDH≥220 U/L remained as independent risk factors for PFS and OS.</p><p><b>CONCLUSION</b>1q21 amplification is an important genetics prognosis indicator in newly diagnosed multiple myeloma patients receiving bortezomib-based first-line treatment. Bortezomib-based treatment can not improve the poor survival in patients with 1q21 amplification.</p>

Transgenic mouse models of the truncated platelet integrin β3 cytoplasmic tail established by stem cell transplantation / 中国实验血液学杂志

This study was purpose to establish the transgenic mouse models of the truncated platelet integrin β3 by retrovirus-infected hematopoietic stem cells (HSCs) transplantation and to provide the basis for further study of the role of integrin β3 cytoplasmic domain in platelet bi-directional signaling pathways. Wild-type β3, β3-Δ759 (R(760) GT(762) truncated β3) and β3-Δ754 (T(755) NITYRGT(762) truncated β3) cDNAs were subcloned into MSCV MigR1 retroviral vector bearing a GFP gene and packaged into infective retrovirus with BOSC23 cell strain. The bone marrow HSCs of the β3 deficient mice were infected by the retroviruses, and transplanted into lethally-irradiated wild type C57BL/6 mice. GFP positive rate and surface β3 expression of the recipients' platelets at 6 to 8 weeks after transplantation were detected by flow cytometry to evaluate the transgenic efficiency. The results showed that four kinds of transgenic mouse models including vector, wild-type β3, β3-Δ759 and β3-Δ754 were established successfully. GFP positive rates of transgenic mouse platelets ranged from 18% to 66% and the β3 expression of transgenic mouse reached heterozygote (β3(+/-) level of mouse). It is concluded that establishment of transgenic mouse models mediated by retrovirus-infected HSCs transplantation is a feasible, fast, and high throughput transgenic approach and laid a solid foundation for further research on the role of integrin β3 cytoplasmic domain for bi-directional signaling of platelets in vivo, and for the gene therapy of platelet disorders.

Correlation between myocardial ischemia and carotid atherosclerosis in hypertensive patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the correlation between myocardial ischemia and carotid atherosclerosis in hypertensive patients.</p><p><b>METHODS</b>The clinical data were collected from 85 hospitalized hypertensive patients admitted between May 2005 and September 2008 without the complication of coronary artery disease as confirmed by cardiac computed tomographic angiography (CTA). According to the results of treadmill exercise test, the patients were divided myocardial ischemia group and ischemia-free group. Univariate and multivariate analyses were used to screen the risk factors of myocardial ischemia. The correlations were analyzed between myocardial ischemia, common carotid artery intima-media thickness (IMT), Crouse score of the carotid plaque, thickness of the intraventricular septum and left artrium. The receiver operating characteristic (ROC) curves were used to evaluate the sensitivity and specificity of IMT and Crouse score in predicting the presence of myocardial ischemia in hypertensive patients.</p><p><b>RESULTS</b>Carotid plaque formation was identified as the major risk factor of myocardial ischemia in hypertensive patients (OR=4.982, P=0.004). The incidence of myocardial ischemia in the hypertensive patients with carotid plaques was significantly higher than that in the patients without the plaque (Chi2=9.317, P=0.002). Myocardial ischemia in hypertensive patients was positively correlated to the thickness of the intraventricular septum (r=0.362, P=0.001) and left artrium (r=0.298, P=0.009), and the IMT of the common carotid artery was positively correlated to the thickness of the intraventricular septum (r=0.231, P=0.045). The area under cure (AUC) of the ROC curve of Crouse score was 0.726-/+0.061 in predicting the presence of myocardial ischemia in the hypertensive patients (P=0.001), and that of IMT was 0.682-/+0.061 (P=0.006).</p><p><b>CONCLUSION</b>Carotid plaque formation is the major risk factor of myocardial ischemia in hypertensive patients and shows a positive correlation to the onset of myocardial ischemia, but both the common carotid artery IMT and the Crouse score of the carotid plaque are not accurate markers for predicting myocardial ischemia in patients with hypertension.</p>