[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) . Methods: In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed. Results: A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively (P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively (P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively (P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively (P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively (P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively (P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively (P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively (P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively (P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion: There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

[Analysing pathogenic bacterial spectrum and drug resistance of bloodstream infection in patients with allogeneic hematopoietic stem cell transplantation].

Objective: To elucidate the clinical characteristics of bloodstream infection in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in our hospital and improves the survival of transplant patients with bloodstream infection. Methods: Two hundred and ten patients with allo-HSCT from the Department of Hematology were retrospectively analyzed between October 2014 and September 2019. Pathogen distribution, drug resistance, risk factors, and outcomes were investigated in 49 allo-HSCT patients with bloodstream infections. Results: Forty-nine of 210 patients with allo-HSCT had bloodstream infection, and 59 pathogenic microorganisms were identified, mainly Gram-negative bacteria (67.8%) , of which E. coli had the highest incidence (23.7%) , CRO accounted for 42.5%, and Grampositive bacteria accounted for 23.7% (without vancomycin or linezolid-resistant strain) . Additionally, fungi accounted for 8.5%. Univariate analysis suggested that the risk factors of bloodstream infection were gender, pretransplant disease status, and conditioning regimen. In contrast, multivariate analysis showed that bloodstream infection was mainly related to conditioning regimens. Further grouping results showed that 77.6% of patients with neutropenia had bloodstream infections, and 22.4% of patients with non-neutropenia had bloodstream infections; 81.0% of patients with active infections before transplantation had bloodstream infections, while bloodstream infection occurred in 16.9% of patients without active infection. Survival analysis showed that long-term survival of patients with bloodstream infection is shorter than that of patients without bloodstream infection and long-term survival of patients with CRO infection is shorter than that of patients without CRO infection. The survival of patients with neutropenia longer than 14 d is shorter than that of patients with neutropenia shorter than 14 d. Furthermore, there is no correlation between whether there is an active infection before transplantation and whether they are in a neutropenic state at the time of infection and survival. Conclusion: Our results suggest that effective prevention of bloodstream infections from drug-resistant bacteria, particularly CRO, shortening the duration of neutropenia, eradication of potential infections before transplantation, and patient-adaptive conditioning could reduce transplant-related mortality and improve prognosis.

Identification potential biomarkers and therapeutic agents in multiple myeloma based on bioinformatics analysis.

OBJECTIVE: The study aimed to identify potential therapeutic biomarkers and agents in multiple myeloma (MM) based on bioinformatics analysis. MATERIALS AND METHODS: The microarray data of GSE36474 were downloaded from Gene Expression Omnibus database. A total of 4 MM and 3 normal bone marrow mesenchymal stromal cells (BM-MSCs) samples were used to identify the differentially expressed genes (DEGs). The hierarchical clustering analysis and functional enrichment analysis of DEGs were performed. Furthermore, co-expression network was constructed by Cytoscape software. The potential small molecular agents were identified with Connectivity Map (cMap) database. RESULTS: A total of 573 DEGs were identified in MM samples comparing with normal samples, including 322 down- and 251 up-regulated genes. The DEGs were separated into two clusters. Down-regulated genes were mainly enriched in cell cycle function, while up-regulated genes were related to immune response. Down-regulated genes such as checkpoint kinase 1 (CHEK1), MAD2 mitotic arrest deficient-like 1 (MAD2L1) and DBF4 zinc finger (DBF4) were identified in cell cycle-related co-expression network. Up-regulated gene of guanylate binding protein 1, interferon-inducible (GBP1) was a hub node in immune response-related co-expression network. Additionally, the small molecular agent vinblastine was identified in this study. CONCLUSIONS: The genes such as CHEK1, MAD2L1, DBF4 and GBP1 may be potential therapeutic biomarkers in MM. Vinblastine may be a potential therapeutic agent in MM.

Identification and expression analysis of components involved in rice Xa21-mediated disease resistance signalling.

Rice Xa21 gene encodes a receptor-like kinase that confers broad-spectrum resistance against Xanthomonas oryzae pv. oryzae (Xoo). Recently, a number of genes involved in the Xa21-mediated disease resistance pathway have been identified. Based on our previous data and the literature, we chose 16 candidate proteins and made corresponding antibodies. Using Western blotting, we systematically investigated the expression profile of the proteins in Xa21-mediated disease resistance response. We found nine proteins with altered expression. We further compared their expression in resistance, susceptible and mock responses, and found that GST expression was up-regulated during the resistance process, indicating GST is a positive regulator in resistance responses. ATPsB expression was down-regulated during both the resistance and susceptible response processes, although it was higher in the resistance response than that in the susceptible response. The total amount of MYB, GAPDH, CatB, Trx and NB-ARC proteins was lower in the resistance than in the susceptible response, but their abundance per unit bacteria in the resistance response was still higher than in the susceptible response, suggesting that these proteins might be positive regulators in the resistance response. In addition, expression of another ERF was induced by inoculation with bacterial blight pathogen, and expression of Zf-LSD1 was activated by wounding stress alone. Interestingly, most proteins showed similar altered expression patterns in the resistance and susceptible responses, but differed to some extents, implying that both responses might share common molecular mechanisms. This study revealed evidence of resistance-related protein expression, providing a foundation for better understanding of their functions.