Background Acute myeloid leukemia (AML) is one of the most common hematologic malignancies with a poor prognosis and high recurrence rate. The discovery of new predictive models and therapeutic agents plays a crucial role. Methods The differentially expressed gene that was explicitly highly expressed in The Cancer Genome Atlas (TCGA) and GSE9476 transcriptome databases were screened and included in the least absolute shrinkage and selection operator (LASSO) regression model to derive risk coefficients and build a risk score model. Functional enrichment analysis was conducted on the screened hub genes to explore the potential mechanisms. Subsequently, critical genes were incorporated into a nomogram model based on risk scores to analyze prognostic value. Finally, this study combined network pharmacology to find potential natural compounds for hub genes and used molecular docking to verify the binding ability of molecular structures to natural compounds to explore drug development for possible efficacy in AML. Results A total of 33 highly expressed genes may be associated with poor prognosis of AML patients. After LASSO and multivariate Cox regression analysis of 33 critical genes, Rho-related BTB domain containing 2 ( RHOBTB2 ), phospholipase A2 ( PLA2G4A ), interleukin-2 receptor-α ( IL2RA ), cysteine and glycine-rich protein 1 ( CSRP1 ), and olfactomedin-like 2A ( OLFML2A ) were found to played a significant role in the prognosis of AML patients. CSRP1 and OLFML2A were independent prognostic factors of AML. The predictive power of these 5 hub genes in combination with clinical features was better than clinical data alone in predicting AML in the column line graphs and had better predictive value at 1, 3, and 5 years. Finally, through network pharmacology and molecular docking, this study found that diosgenin in Guadi docked well with PLA2G4A , beta-sitosterol in Fangji docked well with IL2RA , and OLFML2A docked well with 3,4-di-O-caffeoylquinic acid in Beiliujinu. Conclusions The predictive model of RHOBTB2 , PLA2G4A , IL2RA , CSRP1 , and OLFML2A combined with clinical features can better guide the prognosis of AML. In addition, the stable docking of PLA2G4A , IL2RA , and OLFML2A with natural compounds may provide new options for treating AML.
Background The replacement of doxorubicin with other anthracyclines like epirubicin, pirarubicin, or liposomal adriamycin in the R-CHOP regime showed non-inferiority for DLBCL. Replacing vincristine with vindesine (R-CHVP) in R-CHOP has rarely been compared in efficacy and safety. This study aimed to figure out whether R-CHVP was non-inferior to R-CHOP in both efficacy and toxic effects.Methods This is a retrospective study performed at The First Hospital of Lanzhou University, including all consecutive adult patients aged over 18 years with newly diagnosed DLBCL who received therapy with R-CHOP or R-CHVP from March 2008 to September 2020. We compared the efficacy and safety of the R-CHVP regimen with vincristine and the R-CHOP regimen with vindesine.Results We identified 56 patients with DLBCL, including 18 patients in R-CHOP, 7 in R-CTOP, 12 in R-CEOP, 17 in R-CEVP, 11 in R-CTVP. Complete response was achieved in 12(66.7%), 4(57.1%), 5(41.7%), 7(41.2%) and 4(36.4%) patients respectively. The ORR of the five different schemes is 83.3%, 85.7%, 66.7%,64.07%,and 81.8%, respectively. The most common hematological adverse events during induction were anemia and neutropenia, and the most common non-hematological toxicity are gastrointestinal symptoms and neurotoxicity. The comparison of adverse events between R-CEOP and R-CEVP groups is as follows: the toxicity of hematological adverse events was not statistically significant; among non-hematological toxicity, the R-CEVP group was superior to the R-CEOP group in peripheral neuropathy (p=0.026). The 2-year progression-free survival were 75.5%, 54.6%, 53.2%, 62.7% and 42.4% in R-CHOP, R-CTOP, RCEOP, R-CEVP and R-CTVP group respectively.Conclusion The R-CHVP, in which vincristine was substituted by vindesine, was not inferior to the standard R-CHOP regimen and showed less neurotoxicity. Treatment regimens composed of different anthracyclines have similar therapeutic benefits and adverse events in addition to cardiotoxicity.
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