Eltrombopag can promote platelet implantation after allogeneic hematopoietic stem cell transplantation as safely and similarly to thrombopoietin.

Background: Eltrombopag has demonstrated efficacy in treating low platelet (PLT) levels, but it remains unclear whether eltrombopag can promote PLT engraftment after hematopoietic stem cell transplantation (HSCT). Methods: Forty-one HSCT patients received eltrombopag 50 mg/d from +1 day until PLT >50 × 109/L or 1 month after HSCT. Fifty-one patients in the same period received thrombopoietin (TPO) to promote PLT graft after HSCT and served as a control group. Results: A total of 51 patients who applied TPO during the same period were treated as a control. In the eltrombopag group, the median time to white blood cells (WBC) graft was 12 days (range, 10-17 days) and the PLT graft was 15 days (range, 10-30 days), whereas for the patients in the TPO group, the median time to WBC and PLT graft was 12 days (range, 9-23 days) and 15.5 days (range, 9-41 days), respectively. In the first month after HSCT, the median WBC count in the eltrombopag group was 4.41 × 109/L (range, 0.87-40.01 × 109/L) and the median PLT was 89x109/L (range, 30-401 × 109/L); the median WBC and PLT \counts in the TPO group were 4.65 × 109/L (range, 0.99-23.63 × 109/L) and 86 × 109/L (range, 5-512 × 109/L), respectively. Patients in the TPO or eltrombopag group did not experience serious side effects after drug administration, and the difference in side effects on liver and kidney function between the two groups was not statistically significant. Conclusion: Eltrombopag is safe and similarly promotes platelet engraftment to thrombopoietin after allogeneic HSCT.

Venetoclax combined with daunorubicin and cytarabine (2 + 6) as induction treatment in adults with newly diagnosed acute myeloid leukemia: a phase 2, multicenter, single-arm trial.

BACKGROUND: Venetoclax (Ven) combined with intensive chemotherapy was proven effective in the management of acute myeloid leukemia (AML). However, the severe and prolonged myelosuppression remains a concern to worry about. To explore more appropriate combination regimens, we designed Ven combining daunorubicin and cytarabine (DA 2 + 6) regimen as induction therapy, aimed to evaluate the effectiveness and safety in adults de novo AML. METHODS: A phase 2 clinical trial was performed in 10 Chinese hospitals to investigate Ven combined with daunorubicin and cytarabine (DA 2 + 6) in patients with AML. The primary endpoints were overall response rate (ORR), comprising of complete remission (CR), complete remission with incomplete blood cell count recovery (CRi), and partial response (PR). Secondary endpoints included measurable residual disease (MRD) of bone marrow assessed by flow cytometry, overall survival (OS), event-free survival (EFS), disease-free survival (DFS), and the safety of regimens. This study is a currently ongoing trial listed on the Chinese Clinical Trial Registry as ChiCTR2200061524. RESULTS: Overall, 42 patients were enrolled from January 2022 to November 2022; 54.8% (23/42) were male, and the median age was 40 (range, 16-60) years. The ORR after one cycle of induction was 92.9% (95% confidence interval [CI], 91.6-94.1; 39/42) with a composite complete response rate (CR + CRi) 90.5% (95% CI, 89.3-91.6, CR 37/42, CRi 1/42). Moreover, 87.9% (29/33) of the CR patients with undetectable MRD (95% CI, 84.9-90.8). Grade 3 or worse adverse effects included neutropenia (100%), thrombocytopenia (100%), febrile neutropenia (90.5%), and one mortality. The median neutrophil and platelet recovery times were 13 (5-26) and 12 (8-26) days, respectively. Until Jan 30, 2023, the estimated 12-month OS, EFS, and DFS rates were 83.1% (95% CI, 78.8-87.4), 82.7% (95% CI, 79.4-86.1), and 92.0% (95% CI, 89.8-94.3), respectively. CONCLUSION: Ven with DA (2 + 6) is a highly effective and safe induction therapy for adults with newly diagnosed AML. To the best of our knowledge, this induction therapy has the shortest myelosuppressive period but has similar efficacy to previous studies.

Genomic Characteristics and Phylogenetic Analyses of a Multiple Drug-Resistant Klebsiella pneumoniae Harboring Plasmid-Mediated MCR-1 Isolated from Tai'an City, China.

Klebsiella pneumoniae is a clinically common opportunistic pathogen that causes pneumonia and upper respiratory tract infection in humans as well as community-and hospital-acquired infections, posing significant threats to public health. Moreover, the insertion of a plasmid carrying the mobile colistin resistance (MCR) genes brings obstacles to the clinical treatment of K. pneumoniae infection. In this study, a strain of colistin-resistant K. pneumoniae (CRKP) was isolated from sputum samples of a patient who was admitted to a tertiary hospital in Tai'an city, China, and tested for drug sensitivity. The results showed that KPTA-2108 was multidrug-resistant (MDR), being resistant to 21 of 26 selected antibiotics, such as cefazolin, amikacin, tigecycline and colistin but sensitive to carbapenems via antibiotic resistance assays. The chromosome and plasmid sequences of the isolated strain KPTA-2108 were obtained using whole-genome sequencing technology and then were analyzed deeply using bioinformatics methods. The whole-genome sequencing analysis showed that the length of KPTA-2108 was 5,306,347 bp and carried four plasmids, pMJ4-1, pMJ4-2, pMJ4-3, and pMJ4-4-MCR. The plasmid pMJ4-4-MCR contained 30,124 bp and was found to be an IncX4 type. It was the smallest plasmid in the KPTA-2108 strain and carried only one resistance gene MCR-1. Successful conjugation tests demonstrated that pMJ4-4-MCR carrying MCR-1 could be horizontally transmitted through conjugation between bacteria. In conclusion, the acquisition and genome-wide characterization of a clinical MDR strain of CRKP may provide a scientific basis for the treatment of K. pneumoniae infection and epidemiological data for the surveillance of CRKP.

Identification of miRNA-mRNA Network Associated with Acute Myeloid Leukemia Survival.

BACKGROUND Acute myeloid leukemia (AML) is a common hematologic malignancy of adults. The pathophysiological mechanism of AML is not well understood. The purpose of this study was to examine the crucial miRNAs and mRNAs associated with AML survival. MATERIAL AND METHODS The full clinical dataset of miRNA and mRNA expression profiling of AML patients was downloaded from The Cancer Genome Atlas database. Univariate Cox regression analysis was performed to obtain those miRNAs and mRNAs associated with AML survival. A miRNA-mRNA interaction network was constructed. The underlying functions of mRNAs were predicted through Kyoto Encyclopedia of Genes and Genomes (KEEG) pathway enrichment. The expression levels of miRNAs and mRNAs were detected by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS Fourteen miRNAs and 830 mRNAs associated with AML survival were identified. Of the 14 miRNAs, hsa-mir-425, hsa-mir-1201, and hsa-mir-1978 were identified as risk factors and the other 11 miRNAs were identified as protective factors of AML survival. For target-genes of miRNAs, GTSF1, RTN4R, and CD44 were the top risk factor target-genes associated with AML survival. An interaction network was constructed that including 607 miRNA-target gene pairs associated with AML survival. Target-genes associated with AML survival were significantly enriched in several pathways including pancreatic secretion, calcium signaling pathway, natural killer cell mediated cytotoxicity, and Alzheimer's disease. The qRT-PCR results were consistent with our bioinformatics analyses. CONCLUSIONS The miRNA hsa-mir-425 was identified as the top risk factor miRNA of AML survival and CD44 was identified as one of the top three risk factor target-genes associated with AML survival. Both hsa-mir-425 and CD44 may play key roles in progression and development of AML through calcium signaling pathway and natural killer cell mediated cytotoxicity.