Vorinostat enhances chemosensitivity to arsenic trioxide in K562 cell line

Objective. This study aimed to investigate the chemosensitive augmentation effect and mechanism of HDAC inhibitor Vorinostat (SAHA) in combination with arsenic trioxide (ATO) on proliferation and apoptosis of K562 cells.Methods. The CCK-8 assay was used to compare proliferation of the cells. Annexin-V and PI staining by flow cytometry and acridine orange/ethidium bromide stains were used to detect and quantify apoptosis. Western blot was used to detect expression of p21, Akt, pAkt, p210, Acetyl-Histone H3, and Acetyl-Histone H4 proteins.Results. SAHA and ATO inhibited proliferation of K562 cells in an additive and time- and dose-dependent manner. SAHA in combination with ATO showed significant apoptosis of K562 cells in comparison to the single drugs alone (p < 0.01). Both SAHA and ATO alone and in combination showed lower levels of p210 expression. SAHA and SAHA and ATO combined treatment showed increased levels of Acetyl-Histone H3 and Acetyl-Histone H4 protein expression. SAHA alone showed increased expression of p21, while ATO alone and in combination with SAHA showed no significant change. SAHA and ATO combined therapy showed lower levels of Akt and pAkt protein expression than SAHA or ATO alone.Conclusion. SAHA and ATO combined treatment inhibited proliferation, induced apoptosis, and showed a chemosensitive augmentation effect on K562 cells. The mechanism might be associated with increasing histone acetylation levels as well as regulating the Akt signaling pathway

Emergency Combination of Four Drugs for Bloodstream Infection Caused by Carbapenem-Resistant Enterobacteriaceae in Severe Agranulocytosis Patients with Hematologic Malignancies after Hematopoietic Stem Cell Transplantation

Bloodstream infection (BSI) caused by multidrug-resistant (MDR) bacteria or extensively drug-resistant (XDR) bacteria is a global threat. However, an effective treatment regimen is still controversial and inadequate due to the rapid deterioration caused by the bacteria. In immunocompromised and neutropenic patients, MDR-BSI is an emergency, which causes treatment-related mortality. In this study, four agranulocytosis patients with hematologic malignancies after HSCT receiving treatment for carbapenem-resistant Enterobacteriaceae- (CRE-) BSI were included. Conventional treatment using two to three combined antibiotics was administered in the first and second patients. Combination treatment using four drugs, polymyxin B, high-dose tigecycline, fosfomycin, and double-dose carbapenem, was administered in the third and fourth patients. None of the patients receiving conventional treatment survived. Both patients receiving combination treatment using four drugs survived. Therefore, four-drug combination therapy may be needed in CRE-BSI patients who experienced severe agranulocytosis after HSCT. The efficacy of the four-drug combination treatment for CRE-BSI patients as well as the adverse effects need to be further studied

Lymph Node Flow Cytometry as a Prompt Recognition of Ultra Early Onset PTLD: A Successful Case of Rituximab Treatment

Ultra early posttransplantation lymphoproliferative disorder (PTLD) is a rare and fatal complication after hematopoietic stem cell transplantation (HSCT). Here we report, by lymph node (LN) flowcytometry, that we early recognized ultra early PTLD after an HLA-matched sibling allo-HSCT followed by a successful treatment with anti-CD20 antibody (rituximab) in a patient in progress disease for angioimmunoblastic T-cell lymphoma (AITL). The patient was conditioned with a reduced intensity conditioning (RIC) regimen. One week after transplantation, the patient developed high fever, generalized fatigue, high Epstein-Barr virus (EBV) load, and LN enlargement. An LN lymphocyte suspension and peripheral blood flowcytometry was performed to find majority of LN lymphocytes highly expressed CD20. By highly suspicious PTLD, 4 doses of rituximab (375 mg/m2 qw) were given immediately followed by reducing and withdrawing immunosuppressant reagent. PTLD was later confirmed by pathology. The patient had good response to rituximab, showing absence of fever, reduction in LN size, and no detectable EBV-DNA. Twenty months after HSCT, the patient remains well without evidence of AITL and PTLD. The current report is one of the earliest cases of PTLD after HSCT. Taken together, by LN flowcytometry as a prompt recognition, rituximab can be an effective preemptive therapy for ultra early developed PTLD