Efficacy and quality of life of Romiplostim in adults and children with immune thrombocytopenia: A review.

BACKGROUND: To systematically evaluate the clinical efficacy, drug safety and health-related quality of life (HRQoL) of Romiplostim in adult and child immune thrombocytopenia (ITP) patients. METHODS: PubMed, EMBASE and Cohrane library databases were searched for all randomized controlled trials published until 2022, and the Review Manager 5.3 was used for meta-analysis. RESULTS: A total of 9 randomized controlled trials were included in this study. The results of meta-analysis showed that the total platelet response rate and long-term platelet response rate in treatment group were significantly higher than those in control group (P<0.05). There was no statistical significance in the side effects, serious side effects, bleeding events and serious bleeding events between 2 groups (P>0.05). Compared with control group, the HRQoL in ITP adults and children, and parents of ITP children had no statistical significance (P>0.05). CONCLUSION: Romiplostim has a certain clinical efficacy in ITP adults and children, and relatively small adverse drug reactions. The improvement of Romiplostim on HRQoL in ITP adults and children is not clear.

Bone marrow free immune checkpoints as a potential biomarker for differential diagnosis of acquired bone marrow failures.

OBJECTIVE: Clinically, to make a definite diagnosis of aplastic anemia (AA), idiopathic cytopenia of undetermined significance (ICUS) or myelodysplastic syndrome (MDS), they should be distinguished from each other. AA and ICUS have some incidence to transform into MDS. Immunosuppressive therapy (IST) is effective in AA and partial ICUS patients, while other ICUSs are more likely to progress to MDS without response to IST. To date, we neither found a technical method that could easily identify AA from hypoproliferative MDS, nor a simple parameter that could indicate ICUS with a response to IST. Here, we detected the concentration of free immune checkpoints in bone marrow supernatant of AA, ICUS, and MDS patients, analyzed the differences of immune status among these three diseases, to try to find a way to predict the response to IST in ICUSs. METHODS: Seventy-four novel patients were enrolled with newly diagnosed acquired bone marrow failure (including 29 AA patients, 11 ICUS patients, and 34 MDS patients), bone marrow supernatants were collected. Luminex liquid suspension array technology was used to measure the concentrations of 17 immune checkpoints to analyze the differences of immune status among these three diseases. RESULTS: The levels of 17 free immune checkpoints were elevated in MDS and showed a strong correlation with each other, followed by ICUS, and with the weakest in AA. By drawing the ROC curve, we found eight immune checkpoints, including sCD40, sCD86/B7-2, sCTLA-4, sGITR, sHVEM, sPD-1, sTIM-3, and sTLR-2, could easily distinguish AA from hypoproliferative MDS. ICUSs with lower concentrations of these eight free immune checkpoints predicted a better IST response. CONCLUSION: In conclusion, we found that there were notable differences in the immune status of AA, ICUS, and MDS. The concentrations of sCD40, sCD86/B7-2, sCTLA-4, sGITR, sHVEM, sPD-1, sTIM-3, and sTLR-2 could be used to identify AA and hypoproliferative MDS patients, as well as to distinguish ICUS patients who could benefit from IST.

Myeloid dendritic cells in severe aplastic anemia patients exhibit stronger phagocytosis.

BACKGROUND: A deeper understanding of the pathogenesis of severe aplastic anemia (SAA) is urgently warranted to achieve better therapeutic effects. The objective of this study was to investigate the phagocytosis of myeloid dendritic cell (mDC) in SAA patients. METHODS: Myeloid dendritic cells were induced in vitro from bone marrow mononuclear cells from 26 SAA patients and 12 normal controls (HCs). The phagocytosis of mDCs was detected by flow cytometry using FITC-Dextran (40KD), and its correlation with the immune status and severity of the disease was analyzed. RESULTS: The phagocytosis of mDC from untreated SAA patients was significantly stronger than that from complete remission group and HC group (p < 0.05). There was no statistical difference between the latter two groups (p > 0.05). The phagocytosis of mDC from SAA patients correlated positively with the concentration of interleukin (IL)-2 (r = 0.389, p < 0.05), and IL-4 (r = 0.556, p < 0.05), negatively with CD4+ /CD8+ ratio (r = -0.421, p < 0.05). It also had negative correlations with the level of hemoglobin (r = -0.393, p < 0.05), white blood cell (r = -0.436, p < 0.05), platelet (r = -0.431, p < 0.05), and reticulocyte (r = -0.447, p < 0.05). The phagocytosis of mDC does not correlate with the response to IST. CONCLUSIONS: The increased phagocytosis of mDC in untreated SAA patients may contribute to abnormal activation of T helper (Th) and subsequent cytotoxic T lymphocyte (CTL) activation in these patients. It may be involved in the immune pathogenesis of SAA.