Central venous catheters do not increase the hemorrhagic risk in acute promyelocytic leukemia patients during induction therapy.

In acute promyelocytic leukemia (APL), hemorrhage, particularly intracranial hemorrhage, is the most common cause of early death. A central venous catheter (CVC) may provide a greater guarantee of safety and comfort to APL patients. However, CVCs have seldom been attempted in APL patients during induction therapy because of concerns about increasing the risk of hemorrhagic complications after this invasive procedure. To evaluate the hemorrhagic risk after CVC placement in APL patients during induction therapy, we retrospectively analyzed 95 newly diagnosed patients with APL from January 2010 to December 2022. Among these patients, 39 patients in the CVC group and 56 patients in the non-CVC group were included. Laboratory and clinical parameters of the two groups were collected and compared. There were no significant differences in median platelet, fibrinogen (Fbg), D-dimer, prothrombin time (PT), white blood count (WBC) and hemoglobin (Hb) between the CVC and non-CVC groups on the first day of the visit (day 0) and the following days (day 4, day 7, day 11, day 14, day 18 and day 21) (p = 0.382, p = 0.805, p = 0.456, p = 0.902, p = 0.901 and p = 0.097, respectively). The consumption of transfused platelets and Fbg was not significantly different between the CVC group and non-CVC group (5.0 vs. 4.5 units, p = 0.34, and 6.8 vs. 6.0, p = 0.36, respectively). The last day of platelet and Fbg transfusion was also not significantly different (21 vs. 19, p = 0.238 and 7.5 vs. 8.5, p = 0.684, respectively). The incidences of total hemorrhagic events and hemorrhagic death were lower in the CVC group than in the non-CVC group (17.9% vs. 37.5%, p = 0.04 and 0% vs. 16.1%, p = 0.01, respectively). The 30-day survival rate was not significantly different (92.3% vs. 82.1%, respectively, p = 0.145) for the CVC group compared with the non-CVC group. Our study suggested that CVCs did not increase the hemorrhagic risk in APL patients during induction therapy and that a CVC should be considered in this type of clinical situation.

Enhanced tumor immunotherapy by polyfunctional CD19-CAR T cells engineered to secrete anti-CD47 single-chain variable fragment.

A high recurrence rate of non-Hodgkin's lymphoma (NHL) following chimeric antigen receptor T (CAR T) cell treatment remains a bottleneck, and immunosuppressive tumor microenvironment (TME) compromising CAR T cell efficacy in NHL is the primary cause of relapse. Accordingly, modifying the structure of CAR T cells to attenuate the inhibitory effect of TME thus reducing recurrence rate is a valuable research topic. CD47 has been proved to be a promising therapeutic target and is crucial in regulating macrophage function. Herein, we engineered CD19-CAR T cells to secrete an anti-CD47 single-chain variable fragment (scFv) and validated their function in enhancing antitumor efficacy, regulating T cells differentiation, modifying phagocytosis and polarization of macrophages by in vitro and in vivo researches. The efficacy was analogous or preferable to the combination of CAR T cells and CD47 antibody. Of note, anti-CD47 scFv secreting CAR T cells exert a more potent immune response following specific antigen stimulation compared with parental CAR T cells, characterized by more efficient degranulation and cytokine production with polyfunctionality. Furthermore, locally delivering anti-CD47 by CAR T cells potentially limits toxicities relevant to systemic antibody treatment. Collectively, our research provides a more effective and safer CAR T cell transformation method for enhancing tumor immunotherapy.

Early granulocyte colony stimulating factor administration increases the risk of cytokine release syndrome in acute lymphoblastic leukemia patients receiving anti-CD19 chimeric antigen receptor T-cell therapy.

Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and neutropenia are common toxicities associated with chimeric antigen receptor T (CAR-T) cell therapy. The role of granulocyte colony stimulating factor (G-CSF) in CAR-T-cell-treated patients remains unclear. To explore the efficacy and safety of early G-CSF administration in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) who were receiving autologous anti-CD19 CAR-T cells, we retrospectively collected and summarized clinical data to compare patients receiving G-CSF within 14 days (early G-CSF group) to patients receiving later or no G-CSF (control group) after their CART infusion. The results showed that there was no significant difference in the incidence and duration of neutropenia between the early G-CSF group and the control group (77% vs. 63%, p = 0.65; 8 vs. 4 days, p = 0.37, respectively). However, the incidence and duration of CRS were significantly higher in the early G-CSF group than in the control group (81% vs. 38%, p = 0.03; 3 vs. 0 days, p = 0.004, respectively). Moreover, early G-CSF application had no significant effect on the expansion and efficacy of CAR-T cells. In conclusion, our study suggested that early G-CSF administration did not reduce the incidence and duration of neutropenia but rather increased the incidence and duration of CRS.

Clinical and molecular genetic analysis of a Chinese family with hereditary elliptocytosis caused by a novel mutation in the EPB41 gene.

BACKGROUND: Hereditary elliptocytosis (HE) is a heterogeneous red blood cell membrane disorder characterized by the presence of elliptocytes on a peripheral blood smear. Clinical manifestations of HE vary widely from asymptomatic carriers to patients with severe transfusion-dependent anemia. Most patients are asymptomatic or have mild anemia, which hinders diagnosis. The proband in this case had mild anemia and jaundice over a period of 4 years, the etiology of which was unclear. Hence, he was admitted to our hospital for further diagnosis. METHODS: Peripheral blood smears and routine blood tests were performed and biochemical parameters of the proband, and his family members were determined. To confirm the diagnosis, gene mutations were screened in the proband using next-generation sequencing (NGS) and verified by Sanger sequencing in other family members. RESULTS: A novel mutation (c.1294delA, p.Ser432 fs) in exon 15 of the EPB41 gene was detected in the proband and his family members. This mutation results in a frameshift and a premature stop codon at position 455, encoding a truncated protein. The variant was likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics. SWISS-MODEL protein structure prediction indicated partial loss of the spectrin and actin binding and C-terminal domains. CONCLUSION: A heterozygous mutation 1294delA in exon 15 of the EPB41 gene was identified using NGS and Sanger sequencing in members of a Chinese family. This identification expands the spectrum of EPB41 mutations and contributes to the genetic diagnosis of families with HE.

Serum cytokines and clinical features in patients with fever and thrombocytopenia syndrome.

PURPOSE: To explore the clinical, microbiological and immunological features of patients with fever and thrombocytopenia. METHODS: Patients with unexplained fever and thrombocytopenia were enrolled. Viruses were detected using real-time PCR, and bacteria were measured by culturing methods. Serum cytokines, platelet antibody IgG (PA-IgG) and Helicobacter pylori (HP) were detected using ELISA. RESULTS: Pathogens were detected in 74.68% of patients, which included single fungal/viral/bacterial infection and multiple infection. The pathogens could not be unidentified in 25.32% of cases. Cytokines including Interleukin (IL)-6, IL-10, interferon-γ(IFN-γ), platelet activating factor (PAF) and PA-IgG were significantly higher in patients as compared to healthy controls (P < .01 or P < .05). Principal component analyses extracted four groups of parameters that have a strong positive predicting value, revealing that disease status evaluation would be more accurate if we combined the platelet parameters and inflammatory biomarkers. While event-free survival (EFS) that indicates the time of platelet elevated after therapy was the highest in patients with single bacterial or fungal infection, EFS was affected by the levels of cytokines and PA-IgG. CONCLUSIONS: Differences in immune function may be the main factors affecting the prognosis of patients with fever and thrombocytopenia, while treatment based on precise etiological diagnosis is important for therapeutic efficacy.