FYB1-targeted modulation of CAPG promotes AML progression.

Acute myeloid leukemia (AML) is a rare and heterogeneous disease. Over the past few decades, patient prognosis has improved with continuous improvements in treatment, but outcomes for some patients with primary drug resistance or relapse after treatment remain poor. Additional therapies to improve outcomes for these patients are urgently needed. FYB1 expression differs substantially between AML tissues and normal tissues. High FYB1 expression is correlated with poorer overall survival (OS), indicating that FYB1 may regulate AML progression. Therefore, understanding the effect of FYB1 on AML could improve the success rate of therapeutic approaches and prognosis for patients with AML. In this study, through analysis of large databases and both in vivo and in vitro experiments, we assessed the expression and role of FYB1 in AML and the relationship of FYB with patient prognosis. Downstream targets of the FYB1 gene were analyzed by RNA-seq. Database mining and in vitro experiments were used to further clarify the effect of the downstream target gelsolin-like actin-capping protein (CAPG) on AML cells and its relationship with patient prognosis. FYB1 expression was significantly higher in AML tissue and corresponded with a poor prognosis. FYB1 knockdown inhibited AML cell proliferation, promoted cell apoptosis, reduced cell adhesion capability and significantly reduced the tumor formation rate in mice. In addition, FYB1 knockdown induced a notable decrease in CAPG expression. The suppression of CAPG significantly inhibited cell proliferation and increased cell apoptosis. The conclusions of this study underscore the pivotal role of the FYB1/CAPG axis in promoting AML. We propose that the FYB1/CAPG axis could serve as a new thread in the development of therapeutic strategies for AML.

Comparative study of posaconazole and voriconazole for primary antifungal prophylaxis in patients with pediatric acute leukemia.

Posaconazole and voriconazole are commonly used for preventing invasive fungal disease (IFD), but few studies compared posaconazole with voriconazole for primary antifungal prophylaxis (PAP) in pediatric acute leukemia. To compare posaconazole with voriconazole for PAP in pediatric acute leukemia. This retrospective observational study enrolled pediatric patients with non-M3 acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) between December 2017 and November 2019 in the Second Affiliated Hospital of Anhui Medical University. The patients received voriconazole or posaconazole for PAP. The primary outcome was the breakthrough of IFD. The secondary outcome was the overall survival (OS) and IFD-free survival of patients. A total of the 275 patients were enrolled, of which 120 patients taking voriconazole (43.6%) and 155 patients taking posaconazole (56.4%). The breakthrough of IFD occurred in 19 (15.8%) patients taking voriconazole and in 12 (7.7%) patients taking posaconazole (P = 0.035). There was no significant differences in IFD-free survival (P = 0.336) or OS (P = 0.069) between the patients taking voriconazole and posaconazole. In the subgroup of AML patients, the OS of patients taking posaconazole was better than those receiving voriconazole (P = 0.017). Posaconazole and voriconazole were comparable for PAP in patients with pediatric acute leukemia regarding the OS and IFD-free survival, but posaconazole might achieve a lower IFD breakthrough rate.

Mycobacterium abscessus pulmonary disease presenting with spontaneous pneumomediastinum and subcutaneous emphysema in childhood acute lymphoblastic leukemia: a case report and literature review.

INTRODUCTION: Mycobacterium abscessus is a rapidly growing mycobacterium commonly identified in adults with underlying pulmonary diseases but is rarely observed in children. A better understanding of this pathogen in children is essential. CASE PRESENTATION: We report the case of a 49-month-old female child without previous underlying pulmonary diseases but with acute lymphoblastic leukemia (ALL). The patient was complicated with pneumonia during chemotherapy, which was primarily characterized by spontaneous pneumomediastinum and subcutaneous emphysema on chest computed tomography (CT). M. abscessus sequences were detected by metagenomic next-generation sequencing in bronchoalveolar lavage fluid. With mechanical ventilation, closed thoracic drainage, and anti-infective therapy for 6 months, the patient's infection was controlled. The patient completed 2.5 years of treatment for ALL, and the drugs were discontinued. The patient currently remains in complete hematologic remission. DISCUSSION: We reviewed the literature on 33 children with M. abscessus pulmonary disease. These children mostly had underlying immunodeficiency. Chest CT most often showed nodular shadows, consolidation, and bronchiectasis. Spontaneous pneumomediastinum and subcutaneous emphysema were not reported as major manifestations. CONCLUSION: Spontaneous pneumomediastinum and subcutaneous emphysema were our patient's main characteristics on chest CT, and this study enriches the knowledge regarding possible imaging changes in M. abscessus pulmonary disease in children. This case report reflects good clinical experience in maintaining the balance between chemotherapy and anti-infective therapy in childhood ALL.

[Single Center Clinical Analysis of Bloodstream Infection Pathogens in Children with Acute Leukemia].

OBJECTIVE: To investigate the clinical features, distribution of pathogenic bacteria, and drug resistance of bloodstream infection in children with acute leukemia. METHODS: Clinical data of 93 blood culture-positive children with acute leukemia from January 2015 to December 2019 in Department of Pediatrics, The Second Hospital of Anhui Medical University were analyzed retrospectively. RESULTS: In these 93 cases, 78 cases were in the period of neutrophil deficiency. There were 54 Gram-negative bacteria (G-) (58.1%) found through blood culture, and the top 4 strains were Escherichia coli (15.1%), Klebsiella pneumoniae (13.9%), Pseudomonas aeruginosa (6.5%), and Enterobacter cloacae (6.5%). There were 39 Gram-positive bacteria (G+) (41.9%) detected, and the top 4 strains were Staphylococcus epidermidis (10.8%), Streptococcus pneumoniae (6.5%), Staphylococcus hemolyticus (5.4%), and Staphylococcus human (5.4%). Among 74 strains of pathogenic bacteria from acute lymphoblastic leukemia (ALL) children, there were 29 strains of G+ bacteria (39.2%) and 45 strains of G- bacteria (60.8%). While in 19 strains from acute myeloblastic leukemia (AML) patients, G- bacteria accounted for 47.4% and G+ bacteria accounted for 52.6%. In 15 ALL children without neutropenia, G+ bacteria made up the majority of the strains (66.7%). In the 93 strains of pathogenic bacteria, 13 (13.9%) strains were multidrug-resistant. Among them, extended-spectrum ß-lactamases accounted for 42.9%, carbapenemase-resistant enzyme Klebsiella pneumoniae 15.4%, and carbapenemase-resistant enzyme Enterobacter cloacae strains 33.3%, which were detected from G- bacteria. While, 13.3% of methicillin-resistant coagulase-negative Staphylococci accounted for 13.3% detected from G+ bacteria, but linezolid, vancomycin, teicoplanin Staphylococcus and Enterococcus resistant were not found. The average procalcitonin (PCT) value of G- bacteria infection was (11.02±20.282) ng/ml, while in G+ infection it was (1.81±4.911) ng/ml, the difference was statistically significant (P<0.05). The mean value of C-reactive protein (CRP) in G- infection was (76.33±69.946) mg/L, and that in G+ infection was (38.34±57.951) mg/L. The prognosis of active treatment was good, and only one case died of septic shock complicated with disseminated intravascular coagulation (DIC) and gastrointestinal bleeding caused by carbapenemase-resistant enzyme enterobacteriaceae. CONCLUSION: G- is the major bacteria in acute leukemia children with bloodstream infection, but the distribution of ALL and AML strains is different. G- bacteria dominates in ALL, while G+ bacteria and G- bacteria are equally distributed in AML. Non-agranulocytosis accompanied by bloodstream infections is dominant by G+ bacteria. The mean value of PCT and CRP are significantly higher in G- bacteria infection than in G+ bacteria.

Long-term follow-up of acute lymphoblastic leukemia in young children treated by the SCMC-ALL-2009 protocol.

This study evaluated the long-term therapeutic effect and prognostic factors of acute lymphoblastic leukemia (ALL) in 100 young Chinese children (<2 years old) who were enrolled in the Shanghai Children's Medical Center (SCMC)-ALL-2009 study in five pediatric hematological disease centers based on collaboration. The 5-year and 10-year event-free survivals (EFS) were 74.7 ± 3.2% and 73.3 ± 3.4%. The 10-year EFS rates for low risk, intermediate-risk, and high-risk patients were 81.9 ± 5.0%, 71.3 ± 4.3%, and 22.2 ± 13.9%, respectively. Relapse occurred in 19 patients. MRD results on day 55, good or poor response to prednisolone, and age at diagnosis were shown to have important prognostic and therapeutic implications. Compared with the SCMC-ALL-2005 protocol, showed that the 10-year-EFS and 10-year-overall survival of the SCMC-ALL-2009 protocol were better than that of the -2005 protocol. Notably, the intermediate-risk group was improved after the chemotherapy intensity was strengthened.

[Relationship between Nutritional Status and Nosocomial Infection in Children with Acute Lymphoblastic Leukemia].

OBJECTIVE: To study the risk factors and infection characteristics of nosocomial infection in children with acute lymphoblastic leukemia (ALL) and analyze the relationship between different nutritional status and nosocomial infection, early treatment response. METHOD: The clinical data of 133 children with ALL treated with CCCG-ALL-2015 from June 2016 to June 2019 (chemotherapy stage, risk level, MRD), infection during hospitalization (course of infection, laboratory indicators, sites of infection, outcome) and nutritional status (sex, age, height/ length, weight) were enrolled. The Chi 2 test and Logistic regression analysis were used for statistical analysis. RESULTS: The rate of nosocomial infection was 19.9% in 133 children with ALL, in which 3 were infection-related death. Sex, immunophenotype and risk showed no significantly affect on the occurrence of nosocomial infection (P＞0.05), but neutrophil count, hemoglobin level, platelet count, chemotherapy stage, length of stay in hospital and nutritional status showed affect on the occurrence of nosocomial infection (P＜0.05). Logistic multivariate regression analysis showed that chemotherapy stage, length of hospital stay, neutrophils and nutritional status were the independent risk factors, in which the respiratory tract infection was the most common. Gram-positive bacteria, Gram-negative bacteria and fungi accounted for 44.1%, 52.9% and 2.9% respectively. The negative rate of MRD in day 19 and day 46 between different nutritional status groups showed statistically significant (P＜0.05). CONCLUSION: Neutrophil count, chemotherapy stage, length of stay in hospital and nutritional status are independent risk factors for nosocomial infection. Among of them, nutritional status negatively correlated with nosocomial infection, and the poorer nutritional status, the higher risk of nosocomial infection. Malnutrition, overweight and obesity can affect the early treatment response of ALL children. The level of nutrition at first diagnosis can be used as a bad factor to evaluate the early treatment response of ALL children.

Characteristics of Blood Transfusion During Induction Remission in Children With Acute Lymphoblastic Leukemia: A Single-Center Retrospective Investigation.

OBJECTIVE: To investigate the allogeneic blood transfusion (ABT) characteristics of children with acute lymphoblastic leukemia (ALL) in different risk stratification during vincristine, daunorubicin, L-asparaginase and prednisone (VDLP) induction remission. SUBJECTS AND METHODS: By referring to electronic medical records, the demographic characteristics, diagnosis, test, and treatment information including ABT were collected. According to the risk stratification of the CCCG-ALL-2015 protocol, ABTs between groups were compared, and the differences were statistically analyzed. RESULTS: One hundred sixty-three newly treated children with ALL were enrolled in this study, who received 643.5 U of red blood cells and 377.6 U of platelets (PLTs) during the VDLP. The amount of ABT in the intermediate-risk (IR) group (n=102) was significantly higher than that in the low-risk group (n=61), which were reflected in the red blood cells in the first half of VDLP (P=0.033) and the PLTs in the second half of VDLP (P<0.001). Meanwhile, the PLT counts in the IR group were significantly lower in the same period. The time node was bounded by the minimal residual disease test on the 19th day. CONCLUSIONS: Children in the IR group or with unsatisfactory induction may need more ABTs during the VDLP, and the relatively low PLT counts seem to contribute to this. The results of this study can provide a basis for patient blood management, as well as a reference for studying the long-term effects of ABT on children with ALL.

[Clinical Analysis of Deep Venous Thromboembolism in Children with Acute Lymphocytic Leukemia].

OBJECTIVE: To explore clinical characteristics and outcome of deep vein thrombosis(DVT) in children with acute lymphoblastic leukemia (ALL). METHODS: A tatol of 266 patients were diagnosed as ALL from January 1, 2010 to May 31, 2016. The clinical data of 12 cases of patients with DVT were retrospectively analyzed, 183 cases diagnosed before January 1, 2015 were received chemotherapy with the scheme of SCMC-05. The other cases were treated by the scheme of CCCG. All the patients received central venous catheter. RESULTS: The DVT happened in 12 cases including 10 cases of limb DVT and 2 cases of intacranial venous sinus thrombosis. The DVT mostly occured in intermediate risk ALL patients, the infection and coagulopathy existed in most patients. They were treated with low molecular heparin(LWHP), among them 5 cases were given extubation; the thrombus disappeared in 6 cases after 1 week; the intracranial venous sinus thrombosis in 1 case did not obviously improved after 6 months of treatment. The ALL children with DVT were treated with LWHP when using L-ASP, as a result no thrombuses happened. CONCLUSION: Centralvenous catheter and chemotherapeutic drugs were the major cause of DVT. Abnormal coagulation, infection, and risk stratification are another risk factors for thrombosis. ALL children thrombosis are benefited from LWHP prevention when using L-ASP again.