Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) are one of the most severe complications after hematopoietic stem cell transplantation (HSCT). This study includes 31 cases of aplastic anemia (AA) patients who developed PTLD after haploidentical transplantation, summarizing their clinical characteristics and categorizing them into either rituximab monotherapy group or combination therapy group based on whether their condition improved by 1 log after a single dose of rituximab. The incidence of PTLD after HSCT in children with AA was 10.16%, and the incidence of PTLD in patients with age >10 years was significantly increased ( χ2=11.336, P=0.010). Of the 31 patients, 27 were clinically diagnosed and 4 were pathologically confirmed. Finally, 15 patients were classified into the rituximab treatment group and 15 patients into the combination treatment groups. Finally three patients died, and the 2-year overall survival rate was (89.7±5.6) %. Standard pre-treatment protocols and EBV reactivation are risk factors affecting the prognosis of PTLD. There was no statistically significant difference in the impact of the two treatment schemes on prognosis.

Objective:To investigate the efficacy and safety of venetoclax combined with the decitabine, cytarabine, and homoharringtonine (HHT) regimen and donor lymphocyte infusion (DLI) for the preventive and salvage therapy of pediatric acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (HSCT) .Methods:A total of 29 relapsed pediatric/minimal residual disease-positive AML after HSCT were recruited at the Peking University Institute of Hematology from January 1, 2021, to June 1, 2023. They were treated with the above combination regimen and administered with DLI after 24-48 hours at the end of chemotherapy, and the treatment response and adverse reactions were regularly assessed.Results:The overall response rate (ORR) was 75.8%, CR rate was 88.9% (8/9) in the hematologic relapse group, and MRD negativity rate was 61.1% (11/18) in the MRD-positive group. The incidence of agranulocytosis, anemia, and thrombocytopenia with a classification above grade 3 were 100%, 82.7%, and 100%, respectively. The median time of the granulocyte deficiency period was 15 days. Acute graft-versus-host diseases (aGVHD) with a classification of grades Ⅲ-Ⅳ occurred in 11.1% of the patients after DLI, while moderate or severe cGVHD occurred in 7.4% of the patients. The single risk factor for ORR was MNC counts of less than 10×10 8/kg, and the relapse occurred within 100 days. At a median follow-up of 406 days, the 1-year OS was 65%, and the 1-year OS was 57% in the group with no reaction ( P=0.164) compared with 71% in the group who had an overall reaction. Conclusion:The combined regimen based on the DAC, VEN, and modified HA regimen showed a high response rate in the salvage therapy for pediatric AML after the relapse of HSCT. However, bridging to transplantation should be performed immediately after remission to result in a long survival rate.

In 2006, 2014 and 2020, the positive rates of HBsAg in 560, 384 and 402 children aged 1 to 14 years were 4.5%, 2.6% and 2.5%, respectively, with no statistically significant differences (P>0.05). The positive rate of anti-HBs was highest in 2014 (57.8%) and lowest in 2006 (34.1%) (P<0.05). The positive rate of anti-HBc was highest in 2006 (15.7%), and decreased in 2014 (7.8%) and 2020 (5.7%) (P<0.001). The timely rate of the first dose of hepatitis B vaccine for children in Lhasa in 2006, 2014 and 2020 was 7.7% (43/560), 50.3% (193/384) and 94.8% (381/402), respectively. The overall vaccination rates were 15.4% (86/560), 35.2% (135/384) and 96.0% (386/402), respectively, showing a trend of gradual increases (χtrend values were 718.63 and 589.59, both P values<0.001).
Child ; Humans ; Hepatitis B Vaccines ; Hepatitis B/prevention & control* ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B Antibodies ; Vaccination

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective:To investigate the risk factors of invasive fungal disease after haploid hematopoietic stem cell transplantation in children with acute leukemia.Methods:Four hundred and two children (median age 10 years) with acute leukemia, undergoing haplo-HSCT at this institutute from January 2016 to December 2020,were analyzed retrospectively according to the diagnosis criteria of IFD. The basic information and preoperative indicators of the children were collected, including gender, age, primary disease, remission status of primary disease, and previous IFD history. Postoperative indicators were collected, including long-term granulocyte deficiency time, high-dose glucocorticoids, using CD25 monoclonal antibody, acute and chronic graft-versus-host disease. Count data are expressed as example (%), and comparisons between groups are made using the continuously multifactorial corrected Chi-square test or Fisher exact probability method. Logistic regression model was used to analyze the risk factors of IFD after haplo-HSCT in children.Results:Among 402 cases, 250 were male and 152 were female. The median age at transplantation was 10 years, and the age range was 9 months to 17 years 7 months. Before transplantation, 390 cases achieved complete remission of the primary disease, 9 cases had partial remission, and 3 cases had no remission. The implantation time of neutrophils ranged from +10 to 24 days, with a median time of 12 days. IFD occurred in 17 cases (4.2%), of which 3 cases (0.7%) were proven IFD and 14 cases (3.5%) were probable IFD. IFD occurred from 13 to 275 days after transplantation, with a median time of 30 days. The lungs were the most common site of infection (88.2%,15/17). The multivariate Logistic regression analysis showed that age >10 years old ( P=0.046, odds ratio =3.05, 95% confidence interval: 1.02~9.13), the use of high-dose corticosteroids ( P=0.005, odds ratio =7.72, 95% confidence interval: 1.85~32.20) were risk factors for IFD after haplo-HSCT in children. Conclusions:IFD is an important complication after haplo-HSCT in children with acute leukemia. Age >10 years and the use of high-dose corticosteroid are risk factors for IFD after haplo-HSCT in children with acute leukemia.

Objectives:This study aimed to evaluate the predictive value of the CHA 2DS 2-VASc score for in-hospital outcomes of patients with acute myocardial infarction (AMI). Methods:Data of 23 728 patients from the China patient-centered Evaluative Assessment of cardiac Events (China PEACE)Retrospective Acute Myocardial Infarction Study were analyzed retrospectively. The patients were categorized into 3 groups according to the CHA 2DS 2-VASc scores: the low score group (score 1-3), the middle score group (score 4-6) and the high score group (score 7-9). The in-hospital outcomes included major adverse cardiovascular events (MACE), death, death or withdrawal from treatment, reinfarction, ischemic stroke,etc. The CHA 2DS 2-VASc score was incorporated into multivariate Cox regression analyses to determine its independent impact on in-hospital outcomes. Receiver operating Characteristic (ROC) curves were constructed, and the area under the curve (AUC) was used to evaluate the predictive value of the CHA 2DS 2-VASc score for in-hospital mortality and death or withdrawal from treatment, respectively. Results:The patients had a median age of 66 (56,75) years, and 30.7% of them were females. Patients with higher CHA 2DS 2-VASc scores had a higher in-hospital mortality and more in-hospital complications (all P<0.001). After adjustment of baseline covariates, the subjects in the high score group were associated with high risks of in-hospital mortality ( OR=6.13, 95% CI 4.77-7.87, P<0.001), death or treatment withdrawal ( OR=6.43, 95% CI 5.16-8.00, P<0.001) and MACE ( OR=4.94, 95% CI 4.06-6.01, P<0.001). The AUCs of the CHA 2DS 2-VASc score were comparable with those of the mini-global registry of acute coronary events(mini-GRACE)score in evaluation of in-hospital mortality (0.699 vs. 0.696, P=0.752) and the death or treatment withdrawal risk (0.708 vs. 0.713, P=0.489). Conclusions:The CHA 2DS 2-VASc score is an independent predictor of in-hospital outcomes for patients with AMI. Its predictive value was comparable with the mini-GRACE score, which could be used as a simple tool for early and rapid outcome evaluation for AMI patients.

Objective: To compare and correlate the findings of intravoxel incoherent motion (IVIM) magnetic resonance (MR) imaging and arterial spin labeling (ASL) imaging in characterizing parotid gland tumors. Materials and Methods: We retrospectively reviewed 56 patients with parotid gland tumors evaluated by MR imaging. The true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and fraction of perfusion (f) values of IVIM imaging and tumor-to-parotid gland signal intensity ratio (SIR) on ASL imaging were calculated. Spearman rank correlation coefficient, chi-squared, Mann-Whitney U, and Kruskal-Wallis tests with the post-hoc Dunn-Bonferroni method and receiver operating characteristic curve assessments were used for statistical analysis. Results: Malignant parotid gland tumors showed significantly lower D than benign tumors (p = 0.019). Within subgroup analyses, pleomorphic adenomas (PAs) showed significantly higher D than malignant tumors (MTs) and Warthin’s tumors (WTs) (p < 0.001). The D* of WTs was significantly higher than that of PAs (p = 0.031). The f and SIR on ASL imaging of WTs were significantly higher than those of MTs and PAs (p < 0.05). Significantly positive correlation was found between SIR on ASL imaging and f (r = 0.446, p = 0.001). In comparison with f, SIR on ASL imaging showed a higher area under curve (0.853 vs. 0.891) in discriminating MTs from WTs, although the difference was not significant (p = 0.720). Conclusion IVIM and ASL imaging could help differentiate parotid gland tumors. SIR on ASL imaging showed a significantly positive correlation with f. ASL imaging might hold potential to improve the ability to discriminate MTs from WTs.

Objective:To compare the curative efficacy in the treatment of humeral surgical neck fractures between open reduction and locking plating versus closed reduction and interlocking intramedullary nailing.Methods:From July 2018 to July 2020, 60 patients with humeral surgical neck fracture were treated at Department of Orthorpaedic Trauma, Jiangmen Wuyi Hospital of Traditional Chinese Medicine. They were 24 males and 36 females, aged from 40 to 70 years and injured at the left side in 35 cases and at the right side in 25 ones. Of them, 30 underwent open reduction and locking plating (open group) and the other 30 closed reduction and interlocking intramedullary nailing (closed group). The 2 groups were compared in terms of operation time, intraoperative blood loss, surgical incision length, fracture healing time, Neer shoulder function scoring 3 months after surgery, and postoperative complications.Results:There were no statistically significant differences between the open and closed groups in preoperative general data, showing they were comparable ( P>0.05). The length of surgical incision [(5.2±1.1) cm], operation time [(34.3±12.7) min], intraoperative blood loss [(52.5±7.3) mL] and fracture healing time [(9.2±1.5) weeks] in the closed group were significantly better than those in the open group [(11.1±2.5) cm, (69.4±21.4) min, (123.5±5.2) mL and (14.2±3.4) weeks)] ( P<0.05). The excellent and good rate by Neer shoulder function scoring at 3 months after operation in the closed group (93.3%, 28/30) was significantly higher than that in the open group (66.7%, 20/30) ( P<0.05). There were no postoperative complications in either group. Conclusion:In the treatment of humeral surgical neck fractures, the curative efficacy of closed reduction and interlocking intramedullary nailing is better than that of open reduction and locking plating.

BACKGROUND: High agglomeration of myeloid-derived suppressor cells (MDSCs) in neuroblastoma (NB) impeded therapeutic effects. This study aimed to investigate the role and mechanism of targeted inhibition of MDSCs by low-dose doxorubicin (DOX) to enhance immune efficacy in NB. METHODS: Bagg albino (BALB/c) mice were used as tumor-bearing mouse models by injecting Neuro-2a cells, and MDSCs were eliminated by DOX or dopamine (DA) administration. Tumor-bearing mice were randomly divided into 2.5 mg/kg DOX, 5.0 mg/kg DOX, 50.0 mg/kg DA, and control groups (n = 20). The optimal drug and its concentration for MDSC inhibition were selected according to tumor inhibition. NB antigen-specific cytotoxic T cells (CTLs) were prepared. Tumor-bearing mice were randomly divided into DOX, CTL, anti-ganglioside (GD2), DOX+CTL, DOX+anti-GD2, and control groups. Following low-dose DOX administration, immunotherapy was applied. The levels of human leukocyte antigen (HLA)-I, CD8, interleukin (IL)-2 and interferon (IFN)-γ in peripheral blood, CTLs, T-helper 1 (Thl)/Th2 cytokines, perforin, granzyme and tumor growth were compared among the groups. The Wilcoxon two-sample test and repeated-measures analysis of variance were used to analyze results. RESULTS: The slowest tumor growth (F = 6.095, P = 0.018) and strongest MDSC inhibition (F = 14.632, P = 0.001) were observed in 2.5 mg/kg DOX group. Proliferation of T cells was increased (F = 448.721, P < 0.001) and then decreased (F = 2.047, P = 0.186). After low-dose DOX administration, HLA-I (F = 222.489), CD8 (F = 271.686), Thl/Th2 cytokines, CD4+ and CD8+ lymphocytes, granzyme (F = 2376.475) and perforin (F = 488.531) in tumor, IL-2 (F = 62.951) and IFN-γ (F = 240.709) in peripheral blood of each immunotherapy group were all higher compared with the control group (all of P values < 0.05). The most significant increases in the aforementioned indexes and the most notable tumor growth inhibition were observed in DOX+anti-GD2 and DOX+CTL groups. CONCLUSIONS Low-dose DOX can be used as a potent immunomodulatory agent that selectively impairs MDSC-induced immunosuppression, thereby fostering immune efficacy in NB.
Animals ; Doxorubicin/therapeutic use* ; Mice ; Mice, Inbred C57BL ; Myeloid-Derived Suppressor Cells ; Neuroblastoma/drug therapy* ; Tumor Microenvironment