Lysine methyltransferase 2A( KMT2A) rearrangement (KMT2A-r) is a high-risk gene subtype of acute lymphoblastic leukemia (ALL) in children with a high relapse rate, poor prognosis and suboptimal response to conventional chemotherapy.Improving the treatment and prognosis of childhood KMT2A-r ALL is an urgent problem.In recent years, with an in-depth understanding of the mechanism of KMT2A-r, more accurate risk stratification of KMT2A-r ALL has been carried out, and great progress has also been made in its immune and targeted therapy.In this article, the genetic and biological characteristics, risk stratification, treatment strategies and prognosis of children KMT2A-r ALL were reviewed in order to provide theoretical support for clinical work and future research.

Objective:To explore the clinical characteristics and prognosis of children with chronic myeloid leukemia in the blast phase (CML-BP) .Methods:The clinical characteristics, treatment measures, and survival outcomes of 28 children with CML-BP were analyzed in our hospital from January 2008 to November 2022.Results:The male to female ratio of the 28 children with CML-BP was 1.15∶1. The median age of diagnosis of CML-BP was 10 years, and the median follow-up time was 79 months. During the diagnosis of CML, four children were in the BP, one was in the accelerated phase (AP) and 23 children were in the chronic phase (CP). Among the 23 children with CML-CP, 75% had progressed directly from CP to BP without experiencing the AP. Among the children diagnosed with CML-BP, 71.4% were classified as chronic myeloid leukemia lymphoid blast phase (CML-LBP), 25.0% belonged to the chronic myeloid leukemia myeloid blast phase (CML-MBP), and 3.6% belonged to the chronic myeloid leukemia mixed phenotype acute leukemia (CML-MPAL). Treatment with hemaopoietic stem cell transplantation (HSCT) after tyosine kinase inhibitor (TKI) combined with chemotherapy was administered to 19 children, two children received HSCT after TKI alone, and seven children received TKI combined with chemotherapy but without HSCT. The 5-year overall survival of the 28 children with CML-BP was 59.3%.Conclusion:The direct progression of BP from CP is greater in children with CML-BP compared with adults, and the overall prognosis of children with CML-BP is poor.

Objective To explore method of establishing and evaluating an asthma rat model with phlegm and blood stasis syndrome.Methods 60 SD male rats were randomly divided into 5 groups,a normal group,asthma group,combination of disease and syndrome(combination)group,DM group,and KCLW group,with 12 rats in each group.Asthma models were established using ovalbumin(OVA).A syndrome model of phlegm and blood stasis was established using a high-fat diet combined with the ice water bath method.We evaluated the asthma model through animal behavior observation,pathological section observation,inflammation index detection,and airway reactivity measurements.The phlegm and blood stasis syndrome model was evaluated via measurements of rat body mass,blood glucose,blood lipids,coagulation function,and hemorheological indexes and by observing symptoms and syndrome determination by Kechuan Liuwei mixture.Results(1)After OVA induction,the rats in the asthma model group and combination group showed symptoms such as shortness of breath,open mouth breathing,abdominal movement,restlessness,and irritability.HE staining showed the disordered arrangement of the bronchial mucosa in lung tissue,local detachment,thickening of the basement membrane and the bronchial tube wall,narrowing of the lumen,extensive infiltration of inflammatory cells,and congestion of capillaries.Compared with the normal group,the asthma model group and combination group(P＜0.05)had increased serum IL-4,IL-6,and TGF-β1.Penh values were increased after stimulation with various concentrations of Mch(P＜0.05).(2)Rats in the combination group showed symptoms such as chills,curling up with minimal movement,purple and dark claws,purple and black bruises on the tail,loose stools,and unclean perianal area.Compared with the rats in the asthma model group,rats in the combination group had increased body mass(P＜0.05)and blood glucose,triglyceride,and total cholesterol levels(P＜0.05),a shortened thrombin time(P＜0.05),increased fibrinogen content(P＜0.05),and significantly increased whole-blood viscosity at low,medium,and high shear rates(P＜0.05).The indexes were significantly improved after Kechuan Liuwei mixture administration.Conclusions The asthma rat model with phlegm and blood stasis syndrome can be established through OVA induction and high-fat diet combined with ice water bath.The model can be evaluated through behavioral observation,index measurements,and syndrome determination via formulas.

Objective:To explore the predictive effect of European treatment and outcome study long term survival (ELTS) score on survival outcomes in chronic myeloid leukemia of chronic phase (CML-CP) children.Methods:A single-center retrospective cohort study was conducted. Clinical data of 216 children with CML-CP in Peking University People′s Hospital from January 2010 to December 2023 were analyzed. Children were divided into low, intermediate and high-risk groups according to ELTS score. The survival outcomes and prognostic factors were analyzed. Kaplan-Meier method and Log-Rank test were used for survival analysis.Cox regression model was applied for analysis of prognostic factors.Results:Among the 216 children with CML-CP, there were 122 males and 94 females, with the diagnosis age of 11.0 (8.0, 14.7) years. The follow-up time was 77 (57, 99) months. According to ELTS score, 145, 52, and 19 children were classified as low, intermediate and high-risk group. For the low-risk and intermediate/high-risk groups, the 6-year failure-free survival (FFS) rates were (83.0±3.1)% and (64.6±5.7)%, the 6-year progression-free survival (PFS) rates were (91.4±2.3)% and (78.7±4.8)%, and the 6-year event-free survival (EFS) rates were (80.8±3.3)% and (64.2±5.7)%, with statistically significant difference ( χ2=9.45, 7.16, 7.40, P=0.002, 0.007, 0.007), respectively.The 6-year overall survival (OS) rates were (98.5±1.0)% and (95.6±2.4)%, without statistically significant difference ( χ2=0.35, P=0.550). Multivariate analysis showed that ELTS score was an independent prognostic factor or tendency for FFS ( HR=1.97, 95% CI 1.11-3.49), PFS ( HR=2.95, 95% CI 1.18-7.39), and no independent prognostic factor for EFS and OS were found. Conclusions:ELTS score at diagnosis can help stratify the risk of children with CML-CP. The children in intermediate/high-risk group are more likely to have treatment failure, disease progression than those in low-risk group, but the predictive ability of ELTS score for OS is limited.

Objective:To investigate the safety, economic effect, and short-term clinical efficacy of ambulatory total hip arthroplasty (THA) in the treatment of hip osteopathy within.Methods:This study retrospectively reviewed patients who underwent 48-hour outpatient THA and conventional primary THA from July 2020 to July 2021. Gender, age, body mass index (BMI), clinical diagnosis, place of resident, length of hospital stay, duration of the surgery, hemoglobin, albumin, C-reactive protein (CRP) and D-dimer before and 1 day after surgery, the visual analogue scale (VAS) was obtained postoperative day 2, hip joint modified Harris score before and 1 month after surgery, readmission and reoperation within 1 month after operation as the data of evaluations were extracted and compared in this study.Results:A totally of 150 cases were involved in this study, which including 75 cases with 48-hour outpatient primary THA and 75 cases with conventional primary THA. There was no significant difference between the two groups in terms of age, sex, BMI, education level, preoperative diagnosis, and preoperative Harris score ( P>0.05), but a significant difference was found in term of residence (χ 2=6.29, P=0.043), that the patients in the outpatient group were all from Zhejiang Province and 48% (36/75) of them were from Hangzhou City. While, in the conventional group, 6 patients were from other provinces. The length of stay was 2.13±0.52 days and operation time was 59.73±18.91 minutes in the outpatient group, which were both shorter than those (6.71±1.44 days and 66.91±22.40 min) in the conventional group ( t=25.91, P<0.001 for the length of hospital stay; t=2.12, P=0.036 for operation time). Compared with the conventional group, outpatient group saved the average hospital cost (4.60±0.44 vs. 5.20±0.72 ten thousand yuan, t=6.16, P<0.001). The VAS on the second day after surgery 3.45±0.75 was higher in the outpatient group than in the conventional group (3.45±0.75 vs. 3.16±0.94 points, t=2.09, P=0.039). The modified Harris score was without statistical significance ( t=0.42, P=0.677) 1 month after surgery in both groups. 75 patients in the outpatient group, 7 patients delayed discharge (were not discharge within 48 hours), and the rate of delayed discharge was 9.3%. Reasons for delayed discharge included poor pain control in two cases, one case had postoperative nausea and vomiting, one case had failed to meet rehabilitation standards, hypotension in one case, the intraoperative infection in one case and postoperative fever within 48 hours in one case. Conclusion:Outpatient THA can reduce the length of hospital stay, operative time and total cost of hospitalization. It has similar safety and early clinical efficacy as conventional THA. However, a small proportion of patients would delay discharge.

The clinical data of two children with refractory/relapsed acute B-lymphoblastic leukemia (ALL-B)treated with Blinatumomab in Department of Pediatrics, Peking University People′s Hospital from September 2019 to May 2021 were retrospectively analyzed.After 1 course of Blinatumomab infusion, both children achieved complete hematologic remission.During the infusion process, grade 2 cytokine release syndrome (CRS) was observed, and there were no fatal adverse reactions.One case underwent bridging hematopoietic stem cell transplantation after remission and achieves disease-free survival currently.The other case is still alive after subsequent consolidation chemotherapy.As a novel bispecific antibody, Blinatumomab has a good response rate to refractory/relapsed ALL-B and induces fewer adverse events, so it can be used as a candidate immunotherapy for patients with high tumor burden.

Background::The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with high-risk (HR) T-cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under evaluation. Moreover, relapse is the main factor affecting survival. This study aimed to explore the effect of allo-HSCT (especially haploidentical HSCT [haplo-HSCT]) on improving survival and reducing relapse for HR childhood T-ALL in CR1 and the prognostic factors of childhood T-ALL in order to identify who could benefit from HSCT.Methods::A total of 74 newly diagnosed pediatric T-ALL patients between January 1, 2012 and June 30, 2018 were enrolled in this retrospective study. Patients were stratified into the low-risk chemotherapy cohort ( n = 16), HR chemotherapy cohort ( n = 31), and HR transplant cohort ( n = 27). Characteristics, survival outcomes, and prognostic factors of all patients were then analyzed. Results::Patient prognosis in the HR chemotherapy cohort was significantly worse than that in the low-risk chemotherapy cohort (5-year overall survival [OS]: 58.5% vs. 100%, P = 0.003; 5-year event-free survival [EFS]: 54.1% vs. 83.4%, P = 0.010; 5-year cumulative incidence of relapse [CIR]: 45.2% vs. 6.3%, P = 0.011). In HR patients, allo-HSCT improved the 5-year EFS and CIR compared to that of chemotherapy (5-year EFS: 80.1% vs. 54.1%, P = 0.041; 5-year CIR: 11.6% vs. 45.2%, P = 0.006). The 5-year OS was higher in the HR transplant cohort than that in the HR chemotherapy cohort (81.0% vs. 58.5%, P = 0.084). Minimal residual disease re-emergence was an independent risk factor for 5-year OS, EFS, and CIR; age ≥10 years was an independent risk factor for OS and EFS; and high white blood cell count was an independent risk factor for EFS and CIR. Conclusion::Allo-HSCT, especially haplo-HSCT, could effectively reduce relapse of children with HR T-ALL in CR1.

Objective:To explore the molecular response and prognostic factors of pediatric patients with Ph-positive acute lymphoblastic leukemia (Ph + ALL) treated by tyrosine kinase inhibitors (TKI) with chemotherapy in TKI era. Methods:The clinical data of children newly diagnosed with Ph + ALL admitted at Department of Pediatrics, Peking University People′s Hospital from August 2006 to February 2017 were retrospectively reviewed.The molecular biological characteristics and survival prognosis of the 30 patients who received continuous TKI with chemotherapy from early induction combined and no subsequent transplantation were analyzed. Results:The 30 patients with Ph + ALL had 19 males and 11 females with a median age of 8-year-old (ranging from 2 to 16 years). The complete remission (CR) rate after the first cycle of induction chemotherapy was 96.7% (29/30 cases), with overall CR rate of 100.0%; Before treatment, the mean level of BCR/ ABL mRNA in the 30 patients was 73.2% (0.12%-160.60%) and the level declined significantly with the progression of chemotherapy courses, reaching the plateau stage at the 6 th month of chemotherapy ( Z=-1.922, P>0.05); nine patients had recurrence, with a median recurrence time of 7 months (3.7-58.8 months). Univariate analysis showed that age ( P<0.05), the lever of minimal residual disease (MRD) after induction chemotherapy ( P<0.01) and the MRD level at the 3 th month of induction chemotherapy ( P<0.01) affected the recurrence rate.The median follow-up time of 30 patients was 42.6 months (6.4-96.5 months), and the 3-year overall survival (OS) rate and event-free survival (EFS) rate were (78.6±7.8)% and (72.4±8.4)%, respectively; Cox multivariate analysis showed that the initial white blood cell count ≥34.0×10 9/L ( OR=11.955, 95% CI: 1.075-132.899, P<0.05) and BCR/ ABL mRNA reduction less than 3 log from baseline [major molecular response (MMR)] at the 3 th month of induction chemotherapy ( OR=8.563, 95% CI: 1.254-58.478, P<0.05) were independent risk factors affecting the 3-year EFS rate.In addition, the initial white blood cell count ≥34.0×10 9/L ( OR=14.327, 95% CI: 1.843-243.592, P<0.05) was also an independent risk factor affecting the 3-year OS rate. Conclusions:The application of TKI can significantly deepen the molecular response of Ph + ALL in children.In the TKI era, the initial white blood cell count ≥ 34.0×10 9/L and BCR/ ABL mRNA reduction less than 3 log from baseline (MMR) at the 3 th month of induction chemotherapy are independent risk factors for the long-term survival of pediatric Ph + ALL.

Objective To study the effect of Ilizarov technique on thumb shortening and bone defect after trauma.Methods The clinical data of 20 patients with thumb shortening or bone defect treated by Ilizarov technique from April 2010 to January 2018 were retrospectively analyzed.There were 19 males and 1 female including 15 left fingers and 5 right fingers.The age ranged from 20 to 56 years,with an average of 33.1 years.The osteotomy plane included 9 cases at distal part of the metacarpal,6 cases proximal phalanx base,1 case interphalangeal joint and 1 case distal part of proximal phalanx.Two cases were osteomyelitis after proximal and distal phalanges trauma,which resulted in interphalangeal joint defects after lesion clearance,and the length of the joint defect was 0.5 cm and 0.7 cm respectively.One case was emergency finger shortening fusion,which resulted in metacarpophalangeal joint defect due to nonunion of fusion site,and the length of the joint defect was 0.5 cm.Causes of injury included mechanical strangulation (12 cases),crush injury (6 cases) and traffic injury (2 cases).Semi-ring external fixator was used to extend the extension.There were 15 cases of metacarpal bone osteotomy and 5 cases of proximal phalanx osteotomy,prolonged from the 5th day after surgery.The osteotomy was prolonged by 0.5 mm every day,once every 6 hours.Results The follow-up time ranged from 184 to 446 days with an average of 244.6 days.The average extension period was 62.2 days (26-118 days),and the average extension length was 3.1 cm (1.3-5.9 cm).The healing index was 43.7-84.1 d/cm and the average healing index was 64.8 d/cm.The external fixed extender was used for 114-376 days with an average of 206.3 days.The distraction index was 20.1 c/cm (range,19.5-21.4 d/cm) and the maturity index was 46.5 d/cm (range,39.4-110.1 d/cm) and the external fixation index was 66.5 d/cm (range,60-130.8 d/cm).The finger pointing function and sensory function of thumb were restored after operation.According to the trial criteria of thumb and finger reconstruction function evaluation in the upper limb part evaluation criteria of Hand Surgery Society of Chinese Medical Association,11 cases were excellent,9 cases good,and the excellent and good rate was 100％(20/20).The two-point discrimination was 4-9 mm.The patients were satisfied with the function and appearance.Conclusion Ilizarov technique is a good method to treat thumb shortening and bone defect after trauma.

Objective: To analyze the clinical outcome and the prognostic factor in pediatric patients with core binding factor-acute myeloid leukemia (CBF-AML). Methods: A total of 121 newly diagnosed pediatric CBF-AML patients enrolled from Aug. 2005 to Sep. 2017 were retrospectively reviewed. Cumulative incidence of relapse (CIR), event-free survival (EFS) and overall survival (OS) rates were estimated by Kaplan-Meier method and prognostic factors were evaluated by Cox regression with SPSS. Results: Of the 121 patients, 120 patients were assessed for bone marrow remission after induction chemotherapy. 100 cases (83.3%) achieved complete remission (CR) after the first course of chemotherapy. 119 cases (99.2%) achieved CR after the second course of chemotherapy. Of the 121 patients, 13 patients (10.7%) had recurrence with the median interval of recurrence as 13.8 months (3.7 to 58.8 months). 17 patients (14.0%) died. The CIR, EFS and OS at 3 years were 12.7%, 77.5% and 82.8%, respectively. The factors including age at diagnosis, sex, initial WBC count, presence of extramedullary leukemia, C-KIT expression, additional chromosomal abnormalities, and CR after the first course of chemotherapy were analyzed by multivariate regression analysis of Cox. Multivariate analysis identified that additional chromosomal abnormalities was the only independent risk factor affecting OS (HR=4.289, 95%CI 1.070-17.183, P=0.040). Conclusions Pediatric CBF-AML was a unique setting of prognostic subtypes. Chemotherapy produced good responses. Additional chromosomal abnormalities was the only independent risk factor for OS in pediatric CBF-AML.