Objective:To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL).Methods:A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children′s Hospital, Capital Medical University and Baoding Children′s Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients.Results:Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) ( χ2=1.88, 1.47, P=0.170, 0.224). Conclusions:Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

The protein arginine methyltransferases(PRMTs)family has a wide range of molecular functions and is involved in the generation, development, proliferation and differentiation of hematopoietic cells in the stem cell development.In hematological malignancy diseases, PRMTs can be involved in many important biological processes including cell proliferation, cell cycle, gene transcription, and DNA damage repair through methylation pathways.The abnormal expression of PRMTs can lead to the occurrence and development of malignancy diseases, especially in childhood leukemia.Targeted PRMTs therapy can effectively inhibit the proliferation and survival of tumor cells by reducing the expression of PRMTs.Therefore, the relationship between PRMTs and hematological malignancy diseases has received much attention and is likely to become an important target for treatment in the future.This article reviews the role and mechanism of PRMTs in hematological malignancy diseases, in order to provide new strategies for the treatment of hematological malignancy diseases.

Acute lymphoblastic leukemia(ALL)is the most common malignant tumor in childhood, and T-ALL accounts for 10%~15% of all in children with ALL.Based on the application of MICM classification, risk stratification and multi-drugs intensive therapy, the prognosis of children with T-ALL has been improved, but the overall survival rate and event free survival rate are still less than 70%, and the overall survival rate of relapsed / refractory T-ALL is less than 10%.The treatment of T-ALL in children still faces great challenges.CDl9 targeted chimeric antigen receptor(CAR)modified T cells have shown impressive results in children with refractory B-ALL, with remission rate of 70%~90%.The emergence of CAR-T and CAR modified NK cells(CAR-NK)targeted therapy is expected to improve the prognosis of T-ALL in children.This article reviews the latest progress of CAR-T and CAR-NK in children with T-ALL.

Acute leukemia (AL) is the most common tumor in childhood.With the improvement of risk stratification therapy, the complete remission rate of AL has been significantly improved.However, central nervous system leukemia (CNSL) remains the major cause of recurrence and death of leukemia.This study aims to review the pathogenesis, diagnosis and treatment of CNSL in children, hoping to further improve the understanding.

To analyze the clinical characteristics, treatment and prognosis of mediastinal germ cell tumors (GCTs) with concurrent hematologic malignancy (HM). The clinical features, treatment and prognosis of 3 cases of HM associated with mediastinal GCTs treated in the Department of Medical Oncology, Beijing Children′s Hospital from November 2014 to September 2018 were retrospectively analyzed.Meanwhile, relevant cases were searched in the PubMed and Wanfang database from their establishment to December 2019.Three male cases of HM associated with mediastinal GCTs aged from 12 to 16 years.The pathogenesis of mediastinal masses suggested teratoma or yolk sac tumor.All of them were treated with surgery and chemotherapy.Acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) was diagnosed respectively at 5 months, 9 months and 31 months after initial GCTs in the 3 cases.Two patients died and 1 child survived at the last follow-up.A total of 135 cases of concurrent GCTs and HM (or leukemia) were reviewed in online databases, involving 127 cases (94.1%) with the mediastinal GCTs associated with HM and 8 cases(5.9%) with GCTs related HM from another original sites.One hundred and twenty-six cases (99.2%) were male and the median age of GCTs diagnosis was 22 (10-48) years.Fifty-three cases (41.7%) were teratoma and 94 cases (74.0%) were GCTs containing teratoma with or without yolk sac tumor.Among the types of HM, 72 cases (56.7%) were AML and 31 cases (24.4%) were AML-M7.The median interval between GCTs and HM was 3 (0-122) months.Forty-six cases (36.2%) presented 2 malignancies simultaneously.HM were diagnosed within 12 months of GCTs in 85 cases (66.9%). The survival data were known in 107 cases, involving 94 (87.9%) deaths and 13 (12.1%) survivors.The median survival time after diagnosis of HM was 2 (0-48) months.The tendency of HM must be highly concerned in adolescent male patients with primary mediastinal GCTs, especially those with yolk sac tumor or teratoma.Their prognoses are very poor.Allogeneic hematopoietic stem cell transplantation is an alternative treatment.

Objective:To analyze the early risk warning factors of clinical characteristics in children with acute lymphoblastic leukemia (ALL) complicated with acute pancreatitis (AP).Methods:Retrospective study.A total of 39 children with ALL complicated with AP admitted to the Hematology Center of Beijing Children′s Hospital, Capi-tal Medical University from May 2018 to December 2020 were selected as the case group, and 78 ALL patients were randomly selected as the control group according to the exact matching of 1∶2 of the same age and sex.The measurment data and counting data were analyzed by Rank sum test ( Mann Whitney U test) and χ2 test between the 2 groups, respectively, and further multivariate Logistic regression analysis was performed to find out the risk factors of ALL complicated with pancreatitis.At the same time, the relationship between each index and severity was explored. Results:The incidence of ALL complicated with AP was 8.55% (39/456 cases). The high incidence age was 3-10 years old.Sixty-four point nine percent (24/37 cases) of the pancreatitis occurred in the early stage of chemotherapy, and 66.7% (26/39 cases) was associated with asparaginase.There were significant differences in ALL risk stratification ( χ2=21.404, P<0.001), C-reactive protein (CRP)( U=232.000, P<0.001), procalcitonin (PCT)( t=3.950, P<0.001), hematocrit( t=3.981, P<0.001), serum calcium( t=-9.609, P<0.001), indirect bilirubin( U=1 142.000, P<0.05), triglyceride( t=3.600, P=0.001) and albumin( t=-6.296, P<0.001) between the 2 groups.The sensitivity of abdominal CT, abdominal ultrasound and pancreatic magnetic resonance imaging in the case group were 70.8%, 81.6% and 100.0%, respectively.Multivariate Logistic regression analysis showed that differences between albumin( OR=11.444, 95% CI: 3.240-40.423), triglyceride( OR=18.047, 95% CI: 5.020-65.074) and risk stra-tification( OR=8.894, 95% CI: 1.889-41.885) were statistically significant, and there were obvious differences in PCT( U=3.000, 2.000, all P<0.05) and serum calcium( U=4.500, 8.500, all P<0.05) between patients with severe pancreatitis and patients with mild or moderate severe pancreatitis. Conclusions:ALL complicated with AP often occurs in the early stage of chemotherapy, mainly caused by asparaginase.In imaging examination, the sensitivity of pancreatic magnetic resonance imaging is the highest, followed by abdominal ultrasound.Risk stratification, decreased albumin and elevated triglyceride are risk factors of ALL complicated with AP, which are helpful for early identification of high-risk patients with ALL complicated with AP.PCT and serum calcium may play an important role in severe pancreatitis.

The overall survival rate of children with acute myeloid leukemia(AML) is significantly lower than that of acute lymphoblastic leukemia.The main causes of death include primary disease-related death and treatment-related death.Most of the treatment-related deaths are caused by infection, bleeding and organ failure.Infection is the most common complication of pediatric AML during the myelosuppression period after chemotherapy, and it is also the main cause of early death in AML.Based on the analysis of pathogens, laboratory tests and risk factors, this paper reviews the clinical characteristics and research progress of infection in myelosuppression following chemotherapy for AML, so as to provide a basis for early identification, clinical management and condition judgment, and further improve the survival rate of children with AML.

The clinical data of a WHIM syndrome child with cardiac malformation as the first symptom in December 2017 in Beijing Children′s Hospital Affiliated to Capital Medical University was retrospectively analyzed.A 5-year-old female patient presented with cardiac malformation, neutropenia and recurrent infection.Heterozygous mutation(c.1000C>T) was detected in CXCR4 gene.Echocardiography and CT exhibited cardiac malformation.WHIM syndrome is very rare, and it was the first case with cardiac malformation as the first manifestation in China, thus hoping to improve clinicians′ understanding of this disease.

Objective:To evaluate the heterogeneity in pediatric ETV6-RUNX1 acute lymphoblastic leukemia (ALL) by gene expression profile and to study clinical characteristics in different clusters.Methods:An improved advanced fragment analysis (iAFA) technique was developed to detect 57 marker genes in 264 pediatric ALL patients treated in Beijing Children’s Hospital from August 2016 to June 2019. The 56 ALL patients with ETV6-RUNX1 positive were evaluated by clinical characteristics in gene expression profile, immunophenotype and early response of chemotherapy in different clusters.Results:The 56 ETV6-RUNX1-positive patients were clustered into 2 groups of E/R-1 (45, 80.4%) and E/R-2 (11, 19.6%) . Spearman coefficient was 0.788 and 0.901 in E/R-2 and E/R-1, respectively. The median of initial platelet counts was 104 (27-644) and 50 (8-390) ( P<0.01) in E/R-2 and E/R-1, respectively. The median of proportion of initial bone marrow immature cells was 0.830 (0.270-0.975) and 0.935 (0.445-0.990) ( P<0.05) in E/R-2 and E/R-1, respectively. The most specific immunophenotype at initial diagnosis, CD22 +CD34 +CD20 -CD117 -CD56 -, mainly gathered in E/R-2 ( P<0.001) . Patients negative of minimal residual disease detected by flow cytometry (MRD-FCM) at day 33 were 5 (55.6%) and 32 (88.9%) in E/R-2 and E/R-1, respectively. There was no significant difference in the original analysis ( P=0.064) but difference in sensitivity analysis ( P=0.035) . Nevertheless, patients negative of MRD detected by polymerase chain reaction (MRD-PCR) at day 33 were 7 (77.8%) and 36 (100%) in E/R-2 and E/R-1, respectively, with significant difference ( P=0.047) . Conclusion:Gene expression profile shows heterogeneous in ETV6-RUNX1 ALL, and the E/R-2 profile indicates that these patients may have a less tendency to thrombocytopenia at the initial diagnosis but have poorer response to induction chemotherapy and may influence further outcome.

Objective To discuss thk curk kffkct and sidk kffkcts of donor anti-CD19 chimkric antigkn rkckp-tor T lemphocetks(CD19 CLA-T)for trkating rkcurrknt acutk B-ckll lkuckmia aftkr allogknkic hkmatopoiktic stkm-ckll transplantation(Lllo-HSCT),and to analezk thk influkncing factors for this thkrape. Methods Thk clinical data of 5 acutk B-ckll lkuckmia patiknts wkrk analezkd rktrospkctivkle who rklapskd aftkr Lllo-HSCT and rkckivkd donor CD19 CLA-T thkrape at Bkijing Childrkn＇s Hospital from Jule 2015 to Octobkr 2017. Diskask status bkfork infusion, conditioning rkgimkn,rkinfusion ckll dosk,and sidk-kffkct of CLA-T infusion,changks in thk rklatkd immunological indicators,and follow-up trkatmknt rksults wkrk invkstigatkd. ResuIts Onk patiknt had no kffkct,othkr patiknts got rk-mission or minimal rksidual diskask(MAD)nkgativk within 4 wkkcs aftkr CLA-T infusion,and thk middlk timk was 14 daes. Pkriphkral CLA-T pkac happknkd 2 wkkcs aftkr CLA-T infusion. Be thk last follow,2 patiknts dikd of lkuckmia, 3 patiknts wkrk alivk,and 1 cask of thkm livkd with tumor aftkr CD19 nkgativk rklapsk,othkrs livkd with diskask-frkk condition. Cetocink rklkask sendromk(CAS)was thk most common sidk kffkct,happkning in 1 to 2 wkkcs aftkr infusion, 1 patiknt had nkurologic toxicitiks,and 2 patiknts had suspicious graft -vkrsus -host diskask. ConcIusions Donor CD19 CLA-T thkrape has a good short-tkrm kffkct for rklapskd B -ckll lkuckmia patiknts aftkr Lllo -HSCT,but long-tkrm kffkct rkquirks furthkr obskrvation;CAS is thk most common sidk-kffkct. Off-targkt and ckll kxhaustion ark thk main rkasons for dkfkat.