OBJECTIVETo investigate whether there were differences in the clinical characteristics, cytogenetic characteristics, immunophenotype and prognosis in children with B cell type acute lymphoblastic leukemia (B-ALL) carrying different fusion genes.

METHODSThe research included 80 children with B-ALL from Peking University People's Hospital between March 2006 and December 2008. Eighteen children were positive for TEL/AML1, 14 for E2A/PBX1, 11 for BCR/ABL,and 2 cases for MLL/AF4, and 35 cases were negative for all of the 4 fusion genes. Data including clinical characteristics, morphology, immunophenotype and cytogenetic characteristics were collected, and the disease-free survival (DFS) was evaluated. The children were followed up until April 2009.

RESULTSIn the 18 children with TEL/AML1+B-ALL, 66.7% were younger than 5 years old. They had low tumor load. FAB-L2 morphology was commonly observed, but t(12;21) was often absence in these children. Up to now,17 children who survived were disease-free. In the 14 children with E2A/PBX1+B-ALL, the majority were female. Thirteen children showed FAB-L1 morphology. Twelve children showed pre-B-ALL immunophenotype. The EFS was close to 80%. In the 11 children with BCR/ABL+B-ALL, 10 children showed common B type immunophenotype. FAB-L1 and FAB-L2 morphology was found in 4 children respectively. The DFS was less than 20%. Two children with MLL/AF4 positive B-ALL had high tumor load. Their morphologic diagnosis was FAB-L1. Both showed the Pro-B-ALL immunophenotype. One child discontinued treatment at the early stage of chemotherapy, and the other child survived disease-free until now.

CONCLUSIONSThe B-ALL children with different fusion genes have different clinical characteristics, immunophenotypes and prognosis.

Adolescent ; Child ; Child, Preschool ; Core Binding Factor Alpha 2 Subunit ; genetics ; Female ; Gene Fusion ; Homeodomain Proteins ; genetics ; Humans ; Immunophenotyping ; Infant ; Male ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Oncogene Proteins, Fusion ; genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; immunology

OBJECTIVE: To study the influence of dasatinib treatment on body height in children with acute myeloid leukemia (AML). METHODS: A retrospective analysis was performed for the clinical data of 86 AML children aged <17 years. According to the treatment regimen, these children were divided into a conventional chemotherapy group and a dasatinib chemotherapy group. The 57 children in the conventional chemotherapy group were given conventional chemotherapy drugs without tyrosine kinase inhibitor, and the 29 children in the dasatinib chemotherapy group were given conventional chemotherapy drugs and dasatinib. The two groups were compared in terms of height standard deviation score (HtSDS) at the beginning of treatment and after treatment, as well as the change in HtSDS after 1 and 2 years of treatment. RESULTS: There was no significant difference in HtSDS between the conventional and dasatinib chemotherapy groups before treatment. Within the first two years of treatment, the dasatinib chemotherapy group had a similar change trend of HtSDS as the conventional chemotherapy group. Four children in the dasatinib chemotherapy group reached the final adult height during follow-up, which was significantly lower than the target height (P=0.044). In the conventional chemotherapy group, there was no significant difference between final adult height and target height. In the dasatinib chemotherapy group, the children in adolescence had a significant change in HtSDS after treatment (P=0.032). CONCLUSIONS Dasatinib treatment may affect the final height of children with AML, and the use of dasatinib after the beginning of adolescence may lead to growth disorder, but dasatinib treatment has little effect on body height in the short-term treatment.
Adolescent ; Body Height ; Child ; Dasatinib ; therapeutic use ; Growth Disorders ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Retrospective Studies

OBJECTIVETo study the relationship between loss of sex chromosomes and prognosis in children with acute myeloid leukemia (AML) M2 subtype.

METHODSAccording to cytogenetic characteristics, 106 children with AML were divided into three groups: patients with normal karyotype (Group A, n=26), patients with abnormal karyotype who had no loss of sex chromosomes (Group B, n=52), and patients with abnormal karyotype who had loss of sex chromosomes (Group C, n=28). Prognosis was compared between the three groups.

RESULTSThe 5-year event-free survival (EFS) rates of Groups A, B, and C were (38.9±11.2)%, (59.3±7.3)%, and (66.5±10.5)%, respectively; the EFS of Group C was significantly higher than that of Group A (P=0.035). The 5-year overall survival (OS) rates of Groups A, B, and C were (54.3±13.5)%, (68.1±7.7)%, and (77.9±9.8)%, respectively (P>0.05). The 5-year EFS of 58 patients with t(8;21) was (63.3±7.3)%, significantly higher than that of patients with normal karyotype (P=0.015). All the 28 cases in Group C had t(8;21), and their 5-year EFS was not significantly different from that of patients with t(8;21) in Group B (P>0.05).

CONCLUSIONSLoss of sex chromosomes is a favorable karyotype in children with AML M2 subtype and the patients in this group mostly have t(8;21). Why loss of sex chromosomes indicates a favorable prognosis is probably because it is accompanied by t(8;21) in the patients.

Adolescent ; Child ; Child, Preschool ; Chromosomes, Human, Pair 21 ; Chromosomes, Human, Pair 8 ; Female ; Humans ; Karyotype ; Leukemia, Myeloid, Acute ; genetics ; mortality ; Male ; Prognosis ; Sex Chromosome Aberrations ; Translocation, Genetic

Objective To investigate the clinical characteristics and risk factors of childhood acute leukemia (AL) with severe neurologic complications.Methods From Jun.1991 to Mar.2011,26 AL patients with severe neurologic complications in Peking University People's Hospital were enrolled.The incidence,clinical features,and risk factors for severe neurologic complications were retrospectively analyzed.Results There 26 patients included 8 cases of acute lymphoblastic leukemia,17 cases of acute myeloid leukemia(AML) and 1 case of acute mixed lineage leukemia.There were 20 patients taking CT scan and 17 patients were confirmed with intracranial hemorrhage.Six cases of AML without CT scan were dead.The patients suffering from intracranial hemorrhage all had intraparenchymal hemorrhage.The AML-M5 with intracranial hemorrhage had higher white blood cell count and higher level of L-lactate dehydrogenase than those without intracranial hemorrhage.These were 5 cases(31.25％) of AML with platelet count ＜ 20 × 109/L,12 cases(70.58％) of AML with prolonged prothrombin time,7 cases(41.17％) of AML with prolonged activated partial thromboplastin time,and 8 cases(47.06％) of AML with low fibrinogen when the severe neurologic complication occurred.Conclusions The most common type of severe neurologic complications of childhood AL is intracranial hemorrhage.The patients with AML are prone to occur intracranial hemorrhage.Intensive blood production transfusion may be beneficial to reduce the probability of intracranial hemorrhage in these patients.

Objective: To explore the clinical features and prognostic factors of Ph-positive and/or BCR-ABL positive acute lymphoblastic leukemia (Ph⁺ ALL) in children. Methods: The clinical data of 68 Ph⁺ ALL children who were treated at Peking University People's Hospital from December 2006 to December 2016 was retrospectively reviewed. Survival analysis were estimated by Kaplan-Meier method. Univariate analysis was estimated by Log-rank test and Chi-square, and multivariate analysis was estimated by Cox proportional hazards regression model. Results: In the 68 cases, the proportion of male to female was 2.1∶1, with a median age of 8 (1-16) years, and the median overall survival (OS) and disease free survival (DFS) were 16.8 months and 13.5 months, respectively. The early response rate to treatment was 43.9%, with myeloid-antigens-expression group lower than the non-expression group (29.6% vs 61.3%, χ²=5.814, P=0.020); The complete remission (CR) rate after one-course induction therapy was 86.2% (56/65), with good-response group higher than the poor-response group (100.0% vs 74.2%, χ²=6.680, P=0.003);The CR rate after induction in patients receiving imatinib plus chemotherapy was higher than the patients receiving chemotherapy only (94.9% vs 73.1%, χ²=5.185, P=0.024). The 2-and 5-year OS were (61.4±7.0)% and (50.8±8.1)%, respectively. The 2-and 5-year DFS were (54.6±6.8)% and (48.6±7.3)%, respectively. Univariate analysis showed that the initial WBC, LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year OS rate (all P<0.05). LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year DFS rate (all P<0.05). Multivariate prognostic analysis for OS (RR=45.7, 95% CI 1.4-1 528.2, P=0.033) and DFS (RR=52.3, 95% CI 1.6-1 725.9, P=0.026) showed that the spleen ≥ 3 cm was the independent risk factor. Conclusions: Pediatric Ph⁺ ALL is a special condition with unique clinical and biological features. The early response to treatment was poor in patients with myeloid-antigens-expression, which resulted in a low CR rate after one-course induction and the administration of imatinib can remarkably improve the CR rate. Initial spleen ≥ 3 cm is an independent prognostic factor. The efficacy of chemotherapy alone is poor, and imatinib combined with chemotherapy is applauded in the aim of improving outcomes.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; Benzamides ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Remission Induction ; Retrospective Studies ; Treatment Outcome

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.
Child ; Core Binding Factors ; Disease-Free Survival ; Humans ; Leukemia, Myeloid, Acute ; Prognosis ; Remission Induction ; Retrospective Studies

OBJECTIVETo explore the efficacy and adverse effects of clofarabine for relapsed/refractory acute lymphoblastic leukemia in children.

METHODSTwenty-six pediatric patients with relapsed/refractory acute lymphoblastic leukemia were treated with clofarabine. There were 22 males and 4 females, with a mean age of 9.5 years (ranging from 4 to 17 years). They received clofarabine 52 mg/m2 intravenously over 2 hours daily for 5 days. Thirteen patients received two cycles and one patient received three cycles.

RESULTSIn the first cycle of clofarabine, complete remission was obtained in 11 children (42%) and partial remission was obtained in 7 children (27%). Eight children (31%) were considered unresponsive. In the second cycle, 11 (85%) of the 13 children obtained complete remission, 1 (8%) partial remission and 1 (8%) was unresponsive. One child received three cycles and obtained complete remission in each cycle. The common adverse events were myelosuppression, infection, liver dysfunction and gastrointestinal adverse reactions. There were no chemotherapy-related deaths.

CONCLUSIONSClofarabine is effective in the treatment of children with relapsed/refractory acute lymphoblastic leukemia and its adverse effects can be tolerated. Clofarabine could be a promising new treatment for relapsed/refractory acute lymphoblastic leukemia.

Adenine Nucleotides ; adverse effects ; therapeutic use ; Adolescent ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Arabinonucleosides ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Recurrence

Purpose: Chemotherapy has been the primary treatment for patients with B-cell acute lymphoblastic leukemia (B-ALL). However, there are still patients who are not sensitive to chemotherapy, including those with refractory/relapse (R/R) disease and those experiencing minimal residual disease (MRD) re-emergence. Chimeric antigen receptor-T lymphocytes (CAR-T) therapy may provide a new treatment option for these patients. Materials and Methods: Our institution conducted a single-arm prospective clinical trial (ChiCTR-OPN-17013507) using CAR-T-19 to treat R/R B-ALL and MRD re-emergent patients. One hundred and fifteen patients, aged 1-25 years (median age, 8 years), were enrolled, including 67 R/R and 48 MRD re-emergent CD19-positive B-ALL patients. Results: All patients achieved morphologic complete remission (CR), and within 1 month after infusion, 111 out of 115 (96.5%) patients achieved MRD-negative CR. With a median follow-up time of 48.4 months, the estimated 4-year leukemia-free survival (LFS) rate and overall survival (OS) rate were 68.7%±4.5% and 70.7%±4.3%, respectively. There were no significant differences in long-term efficacy observed among patients with different disease statuses before infusion (4-year OS: MRD re-emergence vs. R/R B-ALL, 70.6%±6.6% vs. 66.5%±6.1%, p=0.755; 4-year LFS: MRD re-emergence vs. R/R B-ALL, 67.3%±7.0% vs. 63.8%±6.2%, p=0.704). R/R B-ALL patients bridging to transplantation after CAR-T treatment had a superior OS and LFS compared to those who did not. However, for MRD re-emergent patients, there was no significant difference in OS and LFS, regardless of whether they underwent hematopoietic stem cell transplantation or not. Conclusion CD19 CAR-T therapy effectively and safely cures both R/R B-ALL and MRD re-emergent patients.

Objective: To investigate the economic burden of bacillus Calmette-Guérin (BCG) lymphadenitis in Shandong Province. Methods: From May 2011 to December 2019, 304 patients applying for the province-level compensation of BCG lymphadenitis was selected from Shandong Province in this study. The basic situation, vaccination, outpatient (inpatient) records, cost and relevant information of those patients were collected to calculate the direct economic burden (including direct medical costs and direct non-medical costs), indirect economic burden and total economic burden. Comparison of the difference of economic burden of cases with different characteristics was taken. Results: The M(Q₁,Q₃) of age of BCG lymphadenitis patients was 3 (2, 4) months, among which 239 cases (78.6%) were male, 71 cases (23.4%) had lymphadenopathy, and 227 cases (74.7%) underwent surgery.The number of outpatient only, inpatient only and outpatient then inpatient was 25.7% (78 cases), 7.2% (22 cases) and 67.1% (204 cases), respectively. The M(Q₁,Q₃) of direct, indirect and total economic burden of single case after discount was 9 910 (5 713, 16 074), 2 081 (1 547, 3 122) and 12 262 (7 694, 18 571) yuan, respectively.The direct medical expenses accounted for 89.4% of the direct economic burden, the direct economic burden accounted for 84.9% of the total economic burden, the total economic burden of 80.0% cases accounted for only about 20.0% of the compensation amount, and the total economic burden of only 2.3% cases accounted for more than 60.0% of the compensation amount.The direct, indirect and total economic burden of patients with inpatient only and outpatient then inpatient was higher than that of patients with outpatient only; the direct, indirect and total economic burden of patients with operation was higher than that of patients with non-operation; the direct and total economic burden of patients with unulcerated lymph node was higher than that of patients with ulcerated lymph node(all P values<0.05). Conclusion: The economic burden of BCG lymphadenitis cases in Shandong Province is influenced by the mode of diagnosis and treatment, with direct medical expenses as the predominant component.
BCG Vaccine ; Cost of Illness ; Financial Stress ; Humans ; Infant ; Lymphadenitis/epidemiology* ; Male ; Vaccination

Objective: To observe the preventive and therapeutic effect of Huanglian Ejiao Tang on myocardial injury induced by anthracycline chemotherapeutic drugs in all kinds of cancer patients undergoing chemotherapy. Method:We chosen all kinds of cancer patients with combined use of anthracycline chemotherapy drugs in our hospital, 21 days as one cycle. The cardiac toxicity reaction was observed after three continuous chemotherapy cycles. A total of 64 patients who met the dialectical criteria of "imbalance between heart-Yang and kidney-Yin" were randomly divided into treatment group (32 cases) and control group (32 cases). Patients in treatment group were treated with Chinese medicine Huanglian Ejiao Tang based on original chemotherapy regimen, adding and subtracting Chinese medical materials according to the symptoms. Patients in control group continued to maintain the original chemotherapy regimen, and both two groups of patients continued to receive 3 cycles of continuous chemotherapy. By comparing the cardiac function classification and cardiac function tolerance between the 3 cycles and 6 cycles of two groups of patients after chemotherapy; changes of echocardiography index, QTc interval, creatine kinase isoenzyme (CK-MB), Myoglobin (MYO), cardiac troponin I (cTNI)and nitrogenous terminal-pro-brain natriuretic peptide(NT-pro-BNP) concentration value were compared between two groups; and the concentrations of adrenaline (E), norepinephrine (NE) and angiotensin Ⅱ(AngⅡ) were observed and compared; meanwhile, the correlation analysis was carried out at the same time. Result:After 6 cycles of chemotherapy in Chinese medicine treatment group, degree of cardiac function classification and the 6 minute walking heart function tolerance were significantly better than those at the 3 cycles of chemotherapy (P<0.05), but there was no significant change in control group; the concentrations of CK-MB, cTNI, MYO and NT-pro-BNP in treatment group were significantly lower than those in control group(P<0.05), and the electrocardiogram QTc interval in the treatment group was significantly lower than that in the control group (P<0.05); echocardiography indexes E/A ratio and left ventricular ejective fraction (LVEF) value in the treatment group were significantly higher than those in control group (P<0.05). There were no significant changes in left ventricular end-systolic diameter (LVDd) and left ventricular end-systolic diameter (LVDs) between the treatment and the control group. After 3 cycles and 6 cycles of chemotherapy, the blood NE,E and AngⅡ concentrations in the treatment group were significantly lower than those in the control group (P<0.05). There were positive linear correlation in concentration changes of blood NE, E and AngⅡ as well as the concentration changes of CK-MB, cTNI, MYO and NT-pro-BNP between 3 cycles and 6 cycles after chemotherapy. After 6 cycles of chemotherapy, the incidence of cardiovascular events in the treatment group was significantly lower than that in the 3 cycles of chemotherapy, while the incidence in control group was increased. Conclusion:Huanglian Ejiao Tang can reduce the excitability of the symppthetic nervous system (SNS) and renin-angiotensin system(RAS) in human body and inhibit the release level of NE, E and AngⅡ by effect of "invigorating the kidney and clearing the heart". It has a certain preventive and treatment effect on the cardiac toxicity of patients with the cumulative use of anthracycline chemotherapy. To a certain extent, it can inhibit myocardial injury, improve cardiac function and reduce the incidence of cardiovascular events.