Analysis of 7 cases of pediatric acute myeloid leukemia with DEK-NUP214 fusion gene / 中华儿科杂志

Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.

Safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia / 中国当代儿科杂志

OBJECTIVES@#To study the safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia (R/R-ALL).@*METHODS@#Six children with R/R-ALL who received blinatumomab treatment from August 2021 to August 2022 were included as subjects, and a retrospective analysis was performed for their clinical data.@*RESULTS@#Among the six children, there were three boys and three girls, with a median age of 10.5 (5.0-13.0) years at the time of inclusion. Of all six children, one had refractory ALL and did not achieve remission after several times of chemotherapy, and 5 relapsed for the first time, with a median time of 30 (9-60) months from diagnosis to relapse. Minimal residual disease (MRD) before treatment was 15.50% (0.08%-78.30%). Three children achieved complete remission after treatment, among whom two had negative conversion of MRD. Five children had cytokine release syndrome (CRS), among whom 3 had grade 1 CRS and 2 had grade 2 CRS. Four children were bridged to allogeneic hematopoietic stem cell transplantation, with a median interval of 50 (40-70) days from blinatumomab treatment to transplantation. The six children were followed up for a median time of 170 days, and the results showed an overall survival rate of 41.7% (95%CI: 5.6%-76.7%) and a median survival time of 126 (95%CI: 53-199) days.@*CONCLUSIONS@#Blinatumomab has good short-term safety and effectiveness in the treatment of childhood R/R-ALL, and its long-term effectiveness needs to be confirmed by studies with a larger sample size.

Clinical features and prognosis of juvenile myelomonocytic leukemia: an analysis of 63 cases / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical features of juvenile myelomonocytic leukemia (JMML) and their association with prognosis.@*METHODS@#Clinical and prognosis data were collected from the children with JMML who were admitted from January 2008 to December 2016, and the influencing factors for prognosis were analyzed.@*RESULTS@#A total of 63 children with JMML were included, with a median age of onset of 25 months and a male/female ratio of 3.2∶1. JMML genetic testing was performed for 54 children, and PTPN11 mutation was the most common mutation and was observed in 23 children (43%), among whom 19 had PTPN11 mutation alone and 4 had compound PTPN11 mutation, followed by NRAS mutation observed in 14 children (26%), among whom 12 had NRAS mutation alone and 2 had compound NRAS mutation. The 5-year overall survival (OS) rate was only 22%±10% in these children with JMML. Of the 63 children, 13 (21%) underwent hematopoietic stem cell transplantation (HSCT). The HSCT group had a significantly higher 5-year OS rate than the non-HSCT group (46%±14% vs 29%±7%, P<0.05). There was no significant difference in the 5-year OS rate between the children without PTPN11 gene mutation and those with PTPN11 gene mutation (30%±14% vs 27%±10%, P>0.05). The Cox proportional-hazards regression model analysis showed that platelet count <40×109/L at diagnosis was an influencing factor for 5-year OS rate in children with JMML (P<0.05).@*CONCLUSIONS@#The PTPN11 gene was the most common mutant gene in JMML. Platelet count at diagnosis is associated with the prognosis in children with JMML. HSCT can improve the prognosis of children with JMML.

Clinical Impact of Drug Adherence of Tyrosine Kinase Inhibitors in Children with Ph-Positive Acute Lymphoblastic Leukemia / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to explore the impact of ABL1–tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients’ prognosis from TKIs intake practices. @*Materials and Methods@#Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated. @*Results@#Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia. @*Conclusion@#TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.

Significance of paroxysmal nocturnal hemoglobinuria clone in immunosuppressive therapy for children with severe aplastic anemia / 中国当代儿科杂志

OBJECTIVES@#To study the association between paroxysmal nocturnal hemoglobinuria (PNH) clone and immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA).@*METHODS@#A retrospective analysis was performed on the medical data of 151 children with SAA who were admitted and received IST from January 2012 to May 2020. According to the status of PNH clone, these children were divided into a negative PNH clone group (n=135) and a positive PNH clone group (n=16). Propensity score matching was used to balance the confounding factors, and the impact of PNH clone on the therapeutic effect of IST was analyzed.@*RESULTS@#The children with positive PNH clone accounted for 10.6% (16/151), and the median granulocyte clone size was 1.8%. The children with positive PNH clone had an older age and a higher reticulocyte count at diagnosis (P<0.05). After propensity score matching, there were no significant differences in baseline features between the negative PNH clone and positive PNH clone groups (P>0.05). The positive PNH clone group had a significantly lower overall response rate than the negative PNH clone group at 6, 12, and 24 months after IST (P<0.05). The evolution of PNH clone was heterogeneous after IST, and the children with PNH clone showed an increase in the 3-year cumulative incidence rate of aplastic anemia-PNH syndrome (P<0.05).@*CONCLUSIONS@#SAA children with positive PNH clone at diagnosis tend to have poor response to IST and are more likely to develop aplastic anemia-PNH syndrome.

Digitalized analysis of the gingival and bone morphology in the maxillary anterior teeth in patient with posterior dental implant / 中华口腔医学杂志

Objective: To explore and analyze the correlation between labial gingival morphology and alveolar bone morphology of maxillary anterior teeth in patients with posterior dental implant, so as to provide reference basis for restoration design and esthetic reconstruction of anterior teeth. Methods: Sixty-four patients [24 males, 40 females (25.6±3.3) years old] who planned to receive posterior dental implant restoration were recruited randomly with the inclusion and exclusion criteria in Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University from May 2020 to May 2021. According to the visibility of periodontal probe through gingival margin, the subjects were divided into thin and thick gingival biotypes, including 29 cases of thin biotype and 35 cases of thick biotype. The 3Shape software was used to perform oral scanning, and cone beam CT (CBCT) was taken for each patient. Geomagic and Mimics software were used to measure and record the labial crown width and length, gingival papilla height, gingival angle, bone papilla height and bone margin angle of maxillary anterior teeth. Results: The crown width length ratios of maxillary central incisors, lateral incisors and canines were 0.85±0.08, 0.80±0.08 and 0.86±0.09 (F=10.71, P<0.01). The height of gingival papilla between maxillary central incisors, between central incisors and lateral incisors, between lateral incisors and canines were (3.93±0.86), (3.47±0.84) and (3.38±0.91) mm respectively (F=7.44, P<0.01), and the height of corresponding bone papilla were (3.44±0.88), (3.12±0.75) and (2.72±0.63) mm respectively (F=14.26, P<0.01). The gingival margin angles of maxillary central incisors, lateral incisors and canines were 88.3°±7.7°, 84.7°±8.9° and 81.2°±6.6° (F=13.15, P<0.01), and the bone margin angles were 103.2°±13.1°, 99.5°±11.2° and 110.6°±13.0° (F=13.25, P<0.01). The crown width length ratio (0.81±0.08), gingival margin angle (82.2°±7.4°) and bone margin angle (99.4°±12.9°) of thin gingival subjects were significantly lower than those of thick gingival subjects (0.85±0.09, 86.5°±8.6°, 108.5°±11.4°) (t=-2.79, 3.63, 5.20, P<0.01). The height of gingival papilla [(3.93±0.81) mm] and bone papilla [(3.43±0.80) mm] in thin gingival subjects were significantly lower than those in thick gingival subjects [(3.34±0.84) and (2.85±0.71) mm, respectively] (t=-4.89, -5.36, P<0.01). The height of labial gingival papilla of upper anterior teeth was positively correlated with that of bone papilla in all patients (r=0.66, P<0.01); the ratio of crown width to length of upper anterior teeth was positively correlated with the angle of bone margin (r=0.42, P<0.01); the height of anterior gingival papilla was negatively correlated with the angle of bone margin (r=-0.58, P<0.01), and the height of bone papilla was negatively correlated with the angle of bone margin (r=-0.82, P<0.01). Conclusions: The crown shape, gingival shape and alveolar bone shape of maxillary anterior teeth were different in different tooth positions. Patients with different periodontal phenotypes had different crown width length ratio, gingival papilla height, bone papilla height, gingival margin angle, and bone margin angle.

Digital analysis of the correlation between gingival thickness and alveolar bone thickness in the maxillary anterior teeth region / 中华口腔医学杂志

Objective: To measure the labial gingival thickness and bone lamella thickness in the maxillary anterior area using digital method, and to analyze the correlation between the two, so as to provide a reference for esthetic restoration and implantation treatment of the upper anterior area. Methods: Fifty-seven patients [23 males, 34 females, (25.8±4.5) years old] who planned to receive posterior dental implant restoration were recruited randomly with the inclusion and exclusion criteria in Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University from May 2020 to October 2020. The 3Shape software was used to perform oral scanning, and cone beam CT (CBCT) was taken for each patient. The image data was fitted and registered by the 3Shape software. The gingival thickness at 2 mm below the gingival margin, bone thickness and gingival thickness at 2 and, 4 mm below the crest of the labial alveolar crest in maxillary central incisors, lateral incisors and canines, were measured. Results: The gingival thickness at 2 mm below the gingival margin of maxillary central incisors, lateral incisors and canines was (1.42±0.21), (1.19±0.17) and (1.23±0.20) mm respectively (F=12.47, P<0.001). The gingival thickness at 2 mm below gingival margin and 4 mm below crest of residual ridge in the male patients were (1.31±0.21) and (0.67±0.22) mm, and those in the female patients were (1.26±0.22) and (0.58±0.19) mm respectively, and there were statistically significant differences in the gingival thickness between the "2 mm below gingival margin" group and the "4 mm below crest of residual ridge" group (t=2.01 and 3.97, P<0.05). There was a positive correlation between gingival thickness and alveolar bone thickness at 2 mm and 4 mm below the crest of residual ridge in maxillary anterior region, and the correlation coefficients (r) were 0.387 and 0.344 respectively (P<0.05). Conclusions: Gingival thickness of maxillary anterior area is related to the tooth position and gender. The gingival thickness of men is greater than that of women.The gingival thickness at 2 and 4 mm below the crest of the alveolar crest is positively correlated with the thickness of the alveolar bone.

Efficacy and prognostic factors in children with non-core binding factor acute myeloid leukemia / 中国当代儿科杂志

OBJECTIVE@#To compare the efficacy of the CAMS-2005 and CAMS-2009 regimens in treating children with non-core binding factor acute myeloid leukemia (non-CBF AML) and to study the prognosis factors.@*METHODS@#A total of 161 children who were initially diagnosed with non-CBF AML from April 2005 to December 2015 were enrolled as study subjects, and were divided into a CAMS-2005 regimen group (n=52) and a CAMS-2009 regimen group (n=109) according to the chemotherapy regimen provided. The efficacy was retrospectively compared between the two groups.@*RESULTS@#The complete remission (CR) rate at the first course of treatment was higher in the CAMS-2009 regimen group than that in the CMAS-2005 regimen group (63.3% vs 46.2%; P0.05). Children who achieved CR at the first course of treatment had significantly higher OS and event-free survival rates than those who did not achieved CR (P<0.01).@*CONCLUSIONS@#The CAMS-2009 regimen is superior to the CAMS-2005 regimen in improving the CR rate in children with non-CBF AML after induction treatment. Whether CR is achieved at the first course of treatment can affect the OS rate of children with non-CBF AML.

Neutralizing Antibody Titer Test of Ebola Recombinant Protein Vaccine and Gene Vector Vaccine pVR-GP-FC / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>In previous studies, we immunized mice with Ebola recombinant protein vaccine and gene vector vaccine. Both stimulated high levels of humoral immunity. In this work, we constructed a pseudovirus containing Ebola membrane proteins to verify whether the two immunization strategies can induce neutralizing antibodies in mice.</p><p><b>METHODS</b>A pseudovirus containing an Ebola virus membrane protein based on the HIV-1 viral gene sequence was constructed and evaluated using a known neutralizing antibody. The titer of the neutralizing antibody in the sera of mice immunized with the recombinant protein and the gene vector vaccine was examined using a neutralization test.</p><p><b>RESULTS</b>Ebola pseudovirus was successfully prepared and applied for neutralizing antibody detection. Immunological experiments showed that recombinant protein GP-Fc and gene vaccine pVR-modGP-Fc had good immunogenicity. The titer of the bound antibody in the serum after 8 weeks of immunization in mice was more than 1:105, and the recombinant protein induced greater humoral immunity. The results of the neutralization test based on the Ebola pseudovirus system demonstrated that both vaccines induced production of protective antibodies, while the gene vaccine induced a higher titer of neutralizing antibodies.</p><p><b>CONCLUSION</b>An Ebola pseudovirus detection system was successfully established and used to evaluate two Ebola vaccines. Both produced good immunogenicity. The findings lay the foundation for the development of new Ebola vaccines and screening for neutralizing monoclonal antibodies.</p>

A New Method for Blood NT-proBNP Determination Based on a Near-infrared Point of Care Testing Device with High Sensitivity and Wide Scope / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To develop a rapid, highly sensitive, and quantitative method for the detection of NT-proBNP levels based on a near-infrared point-of-care diagnostic (POCT) device with wide scope.</p><p><b>METHODS</b>The lateral flow assay (LFA) strip of NT-proBNP was first prepared to achieve rapid detection. Then, the antibody pairs for NT-proBNP were screened and labeled with the near-infrared fluorescent dye Dylight-800. The capture antibody was fixed on a nitrocellulose membrane by a scribing device. Serial dilutions of serum samples were prepared using NT-proBNP-free serum series. The prepared test strips, combined with a near-infrared POCT device, were validated by known concentrations of clinical samples. The POCT device gave the output of the ratio of the intensity of the fluorescence signal of the detection line to that of the quality control line. The relationship between the ratio value and the concentration of the specimen was plotted as a work curve. The results of 62 clinical specimens obtained from our method were compared in parallel with those obtained from the Roche E411 kit.</p><p><b>RESULTS</b>Based on the log-log plot, the new method demonstrated that there was a good linear relationship between the ratio value and NT-proBNP concentrations ranging from 20 pg/mL to 10 ng/mL. The results of the 62 clinical specimens measured by our method showed a good linear correlation with those measured by the Roche E411 kit.</p><p><b>CONCLUSION</b>The new LFA detection method of NT-proBNP levels based on the near-infrared POCT device was rapid and highly sensitive with wide scope and was thus suitable for rapid and early clinical diagnosis of cardiac impairment.</p>