Clinical features and prognosis of children with acute leukemias of ambiguous lineage under different diagnostic criteria / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features and prognosis of children with acute leukemias of ambiguous lineage (ALAL) under different diagnostic criteria.@*METHODS@#A retrospective analysis was performed on the medical data of 39 children with ALAL who were diagnosed and treated from December 2015 to December 2019. Among the 39 children, 34 received treatment. According to the diagnostic criteria for ALAL by World Health Organization and European Group for the Immunological Characterization of Leukemias, the 39 children were divided into two groups: ALAL group (@*RESULTS@#The 34 children receiving treatment had a 3-year event-free survival (EFS) rate of 75%±9% and an overall survival rate of 88%±6%. The children treated with acute myeloid leukemia (AML) protocol had a 3-year EFS rate of 33%±27%, those treated with acute lymphoblastic leukemia (ALL) protocol had a 3-year EFS rate of 78%±10%, and those who had no remission after induction with AML protocol and then received ALL protocol had a 3-year EFS rate of 100%±0% (@*CONCLUSIONS@#ALL protocol has a better clinical effect than AML protocol in children with ALAL, and positive MRD after induction therapy suggests poor prognosis. Hyperleukocytosis and adverse genetic changes are not observed in children with myeloid expression, and such children tend to have a good prognosis, suggesting that we should be cautious to take it as ALAL in diagnosis and treatment.

Prognostic significance of measurable residual disease based on multiparameter flow cytometry in childhood acute myeloid leukemia / 中国当代儿科杂志

OBJECTIVES@#To study the prognostic value of measurable residual disease (MRD) for childhood acute myeloid leukemia (AML) by analyzing MRD-guided risk stratification therapy.@*METHODS@#A total of 93 children with AML were prospectively enrolled in this study. Chemotherapy with the 2015-AML-03 regimen was completed according to the risk stratification determined by genetic abnormality at initial diagnosis and MRD and bone marrow cytology after induction therapy I. Multiparameter flow cytometry was used to dynamically monitor MRD and analyze the prognostic effect of MRD on 3-year cumulative incidence of recurrence (CIR) rate, event-free survival (EFS) rate, and overall survival (OS) rate.@*RESULTS@#The 93 children with AML had a 3-year CIR rate of 48%±6%, a median time to recurrence of 11 months (range 2-32 months), a 3-year OS rate of 65%±6%, and a 3-year EFS rate of 50%±5%. After induction therapy I and intensive therapy I, the MRD-positive children had a significantly higher 3-year CIR rate and significantly lower 3-year EFS and OS rates than the MRD-negative children (@*CONCLUSIONS@#MRD has predictive value for the prognosis of children with AML. Based on the MRD-guided risk stratification therapy, reasonable application of chemotherapy may improve the overall prognosis of children with AML.

Serious adverse events associated with chemotherapy in children with acute lymphoblastic leukemia / 中国当代儿科杂志

OBJECTIVE@#To study the occurrence of serious adverse events (SAEs) related to chemotherapy with CCCG-ALL-2015 regimen in children with acute lymphoblastic leukemia (ALL) and the risk factors for death after the SAEs.@*METHODS@#A retrospective analysis was performed on the medical data of 734 children with ALL. They were treated with CCCG-ALL-2015 regimen from January 2015 to June 2019. The occurrence of SAEs during the treatment was investigated. The children with SAEs were divided into a death group with 25 children and a survival group with 31 children. A multivariate logistic regression analysis was used to analyze the risk factors for death after the SAEs.@*RESULTS@#Among the 734 children with ALL, 56 (7.6%) experienced SAEs (66 cases) after chemotherapy, among which 41 cases occurred in the stage of remission induction therapy. Of all 66 cases of SAEs, 46 (70%) were infection-related SAEs, including 25 cases of septic shock (38%), 20 cases of severe pneumonia (30%), and 1 case of severe chickenpox (2%), and 87% of the children with infection-related SAEs had neutrophil deficiency. The most common infection sites were blood and the lungs. The most common pathogens were Gram-negative bacteria, viruses, fungi, and Gram-positive bacteria. There were 16 cases (24%) of hemorrhage-related SAEs, with 11 cases of gastrointestinal bleeding (17%), 4 cases of pulmonary bleeding (6%), and 1 case of intracranial bleeding (2%). Of all 734 children with ALL, 66 (9.0%) died, among whom 25 died due to SAEs. The treatment-related mortality rate was 3.4%, and infection (72%) and bleeding (24%) were the main causes of death. Severe pneumonia was an independent risk factor for treatment-related death in ALL children (OR=4.087, 95%CI: 1.161-14.384, P=0.028).@*CONCLUSIONS@#SAEs often occur in the stage of remission induction therapy, and infection-related SAEs are more common in ALL children accepting chemotherapy with CCCG-ALL-2015 regimen. The development of severe pneumonia suggests an increased risk for death in these children.

Acute leukemia associated with Down syndrome: clinical analysis of 21 cases / 南方医科大学学报

<p><b>OBJECTIVE</b>To summarize the clinical characteristics, laboratory findings and prognosis of patients with Down syndrome-related acute leukemia (DS-AL).</p><p><b>METHODS</b>The clinical data, laboratory findings, chemotherapy and prognosis of 21 children with DS-AL were analyzed.</p><p><b>RESULTS</b>Most of the children had disease onset of leukemia at 1 to 5 years of age (85.7%), and acute myeloid leukemia accounted for 57.1% of these cases; 61.9% of the patients had increased lactate dehydrogenase level by 2 folds or more. Of the 13 cases undergoing echocardiaography, 10 (67.9%) showed abnormal findings, and complex congenital heart disease was common (38.5%). Six of the children received chemotherapy and complete remission was achieved in 4 cases; 2 patients died of infection, and the treatment-related mortality was 33.3%. The 2 patients receiving reduced intensive chemotherapy have so far had event-free survival for 21 and 43 months.</p><p><b>CONCLUSION</b>Acute myeloid leukemia is the most common subtype of DS-AL. Patients with DS-AL are sensitive to chemotherapy and the prognosis was favorable with reduced intensive chemotherapy.</p>

A clinical study of drug-related toxicities of CCLG-ALL 08 protocol for childhood acute lymphoblastic leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>The Chinese Children's Leukemia Group (CCLG)-acute lymphoblastic leukemia (ALL) 08 protocol for childhood ALL was established in 2008. This study aims to evaluate the drug-related toxicities of CCLG-ALL 08 protocol in the treatment of childhood ALL.</p><p><b>METHODS</b>A total of 114 children with newly diagnosed ALL were treated with the CCLG-ALL 08 protocol. The protocol was divided into five phases: remission induction (VDLD), early reinforcement (CAM), consolidation therapy, delayed reinforcement (DIa & DIb) and maintenance treatment. Drug-related toxicities in each phase were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0.</p><p><b>RESULTS</b>Toxicities were more frequent in phase VDLD than other treatment phases, including hepatotoxicity (87.7%), dental ulcer (20.2%), hyperglycemia (20.2%), prolonged activated partial thromboplastin time (21.1%) and decreased fibrinogen (34.2%), with the incidence rates of severe adverse events at 7%, 0, 1.3%, 0.8% and 2.7% respectively. The incidence of allergic reaction to L-ASP was significantly higher in phase DIa than in phase VDLD (28.0% vs 7.9%; P<0.01), and there were no longer any allergic reactions in 15 patients who received continuing treatment with pegaspargase instead. There was no severe arrhythmia, myocardial ischemia, decreased left ventricular function, osteonecrosis, myopathy, organ failure or treatment-related mortality.</p><p><b>CONCLUSIONS</b>The drug-related toxicities of CCLG-ALL 08 protocol are common in phase VDLD, but they are mild and reversible. There is no treatment-related mortality. The CCLG-ALL 08 protocol for childhood ALL is safe.</p>

Analysis of thirteen cases with secondary coagulation disorder caused by raticide exposure / 中华儿科杂志

<p><b>OBJECTIVE</b>To summarize the clinical characteristics of secondary coagulation disorders caused by exposure to poison (raticide) in children and to investigate the diagnosis and corresponding treatment.</p><p><b>METHOD</b>The process of diagnosis, clinical characteristics, response to treatment and the prognosis were analyzed.</p><p><b>RESULTS</b>The main clinical manifestation was mucosal bleeding (66.6%), including epistaxis, gingival bleeding, hematomas and so on. All these children were previously well and had no history of bleeding. Activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged, factor II was undetectable and the levels of factors VII, IX, and X were lower. The fibrinogen was normal. A raticide was detected in blood and urine of 13 children although 12 of the patients had no definite history of raticide ingestion. Prothrombin complex, fresh frozen plasma and vitamin K(1) were effective in these cases. However, 2 - 3 weeks later, 6 patients presented with recurrent bleeding.</p><p><b>CONCLUSION</b>For children with secondary coagulation disorders of unknown cause, intoxication of raticide should be considered. The administration of blood coagulation factors and vitamin K(1) are effective in early treatment, and the treatment period should be more than 2 months. The PT and APTT should be followed up. Vitamin K(1) should be stopped when PT and APTT are normal.</p>

How to Cultivate the Pediatrics Interns' Clinical Work Ability / 中华医学教育探索杂志

The internship is the transition period of a medico becoming a doctor,the cultivation of clinical work ability of interns is a comprehensive ability cultivation which includes the foundation theories' consolidation and use,the practical operative train- ing,the cultivation of clinical thought ability and communication between doctors and patients,etc.To educate pediatrics intern has its characteristics.

Differentiation of K562 cells induced by antisense oligonucleotide targeting survivin / 中华儿科杂志

<p><b>OBJECTIVE</b>Gene therapy of leukemia is a new and effective method. It is known to all that the pathogenesis and development of leukemia are related to a variety of genes. Survivin is a member of inhibitors of apoptotic proteins (IAP). Its cDNA was cloned from target cell protease receptor-1 (EPR-1). It is expressed in common tumors, but there is no expression in normal and mature tissues. High expression of survivin was detected in leukemic cells. The present study was conducted to examine the role of survivin in the differentiation of leukemic cells by using antisense-oligonucleotides.</p><p><b>METHODS</b>Human leukemic cell K562 was used as the model for the study. K562 cells were divided into 4 groups randomly: antisense oligonucleuotide (ASON) group, nonsense oligonucleotide (NSON) group, lipofectin group and control group. There were 5 samples in each group, and the experiment was repeated for three times. ASON was designed with the reference to targeting survivin mRNA. K562 cells were cultured in RPMI1640 contained fetal cattle serum at a concentration of about 10 percent. Cell transfection was induced by lipofectin. Forty-eight hours after thansfection, the morphology and ultrastructure were observed. Twenty-four hours and 48 hours after thansfection, the function of K562 cells was detected by benzidine staining, POX staining and NBT staining, respectively. The mean fluorescence intensity of CD33 was determined by flow cytometry. The method of immunohistochemistry was used to examine the protein level of survivin.</p><p><b>RESULTS</b>After thansfection with ASON, the size of K562 cells was reduced, but the cytoplasm was increased. The metarubricyte, segment granulocyte, apoptotic cells could be found. Morphologically and ultrastructurally, erythroid and myelocytic differentiation was observed. The positive level of benzidine staining in ASON group (11.90 +/- 2.30 at 24 h and 18.20 +/- 2.93 at 48 h) was higher than that of NSON group, lipofectin group and control group, respectively. The positive level of POX staining in ASON group (17.40 +/- 3.54 at 24 h and 29.40 +/- 3.70 at 48 h) was also higher than that of any other groups. The positive level of NBT staining in ASON group (7.50 +/- 2.26 at 24 h and 12.10 +/- 2.63 at 48 h) was significantly higher than that of NSON group, lipofectin group and control group, respectively (P < 0.01). In ASON group, the mean fluorescence intensity of CD33 (21.43 +/- 1.61 at 24 h and 14.86 +/- 1.20 at 48 h) was significantly lower than that of any other groups (P < 0.01). After thansfection for 24 h, the protein level of survivin in ASON group was decreased significantly compared to that of control group. There was no difference in survivin protein level amongst ASON group, NSON group and lipofectin group at 24 h (P > 0.05). Forty-eight hours after thansfection, the protein level of survivin was decreased significantly.</p><p><b>CONCLUSIONS</b>ASON targeting survivin can induce K562 to erythroid and myelocytic differentiation. Survivin is related to differentiation of K562 cells, and it can be a target of gene therapy for leukemia.</p>