Recent research on cognitive impairment in children with acute lymphoblastic leukemia / 中国当代儿科杂志

Acute lymphoblastic leukemia (ALL) is the most common malignant neoplastic disease in children. With the continuous improvement in diagnosis and treatment, there has been an increasing number of ALL children who achieve long-term survival after complete remission; however, a considerable proportion of these children have cognitive impairment, which has a serious adverse impact on their learning, employment, and social life. This article reviews the latest research on cognitive impairment in children with ALL from the aspects of the influencing factors, detection techniques, and prevention/treatment methods for cognitive impairment.

Changes of intestinal flora in children with acute lymphoblastic leukemia before and after chemotherapy / 中国当代儿科杂志

OBJECTIVES@#To examine the changes of intestinal flora in children newly diagnosed with acute lymphoblastic leukemia (ALL) and the influence of chemotherapy on intestinal flora.@*METHODS@#Fecal samples were collected from 40 children newly diagnosed with ALL before chemotherapy and at 2 weeks, 1 month, and 2 months after chemotherapy. Ten healthy children served as the control group. 16S rDNA sequencing and analysis were performed to compare the differences in intestinal flora between the ALL and control groups and children with ALL before and after chemotherapy.@*RESULTS@#The ALL group had a significant reduction in the abundance of intestinal flora at 1 and 2 months after chemotherapy, with a significant reduction compared with the control group (P<0.05). Compared with the control group, the ALL group had a significant reduction in the diversity of intestinal flora before and after chemotherapy (P<0.05). At the phylum level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Actinobacteria at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05) and a significant increase in the relative abundance of Proteobacteria at 1 and 2 months after chemotherapy (P<0.05). At the genus level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Bifidobacterium at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05); the relative abundance of Klebsiella in the ALL group was significantly higher than that in the control group at 1 and 2 months after chemotherapy and showed a significant increase at 1 month after chemotherapy (P<0.05); the relative abundance of Faecalibacterium in the ALL group was significantly lower than that in the control group before and after chemotherapy and showed a significant reduction at 2 weeks and 1 month after chemotherapy (P<0.05). The relative abundance of Enterococcus increased significantly at 1 and 2 months after chemotherapy in the ALL group (P<0.05), and was significantly higher than that in the control group (P<0.05).@*CONCLUSIONS@#The diversity of intestinal flora in children with ALL is significantly lower than that in healthy children. Chemotherapy significantly reduces the abundance of intestinal flora and can reduce the abundance of some probiotic bacteria (Bifidobacterium and Faecalibacterium) and increase the abundance of pathogenic bacteria (Klebsiella and Enterococcus) in children with ALL.

Prognostic Factors Analysis of Children with Hemophagocytic Lymphohistiocytosis / 中国实验血液学杂志

OBJECTIVE@#To analyze the risk factors affecting prognosis of children with hemophagocytic lymphohistiocytosis (HLH).@*METHODS@#The clinical manifestations and laboratory data of 143 HLH children who met the HLH-2004 diagnostic criteria in Shenzhen Children's Hospital from January 2009 to May 2017 were retrospectively analyzed, and the independent factors affecting prognosis were also analyzed.@*RESULTS@#The median age of 143 HLH children was 1.9 (0.1-14.3) years old, and the median follow-up time was 6.7 years (1 day - 11.9 years). The overall survival rate of 1 month, 1 year, and 10 years was (87.4±5.5)%, (81.1±6.5)%, and (81.1±6.5)%, respectively. The deaths occurred within 1 year after onset. Multivariate analysis showed that central nervous system (CNS) involvement (P=0.047), low hemoglobin (P=0.002), prolonged activated partial thromboplastin time (APTT) (P<0.001), high triglyceride (P=0.005) were all the independent risk factors affecting survival of the children. Receiver operating characteristic curve indicated that APTT (AUC=0.753, P<0.001) was more valuable than other risk factors in predicting death of the children. The cut-off value of APTT was 56.6 s, and the sensitivity and specificity of which was 55.6% and 89.7%, respectively.@*CONCLUSION@#Hypohemoglobinemia, prolonged APTT, hypertriglyceridemia, and CNS involvement the risk factors affecting prognosis of HLH, and prolonged APTT shows a strong predictive value for death.

Brain injury after induction chemotherapy in children with acute lymphoblastic leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the changes in brain injury after the induction chemotherapy in children with acute lymphoblastic leukemia (ALL) by cranial MRI.</p><p><b>METHODS</b>The clinical data and cranial MRI results of 62 children with ALL who were hospitalized from March 2014 to June 2015 were analyzed retrospectively.</p><p><b>RESULTS</b>Before chemotherapy, MRI showed bone marrow infiltration of the skull in 33 patients (53%); the children with WBC<20×10(9)/Lhad a significantly lower incidence rate of bone marrow infiltration of the skull than those with WBC≥20×10(9)/L (16 patients/42% vs 17 patients/71%; P<0.05), and the high-risk group had a significantly higher incidence rate of bone marrow infiltration of the skull than the non-high-risk group (71% vs 44%; P<0.05). Before chemotherapy, there were 4 cases (7%) of brain atrophy, and 2 cases (3%) of abnormal signals in the sensory conduction bundle. MRI reexamination in 28 patients after 3 months of chemotherapy showed 3 new cases (11%) of brain atrophy and 1 aggravated case of brain atrophy.</p><p><b>CONCLUSIONS</b>The children with ALL have bone marrow infiltration of the skull, brain atrophy, and abnormal signals in the sensory conduction bundle before chemotherapy, especially bone marrow infiltration of the skull, and some changes in brain injury disappear after treatment.</p>

One-step multiplex RT-PCR for identifying common fusion transcripts in childhood acute lymphoblastic leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the efficiency of one-step multiplex RT-PCR for identifying four common fusion transcripts (TEL/AML1, E2A/PBX1, MLL/AF4 and BCR/ABL) in children with acute lymphoblastic leukemia (ALL).</p><p><b>METHODS</b>Total RNA was extracted from bone marrow samples of 76 children who were newly diagnosed with ALL between January 2003 and December 2010. These RNAs were analyzed for TEL/AML1, E2A/PBX1, MLL/AF4 and BCR/ABL by one-step multiplex RT-PCR or common nested-multiplex PCR. The PCR products were confirmed by DNA sequencing.</p><p><b>RESULTS</b>TEL/AML1 was found in 12 cases (the length of products was 298 bp in 9 cases and 259 bp in 3 cases), E2A/PBX1 was found in 3 cases (the length of products was 373 bp), BCR/ABL was found in 1 case (the length of products was 2 124 bp), and MLL/AF4 was found in 7 cases (the length of products was 427 bp in 1 case and 673 bp in 6 cases) using one-step multiplex RT-PCR combined with DNA sequencing. The results were consistent with those using common nested-multiplex PCR.</p><p><b>CONCLUSIONS</b>One-step multiplex RT-PCR may be another alternative for detection of common fusion transcripts in children with ALL.</p>

Evaluation of heart and liver iron deposition status in patients with β- thalassemia intermedia and major with MRI T2* technique / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the status of iron deposition in patients with β-thalassemia intermedia and major in mainland China.</p><p><b>METHODS</b>The status of transfusion and chelation was examined in 39 patients with β-thalassemia intermedia or major. Serum ferritin levels were measured. MRI T2* technique was used to detect cardiac and hepatic iron deposition.</p><p><b>RESULTS</b>Serum ferritin levels ranged from the minimum of 1500 ng/mL up to a maximum of 11491 ng/mL. From liver MRI T2* measurement, 15 cases had severe hepatic iron deposition (38%) and moderate deposition was found in 15 cases (38%), mild in 7 cases (18%), and normal in 2 cases (5%). Heart MRI T2* showed severe heart iron deposition in 7 cases (18%), mild in 5 cases (13%), and normal in 27 cases (69%). One case had cardiac arrhythmia. Four cases were over 20 years of age, and presented with gonadal function hypoplasia. The majority of patients did not receive regular transfusion and they had delayed, suboptimal chelation due to financial problems. Serum ferritin level was closely related with timing and dosage of chelation.</p><p><b>CONCLUSIONS</b>In patients with β-thalassemia who do not receive early regular transfusion and iron chelation therapy, iron deposition may occur at an early age. Important organs and tissue functional lesions and related complications also result. Relevant agencies and family members should be aware of this trend and develop appropriate strategies to improve the medical condition and quality of life of patients with this disorder.</p>

Status of iron metabolism and erythropoietic proliferation in children with various genotypes of thalassemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the status of iron metabolism and erythropoietic proliferation in children with various genotypes of thalassemia.</p><p><b>METHODS</b>Serum concentrations of ferritin (SF), transferrin receptor (sTfR) and erythropoietin (EPO) were measured in 158 children with thalassemia. The differences in the concentrations of the three indices among children with different genotypes of thalassemia were compared. The correlations of the hemoglobin level with sereum SF, sTfR and EPO levels were assessed.</p><p><b>RESULTS</b>Among the 158 children with thalassemia, 52(32.9%) were diagnosed with alpha-thalassemia minor, 27(17.1%) with HbH disease, 59(37.4%) with beta-thalassemia minor, 13(8.2%) with beta-thalassemia major, and 7(4.4%) with combining alpha beta thalassemia. The SF levels in children with HbH disease or beta-thalassemia major were significantly higher than those in the other thalassemia groups (P<0.01). The sTfR levels in children with beta-thalassemia major were the highest when compared with those in the other thalassemia groups (P<0.05). The EPO levels in children with beta-thalassemia major were also the highest when compared with those in the other thalassemia groups (P<0.01). There was a negative correlation between hemoglobin and EPO levels in children with HbH disease (r=-0.656, P<0.01) and beta-thalassemia major (r=-0.641; P<0.05).</p><p><b>CONCLUSIONS</b>The status of iron metabolism and erythropoietic proliferation is different in children with different genotypes of thalassemia. A combined measurement of SF, sTfR and EPO may reflect the status of erythropoietic proliferation.</p>

Genetic diagnosis for female carriers of glucose-6-phosphate dehydrogenase deficiency by RT-PCR-DGGE / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the feasibility of genetic diagnosis for female carriers of human glucose-6-phosphate dehydrogenase (G6PD) deficiency by reverse transcriptase-PCR-denaturing gradient gel electrophoresis (RT-PCR-DGGE).</p><p><b>METHODS</b>Blood samples were collected from suspected 54 female carriers of G6PD deficiency. Total RNAs of peripheral blood were prepared and reverse-transcripted into cDNA. Design of 6 primer pairs for DGGE was based on 17 mutation sites of G6PD cDNA described in the Chinese population. Mutations in the coding region of G6PD gene were screened and genotyped by combination of PCR-DGGE and DNA sequencing.</p><p><b>RESULTS</b>One case of 1024C/T, 20 cases of 1376G/T and 12 cases of 1388G/A were detected in the 54 samples. The total detection rate was 66.1% (33/54).</p><p><b>CONCLUSIONS</b>Heterozygous mutation rate in female carriers of G6PD deficiency detected by RT-PCR-DGGE is high. RT-PCR-DGGE is value of clinical diagnosis for G6PD-deficiency female carriers.</p>

Relationship between glucocorticoid receptors and glucocorticoid resistance in children with idiopathic thrombocytopenia purpura / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To identify the relationship between the expression of alpha and beta-isoforms of glucocorticoid receptors (GR) in peripheral blood mononuclear cells (PBMC) and glucocorticoid resistance in children with idiopathic thrombocytopenia purpura (ITP).</p><p><b>METHODS</b>Real-time PCR was used to detect the expression of GR alpha and GR beta mRNA in PBMC from 30 children with ITP (glucocorticoid-sensitive, n=18; glucocorticoid-resistant, n=12) and 10 healthy children (control group). Enzyme immunoassay was used to measure plasma levels of total glucocorticoids.</p><p><b>RESULTS</b>There were no significant differences in PBMC GR alpha mRNA levels among the glucocorticoid sensitive, the glucocorticoid-resistant and the control groups. Compared with the glucocorticoid-sensitive and the control groups, the expression of GR beta mRNA in the glucocorticoid-resistant group was significantly up-regulated (p<0.01). Plasma total glucocorticoids level in the glucocorticoid-resistant group was found to be much higher than that in the glucocorticoid-sensitive and the control groups (p<0.01).</p><p><b>CONCLUSIONS</b>The up-regulated expression of GR beta mRNA may associated with glucocorticoid resistance in children with ITP.</p>

Experimental study on promoting the engraftment of hematopoietic stem/progenitor cell by all-trans retinoic acid / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of all-trans retinoic acid (RA) on the engraftment of unrelated umbilical cord blood stem/progenitor cell transplantation (UCBT) in murine model.</p><p><b>METHODS</b>1 x 10(6) and 0.5 x 10(6) nucleated cells (NC) from C57BL/6 (H-2(b)) fetal and neonatal peripheral blood (FNPB) were separately transfused into lethally cyclophosphamide (380 mg/kg, ip) treated BALB/C (H-2(d)) recipients, 15 mg.kg(-1).d(-1) and 5 mg.kg(-1).d(-1) RA (15 mg and 5 mg RA) were administrated respectively 2 days before and after UCBT. Hematopoiesis and immune recovery, graft versus host disease (GVHD), engraftment and survival rates were then observed.</p><p><b>RESULTS</b>Hematopoiesis and immune recovery occurred faster in RA treated than in untreated mice (P < 0.05). Acute GVHD was absent. The levels of engraftment were higher in both 15 mg and 5 mg RA treated mice than those in untreated controls (P < 0.05). In 1 x 10(6) NC transfused mice, 15 mg and 5 mg RA could significantly increased the 30 and 60 days survival rates from 41.67% (without RA) to 72.23% and 70.83%, respectively (P < 0.05). In 0.5 x 10(6) cells transfused mice, 15 mg and 5 mg RA increased the survival rate from 14.29% (without RA) to 42.86% and 43.48%, respectively (P < 0.05), which were comparable to that of being transfused 1 x 10(6) cells without RA treatment (P > 0.05).</p><p><b>CONCLUSION</b>RA enhances the engraftment of umbilical cord blood stem/progenitor cells in murine model for UCBT. This might provide an experimental evidence of RA in clinical UCBT.</p>

Effects of retinoic acid on adhesion molecules expression and adhesive function in murine bone marrow stromal cell / 中国实验血液学杂志

To explore the effect of retinoic acid (RA) on the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in murine bone marrow stromal cell (BMSC) and adhesive rate of human cord blood mononuclear cell (UCBMNC) to BMSC in vitro, the express ions of ICAM-1 and VCAM-1 of murine BMSC were detected by flow cytometry and the binding capacity of UCBMNC to BMSC was tested by MTT assay after co-culturing with 0.1, 1.0 and 10.0 micro mol/L RA, respectively. The results showed that 1.0 and 10.0 micro mol/L RA increased the expression of ICAM-1 and the adhesive rate of U CBMNC to BMSC, however, RA did not induced the increase of expression of VCAM-1. It was positive correlation between the increments of ICAM-1 expression and the adhesive rate (r = 0.7883, P < 0.05). It is concluded that RA up-regulated ICAM-1 expression of BMSC and increased the adhesion of UCBMNC to BMSC in vitro. These may clarify the correlation between adhesion molecules on BMSC and homing of hematopoietic stem cells, and provide the experimental basis for RA to promote the homing of umbilical cord blood stem cell.