Clinical characteristics and risk factors of pericardial effusion after hematopoietic stem cell transplantation in children with thalassemia major / 中华儿科杂志

Objective: To investigate the characteristics, risk factors and outcomes of thalassemia major (TM) children with pericardial effusion (PE) after allo-geneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Clinical data of 446 TM children received allo-HSCT at Shenzhen Children's Hospital between January 2012 and December 2020 were analyzed retrospectively. Patients were divided into PE and non-PE group according to the occurrence of PE. Chi-square tests were used to investigate the risk factors that were associated with the development of PE. Kaplan-Meier method was used for survival analysis of the 2 groups. Results: Twenty-five out of 446 patients (5.6%) developed PE at a time of 75.0 (66.5, 112.5) days after allo-HSCT. Among these patients, 22 cases (88.0%) had PE within 6 months after allo-HSCT and 19 patients (76.0%) had PE within 100 days after allo-HSCT. The diagnoses of PE were confirmed using echocardiography. Pericardial tamponade was observed in only 1 patient, who later undergone emergency pericardiocentesis. The rest of patients received conservative managements alone. PE disappeared in all patients after treatment. Risk factors that were associated with the development of PE after allo-HSCT included the gender of patients, the type of transplantation, the number of mononuclear cells (MNC) infuse, pulmonary infection after HSCT and transplantation associated thrombotic microangiopathy (TA-TMA) (χ²=3.99, 10.20, 14.18, 36.24, 15.03, all P<0.05). In 239 patients that received haploidentical HSCT, the development of PE was associated with the gender of patients, pulmonary infection after HSCT and TA-TMA (χ²=4.48, 20.89, 12.70, all P<0.05). The overall survival rates of PE and non-PE groups were 96.0% (24/25) and 98.6% (415/421). The development of PE was not associated with the overall survival of TM children after allo-HSCT (χ²=1.73, P=0.188). Conclusions: PE mainly develop within 100 days after allo-HSCT in pediatric TM recipients. Haploidentical grafts, female gender, pulmonary infection after HSCT and TA-TMA are the main risk factors associated with PE development after transplant. However, the presence of PE don't have a significant impact on the outcomes of pediatric TM patients after allo-HSCT.

Correlations between 6-mercaptopurine treatment-related adverse reactions in children with acute lymphoblastic leukemia and polymorphisms of thiopurine methyltransferase gene / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore 6-mercaptopurine (6-MP) treatment-related adverse reactions in children with acute lymphoblastic leukemia (ALL), and to assess the association between the polymorphisms of thiopurine methyltransferase (TPMT) gene and these 6-MP related toxicities.</p><p><b>METHODS</b>Total RNA was extracted from bone marrow samples of 46 children with ALL and was then reversed to cDNA. TPMT(*)1S and (*)3C were screened by denaturing gradient gel electrophoresis (DGGE) combining with DNA sequencing. Drug toxicities were classified according to national cancer institute-common toxicity criteria version 3.0 (NCI CTC 3.0). The relationship between TPMT gene polymorphisms and the adverse reactions of 6-MP treatment was analyzed.</p><p><b>RESULTS</b>During the maintenance treatment period, 22% (10/46) of children discontinued 6-MP treatment because of serious adverse reactions. Two children with TPMT(*)3C genotypes presented severe adverse reactions, including 1 child with homozygotic mutation who had 6-MP dose-related myelosuppression and hepatotoxicity. The main side effects of 6-MP were myelosuppression, hepatotoxicity and gastrointestinal reaction. And there were no significant differences between TPMT(*)1S genotypes and severe myelosuppression or hepatotoxicity caused by 6-MP (P>0.05).</p><p><b>CONCLUSIONS</b>TPMT(*)3C may correlate with severe adverse reactions caused by 6-MP.</p>

Analysis of a G1793A polymorphism of methylenetetrahydrofolate reductase gene in children with acute leukemia / 中华实用儿科临床杂志

Objective To investigate the distribution of methylenetetrahydrofolate reductase (MTHFR) gene G1793A genotype and allele frequency in children with acute leukemia (AL),and to analyze the association between MTHFR gene polymorphism and the risk of AL.Methods Bone marrow samples from 109 childhood patients with AL and peripheral blood samples from 120 control children were obtained to prepare complementary DNAs (cDNAs).The cDNAs were analyzed for MTHFR G1793A polymorphism by reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis and sequencing.Results The frequencies of 1793 GG,GA and AA genotyp(s) in MTHFR of the AL patients,acute lymphoblastic leukaemia (ALL) patients,acute myeloid leukaemia (AML) patients and the control children were 83.5％,15.6％,0.9％ ;82.8％,16.1％,1.1％ ;86.4％,13.6％,0％ and 89.2％,7.5％,3.3％,respectively.While the A allele frequency of MTHFR G1793A in those group were 8.7％,9.2％,6.8％ and 7.1％,respectively.However,no significant difference was observed in MTHFR G1793A genotypes or A allele frequency between the patients and controls (all P ＞0.05).The MTHFR 1793 GA + AA genotype was linked with an increased risk of AL,ALL and AML (AL:OR =1.71,95％ CI:0.77-3.80,P =0.19;ALL:OR =2.00,95％ CI:0.85-4.49,P =0.12;AML:OR =1.36,95％CI:0.33-5.62,P =0.67),but no significant difference in our population(all P ＞ 0.05).The A allele frequency of MTHFR G1793A in the study was 7.9％,significantly different from those reported in Ashkenazi Jewish,African-American,Brazilian,Austrian,Irau and Harbin populations (all P ＜0.05).Conclusion MTHFR G1793A may be not a genetic susceptibility factor for pediatric AL,but may exhibit an ethnic difference.

Association of single nucleotide polymorphism of methylenetetrahydrofolate reductase gene with susceptibility to acute leukemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene is associated with susceptibility to acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) in Chinese Han children.</p><p><b>METHODS</b>The study has included 87 patients with ALL, 22 patients with AML and 120 healthy controls. All subjects were analyzed with reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis and sequencing.</p><p><b>RESULTS</b>A 677CT genotype of the MTHFR gene was associated with decreased risk of ALL (OR=0.23, 95%CI: 0.07-0.79). However, MTHFR A1298C genotypes were not associated with the risk of either disease. 677TT/1298AA and 677CC/1298AC genotypes were associated with increased risk of ALL(OR=3.78, 95% CI: 1.38-10.40; OR=3.17, 95% CI: 1.18-8.53, respectively), whereas the genotype 677CT/1298AA was associated with susceptibility to AML (OR=0.23, 95% CI: 0.06-0.97).</p><p><b>CONCLUSION</b>Our data suggested that C677T polymorphism of MTHFR gene may increase the risk of childhood AML.</p>

Relationship between the methylenetetrahydrofolate reductase gene polymorphism and adverse reactions of high-dose methotrexate in children with acute lymphocytic leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and toxicities after high-dose methotrexate (HD-MTX) infusion in children with acute lymphocytic leukemia (ALL).</p><p><b>METHODS</b>MTHFR variants in 52 children with ALL were determined by reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis and sequencing. Toxicities of children who received HD-MTX chemotherapy were evaluated according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTC).</p><p><b>RESULTS</b>The children carrying MTHFR 1298AC had a higher risk of developing thrombocytopenia compared with the carriers of the 1298 AA genotype (OR=13.7, 95%CI=1.18-159.36, P=0.036). There was no significant difference in HD-MTX chemotherapy-related adverse effects between the patients with different MTHFR C677T or G1793A genotypes.</p><p><b>CONCLUSIONS</b>MTHFR A1298C polymorohism may associate with the toxicity of HD-MTX chemotherapy in children with ALL.</p>

ALK gene mutations in childhood neuroblastoma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate mutations of anaplastic lymphoma kinase (ALK) in Chinese children with neuroblastoma (NB).</p><p><b>METHODS</b>Genomic DNA was extracted from 22 cases of paraffin-embedding NB tumor tissues. Gene mutations in the exons 20-26 which were mutational hotspots of ALK were analyzed by PCR-DNA direct sequencing.</p><p><b>RESULTS</b>A novel synonymous mutation C3586T (Leu1196Leu) and a known synonymous mutation C3375A (Gly1125Gly) were found and located at exon 23 and exon 21 of ALK respectively. There were 10 cases (46%) of known synonymous mutation C3375A in 22 cases of NB. The C3375A allelic frequency was 27%. No statistically significant correlation was found between mutation C3375A and clinical parameters of NB such as age, sex, metastasis and tumor differentiation. Mutation was not found in the other 5 exons.</p><p><b>CONCLUSIONS</b>A novel ALK gene synonymous mutation C3586T was identified using PCR-DNA sequencing. A known mutation C3375A in ALK was successfully identified in children, and its incidence is not influenced by the clinical features of childhood NB.</p>

A novel missense mutation of folypolyglutamate synthetase gene / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To examine allelic frequencies of coding single nucleotide polymorphisms (cSNPs) of folypolyglutamate synthetase (FPGS) gene in Chinese Han children with acute leukemia (AL), in order to provide a basis for detecting the relationship between FPGS genetic polymorphisms and tumor individualized chemotherapy.</p><p><b>METHODS</b>cSNPs of exon 5 were detected with polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) in 91 children with AL and 124 children with upper respiratory infection as controls. Genotypes and allelic frequencies were examined.</p><p><b>RESULTS</b>A novel missense mutation, 502/490 T>C (L151/101P), was found in exon 5 of FPGS from control children. The novel mutation was found in mitochondrial variants in two cases and cytosolic variants in three cases. The cytosolic and mitochondrial variants displayed allelic frequencies of 0.70 % and 0.47 % respectively. The novel mutation was not associated with susceptibility to AL.</p><p><b>CONCLUSIONS</b>A novel missense mutation 502/490 T>C (L151/101P) in exon 5 of FPGS gene is firstly found in Chinese Han children, and the cytosolic and mitochondrial variants display allelic frequencies of 0.70 % and 0.47 % respectively.</p>

Analysis of a 452C/T single nucleotide polymorphism in γ-glutamyl hydrolase gene in children with acute leukemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the distribution of γ-glutamyl hydrolase gene (GGH) 452C/T genotype and allele frequency in children with acute leukemia (AL) and healthy children.</p><p><b>METHODS</b>Bone marrow samples from 92 children with AL and peripheral blood samples from 124 healthy children were obtained to prepare complementary DNAs (cDNAs). The cDNAs were analyzed for a GGH 452C/T polymorphism by reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis (RT-PCR-DGGE) and direct sequencing.</p><p><b>RESULTS</b>The frequencies of the AL patients with TT, CT and CC genotypes were 2.2%, 13.0% and 84.8%, and the frequencies of the control children were 1.6%, 16.9% and 81.5%, respectively. There was no significant difference in GGH genotype or T allele frequency between the two groups (P> 0.05). However, the T allele frequency in Han Chinese children was significantly different from those reported in Japanese, Mexican and African-American populations.</p><p><b>CONCLUSION</b>The frequency of 452C/T polymorphism of GGH gene in Han Chinese children has been determined. The results suggested that an ethnic difference may exist.</p>

Magnetic resonance spectroscopy-guided stereotactic biopsy for brain lesion / 中华外科杂志

<p><b>OBJECTIVE</b>To study the clinical value of magnetic resonance spectroscopy (MRS) image in stereotactic biopsy for brain lesion.</p><p><b>METHODS</b>From April 2008 to April 2010, 126 cases (72 male and 54 female, aged from 10 to 82 years, mean 45 years) of brain lesion which were difficult to diagnose were divided into two groups by random number table, 62 cases were executed for MRI-guided frameless stereotactic biopsy (MRI group), 64 cases were executed for MRI and MRS-guided frameless stereotactic biopsy (MRS group). Operation used MRI and Three-dimensional MRS image to locate, and used frameless CAS-R-2 robots to carry out the positioning operating.</p><p><b>RESULTS</b>No surgery-related deaths and infections. Pathological diagnosis was 106 cases of brain tumors, 6 cases of inflammatory disease, 4 cases of tumor-like demyelinating disease and multiple sclerosis, 3 cases of neurodegenerative disease, 7 cases failed to obtain positive pathological diagnosis. The total rate of positive diagnosis was 94.4%, the positive rate in MRS-guided stereotactic biopsy group was 98.4% (63/64), the positive rate of conventional MRI-guided biopsy group was 90.3% (56/62), and there was statistically significant difference between the two groups (χ(2) = 3.92, P = 0.047). Four cases presented with postoperative complications, the complication rate was 3.2% (4/126); the complications were cerebral hemorrhage associated with aphasia, epilepsy, subcutaneous hematoma, gastrointestinal bleeding, which were improved after treatment.</p><p><b>CONCLUSIONS</b>MRS-guided stereotactic biopsy group has a higher positive rate than MRI-guided stereotactic biopsy group, indicating that this method can improve the positive rate of diagnosis, and thus will help to formulate treatment plan for brain lesion.</p>