RESUMO
Objective:To investigate the cytogenetic characteristics and influencing factors associated with first treatment response in primary childhood B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 49 children with primary B-ALL who were admitted to the First Hospital of Xiamen University from April 2019 to September 2021 were retrospectively collected, and the clinical characteristics, cytogenetic and molecular biology findings and other clinical indicators before and after treatment were obtained. Genotyping, clinical risk stratification after the first induction chemotherapy and chemotherapy regimen development were performed according to the pediatric ALL treatment specification (2018 version). The relationship between different genotypes and clinical indicators in children with B-ALL was analyzed, and the correlation between clinical risk stratification and each indicator was analyzed by Spearman rank correlation analysis.Results:The median age of 49 children was 3.0 years old (interquartile range: 3.2 years old), 32 cases (65.3%) were male and 17 cases (34.7%) were female, with a male-to-female ratio of 1.88∶1. Thirty-five cases (71.4%) had gene mutations before treatment and 14 cases (28.6%) had no mutations. Among the 35 cases with mutations, E2A-PBX1 was found in 5 cases (10.2%), including 1 case with Philadelphia chromosome (Ph)-like; IKZF1 deletion was found in 8 cases (16.3%), including 4 cases with Ph-like, 1 case with Ph-positive, and 1 case with MLL rearrangement; MLL rearrangement was found in 3 cases (6.1%); Ph-like alone was found in 12 cases (24.5%); TEL-AML1 was found in 6 cases (12.2%), including 2 cases with Ph-like; 1 case (2.0%) with Ph-positive alone. The clinical risk stratification showed that 7 cases (14.3%) had high risk, 28 cases (57.1%) had intermediate risk, and 14 cases (28.6%) had low risk. The proportions of patients with high and intermediate clinical risk before induction chemotherapy [20.0% (7/35) vs. 0.0% (0/14), 62.9% (22/35) vs. 42.9% (6/14)] and the proportion of patients with altered mutation status on day 33 of induction chemotherapy [42.9% (15/35) vs. 0.0% (0/14)] were higher in patients with mutations before induction chemotherapy than those in patients without gene mutations before treatment (all P < 0.01). The gene mutation or not before treatment was not correlated with gender, white blood cell count at first diagnosis, hormone sensitivity, minimal residual disease (MRD) from the 15th to the 19th day of induction chemotherapy, and MRD on the 33rd day of induction chemotherapy (all P > 0.05). Clinical risk stratification of children was associated with white blood cell count at first diagnosis ( r = 0.392, P = 0.005), neutrophil count ( r = 0.453, P = 0.001), lymphocyte count ( r = 0.418, P = 0.001), monocyte count ( r = 0.359, P = 0.017), blood uric acid level ( r = 0.378, P = 0.007), and proportion of bone marrow naive lymphocyte count before treatment ( r = 0.316, P = 0.027) and from 15th to the 19th day of induction chemotherapy ( r = 0.399, P = 0.005) and the 33rd day of induction chemotherapy ( r = 0.408, P = 0.028), proportion of children with bone marrow MRD ≥ 0.000 1 on the 33rd day of induction chemotherapy ( χ2 = 15.42, P < 0.001), and proportion of children with gene mutations before treatment ( χ2 = 9.10, P = 0.005). Conclusions:High levels of leukocytes, neutrophils, lymphocytes, monocytes, naive lymphocytes, blood uric acid, and naive lymphocytes from the 15th to the 19th day and the 33rd day of chemotherapy, MRD on the 33rd day of chemotherapy and genotype in children with B-ALL may be associated with poor response to treatment. Clinical risk stratification is associated with gene mutation status, and gene mutation may be an important indicator of treatment response in children with B-ALL.
RESUMO
Objective@#To explore the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C gene polymorphisms and toxicity of Methotrexate(MTX) chemotherapy in pediatric acute lymphoblastic leukemia (ALL).@*Methods@#From January 2015 to June 2018, 128 pediatric patients with ALL in southern Fujian who were admitted at the First Affiliated Hospital of Xiamen University were selected.Their peripheral blood 2 mL was collected and genomic DNA was extracted.The MTHFR genotype was detected by polymerase chain reaction(PCR) direct sequencing method, and the clinical significance of HD-MTX on ALL children with toxic and side effects was evaluated according to the National Cancer Institute-Common Toxicity Criteria.@*Results@#Among 128 children, 54 cases(42.2%) presented rash, 48 cases (37.5%)with mucosal lesions, 51 cases (39.8%) with liver function damage, 23 cases (18.0%) with renal function damage, 52 cases (40.6%) with gastrointestinal reactions, 38 cases (29.7%)with leukopenia, 34 cases (26.6%) with thrombocytopenia and 63 cases (49.2%) with hemoglobin reduction.There was no significant difference in the incidence of MTX adverse reactions (rash, mucosa lesions, liver and renal function damage, gastrointestinal reaction, leukopenia, hemoglobin decrease and thrombocytopenia) between the MTHFR C677T and A1298C polymorphisms (all P>0.05). The different clinical risk (MTX dose) of the children was not statistically signi-ficant in the MTHFR C677T and A1298C genotypes and allele frequencies (χ2=2.573, 2.264, 1.615, 0.267; all P>0.05). There was no significant difference among the abnormal incidence of MTX at 24 h, 48 h and 72 h (all P>0.05).@*Conclusions@#MTHFR C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity and/or outcome in pediatric ALL in southern Fujian, and its clinical application still needs further discussion.
RESUMO
Objective To explore the association between methylenetetrahydrofolate reductase( MTHFR) C677T and A1298C gene polymorphisms and toxicity of Methotrexate(MTX)chemotherapy in pediatric acute lympho-blastic leukemia(ALL). Methods From January 2015 to June 2018,128 pediatric patients with ALL in southern Fu-jian who were admitted at the First Affiliated Hospital of Xiamen University were selected. Their peripheral blood 2 mL was collected and genomic DNA was extracted. The MTHFR genotype was detected by polymerase chain reaction(PCR) direct sequencing method,and the clinical significance of HD-MTX on ALL children with toxic and side effects was evaluated according to the National Cancer Institute-Common Toxicity Criteria. Results Among 128 children,54 cases (42. 2% )presented rash,48 cases(37. 5% )with mucosal lesions,51 cases(39. 8% )with liver function damage,23 ca-ses(18. 0% )with renal function damage,52 cases(40. 6% )with gastrointestinal reactions,38 cases(29. 7% )with leu-kopenia,34 cases(26. 6% )with thrombocytopenia and 63 cases(49. 2% )with hemoglobin reduction. There was no significant difference in the incidence of MTX adverse reactions(rash,mucosa lesions,liver and renal function damage, gastrointestinal reaction,leukopenia,hemoglobin decrease and thrombocytopenia ) between the MTHFR C677T and A1298C polymorphisms(all P>0. 05). The different clinical risk(MTX dose)of the children was not statistically signi-ficant in the MTHFR C677T and A1298C genotypes and allele frequencies( χ2 =2. 573,2. 264,1. 615,0. 267;all P>0. 05). There was no significant difference among the abnormal incidence of MTX at 24 h,48 h and 72 h(all P>0. 05). Conclusions MTHFR C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity and/or outcome in pediatric ALL in southern Fujian,and its clinical application still needs further discussion.
RESUMO
Objective To explore the distribution of prenatal indications , clinical features and pregnant outcomes of chromosomal unbalanced reciprocal translocations atthe second trimester. Methods The data on 35 fetuses with unbalanced reciprocal translocations between May 2011 and March 2016 were retrospectively analyzed and reviewed. Results Of 35 fetuses with unbalanced translocations , 29 (82.86%) showed ultrasound abnormalities,and 6 (17.14%) had no significant clinical features. 8 were de novo, and the other 27 were parental inherited. All the 35 women had to terminate the pregnancy. Conclusions Ultrasound abnormalities are associated with chromosomal unbalanced reciprocal translocations at the second trimester , and most unbalanced translocations fetuses origin from parental carrier of balanced translocations.