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Objective:To investigate the relationship between NUDT15 gene polymorphism and tolerance to treatment with 6-mercaptopurine (6-MP) in children with acute lymphoblastic leukemia (ALL).Methods:Fifty-eight children diagnosed with ALL in Shanxi Children's Hospital from January 2019 to December 2020 were recruited. All of them were treated with CCLG-ALL2018 chemotherapy regimen and the bone marrow showed complete remission. They received 6-MP oral treatment during maintenance treatment. Single nucleotide polymorphism of NUDT15 gene was detected by real-time fluorescence quantitative polymerase chain reaction. The bone marrow suppression after 6-MP treatment and 6-MP tolerance dose in patients with different NUDT15 genotypes were analyzed.Results:Among 58 patients, 3 patients had NUDT15 TT genotype, 46 patients had CC genotype and 9 patients had TC genotype. During maintenance treatment with 6-MP, the differences in leukocyte count, hemoglobin and platelet count among the three groups of patients with different NUDT15 genotypes were statistically significant (all P < 0.05). Among 58 patients, 23 (39.66%) patients had varying degrees of neutropenia after medication, including 16 cases of NUDT15 CC genotype, 5 cases of TC genotype and 2 cases of TT genotype. There was a statistically significant difference in bone marrow suppression among the three groups ( H = 29.10, P < 0.05). The dosages of 6-MP used in patients with TT, CC and TC genotypes were (10.4±8.8) mg·m -2·d -1, (41.5±1.3) mg·m -2·d -1 and (36.7±2.4) mg·m -2·d -1, respectively, and the difference was statistically significant ( F = 16.95, P < 0.05). Conclusions:Children with different NUDT15 genotypes have different tolerance to 6-MP, and NUDT15 gene polymorphism is associated with 6-MP intolerance during maintenance treatment in children with ALL, which may affect the treatment of the disease.
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Objective@#To investigate the current status of family hardiness and its influencing factors in children with leukemia.@*Methods@#The children with leukemia and their caregivers in the Children's Hospital of Shanxi from August to November 2017 were enrolled. A questionnaire survey was conducted using a convenient sampling method, and 100 questionnaires were distributed. The questionnaire included the General Status Questionnaire, the Family Hardiness Index (FHI), the Coping Health Inventory for Parents (CHIP) and the Positive and Negative Affect Scale (PANAS).@*Results@#A total of 92 valid questionnaires were collected. Among the scores of family hardiness in children with leukemia [(3.29±0.43) points], the responsibility score [(3.32±0.45) points] was higher than the control score [(3.31±0.46) points] and the challenge score [(3.23±0.53) points], and the challenge score was the lowest. The score of frequency of coping styles used by the caregiver of the child with leukemia was (3.64±0.70) points, the most frequent coping style used by the caregiver was "family unity, optimism, cooperative attitude" [(3.73±0.89) points], and the positive [(3.28±0.84) points] and negative [(2.51±0.80) points] emotions were in a moderate state. The child's sex, age, stage of chemotherapy and medical insurance status, the caregiver of the child, the age of the caregiver, the family's place of residence, and the education level were the related factors affecting the family hardiness score (all P < 0.01). The age of child, CHIP-1, CHIP-2, positive emotion and negative emotion were independent factors affecting the family hardiness (all P < 0.05). The CHIP, CHIP-1, CHIP-2 and positive emotion were positively correlated with the family hardiness (r values were 0.827, 0.883, 0.707 and 0.846, all P < 0.01); the negative emotion was negatively correlated with the family hardiness (r=-0.832, P < 0.01).@*Conclusion@#The family hardiness of children with leukemia is in the middle and upper level, the children's age, caregiver's coping style, positive emotion and negative emotion are factors affecting the family hardiness.
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Objective@#To investigate the clinical characteristics and prognosis of children B-cell acute lymphoblastic leukemia (B-ALL) with TEL-AML1 fusion gene positive.@*Methods@#Clinical characteristics, therapeutic effects and prognostic factors of 55 children B-ALL patients with TEL-AML1 fusion gene positive in Children's Hospital of Shanxi from January 2013 to June 2018 were retrospectively analyzed. Kaplan-Meier method was used to evaluate 3-year event-free survival (EFS) rate and overall survival (OS) rate. Influencing factors of EFS and OS were evaluated by using Cox regression analysis.@*Results@#TEL-AML1 fusion gene was positive in all 55 children, and no other fusion gene positive was merged. There were 4 patients (7.3%) ≥10 years old. At initial diagnosis, 33 patients (60.0%) had hepatomegaly, 28 patients (50.9%) had splenomegaly, and 27 patients (49.1%) had superficial lymphadenectasis. There were 5 patients (9.1%) with white blood cell count ≥50×109/L, and 19 patients (34.6%) had abnormalities of chromosome. All the 55 children were divided into the low risk group [36 cases (65.5%)], the intermediate risk group [18 cases(32.7%)], high risk group [1 case (1.8%)] according to Morphology, Immunology, Cytogenetics and Molecular Biology (MICM) and adjusted risk. After regular treatments, 50 patients achieved complete remission (CR) on the 15th day. The CR rate after one-course of induction therapy was 100.0%. On the 33rd day, 43 patients (78.2%) had minimal residual disease (MRD) <10-4, 12 patients (21.8%) had MRD≥10-4 and MRD<10-2, 1 patient (1.8%) had MRD≥10-3 at the 12th week. During three to six months, the negative rate of fusion gene was 61.8% (34/55). There were 3 deaths (5.5%), and one (1.8%) of them died of recurrence, and the recurrence time was 27 months from the initial diagnosis; the other 2 cases (3.6%) died of infection during chemotherapy. In 55 patients, the 3-year EFS rate and OS rate was 90.3% and 93.2%, respectively. The 3-year EFS rate and OS rate in the low risk group was 100.0% both; the 3-year EFS rate and OS rate in the intermediate risk group was 78.7% and 86.6%, respectively; the 3-year EFS rate and OS rate in the high risk group was 0 both and one died. EFS rate and OS rate in low risk group were higher than those in the intermediate risk group, and the differences were statistically significant (P < 0.05). The EFS rate was 92.0% and 0 at the 12th week MRD<10-3 group and MRD≥10-3 group, and OS rate was 95.0% and 0 at the 12th week MRD<10-3 group and MRD≥10-3 group (P < 0.05). Cox multivariate analysis showed that MRD at the 12th week was an independent risk factor influencing EFS and OS (OR= 2.971, 95% CI 1.330-6.633, P= 0.008; OR= 2.884, 95% CI 1.295-6.419, P= 0.009).@*Conclusions@#Children B-ALL patients with TEL-AML1 fusion gene positive have a low recurrence rate, high survival rate and good prognosis. Risk stratification and the 12th week MRD are the influencing factors of the prognosis.
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Objective To investigate the clinical characteristics and prognosis of children B-cell acute lymphoblastic leukemia (B-ALL) with TEL-AML1 fusion gene positive. Methods Clinical characteristics, therapeutic effects and prognostic factors of 55 children B-ALL patients with TEL-AML1 fusion gene positive in Childrenˊs Hospital of Shanxi from January 2013 to June 2018 were retrospectively analyzed. Kaplan-Meier method was used to evaluate 3-year event-free survival (EFS) rate and overall survival (OS) rate. Influencing factors of EFS and OS were evaluated by using Cox regression analysis. Results TEL-AML1 fusion gene was positive in all 55 children, and no other fusion gene positive was merged. There were 4 patients (7.3% ) ≥10 years old. At initial diagnosis, 33 patients (60.0% ) had hepatomegaly, 28 patients (50.9%) had splenomegaly, and 27 patients (49.1%) had superficial lymphadenectasis. There were 5 patients (9.1%) with white blood cell count≥50×109/L, and 19 patients (34.6%) had abnormalities of chromosome. All the 55 children were divided into the low risk group [36 cases (65.5%)], the intermediate risk group [18 cases (32.7%)], high risk group [1 case (1.8%)] according to Morphology, Immunology, Cytogenetics and Molecular Biology (MICM) and adjusted risk. After regular treatments, 50 patients achieved complete remission (CR) on the 15th day. The CR rate after one-course of induction therapy was 100.0%. On the 33rd day, 43 patients (78.2%) had minimal residual disease (MRD) <10-4, 12 patients (21.8%) had MRD≥10-4 and MRD<10-2, 1 patient (1.8%) had MRD≥10-3 at the 12th week. During three to six months, the negative rate of fusion gene was 61.8% (34/55). There were 3 deaths (5.5%), and one (1.8%) of them died of recurrence, and the recurrence time was 27 months from the initial diagnosis; the other 2 cases (3.6%) died of infection during chemotherapy. In 55 patients, the 3-year EFS rate and OS rate was 90.3% and 93.2%, respectively. The 3-year EFS rate and OS rate in the low risk group was 100.0% both; the 3-year EFS rate and OS rate in the intermediate risk group was 78.7% and 86.6%, respectively; the 3-year EFS rate and OS rate in the high risk group was 0 both and one died. EFS rate and OS rate in low risk group were higher than those in the intermediate risk group, and the differences were statistically significant (P< 0.05). The EFS rate was 92.0% and 0 at the 12th week MRD<10-3 group and MRD≥10-3 group, and OS rate was 95.0% and 0 at the 12th week MRD<10-3 group and MRD≥10-3 group (P<0.05). Cox multivariate analysis showed that MRD at the 12th week was an independent risk factor influencing EFS and OS ( OR＝2.971, 95% CI 1.330-6.633, P＝0.008; OR＝2.884, 95% CI 1.295-6.419, P＝0.009). Conclusions Children B-ALL patients with TEL-AML1 fusion gene positive have a low recurrence rate, high survival rate and good prognosis. Risk stratification and the 12th week MRD are the influencing factors of the prognosis.
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Objective To analyze the diagnostic status of haemophilia in Chinese children in recent years,and to provide information for increasing the life quality of children with haemophilia in China.Methods The pediatric haemophilia cases registration data were collected and analyzed by using questionnaire,from January 1,2008 to March 30,2014 in 13 haemophilia treatment centers of haemophilia treatment center collaboration network of China pediatric group.These centers were from 12 provinces / municipalities.Results A total of 554 cases were collected;median age was 7.0 years old(0.1 to 17.9 years old);among them,481 cases(86.8％) were hemophilia A,and 73 cases were hemophilia B (13.2％);55 mild cases (9.9％),290 moderate cases (52.4％),and 209 severe cases (37.7％);162 cases(29.2％) had family history,the other 392 cases(70.8％) had no family history.The diagnosis was made at a median age of 12.0 month-old(0 to 180.0 months);the diagnosis time was 0.5 months(0 to 144.0 months) after the first bleeding;diagnosis timing with short interval was in 356 cases(64.3％),long interval was in 198 cases(35.7％).The diagnostic timing was not correlated with disease severity (P =0.812) or the family history (P =0.243);but correlated with the severity of first bleeding(P =0.027) and per capita gross domestic product (P ＜ 0.01) in patients' residence.From 1996 to 2013,the annual number of newly diagnosed cases was increasing year by year,with a higher proportion of short interval of diagnose timing.Conclusions With development of hemophilia work in China,the number of diagnosis of haemophilia children is increasing year by year.Moderate and severe hemorrhage are both taken seriously and diagnosed timely.But the diagnosis is delayed in some children.Chinese haemophilia work still need to be strengthen and the propaganda and diagnostic technology are to be popularized.
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Objective To study the relationship between the cytogenetic and the prognosis in children with acute lymphoblastic leukemia (ALL).Methods RT-PCR was used to detect the common fusion gene,chromosome number and structure in 103 children with ALL.The effects of chromosome and fusion gene changes on treatment response and survival time were analyzed.Resuts Among 103 children with ALL,52 cases had normal gene number and no fusion gene,and 51 cases had fusion gene,including 22 cases with TEL-AML1 positive,10 cases with bcr-abl positive,11 cases with E2A-PBX1 positive,2 cases with MLL-AF4 positive,3 cases with HOX11 positive,1 case with SIL-TAL1,1 case with dupMLL and 1 case with TLS-ERG.The average survival time of bcr-abl group was shorter than that of non-fusion gene group,TEL-AML1 group and E2A/PBX1 group respectively,and there were significant differences [(16.5±3.8) months vs (34.6±1.7) months,(31.6±1.4) months,(34.5±3.3) months,all P ＜ 0.05],but there was no significant difference between bcr-abl group and other fusion gene group [(12.8±1.5) months,P ＞0.05].The average survival time of non-fusion gene group had no significant differences compared with TEL-AML1 group and E2A-PBX1 group(both P ＞ 0.05),but had significant differences with other fusion gene group (P ＜ 0.05).There were 18 patients with abnormal chromosome number and structure,including 4 cases with diploid,14 cases with super diploid.The patients with diploid had shorter survival time [(19.8±4.8) months vs (37.5 ±2.2) months,x2 =7.375,P =0.007] and were easier to relapse than ones with super diploid.The average survival time of patients with different white blood cell count and lactate dehydrogenase levels had significant differences (both P ＜ 0.05).Conclusion Detection of cytogenetics and chromosome fusion genes can be used to determine the prognosis and outcome of children with ALL,which has important guiding significance for the realization of individualized treatment.
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Objective To investigate the significance of bone marrow cell morphology on clinical diagnosis of children hematopoietic diseases.Methods The data of bone marrow cell morphology in the bone marrow puncture specimens from 4 590 children admitted to Children' s Hospital of Shanxi Province from January 2009 to December 2014 were retrospectively analyzed.Results The proportion of infancy patients was the highest in 4 590 bone marrow specimens, accounting for 29.0 ％ (1 333/4 590), then that of the toddler age patients was second highest, accounting for 26.7 ％ (1 224/4 590).The constituent ratio of thrombocytopenic purpura (ITP) at the different ages was the highest.The most common diseases in bone marrow cell morphology diagnosis were in order of ITP, iron deficiency anemia (IDA), infectious bone marrow, leukemia (acute lymphoblastic leukemia, acute myeloid leukemia), aplastic anemia and so on.Conclusions Accurate analysis of bone marrow cell morphology is still the most basic and rapid approach in children with hematopoietic system disease, which has important value.Except hematopoietic system diseases, once fever of unknown origin, hepatosplenomegaly and enlargement of lymph nodes the patients should be early given bone marrow cell morphology check, early diagnosis and therapy.
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Objective To evaluate the clinical significance of minimal residual disease (MRD)detecion in ALL-B of children by flow cytometric (FCM).Methods 52 cases of children with ALL-B were performed bone marrow MRD by FCM analisis after induction therapy,3 moths therapy,and 6 moths therapy.After that,MRD detection was performed every 6 months. According to disease risks, three group were categorized,standard risk (SR),imidiete risk (IR) and high risk(HR).Results After 6 months,SR groups MRD positive cases were 4/21(19 ％),IR groups MRD position cases were 8/23 (35 ％),HR groups MRD position cases were 5/8 (63 ％).9 cases relapsed in all 52 patients.There were significant differrence in replased rate between the positive and negtive MRD (P＜0.001). Conclution The dynamic detection of MRD by FCM can be used to evaluate the therapeutic effect and prognosis of children with ALL-B. It is also useful in adjusting treatment strategy and for following up in children with ALL.