Objective:To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia(TDT),and reveal the changes of metabolic pattern in children with TDT.Methods:23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected,and 11 healthy children who underwent physical examination during the same period were selected as the control group.The routine indexes between children with TDT and the control group were compared,and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry.An OPLS-DA model was established to perform differential analysis on the detected metabolites,and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites.Results:The results of routine testing showed that the indexes of ferritin,bilirubin,total bile acid,glucose and triglycerides in children with TDT were significantly higher than those in healthy controls,while hemoglobin and total cholesterol were significantly lower(all P＜0.05).However there was no significant difference in lactate dehydrogenase between the two groups(P＞0.05).Compared with the control group,190 differential metabolites(VIP＞1)were identified in TDT children.Among them,168 compounds such as arginine,proline and glycocholic acid were significantly increased,while the other 22 compounds such as myristic acid,eleostearic acid,palmitic acid and linoleic acid were significantly decreased.The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism.Conclusion:The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group.This finding is helpful to optimize the treatment choice for children with TDT,and provides a new idea for clinical treatment.

Purpose: Chemotherapy has been the primary treatment for patients with B-cell acute lymphoblastic leukemia (B-ALL). However, there are still patients who are not sensitive to chemotherapy, including those with refractory/relapse (R/R) disease and those experiencing minimal residual disease (MRD) re-emergence. Chimeric antigen receptor-T lymphocytes (CAR-T) therapy may provide a new treatment option for these patients. Materials and Methods: Our institution conducted a single-arm prospective clinical trial (ChiCTR-OPN-17013507) using CAR-T-19 to treat R/R B-ALL and MRD re-emergent patients. One hundred and fifteen patients, aged 1-25 years (median age, 8 years), were enrolled, including 67 R/R and 48 MRD re-emergent CD19-positive B-ALL patients. Results: All patients achieved morphologic complete remission (CR), and within 1 month after infusion, 111 out of 115 (96.5%) patients achieved MRD-negative CR. With a median follow-up time of 48.4 months, the estimated 4-year leukemia-free survival (LFS) rate and overall survival (OS) rate were 68.7%±4.5% and 70.7%±4.3%, respectively. There were no significant differences in long-term efficacy observed among patients with different disease statuses before infusion (4-year OS: MRD re-emergence vs. R/R B-ALL, 70.6%±6.6% vs. 66.5%±6.1%, p=0.755; 4-year LFS: MRD re-emergence vs. R/R B-ALL, 67.3%±7.0% vs. 63.8%±6.2%, p=0.704). R/R B-ALL patients bridging to transplantation after CAR-T treatment had a superior OS and LFS compared to those who did not. However, for MRD re-emergent patients, there was no significant difference in OS and LFS, regardless of whether they underwent hematopoietic stem cell transplantation or not. Conclusion CD19 CAR-T therapy effectively and safely cures both R/R B-ALL and MRD re-emergent patients.

Child ; Humans ; Intracellular Signaling Peptides and Proteins ; Mutation ; Pancytopenia

Humans ; Tuberculosis, Extrapulmonary ; Retrospective Studies ; Paraffin Embedding ; Tuberculosis/diagnosis* ; Mycobacterium tuberculosis/genetics* ; Formaldehyde ; Sensitivity and Specificity ; Sputum

OBJECTIVE: To explore the consistency of flow cytometry (FCM) method and polymerase chain reaction (PCR) technique in the detection of minimal residual disease (MRD) at different treatment stages in pediatric patients with TCF3/PBX1⁺ B-cell acute lymphoblastic leukemia (B-ALL) and the correlations between the detection results and prognosis. METHODS: The clinical data of 64 newly diagnosed pediatric patients with TCF3/PBX1⁺ B-ALL admitted to the Department of Pediatrics of Peking University People's Hospital from January 2005 to December 2017 were retrospectively analyzed. FCM and PCR methods were used to monitor the MRD level in bone marrow samples from 64 children during the same period of treatment on d33 and d90 respectively, and the detection results were analyzed. RESULTS: There were 37 males and 27 females in the 64 patients, with a median age of 8 years(range 0.8 to 16 years). The complete remission (CR) rate after the first cycle of induction chemotherapy was 98.4% (62/63), with overall CR rate of 100%. 12 patients experienced recurrence, with a median recurrence time of 16.9 (5.3-46.3) months. The median follow-up time of the 64 patients was 77.2 (1.0-184.8) months , and the 5-year overall survival (OS) rate and event-free survival (EFS) rate were 82.8%±4.7% and 75.0%±5.4%, respectively. On d90, the concordance rate of the MRD results from the two methods was 98.4%, and the related kappa value was 0.792 (P < 0.001), which were significantly higher than those on d33. After induction chemotherapy (d33), the 5-year EFS rate of MRD-FCM^- group (79.3%±5.3%) was significantly better than that of MRD-FCM⁺ group (40.0%±21.9%) (P =0.028), there were no significant differences in the 5-year OS rate and EFS rate between MRD-PCR⁺ group and MRD-PCR^- group, and the 5-year EFS rate of MRD-FCM^-/PCR^- group (85.4%±5.5%) was significantly better than that of MRD-FCM⁺/PCR⁺ group (40.0 %±21.9%) (P =0.026). CONCLUSION In children with TCF3/PBX1⁺ B-ALL, the MRD results detected by FCM and PCR methods show good consistency, especially in consolidation therapy period (d90). The MRD level at the end of induction therapy (d33) is an important factor affecting the long-term prognosis, especially the MRD results detected by FCM method, which is significantly associated with prognosis.
Male ; Female ; Child ; Humans ; Infant ; Child, Preschool ; Adolescent ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Neoplasm, Residual/diagnosis* ; Clinical Relevance ; Retrospective Studies ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Burkitt Lymphoma ; Basic Helix-Loop-Helix Transcription Factors/therapeutic use*

OBJECTIVES: To study the clinical and prognostic significance of the preferentially expressed antigen of melanoma (PRAME) gene in the absence of specific fusion gene expression in children with B-lineage acute lymphoblastic leukemia (B-ALL). METHODS: A total of 167 children newly diagnosed with B-ALL were enrolled, among whom 70 were positive for the PRAME gene and 97 were negative. None of the children were positive for MLL-r, BCR/ABL, E2A/PBX1, or ETV6/RUNX1. The PRAME positive and negative groups were analyzed in terms of clinical features, prognosis, and related prognostic factors. RESULTS: Compared with the PRAME negative group, the PRAME positive group had a significantly higher proportion of children with the liver extending >6 cm below the costal margin (P<0.05). There was a significant reduction in the PRAME copy number after induction chemotherapy (P<0.05). In the minimal residual disease (MRD) positive group after induction chemotherapy, the PRAME copy number was not correlated with the MRD level (P>0.05). In the MRD negative group, there was also no correlation between them (P>0.05). The PRAME positive group had a significantly higher 4-year event-free survival rate than the PRAME negative group (87.5%±4.6% vs 73.5%±4.6%, P<0.05), while there was no significant difference between the two groups in the 4-year overall survival rate (88.0%±4.4% vs 85.3%±3.8%, P>0.05). The Cox proportional-hazards regression model analysis showed that positive PRAME expression was a protective factor for event-free survival rate in children with B-ALL (P<0.05). CONCLUSIONS Although the PRAME gene cannot be monitored as MRD, overexpression of PRAME suggests a good prognosis in B-ALL.
Acute Disease ; Antigens, Neoplasm/therapeutic use* ; Child ; Humans ; Neoplasm, Residual/diagnosis* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prognosis

OBJECTIVE: To investigate the clinical characteristics, treatment, and prognosis of seizures in children with acute lymphoblastic leukemia (ALL) during chemotherapy. METHODS: Children with ALL with seizures during chemotherapy admitted to the Department of Pediatrics, Peking University People's Hospital from January 2010 to March 2022 were retrospectively analyzed. Clinical data including the incidence of seizure, time at seizure onset, causes, management, and prognosis were collected retrospectively. RESULTS: A total of 932 children with ALL were admitted during the study period, of whom, 75 (8%) were complicated with seizures during the period of chemotherapy. There were 40 males and 35 females, with a median age of 7.5 (1-17) years, and 43 cases (57.3%) occurred within the first 2 months of chemotherapy. The underlying diseases were reversible posterior encephalopathy syndrome (n=15), cerebral hemorrhage (n=10, one of whom was complicated with venous sinus thrombosis), intrathecal or systemic methotrexate administration (n=11), brain abscess (n=7, fungal infection in 3 cases, and bacterial in 4), viral encephalitis (n=2), febrile seizure (n=7), hyponatremia (n=7), hypocalcemia (n=2), and unknown cause (n=14). Sixty-four children underwent neuroimaging examination after seizure occurrence, of whom 37 (57.8%) were abnormal. The electroencephalograhpy (EEG) was performed in 44 cases and was abnormal in 24 (54.4%). Fifty-five patients remained in long-term remission with regular chemotherapy, 8 patients received hematopoietic stem cell transplantation, 9 died and 3 lost to follow-up. Symptomatic epilepsy was diagnosed in 18 cases (24%), and was well controlled in 16 with over 1 year of seizure-free. Whereas 2 cases were refractory to anti-seizure medications. CONCLUSION Seizures are relatively common in children with ALL, most commonly due to reversible posterior encephalopathy syndrome, methotrexate-related neurotoxicity, and cerebral hemorrhage. Seizures occurred within 2 months of chemotherapy in most cases. Neuroimaging and EEG should be performed as soon as possible after the first seizure onset to identify the etiology and to improve the treatment regimen. Some cases developed symptomatic epilepsy, with a satisfactory outcome of seizure remission mostly after concurrent antiseizure medication therapy.
Adolescent ; Brain Diseases/complications* ; Cerebral Hemorrhage/complications* ; Child ; Electroencephalography ; Epilepsy/drug therapy* ; Female ; Humans ; Male ; Methotrexate/adverse effects* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Prognosis ; Retrospective Studies

Objective: To observe the incidence and treatment of radiation rectal injury complicated with anxiety, depression and somatic symptom disorder. Methods: A cross-sectional survey research method was carried out. Patients with radiation rectal injury managed by members of the editorial board of Chinese Journal of Gastrointestinal Surgery were the subjects of investigation. The inclusion criteria of the survey subjects: (1) patients suffered from pelvic tumors and received pelvic radiotherapy; (2) colonoscopy showed inflammatory reaction or ulcer in the rectum. Exclusion criteria: (1) patient had a history of psycho-somatic disease before radiotherapy; (2) patient was unable to use a smart phone, unable to read and understand the questions in the questionnaire displayed on the phone; (3) patient refused to sign an informed consent form. According to the SOMA self-rating scale, PHQ-15 self-rating scale, GAD-7 and PHQ-9 self-rating scale, the electronic questionnaire of "Psychological Survey of Radiation Proctitis" was designed. The questionnaire was sent to patients with radiation rectal injury managed by the committee through the WeChat group. Observational indicators: (1) radiation rectal injury symptom assessment: using SOMA self-rating scale, radiation rectal injury symptom classification: mild group (≤3 points), moderate group (4-6 points) and severe group (> 6 points); (2) incidence of anxiety, depression and physical disorder: using GAD-7, PHQ-9 and PHQ-15 self-rating scales respectively for assessment; (3) correlation of radiation rectal injury symptom grading with anxiety, depression, and somatic symptom disorder. Results: Seventy-one qualified questionnaires were collected, of which 41 (56.9%) were from Guangzhou. Among the 71 patients, 6 were males and 65 were females; the mean age was (55.7±9.3) years old and 48 patients (67.6%) were less than 60 years old; the median confirmed duration of radiation rectal injury was 2.0 (1.0, 5.0) years. (1) Evaluation of symptoms of radiation rectal injury: 18 cases of mild (25.4%), 27 cases of moderate (38.0%), and 26 cases of severe (36.6%). (2) Incidence of anxiety, depression and somatic disorder: 12 patients (16.9%) without comorbidities; 59 patients (83.1%) with anxiety, depression, or somatic disorder, of whom 2 patients only had anxiety, 1 patient only had depression, 9 only had somatic disorder, 2 had anxiety plus depression, 4 had anxiety plus somatic disorder, 2 had depression plus somatic disorder, and 40 had all three symptoms. (3) correlation of radiation rectal injury grading with anxiety, depression, and somatic symptom disorder: as compared to patients in mild group and moderate group, those in severe group had higher severity of anxiety and somatic symptom disorder (Z=-2.143, P=0.032; Z=-2.045, P=0.041), while there was no statistically significant difference of depression between mild group and moderate group (Z=-1.176, P=0.240). Pearson correlation analysis revealed that radiation rectal injury symptom score was positively correlated with anxiety (r=0.300, P=0.013), depression (r=0.287, P=0.015) and somatic symptom disorder (r=0.344, P=0.003). Conclusions: The incidence of anxiety, depression, and somatic symptom disorder in patients with radiation rectal injury is extremely high. It is necessary to strengthen the diagnosis and treatment of somatic symptom disorder, so as to alleviate the symptoms of patients with pelvic perineum pain and improve the quality of life.
Aged ; Anxiety ; Cross-Sectional Studies ; Depression ; Female ; Humans ; Male ; Middle Aged ; Quality of Life ; Rectum ; Surveys and Questionnaires