165 results on '"Fang JP"'
Search Results
2. Nutrient characteristics of throughfall and stemflow in the natural forest of Pinus densata in the Tibetan plateau
- Author
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J, Lu, primary, Zhang, SX, additional, Fang, JP, additional, and Zheng, WL, additional
- Published
- 2016
- Full Text
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3. TARGET based m 6 A methylation-related genes predict prognosis relapsed B-cell acute lymphoblastic leukemia.
- Author
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Qiu KY, Liao XY, Fang JP, and Zhou DH
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- Humans, Prognosis, Child, Female, Male, Heterogeneous-Nuclear Ribonucleoprotein Group C genetics, Methylation, Child, Preschool, Transcriptome, Up-Regulation, Biomarkers, Tumor genetics, Recurrence, Neoplasm Recurrence, Local genetics, Adolescent, Nerve Tissue Proteins, Adenosine analogs & derivatives, Adenosine genetics, RNA-Binding Proteins genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma mortality, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, RNA Splicing Factors genetics
- Abstract
Purpose: The current study aims to investigate the significance of N6-methyladenosine (m
6 A) methylationrelated genes in the clinical prognosis of childhood relapsed B-cell acute lymphoblastic leukemia (B-ALLL) patient., Methods: Transcriptome data and corresponding clinical data on m6 A methylation-related genes (including 20 genes) were obtained from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) database., Results: The bone marrow (BM) samples of 134 newly diagnosed (naive) and 116 relapsed B-ALL from TARGET were enrolled in the current study. Three genes (FTO, HNRNPC, RBM15B) showed significant up-regulation in relapsed B-ALL compared with that in naive B-ALL.The three genes had a significantly worse survival (P < 0.05). The LASSO Cox regression model was used to select the most predictive genes as prognostic indicators, and YTHDC1 and FTO were identified as prognostic factors for relapsed B-ALL. Finally, the results of multivariate regression analysis showed that the risk score of m6 A methylation-related genes was an independent prognostic factor in relapsed B-ALL (P < 0.05)., Conclusion: We found that the expression levels of m6 A methylation-related genes were different in naive and relapsed patients with B-ALL and correlated with survival and prognosis.This implies that m6 A methylation-related genes may be promising prognostic indicators or therapeutic targets for relapsed B-ALL., (© 2024. The Author(s).)- Published
- 2024
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4. Transcranial alternating current stimulation improves quality of life in Parkinson's disease: study protocol for a randomized, double-blind, controlled trial.
- Author
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Zhang HY, Hou TT, Jin ZH, Zhang T, Wang YH, Cheng ZH, Liu YH, Fang JP, Yan HJ, Zhen Y, An X, Du J, Chen KK, Li ZZ, Li Q, Wen QP, and Fang BY
- Subjects
- Humans, Middle Aged, Aged, Quality of Life, Exercise Therapy methods, Double-Blind Method, Randomized Controlled Trials as Topic, Parkinson Disease diagnosis, Parkinson Disease therapy, Parkinson Disease complications, Transcranial Direct Current Stimulation adverse effects, Transcranial Direct Current Stimulation methods
- Abstract
Background: The neural cells in the brains of patients with Parkinson's disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson's disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson's disease based on the central-peripheral-central theory., Methods: The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson's disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes., Discussion: The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP., Trial Registration: Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023., (© 2024. The Author(s).)
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- 2024
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5. Coexistence of ETV6-RUNX1 and MLL aberration among pediatric acute lymphoblastic leukemia: case reports and a literature review.
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Qiu KY, Liao XY, Huang K, Xu HG, Li Y, Zhou DH, and Fang JP
- Abstract
Background: It is known that ETV6 - RUNX1 is usually related to favorable prognosis, but MLL aberration has been associated with poor prognosis among pediatric acute lymphoblastic leukemia (ALL). However, the outcome of coexistence of ETV6 - RUNX1 and MLL aberration in pediatric ALL patients is unknown. Herein, we report 4 cases of the coexistence of ETV6 - RUNX1 and MLL -partial tandem duplications ( MLL -PTD) in pediatric ALL patients and show the favorable outcome, which was never reported before., Case Description: The frequency of coexistence of ETV6 - RUNX1 and MLL aberration at our children's medical center was calculated as 0.98% (4/410). All of them were ETV6 / RUNX1 -positive cases that exhibited MLL -PTD, and the 10-year event-free survival (EFS) and overall survival (OS) were both 75%. With the following keywords of " ETV6 - RUNX1 ", " MLL ", "children" and "acute lymphoblastic leukemia", a literature search of coexistence of ETV6 - RUNX1 and MLL aberration was conducted in the database of PubMed, and 4 articles were retrieved finally, involving 16 cases of children. Among the 16 cases of pediatric ALL, the age ranged from 2 to 7 years old, including 9 males and 7 females and the white blood cell (WBC) count was (2.66-68.6)×10
9 /L. In terms of fusion genes, they all had positive ETV6 / RUNX1 . Among them, MLL deletion was exhibited among 8 ETV6 / RUNX1 -positive patients, and 2 cases of der(21) duplication. MLL allelic deletions were shown among the remaining ETV6 / RUNX1 -positive patients. All patients showed a favorable outcome., Conclusions: The results of our analysis primarily provide compelling evidence that cases with an MLL -PTD or other types of MLL aberration are in fact a distinct subentry among ETV6 - RUNX1 B-cell ALL (B-ALL)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-142/coif). The authors have no conflicts of interest to declare., (2023 Translational Cancer Research. All rights reserved.)- Published
- 2023
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6. Thalassaemia in China.
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Wang WD, Hu F, Zhou DH, Gale RP, Lai YR, Yao HX, Li C, Wu BY, Chen Z, Fang JP, Chen SJ, and Liang Y
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- Pregnancy, Female, Humans, Iron Chelating Agents therapeutic use, Genetic Testing, Blood Transfusion, Thalassemia diagnosis, Thalassemia epidemiology, Thalassemia therapy, beta-Thalassemia diagnosis, beta-Thalassemia epidemiology, beta-Thalassemia genetics
- Abstract
Because of successful thalassaemia prevention programmes in resource-rich countries and it's huge population China now has the greatest number of new cases of thalassaemia globally as well as more people with thalassaemia than any other country. 30 million Chinese have thalassaemia-associated mutations and about 300,000 have thalassaemia major or intermedia requiring medical intervention. Over the past 2 decades there has been tremendous economic growth in China including per capita spending on health care. There is now nation-wide availability and partial or full insurance for prenatal genetic testing, RBC-transfusions, iron-chelating drugs and haematopoietic cell transplants. Prenatal screening and educational programmes have reduced the incidence of new cases. However, substantial challenges remain. For example, regional differences in access to medical care and unequal economic development require innovations to reduce the medical, financial and psychological burdens of Chinese with thalassaemia and their families. In this review we discuss success in preventing and treating thalassaemia in China highlighting remaining challenges. Our discussion has important implications for resource-poor geospaces challenged with preventing and treating thalassaemia., Competing Interests: Declaration of Competing Interest RPG is a consultant to NexImmune Inc. and Ananexa Pharma Ascentage Pharm Group, Antengene Biotech LLC, Medical Director, FFF Enterprises Inc.; partner, AZAC Inc.; Board of Directors, Russian Foundation for Cancer Research Support; and Scientific Advisory Board: StemRad Ltd., (Copyright © 2023. Published by Elsevier Ltd.)
- Published
- 2023
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7. Ruxolitinib inhibits the proliferation and induces the apoptosis of MLL-r ALL cells through inactivating JAK/STAT signaling pathway.
- Author
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Liao XY, Zhou DH, Fang JP, and Qiu KY
- Abstract
Background: The childhood patients with mixed-lineage leukemia rearrangement (MLL-r) gene have worse outcome than non-MLL, and thus often treated with high-risk chemotherapy regimens, so targeted therapy is important for this type of leukemia. This purpose of study was to explore the effects of ruxolitinib on the proliferation, apoptosis, and cell cycle of Nalm-6 cells., Methods: In this study, human acute lymphoblastic leukemia (ALL) cell line Nalm-6 was used as the research object. By constructing an MLL overexpression vector to transfect Nalm-6 cells, exogenous JAK2/STAT3 signal pathway inhibitor ruxolitinib was applied to observe the proliferation, apoptosis, and cell cycle changes of the transfected Nalm-6 cells. Western blot was performed to determine the proteins (MLL-BP, JAK, STAT) involved in the mechanism of action of MLL-r leukemia. CCK8 assay and flow cytometry (FCM) were used for testing the proliferation and apoptosis among MLL-BP transfected Nalm-6 cells., Results: Firstly, we determine the IC50 of ruxolitinib on Nalm-6 cells. Secondly, FCM and CCK8 showed that ruxolitinib dosedependentlyinhibits proliferation of Nalm-6 cells by blocking the cell cycle at G
0 /G1 phase. In addition, FCM showed that ruxolitinib promoted the apoptosis of MLL-BP transfected Nalm-6 cells. Mechanistically, ruxolitinib inactivated JAK/STAT signaling pathway in MLL-BP transfected Nalm-6 cells, mediating ruxolitinib's inhibition of cell proliferation, and inducing apoptosis. Finally, ruxolitinib significantly inhibited the proliferation of MLL-r ALL cells and promoted their apoptosis., Conclusions: These data provide compelling evidence that ruxolitinib is a promising agent against MLL-r leukemia cell line. However, it needs going through multiple more steps to confirm before it can be an option in clinical practice., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-16/coif). The authors have no conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)- Published
- 2023
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8. Intermittent theta-burst stimulation combined with physical therapy as an optimal rehabilitation in Parkinson's disease: study protocol for a randomised, double-blind, controlled trial.
- Author
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Jin ZH, Wang YX, Meng DT, Qin Y, Duan YN, Fang JP, Wang RD, Liu YJ, Liu C, Wang P, Yan HJ, Zhen Y, An X, Chen KK, Yu X, Lyu D, Yan XY, and Fang BY
- Subjects
- Humans, Brain, Double-Blind Method, Physical Therapy Modalities, Quality of Life, Randomized Controlled Trials as Topic, Transcranial Magnetic Stimulation, Middle Aged, Aged, Parkinson Disease diagnosis, Parkinson Disease therapy
- Abstract
Background: First-line rehabilitative strategies to improve motor deficits are based on functional training (physical or occupational therapy), which has been demonstrated to facilitate neural reorganisation. Accumulating evidence suggests that non-invasive brain stimulation techniques, such as repetitive TMS (rTMS), may enhance neuroplasticity, thereby facilitating neural reorganisation and recovery from Parkinson's disease. Evidence also shows that intermittent theta-burst stimulation (iTBS) can improve motor function and quality of life in patients by promoting the excitability and neural remodelling of cerebral cortex. We aimed to combine iTBS stimulation with physiotherapy to improve the rehabilitation effect compared to physiotherapy alone in patients with Parkinson's disease., Methods: This randomised, double-blind clinical trial will enrol 50 Parkinson's disease patients aged 45-70 years with Hoehn and Yahr scale scores of 1-3. Patients are randomly assigned to either the iTBS + physiotherapy or sham-iTBS + physiotherapy group. The trial consists of a 2-week double-blind treatment period and a 24-week follow-up period. iTBS and sham-iTBS will be administered twice daily for 10 days based on physiotherapy. The primary outcome will be the third part of Movement Disorders-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) from the baseline to the first 2 days following completion hospitalised intervention. The secondary outcome will be 39-item Parkinson's Disease Questionnaire (PDQ-39) at 4 weeks, 12 weeks and 24 weeks after intervention. Tertiary outcomes are clinical evaluations and mechanism study outcomes such as NMSS, 6MWD, 10MT, TUG, BBS, MRI, and EEG, the length of time between the drug needs to be adjusted when symptoms fluctuate., Discussion: The aim of this study is to demonstrate that iTBS can promote overall function and quality of life in Parkinson's disease patients using physiotherapy and that this efficacy may be associated with altered neuroplasticity in exercise-related brain regions. The iTBS combined with physiotherapy training model will be evaluated during a 6-month follow-up period. With significant improvement in quality of life and motor function, iTBS combined with physiotherapy can be considered as a first-line rehabilitation option for Parkinson's disease. The potential of iTBS to enhance neuroplasticity in the brain should have a more positive impact in increasing the generality and efficiency of physiotherapy, improving the quality of life and overall functional status of patients with Parkinson's disease., Trial Registration: Chinese Clinical Trial Registry ChiCTR2200056581. Registered on 8 February 2022., (© 2023. The Author(s).)
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- 2023
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9. Vincristine and dexamethasone pulses in addition to maintenance therapy among pediatric acute lymphoblastic leukemia (GD-ALL-2008): An open-label, multicentre, randomized, phase III clinical trial.
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Qiu KY, Wang JY, Huang LB, Li CG, Xu LH, Liu RY, Chen HQ, Ruan YS, Zhen ZJ, Li CK, and Fang JP
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- Child, Humans, Vincristine, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols adverse effects, Dexamethasone, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Antineoplastic Agents therapeutic use
- Abstract
The efficacy and safety on the addition of vincristine (VCR) and dexamethasone (DEX) pulses to maintenance therapy among childhood acute lymphoblastic leukemia (ALL) remain uncertain. Herein, we perform an open-label, multicentre, randomized, phase III clinical trial that was conducted at nine major medical centers in Guangdong Province, China. Patients were randomly assigned either the conventional maintenance therapy (control group, n = 384) or the VCR/DEX pulse (treatment group, n = 375). When limited to the SR cohort, 10-year EFS was 82.6% (95% CI: 75.9-89.9) in the control group and 80.7% (95% CI: 74-88.1) in the treatment group (p
non-inferiority = .0002). Similarly, patients with IR also demonstrated non-inferiority of the treatment group to the control group in terms of 10-year EFS (73.6% [95% CI: 67.6-80] vs. 77.6% [95% CI: 71.8-83.9]; pnon-inferiority = .005). Among the HR cohort, compared with the control group, patients in the treatment group experienced a significant benefit in terms of 10-year EFS (61.1% [95% CI: 47.7-78.2] vs. 72.6% [95% CI: 55.6-94.7], p = .026) and a trend toward higher 10-year OS (73.8% [95% CI: 61.6-88.4] vs. 87.9% [95% CI: 579.2-97.5], p = .068). In the HR cohort, the total rate of drug-induced liver injury and Grade 3 chemotherapy-induced anemia were both lower for patients in the treatment group than in the control group (55.6% vs. 100%, p = .033; 37.5% vs. 60%, p = .036). Conversely, the total prevalence of chemotherapy-induced thrombocytopenia was higher for patients in the treatment group than in the control group (88.9% vs. 40%, p = .027). Pediatric acute lymphoblastic leukemia with high risk is suitable to VCR/DEX pulse during maintenance phase for the excellent outcome, while the standard-to-intermediate-risk patients could eliminate the pulses., (© 2023 Wiley Periodicals LLC.)- Published
- 2023
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10. Outcome and prognostic factors of CBF pediatric AML patients with t(8;21) differ from patients with inv(16).
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Qiu KY, Liao XY, Li Y, Huang K, Xu HG, Fang JP, and Zhou DH
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- Humans, Child, Prognosis, Disease-Free Survival, Cytarabine therapeutic use, Remission Induction, Recurrence, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute metabolism
- Abstract
Purpose: To explore the outcome and prognostic factors between inv(16) and t(8;21) disrupt core binding factor (CBF) in acute myeloid leukemia (AML)., Methods: The clinical characteristic, probability of achieving complete remission (CR), overall survival (OS) and cumulative incidence of relapse (CIR) were compared between inv(16) and (8;21)., Results: The CR rate was 95.2%, 10-year OS was 84.4% and CIR was 29.4%. Subgroup analysis showed that patients with t(8;21) had significant lower 10-year OS and CIR than patients with inv(16). Unexpectedly, there was a trend for pediatric AML receiving five courses cytarabine to have a lower CIR than four courses cytarabine (19.8% vs 29.3%, P = 0.06). Among the cohort of no-gemtuzumab ozogamicin(GO) treatment, inv (16) patients showed a similar 10-year OS (78.9% vs 83.5%; P = 0.69) and an inferior outcome on 10-year CIR (58.6% vs 28.9%, P = 0.01) than those patients with t(8;21). In contrast, inv (16) and t(8;21) patients receiving GO treatment had comparable OS (OS: 90.5% vs. 86.5%, P = 0.66) as well as CIR (40.4% vs. 21.4%, P = 0.13)., Conclusion: Our data demonstrated that more cumulative cytarabine exposure could improve the outcome of childhood patients with t(8;21), while GO treatment was beneficial to the pediatric patients with inv(16)., (© 2023. The Author(s).)
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- 2023
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11. Unconventional treatment for an unusual cauda equina syndrome associated with nontuberculous mycobacteria after allogenic stem cell transplantation in a child with acute lymphoblastic leukemia.
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Li XY, Chen H, Han XW, Peng XM, Li DF, Zhou DH, Xu LH, Fang JP, and Huang K
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- Humans, Child, Nontuberculous Mycobacteria, Stem Cell Transplantation, Cauda Equina Syndrome, Hematopoietic Stem Cell Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
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- 2023
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12. Chidamide as maintenance after chemotherapy or hematopoietic stem cell transplantation in 27 children with T-cell lymphoblastic leukemia: A real-world prospective study.
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Li XY, Han XW, Huang K, Zhang YT, Xu HG, Zhou DH, Xu LH, and Fang JP
- Abstract
Background: The long-term overall survival of children with T-cell acute lymphoblastic leukemia (T-ALL) is limited to approximately 80-85% because of a high incidence of relapse after achieving remission with intensive chemotherapy and hematopoietic stem cell transplantation (HSCT). Novel treatment strategies inducing long-term remission are needed to improve the outcome. Histone deacetylase inhibitors (HDACis) have been reported to be effective in a series of T-ALL cases. Preclinical studies suggested that T-ALL cells are sensitive to Chidamide, which is a selective HDACi., Methods: This preliminary clinical study evaluated the efficacy and safety of Chidamide in combination with chemotherapy or post-HSCT for children with T-ALL at a dose of 0.5 mg/kg weight of patient twice per week for at least 6 months., Results: In total, 27 children with a mean age of 7.88 years were included. The high-risk proportion was 66.7%. After a median follow-up period of 37.8 months (9.5-67.9 months), the overall survival and event-free survival in the patients treated with Chidamide were 94.1 and 95.2%, respectively. All patients except two maintained persistent remission with <0.01% blast cells in minimal residual disease., Conclusion: The combination therapy with Chidamide in a case series of T-ALL shows the promising clinical efficacy and good safety in children., Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2000030357., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Han, Huang, Zhang, Xu, Zhou, Xu and Fang.)
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- 2023
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13. Mutational landscape and clinical outcome of pediatric acute myeloid leukemia with 11q23/KMT2A rearrangements.
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Yuen KY, Liu Y, Zhou YZ, Wang Y, Zhou DH, Fang JP, and Xu LH
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- Child, Humans, Mutation, Translocation, Genetic, Chromosome Aberrations, Prognosis, Gene Rearrangement, Proto-Oncogene Proteins p21(ras) genetics, Leukemia, Myeloid, Acute drug therapy
- Abstract
Background: Alterations of 11q23/KMT2A are the most prevalent cytogenetic abnormalities in acute myeloid leukemia (AML) and the prognostic significance of 11q23/KMT2A-rearranged AML based on various translocation partners varies among different studies. However, few studies evaluated the molecular characteristics of 11q23/KMT2A-rearranged pediatric AML. We aim to analyze the mutational landscape of 11q23/KMT2A-rearranged AML and assess their prognostic value in outcomes., Methods: The mutational landscape and clinical prognosis of 105 children with 11q23/KMT2A-rearranged AML in comparison with 277 children with non-11q23/KMT2A-rearranged AML were analyzed using publicly accessible next-generation sequencing data from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset., Results: Pediatric AML patients with 11q23/KMT2A-rearrangements harbored a low number of mutations (Median, 1 mutation/patient, range, 1-22), 58% of which involved in RAS pathway mutations (KRAS, NRAS, and PTPN11) and 10.5% of which comprised of SETD2 mutations. Compared with non-11q23/KMT2A-rearranged AML, the incidence of KRAS (32.4% vs. 10.1%, P〈0.001) and SETD2 (10.5% vs. 1.4%, P=0.001) gene mutations in 11q23/KMT2A-rearranged AML was significantly higher. Both KRAS and SETD2 mutations occurred more often in t(10;11)(p12;q23). KRAS mutations were correlated with worse 5-year event-free survival [EFS] (Plog-rank = 0.001) and 5-year overall survival [OS] (Plog-rank = 0.009) and the presence of SETD2 mutations increases the 5-year relapse rate (PGray = 0.004). Multivariate analyses confirmed KRAS mutations in 11q23/KMT2A-rearranged AML as an independent predictor for poor EFS (hazard ratio [HR] = 2.10, P=0.05) and OS (HR = 2.39, P=0.054)., Conclusion: Our findings show that pediatric patients with 11q23/KMT2A rearrangements have characteristic mutation patterns and varying clinical outcomes depending on different translocation partners, which could be utilized to develop more accurate risk stratification and tailored therapies., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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14. [Relationship between MTHFR Gene Polymorphism(C677T) and Adverse Reactions of High-Dose Methotrexate in Pediatric Patients with Acute Lymphoblastic Leukemia].
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Yang FY, Xu LH, Wang J, Zhang YT, Lin SF, Wang KM, Zhou DH, and Fang JP
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Objective: To explore the effects of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism on the adverse reactions of high-dose methotrexate (MTX) in pediatric patients with acute lymphoblastic leukemia (ALL)., Methods: A total of 69 children with ALL admitted to the department of Pediatrics of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from November 2018 to October 2020 were included in this study. The clinical data of the children were collected, leukocytes were isolated from their peripheral blood, and MTHFR genotyping was performed by digital fluorescence molecular hybridization techniques. The adverse reactions and plasma drug concentration of MTX were monitored during the chemotherapy. Moreover, the effect of MTHFR gene polymorphism on MTX adverse reactions and plasma drug concentration were analyzed., Results: Among the middle and high risk children, compared with the wildtype group (CC genotype), patients with MTHFR C677T mutations (CT+TT genotypes) had a higher risk of leukopenia ( OR =2.38), neutropenia ( OR =2.2), anemia ( OR =1.83) and hepatoxicity ( OR =1.98). However, no significant difference was found in the MTX plasma concentration between the MTHFR C677T mutantion group and the wildtype group at different timepoints (24 h, 48 h and 72 h). Multivariate analysis revealed that the plasma concentration of MTX (48 h), clinical risk level of ALL and MTHFR C677T gene polymorphism were independent factors for the adverse reactions of high-dose MTX., Conclusion: The MTHFR C677T mutations may be associated with myelosuppression and hepatotoxicity in children with ALL after high-dose MTX treatment.
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- 2023
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15. Prognostic value and outcome for acute lymphocytic leukemia in children with MLL rearrangement: a case-control study.
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Qiu KY, Zhou DH, Liao XY, Huang K, Li Y, Xu HG, Weng WJ, Xu LH, and Fang JP
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- Humans, Child, Case-Control Studies, Prognosis, Retrospective Studies, Chromosome Aberrations, Recurrence, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Purpose: To evaluate the prognostic factors and outcome for acute lymphoblastic leukemia (ALL) in children with MLL rearrangement (MLL-r)., Methods: A total of 124 pediatric patients who were diagnosed with ALL were classified into two groups based on the MLL-r status by using a retrospective case-control study method from June 2008 to June 2020., Results: The prevalence of MLL-r positive in the whole cohort was 4.9%. The complete remission (CR) rate on Day 33 in the MLL-r positive group was not statistically different from the negative group (96.8% vs 97.8%, P = 0.736). Multivariate analysis showed that T-cell, white blood cell counts (WBC) ≥ 50 × 10
9 /L, MLL-AF4, and D15 minimal residual disease (MRD) positive were independent risk factors affecting the prognosis of MLL-r positive children. Stem cell transplantation (SCT) was a favorable independent prognostic factor affecting event-free survival (EFS) in MLL-r positive patients (P = 0.027), and there was a trend toward an independent prognostic effect on overall survival (OS) (P = 0.065). The 10-year predicted EFS for patients with MLL-AF4, MLL-PTD, MLL-ENL, other MLL partner genes, and MLL-r negative cases were 46.67 ± 28.61%, 85.71 ± 22.37%, 75 ± 32.41%, 75 ± 32.41%, and 77.33 ± 10.81%, respectively (P = 0.048). The 10-year predicted OS were 46.67 ± 28.61%, 85.71 ± 22.37%, 75 ± 32.41%, 75 ± 32.41%, and 85.2 ± 9.77%, respectively (P = 0.049). The 124 patients with ALL were followed up and eventually 5 (4%) cases relapsed, with a median relapse time of 3.9 years., Conclusion: Patients with MLL-r positive ALL have moderate remission rates, but are prone to relapse with low overall survival. The outcome of MLL-r positive ALL was closely related to the partner genes, and clinical attention should be paid to screening for MLL partner genes and combining them with other prognostic factors for accurate risk stratification., (© 2022. The Author(s).)- Published
- 2022
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16. [Clinical Analysis of Pediatric Acute Leukemia Complicated with Septic Shock].
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Liu TH, Lei JY, Mai YG, and Fang JP
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- Humans, Child, Adolescent, Retrospective Studies, ROC Curve, Shock, Septic complications, Leukemia, Heart Failure
- Abstract
Objective: To analyze the clinical characteristics of predictors in pediatric acute leukemia complicated with septic shock and explore the prognostic factors., Methods: The clinical characteristics of 70 children with acute leukemia and complicated with septic shock hospitalized in Sun Yat-sen Memorial Hospital from March 2012 to March 2021 were retrospectively analyzed. The clinical characteristics of patients in survival group and death group were analyzed and compared. Multiple logistic regression was used to test for predictors of death., Results: Among the 70 children, 41 were males and 29 were females, with a median age of 7.0 (1.0-15.0) years old. 81.4% were hospital acquired infections. The pathogens were mostly Gram-negative bacteria (50/66, 75.8%) and the clinical manifestations were cold shock. Mortality rate was 34.3% (24/70). The length of hospitalization, duration of fever and antibiotic exposure longevity before the onset of septic shock were significantly different between survival group and death group. At septic shock onset, compared with the survival group, patients in the death group were younger, had lower platelet counts and higher levels of C-reactive protein and procalcitonin, and were more likely to have acute heart failure and more mechanical ventilation (all p <0.05). The results of multivariable analysis showed that mortality was independently associated with pediatric sequential organ failure assessment score (pSOFA) (odds ratio: 1.616, 95% CI : 1.160-2.251, p =0.005) and acute heart failure (odds ratio: 18.308, 95% CI : 1.939-172.911, p =0.011). In addition, the ROC curve analysis showed that pSOFA score had AUC of 0.8551 (95% CI : 0.7607-0.9495, p <0.001) predicting PICU mortality and its best predictive value was >9.5 (sensitivity 75.0%, specificity 87.0%)., Conclusion: Pediatric acute leukemia complicated with septic shock is characterized as rapid deterioration and high mortality. A pSOFA score greater than 9.5 and acute heart failure are associated with poor outcomes.
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- 2022
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17. Analysis of clinical characteristics and prognostic factors associated with EBV-associated HLH in children.
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Qiu KY, Guo SY, Zeng YH, Liao XY, Lin SF, Fang JP, and Zhou DH
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- Child, Herpesvirus 4, Human, Humans, Prognosis, Retrospective Studies, Epstein-Barr Virus Infections complications, Lymphohistiocytosis, Hemophagocytic diagnosis, Lymphohistiocytosis, Hemophagocytic etiology
- Abstract
Purpose Our aim is to analyze the clinical characteristics and prognostic factors of Epstein-Barr (EB) virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in children. Methods Children with newly diagnosed HLH were retrospectively analyzed. Results Finally, a total of 95 children with HLH were enrolled in this study, including 43 (45.3%) with EBV-HLH and 52 (54.7%) with non-EBV-HLH. Laboratory tests showed that the levels of absolute neutrophil count (ANC) decrease ( P = 0.031) and triglycerides (TG) increase ( P = 0.036) in the EBV-HLH group were statistically significant compared with those in the non-EBV-HLH group, respectively. We found that the remission rate during induction period in the EBV-HLH group and non-EBV-HLH group was 75.8% and 89.3%, respectively. The correlation analysis showed that the elevated degree of total bilirubin (TBIL) ( P = 0.042), triglyceride (TG) ( P = 0.009), serum ferritin (SF) ( P = 0.008) and interleukin-8 (IL-8) ( P = 0.004) were related with the remission rate during induction in the EBV-HLH group. Further univariate analysis showed that the elevated degree of TBIL ( P = 0.048) and TG ( P = 0.019) were significant risk factors for the remission rate during induction in the EBV-HLH group. In the multivariate analysis, we observed that there was statistical significance for the degree of TG elevation ( P = 0.015) between the two groups. The correlation analysis showed that the elevated degree of TBIL ( P = 0.030), the elevated degree of SF ( P = 0.020) and the elevated degree of interleukin-6 ( P = 0.010) were related to the induction mortality of children with EBV-HLH. Conclusion TBIL and TG are valid indicators to assess the efficacy and prognosis of EVBHLH among children in induction period.
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- 2022
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18. Impact of posttransplant cyclophosphamide on the outcome of patients undergoing unrelated single-unit umbilical cord blood transplantation for pediatric acute leukemia.
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Li XY, Zhan LP, Liu DD, Han XW, Chen H, Wu ZZ, Wang Y, Que LP, Wu XJ, Liu S, Wang KM, Huang SL, Fang JP, Huang K, and Xu HG
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- Humans, Child, Retrospective Studies, Cyclophosphamide, Acute Disease, Recurrence, Chronic Disease, Graft vs Host Disease epidemiology, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Cord Blood Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute drug therapy
- Abstract
Background: Umbilical cord blood transplantation (UCBT) from unrelated donors is one of the successful treatments for acute leukemia in childhood. The most frequent side effect of UCBT is peri-engraftment syndrome (PES), which is directly associated with the greater prevalence of acute and chronic graft-versus-host-disease (aGvHD and cGvHD). In haploidentical stem cell transplantation, posttransplant cyclophosphamide (PTCY) has been demonstrated to be an effective method against GvHD. However, the effects of PTCY as a GvHD prophylactic in UCBT had not been investigated. This study aimed to evaluate the effects of PTCY on the outcomes of UCBT for pediatric acute leukemia., Methods: This retrospective study included 52 children with acute leukemia who underwent unrelated single-unit UCBT after myeloablative conditioning regimens. The results from the PTCY and non-PTCY groups were compared., Results: The incidence of transplantation-related mortality in non-PTCY and PTCY were 5% and 10% (p = 0.525), respectively. The incidence of relapse in non-PTCY and PTCY were 5% and 23% (p = 0.095), respectively. Second complete remission status (CR2) was an independent risk factor for relapse-free survival (hazard ratio = 9.782, p = 0.001). The odds ratio for sepsis or bacteremia incidence was significantly greater in the PTCY group (9.524, p = 0.017). PTCY group had increased rates of cytomegalovirus activity and fungal infection. The incidence of PES, aGvHD, cGvHD, and hemorrhagic cystitis in the PTCY group was lower than that in the non-PTCY group, although it was not significantly different. Additionally, higher doses of PTCY (29 mg/kg and 40 mg/kg) were associated with lower incidences of aGvHD and severe GvHD (65% and 29%, respectively) than lower doses (93% and 57%, respectively). Engraftment time and graft failure incidence were similar across groups., Conclusion: The results support the safety and efficiency of PTCY as part of PES controlling and GvHD prophylaxis in single-unit UCBT for children with acute leukemia. A PTCY dosage of 29 mg/kg to 40 mg/kg appears to be more effective in GvHD prophylaxis for UCBT patients., (© 2022. The Author(s).)
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- 2022
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19. Prognostic significance of CNSL at diagnosis of childhood B-cell acute lymphoblastic leukemia: A report from the South China Children's Leukemia Group.
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Xu LH, Geng X, Liao N, Yang LH, Mai HR, Wan WQ, Huang LB, Zheng MC, Tian C, Chen HQ, Chen QW, Long XJ, Zhen ZJ, Liu RY, Li QR, Wu BY, Wang LN, Kong XL, Chen GH, Fang JP, and Li Y
- Abstract
Objectives: The prognostic significance of acute lymphoblastic leukemia (ALL) patients with central nervous system leukemia (CNSL) at diagnosis is controversial. We aimed to determine the impact of CNSL at diagnosis on the clinical outcomes of childhood B-cell ALL in the South China Children's Leukemia Group (SCCLG)., Methods: A total of 1,872 childhood patients were recruited for the study between October 2016 and July 2021. The diagnosis of CNSL depends on primary cytological examination of cerebrospinal fluid, clinical manifestations, and imaging manifestations. Patients with CNSL at diagnosis received two additional courses of intrathecal triple injections during induction., Results: The frequency of CNLS at the diagnosis of B-cell ALL was 3.6%. Patients with CNSL at diagnosis had a significantly higher mean presenting leukocyte count ( P = 0.002) and poorer treatment response ( P < 0.05) compared with non-CNSL patients. Moreover, CNSL status was associated with worse 3-year event-free survival ( P = 0.030) and a higher risk of 3-year cumulative incidence of relapse ( P = 0.008), while no impact was observed on 3-year overall survival ( P = 0.837). Multivariate analysis revealed that CNSL status at diagnosis was an independent predictor with a higher cumulative incidence of relapse (hazard ratio = 2.809, P = 0.016)., Conclusion: CNSL status remains an adverse prognostic factor in childhood B-cell ALL, indicating that additional augmentation of CNS-directed therapy is warranted for patients with CNSL at diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Geng, Liao, Yang, Mai, Wan, Huang, Zheng, Tian, Chen, Chen, Long, Zhen, Liu, Li, Wu, Wang, Kong, Chen, Fang and Li.)
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- 2022
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20. [Clinical Characteristic, Diagnosis and Treatment of Acute Lymphoblastic Leukemia Combined with Pneumocystis Carinii Pneumonia in Children].
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Lin SF, Hou LL, Wang J, Xu LH, Liu Y, Mai YG, Fang JP, and Zhou DH
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- Caspofungin therapeutic use, Child, Child, Preschool, Dyspnea, Female, Humans, Male, Respiratory Sounds, Retrospective Studies, Pneumonia, Pneumocystis diagnosis, Pneumonia, Pneumocystis therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Objective: To investigate the clinical characteristics and treatment of pneumocystis carinii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL), in order to improve the early diagnosis and effective treatment., Methods: Clinical data of five children with ALL developing PCP in the post-chemotherapy granulocyte deficiency phase were analyzed retrospectively. The clinical manifestations, laboratory tests, imaging findings, treatment methods and effect were summarized., Results: The male-to-female ratio of the five children was 1∶4, and the median age was 5.5 (2.9-8) years old. All patients developed PCP during granulocyte deficiency phase after induction remission chemotherapy. The clinical manifestations were generally non-specific, including high fever, tachypnea, dyspnea, non-severe cough, and rare rales in two lungs (wet rales in two patients). Laboratory tests showed elevated C-reactive protein (CRP), serum procalcitonin (PCT), (1,3)-β-D-glucan (BDG), lactate dehydrogenase (LDH) and inflammatory factors including IL-2R, IL-6 and IL-8. Chest CT showed diffuse bilateral infiltrates with patchy hyperdense shadows. Pneumocystis carinii(PC) was detected in bronchoalveolar lavage fluid (BALF) or induced sputum by high-throughput sequencing in all patients. When PCP was suspected, chemotherapy was discontinued immediately, treatment of trimethoprim-sulfame thoxazole (TMP-SMX) combined with caspofungin against PC was started, and adjunctive methylprednisolone was used. Meanwhile, granulocyte-stimulating factor and gammaglobulin were given as the supportive treatment. All patients were transferred to PICU receiving mechanical ventilation due to respiratory distress during treatment. Four children were cured and one died., Conclusion: PCP should be highly suspected in ALL children with high fever, dyspnea, increased LDH and BDG, and diffuse patchy hyperdense shadow or solid changes in lung CT. The pathogen detection of respiratory specimens should be improved as soon as possible. TMP/SMZ is the first-line drug against PCP, and the combination of Caspofungin and TMP/SMZ treatment for NH-PCP may have a better efficacy. Patients with moderate and severe NH-PCP may benefit from glucocorticoid.
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- 2022
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21. Umbilical cord blood: A promising source for allogeneic CAR-T cells.
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Liu DD, Hong WC, Qiu KY, Li XY, Liu Y, Zhu LW, Lai WX, Chen H, Yang HQ, Xu LH, and Fang JP
- Abstract
Chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for relapsed and refractory acute lymphoblastic leukemia (R/R ALL). However, autologous CAR-T cells derived from patients with B-ALL often show poor amplification ability, exhaustion, and anergy. To overcome these limitations, allogeneic CAR-T cells may be used as effective substitutes; however, which source would be the best substitute is unclear. In this study, we compared the immunophenotype and antitumor efficacy of anti-CD19 CAR-T cells derived from healthy donor cord blood (CB), healthy donor peripheral blood (PB), and PB of B-ALL patients [PB (patient)] in vitro and NOD-Prkdcem26cd52Il2rgem26Cd22/Nju (NCG)-immunodeficient mice, respectively. The results revealed that CAR-T cells derived from healthy donor CB and PB showed a higher proportion of naive T cells and longer tumor suppression in tumor-bearing mice than those of PB (patient). PB (patient) CAR-T cells had a higher proportion of regulatory T cells (Treg cells) and released high levels of interluekin-10 (IL-10), which also suggest a poor prognosis. Thus, CAR-T cells derived from healthy donors have better antitumor efficacy than CAR-T cells derived from PB (patient), and CB may be a good source of allogeneic CAR-T cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Hong, Qiu, Li, Liu, Zhu, Lai, Chen, Yang, Xu and Fang.)
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- 2022
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22. Pneumocystis jirovecii-associated immune reconstitution inflammatory syndrome-like phenomenon in a child with leukaemia: a case report and literature review.
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Lei JY, Chen H, Zhou DH, Xu LH, Fang JP, and Mai YG
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- Child, Female, Humans, Methylprednisolone, Immune Reconstitution Inflammatory Syndrome diagnosis, Immune Reconstitution Inflammatory Syndrome etiology, Leukemia, Pneumocystis carinii, Pneumonia, Pneumocystis complications, Pneumonia, Pneumocystis diagnosis, Pneumonia, Pneumocystis drug therapy
- Abstract
Background: Immune reconstitution inflammatory syndrome (IRIS) refers to the phenomenon of intense immune responses against pathogens in patients with AIDS undergoing antiretroviral therapy to reconstitute immune function, resulting in functional impairment of multiple organs. Non-AIDS immunosuppressed hosts may also develop similar manifestations to IRIS during immune recovery., Case Presentation: An 8-year-old girl presented with acute lymphoblastic leukaemia was admitted for scheduled chemotherapy treatment. During chemotherapy, she experienced pancytopenia and Pneumocystis jirovecii pneumonia, which was diagnosed based on the abnormal shadows observed on chest computed tomography, the elevation of serum β-D-glucan, and the positive mNGS results of Pneumocystis jirovecii in both sputum and blood. After treatment with Granulocyte Colony-Stimulating Factor, sulfamethoxazole, and caspofungin, aggravation of lung lesions was discovered and severe interstitial lung disease developed in a short period along with a rapidly increasing leukocyte count. Intravenous methylprednisolone pulse therapy was given, but lung function did not improve, and she finally died after the withdrawal of medical care., Conclusions: For patients with acute lymphocytic leukaemia infected with Pneumocystis jirovecii, the rapid aggravation of pulmonary lesions in the process of blood recovery and immune reconstitution should raise vigilance against the possibility of IRIS-like reactions. The use of granulocyte stimulating factors may aggravate the inflammatory response in the lungs. The timing, dosage, and duration of treatment of glucocorticoids and the impact of high-dose methylprednisolone pulse therapy on the prognosis of patients should be explored in further research., (© 2022. The Author(s).)
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- 2022
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23. Poor outcome of pediatric patients with acute myeloid leukemia harboring high FLT3/ITD allelic ratios.
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Qiu KY, Liao XY, Liu Y, Huang K, Li Y, Fang JP, and Zhou DH
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- Child, Genetic Testing, Humans, Mutation, Stem Cell Transplantation, fms-Like Tyrosine Kinase 3 genetics, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
- Abstract
Activating FLT3 mutations are the most common mutations in acute myeloid leukemia (AML), but the optimal threshold of FLT3/ITD allelic ratio (AR) among pediatric AML patients remains controversial. Here, we present the outcome and prognostic significance of FLT3/ITD AR analysis among pediatric patients with AML from the TARGET dataset. Applying fitting curve models and threshold effect analysis using the restrictive cubic spline function following Cox proportional hazards models identifies the cut-off value of 0.5 on FLT3/ITD AR. Moreover, we observe that high FLT3/ITD AR patients have an inferior outcome when compared to low AR patients. Our study also demonstrates that stem cell transplantation may improve the outcome in pediatric AML patients with high FLT3/ITD AR and may be further improved when combined with additional therapies such as Gemtuzumab Ozogamicin. These findings underline the importance of individualized treatment of pediatric AML., (© 2022. The Author(s).)
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- 2022
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24. [Cord blood transplantation with thiotepa containing myeloablative conditioning in a case of pediatric primary myelofibrosis].
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Li XY, Huang K, Xu HG, Shen L, Zhan LP, Wu ZZ, Wu XJ, Huang QW, Huang WQ, Cheng B, and Fang JP
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- Child, Humans, Thiotepa, Transplantation Conditioning, Cord Blood Stem Cell Transplantation, Hematopoietic Stem Cell Transplantation, Primary Myelofibrosis therapy
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- 2022
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25. CEBPA are independent good prognostic factors in pediatric acute myeloid leukemia.
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Liao XY, Fang JP, Zhou DH, and Qiu KY
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- Aged, CCAAT-Enhancer-Binding Proteins genetics, Child, Humans, Mutation, Nucleophosmin, Prognosis, Retrospective Studies, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
- Abstract
To evaluate the outcome and prognostic significance of CEBPA mutations among pediatric acute myeloid leukemia (AML) from TARGET dataset. A total of 1803 pediatric patients who were diagnosed with AML were classified into two groups based on the CEBPA status by using a retrospective cohort study method from September 1996 to December 2016. The incidence of CEBPA mutations was 18%. CEBPA mutations were significantly associated with elder age (p < 0.001), higher WBC (p = 0.004), higher proportion of peripheral blood blast (p < 0.001), normal karyotype (p < 0.001), low risk (p < 0.001) and higher complete remission induction rates (p < 0.05). Overall, CEBPA mutations patients had a significantly better 5-year EFS (p < 0.001) and OS (p < 0.001) compared to CEBPA wild-type patients, and this favorable impact was maintained even in the presence of FLT3/ITD mutations. Stem cell transplantation had no significant impact on the survival of patients with coexistence of CEBPA and FLT3/ITD mutations. Multivariate analysis demonstrated that mutated CEBPA were an independent favorable indicators of better outcome in terms of EFS (p = 0.007) and OS (p = 0.039). Our study demonstrate mutated CEBPA have an excellent outcome in pediatric AML patients. Furthermore, pediatric AML patients with coexistence of CEBPA and FLT3/ITD mutation appear to have favorable prognoses and might not required stem cell transplantation., (© 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)
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- 2022
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26. A Nomogram for Predicting Event-Free Survival in Childhood Acute Lymphoblastic Leukemia: A Multicenter Retrospective Study.
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He YY, Wu XJ, Zhou DH, Yang LH, Mai HR, Wan WQ, Luo XQ, Zheng MC, Zhang JL, Ye ZL, Chen HQ, Chen QW, Long XJ, Sun XF, Liu RY, Li QR, Wu BY, Wang LN, Kong XL, Chen GH, Tang XY, Fang JP, and Liao N
- Abstract
Objective: Even though childhood acute lymphoblastic leukemia (ALL) has an encouraging survival rate in recent years, some patients are still at risk of relapse or even death. Therefore, we aimed to construct a nomogram to predict event-free survival (EFS) in patients with ALL., Method: Children with newly diagnosed ALL between October 2016 and July 2021 from 18 hospitals participating in the South China children's leukemia Group (SCCLG) were recruited and randomly classified into two subsets in a 7:3 ratio (training set, n=1187; validation set, n=506). Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were adopted to screen independent prognostic factors. Then, a nomogram can be build based on these prognostic factors to predict 1-, 2-, and 3-year EFS. Concordance index (C-index), area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance and clinical utility of nomogram., Result: The parameters that predicted EFS were age at diagnosis, white blood cell at diagnosis, immunophenotype, ETV6-RUNX1/TEL-AML1 gene fusion, bone marrow remission at day 15, and minimal residual disease at day 15. The nomogram incorporated the six factors and provided C-index values of 0.811 [95% confidence interval (CI) = 0.792-0.830] and 0.797 (95% CI = 0.769-0.825) in the training and validation set, respectively. The calibration curve and AUC revealed that the nomogram had good ability to predict 1-, 2-, and 3-year EFS. DCA also indicated that our nomogram had good clinical utility. Kaplan-Meier analysis showed that EFS in the different risk groups stratified by the nomogram scores was significant differentiated., Conclusion: The nomogram for predicting EFS of children with ALL has good performance and clinical utility. The model could help clinical decision-making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, Wu, Zhou, Yang, Mai, Wan, Luo, Zheng, Zhang, Ye, Chen, Chen, Long, Sun, Liu, Li, Wu, Wang, Kong, Chen, Tang, Fang and Liao.)
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- 2022
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27. The Role of the Diaphragm in Postural Stability and Visceral Function in Parkinson's Disease.
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Yu X, Jiang HY, Zhang CX, Jin ZH, Gao L, Wang RD, Fang JP, Su Y, Xi JN, and Fang BY
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Background: In normal subjects, the diaphragm plays a key functional role in postural stability, articulation, respiration, defecation, and urination. Objectives: The aim of this study was to investigate the role of the diaphragm in postural stability and visceral function in patients with Parkinson's disease (PD) and to compare the diaphragm function by gender, Hoehn and Yahr (H&Y) staging, and motor subtypes. Methods: In total, 79 patients were enrolled in this cross-sectional study. The severity of the disease was assessed by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale III and by H&Y staging. Postural stability was quantitatively recorded, and respiratory function was evaluated by spirometry. Several scales were used to evaluate visceral function in patients with PD. In addition, diaphragm ultrasound was used to measure the excursion, contraction velocity, and thickness of the diaphragm during quiet breathing, deep breathing, and the sniff test. Significant features were selected by the least absolute shrinkage and selection operator (LASSO) regression and fitted in the multivariate linear regression and Pearson's correlation analysis. Results: Diaphragm thickness and excursion during quiet breathing were significantly different between men and women and between H&Y stage 1-2 and stage 2.5-3, whereas the diaphragm function was not influenced by motor subtypes. It was shown that the diaphragmatic function was significantly correlated with postural stability, voice function, respiratory function, constipation, and urological function to varying degrees in patients with PD. Conclusion: The diaphragmatic function is associated with dysfunction in PD although it remains unclear as to whether the observed changes in the diaphragm are primary or secondary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yu, Jiang, Zhang, Jin, Gao, Wang, Fang, Su, Xi and Fang.)
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- 2021
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28. Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children's Leukemia Group.
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Qiu KY, Xu HG, Luo XQ, Mai HR, Liao N, Yang LH, Zheng MC, Wan WQ, Wu XD, Liu RY, Chen QW, Chen HQ, Sun XF, Jiang H, Long XJ, Chen GH, Li XY, Li CG, Huang LB, Ling YY, Lin DN, Wen C, Kuang WY, Feng XQ, Ye ZL, Wu BY, He XL, Li QR, Wang LN, Kong XL, Xu LH, Li CK, and Fang JP
- Abstract
Purpose: To analyzed the outcome of ETV6/RUNX1-positive pediatric acute B lymphoblastic leukemia (B-ALL) with the aim of identifying prognostic value., Method: A total of 2,530 pediatric patients who were diagnosed with B-ALL were classified into two groups based on the ETV6/RUNX1 status by using a retrospective cohort study method from February 28, 2008, to June 30, 2020, at 22 participating ALL centers., Results: In total, 461 (18.2%) cases were ETV6/RUNX1-positive. The proportion of patients with risk factors (age <1 year or ≥10 years, WB≥50×10
9 /L) in ETV6/RUNX1-positive group was significantly lower than that in negative group ( P <0.001), while the proportion of patients with good early response (good response to prednisone, D15 MRD < 0.1%, and D33 MRD < 0.01%) in ETV6/RUNX1-positive group was higher than that in the negative group ( P <0.001, 0.788 and 0.004, respectively). Multivariate analysis of 2,530 patients found that age <1 or ≥10 years, SCCLG-ALL-2016 protocol, and MLL were independent predictor of outcome but not ETV6/RUNX1. The EFS and OS of the ETV6/RUNX1-positive group were significantly higher than those of the negative group (3-year EFS: 90.11 ± 4.21% vs 82 ± 2.36%, P <0.0001, 3-year OS: 91.99 ± 3.92% vs 88.79 ± 1.87%, P =0.017). Subgroup analysis showed that chemotherapy protocol, age, prednisone response, and D15 MRD were important factors affecting the prognosis of ETV6/RUNX1-positive children., Conclusions: ETV6/RUNX1-positive pediatric ALL showed an excellent outcome but lack of independent prognostic significance in South China. However, for older patients who have the ETV6/RUNX1 fusion and slow response to therapy, to opt for more intensive treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qiu, Xu, Luo, Mai, Liao, Yang, Zheng, Wan, Wu, Liu, Chen, Chen, Sun, Jiang, Long, Chen, Li, Li, Huang, Ling, Lin, Wen, Kuang, Feng, Ye, Wu, He, Li, Wang, Kong, Xu, Li and Fang.)- Published
- 2021
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29. [The Effect of MicroRNA-143 on the Proliferation and Apoptosis of Leukemia Cell Line U-937].
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Huang JL, Fang JP, and Shen JZ
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- Apoptosis, Cell Line, Cell Proliferation, Humans, Leukemia, Myeloid, Acute genetics, MicroRNAs genetics
- Abstract
Objective: To investigate the expression of microRNA-143 (miR-143) in patients with acute myeloid leukemia (AML), and the effect of miR-143 over-expression on the proliferation and apoptosis of AML cells. And to verify the targeting relationship between miR-143 and long non-coding RNA MALAT-1. So as to explore the possible regulatory mechanism of miR-143 in the pathogenesis of AML., Methods: The expression of miR-143 in bone marrow cells of AML patients was detected by RT-qPCR. After miR-143 was over-expressed in U-937 cell lines, the proliferation of U-937 cell lines was detected by CCK-8, clone formation assay, and flow cytometry. In addition, cell apoptosis was detected by Hoechst 33258 fluorescence staining and flow cytometry. At the same time, bioinformatics, RT-qPCR and dual luciferase reporter gene assay were used to predicted and verified the targeting relationship between miR-143 and MALAT-1., Results: Expression of miR-143 in AML patients was significantly lower than those in normal controls. Over-expressed miR-143 could inhibit the proliferation of U-937 cells and promote the apoptosis of the cell. The miR-143 binding site was located on the MALAT-1 RNA sequence, and MALAT-1 was down-regulated in U-937 cells after over-expressed miR-143. However, the expression of miR-143 showed no significantly changed after MALAT-1 silencing., Conclusion: Expression of miR-143 in AML patients is lower than that in normal controls. Over-expression of miR-143 can inhibit the proliferation of U-937 cells and promote its apoptosis. And its mechanism may be related to its targe regulation of MALAT-1.
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- 2021
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30. [Efficacy of Posaconazole for Primary Prophylaxis in the Induction Therapy of Childhood Acute Lymphoblastic Leukemia].
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Zhang YT, Wang J, Zhou DH, and Fang JP
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- Antifungal Agents therapeutic use, Child, Humans, Induction Chemotherapy, Primary Prevention, Triazoles, Mycoses drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Objective: To explore the effect of posaconazole in the primary prevention of invasive fungal disease (IFD) in the induction therapy of childhood acute lymphoblastic leukemia (ALL)., Methods: From August 2018 to November 2020, 144 pediatric patients with ALL treated in Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University were selected, 88 cases received fluconazole as IFD prophylaxis (fluconazole prophylaxis group), 56 cases received posaconazole as IFD prophylaxis (posaconazole prophylaxis group). The incidence of IFD and treatment-related adverse reactions between the two groups were compared, and the safety of posaconazole was evaluated., Results: The incidence of IFD in the fluconazole prophylaxis group was 20.4% (18/88), and in the posaconazole prophylaxis group was 7.1% (4/56). The incidence of IFD between the two groups was statistically significant different(P=0.030). There was no serious adverse reactions in the two groups. The incidence of mild adverse reactions in the posaconazole prophylaxis group (23.2%) was lower than that in the fluconazole prophylaxis group(39.8%), and the difference was statistically significant (P=0.039). There were 12 cases died in the fluconazole prophylaxis group and 4 in the posaconazole prophylaxis group, while no significant difference in the overall survival rate between the two groups (P=0.281)., Conclusion: The effect of posaconazole in the primary prophylaxis of IFD is better and incidence of adverse reactions is lower than fluconazole. Posaconazole can be tolerated, and expected to become the first-line primary prophylaxis drug for IFD during the induction remission therapy of childhood ALL.
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- 2021
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31. [Prevalence Rate and Risk Factors of Hypothyroidism in Children with Beta Thalassemia Major in Zhuhai Area].
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Chen M, Duan L, Zhou CX, and Fang JP
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- Child, Humans, Prevalence, Risk Factors, Hypothyroidism epidemiology, Iron Overload, beta-Thalassemia epidemiology
- Abstract
Objective: To investigate the prevalence rate of hypothyroidism in children with β-thalassemia major (β-TM) and its risk factors., Methods: A total of 86 children with β-TM treated and followed up in the Department of Pediatrics of the Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai Municipal Maternal and Child Health Care Hospital from August 2018 to August 2020 were enrolled. The clinical data of the children were analyzed to investigate the prevalence rate of hypothyroidism in children with β-thalassemia major (β-TM) and its risk factors., Results: The prevalence rate of hypothyroidism in children with β-TM in Zhuhai area was 17.4%. The level of serum ferritin(SF) (4948.27±1225.33 μg/L) in hypothyroidism children was significantly increased(t=10.273,P<0.05). The prevalence rate of hypothyroidism was significantly higher in β-TM children(age ≥10 years old, SF ≥2 500 μg/L and irregular iron removal) (P<0.05). Logistic regression result showed that age ≥10 years old was the independent risk factor affecting the increasing of hypothyroidism rate in the children. The levels of SF(3880.60±1269.17 μg/L), TSH(4.43±1.52 mIU/L) and the prevalence rate of hypothyroidism(37.14%)(P<0.05) were higher for the children in irregular iron removal group., Conclusion: The prevalence rate of hypothyroidism in children with β-TM in Zhuhai area is high, and it is related to the age ≥10 years old, SF ≥2 500 μg/L and irregular iron removal of the children.
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- 2021
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32. Efficacy and safety of eltrombopag in the treatment of Chinese children with chronic immune thrombocytopenia.
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Chen M, Fang JP, Zhou CX, Li XY, Lin SF, and Xu LH
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- Benzoates adverse effects, Child, Child, Preschool, China epidemiology, Chronic Disease, Female, Humans, Hydrazines adverse effects, Infant, Male, Purpura, Thrombocytopenic, Idiopathic epidemiology, Pyrazoles adverse effects, Receptors, Thrombopoietin agonists, Retrospective Studies, T-Lymphocytes, Regulatory drug effects, Treatment Outcome, Benzoates therapeutic use, Hydrazines therapeutic use, Purpura, Thrombocytopenic, Idiopathic drug therapy, Pyrazoles therapeutic use
- Abstract
Objectives: Our aim is to evaluate initial efficacy, safety, and durable response of eltrombopag in the treatment of Chinese children with chronic immune thrombocytopenia (cITP)., Methods: This was a retrospective, single-center cohort study including 30 pediatric patients with cITP administered eltrombopag between 1 July 2017 and 1 January 2019. Patients with at least 12 weeks of eltrombopag treatment and available follow-up data were included. Initial response rate, durable response rate, bleeding events, and adverse events were assessed during the follow-up period., Results: The median duration of eltrombopag administration was 6 months (range 3-8 months). The initial response rate was 73.3%. Patients with megakaryocyte count ≥100/slide or Treg <4.5% were more likely to achieve initial response. The median follow-up period was 10 months (range 6-20 months). A total of 53.2% of pediatric patients had a durable response of up to 20 months. Patients with megakaryocyte count ≥100/slide and Treg<4.5% had more than 60% durable response rates compared with individuals with megakaryocyte count<100/slide and Treg≥4.5%, respectively. No serious bleeding events or serious adverse events occurred during the study period., Conclusion: Eltrombopag not only shows excellent initial response but also has continued efficacy and safety. Patients with megakaryocyte count ≥100/slide and Treg<4.5% achieve increased initial response and more frequent durable response.
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- 2021
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33. A pyruvate kinase deficiency child with novel PK-LR gene mutations was successfully cured by matched unrelated donor peripheral blood stem cell transplantation.
- Author
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Zhan LP, Que LP, Wu ZZ, Liu DD, Wang KM, Xu HG, Fang JP, and Huang K
- Subjects
- Child, Preschool, Humans, Male, Mutation, Unrelated Donors, Anemia, Hemolytic, Congenital Nonspherocytic therapy, Peripheral Blood Stem Cell Transplantation, Pyruvate Kinase deficiency, Pyruvate Kinase genetics, Pyruvate Metabolism, Inborn Errors therapy
- Abstract
Background: Pyruvate kinase deficiency (PKD) is an autosomal recessive disorder caused by a PK-LR gene mutation. Allogeneic hematopoietic cell transplantation (HCT) is an effective cure for PKD. However, the experience of applying HCT in PKD is limited., Methods: We present a child with novel PK-LR gene mutations who was successfully cured by matched unrelated donor peripheral blood stem cell transplantation (MUD-PBSCT)., Results: A 4-year-old, male patient suffered severe hemolytic anemia and jaundice 5 h after birth. Gene sequencing showed that the pyruvate kinase-liver and RBC (PK-LR) gene had a nonsense mutation in exon 5: c.602G>A (p.W201X), and large deletions in exons 3-9. Both of them were novel pathogenic mutations of the PK-LR gene. After transplantation, the hemoglobin level became normal and the nonsense mutation was undetectable. Grade Ⅳ acute graft-versus-host disease (aGVHD) and extensive chronic graft-versus-host disease (cGVHD) occurred in the patient. However, the GVHD was controlled effectively. The patient is alive and has good quality of life 22 months post-transplant, but has mild oral lichen planus-like lesion., Conclusion: Gene sequencing contributes to the diagnosis of PKD. HCT is an effective method for curing PKD, but we should explore how to reduce severe GVHD., (© 2021 Wiley Periodicals LLC.)
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- 2021
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34. Partial Multi-Label Learning via Credible Label Elicitation.
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Zhang ML and Fang JP
- Abstract
Partial multi-label learning (PML) deals with the problem where each training example is associated with an overcomplete set of candidate labels, among which only some candidate labels are valid. The task of PML naturally arises in learning scenarios with inaccurate supervision, and the goal is to induce a multi-label predictor which can assign a set of proper labels for unseen instance. The PML training procedure is prone to be misled by false positive labels concealed in the candidate label set, which serves as the major modeling difficulty for partial multi-label learning. In this paper, a novel two-stage PML approach is proposed which works by eliciting credible labels from the candidate label set for model induction. In the first stage, the labeling confidence of candidate label for each PML training example is estimated via iterative label propagation. In the second stage, by utilizing credible labels with high labeling confidence, multi-label predictor is induced via pairwise label ranking coupled with virtual label splitting or maximum a posteriori (MAP) reasoning. Experimental studies show that the proposed approach can achieve highly competitive generalization performance by excluding most false positive labels from the training procedure via credible label elicitation.
- Published
- 2021
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35. [Research Progress on Gene Therapy for β-thalassemia---Review].
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Hong WC, Fang JP, and Xu LH
- Subjects
- Gene Editing, Genetic Therapy, Genetic Vectors, Humans, beta-Globins genetics, beta-Thalassemia genetics, beta-Thalassemia therapy
- Abstract
β-thalassemia is a monogenetic inherited hemolytic anemia, which results in a series of pathophysiological changes due to partial or complete inhibition of the synthesis of β-globin chain. The curative therapy for this disease is to reconstitute hematopoiesis, and transplantation with genetically modified autologous hematopoietic stem cells can avoid the major difficulties of traditional allogeneic hematopoietic stem cell transplantation,such as HLA matching and immune rejection. β-thalassemia gene therapy strategies mainly include gene integration and genome editing. The former relies on the development of lentiviral vectors and adds a fully functional HBB gene to the chromosome; the latter rapidly develops with the research of specific nuclease which can repair the HBB gene in situ. In this review, the latest progress of the two strategies in gene therapy of β-thalassemia is summarized.
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- 2021
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36. DNA index as prognostic factor in childhood acute lymphoblastic leukemia in the COG-TARGET database.
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Qiu KY, Liao XY, He ZW, Wu RH, Li Y, Xu LH, Zhou DH, and Fang JP
- Subjects
- Child, Databases, Factual, Female, Humans, Male, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Prognosis, Retrospective Studies, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics
- Abstract
Background: This study was aimed to evaluate the value of DNA index(DI) among pediatric acute lymphoblastic leukemia (ALL) treated on Children's Oncology Group (COG) protocols between 2000 and 2015., Methods: Retrospective study were analysis among pediatric ALL patients from the TARGET dataset., Result: Totally, 1668 eligible pediatric patients were enrolled in this study. Of them, 993 are male and 675 are female with a median age of 7.6 years old. The median follow-up for those patients was 7.7 years (range 0.1-15.7 years). The probability of 15-year EFS and OS were reported to be 67.5 ± 3.1% and 78.3 ± 2.5%, respectively. BCR/ABL1 fusion gene affected the early treatment response and the survival of childhood ALL. Moreover, those patients with ETV6/RUNX1 fusion gene were also significantly associated with better EFS (HR = 0.6, 95% CI 0.4-0.8, P = 0.003) and OS (HR = 0.3, 95%CI 0.2-0.5, P < 0.001) compared to patients with no ETV6/RUNX1. On the contrary, BM NR on Day+ 29 showed a significant decrease in EFS (HR = 3.1, 95%CI 2.1-4.5, P < 0.001) and OS (HR = 1.7, 95%CI 1.1-2.8, P = 0.026). Multivariate analysis showed that DI was significantly associated with better EFS and OS. The threshold effect of DI on poor outcome was significant after adjusting for potential confounders. The adjusted regression coefficient (Log RR) was 0.7 (95%CI 0.1-3.2, P = 0.597) for DI < 1.1 while 8.8 (95%CI 1.4-56.0, P = 0.021) for DI ≥ 1.2 and 0.0 (95%CI 0.0-0.8, P = 0.041) for 1.1 ≤ DI < 1.2. Generalized additive models revealed that the lowest rates of the adverse outcomes estimated to occur among DI between 1.1 and 1.2., Conclusion: For those childhood ALL treated on COG protocols between 2000 and 2015, ETV6/RUNX1 and BM NR were closely related to the prognosis. Moreover, the DI between 1.1 and 1.2 can serve as a significant cut-point discriminating the risk group, which indicated a favourable prognostic factor., (© 2021. The Author(s).)
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- 2021
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37. Efficacy of short-term multidisciplinary intensive rehabilitation in patients with different Parkinson's disease motor subtypes: a prospective pilot study with 3-month follow-up.
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Chen KK, Jin ZH, Gao L, Qi L, Zhen QX, Liu C, Wang P, Liu YH, Wang RD, Liu YJ, Fang JP, Su Y, Yan XY, Liu AX, and Fang BY
- Abstract
Parkinson's disease (PD) can be classified into three motor-based subtypes: postural instability/gait difficulty (PIGD), tremor dominant (TD), and indeterminate. The neuropathophysiological mechanisms of the three motor subtypes are different, which may lead to different responses to therapy. Sixty-nine patients with idiopathic Parkinson's disease (Hoehn-Yahr stage ≤ 3) were screened from 436 patients with Parkinsonism recruited through outpatient services and the internet. According to the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) TD/PIGD ratio, the patients were divided into PIGD (TD/PIGD ≤ 0.09; n = 36), TD (TD/PIGD ≥1.15; n = 19), and indeterminate (TD/PIGD = 0.90-1.15; n = 14) groups. All patients received 2 weeks of multidisciplinary intensive rehabilitation treatment (MIRT) during hospitalization, as well as a remote home rehabilitation health education class. Compared with the scores at admission, all patients showed significant improvements in their MDS-UPDRS III score, walking ability, balance, and posture control at discharge. Moreover, the MDS-UPDRS III score improvement was greater in the PIGD group than in the TD group. The follow-up data, collected for 3 months after discharge, showed that overall symptom improvement in each group was maintained for 1-3 months. Furthermore, there were no significant differences in the duration or grade effects of symptom improvement among the three groups. These findings suggest that 2 weeks of MIRT is effective for improving motor performance in all three motor subtypes. Patients in the PIGD group had a better response after hospitalization than those in the TD group. This study was approved by the Institutional Ethics Committee of Beijing Rehabilitation Hospital of Capital Medical University of China (approval No. 2018bkky022) on May 7, 2018 and registered with the Chinese Clinical Trial Registry (registration No. ChiCTR1900020771) on January 19, 2019., Competing Interests: None
- Published
- 2021
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38. Wilms Tumor 1 Mutations Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia.
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Wang Y, Weng WJ, Zhou DH, Fang JP, Mishra S, Chai L, and Xu LH
- Abstract
The prognostic impact of Wilms tumor 1 ( WT1 ) mutations remains controversial for patients with acute myeloid leukemia (AML). Here, we aimed to determine the clinical implication of WT1 mutations in a large cohort of pediatric AML. The clinical data of 870 pediatric patients with AML were downloaded from the therapeutically applicable research to generate effective treatment (TARGET) dataset. We analyzed the prevalence, clinical profile, and prognosis of AML patients with WT1 mutations in this cohort. Our results showed that 6.7% of total patients harbored WT1 mutations. These WT1 mutations were closely associated with normal cytogenetics ( P <0.001), FMS-like tyrosine kinase 3/internal tandem duplication ( FLT3 /ITD) mutations ( P <0.001), and low complete remission induction rates ( P <0.01). Compared to the patients without WT1 mutations, patients with WT1 mutations had a worse 5-year event-free survival (21.7 ± 5.5% vs 48.9 ± 1.8%, P <0.001) and a worse overall survival (41.4 ± 6.6% vs 64.3 ± 1.7%, P <0.001). Moreover, patients with both WT1 and FLT3 /ITD mutations had a dismal prognosis. Compared to chemotherapy alone, hematopoietic stem cell transplantation tended to improve the prognoses of WT1 -mutated patients. Multivariate analysis demonstrated that WT1 mutations conferred an independent adverse impact on event-free survival (hazard ratio 1.910, P = 0.001) and overall survival (hazard ratio 1.709, P = 0.020). In conclusion, our findings have demonstrated that WT1 mutations are independent poor prognostic factors in pediatric AML., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Weng, Zhou, Fang, Mishra, Chai and Xu.)
- Published
- 2021
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39. [Eltrombopag for thrombocytopenia in 24 children after hematopoietic stem cell transplantation].
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Liu S, Que LP, Huang K, Fang JP, Wang KM, Zhan LP, Liu DD, and Xu HG
- Subjects
- Adolescent, Benzoates, Child, Female, Humans, Hydrazines therapeutic use, Male, Pyrazoles, Retrospective Studies, Treatment Outcome, Hematopoietic Stem Cell Transplantation adverse effects, Thrombocytopenia drug therapy, Thrombocytopenia etiology
- Abstract
Objective: To evaluate the efficacy and safety of eltrombopag for children with thrombocytopenia after hematopoietic stem cell transplantation (HSCT). Methods: Clinical data of 24 patients with thrombocytopenia after HSCT,who were treated with eltrombopag in the Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from August 1, 2018 to April 1, 2019 were analyzed retrospectively. The response rate and adverse reactions of eltrombopag were evaluated. Patients were divided into groups by source of hematopoietic stem cells (umbilical cord blood group and peripheral stem cell group) and type of disease (malignant and non-malignant disease group) and the clinical outcomes between groups were compared. Rank Sum test was used for comparisons between groups. Results: Among 24 cases, 15 were males and 9 females, the age of starting eltrombopag was 7.7 (2.6-13.7) years, the time of eltrombopag treatment after HSCT was 27.5 (8.0-125.0) days, the time from treatment to complete response (CR) was 23.5 (6.0-83.0) days, with the treatment course 36.5 (8.0-90.0) days. The total dose of eltrombopag was 1 400(200-5 900) mg. Complete response rate was 92% (22/24),without eltrombopag related adverse reactions. Comparing with peripheral stem cell group ( n= 8), the course and total dose of eltrombopag in umbilical cord blood group ( n= 16) were significantly reduced(24.5 (8.0-81.0) vs . 65.5 (35.0-90.0) d, Z =-3.004, P =0.002; 900.0 (200.0-3 850.0) vs . 2 862.5 (1 175.0-5 900.0) mg, Z= -2.604, P= 0.007), but no significant differences were found in the time from treatment to complete response, platelet count after 2 weeks of eltrombopag withdrawal or platelet count at the end point of follow-up (all P> 0.05). Comparing malignant patients ( n= 12) and non-malignant patients ( n= 12), no significant differences were found in the time from treatment to complete response, course, total dose, platelet count after 2 weeks of eltrombopag withdrawal, and platelet count at the end point of follow-up in non-malignant patients (all P> 0.05). Conclusion: Eltrombopag is safe and maybe effective for thrombocytopenia after HSCT, especially for umbilical cord blood transplantation.
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- 2021
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40. Eltrombopag as first-line treatment for thrombocytopenia among paediatric patients after allogeneic haematopoietic stem cell transplantation.
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Qiu KY, Liao XY, Huang K, Wu RH, Xu HG, Xu LH, Li Y, Weng WJ, Zhou DH, and Fang JP
- Subjects
- Benzoates therapeutic use, Child, Humans, Hydrazines, Pyrazoles, Retrospective Studies, Hematopoietic Stem Cell Transplantation adverse effects, Thrombocytopenia drug therapy, Thrombocytopenia etiology
- Abstract
Aims: The purpose of this study is to examine the safety and efficacy of eltrombopag as first-line treatment for thrombocytopenia among paediatric patients after haematopoietic stem cell transplantation (HSCT)., Methods: Forty-three childhood patients with thrombocytopenia after HSCT who received eltrombopag were retrospectively analysed., Result: Eltrombopag was began at the median of 27 days after HSCT and lasted for 24 days. Thirty-five children responded to eltrombopag therapy, and the cumulative platelet recovery rate was 88.9%. The cumulative incidence of platelet recovery was lower (83.9 vs 100%; P = .035) in patients with decreased numbers of megakaryocytes before starting eltrombopag than in those with normal. Factors associated with a significantly elevated response to eltrobopag from univariate analysis were donor type. Results from the multiple regression analysis found that weight (hazard ratio [HR] = 0.7, 95% confidence interval [CI] 0.5-0.9, P = .022), platelet engraftment time (HR = 1.0, 95%CI 1.0-1.0, P = .012) and bone marrow megakaryocytes (HR = 8.0, 95%CI 1.5-43.3, P = .016) before starting eltrombopag were the independent risk factors. Based on Youden's index algorithm in the receiver-operating characteristic curve, the optimal cut-off value of the maintenance dose of eltrombopag in predicting nonresponders was 4 mg/kg. The area under the receiver-operating characteristic curve was 0.923 with sensitivity of 97.8%, specificity of 87.9%, positive predictive value of 72.3%, and negative predictive value of 92%. None of the paediatric patients stopped using eltrombopag due to side effect or intolerability., Conclusion: Eltrombopag is effective and safe in paediatric patients with thrombocytopenia after HSCT. The number of megakaryocytes in bone marrow before eltrombopag treatment may serve as a predictor of the response to eltrombopag. We recommend that the maintenance dose of eltrombopag should not exceed 4 mg/kg/d., (© 2020 British Pharmacological Society.)
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- 2021
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41. [Analysis of Clinical Characteristics and Prognosis in Children with Acute Megakaryoblastic Leukemia without Down Syndrome].
- Author
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Lin SF, Guo SY, Liu S, Wang J, Huang K, Li Y, Fang JP, and Zhou DH
- Subjects
- Child, Child, Preschool, DEAD-box RNA Helicases, DNA Helicases, Female, Humans, Male, Prognosis, Retrospective Studies, Trisomy, Down Syndrome, Leukemia, Megakaryoblastic, Acute genetics
- Abstract
Objective: To analyze the clinical characteristics and treatment effects of children with acute megakaryoblastic leukemia without down syndrome (non-DS-AMKL)., Methods: The clinical data of 19 children with non-DS-AMKL treated in the Pediatric Hematology Ward in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from May 2008 to April 2018 were analyzed retrospectively. The clinical characteristics, laboratory test and treatment methods of the children were concluded. All patients were followed up to evaluate the effect of treatment., Results: The 19 cases of children included nine male and ten female, the median age of onset was 2 years old. The clinical manifestations showed nonspecific. The median white blood cell of peripheral blood was 15.88×10
9 /L, the median hemoglobin was 67 g/L and median platelet was 16×109 /L. An increase of primitive and naive megakaryocytes was found in the bone marrow sample. The immunophenotypes of bone marrow detected by flow cytometry in 19 children were all positive expressed for CD41, CD61. Genetic tests showed that five cases carrying EVI1, including one complicating with MLL/AF10, one patient carrying HOX11, one carrying GATA1, IKZF1 and DDX11 mutations, one patient carrying missense mutation of NRAS, one with missense mutation of KRAS and two cases with high expression of WT1. Karyotype analysis were performed in 11 cases of children, including four with normal karyotype, four with complex karyotypes, one with trisomy 8, one with 7/13 trisomy 21 without Down syndrome manifestations (considered as abnormal somatic karyotype) and one Robertsonian translocation carrier involving chromosomes 14 and 21. Ten children received treatment, including three cases with allogeneic hematopoietic stem cell transplantation (allo-HSCT) after complete remission (CR), two cases with complete donor implantation, and one without implanted but hematopoietic recovered, these three children were followed up for 26, 15 and 12 months respectively and the minimal residual disease (MRD) were all less than 10-4 . Another three cases achieving CR after chemotherapy but relapsed in 5, 10 and 12 months after the onset respectively, and all the three children were died eventually. One children died of pulmonary hemorrhage during chemotherapy and three children died from discontinuation of treatment after non remission. The remaining nine children died because of without chemotherapy treatment., Conclusion: Non-DS-AMKL was rare in children and difficult to be diagnosed. Determination of MICM classification as early as possible was helpful for diagnosis, and genetic testing played an important role for diagnosis and prognosis evaluation. Early hematopoietic stem cell transplantation in patients with CR after chemotherapy might be an effective way to cure AMKL.- Published
- 2021
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42. C-Gait for Detecting Freezing of Gait in the Early to Middle Stages of Parkinson's Disease: A Model Prediction Study.
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Chen ZY, Yan HJ, Qi L, Zhen QX, Liu C, Wang P, Liu YH, Wang RD, Liu YJ, Fang JP, Su Y, Yan XY, Liu AX, Xi J, and Fang B
- Abstract
Objective: Efficient methods for assessing walking adaptability in individuals with Parkinson's disease (PD) are urgently needed. Therefore, this study aimed to assess C-Gait for detecting freezing of gait (FOG) in patients with early- to middle-stage PD., Method: People with PD (PWP) diagnosis (Hoehn and Yahr stages 1-3) were recruited from April 2019 to November 2019 in Beijing Rehabilitation Hospital. The participants performed six items of walking adaptability on an instrumented treadmill augmented with visual targets and obstacles (C-Mill). The patient's walking adaptability was evaluated by C-Gait assessment and traditional walking tests, and FOG-related indexes were collected as outcome measures. Two discriminant models were established by stepwise discriminant analysis; area under the receiver operating characteristic (ROC) curve (AUC) was used to validate the models., Result: In total, 53 patients were included in this study. Most C-Gait assessment items had no or low correlations with traditional walking tests. The obstacle avoidance ( r = -0.639, P = 0.003) and speed of adaptation ( r = -0.486, P = 0.035) items could lead to FOG with high sensitivity. In addition, the C-Gait assessment model (AUC = 0.755) had slightly better discrimination of freezers from non-freezers compared with traditional walking test models (AUC = 0.672); specifically, obstacle avoidance and speed of adaptation have uniquely discriminant potential., Conclusion: C-gait assessment could provide additional value to the traditional walking tests for PD. Gait adaptability assessment, as measured by C-Gait, may be able to help identify freezers in a PD population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Yan, Qi, Zhen, Liu, Wang, Liu, Wang, Liu, Fang, Su, Yan, Liu, Xi and Fang.)
- Published
- 2021
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43. Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - a multi-centric clinical study of GD-2008-ALL protocol.
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Li XY, Li JQ, Luo XQ, Wu XD, Sun X, Xu HG, Li CG, Liu RY, Sun XF, Chen HQ, Lin YD, Li CK, and Fang JP
- Subjects
- Adolescent, Child, Child, Preschool, Cyclophosphamide administration & dosage, Cytarabine administration & dosage, Daunorubicin administration & dosage, Female, Follow-Up Studies, Humans, Infant, Male, Mercaptopurine administration & dosage, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology, Neoplasm, Residual drug therapy, Neoplasm, Residual pathology, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Prednisone administration & dosage, Prognosis, Remission Induction, Retrospective Studies, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neoplasm Recurrence, Local mortality, Neoplasm, Residual mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality
- Abstract
Background: The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70-85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong (GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity on treatment related mortality (TRM) based on Berlin-Frankfurt-Münster (BFM) 2002 backbone treatment. The study was designed to elucidate whether the reduced intensity is effective and safe for children with ALL., Methods: The clinical data were obtained from February 28, 2008 to June 30, 2016. A total of 1765 childhood ALL cases from 9 medical centers were collected and data were retrospectively analyzed. Patients were stratified into 3 groups according to bone marrow morphology, prednisone response, age, genotype, and karyotype information: standard risk (SR), intermediate risk (IR) and high risk (HR). For SR group, daunorubicin was decreased in induction IA while duration was reduced in Induction Ib (2 weeks in place of 4 weeks). Doses for CAM were same in all risk groups - SR patients received one CAM, others got two CAMs., Results: The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2%) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day 33 positive group (n=7) was 28.6%, while in the MRD Day 33 negative group (n=67) was 7.5% (p=0.129)., Conclusions: The results of GD-2008-ALL protocol are outstanding for reducing TRM in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification.
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- 2021
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44. Prediction, management, and prognosis of mixed chimerism after hematopoietic stem cell transplantation in transfusion-dependent pediatric thalassemia patients.
- Author
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Chen H, Li XY, Zhan LP, Fang JP, Huang K, Li Y, Weng WJ, Xu LH, Xu HG, and Zhou DH
- Subjects
- Adolescent, Child, Child, Preschool, Female, Graft Rejection etiology, Graft vs Host Disease etiology, Humans, Infant, Male, Prognosis, Hematopoietic Stem Cell Transplantation, Thalassemia therapy, Transplantation Chimera
- Abstract
Background: Early-onset mixed chimerism (MC) with a high proportion of residual host cells is considered a signal of graft rejection in patients undergoing allogenic hematopoietic stem cell transplantation for transfusion-dependent thalassemia. In order to prevent graft rejection and minimize the risk of treatment-related graft-versus-host disease (GVHD), we established a hierarchical management system based on chimerism analysis., Method: This retrospective study provides a comprehensive review of the characteristics, interventions, and outcomes of the 38 patients who developed MC after transplantation among the 144 pediatric thalassemia patients between July 2007 and January 2019 at our center., Results: A sibling donor, a blood type-matched donor, conditioning regimens without fludarabine, and transplants containing <10 × 10
8 total nucleated cells/kg were identified to be associated with the development of MC. Among the 38 patients developing MC, only four patients rejected the grafts. The response rate to donor lymphocyte infusion (DLI, only for patients receiving sibling donor transplantation) and cytokine immunomodulation without DLI was 70.6% and 42.9%, respectively. Patients that developed GVHD after DLI or cytokine therapy had a more significant increase in donor cell chimerism (16%, range 0%-35%) than those without (8.5%, range -21% to 40%, P = .049). However, even when treatment-related GVHD was included, patients with MC had a lower cumulative incidence of total acute GVHD than patients with complete donor chimerism (29.2% vs 48.0%, P = .030)., Conclusions: Interventions based on chimerism analysis were effective in preventing graft rejection and did not increase treatment-related GVHD in thalassemia patients with MC., (© 2020 Wiley Periodicals LLC.)- Published
- 2020
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45. [Values of MCV,MCH,ROFT and HbA 2 for Screening α-Thalassemia in Guangdong Area].
- Author
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Liu Y, Lin XY, Huang Y, Huang QW, Chen HL, Shen MN, Ruan JY, Li XY, Xu LH, and Fang JP
- Subjects
- Hemoglobin A2 analysis, Humans, Mass Screening, Sensitivity and Specificity, Erythrocyte Indices, alpha-Thalassemia diagnosis, alpha-Thalassemia genetics
- Abstract
Objective: To investigate the values of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), red cell osmotic fragility test(ROFT) and hemoglobin A2(HbA
2 ) in screening of α-thalassemia in Guangdong area., Methods: A total of 285 peripheral blood samples in patients treated in our hospital from January 2017 to December 2017 were collected. The detection of thalassemia gene was used as the gold standard, while blood routine examination, hemoglobin electrophoresis, and red cell osmotic fragility test were simultaneously performed. The optimal cut-off values in MCV, MCH, ROFT and HbA2 in α-thalassemia were determined by receiver operator characteristic curve (ROC curve)., Results: The most common types of α-thalassemia gene was --SEA/αα (54.59%). Compared with the control group, the differences in MCV, MCH, ROFT and HbA2 showed statistically significantce between different types of α-thalassemia (P<0.05). The best cut-off values of MCV, MCH, ROFT, and HbA2 in the diagnosis of α-thalassemia were 81.45 fl, 27.35 pg, 79.95%, and 2.55% respectively., Conclusion: For different laboratories, the cut-off values need to be established for screening α-thalassemia suitable in their own local region.The values of MCV, MCH, ROFT and HbA2 shows higher accuracy and sensitivity in the diagnosis of α-thalassemia. It is recommended to use MCV<81.45fl, MCH<27.35 pg, ROFT<79.95% and HbA2 <2.55% as the standards for screening α-thalassemia in Guangdong area.- Published
- 2020
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46. [Knockdown of ALAS2 Affects Erythroid Differentiation by Down-regulating Mitophagy Receptor BNIP3L].
- Author
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Hu ST, Li XY, Chen H, Xu LH, and Fang JP
- Subjects
- 5-Aminolevulinate Synthetase metabolism, Apoptosis, Cell Differentiation, Humans, K562 Cells, Membrane Proteins genetics, Membrane Proteins metabolism, Proto-Oncogene Proteins genetics, Tumor Suppressor Proteins, Carrier Proteins, Mitophagy
- Abstract
AbstractObjective: To investigate the effect of ALAS2 downregulation on the expression of BNIP3L and erythroid differentiation in K562 cells., Methods: The expression of ALAS2 was down-regulated by transfection of lentivirus, then quantitative real-time PCR was performed to detect the transfection efficiency. Flow cytometry analysis was applied to evaluate apoptosis of cells, erythroid differentiation, mitochondrial membrane potential and reactive oxygen species (ROS) level. Western blot was used to detect the BNIP3L expression, Co-immunoprecipitation was performed to analyze the relationship between ALAS2 and BNIP3L., Results: Compared with sh-NC group, knockdown of ALAS2 induced downregulation of BNIP3L mRNA and protein expression(P<0.01) and erythroid related transcription factors GATA1, Nrf2 expression, as well as reduction of ROS level(P<0.05). Mitochondrial membrane potential of control (sh-NC) group was lower than that of shALAS2 group(P<0.05), but there was no significant change of cell apoptotic rate in two groups. CD71highCD235ahigh + CD71lowCD235ahigh cells of sh-NC and shALAS2 groups were 53.5%, 92.9% at 96 h after hemin induction, respectively. No direct action between ALAS2 and BNIP3L was observed., Conclusion: The intracellular heme level can affect the expression of BNIP3L which may be related with the regulation of ROS and transcription factors GATA1 and Nrf2. Higher BNIP3L facilitates cell differentiation but lower BNIP3L is favorable for cells survival.
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- 2020
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47. [Acute lymphoblastic leukemia complicated with cerebral venous thrombosis in 14 children].
- Author
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Liu TH, Li XY, Han XW, Zhang YT, Zhou DH, Xu LH, Huang JW, and Fang JP
- Subjects
- Adolescent, Anticoagulants therapeutic use, Cerebral Angiography, Child, Heparin, Low-Molecular-Weight, Humans, Retrospective Studies, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Venous Thrombosis complications, Venous Thrombosis diagnostic imaging
- Abstract
Objective: To explore the clinical characteristics and management of childhood acute lymphoblastic leukemia (ALL) complicated with cerebral venous thrombosis (CVT). Methods: The clinical data of 14 ALL children complicated with CVT who were admitted to Department of Pediatrics of Sun Yat-sen Memorial Hospital and underwent chemotherapy from January 2011 to October 2019 were collected retrospectively. The clinical manifestations, coagulation function, imaging findings, treatment plan and prognosis of patients were analyzed. Results: CVT was diagnosed in 14 (2.8%, 14/505) cases, with a median age of 10 (3-14) years at onset, 11 cases occurred in the stage of induction remission, and the acute onsets were mainly characterized by convulsions (9 cases), consciousness disorders (6 cases) and headache (4 cases). Coagulation function test showed that, before the CVT, antithrombin Ⅲ activity was lower than 60% in 8 cases, D-dimer elevated on the day of onset in 8 cases. Arteriovenous angiography showed filling defects in single (9 cases) or multiple (5 cases) venous sinuses. The most common site of venous sinus enlargement was superior sagittal sinus (10 cases). Secondary cerebral hemorrhage was found in 5 cases. Anticoagulation therapy included combination of low-molecular-weight heparin (LMWH) and warfarin in 9 cases, sequential application of LMWH and warfarin in 2 cases, and LMWH alone in 3 cases. Patients accepted further asparaginase and no CVT recurrence or progression was found. Conclusions: The secondary coagulation dysfunction during induction remission chemotherapy is the major risk factor for CVT in ALL, which needs active monitoring and early prevention. Arteriovenous angiography can diagnose accurately, and the prognosis of anticoagulant therapy with LMWH and warfarin is optimistic.
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- 2020
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48. [Preliminary Study of Chidamide Combined with Hematopoietic Stem Cell Transplantation in the Treatment of Childhood Acute T-Lymphoblastic Leukemia].
- Author
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Zhang YT, Huang K, Xu LH, Han XW, Li XY, and Fang JP
- Subjects
- Aminopyridines, Benzamides, Child, Humans, Recurrence, Transplantation, Homologous, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Abstract
Objective: To investigate the efficacy and safety of combination chidamide and hematopoietic stem cell transplantation (HSCT) in the treatment of childhood acute T lymphoblastic leukemia (T-ALL)., Methods: Seven children with acute T lymphoblastic leukemia received hematopoietic stem cell transplantation in SUN Yat-Sen Memorial Hospital of SUN Yat-Sen University were selected. 7 cases of T-ALL were divided into 2 groups: HSCT plus chidamide-treated group (4 cases) and traditional HSCT-treated group (3 cases) as control. The incidence of GVHD and other related complications, as well as implantation, recurrence and survival were compared between the two groups, and the side effects of chidamide were observed. All the patients were follow-up until January 2019., Results: All the 7 patients were alive and, there was no difference in the incidence of acute GVHD between the HSCT plus chidamides treated group and the traditional HSCT-treated group. The implantation rate of HSCT was 100%, and there were no recurrence occurred. During the application of chidamide, 3 cases showed adverse reactions, of which 2 cases had adverse reactions of grade 3 or higher, and 2 cases were hematological adverse reactions (neutropenia, thrombocytopenia), other adverse reactions were non-hematologic adverse reactions (transaminase elevation, fatigue, nausea, vomiting), there were no serious adverse reactions occurred. In the HSCT plus chidamide-treated group, 2 cases were found that mature lymphocytes were not expressed by tumors, during examing for minimal redidaul disease (MRD). Compared with the immunophenotype and TCR rearrangement at first diagnosis, the results did not support the source of residual T-ALL tumor cells. During the review of MRD, it was found that the abnormal T cells showed an increasing trend, indicating that chidamide might induce leukemia cell differentiation through some pathways., Conclusion: Hematopoietic stem cell transplantation is still an effective method to cure children's T-ALL. In some cases, abnormal T-cell nonclonal amplification occurs during the application of chidamide, and the children with T-ALL can tolerable adverse reactions of chidamide.
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- 2020
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49. Myeloid sarcoma is associated with poor clinical outcome in pediatric patients with acute myeloid leukemia.
- Author
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Xu LH, Wang Y, Chen ZY, and Fang JP
- Subjects
- Adolescent, Child, Child, Preschool, Female, Gene Rearrangement, Histone-Lysine N-Methyltransferase genetics, Humans, Infant, Leukemia, Myeloid, Acute epidemiology, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute pathology, Male, Myeloid-Lymphoid Leukemia Protein genetics, Prognosis, Sarcoma, Myeloid epidemiology, Sarcoma, Myeloid genetics, Sarcoma, Myeloid pathology, Leukemia, Myeloid, Acute diagnosis, Sarcoma, Myeloid diagnosis
- Abstract
Purpose: The impact of myeloid sarcoma (MS) on clinical outcome of pediatric acute myeloid leukemia (AML) patients remains controversial. Moreover, little is known about the role of stem cell transplantation (SCT) in such patients., Methods: Clinical data of patients with AML under 18 years of age were retrieved from the TARGET dataset. We analyzed the prevalence, clinical profile, molecular characteristics, and prognosis of MS in these patients., Results: Among 884 pediatric patients with AML, the frequency of MS was 12.3%. Pediatric AML with MS was associated with age under 1-year, abnormal cytogenetics, and KMT2A rearrangement. Moreover, MS was associated with a low complete remission rate, high induction death, poor 5-year EFS, and OS. KMT2A rearrangement had a negative impact on clinical outcome in AML patients with MS. In addition, SCT had no significant effect on the survival of AML patients with MS. Multivariate analysis revealed that MS was an unfavorable prognostic factor in pediatric AML in terms of EFS (Hazard ratio 1.670, P < 0.001) and OS (Hazard ratio 1.623, P = 0.004)., Conclusions: The presence of MS at diagnosis of pediatric AML is associated with poor clinical outcomes, particularly when associated with KMT2A rearrangements. Moreover, pediatric patients with AML and MS may not benefit from SCT.
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- 2020
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50. [Efficacy of BMMSCs on aGVHD and Its Correlation with SerumInflammatory Cytokines in Pediatric Patients with Severe Refractory Acute Graft-Versus-Host Disease].
- Author
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Guo SY, Qiu KY, Tang XK, Huang K, Xu HG, Li Y, Weng WJ, Xu LH, Fang JP, and Zhou DH
- Subjects
- Acute Disease, Child, Cytokines, Humans, Transplantation, Homologous, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Mesenchymal Stem Cells
- Abstract
Objective: To investigate the efficacy of bone marrow mesenchymal stem cells (BMMSC) on children with refractory graft-versus-host disease (GVHD) and to judge the efficacy of BMMSC by dynamically monitoring the changes of cytokines in children with GVHD before and after infusion of BMMSC, so as to provide a theoretical basis for clarifying the mechanism of BMMSC., Methods: 17 children with refractory aGVHD including 7 of grade II, 6 cases of grade III and 4 cases of grade IV after allo-HSCT were enrolled. All the children with aGVHD, who received routine immunosuppressive therapy, but the state of disease not improved, were treated with immunosuppressive drugs combined with BMMSC infusion. Study endpoints included safety of BMMSC infusion, response to BMMSC, and overall response of aGVHD. The serum levels of IL-2α, IL-6, IL-10, IL-8 and TNF-α in aGVHD patients were measured by chemiluminescence before infusion of BMMSCs and Day 7, Day 14 after infusion of BMMSCs., Results: The cumulative median dose of BMMSCs was 5.5 (3.4-11.1) × 10
6 /kg for average of 3.7 times, and the median time of 16.5 (4-95) days for the first infusion of MSCs. In 17 cases of refractory GVHD, 14 responded to treatment, whereas 3 patients failed. The total effective rate was 82.4% and no adverse reactions occurred. Of the 14 survived cases (82.4%), the median follow-up time was 944 (559-1245) days from the first infusion of MSCs. The levels of TNF-α in children with grade II, III and IV GVHD before treatment were 9.5±4.3 pg/ml, 16.3±10.9 pg/ml and 35.8±21.2 pg/ml respectively. The difference between grade II and IV, III and IV was statistically significant (P<0.05). Compared with the ineffective group of BMMSC infusion, the serum TNF-αlevel in the BMMSCs treatment effective group was 10.8±5.6 pg/ml vs 40.6±14.8 pg/ml (t=-3.901, P<0.05) before treatment. In the effective group of BMMSCs infusion, IL-10 20±17.4 pg/ml of day 14 was significantly higher than that 7.3±3.1 pg/ml before the treatment (t=-2.850, P<0.05), while , the serum levels of IL-2α, IL-6, IL-8, TNF-α were not statistically significantly different (P>0.05)., Conclusion: The infusion of BMMSC is safe and effective in the treatment of refractory GVHD in children. TNF-αlevel relates with the severity of GVHD. BMMSC may play an anti-GVHD role by up regulating the level of cytokine IL-10 in vivo.- Published
- 2020
- Full Text
- View/download PDF
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