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OBJECTIVES: To investigate the clinical features and prognosis of children with fungal bloodstream infection (BSI) following chemotherapy for acute leukemia (AL). METHODS: A retrospective analysis was performed on 23 children with fungal BSI following chemotherapy for AL in three hospitals in Fujian Province, China, from January 2015 to December 2023. Their clinical features and prognosis were analyzed. RESULTS: Among all children following chemotherapy for AL, the incidence rate of fungal BSI was 1.38% (23/1 668). At the time of fungal BSI, 87% (20/23) of the children had neutrophil deficiency for more than one week, and all the children presented with fever, while 22% (5/23) of them experienced septic shock. All 23 children exhibited significant increases in C-reactive protein and procalcitonin levels. A total of 23 fungal isolates were detected in peripheral blood cultures, with Candida tropicalis being the most common isolate (52%, 12/23). Caspofungin or micafungin combined with liposomal amphotericin B had a relatively high response rate (75%, 12/16), and the median duration of antifungal therapy was 3.0 months. The overall mortality rate in the patients with fungal BSI was 35% (8/23), and the attributable death rate was 22% (5/23). CONCLUSIONS: Fungal BSI following chemotherapy in children with AL often occurs in children with persistent neutrophil deficiency and lacks specific clinical manifestations. The children with fungal BSI following chemotherapy for AL experience a prolonged course of antifungal therapy and have a high mortality rate, with Candida tropicalis being the most common pathogen.
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Leucemia , Humanos , Criança , Masculino , Feminino , Estudos Retrospectivos , Pré-Escolar , Prognóstico , Adolescente , Lactente , Leucemia/tratamento farmacológico , Leucemia/complicações , Antifúngicos/uso terapêutico , Micoses/tratamento farmacológico , Micoses/etiologiaRESUMO
OBJECTIVE: To analyze the clinical characteristics and prognosis of children with hypodiploid B-cell precursor acute lymphoblastic leukemia (BCP-ALL). METHODS: The clinical data of 1 287 children with BCP-ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed. According to the results of chromosome karyotype, all the patients were grouped into hypodiploid subgroup and non-hypodiploid subgroup. The clinical characteristics, early treatment response ï¼»minimal residual disease (MRD) on middle stage of induction chemotherapy and end of induction chemotherapyï¼½ and long-term efficacy ï¼»overall survival (OS) and event-free survival (EFS)ï¼½ were compared. The prognostic factors of hypodiploid BCP-ALL were further explored. RESULTS: Among 1 287 BCP-ALL patientsï¼ 28 patients (2.2%) were hypodiploid BCP-ALL. The proportion of patients with white blood cell count ï¼WBCï¼≥50×109/L in the hypodiploid subgroup was significantly higher than that in the non-hypodiploid subgroup (P =0.004), while there was no statistically significant difference in gender ratio, age group at initial diagnosis, and early treatment response between the two groups (all P >0.05). The 5-year EFS and OS rate of the hypodiploid subgroup were 75.0%(95%CI ï¼66.8%-83.2%) and 77.8%(95%CI ï¼69.8%-85.8%), respectively, which were lower than those of non-hypodiploid subgroup ï¼»EFS: 79.6%(95%CI ï¼78.4%-80.8%); OS: 86.4%(95%CI ï¼85.4%-87.5%)ï¼½, but the difference was not statistically significant (all P >0.05). Further subgroup analysis by risk stratification showed that the 5-year EFS and OS rates of the hypodiploid subgroup were significantly lower than those in the low-risk (LR) group ï¼»LR group EFS: 91.4% (95%CI ï¼88.4%-93.6% ), P < 0.001; OS: 94.7% (95%CI ï¼92.1%-96.4%), P < 0.001ï¼½ ; it was similar to that of BCP-ALL children stratified into intermediate-risk (IR) excluding hypodiploid ï¼»IR group EFS: 79.4%(95%CI ï¼74.9%-83.2%), P =0.343; OS: 87.3%(95%CI ï¼83.6%-90.2%), P =0.111ï¼½; while was higher than that of EFS in HR group, but the difference was not statistically significant ï¼»HR group EFS: 58.7%(95%CI ï¼52.6%-64.8%), P =0.178. OS: 69.9%(95%CI ï¼63.5%-75.4%), P =0.417ï¼½. Univariate analysis showed that gender, age, white blood cell count, and MRD on middle stage of induction chemotherapy had no significant impact on OS and EFS; chromosome count< 40 was a risk factor for lower OS (P =0.026), but has no significant effect on EFS; MRD≥0.01% after induction therapy was a risk factor for lower OS and EFS (P =0.002, and 0.001, respectively). CONCLUSION: Children with hypodiploid BCP-ALL have an intermediate prognosis, and MRD ≥0.01% after induction chemotherapy may be a risk factors for poor prognosis.
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Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Prognóstico , Criança , Estudos Retrospectivos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Taxa de Sobrevida , Neoplasia Residual , Cariótipo , Feminino , Masculino , Pré-Escolar , Cariotipagem , AdolescenteRESUMO
OBJECTIVE: To evaluate the efficacy of acute T-cell lymphoblastic leukemia (T-ALL) in children and explore the prognostic risk factors. METHODS: The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed, and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia (B-ALL) in the same period. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and event-free survival (EFS), and COX proportional hazard regression model was used to evaluate the prognostic factors. Among 116 children with T-ALL who received standard treatment, 78 cases received the Chinese Childhood Leukemia Collaborative Group (CCLG)-ALL 2008 protocol (CCLG-ALL 2008 group), and 38 cases received the China Childhood Cancer Collaborative Group (CCCG)-ALL 2015 protocol (CCCG-ALL 2015 group). The efficacy and serious adverse event (SAE) incidence of the two groups were compared. RESULTS: Proportion of male, age≥10 years old, white blood cell count (WBC)≥50×109/L, central nervous system leukemia, minimal residual disease (MRD)≥1% during induction therapy, and MRD≥0.01% at the end of induction in T-ALL children were significantly higher than those in B-ALL children (P <0.05). The expected 10-year EFS and OS of T-ALL were 59.7% and 66.0%, respectively, which were significantly lower than those of B-ALL (P <0.001). COX analysis showed that WBC≥100×109/L at initial diagnosis and failure to achieve complete remission (CR) after induction were independent risk factors for poor prognosis. Compared with CCLG-ALL 2008 group, CCCG-ALL 2015 group had lower incidence of infection-related SAE (15.8% vs 34.6%, P =0.042), but higher EFS and OS (73.9% vs 57.2%, P EFS=0.090; 86.5% vs 62.3%, P OS=0.023). CONCLUSIONS: The prognosis of children with T-ALL is worse than children with B-ALL. WBC≥100×109 /L at initial diagnosis and non-CR after induction (especially mediastinal mass has not disappeared) are the risk factors for poor prognosis. CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.
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Linfoma de Burkitt , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Criança , Humanos , Masculino , Estudos Retrospectivos , Intervalo Livre de Doença , Prognóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Linfócitos T , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resposta Patológica Completa , Neoplasia Residual/diagnóstico , Neoplasia Residual/tratamento farmacológico , Linfoma de Burkitt/tratamento farmacológicoRESUMO
AbstractObjective: To investigate the clinical characteristics and prognostic factors in childhood acute lymphoblastic leukemia with MLL gene-rearrangement-positive (MLL-r+ ALL). METHODS: The clinical data of 1 414 newly diagnosed children with ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed. The clinical characteristics and efficacy of MLL-r+ and MLL-r- subgroup were compared. The prognostic factors of MLL-r ALL were analyzed by COX regression model. RESULTS: Among all children with ALL, the proportion of patients aged less than 1 year old was 1.8%, and the detection rate of MLL-r+ was 3.4% (48/1 414). The positive detection rate of MLL-r in the age groups <1 year old, and ≥1 year old and ≤14 years old was 38.5% (10/26) and 2.7 (38/1 388), respectively, the difference was statistically significant (P<0.000). Compared with MLL-r- group, the MLL-r+ group had a higher proportion of patients with age <1 year, white blood cell (WBC) count ≥50×109/L, combined central nervous system leukemia (CNSL) and testicular leukemia(TL), while MRD <0.01% on d 33 or d 46 of induction chemotherapy was lower (all P<0.05). The expected 10-year event free survival(EFS) rate and overall survival(OS) rate of the MLL-r+ group were significantly lower than those of the MLL-r- group ï¼EFSï¼ 49.9% vs 77.0%ï¼ OS: 55.3% vs 82.9%ï¼ P<0.05). COX regression model analysis showed that age <1 year, minimal residual disease (MRD) ≥0.01% on d 33 or d 46 of induction chemotherapy were independent risk factors for worse OS and EFS in MLL-r+ ALL patients (all P<0.05). CONCLUSION: Age <1 year old, high WBC, concomitant CNSL and TL are more common in children with MLL-r+ ALL at initial diagnosis, with poor early treatment response and long-term prognosis. Age <1 year old at initial diagnosis and MRD positive after induction chemotherapy may be risk factors for poor prognosis.
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OBJECTIVES: To study the clinical features and prognosis of high hyperdiploid (HHD) childhood acute lymphoblastic leukemia (ALL). METHODS: A retrospective analysis was performed on the medical data of 1 414 children who were newly diagnosed with ALL and were admitted to five hospitals in Fujian Province of China from April 2011 to December 2020. According to karyotype, they were divided into two groups: HHD (n=172) and non-HHD (n=1 242). The clinical features and treatment outcome were compared between the two groups, and the factors influencing the prognosis were further explored. RESULTS: Among the 1 414 children with ALL, 172 (12.16%) had HHD. Compared with the non-HHD group, the HHD group had significantly lower proportions of children with risk factors for poor prognosis at diagnosis (age of onset ≥10 years or <1 year, white blood cell count ≥50×109/L, and T-cell phenotype) or positive fusion genes (TEL-AML1, BCR-ABL1, E2A-PBX1, and MLL gene rearrangement) (P<0.05). The HHD group had a significantly higher proportion of children with minimal residual disease (MRD) <0.01% at the end of induction chemotherapy (P<0.05). The 10-year event-free survival (EFS) rate and overall survival (OS) rate in the HHD group were significantly higher than those in the non-HHD group (P<0.05). The univariate analysis showed that the number of chromosomes of 58-66, trisomy of chromosome 10, trisomy of chromosome 17, bone marrow MRD <1% on day 15 or 19 of induction chemotherapy, and bone marrow MRD <0.01% on day 33 or 46 of induction chemotherapy were associated with a higher EFS rate (P<0.05), and trisomy of chromosome 10 was associated with a higher OS rate (P<0.05). The multivariate Cox analysis showed that trisomy of chromosome 17 was closely associated with a high EFS rate (P<0.05). CONCLUSIONS: The ALL children with HHD have few risk factors for poor prognosis at diagnosis and often have good prognosis. The number of chromosomes and trisomy of specific chromosomes are associated with prognosis in these children.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Trissomia , Criança , Humanos , Estudos Retrospectivos , Prognóstico , Resultado do Tratamento , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Neoplasia Residual , Intervalo Livre de DoençaRESUMO
OBJECTIVE: To analyze the gene mutations of children with juvenile myelomonocytic leukemia (JMML) and their correlation with clinical characteristics. METHODS: The genetic mutation results and clinical data of 19 children with JMML in Fujian from January 2015 to December 2018 were collected and analyzed retrospectively. According to the results of gene mutation, they were divided into PTPN11 gene mutation group and non-PTPN11 gene mutation group, and the clinical characteristics and prognosis of children with JMML between two groups were compared. RESULTS: Among the 19 children with JMML, 14 cases were male and 5 cases were female, and male/female ratio was 2.8â¶1. The median age at diagnosis was 13(3-48) months, and 14 cases (73.68%) were less than 2 years old. Abdominal distension and pyrexia were the common initial symptoms, and all the children with JMML had splenomegaly. The median white blood cell count was 39.82(4.53-103.4)×109/Lï¼and monocyte count was 4.37(1.04-23.12)×109/L. HbF was higher than the normal high value of the same age in 8 cases (42.11%). All JMML children's Philadelphia chromosome and BCR-ABL1 fusion gene were negative. Among the 19 patients, there were 1 case without any JMML related gene mutation, 7 cases (36.84%) with PTPN11 mutation, 6 cases (31.58%) with K-Ras mutation, 2 cases with NF1 mutation (10.53%), 2 cases with N-Ras mutation (10.53%), and 1 case (5.26%) with NF1 and N-Ras mutations simultaneously. Fifteen patients who only received supporting therapy all died, with a median survival time 9.2 (0.4-58.1) months. Whereas, among the four JMML children who received hematopoietic stem cell transplantation(HSCT), three cases survived and only one case died. Compared with the non-PTPN11 gene mutation group, the proportion of patients with hemoglobin F higher than the normal value of the same age was higher, and the median survival time was shorter in PTPN11 gene mutation group, and the differences were statistically significant (P=0.048 and 0.046, respectively). CONCLUSION: JMML is more common in male infancy and toddlerhood, and the main gene mutation types are PTPN11 and Ras mutations. Because the JMML children with PTPN11 mutations show particularly rapid disease progression, if there is no timely intervention, most children die in a short period of time. Therefore, early HSCT may improve the prognosis of the children with JMML.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mielomonocítica Juvenil , Criança , Feminino , Humanos , Lactente , Leucemia Mielomonocítica Juvenil/genética , Masculino , Mutação , Prognóstico , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Estudos Retrospectivos , Proteínas ras/genéticaRESUMO
OBJECTIVE: This study was purposed to detect the expressions of ß-catenin and P-GSK-3 ß in Wnt signaling pathway of patients with mantle cell lymphoma(MCL), and investigate its relationship with the pathogenesis of MCL. METHODS: The expression levels of ß -catenin protein and P-GSK-3 protein in mantle cell lymphoma and hyperplastic lymphadenitis were detected by using anti-ß-catenin, P-GSK-3ß polyclonal antibody and S-P staining technique. RESULTS: The abnormal expression of ß-catenin protein(73.33%) in mantle cell lymphoma group was significantly higher than that (6.7%) in reactive lymph node hyperplasia group (P<0.05); and the positive rate of P-GSK-3 ß(66.67%) in mantle cell lymphoma group was significantly higher than that (16.67%) in reactive hyperplasia of lymph node group (P<0.05). Spearman correlation analysis showed that there was obvious positive correlation (R=0.852, P<0.01). CONCLUSION: The abnormal high expressions of ß-catenin and P-GSK-3 ß protein have been confirmed to appeare in mantle cell lymphoma.
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Linfoma de Célula do Manto , Quinase 3 da Glicogênio Sintase , Glicogênio Sintase Quinase 3 beta , Humanos , Transdução de Sinais , Via de Sinalização Wnt , beta CateninaRESUMO
OBJECTIVE: To investigate the effect of short hairpin RNA (shRNA) and XAV939, a specific inhibitor for ß-catenin, on growth and apoptosis of mantle cell lymphoma(MCL) Jeko-1 cell line. METHODS: ß-catenin shRNA eukaryotic expression vector was transfected into Jeko-1 cells, the antiproliferative effect of shRNA on Jeko-1 cells was detected by RT-PCR and Western blot. The proliferation inhibitory rate of Jeko-1 cells treated by different doses of XAV939 was assayed by MTT method; the level of apoptosis of Jeko-1 cells was detected by flow cytometry; the expression levels of apoptosis-related protein BCL-2, BAX, CyclinD1, C-MYC and Caspase-3 in Jeko-1 cells were determined by Western blot. RESULTS: The expression of ß-catenin mRNA and growth of Jeko-1 cell line were inhibited by shRNA; after Jeko-1 cells treated with 0,2 and 8 µmol/L XAV939 for 48 hours, the cell proliferation rate decreased, while the cell apoptosis rate increased, the expressions of apoptosis-related protein BCL-2, CyclinD1 and C-MYC were down-regulated, on the contrary, the expression of BAX and caspase-3 were up-regulated. CONCLUSION: The specific inhibition of ß-catenin can inhibit Jeko-1 cell proliferation and promote the cell apoptosis.
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Proliferação de Células , Apoptose , Caspase 3 , Linhagem Celular Tumoral , Compostos Heterocíclicos com 3 Anéis , Humanos , Linfoma de Célula do Manto , RNA Mensageiro , RNA Interferente Pequeno , Transfecção , beta CateninaRESUMO
OBJECTIVE: To evaluate the effect of the early use of recombinant human erythropoietin (rhu-EPO) on neurobehavioral development in preterm infants. METHODS: Forty-four preterm infants (30 males and 14 females) were randomly divided into two groups: Rhu-EPO treatment and untreated control (n=22 each). From postnatal day 7, the Rhu-EPO treatment group received intravenous rhu-EPO (250 IU/kg3 times weekly) for 4 weeks. A Neonatal Behavioral Neurological Assessment (NBNA) was performed at 40 weeks of corrected gestational age. A Gesell Development Schedule was used to evaluate neurological development 6 and 12 months after birth. RESULTS: The NBNA score in the rhu-EPO treatment group (36.20+/-0.75) was significantly higher than that in the control group (34.40+/-1.05) at 40 weeks of corrected gestational age (P<0.05). The developmental quotient of fine motor in the rhu-EPO treatment group was significantly higher than that in the control group 6 months after birth (P<0.05). By 12 months after birth, the developmental quotient of gross motor, fine motor and language in the rhu-EPO treatment group was significantly higher than that in the control group (P<0.05). CONCLUSIONS: Early use of Rhu-EPO can promote neurobehavioral development in preterm infants.
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Anemia/prevenção & controle , Encéfalo/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Eritropoetina/uso terapêutico , Comportamento do Lactente/efeitos dos fármacos , Doenças do Prematuro/prevenção & controle , Recém-Nascido Prematuro/crescimento & desenvolvimento , Encéfalo/fisiologia , Feminino , Humanos , Recém-Nascido , Masculino , Proteínas RecombinantesRESUMO
AIM: To evaluate the proportion of CD4(+) CD25(+) Tregs in the peripheral blood of the patients suffering from acute lymphocytic leukemia (ALL) with or without chemotherapy and investigate whether the serum from patients could convert peripheral CD4(+) CD25(-) T cells to CD4(+) CD25(+) Tregs. METHODS: The proportion of CD4(+) CD25(+) T cells in the peripheral blood of three groups of people (the patients with ALL before therapy, the patients with ALL who achieved partial remission (PR) or complete remission (CR) and the healthy donors) was evaluated by flow cytometry. The level of Foxp3 mRNA expression of each group was examined by FQ-RT-PCR. Furthermore mononuclear cells isolated from the peripheral blood of the healthy donors were added to laboratory serum of ALL and control serum of healthy donors respectively. Each group was divided into sub-groups according to various serum doses. After culture for 72 h, the cells of all the groups were harvested separately and further tested for the expression of CD4(+) CD25(+) T cells by flow cytometry. The FQ-RT-PCR method was used to examine the expression of Foxp3 mRNA expression. RESULTS: The percentage of CD4(+) CD25(+) T cells and Foxp3 in the patients with ALL after chemotherapy was significantly higher than that of the healthy donors and the patients with ALL without chemotherapy. Although the proportion of CD4(+) CD25(+) T cells in the patients with ALL without chemotherapy was almost the same with that in the healthy donors, the level of Foxp3 mRNA expression in the former was higher. Moreover, the proportion of CD4(+) CD25(+) T cells and the level of Foxp3 mRNA expression in experimental group were statistically higher than those in control group. The expression of Foxp3 mRNA in control group did not vary with the serum dosage. CONCLUSION: The proportion of CD4(+) CD25(+) Foxp3+Tregs in the peripheral blood of the patients with ALL with or without chemotherapy is significantly higher than that of healthy donors. The serum derived from the patients with ALL can convert CD4(+) CD25(-) T cells to CD4(+) CD25(+) Tregs, which might be one of the important reasons for immunosuppression in ALL.