Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 440
Filter
1.
Pediatr. (Asunción) ; 49(2)ago. 2022.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1386700

ABSTRACT

RESUMEN Introducción: En la Leucemia linfoblástica aguda se han estudiado el rol de factores de riesgo ambientales y genéticos. Menos frecuentemente otros como los perinatales y parentales El objetivo del estudio fue analizar los factores de riesgo ambientales, parentales y perinatales de los niños con Leucemia linfoblástica aguda (LLA) en tratamiento en el servicio de oncología de un hospital pediátrico. Materiales y Métodos: estudio de caso-control, realizado en el departamento de oncohematología de un hospital pediátrico. Los casos fueron niños con diagnóstico de leucemia linfoblástica aguda y los controles niños con patología quirúrgica, previamente sanos pareados por edad. Se estudiaron variables ambientales, perinatales y parentales. Los análisis uni y multivariado fueron realizados en SPSS y los resultados se expresaron en OR con IC 95%. El protocolo fue aprobado por el comité de ética institucional. Resultados: se incluyó 66 casos y 132 controles. El 33,3 (22/66) vs el 8,3% (11/132) OR 5,5 (IC 95% 2,4 - 12,5 p=0,0001 de los casos y controles respectivamente, eran residentes desde el nacimiento de los departamentos con mayor área de cultivos. En el análisis multivariado el riesgo de proceder de departamentos con extensas áreas de cultivo fue 3,6 veces mayor, OR 3,6 (IC 95% 1,4 -9) p=0,008 ajustado por la edad materna, antecedente de hospitalización neonatal, ocupación paterna y exposición a rayos X. Conclusiones: La residencia en zonas con gran extensión de cultivos fue el factor de riesgo ambiental en los niños con LLA de una población hospitalaria.


ABSTRACT Introduction: The role of environmental and genetic risk factors has been studied in acute lymphoblastic leukemia, but other factors, such as perinatal and parental factors, less so. The objective of the study was to analyze the environmental, parental and perinatal risk factors of children with acute lymphoblastic leukemia (ALL) being treated in the oncology department of a pediatric hospital. Materials and methods: This was a case-control study, carried out in the oncohematology department of a pediatric hospital. The cases were children diagnosed with acute lymphoblastic leukemia and the controls were previously healthy children diagnosed with a surgical pathology, matched by age. Environmental, perinatal and parental variables were studied. Univariate and multivariate analysis were performed in SPSS and the results were expressed as OR with 95% CI. The protocol was approved by the institutional ethics committee. Results: We included 66 cases and 132 controls. 33.3% (22/66) vs. 8.3% (11/132) OR 5.5 (95% CI 2.4 - 12.5 p=0.0001) of the cases and controls, respectively, had been residents since birth of the departments with larger farmland crop areas. In the multivariate analysis, the risk of being from departments with extensive crop areas was 3.6 times higher, OR 3.6 (95% CI 1.4 -9, p=0.008) adjusted for maternal age, history of neonatal hospitalizations, paternal occupation, and exposure to X-rays. Conclusions: Residence in areas with a large area of crops was the environmental risk factor in children with ALL in a hospital population.

2.
Hematol., Transfus. Cell Ther. (Impr.) ; 44(2): 143-150, Apr.-June 2022. tab, graf
Article in English | LILACS | ID: biblio-1385039

ABSTRACT

Abstract Introduction Flow cytometric immunophenotyping (FCI) plays a major role in diagnosing hematologic malignancies. In patients diagnosed with precursor B-lineage acute lymphoblastic leukemia (B-ALL), expression of certain non-lineage/cross lineage antigens is of prognostic and cytogenetic relevance. There is a paucity of studies that have comprehensively analyzed the clinical and laboratory profiles of B-ALL patients showing aberrant T/natural killer (NK) cell antigen expression. Materials and methods This is a prospective study where 152 consecutive B-ALL patients were analyzed for aberrant expression of T/NK cell antigens (CD1a, CD5, CD4, CD7, CD8 and CD56) by FCI. The clinical and laboratory profile of these T/NK-cell antigen-expressing B-ALL patients was statistically analyzed against conventional B-ALL patients. Results In our B-ALL cohort, CD5, CD7 and CD56 expression were observed in one, six and nine patients, respectively. CD56-expressing B-ALL patients were predominantly children (89%) and presented as standard clinical risk (p = 0.010) disease with frequent ETV6-RUNX1 fusion (p = 0.021) positivity. On the contrary, CD7-expressing B-ALL patients were adolescent-young adult/adult-age skewed (83%) and had an adverse cytogenetic profile (p = 0.001), especially for the frequent presence of BCR-ABL1 fusion (p = 0.004) and KMT2A rearrangement (p = 0.045). CD7-expressing B-ALL patients had inferior event-free survival (p = 0.040) than their CD56-expressing counterparts, but there was no significant difference in the overall survival (p = 0.317). Conclusion In comparison to conventional B-ALL patients, there are significant differences in the age, cytogenetic profile and event-free survival of T/NK-cell antigen-expressing B-ALL patients.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Young Adult , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Flow Cytometry , Immunophenotyping , Antigens, CD7 , CD56 Antigen
3.
Medicina (B.Aires) ; 82(1): 142-146, feb. 2022. graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1365139

ABSTRACT

Resumen Una mujer de 40 años se internó de forma programada para recibir quimioterapia por una leucemia linfoblástica aguda (LLA) B común de alto riesgo, diagnosticada 10 meses antes a raíz de hemato mas y petequias en los miembros inferiores, y metrorragia. En ese momento, presentaba trombocitopenia y una ecografía ginecológica transvaginal normal. Al ingreso de la internación programada, se quejó de dolor inguinal izquierdo con irradiación al muslo e impotencia funcional de 3 meses de evolución, dolor en fosa ilíaca derecha y diarrea. En el examen físico tenía dolor a la palpación profunda en la fosa ilíaca derecha y signo del psoas positivo a la izquierda. La tomografía de abdomen y pelvis reveló una imagen compatible con un absceso del psoas izquierdo y signos de tiflitis. La biopsia del psoas izquierdo demostró infiltración por nidos y cordones de carcinoma escamoso queratinizante moderadamente diferenciado. El examen ginecológico dirigido evidenció anomalías macroscópicas del cuello uterino correlacionadas con el mismo diagnóstico histopatológico. Los se gundos cánceres primarios más frecuentemente asociados a LLA son linfoma de Hodgkin, cáncer escamoso de piel, tumores endocrinos, cáncer renal, linfoma no-Hodgkin y cáncer de mama. Las metástasis musculares de tumores sólidos son infrecuentes, y habitualmente provienen del pulmón, riñón, tiroides y melanoma. El síndrome del psoas maligno es causado por infiltración neoplásica del músculo. El diagnóstico diferencial debe realizarse con el absceso del psoas, que puede originarse en una tiflitis si es secundario. No hemos podido encontrar registros de cáncer de cuello uterino como segundo cáncer primario luego de LLA.


Abstract A 40-year-old woman was scheduled to receive chemotherapy for a high-risk common B-cell acute lymphoblastic leukemia (ALL), diagnosed 10 months earlier in the wake of lower limb bruising and petechiae, and metrorrhagia. At that time, she had thrombocytopenia and a normal transvaginal gynecological ultrasound. Upon admission, she complained of a 3-month history of incapacitating left groin pain radiated to the thigh, and right lower quadrant abdominal pain associated with diarrhea. On physical examination, she had tenderness in the right iliac fossa and a positive psoas sign on the left. Computerized scan of the abdomen and pelvis reported an image compatible with a left psoas abscess and signs of typhlitis. The biopsy of the left psoas muscle demonstrated infiltration by nests and cords of moderately differentiated keratinizing squamous carcinoma. Gynecological examination revealed macroscopic abnormalities of the cervix correlated with the same histopathological diagnosis. The second primary cancers most frequently associated with ALL are Hodgkin lymphoma, squamous skin cancer, endocrine tumors, kidney cancer, non-Hodgkin lymphoma, and breast cancer. Muscle metastases from solid tumors are rare, and usually arise from the lung, kidney, thyroid, and melanoma. Malignant psoas syndrome is caused by neoplastic infiltration of the muscle. The differential diagnosis should be made with a psoas abscess, which may arise from typhlitis if secondary. We have not been able to find records of cervical cancer as second primary cancer after ALL.

4.
Article in Chinese | WPRIM | ID: wpr-928730

ABSTRACT

OBJECTIVE@#To investigate the mechanism of miR-155 promoting drug resistance of children B-ALL to Ara-C by regulating Wnt/β-Catenin signaling pathway.@*METHODS@#The expression of miR-155 in bone marrow tissue and cell line of B-ALL was detected by PCR. The chemotherapy resistant strain REH/ Ara-C was constructed by using REH cells. REH/ Ara-C cells were transfected with miR-155 inhibitor. The proliferation of REH/Ara-C cells was detected by EdU. The apoptosis of REH/ Ara-C cells was detected by flow cytometry. The drug resistance of REH/Ara-C cells were analyzed by CCK-8 method and colony formation assay. The expression of Wnt/β-Catenin signaling pathway related proteins were determined by Western blot. MiR-155 inhibitor and Wnt activator agonist were used to transfect REH/Ara-C cells, and their effects on cell proliferation, apoptosis and drug resistance were determined.@*RESULTS@#Compared with normal tissues and cells, the expression level of miR-155 in B-ALL bone marrow tissue/cell line was increased (P<0.05); Compared with drug sensitive B-ALL tissues/cell lines, the expression level of miR-155 in drug resistant B-ALL tissues and cell lines was increased (P<0.05); Inhibition of miR-155 expression decreased the proliferation of REH/Ara-C cells (P<0.05), promoted apoptosis (P<0.05), enhanced the cytotoxicity of Ara-C (P<0.05), and inhibited Wnt/β-Catenin signaling pathway related protein and MDR1 gene expression (P<0.05), which could be reversed by activating Wnt expression (P<0.05).@*CONCLUSION@#The expression of miR-155 is up-regulated in bone marrow of children with B-ALL, which may be related to the activation of Wnt/β-Catenin signaling pathway promotes the proliferation of B-ALL cells and inhibits apoptosis, which leads to chemotherapy resistance.


Subject(s)
Apoptosis , Cell Line, Tumor , Cell Proliferation , Child , Cytarabine , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Wnt Signaling Pathway , beta Catenin/genetics
5.
Article in Chinese | WPRIM | ID: wpr-928729

ABSTRACT

OBJECTIVE@#To evaluate the prognosis value of average daily platelet amount increase in children with B-cell acute lymphoblastic leukemia(B-ALL) treated by CCCG-ALL-2015 regimen.@*METHODS@#106 children with primary B-ALL were retrospective analyzed, standardized MRD test protocol was used to detect the MRD level (19 d and 46 d) after chemotherapy. The platelet count was measured by Sysmex XE-2100. Kaplan-Meier survival curve statistics was used to analyze the event free survival(EFS) rate of the children.@*RESULTS@#The trend of negative correlation existed between PPC and TPR (rs=-0.519, P=0.021). The 3-year EFS rate of the patients in Ap>5.4×109/L group was 95.7%, which was significantly higher than those in Ap≤5.4×109/L group(79.5%) (χ2=5.236, P=0.035); multivariate analysis showed that Ap≤5.4×109/L was the independent prognostic factor affecting survival of the patients (RR=3.978; 95%CI: 1.336-11.523, P=0.041). With both MRD and Ap≤5.4×109/L as candidate variables, Ap≤5.4×109/L lost its independent prognostic value (RR=1.225; 95%CI: 0.892-13.696, P=0.089), the correlation between d 19/d 46 MRD levels and Ap>5.4×109/L (χ2=4.318, P=0.038) could explain the phenomenon.@*CONCLUSION@#Ap can reflect the effect of B-ALL chemotherapy and can be used to monitor the curative effect and prognosis of B-ALL children.


Subject(s)
Blood Platelets , Burkitt Lymphoma , Child , Disease-Free Survival , Humans , Neoplasm, Residual/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Prognosis , Retrospective Studies
6.
Article in Chinese | WPRIM | ID: wpr-928727

ABSTRACT

OBJECTIVE@#To detect the expression level of suppressors of cytokine signaling 3 (SOCS3) in acute lymphoblastic leukemia (ALL), and to observe the effect of over-expresson of SOCS3 in Jurkat cells on the cytotoxicity of NK cells.@*METHODS@#The expression levels of SOCS3 mRNA in peripheral blood mononuclear cells of 20 children with ALL and 20 healthy children (normal control group) were detected by RT-PCR. The peripheral blood NK cells from healthy subjects were selected by immunomagnetic technique, and the purity was detected by flow cytometry. SOCS3 was overexpressed in Jurkat cells infected with lentivirus vector, and SOCS3 mRNA expression was detected by RT-PCR after lentivirus infection. The NK cells were co-cultured with the infected Jurkat, and LDH release method was used to detect the cytotoxicity of NK cells on the infected Jurkat cells. The concentrations of TNF-α and IFN-γ were determined by ELISA. The expression of NKG2D ligands MICA and MICB on the surface of Jurkat cells were detected by flow cytometry. Western blot was used to detect the effect of SOCS3 overexpression on STAT3 phosphorylation in Jurkat cells.@*RESULTS@#Compared with the control group, the mRNA expression of SOCS3 in the peripheral blood mononucleated cells of ALL children was significantly decreased. The purity of NK cells isolated by flow cytometry could reach more than 70%. The expression of SOCS3 mRNA in Jurkat cells increased significantly after lentivirus infection. Overexpression of SOCS3 in Jurkat cells significantly promoted the killing ability of NK cells and up-regulated the secretion of TNF-α and IFN-γ from NK cells. The results of flow cytometry showed that the expression of NKG2D ligands MICA and MICB on Jurkat cells increased significantly after SOCS3 overexpression. Western blot results showed that overexpression of SOCS3 significantly reduced the phosphorylation level of STAT3 protein in Jurkat cells.@*CONCLUSION@#SOCS3 mRNA expression was significantly decreased in ALL patients, and overexpression of SOCS3 may up-regulate the expression of MICA and MICB of NKG2D ligands on Jurkat cell surface through negative regulation of JAK/STAT signaling pathway, thereby promoting the cytotoxic function of NK cells.


Subject(s)
Child , Histocompatibility Antigens Class I/metabolism , Humans , Killer Cells, Natural/cytology , Leukocytes, Mononuclear/cytology , Ligands , NK Cell Lectin-Like Receptor Subfamily K/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , RNA, Messenger/genetics , Suppressor of Cytokine Signaling 3 Protein/metabolism , Tumor Necrosis Factor-alpha/metabolism
7.
Article in Chinese | WPRIM | ID: wpr-928725

ABSTRACT

OBJECTIVE@#To explore the effect of hypoxia on the chemosensitivity of B-acute lymphoblastic leukemia (B-ALL) cells to Vincristine (VCR) and the mechanisms.@*METHODS@#B-ALL cells SUP-B15, Nalm-6 and RS4;11 were selected as the research objects. The cells were divided into the control group and the hypoxia mimic group (CoCl2 pretreatment). The two groups were treated with VCR at different concentrations for 24 hours, CCK-8 was used to detect cell viability, flow cytometry was used to detect cell apoptosis, and Western bolt method was used to detect hypoxia inducible factor (HIF-1α), BAX, Bcl-2 and β-actin protein expression. Quantitative real-time fluorescent PCR (qRT-PCR) was used to detect BAX and β-actin mRNA levels.@*RESULTS@#CoCl2 could simulate hypoxic environment to induce the expression of HIF-1α. The cells SUP-B15 and RS4;11 of the hypoxia mimic group were lower sensitivity to VCR as compared with the control group; the apoptosis rate of the hypoxia mimic group was lower than that of the control group after 80 nmol/L VCR treatment. The expression levels of BAX protein and mRNA in the hypoxia mimic group were lower than those of the control group, and there was no significant difference in the expression levels of Bcl-2 protein between two groups.@*CONCLUSION@#Under hypoxic conditions, HIF-1α may mediate VCR resistance in B-ALL cells by downregulating the pro-apoptotic protein BAX.


Subject(s)
Actins/pharmacology , Apoptosis , Cell Hypoxia , Humans , Hypoxia , Hypoxia-Inducible Factor 1, alpha Subunit , Proto-Oncogene Proteins c-bcl-2 , RNA, Messenger , Vincristine/pharmacology , bcl-2-Associated X Protein/pharmacology
8.
Article in Chinese | WPRIM | ID: wpr-928713

ABSTRACT

Acute lymphoblastic leukemia (ALL) is a kind of the most common hematopoietic malignancy, its recurrence and drug resistance are closely related to the bone marrow microenvironment. Bone marrow stromal cell (BMSC) is an important part of the bone marrow microenvironment and their interaction with leukemia cells cannot be ignored. BMSC participates in and regulate signaling pathways related to proliferation or apoptosis of ALL cells by secretes cytokines or extracellular matrix proteins, thus affecting the survival of ALL cells. In this review, the research advance of several signaling pathways of the interaction between BMSC and ALL cells was summarized briefly.


Subject(s)
Apoptosis , Bone Marrow , Bone Marrow Cells , Humans , Mesenchymal Stem Cells , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Stromal Cells , Tumor Microenvironment
9.
Article in Chinese | WPRIM | ID: wpr-928663

ABSTRACT

OBJECTIVE@#To analyze the efficacy of children with B-cell acute lymphoblastic leukemia (B-ALL) without prognostic fusion genes treated by CCLG-ALL 2008, and investigate the related factors affecting the recurrence of the patients.@*METHODS@#B-ALL patients without prognostic fusion genes treated by the protocol of CCLG-ALL 2008 in our hospital from March 2008 to December 2012 were retrospectively analyzed. Follow-up time was ended in August 31, 2019. The median follow-up time was 92 months (range 0-136 months). Kaplan-Meier was used to detect the RFS, and COX multivariate regression analysis was employed to identify the independent factors affecting the recurrence of the patients.@*RESULTS@#There were 140 males and 99 females enrolled in this study. The ratio of male to female was 1.41∶1. The median age was 4.4 years old and the median number of WBC at initial stage was 4.98×109/L. There were 77 cases relapsed during the observation while 162 without relapsed, 16 cases lost to follow-up and 72 cases died. The recurrence and mortality rate was 32.22% and 30.1%, respectively, in which 45 cases died of recurrence (62.5% of the total deaths). Univariate analysis showed that the age≥6 years old, WBC >100×109/L, the bone marrow blasts on day 15≥25%, the bone marrow minimal residual disease (MRD) at week 12 >10-4, and the higher risk were the main factors affecting the recurrence of the patients (P<0.05). Multivariate COX regression analysis showed that age≥6 years old, WBC >100×109/L, bone marrow MRD >10-4 at the 12th week were the independent risk factors affecting recurrence of the patients.@*CONCLUSION@#Age, initial WBC, and bone marrow MRD at the 12th week were correlated with recurrence in children with B-ALL without prognostic fusion genes, which can be used as prognostic indices of recurrence risk in clinical.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Child , Child, Preschool , Disease-Free Survival , Female , Humans , Male , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prognosis , Recurrence , Retrospective Studies
10.
Article in Chinese | WPRIM | ID: wpr-928661

ABSTRACT

OBJECTIVE@#To explore the effect and possible mechanism of dimethyl fumarate (DMF) on T-cell acute lymphoblastic leukemia (T-ALL), and provide experimental and theoretical basis for the clinical treatment of T-ALL.@*METHODS@#Jurkat cells were treated with different concentrations of DMF for 24 hours, and then the proportion and absolute count of Ki67-positive Jurkat cells were analyzed by flow cytometry. Meanwhile, the protein levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and E3 ubiquitin ligase HACE1 in Jurkat cells treated with DMF for 24 hours were evaluated by Western blot. Nrf2 proteins were co-immunoprecipitated in Jurkat cells, and then HACE1 protein was assessed by Western blot. Plasmids of Flag-Nrf2 and different gradients of Flag-HACE1 were transfected into HEK293T cells, and the levels of Flag-Nrf2 were detected by Western blot after 48 hours.@*RESULTS@#DMF could significantly inhibit the proportion and absolute count of Ki67-positive Jurkat cells, and DMF inhibited the proliferation of Jurkat cells in a dose-dependent manner (r=0.9595, r=0.9054). DMF could significantly up-regulate the protein levels of Nrf2 and E3 ubiquitin ligase HACE1 in Jurkat cells (P<0.01, P<0.01). HACE1 physically interacted with Nrf2 in Jurkat cells. Overexpression of Flag-HACE1 significantly increased the protein level of Flag-Nrf2 in a dose-dependent manner (r=0.9771).@*CONCLUSION@#DMF inhibits the proliferation of T-cell acute lymphoblastic leukemia cell. The mechanism may be that, DMF significantly up-regulates the protein levels of Nrf2 and E3 ubiquitin ligase HACE1, and HACE1 interacts with Nrf2 and positively regulates Nrf2 protein level.


Subject(s)
Dimethyl Fumarate/pharmacology , HEK293 Cells , Humans , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , T-Lymphocytes , Ubiquitin-Protein Ligases
11.
Article in Chinese | WPRIM | ID: wpr-928642

ABSTRACT

OBJECTIVES@#To examine the changes of intestinal flora in children newly diagnosed with acute lymphoblastic leukemia (ALL) and the influence of chemotherapy on intestinal flora.@*METHODS@#Fecal samples were collected from 40 children newly diagnosed with ALL before chemotherapy and at 2 weeks, 1 month, and 2 months after chemotherapy. Ten healthy children served as the control group. 16S rDNA sequencing and analysis were performed to compare the differences in intestinal flora between the ALL and control groups and children with ALL before and after chemotherapy.@*RESULTS@#The ALL group had a significant reduction in the abundance of intestinal flora at 1 and 2 months after chemotherapy, with a significant reduction compared with the control group (P<0.05). Compared with the control group, the ALL group had a significant reduction in the diversity of intestinal flora before and after chemotherapy (P<0.05). At the phylum level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Actinobacteria at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05) and a significant increase in the relative abundance of Proteobacteria at 1 and 2 months after chemotherapy (P<0.05). At the genus level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Bifidobacterium at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05); the relative abundance of Klebsiella in the ALL group was significantly higher than that in the control group at 1 and 2 months after chemotherapy and showed a significant increase at 1 month after chemotherapy (P<0.05); the relative abundance of Faecalibacterium in the ALL group was significantly lower than that in the control group before and after chemotherapy and showed a significant reduction at 2 weeks and 1 month after chemotherapy (P<0.05). The relative abundance of Enterococcus increased significantly at 1 and 2 months after chemotherapy in the ALL group (P<0.05), and was significantly higher than that in the control group (P<0.05).@*CONCLUSIONS@#The diversity of intestinal flora in children with ALL is significantly lower than that in healthy children. Chemotherapy significantly reduces the abundance of intestinal flora and can reduce the abundance of some probiotic bacteria (Bifidobacterium and Faecalibacterium) and increase the abundance of pathogenic bacteria (Klebsiella and Enterococcus) in children with ALL.


Subject(s)
Bacteria/genetics , Bifidobacterium , Child , Feces/microbiology , Gastrointestinal Microbiome , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
12.
Article in Chinese | WPRIM | ID: wpr-928641

ABSTRACT

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


Subject(s)
Acute Disease , Antigens, Neoplasm/therapeutic use , Child , Humans , Neoplasm, Residual/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prognosis
13.
Article in English | WPRIM | ID: wpr-928605

ABSTRACT

OBJECTIVES@#To investigate the mutation rate of the RAS gene and its clinical significance in children with acute lymphoblastic leukemia.@*METHODS@#A retrospective analysis was performed on the medical data of 120 children with newly diagnosed acute lymphoblastic leukemia, who were admitted to the Third Affiliated Hospital of Zhengzhou University from January 2015 to January 2020 and underwent next-generation sequencing. The clinical and molecular features were analyzed. The impact of RAS gene mutation on the overall survival rate was evaluated in these children.@*RESULTS@#Among the 120 children, 35 (29.2%) had RAS gene mutation, 30 (25.0%) had KRAS gene mutation, and 5 (4.2%) had both NRAS and KRAS gene mutations. All NRAS mutations and 71% (25/35) of KRAS mutations were located at the 12th and 13th codons. RAS gene mutation was detected in 35 (33.3%) out of 105 children with B-lineage acute lymphoblastic leukemia, but it was not detected in those with acute T lymphocyte leukemia. Of all the children, 11 (9.2%) were lost to follow-up, and among the 109 children followed up, 16 (14.7%) died. The children with RAS gene mutation had a significantly lower 2-year overall survival rate than those without RAS gene mutation (P<0.05). The prognosis of children with RAS gene mutation combined with WT1 overexpression and WBC>50×109/L at diagnosis was worse (P<0.05).@*CONCLUSIONS@#RAS gene mutation is commonly observed in children with B-lineage acute lymphoblastic leukemia and may have an adverse effect on prognosis.


Subject(s)
Child , Genes, ras , Humans , Mutation , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prognosis , Retrospective Studies
14.
Article in English | WPRIM | ID: wpr-928584

ABSTRACT

OBJECTIVES@#To study the changes in the distribution and drug resistance profiles of pathogens causing bloodstream infection after chemotherapy in children with acute lymphoblastic leukemia.@*METHODS@#The medical data were collected from the children with acute lymphoblastic leukemia who were admitted to the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2020 and developed bloodstream infection after chemotherapy. The samples were divided into the first three years group and the next three years group according to the time of testing to investigate the differences in the distribution and drug resistance profiles of pathogens as time.@*RESULTS@#A total of 235 strains of pathogens were isolated, among which there were 159 Gram-negative strains (67.7%; mainly Escherichia coli and Klebsiella pneumoniae), 61 Gram-positive strains (26.0%; mainly Staphylococcus epidermidis), and 15 strains of fungi (6.4%; mainly Candida albicans). There were no significant differences between the first three years group and the next three years group in the detection rate of Gram-negative bacteria (68.8% vs 66.9%, P>0.05) or Gram-positive bacteria (29.2% vs 23.7%, P>0.05). Compared with the first three years group, the next three years group had significant increases in the detection rate of Streptococcus mitis (5.8% vs 0.0%, P<0.05) and fungi (9.4% vs 2.1%, P<0.05). There was no significant difference in the drug resistance rate of Gram-negative or Gram-positive bacteria between the two groups (P>0.05).@*CONCLUSIONS@#Enterobacteriaceae bacteria are the main pathogens of bloodstream infection after chemotherapy in children with acute lymphoblastic leukemia, while the detection rates of Streptococcus mitis and fungi tend to increase as time, which needs to be taken seriously in clinical practice.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Child , Drug Resistance, Bacterial , Gram-Negative Bacteria , Humans , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Retrospective Studies , Sepsis/drug therapy
15.
China Pharmacy ; (12): 1492-1499, 2022.
Article in Chinese | WPRIM | ID: wpr-927198

ABSTRACT

OBJECTIVE To systema tically evaluate the efficacy and safety of blinatumomab for acute lymphoblastic leukemia (ALL)in order to provide evidence-based reference for clinical use. METHODS Retrieved from PubMed ,Embase,Web of Science,the Cochrane Library ,CNKI,Wanfang database and CBM during the inception to February 3,2022,randomized controlled trials (RCTs)and cohort studies of blinatumomab (experimental group ) versus conventional chemotherapy (control group )in the treatment of ALL were collected. After literature screening and data extraction ,the quality of RCTs was evaluated by the risk bias evaluation tool recommended by Cochrane handbook 5.1.0,and the quality of cohort studies was evaluated by the Newcastle-Ottawa scale (NOS). Meta-analysis was performed by RevMan 5.4 software. GRADE grading system was used to evaluate the evidence quality of outcomes. The publication bias was analyzed by inverted funnel plot. RESULTS A total of 8 studies were included ,involving 3 RCTs and 5 cohort studies ,with a total of 2 841 patients. Results of Meta-analysis showed that the overall survival rate more than one year [RR =1.30,95%CI(1.14,1.48),P<0.000 1],relapse-free survival rate [RR =1.78,95%CI(1.50,2.12),P<0.000 01],complete remission rate [RR =1.42,95%CI(1.11,1.82),P=0.006],the incidence of tremor [RR =16.98,95%CI(2.17,133.12),P=0.007],and the incidence of cytokine release syndrome [RR =14.11, 95%CI(3.43,58.01),P=0.000 2] in trial group were all significantly higher than control group ,but there was no statistical significance in the incidence of headache between two groups [RR =1.31,95%CI(0.66,2.59),P=0.44]. The incidence of adverse events with grade more than or equal to 3,infection,stomatitis,thrombocytopenia,febrile neutropenia ,anorexia, constipation,diarrhea,abdominal pain ,hypokalemia in trial group were significantly lower than control group (P<0.05). The incidence of cough ,rash and hypogamma globulinemia and fever in the trial group were significantly higher than control group (P<0.05). There was no statistical significance in the total incidence of adverse events ,sepsis,anemia,leucopenia,neutropenia, lymphopenia,nausea,vomiting,hyperglycemia,hypotension,hypertension,elevated transaminase or epistaxis between two groups(P>0.05). Results of subgroup analysis by study type showed that the overall survival rate ,relapse-free survival rate and complete response rate (except for cohort studies )of patients in trial group were significantly higher than control group in both RCTs and cohort studies (P<0.05). The results of GRADE evaluation showed that the overall quality of index evidence included in this study was low. There was little possibility of publication bias in this study based on the publication bias analysis. CONCLUSIONS Blinatumomab is effective in the treatment of ALL ,with low incidence of infection and adverse events of digestive system ,but high incidence of tremor ,cough,rash,fever,hypoproglobulinemia and cytokine release syndrome. The evidence quality of the indicators included in this study is generally low .

16.
Frontiers of Medicine ; (4): 139-149, 2022.
Article in English | WPRIM | ID: wpr-929189

ABSTRACT

The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.


Subject(s)
Antigens, CD19/therapeutic use , Antineoplastic Agents/pharmacology , Humans , Immunotherapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , T-Lymphocytes
17.
Article in Chinese | WPRIM | ID: wpr-930527

ABSTRACT

Objective:To analyze the early risk warning factors of clinical characteristics in children with acute lymphoblastic leukemia (ALL) complicated with acute pancreatitis (AP).Methods:Retrospective study.A total of 39 children with ALL complicated with AP admitted to the Hematology Center of Beijing Children′s Hospital, Capi-tal Medical University from May 2018 to December 2020 were selected as the case group, and 78 ALL patients were randomly selected as the control group according to the exact matching of 1∶2 of the same age and sex.The measurment data and counting data were analyzed by Rank sum test ( Mann Whitney U test) and χ2 test between the 2 groups, respectively, and further multivariate Logistic regression analysis was performed to find out the risk factors of ALL complicated with pancreatitis.At the same time, the relationship between each index and severity was explored. Results:The incidence of ALL complicated with AP was 8.55% (39/456 cases). The high incidence age was 3-10 years old.Sixty-four point nine percent (24/37 cases) of the pancreatitis occurred in the early stage of chemotherapy, and 66.7% (26/39 cases) was associated with asparaginase.There were significant differences in ALL risk stratification ( χ2=21.404, P<0.001), C-reactive protein (CRP)( U=232.000, P<0.001), procalcitonin (PCT)( t=3.950, P<0.001), hematocrit( t=3.981, P<0.001), serum calcium( t=-9.609, P<0.001), indirect bilirubin( U=1 142.000, P<0.05), triglyceride( t=3.600, P=0.001) and albumin( t=-6.296, P<0.001) between the 2 groups.The sensitivity of abdominal CT, abdominal ultrasound and pancreatic magnetic resonance imaging in the case group were 70.8%, 81.6% and 100.0%, respectively.Multivariate Logistic regression analysis showed that differences between albumin( OR=11.444, 95% CI: 3.240-40.423), triglyceride( OR=18.047, 95% CI: 5.020-65.074) and risk stra-tification( OR=8.894, 95% CI: 1.889-41.885) were statistically significant, and there were obvious differences in PCT( U=3.000, 2.000, all P<0.05) and serum calcium( U=4.500, 8.500, all P<0.05) between patients with severe pancreatitis and patients with mild or moderate severe pancreatitis. Conclusions:ALL complicated with AP often occurs in the early stage of chemotherapy, mainly caused by asparaginase.In imaging examination, the sensitivity of pancreatic magnetic resonance imaging is the highest, followed by abdominal ultrasound.Risk stratification, decreased albumin and elevated triglyceride are risk factors of ALL complicated with AP, which are helpful for early identification of high-risk patients with ALL complicated with AP.PCT and serum calcium may play an important role in severe pancreatitis.

18.
Article in Chinese | WPRIM | ID: wpr-929834

ABSTRACT

Objective:To evaluate systematically the association between the c. 415>C polymorphism of NUDT15 gene and the toxicity of 6-mercaptopurine(6-MP)in children with acute lymphoblastic leukemia(ALL).Methods:The literatures in domestic and foreign databases were retrieved: PubMed, EmBase, Cochrane Library, CNKI, CBM, VIP Chinese Sci-tech Journal Database, and Wanfang Database.The language was limited to Chinese or English.A case-control study or cohort study of 6-MP treatment in pediatric ALL related to the toxicity of the NUDT15 gene c. 415>C polymorphism was included.The time of search was set from the establishment of the database to October 1st, 2020.Two researchers screened the literature independently, extracted data from the literature that met the inclusion criteria, and evaluated the quality of the included studies.The association between locus polymorphism and toxicity during 6-MP chemotherapy was analyzed by Meta analysis with Rev Man 5.3 and Stata 12.0 software.Results:Nine studies were finally included, eight of which were cohort studies and one was a case-control study, with a total of 1 068 patients.The results showed that under the five genetic models, the mutation at c. 415>C of NUDT15 gene was significantly associated with the risk of leukopenia and neutropenia( P<0.01), while hepatotoxicity was with no significant association between the occurrence risk of damage( P>0.05). Conclusion:The mutation at c. 415>C of NUDT15 gene significantly increased the incidence of leukopenia and neutropenia during 6-MP chemotherapy, while there was no significant effect on the occurrence of hepatotoxicity.

19.
Article in Chinese | WPRIM | ID: wpr-929792

ABSTRACT

Acute lymphoblastic leukemia(ALL)is the most common malignant tumor in childhood, and T-ALL accounts for 10%~15% of all in children with ALL.Based on the application of MICM classification, risk stratification and multi-drugs intensive therapy, the prognosis of children with T-ALL has been improved, but the overall survival rate and event free survival rate are still less than 70%, and the overall survival rate of relapsed / refractory T-ALL is less than 10%.The treatment of T-ALL in children still faces great challenges.CDl9 targeted chimeric antigen receptor(CAR)modified T cells have shown impressive results in children with refractory B-ALL, with remission rate of 70%~90%.The emergence of CAR-T and CAR modified NK cells(CAR-NK)targeted therapy is expected to improve the prognosis of T-ALL in children.This article reviews the latest progress of CAR-T and CAR-NK in children with T-ALL.

20.
Frontiers of Medicine ; (4): 442-458, 2022.
Article in English | WPRIM | ID: wpr-939877

ABSTRACT

T-cell acute lymphoblastic leukemia (T-ALL) is one of the most dangerous hematological malignancies, with high tumor heterogeneity and poor prognosis. More than 60% of T-ALL patients carry NOTCH1 gene mutations, leading to abnormal expression of downstream target genes and aberrant activation of various signaling pathways. We found that chidamide, an HDAC inhibitor, exerts an antitumor effect on T-ALL cell lines and primary cells including an anti-NOTCH1 activity. In particular, chidamide inhibits the NOTCH1-MYC signaling axis by down-regulating the level of the intracellular form of NOTCH1 (NICD1) as well as MYC, partly through their ubiquitination and degradation by the proteasome pathway. We also report here the preliminary results of our clinical trial supporting that a treatment by chidamide reduces minimal residual disease (MRD) in patients and is well tolerated. Our results highlight the effectiveness and safety of chidamide in the treatment of T-ALL patients, including those with NOTCH1 mutations and open the way to a new therapeutic strategy for these patients.


Subject(s)
Aminopyridines , Benzamides , Cell Line, Tumor , Humans , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Receptor, Notch1/metabolism , Signal Transduction , T-Lymphocytes/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL