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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(9): 890-893, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31506148

RESUMO

OBJECTIVE: To study the long-term clinical effect of the CCLG-ALL2008 regimen in the treatment of children newly diagnosed with acute lymphoblastic leukemia (ALL) with different molecular biological features. METHODS: A total of 940 children who were newly diagnosed with ALL were enrolled in this study. The children were treated with the CCLG-ALL2008 regimen. A retrospective analysis was performed for the long-term outcome of ALL children with different molecular biological features. RESULTS: Among the 940 children with ALL, there were 570 boys and 370 girls, with a median age of onset of 5 years (range 1-15 years) and a median follow-up time of 65 months (range 3-123 months). The complete response (CR) rate was 96.7%, the predicted 10-year overall survival (OS) rate was 76.5%±1.5%, and the event-free survival (EFS) rate was 62.6%±3.0%. After CR was achieved after treatment, the overall recurrence rate was 21.9%. The children with positive ETV6-RUNX1 had the lowest recurrence rate and were prone to late recurrence, and those with positive MLL rearrangement had the highest recurrence rate and were prone to early recurrence. The children with positive ETV6-RUNX1 had a significantly higher predicted 10-year OS rate than those with positive TCF3-PBX1, BCR-ABL, or MLL rearrangement and those without molecular biological features (P<0.05). The children with positive ETV6-RUNX1 had a significantly higher predicted 10-year EFS rate than those with positive BCR-ABL or MLL rearrangement (P<0.05). CONCLUSIONS: Molecular biological features may affect the long-term prognosis of children with ALL, and positive MLL rearrangement and BCR-ABL fusion gene are indicators of poor prognosis. Children with positive ETV6-RUNX1 fusion gene have the highest long-term survival rate.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Proteínas de Fusão bcr-abl , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Estudos Retrospectivos
2.
Zhonghua Xue Ye Xue Za Zhi ; 40(8): 625-632, 2019 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-31495127

RESUMO

Objective: To compare the difference of efficacy between traditional Hyper-CVAD/MA regimen and the adolescents inspired chemotherapy regimen, CH ALL-01, in treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) . Methods: In this study we retrospectively analyzed 158 Ph(+) ALL patients receiving Hyper-CVAD/MA regimen (n=63) or CHALL-01 regimen (n=95) in our center and Changzheng hospital from January 2007 to December 2017, excluding patients with chronic myeloid leukemia in blast crisis. Tyrosine kinase inhibitor (TKI) was administered during induction and consolidation chemotherapy. Patients who underwent hematopoietic stem cell transplantation received TKI as maintenance therapy. Results: Of them, 91.1% (144/158) patients achieved complete remission (CR) after 1-2 courses of induction. CR rate was 90.5% (57/63) for patients in Hyper-CVAD/MA group and 91.6% (87/95) for patients in CHALL-01 group. There was no difference in CR rates between the two groups (χ(2)=0.057, P=0.811) . The last follow-up was June 2018. A cohort of 134 CR patients could be used for further analysis, among them, 53 patients received Hyper-CVAD/MA regimen and other 81 patients received CHALL-01 regimen. The molecular remission rates were significantly higher in CHALL-01 group (complete molecular response: 44.4%vs 22.6%; major molecular response: 9.9% vs 18.9%) (χ(2)=7.216, P=0.027) . For the patients in Hyper-CVAD/MA group, the 4-year overall survival (OS) was 44.81% (95%CI: 30.80%-57.86%) and the 4-year disease free survival (DFS) was 37.95% (95%CI: 24.87%-50.93%) . For patients received CHALL-01 regimen, the 4-year OS was 55.63% (95%CI: 39.07%-69.36%) (P=0.037) and 4 year DFS was 49.06% (95%CI: 34.24%-62.29%) (P=0.015) , while there was no significant difference in 4 year cumulative incidence of relapse (CIR) (P=0.328) or cumulative incidence of nonrelapse mortality (CI-NRM) (P=0.138) . The rate of pulmonary infection was lower in patients received CHALL-01 regimen compared with patients received Hyper-CVAD regimen (43.4% vs 67.9%, χ(2)=7.908, P=0.005) . Conclusions: Outcome with CHALL-01 regimen appeared better than that with the Hyper-CVAD/MA regimen in Ph(+) ALL, which has lower incidence of pulmonary infection, higher molecular remission rate and better OS and DFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Ciclofosfamida , Dexametasona , Doxorrubicina , Humanos , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Retrospectivos , Vincristina
3.
Medicine (Baltimore) ; 98(33): e16811, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415396

RESUMO

Glucocorticoids used to treat acute lymphoblastic leukemia (ALL) are associated with cytotoxicity and obesity. The aim of the study was to investigate the effects of high-proportion medium chain triglyceride (MCT) on body fat distribution and levels of leptin and adiponectin during chemotherapy of children with ALL.New-onset ALL children treated at the Guangzhou Women and Children's Medical Center between March 2016 and March 2017 were enrolled. Children were divided into the MCT and control groups. For the MCT group, high-proportion MCT nutrition preparation was added to the diet, while no MCT was added for the control group. The MCT group was further divided into subgroups A and B based on the amount of supplement. Waist circumference, hip circumference, waist-to-hip ratio, bone marrow concentrations of leptin and adiponectin, and leptin-to-adiponectin ratio were measured before and on days 19 and 46 of chemotherapy. Body weight and body mass index (BMI) were measured on admission and discharge.Waist circumference in the control group increased by day 46 (P = .047), but did not change in the MCT group. The BMI of the children in the control group was higher than those in the MCT group on admission (P = .003), but not different at discharge. No significant differences in hip circumference, leptin levels, adiponectin levels, and body weight were observed between the 2 groups.This preliminary study suggests that short-term supplementation of high-proportion MCT nutrition preparation may help reduce the centripetal distribution of adipose induced by the application of glucocorticoids in children with ALL. This will have to be confirmed in future studies.


Assuntos
Adiponectina/sangue , Adiposidade/efeitos dos fármacos , Suplementos Nutricionais , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Triglicerídeos/farmacologia , Distribuição da Gordura Corporal , Índice de Massa Corporal , Peso Corporal , Criança , Pré-Escolar , Feminino , Glucocorticoides/efeitos adversos , Humanos , Leptina/sangue , Masculino , Obesidade/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Circunferência da Cintura
4.
Rinsho Ketsueki ; 60(7): 773-778, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31391365

RESUMO

A 62-year-old man was referred to our hospital due to pancytopenia and abnormal leukocyte fraction in December 2016. Bone marrow aspiration showed a massive proliferation of blast cells (96%) with rich myeloperoxidase-negative basophilic granules. He was diagnosed with acute basophilic leukemia, and an appropriate treatment for acute myelogenous leukemia was initiated. Blast cells were positive for minor BCR-ABL mutations, and chemotherapy using imatinib was initiated on day 7. The treatment was effective and complete remission was achieved on day 30. The ultrastructural features of blast cells showed typical basophilic granules with high electron density structure on electron microscopy. However, immunohistochemical analysis were positive for CD79a, PAX5, and TdT expression. Rearrangements of immunoglobulin heavy chain and T-cell receptor genes were detected, prompting the diagnosis of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) with basophilic change. The patient continued to be treated with the imatinib combination regimen, as well as umbilical cord blood transplantation. The patient has currently achieved recurrence-free survival. This case represents a rare divergence between morphology and molecular condition.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Proteínas de Fusão bcr-abl , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucócitos , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Indução de Remissão
5.
Anticancer Res ; 39(7): 3531-3542, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262877

RESUMO

BACKGROUND/AIM: Recently, we demonstrated the ability of inhibitors of protein kinase 2 (casein kinase II; CK2) to enhance the efficacy of 5-fluorouracil, a thymidylate synthase (TYMS)-directed drug for anticancer treatment. The present study aimed to investigate the antileukemic effect of simultaneous inhibition of dihydrofolate reductase (DHFR), another enzyme involved in the thymidylate biosynthesis cycle, and CK2 in CCRF-CEM acute lymphoblastic leukemia cells. MATERIALS AND METHODS: The influence of combined treatment on apoptosis and cell-cycle progression, as well as the endocellular level of DHFR protein and inhibition of CK2 were determined using flow cytometry and western blot analysis, respectively. Real-time quantitative polymerase chain reaction was used to examine the influence of silmitasertib (CX-4945), a selective inhibitor of CK2 on the expression of DHFR and TYMS genes. RESULTS: The synergistic effect was correlated with the increase of annexin V-binding cell fraction, caspase 3/7 activation and a significant reduce in the activity of CK2. An increase of DHFR protein level was observed in CCRF-CEM cells after CX-4945 treatment, with the mRNA level remaining relatively constant. CONCLUSION: The obtained results demonstrate a possibility to improve methotrexate-based anti-leukemia therapy by simultaneous inhibition of CK2. The effect of CK2 inhibition on DHFR expression suggests the important regulatory role of CK2-mediated phosphorylation of DHFR inside cells.


Assuntos
Antineoplásicos/farmacologia , Antagonistas do Ácido Fólico/farmacologia , Metotrexato/farmacologia , Naftiridinas/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Apoptose/efeitos dos fármacos , Caseína Quinase II/antagonistas & inibidores , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Tetra-Hidrofolato Desidrogenase/metabolismo
6.
Anticancer Res ; 39(6): 3255-3264, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177176

RESUMO

BACKGROUND/AIM: Chemotherapy-induced cardiotoxicity may be observed during treatment or may cause severe cardiac failure as the main cause of death, even several years after therapy implementation. Herein, the aim was to establish the early diagnosis of cardiotoxicity through the periodic evaluation of the left ventricular (LV) and vascular remodeling parameters, in patients with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: The study population included 35 patients diagnosed with ALL, evaluated before and 3 months after starting chemotherapy, measuring systolic and diastolic parameters of the LV and intima-media thickness (IMT), arterial stiffness aortic pulse wave velocity (PWVAo) and ankle-brachial index (ABI). RESULTS: After the first 2 cycles of chemotherapy, all patients experienced a drop in LV ejection fraction (LVEF) (p<0.001), and 12 patients suffered a decrease of LVEF<50%. The ABI (p<0.05) and the global longitudinal strain (GLS) (p<0.001) decreased, while IMT and PWVAo (p<0.001) increased, proving a subclinical deterioration of the LV function and vascular remodeling. CONCLUSION: Assessment of cardiovascular risk factors before chemotherapy initiation in ALL patients may be helpful for an early diagnosis of chemotherapy-induced cardiotoxicity, thus contributing to early treatment and a subsequent decrease of death caused by such cardiovascular complications.


Assuntos
Índice Tornozelo-Braço , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Ecocardiografia Doppler , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto , Cardiotoxicidade , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/fisiopatologia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Valor Preditivo dos Testes , Fatores de Risco , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Remodelação Vascular/efeitos dos fármacos , Rigidez Vascular/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Adulto Jovem
7.
Int J Clin Pharmacol Ther ; 57(8): 402-407, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31232278

RESUMO

OBJECTIVE: To investigate the population pharmacokinetics of delayed methotrexate (MTX) excretion in children with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A total of 1,659 plasma concentration samples of MTX from 190 patients with 1 - 4 courses (plasma concentrations > 0.1 µmol/L) were collected in this study. The data analysis was performed using Phoenix NLME 1.3 software. The covariates included age, body surface area (BSA), body weight, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminase (ALT), total bilirubin (TBIL), and serum creatinine (SCr). The final model was validated by bootstrap resampling procedures (1,000 runs) and visual predictive check (VPC) method. RESULTS: The data were best described by a two-compartment linear pharmacokinetic model. The mean values of clearance (CL) and distribution volume (Vd) of MTX were 6.53 L/h and 67.88 L, respectively. Analysis of covariates showed that BSA influenced the CL of MTX. CONCLUSION: The final model was demonstrated as appropriate and effective for assessing the pharmacokinetic parameters of delayed MTX excretion in children with ALL.


Assuntos
Antimetabólitos Antineoplásicos/farmacocinética , Metotrexato/farmacocinética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Aspartato Aminotransferases/metabolismo , Bilirrubina/sangue , Criança , Creatinina/sangue , Humanos
8.
J Cancer Res Clin Oncol ; 145(8): 1987-1998, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31214760

RESUMO

PURPOSE: Based on the poor prognosis of drug resistance in pediatric acute lymphoblastic leukemia (ALL) and adverse effects of chemotherapy, this study was aimed to evaluate the effect of several herbal extracts on leukemic cells. METHODS: Two subtypes of T- and B-ALL cell lines, followed by ALL primary cells were treated with cinnamon, ginger, and green tea extracts, alone or in combination with methotrexate (MTX). Possible apoptosis was investigated using Annexin-V/PI double staining. Real-time PCR was applied to evaluate the expression levels of related ABC transporters upon combination therapy. RESULTS: The IC50s for cinnamon, ginger and green tea extracts on ALL cell lines were 300 µg/ml, 167 µg/ml and 70 µg/ml, respectively. Surprisingly, the methotrexate (MTX)-resistant sub-line showed more sensitivity to ginger. Combined treatment with ginger and MTX showed synergistic effects on CCRF-CEM, Nalm-6 and ALL primary cells. It was shown that ginger does not impair the high expression levels of ABCA2 or ABCA3 transporter genes in the ALL malignant cells, suggesting other molecular pathways involved in its anticancer potential. CONCLUSION: To the best of our knowledge, this is the first study that reveals the antileukemic effect of ginger extract on both, pediatric ALL cell lines and primary cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Gengibre/química , Extratos Vegetais/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Cinnamomum zeylanicum/química , Terapia Combinada , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Fitoterapia , Extratos Vegetais/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Chá/química , Células Tumorais Cultivadas , Adulto Jovem
9.
Int J Pediatr Otorhinolaryngol ; 123: 1-4, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31048222

RESUMO

OBJECTIVES: To describe three new cases of vincristine-induced vocal cord paresis or paralysis (VIVCPP) in children and to review the diagnosis and management of this neuropathy. METHODS: Retrospective case series. Diagnosis of VIVCPP was confirmed by laryngoscopy in all children. RESULTS: Less than 20 cases of VIVCPP in children have been previously documented in the literature. Of the three children in our case series, one had unilateral vincristine-induced vocal cord paresis and two had bilateral VIVCPP. The first two patients each had two separate episodes of paresis, lasting 4 months and 1 month respectively. In the last patient, whose medical course was complicated by many additional factors, vocal cord paralysis persisted for over three years. CONCLUSIONS: Clinicians must evaluate children with suspected VIVCPP for concomitant symptoms and signs of vincristine neuropathies and examine the vocal cords via laryngoscopy. The effects of vincristine neurotoxicity can be waxing and waning, demonstrate delayed onset and persist well beyond drug cessation. Further studies are needed to identify effective neuroprotectants and delineate appropriate vincristine dosing in patients with vincristine neurotoxicity and cancer.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Vincristina/efeitos adversos , Paralisia das Pregas Vocais/induzido quimicamente , Adolescente , Pré-Escolar , Feminino , Humanos , Laringoscopia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Retrospectivos , Paralisia das Pregas Vocais/diagnóstico por imagem , Prega Vocal/diagnóstico por imagem
10.
J Coll Physicians Surg Pak ; 29(6): 549-552, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31133155

RESUMO

OBJECTIVE: To determine the frequency of cytogenetic type and its significance in the prognostic outcome of the pediatric patients in acute lymphoblastic leukemia (ALL), aged 1 to 15 years, and also determine the importance of minimal residual disease (MRD) in the management of the condition. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Pediatric Oncology Ward, Shaukat Khanum Cancer Hospital, Lahore, from January 2015 to July 2017. METHODOLOGY: Patients aged 1-15 years, diagnosed with ALL, were included. Studied variables were cytogenetic type and MRD outcome in patients with ALL. Patients under one year of age and more than 15 years, or those having comorbidities, were excluded. RESULTS: Total 150 patients' data were retrieved from the Hospital database. One hundred and thirty-three belonged to age 1 to 5 years group (89%) and 17 (11%) were in 5 to 10 years group. The mean age of the patient was 4.3 +3.1 years. One hundred and two (68%) were males; whereas, 48 (32%) were females. Pre B acute lymphoblastic leukemia was diagnosed in 139 (93%) patients and 11(7%) were diagnosed with Pre T acute lymphoblastic leukemia. Standard risk was observed in 120 (80%) patients and 30 (20%) patients were on high risk as per National Cancer Institute (NCI) Guidelines. Regimen A was used in 125 (83.3%), Regimen B in 16 (10.7%), and Regimen C in 9 (6%) patients. BCR-ABL was positive in 2 (1.30%), TEL-AML in 68 (45%), MLL in 5 (3.30%), and normal in 54 (36%). MRD at day 29 was negative in 40 (93%) and positive in 3 (7%). The karyotyping was done in 128 (85%) patients, out of which 68 (53%) were hyperploids, 41 (32%) euploid, and 19 (15%) were hypoploid. Death was observed in 22 (15%) patients. Nineteen (86%) deaths were due to fungal and bacterial sepsis; and disease-related deaths were noted in 3 (14%) patients. CONCLUSION: The role of MRD and cytogenetics in risk assessment has improved in the early prognosis determination.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasia Residual/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Criança , Pré-Escolar , Citogenética , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Lactente , Masculino , Neoplasia Residual/mortalidade , Neoplasia Residual/patologia , Paquistão/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
11.
J Clin Neurosci ; 66: 149-155, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31104963

RESUMO

Our previous study revealed altered resting-stated brain function in children with acute lymphoblastic leukemia (ALL) on new-onset stage. To investigate the effects after induction chemotherapy, a pilot self-contrast study was conducted to compare the difference in resting-stated brain function between pre- and post-induction chemotherapy of ALL. Fractional amplitude of low-frequency fluctuation (fALFF) was employed for fMRI data analysis. Clinical and resting state functional magnetic resonance imaging (RS-fMRI) data of 14 new-onset pediatric ALL patients were collected before and after 3 months of induction chemotherapy. Fourteen age- and gender-matched healthy controls (HCs) were recruited for comparison. Before induction chemotherapy, fALFF values of ALL patients decreased globally, especially in the default mode network (DMN), left frontal lobe, left occipital lobe, and bilateral postcentral gyri as compared to HCs. After induction chemotherapy, fALFF values of ALL patients decreased significantly in the bilateral cuneus, left lingual and calcarine gyri, and left mid frontal gyrus. Paired-sample t-tests and self-contrast analysis showed fALFF increased in the left precuneus, bilateral cuneus, left occipital lobe, bilateral frontal gyri, and bilateral temporal lobes, whereas fALFF in the bilateral precuneus decreased in the ALL patients after induction, which suggests potential side-effects of the treatment. The alteration of fALFF values suggested that resting brain function was impaired before induction chemotherapy and mostly recovered after treatment. This study suggested that fALFF is a reliable and feasible tool in detecting spontaneous brain activity to monitor early neurocognitive impairments in pediatric ALL to better understand the underlying neurobiological mechanisms of chemotherapy on the brain.


Assuntos
Mapeamento Encefálico , Encéfalo/diagnóstico por imagem , Quimioterapia de Indução , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Criança , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Projetos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
12.
Hematology ; 24(1): 467-472, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31126219

RESUMO

Introduction: Children with newly diagnosed acute lymphoblastic leukemia (ALL) present with low peripheral blood counts caused by bone marrow replacement. The recovery of counts during induction chemotherapy is not well described. Material and methods: Records for 63 children with ALL were reviewed. Peripheral hematology blood counts during five weeks of induction chemotherapy were extracted, and the time to partial recovery with safe counts and complete recovery with normal counts in the three cell lines determined. The number of red cell and platelet transfusions, the number of febrile episodes, and the number of days on intravenous antibiotics were counted. Results: Platelet recovery occurred early: median time to achieving counts >50/nL 14 days, to counts >100/nL 16 days. Neutrophil recovery was relatively slow: median time to counts >0.5/nL 18 days, to counts >1.0/nL 26 days. The time to partial recovery was shorter in high risk than in lower-risk treatment groups. Partial platelet recovery by day 15 indicated early recovery and lower morbidity. Complete platelet recovery day 15 was significantly associated with residual disease <0.1% after four weeks. Lymphocyte counts showed a marked decrease in first two weeks followed by a rise in the next three weeks; a count <0.35/nL on day 15 was associated with poor response. Conclusion: After starting chemotherapy for ALL, platelet recovery can be expected after two to three weeks while neutrophil recovery lasts three to five weeks. Platelet and lymphocyte counts after two weeks treatment may give an indication of residual disease after four weeks.


Assuntos
Contagem de Células Sanguíneas/métodos , Quimioterapia de Indução/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Feminino , Humanos , Masculino , Fatores de Tempo
14.
Mymensingh Med J ; 28(2): 465-469, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31086168

RESUMO

We report three cases of acute lymphoblastic leukemia (ALL) those were suffered from cytomegalovirus retinitis (CMVR) during maintenance phase therapy. Ophthalmologic examination for loss of vision prompted diagnosis of cytomegalovirus retinitis. Administration of anticytomegalovirus drugs led to complete regression of active retinitis. CMVR should be in mind for children with ALL on maintenance of medical aid, even in those without hematopoietic stem cell transplantation state.


Assuntos
Retinite por Citomegalovirus/diagnóstico , Olho/virologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Doença Aguda , Antineoplásicos/efeitos adversos , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Criança , Citomegalovirus , Retinite por Citomegalovirus/tratamento farmacológico , Retinite por Citomegalovirus/virologia , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Acuidade Visual
15.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(5): 405-410, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31104652

RESUMO

OBJECTIVE: To study the long-term clinical effect of CCLG-ALL2008 regimen in the treatment of children and adolescents, aged >10 years, with newly diagnosed acute lymphoblastic leukemia (ALL). METHODS: A retrospective analysis was performed for the clinical data of 150 ALL children and adolescents aged >10 years who were treated with CCLG-ALL2008 regimen from April 2008 to April 2015. The Kaplan-Meier method was used to analyze overall survival (OS) rate and event-free survival (EFS) rate. RESULTS: Among the 150 children and adolescents, there were 87 (58.0%) boys and 63 (42.0%) girls, with a median age of 11 years (range 10-15 years). Of the 150 children and adolescents, 84 (56.0%) had intermediate risk and 66 (44.0%) had high risk; 122 (81.3%) had B-lineage acute lymphoblastic leukemia (B-ALL) and 28 (18.7%) had T-lineage acute lymphoblastic leukemia (T-ALL). The fusion gene test yielded positive results in 51 children and adolescents (34.0%), among whom 16 (31%) had positive BCR-ABL, 11 (22%) had positive TEL-AML1, 8 (16%) had positive E2A-PBX1, and 16 (31%) were positive for other fusion genes. The complete remission rate was 96.0% (144/150) after one course of treatment with CCLG-ALL2008 regimen. The median follow-up time was 52 months (range 3-122 months). The 5-year OS rate was 79.0%±3.5%, and the 5-year EFS rate was 67.3%±4.1%. There were no significant differences in 5-year OS and EFS rates between the children with intermediate or high risk, as well as between the children with B-ALL or T-ALL (P>0.05). The children and adolescents who achieved complete remission of bone marrow at the end of induction therapy had significantly higher 5-year OS and EFS rates than those who did not achieve complete remission (P<0.05). CONCLUSIONS: In ALL children and adolescents aged >10 years, CCLG-ALL2008 regimen can help to achieve high complete remission rate, 5-year OS rate and 5-year EFS rate. The children and adolescents failing to achieve complete remission at the end of induction therapy tend to have a poor prognosis.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica , Criança , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Indução de Remissão , Estudos Retrospectivos
16.
Cytogenet Genome Res ; 158(1): 10-16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30974435

RESUMO

The IKZF1 gene is formed by 8 exons and encodes IKAROS, a transcription factor that regulates the expression of genes that control cell cycle progression and cell survival. In general, 15-20% of the patients with preB acute lymphoblastic leukemia (preB ALL) harbor IKZF1 deletions, and the frequency of these deletions increases in BCR-ABL1 or Ph-like subgroups. These deletions have been associated with poor treatment response and the risk of relapse. The aim of this descriptive study was to determine the frequency of IKZF1 deletions and the success of an induction therapy response in Mexican pediatric patients diagnosed with preB ALL in 2 hospitals from 2017 to August 2018. Thirty-six bone marrow samples from patients at the Instituto Nacional de Pediatría in Mexico City and the Centro Estatal de Cancerología in Tepic were analyzed. The IKZF1 deletion was identified by MLPA using the SALSA MLPA P335 ALL-IKZF1 probemix. Deletions of at least 1 IKZF1 exon were observed in 7/34 samples (20.6%): 3 with 1 exon deleted; 1 with 2 exons, 1 with 5 exons, 1 with 6 exons, and 1 patient with a complete IKZF1 deletion. This study was descriptive in nature; we calculated the frequency of the IKZF1 gene deletion in a Mexican pediatric population with preB ALL as 20.6%.


Assuntos
Fator de Transcrição Ikaros/genética , Proteínas de Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/química , Medula Óssea/patologia , Criança , Pré-Escolar , Éxons/genética , Feminino , Frequência do Gene , Genes Neoplásicos , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Masculino , México , Tipagem de Sequências Multilocus , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologia , Indução de Remissão , Deleção de Sequência , Resultado do Tratamento
17.
Oncol Rep ; 41(6): 3455-3463, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30942469

RESUMO

CD19 chimeric antigen receptor (CAR) T cell therapy has changed the outcomes of relapsed/refractory B­cell leukemia and lymphoma. However, its efficacy in patients with relapsed/refractory non­Hodgkin lymphoma (NHL) has been less impressive compared with that in patients with acute lymphoid leukemia. Furthermore, immune checkpoints have a critical role in the immune system. Several clinical trials have confirmed the dramatic effects of programmed death­1/programmed death­ligand 1 (PD­1/PD­L1) inhibitors in numerous malignancies, but the immune­associated adverse events of PD­1/PD­L1 inhibitors may occur in a number of systems. The aim of the present study was to investigate the combination of CD19 CAR­T cells with a reduced dose of PD­1 inhibitor. This method is expected to overcome the side-effects of PD­1 inhibitors, while maintaining therapeutic efficacy. The findings demonstrated that a reduced dose of PD­1 inhibitor did not affect the transfection rate, proliferation rate or cytokine secretion of CD19 CAR­T cells. An interesting finding of the present study was that the number of PD­1­positive cells CAR­T cells, measured by flow cytometry, declined when they were cultured in vitro, but returned to high levels with gradual prolongation of the co­culture time of CD19 CAR­T cells with lymphoma cells; however, there was no change in the mRNA expression of T cells and CAR­T cells during this process. This phenomenon may be one of the reasons why the curative effect of CAR­T cells on B­cell lymphoma is unsatisfactory compared with B­cell leukemia. The synergistic effect of a reduced­dose PD­1 inhibitor combined with CD19 CAR­T cells from T cells highly expressing PD­1 was confirmed in a mouse trial. Mice in the combined treatment group achieved the longest survival time. In this group, the proportion of CAR­T cells and the level of interleukin­6 were higher compared with those in the CAR­T cell group. In conclusion, a reduced dose of a PD­1 inhibitor combined with CD19 CAR­T cells appears to be a promising treatment option for relapsed/refractory B­NHL exhibiting high PD­1 expression by T cells. This method may achieve good clinical efficacy while reducing the side-effects of PD­1 inhibitors.


Assuntos
Linfoma/terapia , Nivolumabe/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Antígenos CD19/genética , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Proliferação de Células/efeitos dos fármacos , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Imunoterapia Adotiva/métodos , Linfoma/genética , Linfoma/imunologia , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Receptor de Morte Celular Programada 1/genética , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
BMC Cancer ; 19(1): 358, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30991992

RESUMO

BACKGROUND: Micafungin is a well-tolerated and effective prophylactic antifungal agent used in hematologic diseases. In this prospective trial, we evaluated the efficacy and safety of prophylactic micafungin during first induction chemotherapy in patients with acute leukemia. We also compared outcomes of prophylactic micafungin with those of prophylactic posaconazole in acute myeloid leukemia (AML). METHODS: Medically fit patients with newly diagnosed acute leukemia received 50 mg micafungin intravenously once daily from the initiation of first induction chemotherapy to recovery of neutrophil count, suspected fungal infection, or unacceptable drug-related toxicity ( Clinicaltrials.gov number, NCT02440178). The primary end point was incidence of invasive fungal infection, and the secondary end points were adverse events of prophylactic micafungin and mortality during induction therapy. RESULTS: The 65 patients (median age = 51 years, male:female = 34:31) enrolled in this study had diagnoses of AML (33, 50.8%), acute lymphoblastic leukemia (31, 47.7%), and acute biphenotypic leukemia (1, 1.5%). Median duration of micafungin treatment was 24 days (range 1-68), with proven invasive fungal disease in one patient (1.5%) and possible fungal infection in two patients (3.1%). Three of the patients (4.6%) experienced the following adverse events, but all events were tolerable: liver function abnormality (Grade 2, n = 1; Grade 3, n = 1) and allergic reaction (Grade 2, n = 1). Three patients died during induction therapy, and invasive aspergillosis pneumonia was the cause of death for one of those patients. Overall, 19 patients (29.2%) discontinued prophylactic micafungin, and 18 (27.7%) patients switched to another antifungal agent. We observed no fungal infections caused by amphotericin B-resistant organisms. In AML patients, outcomes of prophylactic micafungin during induction chemotherapy did not differ significantly with those of prophylactic posaconazole with regard to incidence of fungal infections, rate of discontinuation, or safety. CONCLUSIONS: Our study demonstrates that prophylactic micafungin is safe and effective in patients with acute leukemia undergoing induction chemotherapy. Outcomes in patients with AML were similar to those of prophylactic posaconazole, indicating the usefulness of micafungin as a prophylactic antifungal agent during induction chemotherapy for AML. TRIAL REGISTRATION: Clinicaltrials.gov NCT02440178, registered May 12th 2015.


Assuntos
Antifúngicos/uso terapêutico , Quimioterapia de Indução/efeitos adversos , Leucemia Mieloide Aguda/complicações , Micafungina/uso terapêutico , Micoses/etiologia , Micoses/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Quimioterapia de Indução/métodos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Micoses/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Resultado do Tratamento , Adulto Jovem
19.
J Clin Neurosci ; 64: 11-14, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30948308

RESUMO

We report a rare case of distinctive extensive punctate intracranial haemorrhage associated with acute lymphoblastic leukaemia with hyperleukocytosis. A 7-year-old girl presented with hyperleukocytosis (white cell count 788.7 × 109/L; 94% peripheral blasts) and laboratory tumour lysis syndrome. The diagnosis of T-cell acute lymphoblastic leukaemia was established and confirmed by immunophenotyping of peripheral blood and chemotherapy was commenced promptly. On day 3 of treatment, she developed progressive encephalopathy, left sided hemiparesis with left 6th and upper motor neuron 7th cranial nerve palsy. Brain MRI scan showed extensive punctate haemorrhages with perilesional oedema over the frontal, parietal, occipital, temporal, brainstem and cerebellar regions. The lesions were predominantly over the juxtacortical grey matter. She made a full neurological recovery after 3 months. Our report widens the neuroradiological features of intracranial haemorrhage associated with hyperleukocytosis and highlights the importance of prompt chemotherapy in these patients.


Assuntos
Hemorragias Intracranianas/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Criança , Feminino , Humanos , Leucocitose/etiologia , Imagem por Ressonância Magnética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
20.
Life Sci ; 227: 153-165, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31004657

RESUMO

AIMS: Alantolactone (ALT) is active component of natural product Inula helenium with a lot of pharmacological effects, including anti-tumor effect. The present work aimed to explore the antitumor effect of ALT in B cell acute lymphoblastic leukemia (B-ALL). MAIN METHODS: B-ALL cells were treated with various concentrations of ALT, and then trypan blue assay, Annexin V/PI staining assay, PI staining assay, western blot analysis were employed to measure the effect of ALT on viability, apoptosis and cell cycle in B-ALL cells. In addition, a synthetic bioinformatics method was used to predict the underlying mechanism of antitumor effect of ALT. Then Reactive Oxygen Species (ROS) probe Dihydroethidium (DHE) and 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) were used to detect accumulation of cellular ROS. Meanwhile, DNA damage was identified by 8-oxoG, p-ATM1987, γ-H2AX and comet assay. In addition, activity of glutathione reductase (GR), thioredoxin reductase (TrxR) and catalase were measured and overexpressed in SEM and RS4;11 cells to study the inhibition on these enzymes. Finally, B-ALL NOD-SCID mouse model was used to test its performance in vivo. KEY FINDINGS: ALT showed good antitumor effect in B-ALL in vivo and in vitro through inducing ROS overload, which led to DNA damage. In addition, we found ROS overload caused by ALT was due to its direct inhibition on reductase. SIGNIFICANCE: We found that ALT, a natural product, showing a promising tactic in the therapy of B-ALL by targeting ROS pathway.


Assuntos
Lactonas/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Sesquiterpenos de Eudesmano/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linfócitos B/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Lactonas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Mitocôndrias/efeitos dos fármacos , Cultura Primária de Células , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos de Eudesmano/metabolismo
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