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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1451-1458, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067936

RESUMO

OBJECTIVE: To investigate the proliferation inhibition and pro-apoptotic effect of Huaier aqueous extract combined with routine chemotherapeutic drugs including Vincristine (VCR), Daunorubicin (DNR), L-aspartase (L-Asp) on human acute lymphoblastic leukemia cell lines Nalm-6 and Sup-B15. METHODS: Nalm-6 and Sup-B15 cell lines were treated with different concentrations of Huaier aqueous extract and chemotherapeutics including VCR, DNR, L-Asp alone or in combination for 48 h, and the growth inhibitory effect and IC50 values (the half maximal inhibitory concentration) were detected by CCK-8. Jin's formula was used to estimated the synergistic effect of these combinations. Apoptosis rates of Nalm-6 and Sup-B15 cells and expression of apoptosis-related proteins BAX, BCL-2, cleaved Caspase-3 were determined by flow cytometry and Western blot respectivcly. RESULTS: Huaier aqueous extract, VCR, DNR and L-Asp had inhibition effect on Nalm-6 and Sup-B15 cell lines. The inhibition rate of Huaier aqueous extract combined with VCR, DNR and L-Asp were all higher than those of each dug alone (P<0.05) and the combination index (q) was between 0.85 and 1.15 or greater than 1.15. The two kinds of drugs showed had additive or synergistic effects. The results of flow cytometry showed that the cell apoptosis rates in combined treatment group were higher than those of each drug alone (P<0.05). The results of Western blot revealed that Huaier aqueous extract and VCR all decreased protein expression of BCL-2 (P<0.05) and increase protein expression of BAX (P<0.05) and cleaved Caspase-3 (P<0.05) in Nalm-6 and Sup-B15 cells. Compared with Huaier aqueous extract or VCR alone, the effect of two drug combination were more significant. DNR down-regulated protein expression of BCL-2 (P<0.05) and up-regulated cleaved Caspase-3 (P<0.05). However, it had no effect on the expression of BAX in Nalm-6 and Sup-B15 cells. When it was combined with Huaier aqueous extract, the expression of cleaved Caspase-3 and BCL-2 showed more significant changes. The expression of BAX in combined treated group did not show significant difference, compared with group treated with Huaier aqueous extract in Nalm-6 and Sup-B15 cells. L-Asp did not show significant effect on the three apoptosis-related proteins and there was no significant difference between the combination group and the Huaier aqueous extract group. CONCLUSION: the combination of Huaier aqueous extract and VCR, DNR, L-Asp shows additive or synergistic effects on human acute lymphoblastic leukemia cell lines Nalm-6 and Sup-B15.


Assuntos
Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Misturas Complexas/uso terapêutico , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Trametes
3.
Ann Hematol ; 99(11): 2629-2637, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32980890

RESUMO

Treatment of acute lymphoblastic leukemia (ALL) requires the combination of multiple drugs to integrate a complete remission. The different prognostic factors (age, leukocytes, risk, cytogenetic alterations) allow identifying those patients with a high risk of relapse, but there are few described factors that impact the induction response. The objective was to identify the utility of different risk factors (overexpression of the ABCB1 drug resistance gene, favorable response to steroids (FRS) and early response at day + 8 of treatment) on the percentage of complete remissions and overall survival. This is a prospective, observational study in adult patients with B-ALL without specific cytogenetic alterations, who started induction treatment based on a pretreatment with prednisone and subsequently vincristine (1.6 mg/m2 subcutaneous) plus daunorubicin (45 mg/m2 subcutaneously) on days + 1, + 8, + 15. The ABCB1 resistance gene was evaluated at diagnosis, the FRS at the end of the pretreatment and the early response during day + 8. A total of 53 adult patients diagnosed with ALL Philadelphia negative chromosome (Ph-), with immunophenotype B, with a normal karyotype, were studied. Cases with genetic abnormalities with a poor prognosis were excluded in order to reduce bias. The mean age was 48 years (range 17-68 years). 62.3% of patients were at high risk of relapse. When analyzing the risk factors, 30.2% showed high levels of the ABCB1 resistance gene, without showing an impact on the induction response (OR: 1.218, p = 0.743), but its overexpression was associated with a poor response to steroids as in the absence of early response. Individually, both the FRS (OR: 5.7, p = 0.004) and the absence of early response to day + 8 (OR: 6.42, p = 0.002) showed significance. By combining the different factors, having more than 2 was directly related to a failure (OR: 9.514, p = 0.000). The identification of factors such as FRS such as the persistence of blasts at the end of the first week of treatment is useful to identify patients at risk of failure in induction.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Quimioterapia de Indução , Proteínas de Neoplasias/biossíntese , Leucemia-Linfoma Linfoblástico de Células Precursoras , Subfamília B de Transportador de Cassetes de Ligação de ATP/biossíntese , Adolescente , Adulto , Idoso , Daunorrubicina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prednisolona/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Vincristina/administração & dosagem
4.
BMC Infect Dis ; 20(1): 658, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912165

RESUMO

BACKGROUND: Stenotrophomonas maltophilia-induced pulmonary haemorrhage is considered a fatal infection among haematological patients. The outcome can be explained by the patients' immunity status and late diagnosis and treatment. CASE PRESENTATION: We present the rare case of successful outcome in a 61-year-old female who developed alveolar haemorrhage and acute respiratory distress syndrome 8 days after a chemotherapy session for her acute lymphoblastic leukaemia, in the context of secondary bone marrow aplasia. Stenotrophomonas maltophilia was isolated in sputum culture. The patient benefitted from early empirical treatment with colistin followed by trimethoprim/sulfamethoxazole, according to the antibiogram. Despite a severe initial clinical presentation in need of mechanical ventilation, neuromuscular blocking agents infusion, and ventilation in prone position, the patient had a favourable outcome and was discharged from intensive care after 26 days. CONCLUSIONS: Stenotrophomonas maltophilia severe pneumonia complicated with pulmonary haemorrhage is not always fatal in haematological patients. Empirical treatment of multidrug-resistant Stenotrophomonas maltophilia in an immunocompromised haematological patient presenting with hemoptysis should be taken into consideration.


Assuntos
Antibacterianos/uso terapêutico , Colistina/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Hemorragia/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Stenotrophomonas maltophilia/isolamento & purificação , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/complicações , Feminino , Infecções por Bactérias Gram-Negativas/etiologia , Hemorragia/etiologia , Humanos , Hospedeiro Imunocomprometido , Pessoa de Meia-Idade , Pneumonia Bacteriana/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Alvéolos Pulmonares/patologia , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/microbiologia , Escarro/microbiologia , Resultado do Tratamento
5.
Orv Hetil ; 161(38): 1623-1628, 2020 09.
Artigo em Húngaro | MEDLINE | ID: mdl-32924966

RESUMO

Maintenance therapy has been the strong and standard element of many acute lymphoblastic leukaemia protocols, used much less frequently and systematically in adult oncohematological disorders. The first adult maintenance efforts appeared in follicular and mantle cell lymphoma (mostly monoclonal antibody based), along with an early maintenance effort to prolong the plateau phase of myeloma. For the time being, after a long debate, the prognosis-dependent type of consolidation and maintenance became - sometimes until relapse - the standard approach in myeloma patients. The so-called small molecules, which turned out to be effective as induction and relapse agents, are continuously moving toward maintenance settings. Moreover, maintenance efforts seem to be more and more considered and used in transplanted or some non-transplanted acute myeloid leukaemia patients as well. Nevertheless, maintenance should be patient-friendly, easy to use (e.g., tablets) by enabling short outpatient office time, done not very frequently, and as much quality-of-life-based as possible. Orv Hetil. 2020; 161(38): 1623-1628.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Mieloma Múltiplo/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto , Humanos , Leucemia Mieloide Aguda/patologia , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
6.
Medicine (Baltimore) ; 99(38): e22208, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957354

RESUMO

BACKGROUND: Acute lymphoblastic leukemia (ALL) is one of the most commonly seen cancers in children, which mainly relates with inherited genetic variations. Consolidation chemotherapy is usually given to the pediatric ALL patients, however there is no meta-analysis and network analysis conducting the efficacy of the chemotherapy. Therefore, we perform a protocol to assess the efficacy of chemotherapeutics for pediatric ALL. METHODS: A literature search for randomized controlled trials about some specific chemotherapy regimens for pediatric ALL will be carried out in 7 electronic databases from their establishment to June 2019: the Cochrane Library, Embase, MEDLINE, the Chinese National Knowledge Infrastructure (CNKI), the Sino Med, the Chinese Scientific Journal Database (VIP) and the Wanfang Database. Complete continuous remission will be measured as primary outcome. Stata 14.0 will be utilized to perform a standard pairwise meta-analysis and the NMA, as well as draw Network Plots of Network Meta. RESULTS: This network meta-analysis will evaluate the efficacy of different consolidation chemotherapy regimens. CONCLUSION: This study will furnish decision-making reference on optimum proposal of chemotherapy regimens for pediatric ALL. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019134518.


Assuntos
Antineoplásicos/administração & dosagem , Quimioterapia de Consolidação , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
7.
Ann Hematol ; 99(11): 2611-2617, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32980888

RESUMO

EP300-ZNF384 fusion is a rare recurrent cytogenetic abnormality associated with B cell acute lymphoblastic leukemia (B-ALL), which was rarely studied in Chinese patient cohort. Here, we used a customized RNA fusion gene panel to investigate gene fusions in 56 selected acute leukemia patients without conventional genetic abnormalities. Two EP300-ZNF384 fusion forms were detected in ten cases, which were in-frame fusions of EP300 exon 6 fused with exon 3 or 2 of ZNF384. The fusions led to the lack of most functional domains of EP300. We firstly reported EP300-ZNF384 fusion in a mixed-phenotype acute leukemia (MPAL) patient whose CD33 and CD13 were negative. The rest nine B-ALL patients with EP300-ZNF384 fusion expressed CD33 and/or CD13. Fifty-six percent of B-ALL patients (5/9) with EP300-ZNF384 fusion were positive with CD10. After the diagnosis of EP300-ZNF384 fusion, 70% of the patients achieved remission after chemotherapy. Our observations indicated that EP300-ZNF384 fusion consists of a distinct subgroup of B-ALL with a characteristic immunophenotype. These patients are sensitive to current chemotherapy regimen and have an excellent outcome.


Assuntos
Proteína p300 Associada a E1A , Proteínas de Fusão Oncogênica , Leucemia-Linfoma Linfoblástico de Células Precursoras , RNA Neoplásico , Análise de Sequência de RNA , Transativadores , Adulto , Estudos de Coortes , Proteína p300 Associada a E1A/genética , Proteína p300 Associada a E1A/metabolismo , Feminino , Humanos , Masculino , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Transativadores/genética , Transativadores/metabolismo
8.
Rinsho Ketsueki ; 61(8): 922-928, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32908056

RESUMO

In 2018, two novel antibody therapies, inotuzumab ozogamicin (InO) and blinatumomab, against relapsed or refractory acute lymphoblastic leukemia were approved in Japan. In InO, the antitumor drug ozogamicin is conjugated to the anti-CD22 antibody. Blinatumomab is a bispecific T cell engager antibody comprising the variable regions of the anti-CD19 and the anti-CD3 antibodies. The remission rate of InO is about 75%; however, the frequency of sinusoidal obstruction syndrome is increased when allogeneic hematopoietic cell transplantation is performed after InO treatment. Blinatumomab has a remission rate of 45-70%. The management of cytokine release syndrome during blinatumomab treatment is required in certain cases. Although both the treatments have higher remission and negativity of minimal residual disease rates compared to those in conventional chemotherapy, it is difficult to maintain remission in the long term. Allogeneic hematopoietic stem cell transplantation should be performed as commonly as possible.


Assuntos
Anticorpos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras , Antineoplásicos , Humanos , Inotuzumab Ozogamicina , Japão , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Indução de Remissão
9.
Ann Hematol ; 99(10): 2393-2404, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32803312

RESUMO

The prognostic impacts of BCR-ABL1 fusion gene mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remain unknown. Using data from a nationwide Japanese registry, we have evaluated the prognostic impact of BCR-ABL1 mutations prior to the first allogeneic hematopoietic cell transplantation (HCT). The cohort included 289 patients with a median of 48 years of age (range: 16-70). Point mutations were detected in 110 patients. Of these, 90 (82%) harbored T315I mutations, while 20 had other mutations. With a median follow-up period of 29 months (range: 1-125), outcomes after 2 years were worse with mutations than without (overall survival [OS]: 34% vs 68%, p < 0.001; relapse rate [RR]: 48% vs 18%, p < 0.001), particularly with the presence of the T315I mutation (OS: 29% vs 68%, p < 0.001; RR: 54% vs 18%, p < 0.001). OS was significantly worse in the T315I group even among the cohort with hematological (p < 0.001) or molecular complete remission (p = 0.025) as compared to the no mutation group. Multivariate analysis determined the prognostic impact of the T315I mutation (OS: hazard ratio [HR] = 2.19, 95% confidence interval [CI]: 1.5-3.3, p < 0.001; RR: HR = 2.51, 95% CI: 1.5-4.2, p < 0.001). This study is the first to report on the prognostic significance of BCR-ABL1 mutations in Ph + ALL.


Assuntos
Proteínas de Fusão bcr-abl/genética , Transplante de Células-Tronco Hematopoéticas , Mutação de Sentido Incorreto , Cromossomo Filadélfia , Mutação Puntual , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Idoso , Aloenxertos , Antineoplásicos/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Recidiva , Sistema de Registros , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1075-1080, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798380

RESUMO

OBJECTIVE: To study the long-term efficacy of CCLG-ALL2008 protocol used for treatment of childhood acute lymphoblastic leukemia (ALL). METHODS: Nine hundred and forty children with newly diagnosed ALL from January 2008 to April 2015 were treated with CCLG-ALL2008 protocol. Overall survival (OS) and event-free survival (EFS) rates were estimated by the Kaplan-Meier method. Cox proportional hazards model was used for analyses of prognostic factors. RESULTS: Among the 940 newly diagnosed ALL patients, 570 patients were male, and 370 patients were female, the median age of onset was 5 years old (from 1 to 15 years old). The complete reaction rate (CR) was 96.7%. Survival analysis of 916 ALL patients with CR estimated by follow up [ (median follow up period 64 months (from 3 to 123 months) ] showed that, the expected 10 year OS rate was (78.6±1.5)% and the EFS rate was (66.0±1.8)%. The long-term OS rate of standard risk, intermediate risk and high risk patients was (93.0±1.5)%, (77.6±2.7)%, and (59.3±3.7)%, respectively, and the long-term EFS rate in standard risk, intermediate risk and high risk patients was (84.2±2.2)%. (67.8±2.9)%, and (42.1±3.9)% respectively. 10 year OS rate in B-ALL patients (79.8±1.6)% was significantly higher than that in T-ALL patients (53.5±6.3)% (P<0.01). Among of all the patients, patients 201 (21.9%) relapsed, the median relapse time was 19 months (from 2 months to 81 months). The 10 year EFS rate was (81.7±3.7)% in the patients with MRD rate <0.01% after induction therapy, which was significantly higher than that in the patients with MRD rate>0.01% (48.4±9.8)%. CONCLUSION: The therapeutic efficacy of the CCLG-ALL2008 protocol is closed to the level of supior study group in the world. Risk stratification can improve the outcome for childhood ALL. Immunophenotyping shows the outcome of B-ALL is better than that of T-ALL. MRD negative patients after induction therapy shows better prognosis compared with that of MRD positive patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , China , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Prognóstico , Estudos Prospectivos , Resultado do Tratamento
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(8): 828-833, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32800028

RESUMO

OBJECTIVE: To study the occurrence of serious adverse events (SAEs) related to chemotherapy with CCCG-ALL-2015 regimen in children with acute lymphoblastic leukemia (ALL) and the risk factors for death after the SAEs. METHODS: A retrospective analysis was performed on the medical data of 734 children with ALL. They were treated with CCCG-ALL-2015 regimen from January 2015 to June 2019. The occurrence of SAEs during the treatment was investigated. The children with SAEs were divided into a death group with 25 children and a survival group with 31 children. A multivariate logistic regression analysis was used to analyze the risk factors for death after the SAEs. RESULTS: Among the 734 children with ALL, 56 (7.6%) experienced SAEs (66 cases) after chemotherapy, among which 41 cases occurred in the stage of remission induction therapy. Of all 66 cases of SAEs, 46 (70%) were infection-related SAEs, including 25 cases of septic shock (38%), 20 cases of severe pneumonia (30%), and 1 case of severe chickenpox (2%), and 87% of the children with infection-related SAEs had neutrophil deficiency. The most common infection sites were blood and the lungs. The most common pathogens were Gram-negative bacteria, viruses, fungi, and Gram-positive bacteria. There were 16 cases (24%) of hemorrhage-related SAEs, with 11 cases of gastrointestinal bleeding (17%), 4 cases of pulmonary bleeding (6%), and 1 case of intracranial bleeding (2%). Of all 734 children with ALL, 66 (9.0%) died, among whom 25 died due to SAEs. The treatment-related mortality rate was 3.4%, and infection (72%) and bleeding (24%) were the main causes of death. Severe pneumonia was an independent risk factor for treatment-related death in ALL children (OR=4.087, 95%CI: 1.161-14.384, P=0.028). CONCLUSIONS: SAEs often occur in the stage of remission induction therapy, and infection-related SAEs are more common in ALL children accepting chemotherapy with CCCG-ALL-2015 regimen. The development of severe pneumonia suggests an increased risk for death in these children.


Assuntos
Antineoplásicos/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Bactérias Gram-Negativas , Humanos , Neutrófilos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco
12.
Ann Hematol ; 99(10): 2429-2436, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32839869

RESUMO

Patients receiving vinca alkaloids for hematological malignancies frequently experience constipation that is unresponsive to laxatives. Research on treatment of vinca alkaloid-induced constipation is limited. This study aimed to determine whether the chloride channel activator lubiprostone ameliorates vinca alkaloid-induced constipation in patients with hematological malignancies. In this retrospective cohort study, vinca alkaloid-induced constipation (grade ≥ 3 using the Common Terminology Criteria for Adverse Events) was investigated in patients treated for hematological malignancies between July 2014 and June 2019 who had already been prescribed osmotic laxatives and additionally received either a stimulant laxative or lubiprostone. Univariate and multivariate analyses were performed to identify the risk factors for persistent constipation after introduction of the second laxative. A propensity score model was used to match 67 patients taking a stimulant laxative and 67 treated with lubiprostone, and the occurrence of intractable constipation was compared between groups. Overall, 203 patients were included, among whom 50 (25%) had constipation. On multivariate analysis, body mass index, opioid use, and addition of lubiprostone were independently associated with constipation. Patients treated with lubiprostone were significantly less likely to experience intractable constipation than did those treated with stimulant laxatives (10% vs. 34%, P = 0.002). Moreover, post-constipation diarrhea was significantly less frequent among patients treated with lubiprostone (42% vs. 63%, P = 0.024). Lubiprostone was more effective than stimulant laxatives at treating vinca alkaloid-induced intractable constipation in patients with hematological malignancies, and its use could enable safe vinca alkaloid chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Agonistas dos Canais de Cloreto/uso terapêutico , Constipação Intestinal/tratamento farmacológico , Neoplasias Hematológicas/tratamento farmacológico , Lubiprostona/uso terapêutico , Linfoma/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Alcaloides de Vinca/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Constipação Intestinal/induzido quimicamente , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Avaliação de Medicamentos , Quimioterapia Combinada , Famotidina/uso terapêutico , Feminino , Humanos , Laxantes/farmacologia , Laxantes/uso terapêutico , Óxido de Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Entorpecentes/efeitos adversos , Prednisona/administração & dosagem , Pontuação de Propensão , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Senosídeos/uso terapêutico , Alcaloides de Vinca/administração & dosagem , Vincristina/administração & dosagem
14.
Rinsho Ketsueki ; 61(6): 657-664, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32624540

RESUMO

Recent advances in genomic analysis technology have revolutionized precision medicine, especially with respect to the diagnosis, prognosis, and treatment of pediatric cancers. Pediatric acute lymphoblastic leukemia (ALL) is the most common pediatric cancer; genetic abnormalities associated with ALL are useful for the diagnosis and risk stratification in patients with ALL. Thus, genomic medicine (clinical sequencing) in pediatric ALL at diagnosis would help in the improvement of prognostic prediction and risk stratification. Recently, integrated genetic analysis using next generation sequencing technology revealed the full genetic landscape of pediatric ALL. These studies disclosed that in addition to fusion genes, aberrations of cell proliferation pathways and epigenetic regulations are also involved in the pathogenesis of pediatric ALL. Therefore, the realization of genomic medicine is an urgent necessity for improving the outcomes of pediatric patients diagnosed with ALL.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Terapia de Alvo Molecular , Medicina de Precisão , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico
15.
Medicine (Baltimore) ; 99(29): e21015, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702842

RESUMO

BACKGROUND: Down syndrome (DS) also known as Trisomy 21, is a chromosomal disorder affecting approximately 1 in 732newborns annually in the United States. Children with DS are more likely to develop acute lymphoblastic leukemia (ALL). For the management of pediatric ALL, different treatment protocols have been set up since years. However, ALL children with coexisting DS have shown to have increased therapy-related toxicities compared to those without DS. Therefore, in this study, we aimed to systematically analyze the treatment outcomes in acute ALL children with versus without coexisting DS. METHODS: Electronic databases including the Web of Science, EMBASE, Cochrane Central, MEDLINE, http://www.ClinicalTrials.gov, and Google scholar were searched for publications reporting treatment related outcomes in ALL children with versus without co-existing DS. Several treatment protocols were used accordingly. This study had a long-term follow-up time period ranging from 5 to 10 years. The RevMan 5.3 software was used to carry out this analysis. Odds ratios (OR) with 95% confidence intervals (CI) were used to represent the results post analysis. RESULTS: A total number of 31,476 children with ALL enrolled between the years 1981 and 2011 were included. Among the total number of children with ALL, 1303 had coexisting DS. Our results showed that event-free survival was similar in ALL children with versus without DS (odds ratio [OR]: 1.34, 95% confidence interval [CI]: 0.51-3.50; P = .55). Overall mortality (OR: 1.63, 95% CI: 0.86-3.10; P = .13) and participants who achieved clinical remission (OR: 1.04, 95% CI: 0.12-9.29; P = .97) were also similarly manifested. However, treatment-related mortality (OR: 4.29, 95% CI: 2.90-6.36; P = .00001) and induction failure (OR: 2.77, 95% CI: 1.08-7.07; P = .03) were significantly higher in the DS group. Also, total (OR: 1.38, 95% CI: 1.02-1.88; P = .04) and bone marrow relapses (OR: 1.29, 95% CI: 1.00-1.67; P = .05) were significantly higher in ALL children with DS. Nevertheless, central nervous system relapse (OR: 1.15, 95% CI: 0.60-2.20; P = .67), testicular relapse (OR: 0.84, 95% CI: 0.38-1.85; P = .87), and other relapses (OR: 1.12, 95% CI: 0.27-4.62; P = .88) were not significantly different when these outcomes were separately analyzed. CONCLUSION: Based on this analysis of the treatment outcomes in ALL children with versus without DS, event-free survival, overall mortality, and patients who achieved clinical remission were similar during this long-term follow-up time period. However, due to the significantly higher treatment-related mortality, induction failure, and certain relapses in ALL children with DS, new guidelines might have to focus on reconsidering or modifying treatment regimens for ALL children with DS.


Assuntos
Síndrome de Down/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Recidiva Local de Neoplasia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Indução de Remissão , Falha de Tratamento
16.
Mikrobiyol Bul ; 54(2): 326-333, 2020 Apr.
Artigo em Turco | MEDLINE | ID: mdl-32723287

RESUMO

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease that can be presented with fever, fatigue, generalized joint/body pain, diarrhea and bleeding in various parts of the body. The risk of developing a severe fatal disease in humans, the possibility of being infected with aerosols and the risk of being used as a biological weapon make the disease still an important health problem all over the world as there is no a specific treatment and vaccine that has proven effective againt the virus today. The pathogenesis of the disease is not known, but vascular endothelial damage is prominent. Therefore, it progresses with thrombocytopenia, anemia, leukopenia and this hematological findings can be confused with hematological malignancies. Acute lymphoblastic leukemia (ALL) is a malignancy included in differential diagnoses and occurs as a result of mutations occuring at a stage of differentiation in the lymphoid precursor cells in the bone marrow. In this study, we present a case of ALL who was diagnosed with CCHF simultaneously. A 43-year old female patient who works in the library and does not have a chronic disease other than asthma and thyroid disorder, has admitted to our hospital with the complaints of intermittent fever, weakness, generalized joint and body pain for about 3 weeks. She had fever and the physical examination revealed bilateral cervical and right postauricular lymphadenopathies. Her aspartate aminotransferase: 77 U/L, alanine aminotransferase: 117 U/L, lactate dehydrogenase: 616 U/L, hemoglobin: 8.27 g/dl, leukocyte count: 15.690/mm3 , neutrophil count: 550/mm3 (%3.5), lymphocyte count: 6690/mm3 (%42.6), platelet count: 102.100/mm3 , C-reactive protein: 163.6 mg/L was detected and the patient was hospitalized on 5 August 2019 for further examination and treatment. Considering that the patient may have viral infection in the foreground the requested test results were detected as; anti-CMV IgM negative, anti-CMV IgG positive, anti-toxoplasma IgM negative, anti-toxoplasma IgG positive, anti-rubella IgM negative, anti-rubella IgG positive, HBsAg negative, anti-HBc IgM negative, antiHBs positive, anti-HAV IgM negative, anti-HAV IgG positive, anti-HCV negative, anti-HIV negative, EpsteinBarr virus (EBV) VCA IgM negative, EBV VCA IgG positive, EBV EBNA IgG positive. Brucella Rose Bengal and Coombs tube agglutination was found be negative. As the cytopenia of the patient deepened, the patient was accepted to have neutropenic fever and it was planned to start piperacillin-tazobactam 4 x 4.5 g/day and two units of erythrocyte replacement therapy. When the patient's history was questioned again, it was learned that she had a tick on her neck about three weeks ago and she had removed the tick herself; 4-5 days later she had the complaints of fever and flu like symptoms and also diarrhea complaints lasting for 3-4 days. Considering the current anamnesis and laboratory findings, the patient was thought to have CCHF and the patient was isolated. The serum sample taken from patient with an initial diagnosis of CCHF and sent to Department of Microbiology Reference Laboratory Public Health Agency of Turkey. The patient was referred to the Antalya Training and Research Hospital. The patient's CCHF serum result was positive. Ribavirin treatment was not initiated in the patient who was accepted to be in the convalescence period, piperacillin-tazobactam 4 x 4.5 g/day treatment was continued and supportive treatment was given. In the follow-up, as the patient's neutropenia, thrombocytopenia and lymphocytopenia still continuing, she was transferred to hematology clinic for malignancy examination and bone marrow biopsy performed by hematology and B cell ALL was diagnosed. She was accepted to be convalescent in terms of CCHF and chemotherapy was started for ALL treatment by hematology. The patient is still being followed up by the hematology clinic and allogenic hematopoietic stem cell tranplantation is planned for the patient. As a result, CCHF is a disease that can be confused with many differential diagnosis. With this case, it is aimed to draw attention to the diagnostic difficulties of CCHF and ALL and to be the first case in the literature.


Assuntos
Vírus da Febre Hemorrágica da Crimeia-Congo , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Animais , Diagnóstico Diferencial , Feminino , Febre Hemorrágica da Crimeia/complicações , Febre Hemorrágica da Crimeia/diagnóstico , Febre Hemorrágica da Crimeia/tratamento farmacológico , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Carrapatos/virologia , Resultado do Tratamento , Turquia
17.
Ann Hematol ; 99(9): 2201-2203, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32699943
18.
BMC Infect Dis ; 20(1): 535, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703183

RESUMO

BACKGROUND: Breakthrough invasive fungal infections (bIFIs) are an area of concern in the scarcity of new antifungals. The mixed form of bIFIs is a rare phenomenon but could be potentially a troublesome challenge when caused by azole-resistant strains or non-Aspergillus fumigatus. To raise awareness and emphasize diagnostic challenges, we present a case of mixed bIFIs in a child with acute lymphoblastic leukemia. CASE PRESENTATION: A newly diagnosed 18-month-old boy with acute lymphoblastic leukemia was complicated with prolonged severe neutropenia after induction chemotherapy. He experienced repeated episodes of fever due to extended-spectrum beta-lactamase-producing Escherichia coli bloodstream infection and pulmonary invasive fungal infection with Aspergillus fumigatus (early-type bIFIs) while receiving antifungal prophylaxis. Shortly after pulmonary involvement, his condition aggravated by abnormal focal movement, loss of consciousness and seizure. Cerebral aspergillosis with Aspergillus niger diagnosed after brain tissue biopsy. The patient finally died despite 108-day antifungal therapy. CONCLUSIONS: Mixed bIFIs is a rare condition with high morbidity and mortality in the patients receiving immunosuppressants for hematological malignancies. This case highlights the clinical importance of Aspergillus identification at the species level in invasive fungal infections with multiple site involvement in the patients on antifungal prophylaxis.


Assuntos
Antifúngicos/uso terapêutico , Aspergillus fumigatus/imunologia , Aspergillus niger/genética , Coinfecção/diagnóstico , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Neuroaspergilose/diagnóstico , Antígenos de Fungos/análise , Aspergillus fumigatus/isolamento & purificação , Aspergillus niger/isolamento & purificação , Cerebelo/microbiologia , Cerebelo/patologia , Criança , Coinfecção/microbiologia , Evolução Fatal , Humanos , Quimioterapia de Indução/efeitos adversos , Lactente , Aspergilose Pulmonar Invasiva/sangue , Aspergilose Pulmonar Invasiva/microbiologia , Masculino , Neuroaspergilose/microbiologia , Neutropenia/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
20.
Rinsho Ketsueki ; 61(5): 462-467, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32507809

RESUMO

A 46-year-old man who had previously undergone open surgery for renal cell carcinoma (RCC) developed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL). After the induction therapy, he achieved complete molecular remission. However, fever and bilateral buttock pain continued during the consolidation therapy. 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) showed FDG accumulation in both iliac bones and in the sacrum; however, no causative diseases, including relapse of Ph-ALL and RCC, were detected. Iliac bone marrow biopsy revealed bone marrow necrosis (BMN), the etiology of which was presumed to be the leukemia itself and the therapeutic response to chemotherapy. Fever resolution and buttock pain alleviation were observed over the next months. We observed diffuse fibrosis in the bone marrow at day 162 and day 364 after cord blood transplantation. Moreover, the FDG accumulation was significantly reduced on PET-CT. BMN is not widely recognized despite its potential association with hematologic malignancies. Additional cases of BMN should be reviewed to clarify BMN etiology and clinical features.


Assuntos
Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Medula Óssea , Quimioterapia de Consolidação , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
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