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Background: Fibromyalgia Syndrome (FMS) has been linked to decreased social functioning, poor mental health, and quality of life (QOL). Increased physical functioning and activity can result in improvements in social, mental and overall health, as well as lowered depression and anxiety levels. Objectives: The aim of this study was to determine physical activity levels and QOL amongst patients diagnosed with fibromyalgia in the Johannesburg region of South Africa. Methods: The research design was cross-sectional. Descriptive and quantitative data were collected. FMS patients (n=38) completed an online questionnaire on the Google Forms platform. The questionnaire was comprised of four components, namely Demographics, the Global Physical Activity Questionnaire (GPAQ), the Fibromyalgia Impact Questionnaire (FIQR), and the Short Form-36 (SF-36). During data analysis, descriptive characteristics and correlations were computed. The significance level was set at p ≤ 0.05. Results: Results revealed high FIQR scores (67%) accompanied with low QOL scores (<50% in all domains). There was no correlation between physical activity and FIQR, and physical activity and QOL. Conclusion: High scores on the impact of FMS were associated with lower overall QOL scores. However, the relationship between physical activity, and the impact of FMS and QOL remain inconclusive.
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ExerciseABSTRACT
@#ObjectiveTo develop a highly sensitive method for detection of mutation of FMS-like tyrosine kinase-3-tyrosine kinase domain(FLT3-TKD)of acute myeloid leukemia(AML)and apply to the monitor of minimal residual disease(MRD).MethodsRecombinant plasmids containing wild FLT3 and mutant FLT3-D835Y were constructed respectively and mixed at certain ratios.The obtained standard plasmids with mutation rates of 50%,1%,0.1% and 0% respectively were determined by restriction fragment length polymorphism(RFLP)in combination with Sanger method.The plasmid DNA standards and blood DNA standards,at various FLT3-D835Y mutation rates,were determined by the developed method to verify the sensitivity.The genomic DNA samples of patients with AML before and after treatment were determined by the developed method to monitor the MRD.ResultsSequencing proved that both the recombinant plasmids containing wild FLT3 and mutant FLT3-D835Y were constructed correctly.The sensitivity of developed method increased to 0.1% through Sanger method combined with digestion with EcoR Ⅴ/Xho Ⅰ and recovery of mutant fragments in determination of purified plasmid DNA and collected blood DNA samples.MRD was detected in the peripheral blood sample of a patients with AML in complete remission period by the developed method but not by Sanger method.ConclusionA highly sensitive method for detection of FLT3-TKD mutation was developed,which was of an important clinical significance in guiding the treatment of AML and monitoring the MRD in complete remission period.
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Acute myeloid leukemia (AML) patients with FLT3 mutation have a high risk of recurrence and poor prognosis. The first generation of drugs targeting FLT3 represented by sorafenib show poor selectivity and efficacy in the treatment of AML, whereas the new second-generation FLT3 inhibitors represented by gilteritinib have a stronger inhibitory effect on FLT3, higher specificity and lower off-target toxicity, which greatly improves the outcomes of AML patients with FLT3 mutation. This article reviews the action mechanism and the clinical progress of gilteritinib.
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Background: The purpose of the study was to analyze the expression of nucleophosmin (NPM1), CCAT/enhancer-binding protein alpha (CEBPA), and FMS-like tyrosine kinase 3 (FLT3) with immunohistochemistry and evaluate the relationship with clinicopathologic data with special emphasis on prognosis in bone marrow biopsy specimens diagnosed with acute myeloid leukemia (AML). Materials and Methods: Bone marrow biopsies of 104 patients who were diagnosed with AML were re-evaluated for diagnosis and subclassification. Immunohistochemically, anti-NPM1, anti-CEBPA, and anti-FLT3 antibodies were applied to slides prepared from formalin-fixed paraffin-embedded tissues. Sixty-three of these patients had their follow-up in our institutional hematology clinic and these patients' clinical, biochemical, and radiological data were obtained and analyzed from patient files. These data were analyzed with survival times statistically. Results: Except for age, no significant effect of clinical data on prognosis was detected. Immunohistochemical results were also statistically compared with clinical data. No correlation was found between overall survival and disease-free survival with the expression of anti-CEBPA or anti-NPM1 antibodies. However, immunohistochemical reactivity for anti-FLT3 antibody was found to be a poor prognostic factor and statistically significant. Also, when the expression of FLT3 was analyzed with that of NPM1 or CEBPA, a correlation (dependent on the expression of FLT3) was found with disease-free survival. Conclusions: FLT3 is an independent prognostic factor for AML. CEBPA and NPM1 should be considered as good prognostic factors only in the absence of FLT3 abnormalities.
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Abstract Objective It is a challenge to consider preeclampsia (PE) diagnosis and management in low and middle-income settings, where it represents a major public health concern. The placenta is the underlying cause of disease, and the plasma concentrations of proangiogenic and antiangiogenic factors released by the placenta can reflect the risks of disease progression. Antiangiogenic proteins, such as soluble fms-like tyrosine kinase 1 (sFlt-1), and proangiogenic, like placental growth factors (PlGF), are directly and inversely correlated with the disease onset, respectively. Methods Narrative review on the use of biomarkers (sFlt-1 to PlGF ratio) with a suggested guidance protocol. Results Key considerations on the use of biomarkers: the sFlt-1/PlGF ratio is mainly relevant to rule out PE between 20 and 36 6/7 weeks in cases of suspected PE; however, it should not replace the routine exams for the diagnosis of PE. The sFlt-1/PlGF ratio should not be performed after confirmed PE diagnosis (only in research settings). In women with suspected PE, sFlt-1/PlGF ratio < 38 can rule out the diagnosis of PE for 1 week (VPN = 99.3) and up to 4 weeks (VPN= 94.3); sFlt-1/PlGF ratio > 38 does not confirm the diagnosis of PE; however, it can assist clinical management. In cases of severe hypertension and/or symptoms (imminent eclampsia), hospitalization is imperative, regardless of the result of the sFlt-1/PlGF ratio. Conclusion The use of biomarkers can help support clinical decisions on the management of suspected PE cases, especially to rule out PE diagnosis, thus avoiding unnecessary interventions, especially hospitalizations and elective prematurity
Resumo Objetivo um desafio considerar o diagnóstico e o tratamento da pré-eclâmpsia (PE) em locais de baixa e média renda, onde a doença representa um grande problema de saúde pública. A placenta é a causa subjacente da doença, e as concentrações plasmáticas de fatores pró-angiogênicos e antiangiogênicos liberados pela placenta podem refletir os riscos de progressão da doença. Proteínas antiangiogênicas, como a tirosina quinase fms solúvel tipo 1 (sFlt-1), e pró-angiogênicas, como o fator de crescimento placentário (PlGF), estão direta e inversamente correlacionados com o início da doença, respectivamente. Métodos Revisão narrativa sobre o uso de biomarcadores (razão sFlt-1/PlGF) com sugestão de protocolo de orientação para uso clínico. Resultados Principais considerações sobre o uso de biomarcadores: a razão sFlt-1/PlGF é principalmente relevante para descartar PE entre 20 e 36 6/7 semanas em casos de suspeita de PE; entretanto, não deve substituir os exames de rotina para o diagnóstico de PE. A relação sFlt-1/PlGF não deve ser realizada após a confirmação do diagnóstico de PE (apenas em ambientes de pesquisa). Em mulheres com suspeita de PE, a razão sFlt-1/PlGF < 38 pode descartar o diagnóstico de PE por 1 semana (VPN = 99,3) e até 4 semanas (VPN = 94,3); A relação sFlt-1/PlGF > 38 pode auxiliar no manejo clínico. Em casos de hipertensão grave e/ou sintomas (eclâmpsia iminente), a hospitalização é imprescindível, independentemente do resultado da relação sFlt-1/PlGF. Conclusão O uso de biomarcadores pode auxiliar na tomada de decisões clínicas no manejo de casos suspeitos de PE, principalmente para afastar o diagnóstico da doença, evitando intervenções desnecessárias, tais como internações e prematuridade iatrogênica.
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Humans , Female , Pregnancy , Pre-Eclampsia , HypertensionABSTRACT
Objective:To investigate the effect of chemotherapy combined with sorafenib on the prognosis of FLT3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukemia and to find a more effective treatment.Methods:The clinical data of 60 patients who were newly diagnosed with acute myeloid leukemia and who received treatment in The Second Affiliated Hospital of Qiqihar Medical University from January 2015 to January 2017 were retrospectively analyzed. The patients were divided into three groups according to whether they were positive for FLT3-ITD and the treatment method they used. The observation group (FLT3-ITD-positive, n = 19) were treated with sorafenib based on routine chemotherapy. The control group 1 (FLT3-ITD-positive, n = 21) was treated only with routine chemotherapy. The control group 2 (FLT3-ITD-negative, n = 20) was treated only with routine chemotherapy. After the first and fourth courses of treatment, clinical efficacy was compared among the three groups. Results:After the first course of treatment, the complete remission rate in control group 2 was 50.0% (10/20), which was significantly higher than 15.8% (3/19) in the observation group and 4.8% (1/21) in the control group 1 ( H = 13.39, P < 0.05). After the fourth course of treatment, the complete remission rate in the observation group, control group 2, and control group 1 was 63.2% (12/19), 60.0% (12/20), and 4.8% (1/21), respectively, and the differences were statistically significant ( H = 19.21, P < 0.05). Four-year follow-up results showed that the median survival time in the observation group, control group 1, and control group 2 was 36.63, 24.15, and 45.00 months respectively. The event-free survival in the observation group, control group 1, and control group 2 was 18.00, 9.82, and 24.90 months, respectively. The median survival time and the event-free survival in the control group 2 were significantly longer than those in the observation group and control group 1 ( χ2 = 19.93, 23.04, both P < 0.001). Conclusion:Chemotherapy combined with sorafenib for treating newly-diagnosed FLT3-ITD-positive acute myeloid leukemia can provide comprehensive benefits and have advantages for survival over chemotherapy without sorafenib and chemotherapy alone.
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Objective:To investigate the efficacy and safety of geritinib in the treatment of acute myeloid leukemia (AML) with FLT3 mutation.Methods:The clinical data of 5 AML patients with FLT3 mutation who were diagnosed in the University of Hong Kong-Shenzhen Hospital, Shenzhen People's Hospital, Shenzhen Second People's Hospital, Shenzhen University General Hospital from March 2020 to April 2021 were retrospectively analyzed. Relapsed patients concurrently received two- or three-drug chemotherapy combined with geritinib. Blood routine was checked once a week; liver function and renal function were checked once every 2 weeks during treatment. Bone marrow puncture was performed once every 1 to 3 months to monitor the bone marrow morphology, minimal residual disease (MRD) and FLT3 mutation expression levels. The efficacy, side effects, overall survival of these patients were analyzed after treatment with geritinib.Results:The white blood cell was increased in all the 5 patients at the initial diagnosis. FLT3 mutations analysis showed FLT3-internal tandem duplication (ITD) (3 cases) and FLT-3 tyrosine-kinase domain (TKD) (2 cases). Among 5 patients, 1 patient was relapse-free with maintenance therapy of oral geritinib after hematological stem cell transplantation (HSCT) for 60 days; among other 4 relapsed and refractory patients, 1 female patient after pregnancy relapsed after transplantation and then achieved complete remission followed by the maintenance therapy with geritinib after oral geritinib, 1 16-year-old patient achieved treatment outcome close to the complete remission after treatment with geritinib, 1 patient achieved complete remission after treatment with geritinib, and then underwent haplo-HSCT followed by the maintenance therapy with geritinib and the other 1 relapsed patient achieved complete remission after treatment with geritinib. After transplantation, 3 patients receiving maintenance treatment of geritinib did not relapse. The main side effects included anemia, decreased neutrophil count, rash, and increased aminotransferase. The median follow-up time of 5 patients was 15 months (6-20 months). All 5 cases survived until the last follow-up in November 2021 and 4 patients were disease-free.Conclusions:Relapsed and refractory AML patients with FLT3 mutation can achieve complete remission after treatment with geritinib and get a chance for transplantation. Geritinib may reduce the risk of recurrence after transplantation and improve survival rate. No serious side effects occur in geritinib treatment.
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Objective:To explore the coexisting gene mutations of FLT3-ITD mutation and its association with partial clinical parameters in acute myeloid leukemia (AML).Methods:The clinical data of 236 newly diagnosed AML outpatients and hospitalized patients of Changzhou No.2 People's Hospital and the Second People's Hospital of Wuxi between December 2012 and August 2019 were retrospectively analyzed. Genome DNA-polymerase chain reaction (PCR) combined with Sanger sequencing was used to detect FLT3-ITD mutations, and 51 tumor target gene mutations in patients with FLT3-ITD mutations were detected by using high-throughput DNA sequencing combined with Sanger sequencing.Results:Among 236 AML patients, FLT3-ITD mutations were found in 71 cases (30.1%). About 97.2% (69/71) patients with FLT3-ITD mutations were accompanied by additional mutations, of which 19 patients harbored double coexisting genes mutations, 24 patients harbored 3 coexisting genes mutations and 26 patients harbored ≥ 4 coexisting genes mutations. The most common coexisting genes mutations were NPM1 (55 cases, 77.5%), followed by DNMT3A (36 cases, 50.7%), TET2 (9 cases, 12.7%), CEBPA (5 cases, 7.0%), IDH1 (4 cases, 5.6%) and NRAS (4 cases, 5.6%). In FLT3-ITD mutation group, the hemoglobin level of patients with DNMT3A mutation type was lower than that of those with DNMT3A wild type ( t = -2.37, P = 0.020); the hemoglobin level of patients with NPM1 mutation type was higher than that of those with NPM1 wild type ( t = 2.04, P = 0.045). The platelet in patients with 3 mutations and ≥ 4 mutations was higher than that in those with double mutations ( χ2 = 7.72, P = 0.021). After chemotherapy in 71 patients, the curative effect of 66 cases was evaluable, and the white blood count of 18 patients who did not reach complete remission was higher than that of 48 patients who reached complete remission ( Z = -2.74, P = 0.006). Conclusions:Most FLT3-ITD mutated patients with AML commonly show coexisting gene mutations, and the mutation types of coexisting genes are correlated with the clinical features of patients.
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O objetivo deste estudo foi classificar e comparar as habilidades motoras fundamentais de crianças de escolas públicas e privadas e verificar a compatibilidade das habilidades motoras fundamentais com a idade cronológica dos alunos. Os participantes foram 81 crianças saudáveis (10.6 ± 1.2 anos). O Test of Gross Motor Development - edition 2 foi usado para avaliar a habilidades motoras fundamentais. Os subtestes de habilidades motoras fundamentais foram comparados entre as escolas, usando o teste t para amostras independentes e o teste U de Mann Whitney. A idade cronológica foi comparada com a idade motora equivalente nos dois subtestes para cada escola separadamente, usando o teste estatístico de Wilcoxon. Alunos de escolas privadas obtiveram pontuação maior no subteste locomotor do que alunos de escolas públicas (p = 0.032), sem diferença no subteste controle de objetos (p = 0.733). O Quociente Motor Bruto indicou que os alunos de ambas as escolas apresentaram classificações de desempenho semelhantes classificadas como "muito ruim", "ruim" e "abaixo da média". Para os subtestes locomotor e controle de objetos, todos os escolares apresentaram idade motora equivalente menor que a cronológica. Alunos de ambas escolas apresentaram atraso no desenvolvimento motor, enquanto alunos de escolas privadas demonstraram maior eficiência nas habilidades motoras fundamentais de locomoção.(AU)
The purpose of this study was to classify and compare the fundamental motor skills of children from public and private schools and verify the compatibility of fundamental motor skills with students' chronological age. Participants were 81 healthy children (10.6±1.2 years). The Test of Gross Motor Development - edition 2was used to evaluate fundamental motor skills. Fundamental motor skills subtests were compared among schools, using the independent samples t-test and Mann Whitney U-test. Chronological age was compared with equivalent motor age in the two subtests for each school separately, using the Wilcoxon statistical test. Private school students had a higher score on the locomotor subtest than public school students (p=.032), with no difference on the object control subtest (p=.733). The Gross Motor Quotient indicated that the students of both schools presented similar performance ratings classified as "very poor", "poor" and "below average". For the locomotor and object control subtests, all schoolchildren had equivalent motor ages lower than their chronological age. Students from both schools had a delay in motor development, while private school students demonstrated greater efficiency in locomotor fundamental motor skills.(AU)
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Humans , Male , Female , Child , Psychomotor Performance , Exercise , Child Development , Growth and Development , Motor Skills , Physical Education and Training , Schools , Child , Motor ActivityABSTRACT
Objective: To discuss the proliferation inhibition and apoptosis induction of shikonin on the FMS-like tyrosine kinase-3 receptor internal tandem duplication (FLT3-ITD) mutated acute myeloid leukemia (AMD MV4-11 cells, and to preliminarily clarify the molecular mechanisms. Methods: The MV4-11 cells were divided into DMSO group and different concentrations (0.5, 1.0, 2.0, 4.0, and 8.0 μmol · L-1) of shikonin groups, and treated for 24 and 48 h. The inhibitory rate of proliferation was analyzed by CCK-8 assay, and half inhibitory concentration (IC50) was calculated. The MV4-11 cells were divided into blank control group, DMSO group, and different concentrations (0.25, 0.50, and 1. 00 μmol · L-1) of shikonin groups, and treated for 48 and 72 h; the proliferation rate of cells was analyzed by carbox fluorescenceindiacetate succinimidyl este (CFSE). The MV4-11 cells were divided into DMSO group and different concentrations (0.702, 1. 404, and 2. 808 μmol · L-1) of shikonin groups, and treated for 48 h; the apoptotic rate was determined by flow cytometry. The MV4-11 cells were divided into DMSO group and different concentrations (0.351, 0.702, and 1. 404 μmol · L-1) of shikonin groups, and treated for 48 h; the microRNA-155 (miR-155) expression level was detected by Real-time PCR. Results: The results of CCK-8 and CFSE methods indicated that the inhibitory rates of proliferation of MV4-11 cells in different concentrations of shikonin groups were increased compared with DMSO grpup (P<0.05 or P<0.01), and the proliferation rates were decreased (P<0.05 or P<0.01) in a concentration-dependent manner; the IC50 of 24 and 48 h were 1. 743 and 1. 404 μmol · L-1, respectively. The flow cytometry results showed that the apoptotic rates of the cells in different concentrations of shikonin groups were increased compared with DMSO group (P<0.01) in a concentration-dependent manner. The Real-time PCR results showed that the expression levels of miR-155 in the cells in different concentrations of shikonin groups were decreased significantly (P<0.01), and the expression level in 1.404 μmol · L-1 shikonin group was decreased by more than 75%. Conclusion: Shikonin could inhibit the proliferation and promote the apoptosis of FLT3-ITD mutated AML MV4-11 cells, and down-regulate the expression of miR-155, suggesting that shikonin may be one of the potential therapeutic drugs for FLT3-ITD mututed AML.
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Preeclampsia (PE) is a serious complications during pregnancy, with a global incidence of 2%–8%. It is one of the important causes of the incidence and death of pregnant women and parturients. The main clinical manifestations are hypertension (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg), proteinuria (>0.3 g/24 h) can be accompanied by renal dysfunction, thrombocytopenia, liver dysfunction, pulmonary edema and other multi-system and multiple organ involvement. Antiphospholipid antibody syndrome, hypertension, diabetes, chronic kidney disease, obesity, PE family history, multiple pregnancy, maternal old age are the risk factors of PE. At present, the pathogenesis of PE is not completely clear, but more and more evidences suggest that the abnormal level of angiogenic factors and coagulation dysfunction are the main causes of the disease. The research progress in recent years has been reviewed in present paper in the pathogenesis and clinical treatment of PE, so as to provide a reference for clinical use.
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Objective To systematically evaluate the effect of FMS﹣like tyrosine kinase 3 (FLT3) mutations on prognosis of acute promyelocytic leukemia. Methods The databases of CNKI, Wanfang, VIP, China Biology Medicine disc, PubMed, EMBase, and Cochrane Library were retrieved, and the cohort studies and case﹣control studies published from the establishment of the databases to December 2017 were selected according to the inclusion and exclusion criteria. The quality assessment and data extraction was performed and the statistical analysis was performed by using RevMan 5.3 software. Results Twenty﹣three studies were included, covering a total of 2 632 patients. Meta﹣analysis showed that patients with FLT3 internal tandem duplication (FLT3﹣ITD) mutation had lower complete remission rate ( RR＝0.92, 95% CI 0.86-0.99, P＝0.02), 3﹣year overall survival rate ( RR＝0.72, 95% CI 0.60-0.88, P＝0.001) and 5﹣year overall survival rate ( RR＝0.89, 95% CI 0.81-0.99, P＝ 0.03), while the proportion of high﹣risk group ( RR＝ 3.13, 95% CI 2.26-4.35, P< 0.01), the early mortality rate ( RR＝ 2.26, 95% CI 1.75-2.90, P< 0.01) and the recurrence rate ( RR＝1.50, 95% CI 1.11-2.02, P＝0.008) were relatively high, and the differences were statistically significant. The patients with FLT3 tyrosine kinase domain (FLT3﹣TKD) mutation had higher early mortality rate ( RR＝ 3.00, 95% CI 1.74-5.20, P< 0.01), and the difference was statistically significant. Conclusion The FLT3 mutations can influence the prognosis of acute promyelocytic leukemia, which contributes to the research direction of better prognosis stratification, perfect treatment regimen and improved prognosis.
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Introducción La parálisis cerebral infantil (PC) se clasifica en términos de función según varias escalas: unas son clínicas, como el GMFCS (Gross Motor Function Classification System), FMS (Functional Mobility Scale) y el cuestionario de evaluación funcional FAQ, (Gillette Functional Assessment Walking Scale), y otras, realizadas en el laboratorio de movimiento, como el GDI (Gait Deviation Index) y el GPS (Gait Profile Score). El objetivo del estudio fue establecer la concordancia entre las escalas clínicas y las escalas derivadas del laboratorio de análisis de movimiento. Metodología Se incluyó a 104 niños entre 5 y 16 años con diagnóstico de PC. Se realizó un estudio transversal y retrospectivo en que se analizaron los datos de 3 escalas clínicas de movilidad funcional y un análisis en 3D de la marcha, realizado en el laboratorio de análisis de movimiento con un equipo SMART-D/BTS y dos plataformas de fuerza. Resultados Respecto a la concordancia entre las escalas evaluadas, encontramos que el valor más alto de kappa (0,416) se obtuvo al confrontar FAQ y FMS a 50 m, lo que demostró una concordancia moderada. El resto de valores de kappa al comparar las diferentes escalas fueron menores a 0,4. Al relacionar las escalas según el porcentaje de acuerdo, encontramos que el mayor fue entre FMS y GPS con el 62,5%, seguido del 60,5% entre FAQ y FMS. Discusión No siempre una correlación aceptable significa una alta concordancia para clasificar a los pacientes en el mismo nivel de compromiso. La baja concordancia entre la mayoría de las escalas indica que el análisis de la marcha en el niño con PC debe realizarse de manera complementaria y llevar a cabo una evaluación con escalas clínicas, de calidad de vida, de funcionalidad y con el laboratorio de análisis de movimiento. Nivel de evidencia clínica. Nivel II.
Background Cerebral Palsy (CP) in children can be classified in terms of function according to several scales, some clinics such as GMFCS (Gross Motor Function Classification System), FMS (functional mobility Scale), FAQ (Gillette Functional Assessment Walking Scale); and others carried out in gait analysis such as the GDI (Gait Deviation Index), GPS (Gait Profile Score). The aim of this study was to determine the concordance between the clinical and gait analysis scales. Methods 104 children between five and sixteen years old diagnosed with Cerebral palsy were included. A cross sectional and retrospective study analyzed data from three clinical scales of functional mobility and a 3D gait analysis were carried out in gait analysis laboratory, using a SMART-D/BTS equipment and two strength platforms. Results Regarding the concordance between the scales evaluated, we found that the highest value of kappa (0416), occurred when confronting FAQ and FMS at 50 m, showing a moderate concordance. The remaining values of Kappa when comparing the different scales were smaller than 0.4. While when comparing the scales according to the percentage of agreement we found that the highest percentage was 62.50% when comparing FMS against GPS, followed by 60.50% when comparing FAQ against FMS. Discussion Not always an acceptable correlation means a high agreement to classify patients at the same level of involvement. The low correlation between most of the scales indicates that the gait analysis in children with Cerebral Palsy should be performed in a complementary manner, performing an assessment with clinical scales, quality of life, and functionality and with instrumented motion analysis. Evidence level. II.
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Humans , Child , Cerebral Palsy , Child , Health Classifications , GaitABSTRACT
Midostaurin is an orally administered inhibitor of multiple tyrosine kinase receptors developed by Novartis Pharmaceuti-cals. In May 2017,it was approved in the USA for the treatment of adult patients with newly diagnosed FMS-like tyrosine kinase 3 (FLT3) mutation-positive acute myeloid leukaemia (AML). Its pharmacokinetics,pharmacodynamics,clinical trials,adverse effects and drug interactions were introduced in the paper.
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Patients with acute myeloid leukaemia (AML) who have FMS-like tyrosine kinase 3 (FLT3) mutations are a concern for haematologists. Many studies indicate that these patients have poor prognosis. Due to the dearth of research in this area, the role of allogeneic transplantation as a therapy is still controversial. But the available limited data suggest that transplantation in first remission is possibly the first choice. As FTL3 mutations in AML result in poor patient outcomes, different FLT3 inhibitors are used as specific targeted therapy.
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FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation is a commonly found type of mutation in acute myeloid leukemia (AML), and this mutation is closely related to the development of AML and affects the prognosis of patients. FLT3-ITD-positive AML patients have poor prognosis and high relapse rate after treated with chemotherapy alone. The efficacy of allogeneic hematopoietic stem cell transplantation for this disease is controversial. Targeted therapies such as sorafenib and the combination of different type of therapies have been carried out and have shown preliminary effect in preclinical or clinical trials. In this paper, the clinical effect of FLT3-ITD in AML patients and the latest progress of its treatment were reviewed.
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BACKGROUND: Management of pregnant women at high risk of pre-eclampsia (PE) requires frequent monitoring, with referral to specialized perinatal care centers. Reliable tests are necessary to improve prediction of PE and related complications and to assess disease severity and progression. An imbalance in two biomarkers, soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF), is involved in PE pathogenesis. The sFlt-1 to PlGF ratio is increased in pregnant women before the onset of PE. An elevated ratio is highly predictive of PE, whereas the diagnosis of PE can be ruled out within one week for low ratios. The main objective of this study was to assess whether a low sFlt-1/PlGF ratio, below a cutoff of 38, can predict the absence of PE within one week. METHODS: We performed a prospective, monocentric, observational study to evaluate serum sFlt-1/PlGF ratio (Roche Diagnostics Cobas e411 system) for predicting -PE in a group of 67 high-risk pregnant women (20–37 gestation weeks). RESULTS: Among the 67 patients included, 53 had a sFlt-1/PlGF ratio lower than 38; none developed subsequent PE leading to a negative predictive value of 100%. Eight patients developed clinical PE. The positive predictive value was 21% at one week and 18% at four weeks, in accordance with previous studies. CONCLUSIONS: The serum sFlt-1/PlGF ratio showed highly predictive performances for ruling out PE. Using these biomarkers in routine management of PE may improve clinical care and avoid inappropriate hospitalization, which has a significant economic impact.
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Female , Humans , Pregnancy , Biomarkers , Diagnosis , Hospitalization , Observational Study , Perinatal Care , Pre-Eclampsia , Pregnant Women , Prospective Studies , Referral and Consultation , Vascular Endothelial Growth Factor Receptor-1ABSTRACT
To explore the efficacy of sorafenib combined with chemotherapy and donor lymphocyte infusion (DLI) in patients with FLT3-positive acute myeloid leukemia (AML) relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Of the 14 patients relapsed after allo-HSCT,9 achieved complete remission after salvage therapy of sorafenib combined with chemotherapy and DLI,6 with complete molecular remission,2 with partial remission,and 3 with no response.With a median follow up of 220 (range,30-1 782) days after post-transplantation relapse,7 patients were still alive and 7 died.Salvage therapy of sorafenib combined with chemotherapy and DLI shows a decent therapeutic effect for FLT3-positive AML relapsed after allo-HSCT.
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ABSTRACT CONTEXT: Acute promyelocytic leukemia (APL) accounts for 8% to 10% of cases of acute myeloid leukemia (AML). Remission in cases of high-risk APL is still difficult to achieve, and relapses occur readily. CASE REPORT: Here, we describe a case of APL with high white blood cell counts in blood tests and hypogranular variant morphology in bone marrow, together with fms-like tyrosine kinase-3 with internal tandem duplication mutations (FLT3-ITD), and bcr-3 isoform of PML-RARα. Most importantly, we detected high level of Wilms’ tumor gene (WT1) in marrow blasts, through the reverse transcription polymerase chain reaction (RT-PCR). To date, no clear conclusions about an association between WT1 expression levels and APL have been reached. This patient successively received a combined treatment regimen consisting of hydroxycarbamide, arsenic trioxide and idarubicin plus cytarabine, which ultimately enabled complete remission. Unfortunately, he subsequently died of sudden massive hemoptysis because of pulmonary infection. CONCLUSION: Based on our findings and a review of the literature, abnormal functioning of WT1 may be a high-risk factor in cases of APL. Further studies aimed towards evaluating the impact of WT1 expression on the prognosis for APL patients are of interest.
RESUMO CONTEXTO: Leucemia promielocítica aguda (LPA) compreende 8% a 10% dos casos de leucemia mieloide aguda (LMA). A remissão em casos de LPA de alto risco ainda é dificilmente conseguida, e recorrência é comum. RELATO DE CASO: Descrevemos aqui um caso de LPA com glóbulos brancos elevados no exame de sangue e a morfologia variante hipogranular na medula óssea, juntamente com fms-like tirosina-quinase-3 com mutações de duplicação em tandem interna (FLT3-ITD) e a isoforma bcr-3 de PML- RARα. Mais importante, detectamos alto nível de gene do tumor de Wilms (WT1) em blastos medulares por RT-PCR (reverse transcription polimerase chain reaction). Até agora, não há conclusões claras sobre a associação entre os níveis de expressão WT1 e APL. Este paciente recebeu sucessivamente regime de tratamento combinado, de hidroxicarbamida, trióxido de arsênico e idarrubicina e citarabina, alcançando finalmente a remissão completa. Infelizmente, em seguida, ele morreu de repente de hemoptise maciça devido a uma infecção pulmonar. CONCLUSÃO: Com base em nossos resultados e numa revisão da literatura, a função anormal de WT1 pode ser um fator de alto risco em casos de APL. Novos estudos, com o objetivo de avaliar o impacto da expressão de WT1 no prognóstico dos doentes com APL, são de interesse.
Subject(s)
Humans , Male , Adult , Leukemia, Promyelocytic, Acute/genetics , Genes, Wilms Tumor , fms-Like Tyrosine Kinase 3/genetics , Prognosis , Leukemia, Promyelocytic, Acute/pathology , Leukemia, Promyelocytic, Acute/drug therapy , Polymerase Chain Reaction , Risk Factors , Proto-Oncogene Proteins c-bcr , MutationABSTRACT
Objective To investigate the prognostic value of Fms-like tyrosine kinase3, intenal tandem duplication (FLT3-ITD) detection by DNA extracted from stored bone marrow slides in chemical method. Methods Trace DNA was extracted from 58 bone marrow slides which were stored for 1-5 years below 20 ℃, including 48 patients with de novo acute myeloid leukemia (AML) and 10 controls without hematologic malignancies. Polymerase chain reaction (PCR) was used to detect the FLT3-ITD of these bone marrow slides samples. Results There were 6 patients of FLT3-ITD+ detected in these 48 AML patients (12.5 %, 6/48). No FLT3-ITD was found in 10 healthy controls. AML patients with FLT3-ITD+ had low complete time compared with FLT3-ITD-patients (x2= 7.274, P= 0.007). Splenohepatomegalia and FLT3 mutation were the risk factors affecting AML patients with CR after the first chemotherapy (OR= 7.2, P=0.12; OR=36.3, P=0.10). FLT3-ITD was a risk factor of poor prognosis in patients with newly diagnosed AML (RR=9.088, P= 0.029). Conclusion Extraction of AML bone marrow slides trace DNA by using chemical method can be widely applied in clinic and is a key experimental way to study the molecular biology retrospectively. Furthermore, the detection of FLT3-ITD by trace DNA extracted from stored bone marrow slides can be used to predict the prognosis of AML.