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1.
Medicine (Baltimore) ; 100(35): e26959, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477125

RESUMO

ABSTRACT: The purpose of this study was to evaluate the correlation of long non-coding RNA maternally expressed gene 3 (Lnc-MEG3) with disease features, treatment response, and survival in pediatric acute myeloid leukemia (AML) patients.Among 92 de novo pediatric AML patients (before treatment and after 1 course of induction) and 40 controls, bone marrow mononuclear cells were obtained. Then, Lnc-MEG3 expression was determined by reverse transcription quantitative polymerase chain reaction. After 1 course of standard induction therapy of pediatric AML patients, complete remission (CR) was assessed. Furthermore, event-free survival (EFS) and overall survival (OS) were determined according to follow-up data.Lnc-MEG3 was reduced in pediatric AML patients compared with controls. In pediatric AML patients, Lnc-MEG3 was correlated with French-American-Britain subtypes and lower Chinese Medical Association risk stratification, while it was not associated with cytogenetic features, FLT3-ITD mutation, CEBPA mutation, NPM1 mutation, WT1 mutation, or National Comprehensive Cancer Network risk stratification. After 1 course of treatment, Lnc-MEG3 exhibited an up-regulation trend. Furthermore, Lnc-MEG3 was of no difference before treatment between patients with and without CR, while elevated Lnc-MEG3 and change of Lnc-MEG3 after 1 course of treatment were associated with increased CR rate. Additionally, increased Lnc-MEG3 expression before treatment was associated with longer EFS but not OS, while enhanced Lnc-MEG3 expression after 1 course of treatment was correlated with both prolonged EFS and OS.Lnc-MEG3 may have clinical significance as a biomarker for assisting with disease management, treatment optimization, and prognosis improvement in pediatric AML patients.


Assuntos
Biomarcadores Tumorais/análise , Leucemia Mieloide/genética , Leucemia Mieloide/mortalidade , RNA Longo não Codificante/análise , Criança , Pré-Escolar , Feminino , Humanos , Leucemia Mieloide/complicações , Masculino , Prognóstico , Indução de Remissão
2.
Rinsho Ketsueki ; 62(8): 978-987, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497238

RESUMO

Recurrence in acute myeloid leukemia (AML) is a major barrier in patients who achieve complete remission after induction of remission and consolidation therapy and desire long-term survival. Allogeneic hematopoietic stem cell transplantation lowers recurrence risk in patients; however, recurrence is common even after transplantation. Many maintenance therapies for AML aim to lower recurrence risk; therefore, research has focused on identifying drugs with a tolerable adverse-effect profile. Thus far, many trials of cytotoxic anticancer drugs used in maintenance therapy have showed no improvement in survival rates. In contrast, recent studies on immunomodulation, epigenetics, molecular-targeted drugs, etc. have demonstrated promising results. Therefore, we plan to review various maintenance therapies, such as immunotherapy, demethylating agents, and targeted therapies (including fms-like tyrosine kinase 3 inhibitors in particular) based on the current evidence. Moreover, we describe a new strategy that incorporates the assessment of measurable minimal residual disease.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Preparações Farmacêuticas , Humanos , Japão , Leucemia Mieloide Aguda/tratamento farmacológico , Uso Off-Label , Indução de Remissão
3.
JNMA J Nepal Med Assoc ; 59(240): 791-794, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34508471

RESUMO

INTRODUCTION: Treatment of lupus nephritis consists of six months of induction immunosuppression followed by years of maintenance immunosuppression. The aim of present study was to find the prevalence of remission after six months of induction immunosuppressive treatment with induction therapy in patients with lupus nephritis. METHODS: A descriptive cross-sectional study was conducted in the nephrology unit of department of internal medicine of a tertiary care hospital from September 2018 to September 2020. The study was approved by institutional review committee of same institution (reference number 184/2018). Convenience sampling method was used and Statistical Package for Social Sciences version 26 was used for statistical analysis. Point estimate at 90% Confidence Interval was calculated along with frequency and proportion for binary data. RESULTS: Out of 24 patients, overall remission was seen in 21 patients (87.4%) (90% Confidence Interval= 76.26-98.54). Complete remission and partial remission were seen in 16 (66.6%) and 5 (20.8%) patients respectively resulting in an at the end of six months of induction immunosuppressive treatment. The most common class of lupus nephritis was class IV, 7 patients, followed by class IV+V, and class V, 6 patients in each respectively. The mean 24-hour urinary total protein, serum albumin and serum creatinine were 2492±1051 mg, 2.1±0.4 g/dl, and 0.9±0.1 mg/dl respectively. Adverse events were observed in 6 (25%) patients. CONCLUSIONS: Our study shows that good proportions of patients with lupus nephritis achieve clinical remission at the end of six months of induction immunosuppressive treatment with induction therapy, however, at the cost of some tolerable side effects.


Assuntos
Nefrite Lúpica , Ácido Micofenólico , Estudos Transversais , Humanos , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/epidemiologia , Prednisolona/uso terapêutico , Indução de Remissão , Resultado do Tratamento
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1011-1018, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362476

RESUMO

OBJECTIVE: To the clinical characteristics and prognostic value of the patients with complete deletion of TET_JBP domain (ΔJBP) in TET2 acute myeloid leukemia (AML). METHODS: Next Generation Sequencing technology was used to determine the mutations of 34 AML-related genes (including TET2 gene). The I-TASSER tool was used to predict the tertiary structure of the full-length TET2 protein and TET_JBP structure deletion. RESULTS: Among 38 AML patients with TET2 mutations, 22(57.9%) showed truncation mutations, of which 16 (72.7%) produced TET2ΔJBP truncation mutants. Protein structure prediction showed that the deletion of TET_JBP domain lead to the significant changes of tertiary structure in TET2 protein. Compared with the patients in non-ΔJBP group, the age of patients in ΔJBP group were older (63 vs 54 years old, P=0.047), and the occurrence rate of CEBPA double mutation (CEBPAdm) were more frequency (31.3% vs 0, P=0.009), the complete remission (CR) rate after induction chemotherapy(37.5% vs 81.8%, P=0.008) were lower, the median EFS (5 vs 19 months, P=0.000) and median OS (16 vs 22 months, P=0.041) were shorter. Univariate analysis showed that platelets <50×109/L (P=0.004) and CEBPAdm (P=0.001) were related to the shorter OS of the patients. Further COX multivariate analysis showed that CEBPAdm is an independent prognostic factors of OS in TET2ΔJBP patients (P=0.010). In addition, ΔJBP patients with CEBPAdm showed lower hemoglobin levels (62 vs 75g/L, P=0.030) and lower median OS (9 months vs 18 months, P=0.000) than the patients without CEBPAdm. CONCLUSION: AML patients with TET2ΔJBP truncation mutant shows lower CR rate, shorter EFS and OS after induction chemotherapy, which may be related to the poor prognosis, and co-mutation with CEBPAdm, which is the independent prognostic factors of OS in AML patients with TET2ΔJBP.


Assuntos
Leucemia Mieloide Aguda , Proteínas de Ligação a DNA/genética , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Proto-Oncogênicas/genética , Indução de Remissão
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1071-1079, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362484

RESUMO

OBJECTIVE: To compare the efficacy and safety of different doses of daunorubicin combined with a standard dose of cytarabine as induction chemotherapy in newly diagnosed primary acute myeloid leukemia (AML) patients. METHODS: The clinical data and outcome were retrospectively analyzed in 86 newly diagnosed primary AML patients who were under 65 years old and treated with daunorubicin combined with cytarabine (DA regimen) at West China Hospital of Sichuan University from January 2017 to June 2019. Patients were divided into 2 groups based on the dose of daunorubicin they received, 35 cases in the escalated-dose group ï¼»75 mg/(m2·d)ï¼½ and 51 cases in the standard-dose group ï¼»60 mg/(m2·d)ï¼½. And then the effects of different doses of daunorubicin on complete remission (CR) rate, minimal residual disease (MRD)-negative CR rate, relapse-free survival (RFS), overall survival (OS), and adverse events were analyzed. RESULTS: Median follow-up time of all the patients was 15 months. The CR rate and MRD- CR rate of the escalated-dose group was 88.5% and 71.4%, respectively, which were higher than 64.7% and 41.2% of the standard-dose group (P=0.029, P=0.008). The estimated 2-year RFS of the escalated-dose group was 68.4%, which was higher than 38.5% of the standard-dose group (P=0.015), but estimated 2-year OS showed no statistically significant difference (77.1% vs 66.7%, P=0.059), as well as grade 3-4 adverse events. The escalated dose of daunorubicin had prolonged RFS (13 months vs not reached, P=0.022) and OS (23 months vs not reached, P=0.029) in the FLT3-ITD- AML patients. CONCLUSION: The escalated dose of daunorubicin can induce higher complete remission rate, deeper remission and longer duration of remission without increasing adverse events in newly diagnosed primary AML patients.


Assuntos
Daunorrubicina , Leucemia Mieloide Aguda , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Citarabina/uso terapêutico , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Indução de Remissão , Estudos Retrospectivos
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1080-1084, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362485

RESUMO

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with acute myeloid leukemia(AML) combined with paroxysmal nocturnal hemoglobinuria(PNH). METHODS: The clinical data of 13 AML combined with PNH patients treated in our hospital from January 2017 to May 2019 were collected and retrospective analyzed. The complete remission(CR) rate for induction chemotherapy was analyzed. The level of PNH+ cell before and after chemotherapy were tested by Paired t test. Kaplan-Meier method and multi-factorial Cox regression model were used to analyze the influencing factors of prognosis. RESULTS: Among the 13 patients, 11 (84.6%) cases were CR after first induction chemotherapy. The median overall survival(OS) time was 17 months(0-30 months), the median progression-free survival(PFS) time was 16 months(2-26 months). There were no significant difference in the number of PNH+ cell before and after chemotherapy (P>0.05). Multivariate Cox regression analysis showed that age,sex,the level of hemoglobin, platelet were not related to the OS of the patients(P>0.05), the level of WBC, LDH and risk stratification at first diagnosed were related to the OS of the patients(P<0.05). Kaplan-Meier survival analysis showed that the OS rate of AML combined with PNH patients with leukocyte lower than 10×109/L at first diagnosed was better than that of the patients with leukocyte higher than 10×109/L (P=0.0261). The OS rate of patients with low or standard risk was better than the patients with high risk group(P=0.0010). CONCLUSION: The patients of AML combined with PNH have higher CR rate after the first induction chemotherapy. The level of WBC and LDH at first diagnosed are the factors that affecting the OS of the patients. The OS of patients with WBC lower than 10×109/L, at first diagnosed low and medium risk are better than the other patients.


Assuntos
Hemoglobinúria Paroxística , Leucemia Mieloide Aguda , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Prognóstico , Indução de Remissão , Estudos Retrospectivos
7.
BMC Gastroenterol ; 21(1): 316, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362299

RESUMO

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) is widely used as a remission induction therapy for active ulcerative colitis (UC) patients. However, there are no available biomarkers for predicting the clinical outcome of GMA. We investigated the utility of Fecal calprotectin (FC) as a biomarker for predicting the clinical outcome during GMA therapy in active UC patients. METHODS: In this multicenter prospective observation study, all patients received 10 sessions of GMA, twice a week, for 5 consecutive weeks. FC was measured at entry, one week, two weeks, and at the end of GMA. Colonoscopy was performed at entry and after GMA. The clinical activity was assessed based on the partial Mayo score when FC was measured. Clinical remission (CR) was defined as a partial Mayo score of ≤ 2 and endoscopic remission (ER) was defined as Mayo endoscopic subscore of either 0 or 1. We analyzed the relationships between the clinical outcome (CR and ER) and the change in FC concentration. RESULT: Twenty-six patients were included in this study. The overall CR and ER rates were 50.0% and 19.2%, respectively. After GMA, the median FC concentration in patients with ER was significantly lower than that in patients without ER (469 mg/kg vs. 3107 mg/kg, p = 0.03). When the cut-off value of FC concentration was set at 1150 mg/kg for assessing ER after GMA, the sensitivity and specificity were 0.8 and 0.81, respectively. The FC concentration had significantly decreased by one week. An ROC analysis demonstrated that the reduction rate of FC (ΔFC) at 1 week was the most accurate predictor of CR at the end of GMA (AUC = 0.852, P = 0.002). When the cut-off value of ΔFC was set at ≤ 40% at 1 week for predicting CR at the end of GMA, the sensitivity and specificity were 76.9% and 84.6%, respectively. CONCLUSION: We evaluated the utility of FC as a biomarker for assessing ER after GMA and predicting CR in the early phase during GMA in patients with active UC. Our findings will benefit patients with active UC by allowing them to avoid unnecessary invasive procedures and will help establish new strategies for GMA.


Assuntos
Remoção de Componentes Sanguíneos , Colite Ulcerativa , Biomarcadores , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Fezes , Granulócitos , Humanos , Mucosa Intestinal , Complexo Antígeno L1 Leucocitário , Monócitos , Estudos Prospectivos , Indução de Remissão , Resultado do Tratamento
9.
Zhonghua Nei Ke Za Zhi ; 60(9): 784-790, 2021 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-34445813

RESUMO

Lupus nephritis (LN) refers to renal involvement in systemic lupus erythematosus and is characterized by hematuria, proteinuria, edema, hypertension and renal insufficiency. The complete remission rate of proliferative LN remains low using the current induction protocols and LN tends to flare. Scientific and standardized diagnosis and therapy are crucial for the treatment of LN. Therefore, based on the current international and domestic experiences and guidelines, the Chinese Rheumatology Association developed the recommendations of diagnosis and therapy for LN, with the purpose of enhancing efficacy, reducing flare, halting renal progression and improving outcome of LN.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , China , Humanos , Rim , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/terapia , Indução de Remissão
10.
Eur J Endocrinol ; 185(4): 587-595, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34374649

RESUMO

Objective: Transsphenoidal surgery (TSS) is mainly indicated in prolactinomas when dopamine agonist treatment fails. However, there is no established early predictor of cabergoline (CBG) response. The present study was aimed to identify predictors of CBG resistance in order to select patients who may benefit from early TSS. Design: Retrospective longitudinal study. Methods: We reviewed the medical record of patients diagnosed with prolactinoma after 2010. Inclusion criteria: macroprolactinomas under CBG treatment with serial prolactin levels and MRI before treatment and 3 and 12 months afterwards. The main outcome was tumour size shrinkage ≥ 50% (using the two largest diameters in sagittal view) after 12 months of CBG (TS_50). The capacity of the most important clinical and biochemical variables in predicting the main outcome was examined. Results: A total of 185 prolactinomas where included: 124 (67.0%) were microadenomas and 61 (33.0%) were macroadenomas of which 27 patients meet de inclusion criteria; median age (42.5 years; (IQR: 28.0)). The median follow-up was (67.5 months; (IQR: 30.2)). Ten patients (37.0%) underwent surgery after more than 1 year of CBG. The volume reduction at the first MRI (3-4 months) was the unique valuable predictor: (OR: 1.16 (95% CI: 1.02-1.32)) of TS_50. A tumour volume shrinkage of ≥ 30% in the first 3-4 months of CBG therapy predicts TS_50 with an AUC (0.95 (CI: 0.76-0.99)). Conclusion: Tumour shrinkage in the first 3-4 months after starting treatment with CBG is a good tool for predicting the long-term response and can help clinicians to take more appropriated and personalized decisions.


Assuntos
Cabergolina/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Carga Tumoral/efeitos dos fármacos , Adolescente , Adulto , Idoso , Cabergolina/farmacologia , Criança , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/patologia , Prognóstico , Prolactinoma/diagnóstico , Prolactinoma/patologia , Indução de Remissão , Estudos Retrospectivos , Espanha , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
Eur J Endocrinol ; 185(4): 553-563, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34342595

RESUMO

Objective: Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. Design: Participants with newly diagnosed Graves' disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. Results: Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). Conclusion: Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.


Assuntos
Tecido Adiposo Marrom/metabolismo , Hipertireoidismo/metabolismo , Hipertireoidismo/reabilitação , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/efeitos dos fármacos , Adulto , Idoso , Antitireóideos/farmacologia , Antitireóideos/uso terapêutico , Composição Corporal/efeitos dos fármacos , Composição Corporal/fisiologia , Carbimazol/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Feminino , Fluordesoxiglucose F18 , Doença de Graves/tratamento farmacológico , Doença de Graves/metabolismo , Doença de Graves/reabilitação , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Metimazol/uso terapêutico , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Indução de Remissão , Singapura , Termogênese/efeitos dos fármacos , Termogênese/fisiologia , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/fisiologia , Adulto Jovem
12.
Medicine (Baltimore) ; 100(29): e26733, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398050

RESUMO

ABSTRACT: Treatment of ANCA-associated vasculitis (AAV) improved over the last decades but disease-unspecific agents such as cyclophosphamide are still associated with serious adverse events, including high rates of infectious complications and malignancy with increased mortality.In this comparative cohort study, we included 121 AAV patients with renal involvement from 2 German vasculitis centers. Patients were separated into subsequent groups: 2.5 to 3 g vs >3 g cumulative cyclophosphamide induction dose. We investigated if a cyclophosphamide induction dose of 2.5 to 3 g could maintain efficacy while minimizing adverse events in AAV patients with renal involvement.Patients with 2.5 to 3 g vs >3 g cumulative cyclophosphamide (median 3.0 g vs 5.5 g, P < .001) had a comparable time to remission (median 4.0 vs 3.8 months, log-rank P = .87) with 90.6% and 91.5% achieving remission after 12 months. Refractory disease was low in both groups (median 3.6% vs 6.2%, P = .68) and relapse rate did not differ (median 36% vs 42%, log-rank P = .51). Kidney function was comparable at disease onset in both groups (eGFR, mean ±â€ŠSD 29 ±â€Š20 mL/min/1.73 m2 vs 35 ±â€Š26 mL/min/1.73 m2, P = .34) and improved after 2 years irrespective of the cyclophosphamide dose (ΔeGFR, mean ±â€ŠSD +8.9 ±â€Š1.4 mL/min/1.73 m2 vs +6.0 ±â€Š1.1 mL/min/1.73 m2, P = .33). The 2.5-3 g group had a lower rate of leukopenia (HR = 2.73 [95% CI, 1.2-6.3], P = .014) and less infectious episodes per patient (median 1.2 vs 0.7, P = .012), especially urinary tract infections (HR = 2.15 [95% CI, 1.1-4.5], P = .032).A cyclophosphamide induction dose of 2.5 to 3 g was able to induce remission and prevent from relapses with fewer cases of leukopenia and less infectious episodes during follow-up. Especially elderly AAV patients who are particularly susceptible to infectious complications could benefit from minimizing dosing regimens with maintained efficacy to control disease activity.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Resultado do Tratamento
13.
Blood Adv ; 5(17): 3279-3289, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34459887

RESUMO

The tyrosine-protein phosphatase nonreceptor type 11 (PTPN11) is an important regulator of RAS signaling and frequently affected by mutations in patients with acute myeloid leukemia (AML). Despite the relevance for leukemogenesis and as a potential therapeutic target, the prognostic role is controversial. To investigate the prognostic impact of PTPN11 mutations, we analyzed 1529 adult AML patients using next-generation sequencing. PTPN11 mutations were detected in 106 of 1529 (6.93%) patients (median VAF: 24%) in dominant (36%) and subclonal (64%) configuration. Patients with PTPN11 mutations were associated with concomitant mutations in NPM1 (63%), DNMT3A (37%), and NRAS (21%) and had a higher rate of European LeukemiaNet (ELN) favorable cytogenetics (57.8% vs 39.1%; P < .001) and higher white blood cell counts (P = .007) compared with PTPN11 wild-type patients. In a multivariable analysis, PTPN11 mutations were independently associated with poor overall survival (hazard ratio [HR]: 1.75; P < .001), relapse-free survival (HR: 1.52; P = .013), and a lower rate of complete remission (odds ratio: 0.46; P = .008). Importantly, the deleterious effect of PTPN11 mutations was confined predominantly to the ELN favorable-risk group and patients with subclonal PTPN11 mutations (HR: 2.28; P < .001) but not found with dominant PTPN11 mutations (HR: 1.07; P = .775), presumably because of significant differences within the rate and spectrum of associated comutations. In conclusion, our data suggest an overall poor prognostic impact of PTPN11 mutations in AML, which is significantly modified by the underlying cytogenetics and the clonal context in which they occur.


Assuntos
Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Mutação , Fosfoproteínas Fosfatases , Prognóstico , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Indução de Remissão
14.
Hematology ; 26(1): 552-555, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34348601

RESUMO

OBJECTIVE AND IMPORTANCE: Rosai-Dorfman disease (RDD) is a benign and rare non-Langerhans cell histiocytic proliferative disorder. Laryngeal involvement is an unusual site of extranodal involvement of RDD. Laryngeal RDD can cause life-threatening airway obstruction that requires effective control of the disease. In this study, we report three cases of laryngeal RDD with excellent and durable responses to thalidomide. CLINICAL PRESENTATION: Patient 1 was a 39-year-old male who presented with a two-year history of nasal obstruction. Patient 2 was a 26-year-old woman who presented complaining of a hoarse voice for one year. Patient 3 was a 24-year-old man who presented with complaints of a hoarse voice and progressing dyspnea for five months. Electronic laryngoscopy revealed submucous nodular lesions in the nasal cavity, nasopharynx, and larynx of the three patients. Biopsy of the lesions showed large histiocytes with abundant pale cytoplasm which were S-100 and CD68 positive consistent with RDD. INTERVENTION: Before thalidomide treatment, patient 1 received chemotherapy and six times surgical excision due to the recurrence of laryngeal lesions. Patient 2 failed steroid treatment. Patient 3 underwent an emergency tracheostomy due to airway obstruction. All three patients then received thalidomide 100 mg/d treatment and achieved satisfactory and durable responses with the longest follow-up of 45 months. CONCLUSION: Thalidomide may induce long-term remission in laryngeal RDD.


Assuntos
Histiocitose Sinusal/tratamento farmacológico , Doenças da Laringe/tratamento farmacológico , Talidomida/administração & dosagem , Adulto , Feminino , Histiocitose Sinusal/metabolismo , Histiocitose Sinusal/patologia , Humanos , Doenças da Laringe/metabolismo , Doenças da Laringe/patologia , Laringe/metabolismo , Laringe/patologia , Masculino , Indução de Remissão
15.
Zhonghua Yi Xue Za Zhi ; 101(30): 2387-2391, 2021 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-34404132

RESUMO

Objective: To analyze the effect of triple-induction regimen including all-trans retinoic acid(ATRA), arsenic trioxide(ATO) plus anthracyclines and double-induction regimen including ATRA and ATO for adults with non-high-risk acute promyelocytic leukemia(APL). Methods: The clinical data of adult patients with non-high-risk APL who were first diagnosed and admitted to the Henan Provincial People's Hospital from January 2009 to December 2019 were retrospectively analyzed. All patients were divided into triple-induction group and double-induction group according to the treatment. The general data of patients, blood routine, coagulation function changes and blood transfusions during the induction period were collected, and the complete remission rate, early mortality and prognosis of two groups were analyzed. Results: A total of 164 patients were enrolled, including 86 males and 78 females, and the M(Q1,Q3) of their age was 41(18, 70) years. Among them, 75 were in triple-induction group and 89 in double-induction group. The white blood cell(WBC) counts of triple-induction group on day 7th and 14th after induction were (9.49±6.10)×109/L and (5.43±3.97)×109/L, while those in double-induction group were (15.17±17.06)×109/L and (13.37±12.59)×109/L, the differences were statistically significant (both P<0.05). In addition, the peak of WBC in the triple-induction group was lower than that in the double-induction group [13.8(6.3,89.7)×109/L vs 19.2(3.8,112.8)×109/L, P=0.019]. On day 7th after induction, the platelet(PLT) counts in the triple-induction group was lower than that in the double-induction group [27(11,147)×109/L vs 45(8, 183)×109/L, P=0.014]. However, the difference was not statistically significant in PLT counts between the two groups on day 14th, 21st and 28th, or in PLT transfusions during induction (all P>0.05). After treatment, it was observed only in a few patients of two groups that the prothrombin time(PT) elongation ≥3 s and/or activated partial thromboplastin time(APTT) elongation ≥10 s, and the difference was not statistically significant (all P>0.05). The incidence of induced differentiation syndrome in the triple-induction group was lower than that in the double-induction group (2.7% vs 12.4%, P=0.022) The early mortality rate was lower than that in the double-induction group (1.3% vs 5.6%), but the difference was not statistically significant (P>0.05). There were no statistically significant differences in the early complete remission rate, genetic remission rate, molecular remission rate, relapse rate, overall survival (OS) rate and disease-free survival (DFS) rate between the two groups. Conclusion: For adults with non-high-risk APL, the triple-induction therapy can reduce the counts and peaks of WBC, and reduce the incidence of induced differentiation syndrome.


Assuntos
Arsenicais , Leucemia Promielocítica Aguda , Adulto , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Trióxido de Arsênio/uso terapêutico , Arsenicais/uso terapêutico , Feminino , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Masculino , Óxidos/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Tretinoína/uso terapêutico
16.
Zhonghua Er Ke Za Zhi ; 59(7): 557-562, 2021 Jul 02.
Artigo em Chinês | MEDLINE | ID: mdl-34405637

RESUMO

Objective: To analyze the efficacy and safety of the biological agent infliximab (IFX) in the treatment of pediatric Crohn's disease. Methods: A total of 86 children with Crohn's disease who had received IFX in three hospitals (Ruijin Hospital, Ruijin Hospital North and Shanghai Children's Hospital) in Shanghai from January 2007 to December 2017 were included in this retrospective study. The efficacy of IFX was assessed by comparing clinical and laboratory data before and after IFX treatment. Student t test, Mann-Whitney U test or chi-square test were used to analyze the data of the two groups. Logistic reggression analysis were used to analyze the effects of variables such as age, clinical characteristics, disease behavior and combined medications on the efficacy and safety of IFX. Results: Among the 86 children with Crohn's disease in the study, 50 were males and 36 females. The IFX treatment was initiated at 12.0 (7.1, 13.6) years of age, and the follow-up period was 94.1 (47.8, 185.5) weeks. Efficacy analysis showed that in the induction remission phase, the clinical response rate was 97% (79/81) and the remission rate was 74% (60/81). In the maintenance remission phase, the clinical response rate was 75% (51/68) and the remission rate was 68% (46/68). After 34 weeks of treatment with IFX, pediatric Crohn's disease activity index (PCDAI) (5 (0, 10) vs. 36 (26, 45)), C-reactive protein (3 (1, 8) vs. 8 (3, 31) mg/L), erythrocyte sedimentation rate (10 (6, 10) vs. 35 (20, 50) mm/1 h), platelet ( (327±107)×109 vs. (438±159) ×109/L), albumin ((37±6) vs. (30±6) g/L), hemoglobin ((116±16) vs. (103±18) g/L), change of body weight (-0.5±1.2 vs. -1.0±0.9), anemia (29% (20/68) vs. 75% (51/68)), and perianal disease (13/21 vs. 0) were significantly improved (all P<0.05). By the end of 34 weeks of IFX treatment, 25% (17/68) of children experienced secondary loss of response to IFX. Logistic reggression analysis showed that PCDAI>30 was positively correlated with secondary loss of response (OR=3.823, 95%CI 1.015-15.328, P=0.048), and combined with azathioprine was conducive to maintaining efficacy of IFX (OR=0.440, 95%CI 0.106-1.033, P=0.044). The IFX-related adverse events included infusion reactions in 17% (15/86) and infections in 42% (36/86) of children. Analysis showed that age<6 years was a risk factor for infusion reactions (χ2=6.556, P=0.010), and combined use of steroids (χ2=5.230, P=0.022) may increase the incidence of infection. Conclusions: IFX is effective in the treatment of pediatric Crohn's disease with favorable safety. Reducing secondary loss of response to IFX is an urgent issue that need to be addressed. At the same time, it is necessary to pay close attention to the adverse events during IFX treatment.


Assuntos
Doença de Crohn , Criança , China , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Infliximab/efeitos adversos , Masculino , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
17.
Trials ; 22(1): 530, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380536

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that can involve multiple organs or systems. Lupus nephritis (LN) is associated with high mortality and morbidity. However, plenty of patients do not respond to present treatment or relapse. Iguratimod (IGU) is a new small molecular, anti-rheumatic drug and has shown the potential for drug repurposing from rheumatoid arthritis (RA) to LN treatment. It has been approved for treating RA in northeast Asia. Beyond expectation in a recent observational study, over 90% of thirteen refractory LN patients responded to iguratimod monotherapy in 24 weeks, with no steroids dose increasing or any other medication add-on during the entire follow-up. METHODS/DESIGN: This study is a multi-center, randomized, 52-week parallel positive drug-controlled study. The study was designed as a head-to-head comparison between the iguratimod and present first-line therapy on LN patients. A total of 120 patients (60 patients each group) is in the enrolling plan. All enrolled patients are assigned randomly into trial and control groups. The patients will be selected from six study sites in China and will all have biopsy-proven active lupus nephritis. In the first 24 weeks of the trial, IGU is compared with cyclophosphamide as an induction therapy, and in the second 24 weeks, IGU is compared with azathioprine as a maintenance therapy. The primary outcome is renal remission rate including both complete remission and partial remission at week 52, which will be analyzed using a non-inferiority hypothesis test. DISCUSSION: Most patients diagnosed with SLE will develop LN within 5 years and LN remains a major cause of morbidity and death for SLE patients. Although some medications are proven effective for the treatment of this condition, at least 20-35% LN patients have to suffer from relapse or ineffective treatment and medication intolerance is also frequent. This trial is designed to demonstrate whether iguratimod can be used as an alternative induction or maintenance therapy in subjects who have lupus nephritis. Data from this study will provide an evidence on whether or not iguratimod should be recommended to active LN patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02936375 . Registered on October 18, 2016.


Assuntos
Azatioprina , Nefrite Lúpica , Azatioprina/efeitos adversos , Cromonas , Ciclofosfamida/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/tratamento farmacológico , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Sulfonamidas , Resultado do Tratamento
18.
BMC Gastroenterol ; 21(1): 312, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344314

RESUMO

BACKGROUND: Deep remission (DR) is a treatment target in IBD associated with reduced hospitalization and improved outcome. Randomized control trial (RCT) data demonstrates efficacy of anti-TNFα agents in achieving DR; however, real-world data (RWD) can provide information complementary to RCTs, specifically regarding treatment duration. In this systematic review with meta-analysis, we use real-world data (RWD) to determine rates of DR in IBD treated with anti-TNFα. METHODS: We completed a systematic search of MEDLINE and EMBASE on July 8, 2019 with review of major gastrointestinal conference abstracts from 2012 to 2019. Studies utilizing RWD (data not from phase I-III RCTs) of adult IBD patients treated with anti-TNFα agents were included. DR was defined by clinical and endoscopic remission at minimum. DR was assessed at 8 weeks, 6 months, 1 year, and 2 years. Risk of bias was assessed with the Newcastle Ottawa Scale. RESULTS: 29,033 publications were identified. Fifteen publications, nine manuscripts and six conference abstracts, were included encompassing 1212 patients (769 Crohn's disease-CD, 443 ulcerative colitis-UC), and analyzed using Comprehensive Meta-Analysis. Rate of DR was 36.4% (95% CI 12.6-69.4%) at 8 weeks, 39.1% (95% CI 10.4-78%) at 6 months, 44.4% (95% CI 34.6-54.6%) at 1 year, and 36% (95% CI 18.7-58%) at 2 years. DR in CD at 1 year was 48.6% (95% CI 32.8-64.7%) and in UC was 43.6% (95% CI 32.8-55.1%). CONCLUSIONS: The rate of DR was highest after 1 year of therapy, in nearly 45% of IBD patients treated with anti-TNFα. Similar rates were achieved between patients with UC and CD. The findings highlight the efficacy of anti-TNFα in real-world setting. Future studies using RWD can determine efficacy of newer IBD therapeutics in routine clinical practice.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Adulto , Colite Ulcerativa/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Indução de Remissão
19.
Zhonghua Yi Xue Za Zhi ; 101(29): 2322-2327, 2021 Aug 03.
Artigo em Chinês | MEDLINE | ID: mdl-34333949

RESUMO

Objective: To investigate the efficacy of an etoposide-containing regimen in the treatment of adult-onset Still's disease related hemophagocytic syndrome(AOSD-HLH). Methods: This study adopted the method of retrospective analysis to collect clinical data of 43 AOSD-HLH patients, including the clinical characteristics, laboratory indexes, treatment regimen and prognosis. There were 7 males and 36 females, aged 24-40 years, with a median age of 30. All of them were diagnosed and treated in Beijing Friendship Hospital of Capital Medical University from December 2014 to December 2019. According to whether or not etoposide (VP-16) was included in the initial therapy, patients were divided into group 1 (VP-16 was not administrated in the initial treatment, n=31) and group 2 (the initial treatment included etoposide, n=12). Patients in group 1 who did not respond to the initial treatment were retreated with VP-16-containing regimen, and the effect of initial treatment was compared between the 2 groups. Similarly, according to whether the VP-16-containing regimen was applied or not, patients achieving remission of HLH were divided into group a (not applied, n=6) and group b (applied, n=33), and the laboratory indicators of the two groups were compared. Results: The overall response rate (ORR, 6/31 vs 11/12) and complete response rate (CRR, 1/31 vs 5/12) of patients in group 1 were significantly lower than those in group 2 (both P<0.05). Patients in group 1 who did not respond to the initial treatment were retreated with a VP-16-containing regimen, and we found that the ORR reached 22/24. Among patients in remission, the natural killer cell activity [16.3(14.2, 17.5)% vs 13.1(12.2, 13.8)%] and granulocyte counts [5.6(3.4, 9.3) ×109/L vs 3.9(2.3, 4.7) ×109/L] of patients was significantly higher in group B than that in group A(both P<0.05). There was no statistically significant difference in haemoglobin [103.0 (97.0, 109.5) g/L vs 91.5 (70.0, 118.0) g/L] and platelet counts [(212.2±74.2)×109/L vs (226.0±114.9)×109/L] between the two groups(both P>0.05). Conclusion: The remission status of HLH has an impact on the prognosis of patients. The use of VP-16 in initial treatment can significantly increase the ORR and CRR of AOSD-HLH patients. The application of VP-16 does not cause bone marrow suppression.


Assuntos
Linfo-Histiocitose Hemofagocítica , Doença de Still de Início Tardio , Adulto , Etoposídeo , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Masculino , Indução de Remissão , Estudos Retrospectivos
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