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Globally, postpartum hemorrhage (PPH) is the leading cause of maternal death. Women with immune thrombocytopenia (ITP) are at increased risk of developing PPH. Early identification of PPH helps to prevent adverse outcomes, but is underused because clinicians do not have a tool to predict PPH for women with ITP. We therefore conducted a nationwide multicenter retrospective study to develop and validate a prediction model of PPH in patients with ITP. We included 432 pregnant women (677 pregnancies) with primary ITP from 18 academic tertiary centers in China from January 2008 to August 2018. A total of 157 (23.2%) pregnancies experienced PPH. The derivation cohort included 450 pregnancies. For the validation cohort, we included 117 pregnancies in the temporal validation cohort and 110 pregnancies in the geographical validation cohort. We assessed 25 clinical parameters as candidate predictors and used multivariable logistic regression to develop our prediction model. The final model included seven variables and was named MONITOR (maternal complication, WHO bleeding score, antepartum platelet transfusion, placental abnormalities, platelet count, previous uterine surgery, and primiparity). We established an easy-to-use risk heatmap and risk score of PPH based on the seven risk factors. We externally validated this model using both a temporal validation cohort and a geographical validation cohort. The MONITOR model had an AUC of 0.868 (95% CI 0.828-0.909) in internal validation, 0.869 (95% CI 0.802-0.937) in the temporal validation, and 0.811 (95% CI 0.713-0.908) in the geographical validation. Calibration plots demonstrated good agreement between MONITOR-predicted probability and actual observation in both internal validation and external validation. Therefore, we developed and validated a very accurate prediction model for PPH. We hope that the model will contribute to more precise clinical care, decreased adverse outcomes, and better health care resource allocation.
Assuntos
Hemorragia Pós-Parto/etiologia , Complicações Hematológicas na Gravidez , Púrpura Trombocitopênica Idiopática/complicações , Adulto , Área Sob a Curva , China/epidemiologia , Estudos de Coortes , Suscetibilidade a Doenças , Registros Eletrônicos de Saúde , Feminino , Seguimentos , Previsões , Geografia Médica , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Recém-Nascido , Modelos Logísticos , Modelos Teóricos , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/prevenção & controle , Prednisona/uso terapêutico , Gravidez , Resultado da Gravidez , Prognóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/terapia , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária/estatística & dados numéricosRESUMO
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening haematological emergency. Although therapeutic plasma exchange together with corticosteroids achieve successful outcomes, a considerable number of patients remain refractory to this treatment and require early initiation of intensive therapy. However, a method for the early identification of refractory iTTP is not available. To develop and validate a model for predicting the probability of refractory iTTP, a cohort of 265 consecutive iTTP patients from 17 large medical centres was retrospectively identified. The derivation cohort included 94 patients from 11 medical centres. For the validation cohort, we included 40 patients from the other six medical centres using geographical validation. An easy-to-use risk score system was generated, and its performance was assessed using internal and external validation cohorts. In the multivariable logistic analysis of the derivation cohort, three candidate predictors were entered into the final prediction model: age, haemoglobin and creatinine. The prediction model had an area under the curve of 0.886 (95% CI: 0.679-0.974) in the internal validation cohort and 0.862 (95% CI: 0.625-0.999) in the external validation cohort. The calibration plots showed a high agreement between the predicted and observed outcomes. In conclusion, we developed and validated a highly accurate prediction model for the early identification of refractory iTTP. It has the potential to guide tailored therapy and is a step towards more personalized medicine.
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Creatinina/sangue , Bases de Dados Factuais , Hemoglobinas/metabolismo , Modelos Biológicos , Púrpura Trombocitopênica Trombótica/sangue , Adulto , Fatores Etários , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
The previously published data on the association between CYP1A2*1C (rs2069514) and CYP1A2*1F (rs762551) polymorphisms and cancer risk have remained controversial. Hence, we performed a meta-analysis to investigate the association between CYP1A2*1F and CYP1A2*1C polymorphisms and cancer risk under different inheritance models. Overall, significant association was observed between CYP1A2*1F and cancer risk when all the eligible studies were pooled into the meta-analysis (dominant model: OR 1.08, 95 % CI 1.02-1.15; heterozygous model: OR 1.06, 95 % CI 1.01-1.12; additive model: OR 1.07, 95 % CI 1.02-1.13). In the further stratified and sensitivity analyses, for CYP1A2*1F polymorphism, significantly increased lung cancer risk and significantly decreased bladder cancer risk were observed in Caucasians. For CYP1A2*1C polymorphism, no significant association was found in overall and all subgroup analyses. In summary, this meta-analysis suggests that CYP1A2*1F polymorphism is associated with lung cancer and bladder cancer risk in Caucasians.
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Citocromo P-450 CYP1A2/genética , Neoplasias Pulmonares/genética , Neoplasias da Bexiga Urinária/genética , Estudos de Casos e Controles , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , RiscoRESUMO
The Arg194Trp polymorphism in the X-ray cross-complementing group 1 (XRCC1) had been implicated in cancer susceptibility. The previous published data on the association between XRCC1 Arg194Trp polymorphism and cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and XRCC1 Arg194Trp (59,227 cases and 81,587 controls from 201 studies) polymorphism in different inheritance models. We used odds ratios with 95 % confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was found (recessive model: (odds ration [OR] = 1.18, 95% confidence interval [CI] = 1.09-1.27; homozygous model: OR = 1.21, 95% CI = 1.10-1.33; additive model: OR = 1.05, 95% CI = 1.01-1.09) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, significantly increased glioma risk was found among Asians, significantly decreased lung cancer risk was found among Caucasians, and significant increased breast cancer risk was found among hospital-based studies. In summary, this meta-analysis suggests that Arg194Trp polymorphism may be associated with increased breast cancer risk, Arg194Trp polymorphism is associated with increased glioma risk among Asians, and Arg194Trp polymorphism is associated with decreased lung cancer risk among Caucasians. In addition, our work also points out the importance of new studies for Arg194Trp association in some cancer types, such as gastric, pancreatic, prostate, and nasopharyngeal cancers, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the XRCC1 Arg194Trp polymorphism in cancer development (I (2) > 75%).
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Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Neoplasias/genética , Polimorfismo Genético/genética , Estudos de Casos e Controles , Humanos , Metanálise como Assunto , Prognóstico , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
OBJECTIVES: The purpose of this study was to compare the effectiveness of the combination of venetoclax and hypomethylating agents with the HAG regimen. METHODS: We studied 52 cases of newly diagnosed AML and 26 cases of relapsed refractory AML, (including AML patients with treatment-related and ELN-adverse risk disease (n = 50)). These patients were treated with venetoclax and hypomethylating agents and HAG regimens, respectively. RESULTS: Twenty-nine patients newly diagnosed with acute myeloid leukemia were treated with VEN-HMA (venetoclax-hypomethylating agent), while 23 patients were treated with HAG. The median age of the VEN-HMA group was 70 years, while the HAG group had a median age of 69 years. The VEN-HMA group achieved a significantly higher rate of complete remission (82.7%) compared to the cohort treated with the HAG regimen (21.7%) (P < 0.001). At the same time, the VEN-HMA group exhibited a significant survival advantage compared to the HAG treatment group(HR = 0.328, 95%CI: 0.158-0.683, P = 0.003).In patients with relapsed and refractory acute myeloid leukaemia, 43.8% of patients in the VEN-HMA treatment group achieved complete remission, which was similar to the 50% in the HAG treatment group (P > 0.99). The median overall survival was similar between the VEN-HMA and HAG groups, with 4 and 3.67 months, respectively (P = 0.290). CONCLUSIONS: In conclusion, our analyses indicated that VEN-HMA resulted in better therapeutic outcomes compared to HAG for newly diagnosed AML patients, with higher rates of complete remission and overall survival. In relapsed/refractory AML patients, there was no significant difference in the efficacy of the two treatments and further studies with larger sample sizes are warranted.
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Protocolos de Quimioterapia Combinada Antineoplásica , Compostos Bicíclicos Heterocíclicos com Pontes , Leucemia Mieloide Aguda , Sulfonamidas , Humanos , Sulfonamidas/uso terapêutico , Sulfonamidas/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso de 80 Anos ou mais , Adulto , Resultado do Tratamento , Azacitidina/uso terapêutico , Azacitidina/administração & dosagemRESUMO
PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).
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Antineoplásicos , Arsênio , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Antineoplásicos/efeitos adversos , Arsênio/uso terapêutico , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pandemias , Resultado do TratamentoRESUMO
In the era of molecular targeted drugs, elderly patients with acute myeloid leukemia (AML) are still very difficult to treat, especially those older than 70 years. The decline in immune function leads to serious infection and disease recurrence. The microtransplant treatment regimen (MST) chemotherapy combined with allogeneic hematopoietic stem cell infusion is a new cell therapy regimen. The aim of this MST study was to improve the survival of elderly patients by graft versus leukemia action and improving T-cell immune function. From May 2012 to July 2020, one hundred and eleven patients aged 70 to 88 years with de novo AML were analyzed retrospectively. After induction chemotherapy, patients whom complete remission (CR) was achieved were given another 2 cycles of postremission therapy. The MST groups were given allogeneic stem cell infusion after each chemotherapy cycle. CR, leukemia-free survival, and overall survival (OS) were compared between groups. Additionally, the immune function and the T cell receptor (TCR) library of T cells were detected and analyzed. The MST group exhibited an encouragingly high CR rate (63.8%), even in high-risk patients (54%), and this rate was significantly higher than that in the chemotherapy alone group. The 1-year OS of MST patients was 57.7%, and it was 55.9% in the high-risk group. It was only 37.3% in the chemotherapy alone group. Higher numbers of naive T cells were found in the MST population than in the chemotherapy alone group. More updated T-cell clones were observed in MST patients by T-cell receptor repertoire analysis with a next-generation sequencing methodology. These results suggest that MST is a safe and practical regimen conducive to longer-term survival in patients of a highly advanced age with AML. Furthermore, it has broad clinical value in the recovery of immune function in elderly patients.
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Rare but critical bleeding events in primary immune thrombocytopenia (ITP) present life-threatening complications in patients with ITP, which severely affect their prognosis, quality of life, and treatment decisions. Although several studies have investigated the risk factors related to critical bleeding in ITP, large sample size data, consistent definitions, large-scale multicenter findings, and prediction models for critical bleeding events in patients with ITP are unavailable. For the first time, in this study, we applied the newly proposed critical ITP bleeding criteria by the International Society on Thrombosis and Hemostasis for large sample size data and developed the first machine learning (ML)-based online application for predict critical ITP bleeding. In this research, we developed and externally tested an ML-based model for determining the risk of critical bleeding events in patients with ITP using large multicenter data across China. Retrospective data from 8 medical centers across the country were obtained for model development and prospectively tested in 39 medical centers across the country over a year. This system exhibited good predictive capabilities for training, validation, and test datasets. This convenient web-based tool based on a novel algorithm can rapidly identify the bleeding risk profile of patients with ITP and facilitate clinical decision-making and reduce the occurrence of adversities.
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Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Púrpura Trombocitopênica Idiopática/complicações , Qualidade de Vida , Estudos Retrospectivos , Estudos Prospectivos , Hemorragia/diagnóstico , Trombocitopenia/complicaçõesRESUMO
Background: Several meta-analyses have analyzed the association of GSTM1 present/null, GSTT1 present/null, and GSTP1 IIe105Val polymorphisms with leukemia risk. However, the results of these meta-analyses have been conflicting. Moreover, they did not evaluate the combined effects of the three aforementioned gene polymorphisms. Furthermore, they did not appraise the credibility of the positive results. Finally, many new studies have been published. Therefore, an updated meta-analysis was conducted. Objectives: To further explore the relationship of the three aforementioned gene polymorphisms with leukemia risk. Methods: The crude odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the association of the individual and combined effects of the three aforementioned genes. Moreover, the false-positive report probability (FPRP) and Bayesian false discovery probability (BFDP) were applied to verify the credibility of these statistically significant associations. Results: Overall, the individual GSTM1, GSTT1, and GSTP1 IIe105Val polymorphisms added leukemia risk. On combining GSTM1 and GSTT1, GSTM1 and GSTP1, and GSTT1 and GSTP1 polymorphisms, positive results were also observed. However, no significant association was observed between the combined effects of these three polymorphisms with leukemia risk in the overall analysis. Moreover, when only selecting Hardy-Weinberg equilibrium (HWE) and medium- and high-quality studies, we came to similar results. However, when the FPRP and BFDP values were applied to evaluate the credibility of positive results, the significant association was only observed for the GSTT1 null genotype with leukemia risk in Asians (BFDP = 0.367, FPRP = 0.009). Conclusion: This study strongly suggests a significant increase in the risk of leukemia in Asians for the GSTT1 null genotype.
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Background: The responses of intravenous immunoglobulin (IVIg) or corticosteroids as the initial treatment on pregnancy with ITP were unsatisfactory. This study aimed to assess the safety and effectiveness of prednisone plus IVIg versus prednisone or IVIg in pregnant patients with immune thrombocytopenia (ITP). Methods: Between 1 January 2010 and 31 December 2020, 970 pregnancies diagnosed with ITP at 19 collaborative centers in China were reviewed in this observational study. A total of 513 pregnancies (52.89%) received no intervention. Concerning the remaining pregnancies, 151 (33.04%) pregnancies received an initial treatment of prednisone plus IVIg, 105 (22.98%) pregnancies received IVIg alone, and 172 (37.64%) pregnancies only received prednisone. Results: Regarding the maternal response to the initial treatment, no differences were found among the three treatment groups (41.1% for prednisone plus IVIg, 33.1% for prednisone, and 38.1% for IVIg). However, a significant difference was observed in the time to response between the prednisone plus IVIg group (4.39 ± 2.54 days) and prednisone group (7.29 ± 5.01 days; p < 0.001), and between the IVIg group (6.71 ± 4.85 days) and prednisone group (p < 0.001). The median prednisone duration in the monotherapy group was 27 days (range, 8-195 days), whereas that in the combination group was 14 days (range, 6-85 days). No significant differences were found among these three treatment groups in neonatal outcomes, particularly concerning the neonatal platelet counts. The time to response in the combination treatment group was shorter than prednisone monotherapy. The duration of prednisone application in combination group was shorter than prednisone monotherapy. The combined therapy showed a lower predelivery platelet transfusion rate than IVIg alone. Conclusion: These findings suggest that prednisone plus IVIg may represent a potential combination therapy for pregnant patients with ITP.
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Gain-of-function mutations of JAK2 play crucial roles in the development of myeloproliferative neoplasms; however, the underlying downstream events of this activated signaling pathway are not fully understood. Our experiment was designed and performed to address one aspect of this issue. Here we report that AG490, a potent JAK2V617F kinase inhibitor, effectively inhibits the proliferation of HEL cells. Interestingly, AG490 also decreases the expression of PTTG1, a possible target gene of the aberrant signaling pathway, in a dose- and time-dependent manner. Furthermore, the promoter activity analyses reveal that the inhibition of the PTTG1 expression is affected at the transcriptional level. Thus, our results suggest that the JAK2V617F/STAT5 signaling pathway promotes cell proliferation through the transcriptional activation of PTTG1.
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Proliferação de Células , Janus Quinase 2/metabolismo , Proteínas de Neoplasias/genética , Fator de Transcrição STAT5/metabolismo , Ativação Transcricional , Linhagem Celular , Humanos , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/genética , Inibidores de Proteínas Quinases/farmacologia , Securina , Transcrição Gênica , Tirfostinas/farmacologiaRESUMO
Infection is one of the primary causes of death from immune thrombocytopenia (ITP), and the lungs are the most common site of infection. We identified the factors associated with hospitalization for community-acquired pneumonia (CAP) in nonsplenectomized adults with ITP and established the [corrected] (ACPA) prediction model to predict the incidence of hospitalization for CAP. This was a retrospective study of nonsplenectomized adult patients with ITP from 10 large medical centers in China. The derivation cohort included 145 ITP inpatients with CAP and 1360 inpatients without CAP from 5 medical centers, and the validation cohort included the remaining 63 ITP inpatients with CAP and 526 inpatients without CAP from the other 5 centers. The 4-item ACPA model, which included age, Charlson Comorbidity Index score, initial platelet count, and initial absolute lymphocyte count, was established by multivariable analysis of the derivation cohort. Internal and external validation were conducted to assess the performance of the model. The ACPA model had an area under the curve of 0.853 (95% confidence interval [CI], 0.818-0.889) in the derivation cohort and 0.862 (95% CI, 0.807-0.916) in the validation cohort, which indicated the good discrimination power of the model. Calibration plots showed high agreement between the estimated and observed probabilities. Decision curve analysis indicated that ITP patients could benefit from the clinical application of the ACPA model. To summarize, the ACPA model was developed and validated to predict the occurrence of hospitalization for CAP, which might help identify ITP patients with a high risk of hospitalization for CAP.
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Pneumonia , Púrpura Trombocitopênica Idiopática , Adulto , China , Hospitalização , Humanos , Pneumonia/epidemiologia , Púrpura Trombocitopênica Idiopática/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Tissue factor (TF) plays a pivotal role in thrombus formation and atherogenesis in acute coronary syndrome. Tissue factor pathway inhibitor (TFPI) is a specific physiological inhibitor of TF/FVIIa complex that regulates TF-induced coagulation. Adiponectin (Adp) is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties. Adp inhibits inflammatory cytokine and adhesion molecules expression, and it can prevent endothelial dysfunction. In this study, we investigated the effects of Adp on tumor necrosis factor-alpha (TNF-alpha)-induced expression of TF and TFPI in human umbilical vein endothelial cells (HUVECs), and the signaling transduction pathways involved. It was found that Adp significantly inhibited both TF protein expression and activity in TNF-alpha-stimulated HUVECs. In the meanwhile, it increased TFPI protein expression and activity for about two folds. Adp also inhibited TF mRNA expression induced by TNF-alpha, but had no effect on TFPI mRNA expression. The inhibitory effect of Adp on TNF-alpha-induced TF expression was prevented by pretreatment with Rp-cAMPs, a PKA inhibitor. Adp increased intracellular cAMP content and PKA activity levels in a dose-dependent manner. Phosphorylation of IkappaB-alpha was decreased by Adp, but phosphorylation of p44/42 MAPK, SAPK/JNK, and p38 MAPK were not affected. These results suggested that Adp inhibits TF expression through inhibition of a PKA dependent nuclear factor-kappaB (NF-kappaB) signaling pathway. It was also found that adiponectin promoted Akt and AMP-activated protein kinase phosphorylation. The inhibitory effect of Adp on TNF-alpha-induced TF synthesis was abrogated in part by pretreatment with the PI3kinase inhibitor LY294002, suggesting that Akt activation might inhibit TF expression induced by TNF-alpha. The inhibitory effect of Adp is almost completely abrogated by inhibition of both the cAMP/PKA pathway and PI3K/Akt pathway. In conclusion, our data indicated that inhibition of NF-kappaB through stabilization of IkappaB-alpha and activation of Akt phosphorylation may mediate the inhibitory effect of Adp on TF expression; but the enhancement effect of Adp on the TFPI production might occur via translational rather than transcriptional regulation.
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Células Endoteliais/metabolismo , Lipoproteínas/metabolismo , Adiponectina/metabolismo , Adiponectina/farmacologia , AMP Cíclico/análogos & derivados , AMP Cíclico/metabolismo , AMP Cíclico/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipoproteínas/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NF-kappa B/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Tionucleotídeos/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Veias Umbilicais/citologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
IMPORTANCE: The outcome of older patients with acute myeloid leukemia (AML) remains unsatisfactory. Recent studies have shown that HLA-mismatched microtransplant could improve outcomes in such patients. OBJECTIVE: To evaluate outcomes in different age groups among older patients with newly diagnosed AML who receive HLA-mismatched microtransplant. DESIGN, SETTING, AND PARTICIPANTS: This multicenter clinical study included 185 patients with de novo AML at 12 centers in China, the United States, and Spain in the Microtransplantation Interest Group. Patients were divided into the following 4 age groups: 60 to 64 years, 65 to 69 years, 70 to 74 years, and 75 to 85 years. The study period was May 1, 2006, to July 31, 2015. EXPOSURES: Induction chemotherapy and postremission therapy with cytarabine hydrochloride with or without anthracycline, followed by highly HLA-mismatched related or fully mismatched unrelated donor cell infusion. No graft-vs-host disease prophylaxis was used. MAIN OUTCOMES AND MEASURES: The primary end point of the study was to evaluate the complete remission rates, leukemia-free survival, and overall survival in different age groups. Additional end points of the study included hematopoietic recovery, graft-vs-host disease, relapse rate, nonrelapse mortality, and other treatment-related toxicities. RESULTS: Among 185 patients, the median age was 67 years (range, 60-85 years), and 75 (40.5%) were female. The denominators in adjusted percentages in overall survival, leukemia-free survival, relapse, and nonrelapse mortality are not the sample proportions of observations. The overall complete remission rate was not significantly different among the 4 age groups (75.4% [52 of 69], 70.2% [33 of 47], 79.1% [34 of 43], and 73.1% [19 of 26). The 1-year overall survival rates were 87.7%, 85.8%, and 77.8% in the first 3 age groups, which were much higher than the rate in the fourth age group (51.7%) (P = .004, P = .008, and P = .04, respectively). The 2-year overall survival rates were 63.7% and 66.8% in the first 2 age groups, which were higher than the rates in the last 2 age groups (34.2% and 14.8%) (P = .02, P = .03, P < .001, and P < .001, respectively). The 1-year cumulative incidences of nonrelapse mortality were 10.2%, 0%, 3.4%, and 26.0% in the 4 age groups and 8.1% in all patients. The median times to neutrophil and platelet recovery were 12 days and 14 days after induction chemotherapy, respectively. Five patients had full or mixed donor engraftment, and 30.8% (8 of 26) of patients demonstrated donor microchimerism. Two patients (1.1%) developed severe acute graft-vs-host disease. CONCLUSIONS AND RELEVANCE: Microtransplant achieved a high complete remission rate in AML patients aged 60 to 85 years and higher 1-year overall survival in those aged 60 to 74 years.
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Envelhecimento , Aloenxertos/fisiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/terapia , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/imunologia , Aloenxertos/imunologia , China/epidemiologia , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Teste de Histocompatibilidade/efeitos adversos , Teste de Histocompatibilidade/estatística & dados numéricos , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Espanha/epidemiologia , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia , Doadores não RelacionadosAssuntos
Mieloma Múltiplo , Insuficiência Renal , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Bortezomib/efeitos adversos , Talidomida/efeitos adversos , Insuficiência Renal/complicações , Insuficiência Renal/diagnóstico , Dexametasona/efeitos adversosRESUMO
OBJECTIVE: To investigate the changes of CD4+ T lymphocytes in peripheral blood of patients with follicular lymphoma and its clinical significance. METHODS: Blood samples were collected for detection of whole blood cells, including absolute monocyte count (AMC), absolute lymphocyte count (ALC), hemoglobin (Hb), platelet count (Plt). Age, sex, pathological grade, number of involved lymph nodes, bone marrow involvement (BMI), Ann Arbor stage, B symptoms, serum lactate dehydrogenase (LDH) and serum ß-2 microglobulin (ß2-MG) were recorded, the prognostic stratification was performed by using FLIPI and FLIPI-2. The T lymphocyte subsets were analyzed by flow cytometry, including the absolute number of CD4+ T lymphocytes (ACD4C) and the absolute number of CD8+ T lymphocytes (ACD8C). RESULTS: Patients were with higher Ann Arbor stage, Hb<120 g/L, LDH greater than the upper limit of normal, the number of lymph nodes were involved> 4, the bone marrow was involvement, ß2-MG levels were high FLIPI score and FLIPI-2 score, AMC level was higher (P<0.05). There were no significant differences in ACD4C levels among different groups. Patients with AMC≥0.89×109/L showed a shorter progression-free survival (PFS) and a shorter overall survival time (OS) (P=0.010,0.002) as compared with patients with AMC<0.89×109/L. The patients with ACD4C>0.16×109/L had longer progression-free survival and overall survival time, as compared with patients with ACD4C ≤0.16×109/L (P=0.016,0.012). Low ACD4C and high AMC related with shorter PFS and OS (P=0.013, 0.020). Univariate Cox regression analysis showed that age (P=0.026), bone marrow involvement (P=0.017), elevated LDH (P=0.001), ß2-MG (P=0.014), FLIPI and FLIP2 score (P= 0.004 and 0.000) related with a shorter PFS. Multivariable Cox regression analysis showed that Hb (P=0.015), elevated LDH (P=0.003), ß2-MG (P=0.045), bone marrow involvement (P=0.016) and FLIPI-2 score(P=0.003) related with short OS. ACD4C ≤0.16×109/L was a factor influencing prognosis of FL patients (PFS and OS) (P<0.05). CONCLUSIONS: Low ACD4C levels relatees with poor prognosis of patients with FL, and the ACD4C levels may be an important predictor for FL disease and prognosis.
Assuntos
Linfócitos T CD4-Positivos , Contagem de Linfócitos , Linfoma Folicular/diagnóstico , Intervalo Livre de Doença , Humanos , Prognóstico , Estudos RetrospectivosRESUMO
Acute myeloid leukemia (AML) is a malignant clonal hematologic disease from hematopoietic stem and progenitor cells. The isocitrate dehychogenase 2 (IDH2) gene mutation has been recently found, which may be associated with the course of AML. The incidence of IDH2 gene mutation in the patients with acute myeloid leukemia is high, especially in the AML patients with normal karyotype. Different subtypes of IDH2 mutation, or companing other molecular biology, will make different influence on clinical features and progress of patients with AML. IDH2 mutation is stable, which can be used as the test sign of AML and minimal residual disease (MRD), and for guiding the clinical treatment and predicting the progress. In this article, the research progress of IDH2 mutation in acute myeloid leukemia is reviewed.
Assuntos
Isocitrato Desidrogenase/genética , Leucemia Mieloide Aguda/genética , Humanos , Mutação , Neoplasia Residual , PrognósticoRESUMO
In 2008, WHO made the JAK2V617F gene mutation as one of the specific molecular diagnostic markers of BCR/ABL-negative myeloproliferative neoplasms (MPN). In 2013 two research teams demonstrated that whole genome sequencing technology (WGS) was used to detect calreticulin gene mutation in essential thrombocythaemia (ET) and primary myelofibrosis (PMF) patients with JAK2V617Fâ» and MPLâ» mutations. In this review, the relationship of CALR gene mutation with MPN is briefly summarized.
Assuntos
Neoplasias da Medula Óssea/genética , Calreticulina/genética , Janus Quinase 2/genética , Transtornos Mieloproliferativos/genética , Receptores de Trombopoetina/genética , Humanos , MutaçãoRESUMO
During the past few years, a novel family of CD4âºT cell lineage was detected and named as Th17 cells because of its unique ability expressing IL-17, which also can produce IL-17A, IL-17F, IL-21, IL-22 and IL-26. Some cytokines, such as TGF-ß, IL-6, L-23 may promote the differentiation of Th17 subset, whereas some cytokines, such as IL-21, IL-2, IFN-γ, may have inhibitory effects. Th17 cells serving as immune effectors play an important role in autoimmune diseases caused by chronic inflammation injury. More and more studies confirmed that Th17 cells have closely correlations with the development of aplastic anemia, and may be a new target in the diagnosis, therapy, prognosis and prophylaxis of aplastic anemia.
Assuntos
Anemia Aplástica/imunologia , Células Th17/imunologia , Doenças Autoimunes , Diferenciação Celular , Citocinas , Humanos , Inflamação , Células Th17/citologiaRESUMO
BACKGROUND: The XPG (xeroderma pigmentosum type G) Asp1104His and XPF (xeroderma pigmentosum type F) Arg415Gln polymorphisms had been implicated in cancer susceptibility. The previous published data on the association between XPG Asp1104His and XPF Arg415Gln polymorphisms and cancer risk remained controversial. METHODOLOGY/PRINCIPAL FINDINGS: To derive a more precise estimation of the association between the XPG Asp1104His and XPF Arg415Gln polymorphisms and overall cancer risk, we performed a meta-analysis to investigate the association between cancer susceptibility and XPG Asp1104His (32,162 cases and 39,858 controls from 66 studies) and XPF Arg415Gln polymorphisms (17,864 cases and 20,578 controls from 32 studies) in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly elevated cancer risk was found when all studies were pooled into the meta-analysis of XPG Asp1104His (dominant model: OR = 1.05, 95% CI = 1.00-1.10; Asp/His vs. Asp/Asp: OR = 1.06, 95% CI = 1.01-1.11). In the further stratified and sensitivity analyses, significantly decreased lung cancer risk was found for XPF Arg415Gln (dominant model: OR = 0.82, 95% CI = 0.71-0.96; Arg/Gln versus Arg/Arg: OR = 0.83, 95% CI = 0.71-0.97; additive model: OR = 0.83, 95% CI = 0.72-0.95) and significantly increased other cancer risk was found among hospital-based studies for XPG Asp1104His (dominant model: OR = 1.23, 95% CI = 1.02-1.49). CONCLUSIONS/SIGNIFICANCE: In summary, this meta-analysis suggests that XPF Arg415Gln polymorphism may be associated with decreased lung cancer risk and XPG Asp1104His may be a low-penetrant risk factor in some cancers development. And larger scale primary studies are required to further evaluate the interaction of XPG Asp1104His and XPF Arg415Gln polymorphisms and cancer risk in specific populations.