1.Safety of butylphthalide and edaravone in patients with ischemic stroke: a multicenter real-world study.
Shu-Xian LYU ; Dong-Fang QIAN ; Yu-Fei FENG ; Cheng-Wu SHEN ; Lu-Bo GUO ; Jian-Tao LYU ; Peng-Fei JIN ; Ting LI ; Si-Yuan TAN ; Zi-Xuan ZHANG ; Lin HUANG ; Xue ZHONG ; Le-Qun SU ; Xin HU ; Xin HUANG ; Xue-Yan CUI
Journal of Geriatric Cardiology 2023;20(4):293-308
BACKGROUND:
Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations.
METHODS:
In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively.
RESULTS:
81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count.
CONCLUSIONS
In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.
2.Evaluation of left ventricular function with left atrio-ventricular longitudinal strain in patients with lymphoma underwent anthracycline therapy.
Zheng LI ; Qun Ling ZHANG ; Yi Hui SHEN ; Xian Hong SHU ; Lei Lei CHENG
Chinese Journal of Cardiology 2022;50(11):1064-1068
Objective: To analyze the value of 3-dimensional speckle tracking echocardiograghy (3D-STE) derived strain parameters on the detection of subclinical myocardial deformation alterations in patients with lymphoma treated with anthracycline agents. Methods: This study was a retrospective study. A total of 37 patients with newly diagnosed diffuse large B cell non-Hodgkin lymphoma between December 2012 and December 2014 in Cancer Center, Fudan university were included. 3D-STE strain measurements were performed at baseline (T0),after the completion of two therapy circles (T1) and at the end of anthracycline regimen chemotherapy (Te). Echocardiography images were analyzed on the TTA workstation, and the indexes included left atrial minimum volume (LAVmin), left atrial emptying index (LAEF), left atrial active emptying index (LAAEF), as well as the left ventricular global longitudinal strain (LVGLS), left ventricular global circumferential strain (LVGCS), left atrial global longitudinal strain (LAGLS). The overall left atrioventricular longitudinal strain (LAVGLS) was calculated, which was the sum of the absolute values of LVGLS and LAGLS. The changes of left ventricular strain indexes measured by 3D-STE at different time points of patients were evaluated. Results: Thirty-seven patients with DLBCL, aged (48.3±12.1)years, including 23 males (63.9%), were enrolled. Compared with baseline, LVGLS (T1: (-18.63±4.73)% vs. (-22.13±4.40)%, P=0.001; Te:(-18.26±4.64)% vs. (-22.13±4.40)%, P<0.001), LAGLS (T1: (20.41±5.56)% vs. (23.98±5.59)%, P=0.003; Te: (17.60±3.96)% vs. (23.98±5.59)%, P<0.001) and LAVGLS (T1: (39.05±7.60)% vs. (46.11±7.77)%, P<0.001; Te: (40.34±8.55)% vs. (46.11±7.77)%, P<0.001) were all deteriorated at the T1 and Te. While LVGCS ((-21.98±5.82)% vs. (-26.15±7.51)%, P=0.010), LAVmin ((23.93±7.29)ml vs. (20.33±7.03)ml, P=0.029), LAEF ((28.94±11.16)% vs. (35.79±11.12)%, P=0.002) and LAAEF ((11.93±10.00)% vs. (18.10±9.96)%, P=0.013) were decreased only until Te. Conclusions: 3D-STE strain measurements could detect early myocaridial function alteration in patients receiving anthracycline regimen chemotherapy, thus may provide a novel approach to monitor anthracycline caused myocardial toxicity.
Male
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Humans
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Anthracyclines/therapeutic use*
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Ventricular Function, Left
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Retrospective Studies
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Heart Ventricles
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Antibiotics, Antineoplastic/adverse effects*
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Polyketides/pharmacology*
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Lymphoma/drug therapy*
3.Cardiovascular and Cerebrovascular Diseases Induced by Air Pollution.
Yi-Cheng YANG ; Jia-Wen LI ; Bo SUN ; Yi-Lin CHEN ; Shu-Qun SHEN ; Chao YUAN
Acta Academiae Medicinae Sinicae 2022;44(2):318-323
Air pollution has severe detrimental effects on public health.A substantial number of studies have demonstrated that air pollution exposure is a risk factor for the occurrence of cardiovascular and cerebrovascular diseases and a cause of non-communicable diseases.Both long-term and short-term exposure to air pollution are associated with respiratory diseases,stroke,coronary artery disease,and diabetes.Aiming to better understand the association,we reviewed the latest studies about the association of air pollution with cardiovascular and cerebrovascular diseases,especially stroke,coronary heart disease,arrhythmia,hypertension,and heart failure,and summarized the underlying mechanisms of the health damage caused by long-term and short-term exposure to air pollution.
Air Pollutants/analysis*
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Air Pollution/adverse effects*
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Cardiovascular Diseases/etiology*
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Cerebrovascular Disorders/etiology*
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Environmental Exposure/analysis*
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Humans
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Particulate Matter/analysis*
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Stroke/complications*
4.Analysis on the rationality of input and output of occupational health funds in an iron and steel enterprise.
Xu ZHANG ; Hui LIU ; Shu Ling YUE ; Qun ZHANG ; Fu Hai SHEN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2022;40(8):626-631
Objective: To analyzes the various occupational health investment and occupational health output of a steel enterprise, and propose a reasonable occupational health investment plan for this enterprise. Methods: In march 2016, various occupational health input and output data of various branches of an iron and steel company in 2015 were collected, and the efficiency of occupational health inputs and outputs of each branch was evaluated using data envelopment analysis (DEA) , and the branches with non-optimal efficiency were adjusted to propose a reasonable occupational health investment plan. Results: Among the branch plants investigated by this steel company, the occupational health input-output efficiency values of ironmaking north plant, power plant, hot rolling plant and stainless steel plant were 1, while the occupational health input-output efficiency of gas making plant, cold rolling plant, metallurgical furnace charge plant, coking plant, ironmaking south plant and long product plant were not the best, and the cold rolling plant has the lowest efficiency value of 0.759. For the cold rolling plant, only the parameters of acid rolling plant satisfy α=1 and s(-)=0, s(+)=0, while the remaining four workshops do not meet. After adjusting the inputs of each part according to the parameters, the occupational health output of the remaining four workshops can reach 1.7044, 2.0238, 1.3152 and 1.2136 times of the current workshop, respectively. Adjustment plans for other branch factories with unreasonable investment structures are also presented in the corresponding tables. Conclusion: The occupational health investment structure of the ironmaking south plant and other branches in this steel enterprise is unreasonable, and the adjustment using data envelopment analysis can maximize the benefits of its occupational health output.
Financial Management
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Iron
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Metallurgy
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Occupational Health
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Steel
5.Does Early Postsurgical Temozolomide Plus Concomitant Radiochemotherapy Regimen Have Any Benefit in Newly-diagnosed Glioblastoma Patients? A Multi-center, Randomized, Parallel, Open-label, Phase II Clinical Trial.
Ying MAO ; Yu YAO ; Li-Wei ZHANG ; Yi-Cheng LU ; Zhong-Ping CHEN ; Jian-Min ZHANG ; Song-Tao QI ; Chao YOU ; Ren-Zhi WANG ; Shu-Yuan YANG ; Xiang ZHANG ; Ji-Sheng WANG ; Ju-Xiang CHEN ; Qun-Ying YANG ; Hong SHEN ; Zhi-Yong LI ; Xiang WANG ; Wen-Bin MA ; Xue-Jun YANG ; Hai-Ning ZHEN ; Liang-Fu ZHOU
Chinese Medical Journal 2015;128(20):2751-2758
BACKGROUNDThe radiochemotherapy regimen concomitantly employing temozolomide (TMZ) chemotherapy and radiotherapy (RT) 4 weeks after surgery, followed by 6 cycles of TMZ is a common treatment for glioblastoma (GBM). However, its median overall survival (OS) is only 14.6 months. This study was to explore the effectiveness and safety of early TMZ chemotherapy between surgery and chemoradiotherapy plus the standard concomitant radiochemotherapy regimen.
METHODSA randomized, parallel group, open-label study of 99 newly diagnosed GBM patients was conducted at 10 independent Chinese neurosurgical departments from June 2008 to June 2012. Patients were treated with concomitant radiochemotherapy regimen plus early postsurgical temozolomide (early TMZ group) or standard concomitant radiochemotherapy regimen (control group). Overall response was assessed based on objective tumor assessments, administration of corticosteroid and neurological status test. Hematological, biochemical, laboratory, adverse event (AE), and neurological condition were measured for 24 months of follow-up. The primary efficacy endpoint of this study was overall survival (OS). The secondary endpoint was progression free survival (PFS).
RESULTSThe median OS time in the early TMZ group was 17.6 months, compared with 13.2 months in the control group (log-rank test P = 0.021). In addition, the OS rate in the early TMZ group was higher at 6, 12, and 18 months than in the control group, respectively (P < 0.05). The median PFS time was 8.7 months in the early TMZ group and 10.4 months in the control group (log-rank test P = 0.695). AEs occurred in 29 (55.8%) and 31(73.8%) patients respectively in early and control groups, including nausea (15.4% vs. 33.3%), vomiting (7.7% vs. 28.6%), fever (7.7% vs. 11.9%), and headache (3.8% vs. 23.8%). Only 30.8% and 33.3% were drug-related, respectively.
CONCLUSIONSAddition of TMZ chemotherapy in the early break of the standard concomitant radiochemotherapy regimen was well tolerated and significantly improved the OS of the GBM patients, compared with standard concomitant radiochemotherapy regimen. However, a larger randomized trial is warranted to verify these results.
Adult ; Aged ; Antineoplastic Agents, Alkylating ; therapeutic use ; Chemoradiotherapy ; methods ; Dacarbazine ; analogs & derivatives ; therapeutic use ; Glioblastoma ; drug therapy ; radiotherapy ; Humans ; Middle Aged ; Treatment Outcome ; Young Adult
6.Interleukin-18 promoter gene -607C/A polymorphism and tuberculosis risk: a meta-analysis.
Dian-Dian LI ; Liu-Qun JIA ; Shu-Jin GUO ; Yong-Chun SHEN ; Fu-Qiang WEN
Chinese Medical Journal 2013;126(17):3360-3363
BACKGROUNDNumerous studies have evaluated the association between interleukin-18 (IL-18) promoter gene -607C/ A (rs1946518) polymorphism and tuberculosis (TB) risk. However, the results remain apparently conflicting. The aim of this study was to investigate whether IL-18-607C/A polymorphism is associated with susceptibility to TB.
METHODSPublications addressing the association between the IL-18-607C/A polymorphism and TB risk were selected from the Pubmed, Cochrane Library, Embase, CNKI and Wanfang databases. Data were extracted from the studies by two independent reviewers. Statistical analysis was performed using RevMan 5.0.25 and STATA 11.0 software.
RESULTSEight case-control studies with a total of 1166 TB patients and 1734 controls were retrieved. Meta-analysis results showed significant association between IL-18-607C/A polymorphism and TB risk in all comparisons of the A allele versus C allele (OR=1.17, 95% CI 1.05-1.30, P=0.004), AA versus CC (OR=1.43, 95% CI 1.14-1.81, P=0.002), CA+AA versus CC (OR=1.20, 95% CI 1.01-1.42, P=0.04) and AA versus CA+CC (OR=1.30, 95% CI 1.07-1.58, P=0.007). In subgroup analysis by nationality, a significant association between IL-18-607C/A polymorphism and TB risk in the comparisons of A versus C, CA+AA versus CC and AA versus CA+CC (OR=1.22, 95% CI 1.07-1.38, P=0.002; OR=1.31, 95% CI 1.06-1.61, P=0.01; OR=1.32, 95% CI 1.07-1.63, P=0.01, respectively) were found in Chinese population but not in Indian and Iranian populations.
CONCLUSIONThis study suggests that the -607C/A polymorphism of IL-18 gene would be a risk factor for TB, especially in Chinese population. To further evaluate gene-to-gene and gene-to-environment interactions on -607C/A polymorphism and tuberculosis risk, more studies with thousands of patients are required.
Genetic Predisposition to Disease ; genetics ; Humans ; Interleukin-18 ; genetics ; Promoter Regions, Genetic ; genetics ; Tuberculosis ; epidemiology ; genetics
7.Distribution characteristics of cancerous foci in the prostate among patients undergoing single positive core biopsy.
Xi-Gao LIU ; Cheng SHEN ; Jian LI ; Kai ZHANG ; Wei YU ; Qun HE ; Shu-Qing LI ; Gang-Zhi SHAN ; Shi-Liang WU ; Jie JIN
National Journal of Andrology 2012;18(2):155-159
OBJECTIVETo determine the distribution characteristics of cancerous foci in the prostate by retrospective analysis on the radical prostatectomy (RP) samples from patients with prostate cancer diagnosed by single positive core biopsy and treated by RP.
METHODSThirty-seven patients with prostate cancer diagnosed by ultrasound-guided biopsy and single positive core biopsy underwent RP. We reviewed the pre- and post-operative data of the patients, compared the results of biopsies and pathological examination of the RP samples, and analyzed the factors that led to the underestimation of the overall prostate cancer risks.
RESULTSPost-operative pathological results showed multifocal distribution of the tumors in 70% of the patients (26/37) and obviously increased Gleason score (7-9) in 56% (21/37). The clinical stages of the tumors had been significantly underestimated preoperatively. The underestimation of their clinical stages might be due to a larger proportion of cancer tissues in a single positive core biopsy, and that of the overall cancer risks attributed to PSAD > 0.2 microg/L. Larger prostate volume (> or = 40 ml) increased the possibility of multifocal distribution.
CONCLUSIONThe risk of prostate cancer diagnosed by single positive core biopsy might be underestimated, and the cancerous foci were characterized by multifocal distribution in the prostate.
Aged ; Biopsy, Needle ; methods ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Prostate ; pathology ; Prostatic Neoplasms ; pathology ; Retrospective Studies
8.Diagnostic significance of Th1/Th2 cytokine pattern in childhood hemophagocytic lymphohistiocytosis.
Xiao-jun XU ; Yong-min TANG ; Ning ZHAO ; Hua SONG ; Shi-long YANG ; Shu-wen SHI ; Wei-qun XU ; Bin-hua PAN ; Ling-yan ZHANG ; Jun-qing MAO ; He-ping SHEN ; Min-er GU ; Jing XIA
Chinese Journal of Pediatrics 2011;49(9):685-689
OBJECTIVETo illustrate the diagnostic value of Th1/Th2 cytokine pattern in childhood hemophagocytic lymphohistiocytosis (HLH) and its diagnostic accuracy.
METHODThe BD(TM) CBA Human Th1/Th2 Cytokine Kit II was used to measure the serum Th1 and Th2 cytokines, including Interferon-gamma (IFN-γ), tumor necrosis factor (TNF), interleukin (IL)-10, IL-6, IL-4 and IL-2 in 50 patients with de novo HLH admitted to our hospital from Oct. 2005 to Aug. 2009. The above cytokine levels were also determined in 250 healthy volunteers and 235 patients with sepsis as controls.
RESULTThe primary features of these patients were prolonged high-grade fever (50/50), hepatomegaly (44/50), splenomegaly (38/50), hemocytopenia (47/50), hyperferritinemia (49/50), coagulopathy (44/50), hemophagocytosis in bone marrow (42/50), liver dysfunction (42/50) and hypertriglyceridemia (42/50). The IFN-γ, TNF, IL-10, IL-6, IL-4 and IL-2 levels for healthy children were (4.6 ± 1.8) ng/L, (4.0 ± 1.2) ng/L, (6.5 ± 1.3) ng/L, (6.0 ± 1.5) ng/L, (2.9 ± 0.8) ng/L and (2.6 ± 0.7) ng/L, while the median levels of them in acute phase of HLH children were 1138.5 (49.2 - 5000.0) ng/L, 3.4 (1.0 - 25.1) ng/L, 740.5 (26.5 - 5000.0) ng/L, 66.1 (3.9 - 4472.6) ng/L, 3.9 (1.0-32.8) ng/L and 4.0 (1.0 - 51.1) ng/L, respectively. The cytokine levels decreased to 9.1 (1.9 - 180.1) ng/L, 2.9 (1.0 - 11.0) ng/L, 11.4 (2.9 - 184.2) ng/L, 6.5 (1.0 - 44.8) ng/L, 2.7 (1.0 - 6.5) ng/L and 4.1 (1.0 - 12.0) ng/L respectively after remission. The IFN-γ, IL-10 and IL-6 levels in acute phase were significantly higher than those after remission and those of the healthy control (P all < 0.001). IL-4, IL-2 and TNF slightly elevated or at normal range in acute phase of HLH. The patients with sepsis showed a different cytokine pattern, with an extremely high level of IL-6 (median: 251.3 ng/L, range: 8.4- > 5000.0 ng/L) and moderately elevated level of IL-10 (median: 46.5 ng/L, range: 3.1 - 5000.0 ng/L), whereas IFN-γ was only slightly elevated (median: 9.2 ng/L, range: 1.3 - 498.8 ng/L). When the criteria for HLH set as the following: IFN-γ > 100 ng/L, IL-10 > 60 ng/L and the concentration of IFN-γ higher than that of IL-6, the specificity reached as high as 98.7% and the sensitivity was 88.0% for the diagnosis of HLH among patients with HLH and sepsis. Meanwhile, the positive predictive value (PPV) and negative predictive value (NPV) could reach 93.6% and 97.5%, respectively.
CONCLUSIONThe significant increase of IFN-γ and IL-10 with slightly increased level of IL-6 is a sensitive and specific cytokine pattern for childhood HLH, which is helpful for its diagnosis and differential diagnosis.
Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; Cytokines ; blood ; Female ; Humans ; Infant ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Interleukin-4 ; blood ; Interleukin-6 ; blood ; Lymphohistiocytosis, Hemophagocytic ; blood ; diagnosis ; Male ; Sensitivity and Specificity ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism ; Tumor Necrosis Factor-alpha ; blood
9.Efficacy and safety of Firebird sirolimus-eluting stent in treatment of complex coronary lesions in Chinese patients: one-year clinical and eight-month angiographic outcomes from the FIREMAN registry.
Yan LI ; Cheng-xiang LI ; Hai-chang WANG ; Bo XU ; Wei-yi FANG ; Jun-bo GE ; Wei-min WANG ; Shu-bin QIAO ; Jack-P CHEN ; Wen-kuang SHEN ; Hong JIANG ; Hong-liang CONG ; Xiao-qun PU ; Yong-wen QIN ; Hui-gen JIN ; Yu CAO ; He HUANG
Chinese Medical Journal 2011;124(6):817-824
BACKGROUNDOff-label application of drug-eluting stents (DES) during percutaneous coronary intervention (PCI) was not uncommon in daily practice, however DES in treating Chinese patients with complex lesion subset was under-investigated. The primary objective of the FIREMAN registry was to evaluate the long term efficacy and safety of the Firebird sirolimus-eluting stent (SES) in treating patients with complex coronary lesions. Here we report the mid-term of one-year clinical outcomes and eight-month angiographic follow-up results of FIREMAN registry.
METHODSThe FIREMAN registry was a prospective multi-center registry, which included 1029 consecutive patients undergoing PCI with Firebird SES implantation between September 2006 and July 2007 in 45 centers in China. The clinical follow-up was designed to be performed at 1, 6, 12, 18, 24, 30 and 36 months post index procedure, and non-mandatory angiographic follow-up at 8 months was planned. One hundred percent site monitoring was conducted.
RESULTSLong lesions (59.2%), multi-vessel disease (50.4%), and small vessel disease (31.6%) were mostly found in angiography. Major adverse cardiac events (MACE) occurred in 51 (5.1%) patients at 1 year clinical follow-up, including cardiac mortality in 6 (0.6%), non-fatal myocardial infarction in 11 (1.1%), and target lesion revascularization in 36 (3.5%) of the patients. Definite and probable stent thrombosis (ST) by Academic Research Consortium (ARC) definition occurred in 12 (1.36%) patients at one-year clinical follow-up. The 8-month binary restenosis rate was 5.7% in-segment and 4.3% in-stent, respectively. Late lumen loss was (0.21 ± 0.40) mm in-segment and (0.23 ± 0.36) mm in-stent, respectively. Furthermore, Cox regression analysis revealed that diabetes, small vessel diameter, and chronic total occlusion were independent predictors of ST.
CONCLUSIONSThe results showed that the Firebird SES was effective and safe in treating Chinese patients with complex coronary lesions and occurrence of ST rate at one-year clinical follow-up was acceptable, however further long-term follow-up was still necessary. (NCT00552656)
Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; methods ; Asian Continental Ancestry Group ; Coronary Angiography ; Coronary Disease ; diagnostic imaging ; therapy ; Drug-Eluting Stents ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Sirolimus ; therapeutic use ; Treatment Outcome
10.Monitoring of minimal residual disease in children with acute lymphoblastic leukemia and its prognostic significance.
Xiao-jun XU ; Yong-min TANG ; Hua SONG ; Shu-wen SHI ; Shi-long YANG ; Hong-qiang SHEN ; Jian WEI ; Wei-qun XU ; Bin-hua PAN ; Fen-ying ZHAO
Chinese Journal of Pediatrics 2010;48(3):180-184
OBJECTIVEMonitoring of minimal residual disease (MRD) is proven to be increasingly valuable for predicting relapse and outcome of childhood acute lymphoblastic leukemia (ALL) and is used to identify patients' risk groups in several current clinical trials. However, the limitation is that most studies focused on the cut-off value at 10(-4) and the time point after induction. The aim of this study was to investigate the predictive values of different MRD levels detected at different chemotherapy phases in childhood ALL.
METHODSOne hundred and two patients were enrolled in this study from January 2002 to December 2004 in our hospital. All the patients were treated with modified National Protocol of Childhood ALL in China 1997. MRD levels were detected on the 15th day, 29th day, at 3 months, 6 months and 12 months after initial chemotherapy. All samples were stained with a panel of four colour combinations of fluorochrome conjugated monoclonal antibodies according to the leukemia-associated immunophenotype (LAIP) defined at diagnosis and analyzed by multi-parametric flow cytometry. CD45CD19CD34CD10, CD45CD19CD34CD20 and CD45CD19CD10CD20 were the most common combinations in B lineage ALL, while CD45CD2CD3CD7 and CD45CD2CD3CD34 were the most frequently used immunophenotypes for T lineage ALL. The median follow-up time was 63.3 months ranged from 40.6 to 87.5 months.
RESULTSOf the 102 patients, 64 were male and 38 were female, with a median age of 5.7 (0.2 - 14.8) years. Eighty-eight cases were diagnosed as B lineage ALL and the remaining 14 were T-ALL. The 5-year overall survival (OS) rate and event free survival (EFS) rate for this cohort were (86.9 +/- 3.4)% and (79.9 +/- 4.0)%, respectively. Twelve patients underwent relapse. Among the 102 patients, 14.3% had negative MRD (MRD < 10(-4)) on day 15, 43.9% on day 29, 39.1%, 39.7% and 45.6% had negative MRD at the third, sixth and twelfth month after chemotherapy. Patients who could achieve negative MRD within one year had superior outcome to the others [5-year EFS rates: (92.5 +/- 3.2)% vs. (58.3 +/- 8.6)%, P < 0.001]. The EFS for patients based on MRD levels measured at different stages of therapy were compared by Kaplan-Meier analyses. MRD was predictive of outcome at all 5 time points at a range of thresholds. The optimum threshold, selected for each time point on the basis of log rank analysis, progressively dropped from 10(-2) of day 15 [5-year EFS rates (79.8 +/- 10.3)% vs. (28.6 +/- 17.1)%, P < 0.001], to 10(-3) of day 29 [5-year EFS rates (88.3 +/- 4.9)% vs. (51.3 +/- 14.4)%, P < 0.003], to 10(-4) at 3 [5-year EFS rates (92.4 +/- 5.1)% vs. (65.5 +/- 7.5)%, P < 0.015], 6 [5-year EFS rates (96.3 +/- 3.6)% vs. (65.4 +/- 7.5)%, P < 0.003] and 12 [5-year EFS rates (100.0 +/- 0.0)% vs. (67.7 +/- 8.4)%, P < 0.002] months. And the hazard ratios for relapse and death at higher MRD level groups were 5.91 (95%CI: 1.9 - 18.9), 5.02 (95%CI: 1.5 - 16.5), 5.21 (95%CI: 1.2 - 22.9) and 11.10 (95%CI: 1.5 - 84.5) on day 15, day 29, at month 3 and month 6, respectively. And MRD >or= 10(-2) on day 15 was proven to be an independent predictor by multivariate Cox proportional-hazards regression model.
CONCLUSIONDynamic MRD detection by multi-parametric flow cytometry is highly predictive of outcome for childhood ALL, and the cut-off values at different time points were different.
Adolescent ; Child ; Child, Preschool ; Female ; Flow Cytometry ; Humans ; Infant ; Infant, Newborn ; Male ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; pathology ; Predictive Value of Tests ; Prognosis

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