P204 Re-established CRP cut-off in UC; it may be a better predictor of mucosal remission

Abstract Background Although faecal calprotectin can predict mucosal remission in ulcerative colitis, the CRP level in this context is insufficient and frequently stay under the current cut off level. While some patients with active mucosal disease have normal CRP levels most patients in mucosal remission have much lower CRP levels. The aim of this study is to define CRP cut off levels in the prediction of mucosal remission, considering both extensiveness and severity, in ulcerative colitis. Methods We retrospectively reviewed colonoscopy reports of ulcerative colitis patients (who are not on any steroid treatment at that time) which were performed between December 2016 and March 2019 and also their CRP levels which were obtained at the same week of the colonoscopy examination. We excluded the data of patients with any other possible cause of inflammation or infection at the time of laboratory assessment. Degree of mucosal disease at colonoscopy was evaluated according to endoscopic Mayo score. Mucosal remission was defined as endoscopic Mayo score 0 or 1. The extent of mucosal inflammation was classified according to Montreal classification. The CRP level with optimal sensitivity and specificity for mucosal remission prediction was assessed by ROC curve analysis and positive and negative predictive values were also calculated. Results A total of 331 colonoscopy reports of 260 patients (122 m, 138 f) were involved in this study. There were no significant differences between ages of patients when compared with ex, and Montreal classification and we did not find any correlation between age and CRP levels. Sensitivity, specificity, positive predictive value and negative predictive values for 5 mg/l, 3 mg /l and 2 mg/l are summarised in Table 1. CRP levels which predict Mayo 0 disease, mucosal remission (Mayo 0–1) and Mayo 3 disease are shown in Table 2. At the ROC curve analysis, we found that CRP level of approximately 2.9 mg/l can predict mucosal remission with a 77% sensitivity and % 80 specificity in all examinations without grouping into a separate segmental disease. For subgroups with Montreal E1, E2 and E3 ROC curve analysis suggested 1,8 mg/l (sn. 84%, sp. 90%), 2,7 mg/l (sn. 75%, sp. 75%) and 3 mg/l (sn. 80%, sp. 80%) CRP levels can be used for prediction of mucosal remission respectively (Table 3). It is important to emphasise that 30% of all patients with Mayo 3 colonoscopy and further 23% of patients with Montreal E3–Mayo 3 activity have CRP levels below the regular cut-off value of 5 mg/l. Conclusion CRP cut-off level of approximately 2.9 mg/l can predict mucosal remission in ulcerative colitis better than standard cut-off of 5 mg/l which has a low positive predictive value and specificity even at extended and active mucosal disease.

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Combine preoperative estimation of serum thyroglobulin and ACR-thyroid imaging reporting and data system scoring could accurately define malignant thyroid nodules

International Surgery Journal ◽

10.18203/2349-2902.isj20205866 ◽

2020 ◽

Vol 8 (1) ◽

pp. 32

Author(s):

Waseem A. Shoda

Keyword(s):

Roc Curve ◽

Predictive Value ◽

Thyroid Nodules ◽

Curve Analysis ◽

Data System ◽

Operating Characteristics ◽

Roc Curve Analysis ◽

Serum Thyroglobulin ◽

Thyroid Imaging ◽

Significant Difference

Background: Evaluation of diagnostic ability of preoperative estimation of serum thyroglobulin (TG) to detect malignant thyroid nodules (TN) in comparison to the American College of Radiology, Thyroid imaging reporting and data system (ACR-TIRADS), fine needle aspiration cytology (FNAC) and intraoperative frozen section (IO-FS).Methods: 34 patients with ACR-TIRADS 2-4 TN were evaluated preoperatively for identification of malignancy and all underwent total thyroidectomy with bilateral neck block dissection if indicated. Results of preoperative investigations were statistically analyzed using the Receiver operating characteristics (ROC) curve analysis as predictors for malignancy in comparison to postoperative paraffin sections.Results: Preoperative serum TG levels had 100% sensitivity and negative predictive value, while ACR-TIRADS scoring had 100% specificity and positive predictive value with accuracy rates of 95.35% and 97.67% for TG and TIRADS, respectively. ROC curve analysis defined preoperative ACR-TIRADS class and serum TG as highly diagnostic than FNAC for defining malignancy with non-significant difference between areas under curve for TIRADS and TG. For cases had intermediate risk of malignancy on TIRADS, IO-FS had missed 3, FNAC missed 4, while serum TG levels were very high in the 13 cases and were defined by ROC curve as the only significant predictor for malignancy.Conclusions: Preoperative estimation of serum TG showed higher diagnostic validity than FNAC, high predictability of cancer and ability to verify the intermediate findings on TIRADS. Combined preoperative TIRADS and TG estimation could accurately discriminate malignant TN with high accuracy and spare the need for preoperative FNAC or IO-FS.

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A comparative study of RIPASA score and ALVARADO score in diagnosis of acute appendicitis

International Surgery Journal ◽

10.18203/2349-2902.isj20180430 ◽

2018 ◽

Vol 5 (3) ◽

pp. 796

Author(s):

Vamsavardhan Pasumarthi ◽

C. P. Madhu

Keyword(s):

Acute Appendicitis ◽

Positive Predictive Value ◽

Diagnostic Accuracy ◽

Roc Curve ◽

Predictive Value ◽

Scoring System ◽

Alvarado Score ◽

Predictive Values ◽

Sensitivity Specificity ◽

Ripasa Score

Background: The RIPASA Score is a new diagnostic scoring system developed for the diagnosis of Acute Appendicitis which showed higher sensitivity, specificity and diagnostic accuracy compared to ALVARADO Score, particularly when applied to Asian population. Not many studies have been conducted to compare RIPASA and ALVARADO scoring systems. Hence, author want to compare prospectively Alvarado and RIPASA score by applying them to the patients attending the hospital with right iliac fossa pain that could probably be acute appendicitis.Methods: A prospective analysis of 116 cases admitted with RIF pain during a 2 years period was performed. Patients between 15-60 years were scored as per Alvarado and RIPASA scoring system. Histopathological reports of the cases were collected and compared with the scores. ROC curve area analysis was performed to examine diagnostic accuracy of RIPASA and ALVARADO scores.Results: The sensitivity of ALVARADO score is estimated to be 52.08 for a cut off of 6. The specificity is 80%, positive predictive value is 92.59, negative predictive value is 25.81. The Diagnostic accuracy of ALVARADO scoring is found to be 56.9. The sensitivity, specificity, positive predictive value and negative predictive values of RIPASA scoring system are 75%, 65%, 91.14%, 35.14%. The diagnostic accuracy of RIPASA score is 73.28.Conclusions: The difference in the diagnostic accuracy between ALVARADO and RIPASA scoring system is significant indicating that the RIPASA score is a much better diagnostic tool for the diagnosis of acute appendicitis. When the ROC curve was observed the area under the curve is high for RIPASA scoring system.

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Predictive value of plasma parameters in the risk of postpartum ketosis in dairy cows

Journal of Veterinary Research ◽

10.1515/jvetres-2017-0011 ◽

2017 ◽

Vol 61 (1) ◽

pp. 91-95 ◽

Cited By ~ 7

Author(s):

Yu Cao ◽

Jiang Zhang ◽

Wei Yang ◽

Cheng Xia ◽

Hong-You Zhang ◽

...

Keyword(s):

Dairy Cows ◽

Roc Curve ◽

Predictive Value ◽

Curve Analysis ◽

Paraoxonase 1 ◽

Roc Curve Analysis ◽

Plasma Parameters ◽

Holstein Friesian ◽

Plasma Activity ◽

Friesian Cows

AbstractIntroduction:The predictive value of selected parameters in the risk of ketosis and fatty liver in dairy cows was determined.Material and Methods:In total, 21 control and 17 ketotic Holstein Friesian cows with a β-hydroxybutyrate (BHBA) concentration of 1.20 mmol/L as a cut-off point were selected. The risk prediction thresholds for ketosis were determined by receiver operating characteristic (ROC) curve analysis.Results:In the ketosis group, paraoxonase-1 (PON-1) activity and concentration of PON-1 and glucose (GLU) were decreased, and aminotransferase (AST) activity as well as BHBA and non-esterified fatty acid (NEFA) contents were increased. The plasma activity and concentration of PON-1 were significantly positively correlated with the level of plasma GLU. The plasma activity and concentration of PON-1 were significantly negatively correlated with the levels of AST and BHBA. According to ROC curve analysis, warning indexes of ketosis were: plasma PON-1 concentration of 46.79 nmol/L, GLU concentration of 3.04 mmol/L, AST concentration of 100 U/L, and NEFA concentration of 0.82 mmol/L.Conclusion:This study showed that the levels of PON-1, GLU, AST, and NEFA could be used as indicators to predict the risk of ketosis in dairy cows.

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On the Binormal Predictive Receiver Operating Characteristic Curve for the Joint Assessment of Positive and Negative Predictive Values

Entropy ◽

10.3390/e22060593 ◽

2020 ◽

Vol 22 (6) ◽

pp. 593 ◽

Cited By ~ 3

Author(s):

Gareth Hughes

Keyword(s):

Receiver Operating Characteristic ◽

Roc Curve ◽

Operating Characteristic ◽

Statistical Evaluation ◽

Characteristic Curve ◽

Disease Status ◽

Curve Analysis ◽

Roc Curve Analysis ◽

Predictive Values ◽

Receiver Operating

The predictive receiver operating characteristic (PROC) curve is a diagrammatic format with application in the statistical evaluation of probabilistic disease forecasts. The PROC curve differs from the more well-known receiver operating characteristic (ROC) curve in that it provides a basis for evaluation using metrics defined conditionally on the outcome of the forecast rather than metrics defined conditionally on the actual disease status. Starting from the binormal ROC curve formulation, an overview of some previously published binormal PROC curves is presented in order to place the PROC curve in the context of other methods used in statistical evaluation of probabilistic disease forecasts based on the analysis of predictive values; in particular, the index of separation (PSEP) and the leaf plot. An information theoretic perspective on evaluation is also outlined. Five straightforward recommendations are made with a view to aiding understanding and interpretation of the sometimes-complex patterns generated by PROC curve analysis. The PROC curve and related analyses augment the perspective provided by traditional ROC curve analysis. Here, the binormal ROC model provides the exemplar for investigation of the PROC curve, but potential application extends to analysis based on other distributional models as well as to empirical analysis.

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Predictive value of cerebrospinal fluid lactate for the diagnosis and treatment efficacy of post-neurosurgery bacterial meningitis

10.21203/rs.2.18481/v1 ◽

2019 ◽

Author(s):

Yufang Wang ◽

Jingchao Li ◽

Mingli Yao ◽

Lingyan Wang ◽

Bin Ouyang

Keyword(s):

Cerebrospinal Fluid ◽

Linear Regression ◽

Bacterial Meningitis ◽

Roc Curve ◽

Predictive Value ◽

Treatment Efficacy ◽

Curve Analysis ◽

Diagnosis And Treatment ◽

Roc Curve Analysis ◽

Csf Lactate

Abstract Background: Post-neurosurgical bacterial meningitis (PNBM) is a severe complication with high morbidity and mortality. Rapid and accurate diagnosis of PNBM is difficult. Therefore, it is necessary to find more reliable markers to assist the diagnosis. This study aims to evaluate the predictive value of cerebrospinal fluid (CSF) lactate for PNBM diagnosis and treatment efficacy.Methods: Total 105 cases were enrolled in patients with clinically suspected PNBM who underwent neurosurgeries during October 2015 to December 2016. CSF lactate as well as CSF routine and biochemistry test was measured. Receivers operating characteristic (ROC) curve analysis was used to evaluate the diagnostie power of CSF lactate for PNBM. To assess the predictive value of CSF lactate for treatment efficacy, a linear regression was used and tendency diagrams of CSF lactate and glucose for each patient were drawn.Results: Fifty-four of 105 patients were diagnosed with PNBM. CSF lactate level was significantly higher in PNBM than in non-PNBM patients (p < 0.001). The ROC curve analysis showed a great diagnostic power of CSF lactate for PNBM, and the cut-off value was 4.15 mmol/L (AUC = 0.92, sensitivity, 92.6%; specificity, 74.5%). The combination of CSF lactate and glucose showed better diagnostic efficacy (AUC = 0.97, sensitivity, 94.4%; specificity, 90.2%). The linear regression showed thatΔCSF lactate inversely correlated with ΔCSF glucose and directly correlated with ΔCSF leucocyte (both p < 0.001). The tendency diagrams showed CSF lactate a better predictor for PNBM treatment efficacy than CSF glucose.Conclusion: Our study showed CSF lactate had an excellent discriminatory power in distinguishing between PNBM and non-PNBM. The combination of CSF lactate and glucose had a better diagnostic accuracy than other CSF parameters alone. CSF lactate was a reliable predictor of treatment efficacy in PNBM patients.

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Performance of the dipstick screening test as a predictor of negative urine culture

Einstein (São Paulo) ◽

10.1590/s1679-45082017ao3936 ◽

2017 ◽

Vol 15 (1) ◽

pp. 34-39 ◽

Cited By ~ 6

Author(s):

Alexandre Gimenes Marques ◽

André Mario Doi ◽

Jacyr Pasternak ◽

Márcio dos Santos Damascena ◽

Carolina Nunes França ◽

...

Keyword(s):

Roc Curve ◽

Screening Test ◽

Urine Culture ◽

Curve Analysis ◽

Roc Curve Analysis ◽

Dipstick Test ◽

Predictive Values ◽

Urinary Sediment ◽

Urine Dipstick ◽

Negative Urine Culture

ABSTRACT Objective To investigate whether the urine dipstick screening test can be used to predict urine culture results. Methods A retrospective study conducted between January and December 2014 based on data from 8,587 patients with a medical order for urine dipstick test, urine sediment analysis and urine culture. Sensitivity, specificity, positive and negative predictive values were determined and ROC curve analysis was performed. Results The percentage of positive cultures was 17.5%. Nitrite had 28% sensitivity and 99% specificity, with positive and negative predictive values of 89% and 87%, respectively. Leukocyte esterase had 79% sensitivity and 84% specificity, with positive and negative predictive values of 51% and 95%, respectively. The combination of positive nitrite or positive leukocyte esterase tests had 85% sensitivity and 84% specificity, with positive and negative predictive values of 53% and 96%, respectively. Positive urinary sediment (more than ten leukocytes per microliter) had 92% sensitivity and 71% specificity, with positive and negative predictive values of 40% and 98%, respectively. The combination of nitrite positive test and positive urinary sediment had 82% sensitivity and 99% specificity, with positive and negative predictive values of 91% and 98%, respectively. The combination of nitrite or leukocyte esterase positive tests and positive urinary sediment had the highest sensitivity (94%) and specificity (84%), with positive and negative predictive values of 58% and 99%, respectively. Based on ROC curve analysis, the best indicator of positive urine culture was the combination of positives leukocyte esterase or nitrite tests and positive urinary sediment, followed by positives leukocyte and nitrite tests, positive urinary sediment alone, positive leukocyte esterase test alone, positive nitrite test alone and finally association of positives nitrite and urinary sediment (AUC: 0.845, 0.844, 0.817, 0.814, 0.635 and 0.626, respectively). Conclusion A negative urine culture can be predicted by negative dipstick test results. Therefore, this test may be a reliable predictor of negative urine culture.

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Discriminating Capacity of Indole Markers in the Diagnosis of Carcinoid Tumors

Clinical Chemistry ◽

10.1093/clinchem/46.10.1588 ◽

2000 ◽

Vol 46 (10) ◽

pp. 1588-1596 ◽

Cited By ~ 79

Author(s):

Wim G Meijer ◽

Ido P Kema ◽

Marcel Volmer ◽

Pax H B Willemse ◽

Elisabeth G E de Vries

Keyword(s):

Positive Predictive Value ◽

Carcinoid Tumor ◽

Predictive Value ◽

Roc Analysis ◽

Reference Group ◽

Curve Analysis ◽

Carcinoid Tumors ◽

Healthy Controls ◽

Roc Curve Analysis ◽

Platelet Serotonin

Abstract Background: We evaluated the discriminating capacity of the indole markers urinary 5-hydroxyindoleacetic acid (5-HIAA), urinary serotonin, and platelet serotonin in the diagnosis of carcinoid tumors. Methods: Indole markers were measured in 688 patients with suspected carcinoid disease. The initial values of indole markers from patients in whom a carcinoid tumor was confirmed during follow-up (n = 98) were used for ROC analysis. Two groups served as reference populations. The first consisted of 45 healthy individuals (“healthy controls”). The second was a random sample of 40 patients, drawn from the 590 (688 minus 98) patients with carcinoid-like symptoms but without a carcinoid tumor (“clinically suspected patients”). Results: ROC curve analysis showed platelet serotonin to have the highest discriminating capacity, especially in foregut carcinoids. Cutoff values for platelet serotonin obtained from ROC analysis with healthy controls as reference group (5.4 nmol/109 platelets) gave a sensitivity of 74%, specificity of 91%, positive predictive value of 63%, and negative predictive value of 95% when applied to the initial 688 patients. Using the cutoff value with the clinically suspected patients as the reference group (9.3 nmol/109 platelets) gave a sensitivity of 63%, specificity of 99%, positive predictive value of 89%, and negative predictive value of 93%. Indole markers were increased in 169 (25%) of 688 patients. In 76 (45%) of these 169 patients, a carcinoid tumor was present. Slight increases of markers were associated with non-carcinoid neuroendocrine tumors, non-neuroendocrine tumors, and disturbed bowel motility. Conclusions: ROC curve analysis shows that platelet serotonin is the most discriminating indole marker for the diagnosis of carcinoid tumors. Platelet serotonin especially improves the diagnosis of carcinoids producing small amounts of serotonin.

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Abstract 12875: Serum Neutrophil Gelatinase-associated Lipocalin Has a Predictive Value for the Neurological Outcome of Post Cardiac Arrest Victims

Circulation ◽

10.1161/circ.132.suppl_3.12875 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Tadashi Kaneko ◽

Motoki Fujita ◽

Yasuaki Ogino ◽

Hiroki Irie ◽

Shinsuke Iwashita ◽

...

Keyword(s):

Cardiac Arrest ◽

Roc Curve ◽

Predictive Value ◽

Neurological Outcome ◽

Neuron Specific Enolase ◽

Area Under The Curve ◽

Curve Analysis ◽

Roc Curve Analysis ◽

Significant Difference ◽

Neutrophil Gelatinase

Introduction: Neutrophil gelatinase-associated lopocalin (NGAL) is well known as the biomarker of acute kidney injury. Currently, serum NGAL is reported as the biomarker which is associated with mortality and multiple organ dysfunction syndrome in septic patients. In this study, we measured serum NGAL in post cardiac arrest syndrome (PCAS) patients to investigate the predictive value of neurological outcome. Hypothesis: Serum NGAL is associated with favorable neurological outcome of PCAS patients. Methods: 43 cases of PCAS patients were measured serum NGAL on day 1 and 2, and serum neuron specific enolase (NSE) was also measured on day 2. Patients were divided into two group (group G: CPC 1-2 and group P: CPC 3-5, CPC: cerebral performance categories). Serum NGAL and NSE were compared between group G and P. Receiver operation characteristic (ROC) curve analysis were performed of both NGAL and NSE. Results: Group G (n = 20) and P (n = 23) were analyzed. Serum NGAL showed significant difference in day 2 (G: 282±116 ng/mL v.s. P: 299±87 ng/mL in day1: P = 0.609, G: 185±124 ng/mL v.s. P: 353±110 ng/mL in day 2: P<0.001). The ROC curve analysis showed area under the curve of NGAL in day 2 was 0.871, and the area of NSE in day2 showed 0.918. Conclusions: Serum NGAL in PCAS patients had the predictive value for neurological outcome which is comparable to serum NSE. (This study was supported by grants from Japanese Ministry of Health, Labour and Welfare: No. 25462824)

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The Plasma Level of Leukemia Stem Cell Specific Antigens - CLL1 and TIM3 Are Predictive of Overall Survival in Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v126.23.1407.1407 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1407-1407

Author(s):

Chin-Hin Ng ◽

Ma Thin Mar Win ◽

Elaine Seah ◽

Wee-Joo J Chng

Keyword(s):

Overall Survival ◽

Complete Remission ◽

Roc Curve ◽

Predictive Value ◽

Function Analysis ◽

Survival Function ◽

Survival Outcome ◽

Curve Analysis ◽

Roc Curve Analysis ◽

Cox Regression Analysis

Abstract Background: Despite intensive chemotherapy, acute myeloid leukemia (AML) is still associated with significant relapse rate. This was thought to be due to a sub clone of leukemic blasts that was resistant to chemotherapy. This sub clone of resistant blasts were later identified to be leukemic stem cell (LSC). Many studies have demonstrated that high initial load of LSC at diagnosis was associated with relapse and poor overall outcome. This study aimed to use a clinically practical method - ELISA to identify plasma biomarkers that are closely related to LSC and study their predictive value in term of complete remission (CR), relapse, and overall survival. Method: Peripheral blood of 27 newly diagnosed AML patients were collected at diagnosis. Plasma component of the blood was separate from cellular component using Ficoll separation method. 9 biomarkers were shortlisted based on surface antigens of LSC that were commonly reported in literature as well as genes that were reported to be highly expressed in LSC. These are CD25, CD32, CD96, CD123, TIM3, CLL-1, HCK, FLT3 and WT1. Commercially available ELISA kits with high sensitivity and specificity to these 9 human biomarkers were sourced. All 9 biomarkers were measured on 80 normal blood donors' plasma to use as control and to establish the normal range (Mean+/-2SD). The plasma of the 27 study subjects was measured in duplicate for all 9 biomarkers. ROC curve analysis was done in relation to complete remission, relapse, and survival outcome on all 9 candidates biomarkers. Results: A total 27 newly diagnosed AML patients with curative intent were included in this analysis. Median age for this cohort was 41 years old (range: 22-70). Induction death rate 14.8% (n=4), and complete remission (CR) rate of 77.8%. A total of 8 relapsed refractory cases and 6 deaths were observed over the median follow-up of 10.2 months (range: 0.6-31.2). ROC curve analysis was carried out on all 9 candidates plasma biomarkers, CLL-1 and TIM3 came out to be of significant predictive value of survival outcome. No biomarker was found to be predictive of relapse or CR. ROC curve analysis of plasma CLL-1 level in relation to survival outcome showed an AUC of 0.77 with a plasma cut-off level of 54pg/ml giving the best discriminative result. Chi-square test using this cut off level for survival outcome showed a better survival in patients with plasma CLL-1 level of <54pg/ml (p= 0.001). This cut-off level gave a sensitivity of 83.3% and a specificity of 85.7%, with a high negative predictive value (NPV) of 94.7% but moderate positive predictive value (PPV) of 62.5%. Using this cut-off level to predict CR also showed a significant result (50% CR rate for those with plasma CLL-1 of >54 pg/ml compared to 89.5% in patients with <54pg/ml, p=0.024). Survival function analysis using this cut-off level showed a significantly prolonged survival in patients with plasma CLL-1 level of <54pg/ml with mean survival of 29.63 months (95%CI: 26.70-32.56) as compared to those with plasma CLL-1 level of >54pg/ml (Mean survival: 8.1 months, 95%CI:3.2-13.0). Cox-regression analysis on overall survival showed a significantly high Hazard Ratio of 18.3 for plasma CLL-1 level >54pg/ml (p=0.09, 95%CI:2.09-160.2), see the figure 1 below. ROC curve analysis of plasma TIM3 level in relation to survival outcome revealed an AUC of 0.73 with a plasma cut-off level of 615pg/ml to be the best discriminative cut-off. Chi-square test using this cut-off level for survival outcome showed significant better survival in patients with plasma TIM3 level of <615pg/ml (p=0.016). This cut-off level gave a sensitivity of 83.3% and a specificity of 71.43% with high NPV of 93.75% but a rather low PPV of 45.45%. Survival function analysis again confirmed a much longer mean survival in patients with plasma TIM3 level of <615pg/ml (Mean survival: 29.2 months, 95%CI:25.5-32.9) as compared to TIM3 level of >615pg/ml (Mean survival: 13.8 months, 95%CI:7.2-20.4), p=0.014. Cox-regression analysis again showed a significant Hazard Ratio of 9.2 for plasma TIM3 level of >615pg/ml (p=0.043, 95%CI:1.01-78.7), see figure 2 below. Conclusion: A raised plasma CLL-1 level of more than 54pg/ml and TIM3 level of more than 615pg/ml were predictive of survival outcome in this small cohort of AML patients who underwent curative chemotherapy. A larger cohort of AML patients would be needed to confirm this novel finding. Disclosures No relevant conflicts of interest to declare.

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Evaluation of BCR-ABL/ABL Ratio Increase That Corresponds to BCR-ABL Mutation In Chronic Myeloid Leukemia Patients Treated by Imatinib.

Blood ◽

10.1182/blood.v116.21.3422.3422 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3422-3422

Author(s):

Grigory Tsaur ◽

Anna Ivanova ◽

Alexander Popov ◽

Yulia Yakovleva ◽

Tatyana Riger ◽

...

Keyword(s):

Treatment Failure ◽

Roc Curve ◽

Mutation Detection ◽

Mutation Screening ◽

Point Mutations ◽

Threshold Level ◽

Curve Analysis ◽

Roc Curve Analysis ◽

Ratio Increase ◽

Predictive Values

Abstract Abstract 3422 Introduction. Currently there is no consensus in definition what level of BCR-ABL/ABL ratio increase predicts presence of kinase domain (KD) mutations. Several research groups use relatively low cut-off levels equal to 2.0- and 2.6-fold (S. Branford et al, Blood, 2004, R. Press et al Blood, 2009, respectively), that are close to the discrimination ability of real–time quantitative PCR (RQ-PCR) method. Alternatively, an NCCN guideline recommends beginning of mutation screening in case of 10-fold or greater elevation of BCR-ABL/ABL ratio. Aim. To define a threshold level of BCR-ABL/ABL increase that predicts presence of BCR-ABL mutations. Methods. Among 531 CML patients on imatinib (IM), both newly diagnosed and pre-treated with interferon-α, in 47 ones BCR-ABL mutation detection was performed. These were patients with suboptimal response or treatment failure according to the European LeukemiaNet criteria (M. Baccarani et al, 2009). Conventional cytogenetic analysis was performed every 6 months. Quantitative measurement of BCR-ABL/ABL transcripts ratio by RQ-PCR was done every 3–6 months. A major molecular response was defined as BCR-ABL/ABL transcripts level of 0.059% corresponded to 3 log reduction from the laboratory defined baseline level. Point mutations in the BCR-ABL KD were detected by reverse-transcriptase PCR and direct sequencing. Elevation of BCR-ABL/ABL was calculated by dividing of BCR-ABL/ABL value at the time point (TP) where mutation detection was performed to the BCR-ABL/ABL value at TP prior to mutation screening. Event-free survival (EFS) was defined as the time from IM beginning until any of the following events occurred: loss of complete hematological response, loss of major cytogenetic response, progression to AP/BC, death of any reason. Threshold level was defined by receiver operator characteristics (ROC) curve analysis. Positive and negative predictive values (PPV, NPV), sensitivity, specificity and overall correct prediction (OCP) were calculated. Results. 10 different point mutations of BCR-ABL gene were detected, including 3 ones in P-loop, 2 in IM-binding site, 3 in A-loop, and 2 mutations outside the KD. None of patients had 2 or more mutations simultaneously. Patients were divided into two groups: with (n=18) and without (n=29) BCR-ABL mutations. Groups did not differ in age, sex distribution, type of BCR-ABL transcript, frequency of cumulative achievement of CHR, CCyR, MMR and level of BCR-ABL/ABL increase (table 1). Median time between BCR-ABL/ABL measurement was similar in both groups: 6 months (range 1–12 months) (p=0.227). ROC curve analysis determined that increasing of BCR-ABL/ABL level in 5.5-fold corresponds to 92.9% of NPV. Area under curve was 68% (95% CI 50–95%) (p=0.022). Sensitivity, PPV and OCP were relatively low (40.6%, 40.6%, 56.5%, respectively) while specificity was high (92.9%). Conclusions. In our series 5.5-fold increase of BCR-ABL/ABL clearly predicts presence of BCR-ABL mutations and indicates the exact time for mutation detection performing in patients with suboptimal response and treatment failure. Nowadays, with availability of primary reference material for BCR-ABL quantification, approved by WHO (H. White at al, Hematologica, 2010) and successful harmonization of molecular monitoring of CML therapy (M. Mueller et al, Leukemia 2009) elevation level that corresponds with mutation presence could also be standardized. Application of international standardized threshold level would help to avoid unnecessary or late mutation tests. Disclosures: Ivanets: Novartis Pharma: Employment.

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