Predictor Of Clinical Relapse Research Articles

Effects of Delay Discounting and Other Predictors on Smoking Relapse.

Despite the substantial decrease in the prevalence of tobacco smoking and the availability of effective smoking cessation treatments, smoking relapse after formal treatments remains extremely high. Evidence regarding clinical predictors of relapse after quitting is essential to promote long-term abstinence among those who successfully quit. This study aimed to explore whether baseline delay discounting (DD) rates and other sociodemographic, psychological, and smoking-related variables predicted relapse to smoking at six-month follow-up. Participants were 188 adult smokers (mean age = 42.9, SD = 12.9; 64.4% females) who received one of three treatment conditions: 6-weeks of cognitive-behavioral treatment (CBT) alone; or combined with contingency management (CBT + CM); or combined with cue exposure treatment (CBT+CET). Smoking status was biochemically verified. Logistic regression was conducted to examine prospective predictors of smoking relapse at six months after an initial period of abstinence. Greater DD rates (OR: 0.18; 95% CI [0.03, 0.93]), being younger (OR: 0.96; 95% CI [0.94, 0.99]), high nicotine dependence (OR: 1.34; 95% CI [1.13, 1.60]), and a higher number of previous quit attempts (OR: 4.47; 95% CI [1.14, 17.44]) increased the likelihood of smoking relapse at six-month follow-up. Besides sociodemographic and smoking-related characteristics, greater DD predisposes successful quitters to relapse back to smoking. These results stress the relevance of incorporating specific treatment components for reducing impulsivity.

Entyvio lengthen dose-interval study: lengthening vedolizumab dose interval and the risk of clinical relapse in inflammatory bowel disease

Vedolizumab (VDZ), an α4β7 anti-integrin antibody, is efficacious in the induction and maintenance of remission in ulcerative colitis (UC) and Crohn's disease (CD). In the GEMINI long-term safety study, enrolled patients received 4-weekly VDZ. Upon completion, patients were switched to 8-weekly VDZ in Australia. The clinical success rate of treatment de-escalation for patients in remission on VDZ has not been described previously. To determine the proportion of patients who relapsed after switching from 4 to 8-weekly VDZ, the mean time to relapse, and the recapture rate when switching back to 8-weekly dosing. This was a retrospective, observational, multicenter study of patients previously recruited into GEMINI long-term safety in Australia. Data on the demographics and biochemical findings were collected. There were 34 patients [23 men, mean age 49.1 (±13.1) years] and their mean disease duration was 17.6 (±8.5) years. The mean 4-weekly VDZ infusion duration was 286.5 (±48.8) weeks. A total of five (15%) patients relapsed on dose-interval increase (4/17 UC, 1/17 CD) at a median duration from dose interval lengthening to flare of 14 weeks (interquartile range=6-25). Eighty percent (4/5) of patients re-entered remission following dose-interval decrease back to 4-weekly. No clinical predictors of relapse could be determined because of the small cohort size. The risk of patients relapsing when switching from 4 to 8-weekly VDZ ∼15% and is similar between CD and UC. Dose-interval decrease recaptures 80% of patients who relapsed. Therapeutic drug monitoring of VDZ may be of clinical relevance.

Impact of clinical and molecular features on risk of recurrence following curative intent resection of metastases in metastatic colorectal cancer.

785 Background: Resection of metastases with curative intent is an integral component of mCRC management. However, relapse rates are high and identifying patients most likely to benefit from this approach is of considerable importance. Among patients with mCRC, mutations (mt) in RAS and BRAF genes portent a worse prognosis. Our hypothesis, therefore, is that patients harbouring these mutations may have a higher relapse rate after resection of metastases. We also wished to analyse clinical predictors of relapse, including site of metastases. Methods: We interrogated the TRACC database of patients undergoing resection with curative intent who had mutation status available. The frequency of RAS and BRAF mt was established and their association with clinical parameters determined. Relapse free (RFS) and overall survival (OS), from the date of resection, was estimated for the mt and wild type (wt) groups using the Kaplan Meier method. Multivariate analysis is planned to investigate factors associated with RFS, including stage of the primary tumour, synchronous metastases, site and number of metastases, CEA, peri-operative chemotherapy use, site of the primary (left v right) and RAS and BRAF mutation status. Results: 188 patients were identified. 89 were KRAS/BRAF wt, 92 KRAS mt and 7 BRAF mt. 40% had presented with metastatic disease and 27% had a right sided primary. 76%, 22% and 2% underwent resection of liver, lung or both metastases. Microscopic resection margin was involved in 6%. Resection was performed prior to any chemotherapy in 48%. No difference was seen in relapse free or overall survival between the mt and wt groups. Conclusions: We found no difference in relapse free or overall survival by mutation subgroup suggesting this should not influence suitability for curative intent resection, but analyses is planned on a much larger cohort once data is available. A multivariate analysis, adjusting for important prognostic variables, is planned.

P473 How to monitor the withdrawal of maintenance treatment with azathioprine in IBD patients with deep remission: results from a prospective study on multiple non invasive tests

Background: There is uncertainty regarding the optimal duration of maintenance treatment with azathioprine (AZA) in Crohn's disease (CD) and ulcerative colitis (UC), with some studies suggesting durations up to 4–5 years and others supporting long-term indefinite use. More recent guidelines state that for patients in long term remission, cessation of treatment may be considered in the absence of objective signs of inflammation, but no data are available on how to monitor these patients after AZA withdrawal. Methods: A prospective observational study was performed on consecutive patients with CD or UC who stopped their maintenance treatment with AZA while being in steroid-free, deep remission, defined as normal clinical and endoscopic indexes, normal C-reactive protein (CRP) and normal fecal calprotectin. After AZA withdrawal, all patients received maintenance treatment with salicylates. Every 3 months, blood samples were collected for standard biochemical tests (including CRP, full blood count and protein electrophoresis), as well as stool samples for fecal calprotectin dosage. Bowel ultrasonography and ileocolonoscopy were performed every 6 and 12 months, respectively, as well as in case of clinical relapse. Multiple logistic regression and Cox proportional-hazards models were used to assess the predictors of disease relapse. Results: 41 patients (23 males, median age 45 years) who stopped AZA after median 7 years (range 5–14) were enrolled. After a mean follow-up of 24 months (range 5–48), 19 patients (46%; 7/19 CD, 12/22 UC) relapsed, within median 13 months (range 2–35). Predictors of clinical relapse at the time of AZA withdrawal were female gender (p=0.045) and age ≤45 years (p=0.035) only for UC. Fecal calprotectin was the only predictor of clinical relapse during the non invasive monitoring performed after AZA withdrawal, both in UC (p=0.019) and in CD (p=0.017). Moreover, fecal calprotectin was positive in all patients with UC and in 57% of CD patients at the time of relapse. Conclusions: Up to half of patients with IBD relapses after AZA withdrawal at different times. Fecal calprotectin can predict subsequent clinical relapse after AZA withdrawal. This can be useful in the non invasive monitoring of patients to detect preclinical relapse and to early correct our therapeutic strategy after AZA withdrawal. Prospective randomized studies are needed to validate such strategy.

Histological Disease Activity as a Predictor of Clinical Relapse Among Patients With Ulcerative Colitis: Systematic Review and Meta-Analysis.

Endoscopic remission in ulcerative colitis (UC) is associated with improved clinical outcomes. We assessed whether histological remission predicts clinical outcomes, estimated the magnitude of effect, and determined whether histological remission provides additional prognostic utility beyond clinical or endoscopic remission. Bibliographic databases were searched for studies in inflammatory bowel disease providing baseline histological status and relation to an outcome of clinical relapse or exacerbation. Our primary analysis compared the proportion of patients with study-defined histological remission vs. the proportion with histological activity who developed clinical relapse/exacerbation. Additional analyses compared the proportion with relapse/exacerbation for the presence vs. absence of different histological features and for histological remission vs. endoscopic remission and clinical remission. A fixed-effect model was used for meta-analysis, with a random-effects model if statistical heterogeneity was present. Fifteen studies met inclusion criteria. The major methodological shortcoming was lack of blinding of the assessor of clinical relapse/exacerbation to baseline histological status in 13 of the 15 studies. Relapse/exacerbation was less frequent with baseline histological remission vs. histological activity (relative risk (RR)=0.48, 95% confidence interval (CI) 0.39-0.60) and vs. baseline clinical and endoscopic remission (RR=0.81, 95% CI 0.70-0.94). Relapse/exacerbation was also less common in the absence vs. presence of specific histological features: neutrophils in epithelium (RR=0.32, 95% CI 0.23-0.45), neutrophils in lamina propria (RR=0.43, 95% CI 0.32-0.59), crypt abscesses (RR=0.38, 95% CI 0.27-0.54), eosinophils in the lamina propria (RR=0.43, 95% CI 0.21-0.91), and chronic inflammatory cell infiltrate (RR=0.28, 95% CI 0.10-0.75). Histological remission was present in 964 (71%) of the 1360 patients with combined endoscopic and clinical remission at baseline. UC patients with histological remission have a significant 52% RR reduction in clinical relapse/exacerbation compared with those with histological activity. Histological remission is also superior to endoscopic and clinical remission in predicting clinical outcomes. As ~30% of patients with endoscopic and clinical remission still have histological activity, addition of histological status as an end point in clinical trials or practice has the potential to improve clinical outcomes.

Relapse of chronic hepatitis B after discontinuation of nucleos(t)ide analogs: Is the glass half full or half empty?

Relapse of chronic hepatitis B after discontinuation of nucleos(t)ide analogs: Is the glass half full or half empty?

PDCD2 functions in cancer cell proliferation and predicts relapsed leukemia

PDCD2 is an evolutionarily conserved eukaryotic protein with unknown function. The Drosophila PDCD2 ortholog Zfrp8 has an essential function in fly hematopoiesis. Zfrp8 mutants exhibit marked lymph gland hyperplasia that results from increased proliferation of partially differentiated hemocytes, suggesting Zfrp8 may participate in cell growth. Based on the above observations we have focused on the role of PDCD2 in human cancer cell proliferation and hypothesized that aberrant PDCD2 expression may be characteristic of human malignancies. We report that PDCD2 is highly expressed in human acute leukemia cells as well as in normal hematopoietic progenitors. PDCD2 knockdown in cancer cells impairs their proliferation, but not viability relative to parental cells, supporting the notion that PDCD2 overexpression facilitates cancer cell growth. Prospective analysis of PDCD2 in acute leukemia patients indicates PDCD2 RNA expression correlates with disease status and is a significant predictor of clinical relapse. PDCD2’s role in cell proliferation and its high expression in human malignancies make it an attractive, novel potential molecular target for new anti-cancer therapies.

Long-Term Clinical Outcomes and Factors Predictive of Relapse After 5-Aminosalicylate or Sulfasalazine Therapy in Patients With Intestinal Behcet Disease

Currently, 5-aminosalicylic acid (5-ASA)/sulfasalazine is used to empirically treat patients with intestinal Behcet disease (BD) without clear clinical evidence. In this study, we investigated long-term clinical outcomes and predictors of clinical relapse in patients with intestinal BD receiving 5-ASA/sulfasalazine maintenance therapy. We reviewed the medical records of all the patients with intestinal BD, who received 5-ASA/sulfasalazine therapy in a single tertiary academic medical center between March 1986 and January 2011. The cumulative probabilities of clinical relapse after remission were calculated using the Kaplan-Meier method. Predictors of clinical relapse were identified by univariate analysis using the log-rank test and by multivariate analysis using Cox proportional hazards regression models. Among the 143 patients enrolled, 46 (32.2%) had a clinical relapse while they were being treated with 5-ASA/sulfasalazine therapy. The cumulative relapse rates at 1, 3, 5, and 10 years after remission were 8.1%, 22.6%, 31.2%, and 46.7%, respectively. By multivariate analysis, a younger age (<35 y) at the time of diagnosis, higher C-reactive protein level (≥1.5 mg/dL), and a higher disease activity index for intestinal Behcet disease score (≥60) at the time of 5-ASA/sulfasalazine initiation were independent predictors of relapse in patients with intestinal BD receiving 5-ASA/sulfasalazine maintenance therapy. This study has shown that 5-ASA/sulfasalazine therapy has a positive effect in maintaining remission in patients with intestinal BD. However, a younger age (<35 y), higher C-reactive protein level (≥1.5 mg/dL), and a higher disease activity index for intestinal Behcet disease score (≥60) were associated with a poor response to 5-ASA/sulfasalazine therapy, making careful observation and intensive treatment necessary in these risk groups.

Clinical outcomes and prognostic factors for thiopurine maintenance therapy in patients with intestinal Behcetʼs disease

To date, there have been no studies focusing on the efficacy of thiopurine therapy in intestinal Behcet's disease (BD). We conducted this study to investigate clinical outcomes and predictors of clinical relapse in intestinal BD patients receiving thiopurine maintenance therapy. We reviewed the medical records of all patients with intestinal BD who received thiopurine therapy in a single tertiary academic medical center between March 1986 and October 2010. The cumulative probabilities of clinical relapse after remission were calculated using the Kaplan-Meier method. Predictors of clinical relapse were identified by univariate analysis using the log-rank test and by multivariate analysis using Cox proportional hazards regression models. Of a total of 272 patients with intestinal BD, 67 (24.6%) received their first course of thiopurine therapy at our center. Thirty-nine (58.2%) of the 67 patients constantly received thiopurines for maintaining medically or surgically induced remission. The cumulative relapse rates at 1 year, 2 years, 3 years, and 5 years after remission were 5.8%, 28.7%, 43.7%, and 51.7%, respectively. On multivariate analysis, a younger age (<25 years) at diagnosis and a lower hemoglobin level (<11 g/dL) were independent predictive factors for relapse in intestinal BD patients receiving thiopurine maintenance therapy. Thiopurine therapy showed a relatively good effect for maintenance of remission in intestinal BD patients. However, a younger age at diagnosis and a lower hemoglobin level were associated with a poor response to thiopurines, necessitating early adoption of effective alternative therapeutic options in these risk groups.

Predictors of relapse in Chinese schizophrenia patients: a prospective, multi-center study

Relapse prevention is the main goal of maintenance treatment in schizophrenia. This study aimed to determine the rate and the socio-demographic and clinical predictors of relapse in Chinese schizophrenia patients following treatment of the acute phase of the illness. In a multi-center, randomized, controlled, longitudinal study, 404 patients with schizophrenia who were clinically stabilized following an acute episode were randomly assigned to either the maintenance (i.e., initial optimal therapeutic doses continued throughout the study) or the dose-reduction group (i.e., initial optimal therapeutic doses continued for 4 or 26 weeks followed by a 50% dose reduction that was maintained until the end of the study). Participants were interviewed at entry using standardized assessment instruments, and followed up for 12-26 months. In univariate analyses, relapse was significantly associated with the membership of the dose-reduction group, poor medication adherence, and having a diagnosis of the paranoid type of schizophrenia. In Cox proportional-hazards regression analysis the membership of the dose-reduction group, poorer medication adherence, more severe drug-induced side effects and prominent paranoid symptoms independently predicted a higher risk of relapse. The study confirmed the importance of maintenance medication in preventing relapse in Chinese schizophrenia patients underscoring the risk of relapse associated with lack of treatment adherence, severe side effects and the patients' paranoid attitude. Socio-demographic characteristics were not associated with relapse in Chinese schizophrenia patients. Potential residual confounding caused by unmeasured variables should be fully considered in future studies.

Clinical Predictors of Relapse after Treatment of Primary Gastrointestinal Cytomegalovirus Disease in Solid Organ Transplant Recipients

Primary gastrointestinal cytomegalovirus (CMV) disease after solid organ transplantation (SOT) is difficult to treat and may relapse. Herein, we reviewed the clinical records of CMV D+/R- SOT recipients with biopsy-proven gastrointestinal CMV disease to determine predictors of relapse. The population consisted of 26 kidney (13 [50%]), liver (10 [38%]) and heart (3 [12%]) transplant recipients who developed gastrointestinal CMV disease at a median of 54 (interquartile range [IQR]: 40-70) days after stopping antiviral prophylaxis. Except for one patient, all received induction intravenous ganciclovir (mean+/-SD, 33.8+/-19.3 days) followed by valganciclovir (27.5+/-13.3 days) in 18 patients. Ten patients further received valganciclovir maintenance therapy (41.6+/-28.6 days). The median times to CMV PCR negativity in blood was 22.5 days (IQR: 16.5-30.7) and to normal endoscopic findings was 27.0 days (IQR: 21.0-33.5). CMV relapse, which occurred in seven (27%) patients, was significantly associated with extensive disease (p=0.03). CMV seroconversion, viral load, treatment duration, maintenance therapy and endoscopic findings at the end of therapy were not significantly associated with CMV relapse. In conclusion, an extensive involvement of the gastrointestinal tract was significantly associated with CMV relapse. However, endoscopic evidence of resolution of gastrointestinal disease did not necessarily translate into a lower risk of CMV relapse.

Predicting relapse in Crohn’s disease: a biopsychosocial model

Background:Crohn’s disease (CD) is a chronic relapsing inflammatory bowel disorder. Both biological and psychosocial factors may modulate the illness experience.Aim:The aim of this study was to identify clinical, biological and...

Bcr-Abl mutations in imatinib-resistant CML and Ph+ALL patients (pts) enrolled in a phase I study of AMN107

6527 Background: AMN107 is a potent, highly selective, aminopyrimidine inhibitor which in vitro is 30-fold more potent than imatinib and active against 32/33 imatinib resistant Bcr-Abl mutations. Methods: The spectrum of mutations in Bcr-Abl was evaluated by direct sequencing of the kinase domain and surrounding regions on samples from pts with imatinib-resistant Ph+ CML or ALL in a phase I study of AMN107 (total daily dose range 50 to 1200 mg administered qd or bid). The template was created by semi-nested PCR using primers in the BCR and ABL regions of the gene. Mutations were correlated with clinical response. Results: Among 119 pts, 86 had both pre and post tx analyses: 39 (45%) had mutations at baseline, of whom 27 (69%) responded. 47 (55%) had no mutation at baseline, of whom 34 (72%) responded. The most common baseline mutations were G250E, E255K/V, E355G, F317L, H396R and M351T. New mutations were found during median follow-up of 112 (6 - 350) days in 37 pts (26 without baseline mutations). New mutations most commonly included F349V, E255K/V, E355G, G250E, M244V and T315I. Of the 37 pts, 30 had evaluations after mutations emerged, and 15 continued to respond for median of 160 (41–351) days. Fourteen mutations not previously reported occurred, 6 at codons with known imatinib resistance mutations resulting in novel amino acid substitutions. Novel mutations in multiple pts and/or multiple timepoints included E344G, F311I, E453K, E459Q and L248L. The T315I mutation was present at baseline in 1 pt who failed to respond and emerged in 4 pts, of whom follow-up was available for 3. Two continued to respond ≥ 80 days after developing the mutation and one progressed when the mutation emerged. Conclusions: AMN107 has clinical activity in pts with Ph+CML/ALL with nonmutated and mutated Bcr-Abl. At AMN107 doses used in this phase I study, new mutations often emerged, but were not a reliable predictor of clinical relapse. [Table: see text]

New Insights into the Biological and Clinical Significance of Fecal Calprotectin in Inflammatory Bowel Disease

Nowadays, calprotectin, a cytoplasmatic protein, released by activated neutrophilic polymorphonuclear cells (PMN) and/or monocytes-macrophages (MØ), is considered a good indicator of inflammation in several diseases. Accordingly, fecal calprotectin represents a good predictor of clinical relapse in ulcerative colitis (UC) patients, whereas conflicting results have been reported in Crohn's disease (CD) patients. In our study, in 76 IBD patients (29 CD and 47 UC) fecal calprotectin has been evaluated by a commercial ELISA kit. Results demonstrate that levels of this protein in the stool are significantly more elevated in active CD and UC patients than in normal volunteers. In quiescent CD and UC a trend to higher levels of calprotectin than in the normal counterpart is, however, evident. These data suggest that a low-grade inflammation of the intestinal wall is always present in CD and UC patients, which may predict a clinical relapse risk. In the same group of patients calprotectin levels also were analyzed according to sex and age. A trend to higher values of calprotectin was present in male patients with active or quiescent CD than in their female counterparts. Only in UC patients in remission a trend to calprotectin increase was more marked in the male group than in the female counterpart. When CD and UC patients were divided up according to age, calprotectin positivity peaked between 30–39 years in active CD patients, while in quiescent CD maximum positivity was between 40 and 49 years. However, in both active and quiescent UC patients, calprotectin positivity increased with age. The more precocious detectability of fecal calprotectin in CD patients, as a marker of intestinal mucosa inflammation, may be related to the different histopathology of the two diseases (CD versus UC). However, reduced PMN and/or MØ trafficking from peripheral blood to intestinal mucosa with age by effects of chronic treatment should not be ignored in CD patients.

Serum CA125 assay in the early diagnosis of recurrent epithelial ovarian cancer

The present retrospective study included 59 patients who had been treated for epithelial ovarian cancer and who showed an elevation of serum CA125 above 35 U/ml without clinical evidence of disease. Eight patients underwent chemotherapy at the time of serum antigen elevation (group A). The other 51 patients (group B) were periodically checked, and received further chemotherapy only when recurrent disease was detected. Forty-four of the 59 patients relapsed. One patient of group B experienced two different recurrences with two distinct time intervals. The median follow-up of survivors from CA125 elevation was 10 months (range 2-92 months). Of the 8 patients of group A, 3 (37.5%) developed recurrent disease after 14, 17 and 22 months, respectively, from antigen elevation. Of the 51 patients of group B, 41 (80.4%) relapsed. The overall recurrence rate was 82.4% (42/51). The median lead time between CA125 increase and clinical detection of relapse was 3 months (range 2-27 months). The present data confirmed the reliability of serum CA125 assay as predictor of clinical relapse in epithelial ovarian cancer. The recurrence rate seemed to be lower for patients who received chemotherapy at the time of CA125 elevation (37.5% versus 82.4%, p=0.02). However, the small number of patients, the short follow-up, and the non-randomized design of the study do not allow to draw any conclusion on the appropriate timing for second-line chemotherapy.

Clinical predictors of relapse following neuroleptic withdrawal

The validity of previously hypothesized predictors of elapse following neuroleptic discontinuation was examined. One hundred sixty-two outpatients, with either Research Diagnotic Criteria schizophrenia or schizoaffective disorder, were discontinued from neuroleptic medication for a 28-day period or until judged to be relapsed. Pre-discontinuation neuroleptic dosage level, the severity of psychotic symptoms, and the presence of dyskinetic movements prior to neuroleptic discontinuation were the predictor variables. Of the 162 patients, 62.7% did not relapse during the study period. There were no differences in the survival rates between the patients withdrawn from oral versus depot neuroleptics. Neuroleptic dosage, but not severity of psychotic symptoms or dyskinetic movements, predicted relapse. These results support the hypothesis that pre-withdrawal neuroleptic dosage level predicts relapse, but fail to validate either severity of psychotic symptoms or presence of dyskinetic movements as predictors of relapse.