DOP006. Histological normalisation is associated with superior clinical relapse free survival compared to histological activity and histological quiescence in ulcerative colitis

Objectives Useful indices to determine whether to reduce the dose of 5-aminosalicylic acid (5-ASA) in patients with ulcerative colitis (UC) during remission remain unclear. We aimed to analyze the rate and risk factors of relapse after reducing the dose of oral 5-ASA used for maintenance therapy of UC. Methods UC patients whose 5-ASA dose was reduced in clinical remission (partial Mayo score of ≤ 1) at our institution from 2012 to 2017 were analyzed. Various clinical variables of patients who relapsed after reducing the dose of oral 5-ASA were compared with those of patients who maintained remission. Risk factors for relapse were assessed by univariate and multivariate logistic regression analyses. Cumulative relapse-free survival rates were calculated using the Kaplan–Meier method. Results A total of 70 UC patients were included; 52 (74.3%) patients maintained remission and 18 (25.7%) patients relapsed during the follow-up period. Multivariate analysis indicated that a history of acute severe UC (ASUC) was an independent predictive factor for clinical relapse (p = 0.024, odds ratio: 21, 95% confidence interval: 1.50–293.2). Based on Kaplan–Meier survival analysis, the cumulative relapse-free survival rate within 52 weeks was 22.2% for patients with a history of ASUC, compared with 82.0% for those without. the log-rank test showed a significant difference in a history of ASUC (p < 0.001). Conclusions Dose reduction of 5-ASA should be performed carefully in patients who have a history of ASUC.

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Segmental Histological Normalisation Occurs in Ulcerative Colitis but Does Not Improve Clinical Outcomes

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa068 ◽

2020 ◽

Vol 14 (10) ◽

pp. 1345-1353 ◽

Cited By ~ 1

Author(s):

Britt Christensen ◽

Stephen B Hanauer ◽

Peter R Gibson ◽

Jerrold R Turner ◽

John Hart ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Outcomes ◽

Clinical Relapse ◽

Relapse Free Survival ◽

Disease Extent ◽

Free Survival ◽

Current Smoking ◽

Younger Age ◽

Age Of Diagnosis ◽

Distal Direction

Abstract Background and Aims Complete histological normalisation and reduction of inflammation severity in patients with ulcerative colitis are associated with improved clinical outcomes, but the clinical significance of normalisation of only segments of previously affected bowel is not known. We examined the prevalence, pattern, predictors, and clinical outcomes associated with segmental histological normalisation in in patients with ulcerative colitis. Methods Medical records of patients with confirmed ulcerative colitis and more than one colonoscopy were sought. Segmental histological normalisation was defined as histological normalisation of a bowel segment [rectum, left-sided or right-sided colon] that had previous evidence of chronic histological injury. We assessed the variables influencing these findings and whether segmental normalisation was associated with improved clinical outcomes. Results Of 646 patients, 32% had segmental and 10% complete histological normalisaton when compared with their maximal disease extent. Most [88%] had segmental normalisation in a proximal-to-distal direction. Others had distal-to-proximal or patchy normalisation. On multivariate analysis, only current smoking [p = 0.040] and age of diagnosis ≤16 years [p = 0.028] predicted segmental histological normalisation. Of 310 who were in clinical remission at initial colonoscopy, 77 [25%] experienced clinical relapse after median 1.3 [range 0.06–7.52] years. Only complete histological normalisation of the bowel was associated with improved relapse-free survival (hazard ratio [HR] 0.23; 95% confidence interval [CI] 0.08–0.68; p = 0.008]. Conclusions Segmental histological normalisation occurs in 32% of patients with ulcerative colitis and is increased in those who smoke or were diagnosed at younger age. Unlike complete histological normalisation, segmental normalisation does not signal improved clinical outcomes.

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Prostate-Specific Antigen Persistence After Radical Prostatectomy as a Predictive Factor of Clinical Relapse-Free Survival and Overall Survival: 10-Year Data of the ARO 96-02 Trial

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2014.09.039 ◽

2015 ◽

Vol 91 (2) ◽

pp. 288-294 ◽

Cited By ~ 41

Author(s):

Thomas Wiegel ◽

Detlef Bartkowiak ◽

Dirk Bottke ◽

Reinhard Thamm ◽

Axel Hinke ◽

...

Keyword(s):

Overall Survival ◽

Radical Prostatectomy ◽

Prostate Specific Antigen ◽

Predictive Factor ◽

Specific Antigen ◽

Clinical Relapse ◽

Relapse Free Survival ◽

Free Survival ◽

Antigen Persistence

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Nordic Mantle Cell Lymphoma (MCL) Project: Preemptive Rituximab Treatment of Molecular Relapse Following Autotransplant Can Reinduce Molecular Remission and Prolonged Disease-Free Survival.

Blood ◽

10.1182/blood.v106.11.2429.2429 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2429-2429

Author(s):

Christian H. Geisler ◽

Erkki Elonen ◽

Arne Kolstad ◽

Anna Laurell ◽

Lone B. Pedersen ◽

...

Keyword(s):

Stem Cell ◽

Cell Lymphoma ◽

Disease Free Survival ◽

High Dose ◽

Clinical Relapse ◽

Relapse Free Survival ◽

Molecular Remission ◽

Free Survival ◽

Mantle Cell ◽

Disease Free

Abstract The 2nd. Nordic Lymphoma Group mantle cell lymphoma (MCL2) protocol has demonstrated the importance of Ara-C and Rituximab in the induction chemotherapy and stem-cell mobilisation before high-dose therapy and autologous stem-cell transplant (1). By July 2005, 128 patients (83% stage IV) had completed protocol treatment consisting of 3 series of R-CHOP and 3 series of R-Ara-C, stem-cell harvest and high-dose therapy with BEAM/BEAC with ASCT. The 5-year failure-free and overall survival is 50% and 83% respectively, significantly higher than the historic control group of the Nordic MCL1 protocol with the same treatment without HD-Ara-C and Rituximab (P<0.0001). Patients with a molecular marker (t(11;14) or clonal IgH rearrangement) identified at the time of diagnosis in bone marrow and blood, undergo regular molecular follow-up posttransplant,. Patients who turn PCR-positive or increase their qPCR signal, without clinical disease, are offered preemptive treatment with Rituximab 375 mg/m2 Wx4. Of 75 patients with molecular markers who had completed treatment, 55 remain PCR-negative and 20 have become/remained PCR-pos. posttransplant. Clinical relapse ocurred significantly more often in the latter group (11 of 20) than in the PCR-neg. patients (4 of 55) (P<0.0001) (Fig.1). Ten of the 20 PCR-positive patient did not receive preemptive rituximab: five due to immediate clinical relapse, 2 due to stable qPCR signals, one due to protocol error and two await treatment. Of 10 patients who did receive preemptive rituximab 8 again became PCR-negative and 2 remain PCR-positive. Six of the 10 Rituximab treated patients remain in clinical and molecular remission 200–600 days after the Rituximab treatment (Fig. 2). Conclusions: In MCL, molecular relapse is a harbinger of imminent clinical relapse, whereas continuous molecular remission is associated with prolonged disease-free survival (89% at 4 years) Rituximab preemptive treatment can reinduce molecular remission and may delay clinical relapse. Following molecular relapse, only Rituximab treated patients (6 of 8 evaluable) remain disease-free. FIG. 1. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL ACC. TO MOLECULAR STATUS POSTTRANSPALNT FIG. 1. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL ACC. TO MOLECULAR STATUS POSTTRANSPALNT FIG. 2. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL FROM TIME OF MOLECULAR RELAPSE. FIG. 2. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL FROM TIME OF MOLECULAR RELAPSE.

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Moderately hypofractionated radiotherapy for localized prostate cancer: Long-term outcomes for 854 consecutive patients treated over 10 years (70 Gy in 2.5 Gy/fraction).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.78 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 78-78

Author(s):

Omar Y. Mian ◽

Ibrahim Abu-Gheida ◽

Rupesh Kotecha ◽

Michael A. Weller ◽

Chandana A. Reddy ◽

...

Keyword(s):

Prostate Cancer ◽

Localized Prostate Cancer ◽

Oncologic Outcomes ◽

Hypofractionated Radiotherapy ◽

Clinical Relapse ◽

Intermediate Risk ◽

Relapse Free Survival ◽

Free Survival ◽

Number Of Patients ◽

Grade 3

78 Background: Moderately hypofractionated radiotherapy has been increasingly adopted in the management of localized prostate cancer (PCa). We report 10-year outcomes for patients treated with intensity modulation radiation therapy (IMRT) for localized PCa with 70 Gy in 28 fractions at 2.5 Gy/fraction. Methods: This retrospective study included 854 consecutive patients with localized PCa treated with image-guided moderately hypofractionated IMRT at a single institution between 1998 and 2012. Patients with a single intermediate-risk factor were considered to have favorable intermediate-risk (FIR) disease; multiple intermediate-risk factors were considered unfavorable (UIR). Biochemical relapse free survival (bRFS), clinical relapse free survival (cRFS), overall survival (OS) and PCa specific mortality (PCSM) were analyzed used Kaplan-Meier analysis. Grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicities were recorded (CTCAE v4.03). Results: The median follow-up was 11.3 years (Max. 19 years). For patients with low-risk (LR, 31%), FIR (28%), UIR (12.5%), and high-risk (HR, 28.5%) disease the 10 year bRFS rates were 88%, 78%, 71% and 42%, respectively (p < 0.0001). The number of patients receiving no ADT, 1-6 months, or > 6 months of ADT were 39%, 50%, and 11%, respectively, reflecting practice patterns during this treatment period. The 10-year cRFS were 95%, 91%, 85% and 72% for patients with LR, FIR, UIR, and HR, respectively (p < 0.0001). The 10-year actuarial OS rate was 69% (95% CI 66-73%) and the 10-year PCSM was 6.8% (95% CI 5.1-8.6%) overall. For patients with LR, FIR, UIR and HR disease, the 10 year PCSM rates were 2%, 5%, 5% and 15%. 10-year cumulative incidence of grade ≥3 GU and GI toxicity was 2% and 1%, respectively. Multivariate analysis identified associations between clinical variables (ADT use, PSA nadir < 0.5ng/ml, and ISUP Grade Group) and bRFS, cRFS, and PCSM. Conclusions: Moderately hypofractionated IMRT with daily image guidance for localized PCa demonstrates favorable 10-year oncologic outcomes with a low incidence of toxicity for patients across all risk groups.

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Intravenous tacrolimus is a superior induction therapy for acute severe ulcerative colitis compared to oral tacrolimus

BMC Gastroenterology ◽

10.1186/s12876-021-02043-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hiromichi Shimizu ◽

Toshimitsu Fujii ◽

Kenji Kinoshita ◽

Ami Kawamoto ◽

Shuji Hibiya ◽

...

Keyword(s):

Ulcerative Colitis ◽

Cohort Study ◽

Primary Outcome ◽

Remission Rate ◽

Survival Rates ◽

Efficacy And Safety ◽

Relapse Free Survival ◽

Free Survival ◽

Severe Ulcerative Colitis ◽

Intravenous Corticosteroid

Abstract Background Intravenous corticosteroid is the mainstay for managing acute severe ulcerative colitis, but one-third of patients do not respond to intravenous corticosteroid. Tacrolimus, a salvage therapy before colectomy, is usually orally administered, though its bioavailability is low compared intravenous administration. The efficacy of intravenous tacrolimus has not been widely studied. Aim To determine the efficacy and safety of intravenous tacrolimus for the treatment of acute severe ulcerative colitis. Methods Eighty-seven hospitalized acute severe ulcerative colitis patients were enrolled for a prospective cohort study between 2009 and 2017. Sixty-five patients received intravenous tacrolimus and 22 received oral tacrolimus. The primary outcome was the achievement of clinical remission within 2 weeks. Relapse and colectomy incidence and adverse events were assessed at 24 weeks. Results Response rates of both treatments exceeded 50% but were not significantly different. The remission rate was higher in intravenous tacrolimus compared with oral tacrolimus. At 24 weeks, oral and intravenous tacrolimus showed similar relapse-free survival rates; however, colectomy-free survival rates were higher in intravenous tacrolimus compared with oral tacrolimus. Conclusions Patients receiving intravenous tacrolimus achieved superior remission and colectomy-free survival rates compared with patients receiving oral tacrolimus. Safety was similar between the two treatments.

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Effectiveness and Nephrotoxicity of Long-Term Tacrolimus Administration in Patients with Ulcerative Colitis

Journal of Clinical Medicine ◽

10.3390/jcm9061771 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1771

Author(s):

Keiichi Haga ◽

Tomoyoshi Shibuya ◽

Kei Nomura ◽

Koki Okahara ◽

Osamu Nomura ◽

...

Keyword(s):

Ulcerative Colitis ◽

Renal Function ◽

Medical Records ◽

Careful Monitoring ◽

Relapse Free Survival ◽

Free Survival ◽

Effective Option ◽

Term Administration ◽

Potential Use

Background: Tacrolimus (TAC) is used for the management of ulcerative colitis (UC). However, there are few reports on the effectiveness of its long-term administration. TAC is also known to cause renal toxicity. The aim of this study was to evaluate long-term effectiveness and monitor changes in renal function during prolonged TAC use in patients with UC. Methods: Medical records of 50 UC patients treated with TAC were retrospectively reviewed. Clinical outcomes were assessed at 6, 12, 24, and 36 months after initiating TAC. We also monitored chronological changes in renal function. Results: Thirty-nine patients were treated with TAC for more than 3 months. Relapse-free survival among these patients at 6, 12, 24, and 36 months was 82%, 69%, 41%, and 23%, respectively. On the other hand, renal function was reduced in 35.9% of patients. We found that irreversible renal dysfunction was more likely to occur in cases in which the estimated glomerular-filtration rate (eGFR) was reduced by more than 30%. Conclusion: This study demonstrated the potential use of TAC as an effective option in the long-term medical management of UC, although it tended to increase the risk of nephrotoxicity. There is a need for the careful monitoring of renal function during TAC administration.

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Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL

Blood ◽

10.1182/blood-2012-07-441030 ◽

2012 ◽

Vol 120 (26) ◽

pp. 5185-5187 ◽

Cited By ~ 323

Author(s):

Max S. Topp ◽

Nicola Gökbuget ◽

Gerhard Zugmaier ◽

Evelyn Degenhard ◽

Marie-Elisabeth Goebeler ◽

...

Keyword(s):

Lymphoblastic Leukemia ◽

Study Cohort ◽

Clinical Relapse ◽

Phase 2 ◽

Relapse Free Survival ◽

Hematopoietic Stem ◽

Free Survival ◽

Kaplan Meier ◽

B Lineage

Abstract Persistence or recurrence of minimal residual disease (MRD) after chemotherapy results in clinical relapse in patients with acute lymphoblastic leukemia (ALL). In a phase 2 trial of B-lineage ALL patients with persistent or relapsed MRD, a T cell–engaging bispecific Ab construct induced an 80% MRD response rate. In the present study, we show that after a median follow-up of 33 months, the hematologic relapse-free survival of the entire evaluable study cohort of 20 patients was 61% (Kaplan-Meier estimate). The hema-tologic relapse-free survival rate of a subgroup of 9 patients who received allogeneic hematopoietic stem cell transplantation after blinatumomab treatment was 65% (Kaplan-Meier estimate). Of the subgroup of 6 Philadelphia chromosome–negative MRD responders with no further therapy after blinatumomab, 4 are in ongoing hematologic and molecular remission. We conclude that blinatumomab can induce long-lasting complete remission in B-lineage ALL patients with persistent or recurrent MRD. The original study and this follow-up study are registered at www.clinicaltrials.gov as NCT00198991 and NCT00198978, respectively.

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Histological Markers of Clinical Relapse in Endoscopically Quiescent Ulcerative Colitis

Inflammatory Bowel Diseases ◽

10.1093/ibd/izz308 ◽

2019 ◽

Vol 26 (11) ◽

pp. 1722-1729 ◽

Cited By ~ 5

Author(s):

David Kevans ◽

Richard Kirsch ◽

Callum Dargavel ◽

Boyko Kabakchiev ◽

Robert Riddell ◽

...

Keyword(s):

Ulcerative Colitis ◽

Mucosal Healing ◽

Mucosal Inflammation ◽

Clinical Relapse ◽

Disease Relapse ◽

Mayo Score ◽

Therapeutic Decisions ◽

First Relapse ◽

Histological Activity

Abstract Background In ulcerative colitis (UC) patients who have achieved mucosal healing, active microscopic colonic mucosal inflammation is commonly observed. We aimed to assess the association between histological activity and disease relapse in endoscopically quiescent UC. Methods Ulcerative colitis patients with endoscopically quiescent disease and ≥12 months of follow-up were included. Biopsies were reviewed for the presence of basal plasmacytosis (BPC) and active histological inflammation, defined as a Geboes score (GS) ≥3.2. Primary outcome measures were disease relapse at 18 months and time to first relapse after index colonoscopy. Results Seventy-six UC patients (51% male; mean age, 38.6 years; median follow-up [range], 75.2 [2–118] months) were included. Sixty-two percent had an endoscopic Mayo score of 0 at index colonoscopy. Basal plasmacytosis was present in 46% and active histological inflammation in 30% of subjects. Presence of BPC was associated with a significantly shorter time to disease relapse (P = 0.01). Active histological inflammation was significantly associated with clinical relapse at 18 months (P = 0.0005) and shorter time to clinical relapse (P = 0.0006). Multivariate analysis demonstrated active histological inflammation to be independently associated with clinical relapse at 18 months and time to clinical relapse. Conclusions In endoscopically quiescent UC, active histological inflammation and the presence of BPC are adjunctive histological markers associated with increased likelihood of disease relapse. Although prospective studies are required, the presence of these histological markers should be a factor considered when making therapeutic decisions in UC.

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