scholarly journals Allogeneic Stem Cell Transplantation Versus B-Cell-Receptor Inhibitors in 17p Deletion and/or Refractory Chronic Lymphocytic Leukemia: A Retrospective Comparative Analysis of 'Real Life' Approaches to High Risk Patients, on Behalf of Rete Ematologica Lombarda (REL) and Gruppo Italiano Trapianto Di Midollo Osseo (GITMO)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4695-4695
Author(s):  
Lucia Farina ◽  
Francesca Patriarca ◽  
Maddalena Mazzucchelli ◽  
Chiara Salvetti ◽  
Giulia Quaresmini ◽  
...  
Keyword(s):  
High Risk ◽  
Progressive Disease ◽  
De Novo ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Early Relapse ◽  
High Risk Patients ◽  
Risk Patients

Abstract Introduction: chronic lymphocytic leukemia (CLL) is an indolent disease, but 17p deleted (del) and/or patients who experience early relapse or not responding to chemoimmunotherapy have a very poor outcome. In these patients an allogeneic stem cell transplantation (alloSCT) is indicated, whenever possible. B-cell receptor inhibitors (BCRi) have shown high efficacy with a low toxicity, making the choice of an alloSCT challenging even in high risk patients. The aim of the study is to highlight the outcome of different clinical approaches available in the era of the new drugs. Method: this is a multicenter retrospective analysis on 88 high risk patients treated in 8 Italian Centers. Inclusion criteria were: i) age ≤ 70 years; ii) responding to one of the EBMT (European Bone Marrow Transplantation) criteria for elegibility to alloSCT: relapse within one year after purine-analogues or two years after chemioimmunoterapy or autologous-SCT (ASCT); de novo or acquired 17p del; iii) alloSCT from 2001. Patients who received BCRi before alloSCT or ineligible to alloSCT due to comorbidities were excluded. Patients were assigned to alloSCT or BCRi based on physician and/or patient choice or unavailability of a donor. The analysis started from the transplant date or the start date of BCRi therapy. Results: 50 patients (M/F: 42/8) received an alloSCT, and 38 (M/F 30/8) were treated with BCRi (ibrutinib n=28, rituximab-idelalisib n=10). Median age was 55 (range, 34-68) in alloSCT and 60 years (42-69) in BCRi (p=0.06). Time from diagnosis to alloSCT or BCRi was 59,4 (range, 5-210) and 86,3 months (1-211) (p=0.15), respectively. Fluorescence in situ hybridization (FISH) data were available in 34/50 (68%) alloSCT patients: 17p del was positive in 21 (62%) (de novo n=12, acquired n=8, unknown n=1). Elegibility criteria for alloSCT group were: early relapse n=11, refractory n= 7, ASCT relapse n=11, 17p del n=21 (of which 11 were also chemorefractory). FISH data were available in all BCRi patients: 17p del was positive in 26 (68%) (de novo n=8, acquired n=14, unknown n=4). Elegibility criteria for BCRi group were: early relapse n=2, refractory n= 9, ASCT relapse n=1, 17p del n=26 (of which 16 were also chemorefractory). AlloSCT group had more patients in early relapse or with a failed ASCT (p=0.03 and p=0.01). Heavy chain gene rearrangement was available in 26/50 (52%) alloSCT and 35/38 (92%) BCRi patients and was unmutated in 87% and 86%, respectively. The median number of previous therapy was 2 in both groups (alloSCT: range 1-7; BCRi: range 0-8, p=0.25). Reduced-intensity conditioning regimen was used in 48/50 alloSCT patients, and donor type was sibling in 19, matched unrelated in 26 and haploidentical in 5 cases. Disease status before alloSCT was complete remission (CR)=20, partial remission (PR)=17, stable/progressive disease (SD/PD)=13. The median follow-up was 33 months (1-134) and 14 months (3-32), respectively for alloSCT and BCRi group (p=0.0008). Two-year OS was 59% vs 79% in alloSCT and BCRi, respectively (p=0.32). The cumulative incidence of relapse at 2 years was 30% in alloSCT and 23% in BCRi, with a non-relapse mortality of 20% after alloSCT. Median PFS was 18,6 months (range 1-134) and 12,6 (range 3-24,6) in alloSCT and BCRi, respectively. Two-year PFS was 54% in alloSCT and 77% in BCRi (p=0.19). The main cause of treatment failure was disease progression. In the BCRi group, 8 patients achieved CR at the last follow-up, 5 patients relapsed and died of progressive disease (2 with Richter's transformation), 1 patient died of second cancer. In the alloSCT group, 17 patients were alive and in CR, 11 CR patients died of transplant-related-mortality (6 graft-versus-host disease, 2 infections, 1 embolism, 2 second cancers), 19 patients died in SD/PD at the last follow-up. Conclusions: these retrospective data showed that so far no significant difference in the outcome of 17p del and/or refractory CLL patients have been observed after either alloSCT or BCR inhibitors. The significant different follow-up of the two groups implies some limits: i) BCR inhibitors still have to show long term responses; ii) alloSCT results may improve over the next future by a better selection of eligible patients and the improvement of the transplant procedures. Hopefully, the combination of the two strategies will increase the chance of cure of poor risk CLL patients. Disclosures Reda: Roche: Membership on an entity's Board of Directors or advisory committees; Gilead: Research Funding.

Evaluation of Integrated CLL Scoring System (ICSS) in 420 Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5563-5563 ◽  
Author(s):  
Andrea Visentin ◽  
Federica Frezzato ◽  
Silvia Imbergamo ◽  
Valentina Trimarco ◽  
Veronica Martini ◽  
...  
Keyword(s):  
High Risk ◽  
Predictive Accuracy ◽  
Lymphocytic Leukemia ◽  
Low Risk ◽  
Rank Test ◽  
High Risk Patients ◽  
Log Rank Test ◽  
Risk Patients ◽  
Normal Fish

Abstract BACKGROUND Chronic Lymphocytic Leukemia (CLL) is one of the most common hematological malignancies in Western countries. The disease is characterized by heterogeneous clinical course and outcome. During the last 15 years several clinical, biological and molecular prognostic factors have been identified, validated and some of them are currently used in patients' and treatment management. To improve the predictive accuracy of these markers, they have been combined into prognostic indexes (W. Wierda, JCO 2011, D. Rossi, Blood 2012, J. Bahlo, Haematologica 2015). Werecently proposed the Integrated CLL Scoring System (ICSS) based on cytogenetic abnormalities by FISH, IGHV mutational status and CD38 expression from 212 patients (A. Visentin et al, Clin Lymph Myeloma & Leuk 2015). The aim of this study was to validate the prognostic power of our index into a larger series of 420 CLL patients. METHODS 420 CLL patients referred to the Hematology Unit of Padua University Hospital from 1989 to 2015 were recruited in this study. According to ICSS, patients were classified as: low-risk, those patients with 13q deletion or normal FISH, IGVH mutated and CD38<30%; high-risk, subjects with 17p or 11q deletion and/or IGVH unmutated and CD38>30%; intermediate-risk, all remaining patients. Treatment free survival (TFS) was calculated as time from diagnosis to treatment (event), death or last known follow-up (censored). Overall survival (OS) was calculated from the date of diagnosis to death for any cause (event) or last known follow-up (censored). TFS and OS were compared with log-rank test and plotted using Kaplan-Meier method. The predictive accuracy of ICSS was evaluated by the Harrel's concordance index (c-index); a value >0.5 implies a good predictive ability. RESULTS The median age of our cohort was 62 years; 64% were male and 85% were Binet stage A at diagnosis. Cytogenetic analysis by FISH showed that 41 patients harbored 17p deletion, 50 11q deletion, 236 13q deletion, 44 trisomy 12 and 49 had normal FISH. 236 (56%) patients had IGHV gene homology >98% (i.e. mutated IGHV) and 103 (25%) expressed more then 30% of CD38. According to ICSS 202 (48%) subjects were classified as low-risk, 83 (20%) intermediate-risk and 135 (32%) high-risk. After a median follow-up of 81 months, the median TFS for ICSS classes of risk were 211, 70 and 27 months (log-rank test, p<0.0001, Figure 1A). The estimated 10-year TFS were 61%, 37% and 10% for low, intermediate and high-risk patients. The median OS were 213 and 136 months for intermediate and high-risk, while it was not reached for low-risk patients (Log-rank test, p<0.0001, Figure 1B). After 10 years from diagnosis the estimated OS were 88%, 79% and 57%, respectively. These data were confirmed by a multivariate analyses. In fact, high-risk patients had 5.3 and 4.0 times risk of start treatment and death than low-risk subjects, respectively (p<0.0001). This model was statistically internally validated, showing c-indexed of 0.712 and 0.693 for TFS and OS, respectively. In multivariate analyses, variables confirmed to predict adverse prognosis were male gender (p=0.0183), age>65years (p<0.0001), Rai III-IV (p=0.0025), Binet C (p=0.0002), 17p deletion (p=0.0002), TP53 abnormalities (p=0.0051), unmutated IGVH (p<0.0001), CD38>30% (p=0.0044) and high-risk ICSS (p<0.0001). CONCLUSIONS We herein provide evidence of the prognostic power and feasibility of ICSS into a large population of CLL patients. The use of this prognostic index could help physician into follow-up schedule, since high-risk patients should be monitored more often given the estimated increased risk of progression. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Results from the International Silver Graft Registry for high-risk patients treated with a metallic-silver impregnated vascular graft

Vascular ◽  
2013 ◽  
Vol 21 (3) ◽  
pp. 137-147 ◽  
Author(s):  
Max Zegelman ◽  
Gisela Guenther ◽  
Matthias Waliszewski ◽  
Fryderyk Pukacki ◽  
Michal Goran Stanisic ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
De Novo ◽  
Graft Infection ◽  
Graft Patency ◽  
Metallic Silver ◽  
High Risk Patients ◽  
Co Morbidity ◽  
Risk Patients

The purpose of this postmarket surveillance registry was to document the efficacy of a vascular prosthesis coated with metallic silver in high-risk patients undergoing vascular reconstructions. Patency (primary endpoint) and freedom from graft infection (secondary endpoint) data were assessed at a minimum of 12 months in patients with significant co-morbidity and/or confirmed graft infections or infected native vessels. Between November 2006 and December 2009, 230 patients with high-risk factors underwent aortic, peripheral and/or extra-anatomic reconstructions with Silver Graft® (SG) in six German, one French and one Polish vascular center. All participating centers used the metallic silver-coated polyester graft (SG) in various diameters and lengths including tubular and bifurcate vascular grafts. Doppler ultrasound follow-ups to determine graft patency were planned at 12 months or done at an earlier time in case the patient became symptomatic. A total of 230 patients were studied. Ten of these 230 patients had graft infections at baseline whereas the remaining 220 subjects had significant risk factors such as coronary artery disease (62.7%, 138/220), vascular access in scar tissue (27.3%, 60/220), Fontaine III/IV (38.2%, 84/220), chronic renal insufficiency (26.8%, 59/220) and diabetes (21.0%, 46/220). The long-term follow-up at 15.5 ± 8.3 months revealed a secondary patency rate of 93.2% (205/220) and an ‘all cause’ mortality rate of 18.6% (41/220). There was a freedom from de novo graft infection rate of 95.9% (211/220) in the high-risk group without graft infections at baseline. One regraft infection occurred distal of the revisional reconstruction in the 10 patients with graft infection at baseline. The presence of perigraft fluid at follow-up and Fontaine III/IV at baseline were found to be predictors for graft patency whereas perigraft fluid presence was the only predictor for de novo graft infections. This registry revealed favorable patency and freedom from de novo infections rates in a ‘high-risk’ population with significant co-morbidities.

scholarly journals Accuracy of upper endoscopies with random biopsies to identify patients with gastric premalignant lesions who can safely be exempt from surveillance

2021 ◽  
Vol 24 (3) ◽  
pp. 680-690
Author(s):  
Michiel C. Mommersteeg ◽  
Stella A. V. Nieuwenburg ◽  
Wouter J. den Hollander ◽  
Lisanne Holster ◽  
Caroline M. den Hoed ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Low Risk ◽  
Premalignant Lesions ◽  
High Risk Patients ◽  
European Guidelines ◽  
Progression Of Disease ◽  
Risk Patients ◽  
Progression Risk

Abstract Introduction Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance. Methods This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1–6 years. Patients were defined ‘low risk’ if they fulfilled requirements for discharge, and ‘high risk’ if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined ‘low risk’ with progression of disease during follow-up (FU) were considered ‘misclassified’ as low risk. Results 334 patients (median age 60 years IQR11; 48.7% male) were included and followed for a median of 48 months. At baseline, 181/334 (54%) patients were defined low risk. Of these, 32.6% were ‘misclassified’, showing progression of disease during FU. If MAPS-2019 were followed, 169/334 (51%) patients were defined low risk, of which 32.5% were ‘misclassified’. If BSG were followed, 174/334 (51%) patients were defined low risk, of which 32.2% were ‘misclassified’. Seven patients developed gastric cancer (GC) or dysplasia, four patients were ‘misclassified’ based on MAPS-2012 and three on MAPS-2019 and BSG. By performing one additional endoscopy 72.9% (95% CI 62.4–83.3) of high-risk patients and all patients who developed GC or dysplasia were identified. Conclusion One-third of patients that would have been discharged from GC surveillance, appeared to be ‘misclassified’ as low risk. One additional endoscopy will reduce this risk by 70%.

scholarly journals Implementation of the acutely presenting older patient (APOP) screening program in routine emergency department care

2021 ◽  
Author(s):  
Laura C. Blomaard ◽  
Bas de Groot ◽  
Jacinta A. Lucke ◽  
Jelle de Gelder ◽  
Anja M. Booijen ◽  
...  
Keyword(s):  
Emergency Department ◽  
High Risk ◽  
Older Patients ◽  
Screening Program ◽  
Admission Rate ◽  
Older Patient ◽  
Hospital Admission Rate ◽  
High Risk Patients ◽  
Risk Patients

Abstract Objective The aim of this study was to evaluate the effects of implementation of the acutely presenting older patient (APOP) screening program for older patients in routine emergency department (ED) care shortly after implementation. Methods We conducted an implementation study with before-after design, using the plan-do-study-act (PDSA) model for quality improvement, in the ED of a Dutch academic hospital. All consecutive patients ≥ 70 years during 2 months before and after implementation were included. The APOP program comprises screening for risk of functional decline, mortality and cognitive impairment, targeted interventions for high-risk patients and education of professionals. Outcome measures were compliance with interventions and impact on ED process, length of stay (LOS) and hospital admission rate. Results Two comparable groups of patients (median age 77 years) were included before (n = 920) and after (n = 953) implementation. After implementation 560 (59%) patients were screened of which 190 (34%) were high-risk patients. Some of the program interventions for high-risk patients in the ED were adhered to, some were not. More hospitalized patients received comprehensive geriatric assessment (CGA) after implementation (21% before vs. 31% after; p = 0.002). In 89% of high-risk patients who were discharged to home, telephone follow-up was initiated. Implementation did not influence median ED LOS (202 min before vs. 196 min after; p = 0.152) or hospital admission rate (40% before vs. 39% after; p = 0.410). Conclusion Implementation of the APOP screening program in routine ED care did not negatively impact the ED process and resulted in an increase of CGA and telephone follow-up in older patients. Future studies should investigate whether sustainable changes in management and patient outcomes occur after more PDSA cycles.

Minimally Invasive Direct Coronary Artery Bypass in High-Risk Patients with Multivessel Disease

2021 ◽  
Author(s):  
Grischa Hoffmann ◽  
Christine Friedrich ◽  
Katharina Huenges ◽  
Rainer Petzina ◽  
Astrid-Mareike Vogt ◽  
...  
Keyword(s):  
Coronary Artery ◽  
High Risk ◽  
Minimally Invasive ◽  
Coronary Artery Bypass ◽  
Artery Bypass ◽  
Multivessel Disease ◽  
Complete Revascularization ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background High-risk patients with multivessel disease (MVD) including a complex stenosis of the left anterior descending coronary may not be ideal candidates for guideline compliant therapy by coronary artery bypass grafting (CABG) regarding invasiveness and perioperative complications. However, they may benefit from minimally invasive direct coronary artery bypass (MIDCAB) grafting and hybrid revascularization (HCR). Methods A logistic European system for cardiac operative risk evaluation score (logES) >10% defined high risk. In high-risk patients with MVD undergoing MIDCAB or HCR, the incidence of major adverse cardiac and cerebrovascular events (MACCEs) after 30 days and during midterm follow-up was evaluated. Results Out of 1,250 patients undergoing MIDCAB at our institution between 1998 and 2015, 78 patients (logES: 18.5%; age, 76.7 ± 8.6 years) met the inclusion criteria. During the first 30 days, mortality and rate of MACCE were 9.0%; early mortality was two-fold overestimated by logES. Complete revascularization as scheduled was finally achieved in 64 patients (82.1%). Median follow-up time reached 3.4 (1.2–6.5) years with a median survival time of 4.7 years. Survival after 1, 3, and 5 years was 77, 62, and 48%. Conclusion In high-risk patients with MVD, MIDCAB is associated with acceptable early outcome which is better than predicted by logES. Taking the high-risk profile into consideration, midterm follow-up showed satisfying results, although scheduled HCR was not realized in a relevant proportion. In selected cases of MVD, MIDCAB presents an acceptable alternative for high-risk patients.

scholarly journals Uptake and detection rate of a stepwise cardiometabolic disease detection program in primary care—a cohort study

2019 ◽  
Vol 30 (3) ◽  
pp. 402-407
Author(s):  
Daphne M Stol ◽  
Monika Hollander ◽  
Ilse F Badenbroek ◽  
Mark M J Nielen ◽  
François G Schellevis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Primary Care ◽  
Cohort Study ◽  
High Risk ◽  
Newly Diagnosed ◽  
Additional Risk ◽  
High Risk Patients ◽  
Detection Program ◽  
Risk Patients

Abstract Background Early detection and treatment of cardiometabolic diseases (CMD) in high-risk patients is a promising preventive strategy to anticipate the increasing burden of CMD. The Dutch guideline ‘the prevention consultation’ provides a framework for stepwise CMD risk assessment and detection in primary care. The aim of this study was to assess the outcome of this program in terms of newly diagnosed CMD. Methods A cohort study among 30 934 patients, aged 45–70 years without known CMD or CMD risk factors, who were invited for the CMD detection program within 37 general practices. Patients filled out a CMD risk score (step 1), were referred for additional risk profiling in case of high risk (step 2) and received lifestyle advice and (pharmacological) treatment if indicated (step 3). During 1-year follow-up newly diagnosed CMD, prescriptions and abnormal diagnostic tests were assessed. Results Twelve thousand seven hundred and thirty-eight patients filled out the risk score of which 865, 6665 and 5208 had a low, intermediate and high CMD risk, respectively. One thousand seven hundred and fifty-five high-risk patients consulted the general practitioner, in 346 of whom a new CMD was diagnosed. In an additional 422 patients a new prescription and/or abnormal diagnostic test were found. Conclusions Implementation of the CMD detection program resulted in a new CMD diagnosis in one-fifth of high-risk patients who attended the practice for completion of their risk profile. However, the potential yield of the program could be higher given the considerable number of additional risk factors—such as elevated glucose, blood pressure and cholesterol levels—found, requiring active follow-up and presumably treatment in the future.

Sign in / Sign up

Export Citation Format

Share Document