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The long-term outcome of patients in the LRF CLL4 trial: the effect of salvage treatment and biological markers in those surviving 10 years.

ABSTRACT: With 10+ years follow-up in the Leukaemia Research Fund (LRF) CLL4 trial, we report the effect of salvage therapy, and the clinical/biological features of the 10-year survivors treated for chronic lymphocytic leukaemia (CLL). Overall survival (OS) was similar in the three randomized arms. With fludarabine-plus-cyclophosphamide (FC), progression-free survival (PFS) was significantly longer (P < 0.0001), but OS after progression significantly shorter, than in the chlorambucil or fludarabine arms (P < 0.0001). 614/777 patients progressed; 524 received second-line and 260 third-line therapy, with significantly better complete remission (CR) rates compared to first-line in the chlorambucil arm (7% vs. 13% after second-, 18% after third-line), but worse in the FC arm (38% vs. 15% after both second and third-line). OS 10 years after progression was better after a second-line CR versus a partial response (36% vs. 16%) and better with FC-based second-line therapy (including rituximab in 20%) or a stem cell transplant (28%) versus all other treatments (10%, P < 0.0001). The 176 (24%) 10-year survivors tended to be aged <70 years, with a "good risk" prognostic profile, stage A-progressive, achieving at least one CR, with a first-line PFS >3 years and receiving ≤2 lines of treatment. In conclusion, clinical/biological features and salvage treatments both influence the long-term outcome. Second-line therapies that induce a CR can improve OS in CLL patients.

SUBMITTER: Else M

PROVIDER: S-EPMC4832371 | biostudies-other | 2016 Jan

REPOSITORIES: biostudies-other

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Project description:BackgroundCreatinine clearance (CrCl) is an independent determinant of mortality in predictive models of revascularisation outcomes for complex coronary artery disease.AimsThis study aimed to investigate the impact of preprocedural biological markers on 10-year mortality following coronary revascularisation.MethodsThe SYNTAX Extended Survival (SYNTAXES) study evaluated the 10-year vital status follow-up of 1,800 patients with de novo three-vessel (3VD) and/or left main coronary artery disease (LMCAD) randomised to include percutaneous or surgical coronary revascularisation. The associations between mortality and preprocedural C-reactive protein (CRP), haemoglobin, HbA1c, CrCl, fasting triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were analysed.ResultsOut of 1,800 patients, 460 patients died before the 10-year follow-up. CRP, HbA1c and CrCl with threshold values of ≥2 mg/L, ≥6% (42 mmol/mol) and <60 ml/min, respectively, were associated with 10-year all-cause death (adjusted hazard ratio [95% confidence interval]: 1.35 [1.01-1.82], 1.51 [1.16-1.95], and 1.46 [1.07-2.00], respectively). There was no significant interaction between the biological markers on all-cause mortality and the type of revascularisation. Preprocedural lipid markers were not significantly associated with 10-year all-cause death, but the non-use of statins was a determinant factor of worse prognosis (adjusted hazard ratio [95% confidence interval]: 1.68 [1.26-2.25]).ConclusionsPreprocedural biomarkers, such as CRP and HbA1c, are associated with long-term mortality post revascularisation, regardless of the revascularisation technique. Conventional lipidic biomarkers associated with high-risk of cardiovascular events seem to be effectively mitigated by the long-term use of statins, whereas the non-use of statins was a factor of a worse prognosis, emphasising the importance of pharmacological treatment.Trial registrationSYNTAXES ClinicalTrials.gov: NCT03417050. SYNTAX ClinicalTrials.gov: NCT00114972.

Project description:Background: Cognitive impairment may be a risk factor for, as well as a consequence of, psychosis. Non-remitting symptoms, premorbid functioning, level of education, and socioeconomic background are known correlates. A possible confounder of these associations is substance use, which is common among patients with psychosis and linked to worse clinical outcomes. Studies however show mixed results for the effect of substance use on cognitive outcomes. In this study, the long-term associations of substance use with cognition in a representative sample of first-episode psychosis patients were examined. Methods: The sample consisted of 195 patients. They were assessed for symptom levels, function, and neurocognition at 1, 2, 5, and 10 years after first treatment. Test scores were grouped into factor analysis-based indices: motor speed, verbal learning, visuomotor processing, verbal fluency, and executive functioning. A standardized composite score of all tests was also used. Patients were divided into four groups based on substance-use patterns during the first 2 years of treatment: persistent users, episodic users, stop-users, and nonusers. Data were analyzed using linear mixed effects modeling. Results: Gender, premorbid academic functioning, and previous education were the strongest predictors of cognitive trajectories. However, on motor speed and verbal learning indices, patients who stopped using substances within the first 2 years of follow-up improved over time, whereas the other groups did not. For verbal fluency, the longitudinal course was parallel for all four groups, while patients who stopped using substances demonstrated superior performances compared with nonusers. Persistent users demonstrated impaired visuomotor processing speed compared with nonusers. Within the stop- and episodic use groups, patients with narrow schizophrenia diagnoses performed worse compared with patients with other diagnoses on verbal learning and on the overall composite neurocognitive index. Discussion: This study is one of very few long-term studies on cognitive impairments in first-episode psychosis focusing explicitly on substance use. Early cessation of substance use was associated with less cognitive impairment and some improvement over time on some cognitive measures, indicating a milder illness course and superior cognitive reserves to draw from in recovering from psychosis.

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The long-term outcome of patients in the LRF CLL4 trial: the effect of salvage treatment and biological markers in those surviving 10 years.

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