Outcomes of older patients with primary central nervous system lymphoma treated in routine clinical practice in the UK: methotrexate dose intensity correlates with response and survival.

Data on older patients with primary central nervous system lymphoma (PCNSL) are scarce. Comorbidities and performance status frequently compromise outcomes in this group. Medical records for consecutive patients ≥65 years (n = 244) with PCNSL diagnosed 2012-2017 from 14 UK centres were retrospectively reviewed. Of these 192 patients received methotrexate (MTX)-based treatment. Patients were categorised based on clinician's treatment choice into 'palliative' (n = 52), 'less intensive: MTX ± rituximab ± alkylators' (n = 74) and 'intensive: MTX/cytarabine combinations' (n = 118) groups. Complete remission (CR) rate, two-year progression-free survival (PFS) and overall survival (OS) rates were 49%, 11% and 24% for the less intensive and 69%, 40% and 50% for the intensive groups. Treatment-related mortality (TRM) was 6·8% for MTX-treated patients. Median MTX cumulative dose was 8·8 g/m2 (range 1·5-21) over a median of three cycles. Higher relative dose intensity of MTX (MTX-RDI) was associated with improved PFS and OS in both groups adjusting for age, Eastern cooperative oncology group (ECOG) score and baseline parameters. Two-year PFS and OS for patients receiving four or more induction cycles followed by consolidation (n = 36) were 65% and 70% respectively. Older patients completing MTX-based induction and consolidation had clinical outcomes similar to those in younger cohorts. These retrospective data suggest that maximising MTX-RDI and delivering consolidation in a subgroup of older patients may improve clinical outcomes.

Does left ventricular diastolic dysfunction progress through stages? Insights from a community heart failure study.

UNLABELLED: We performed a retrospective pilot study on a group of symptomatic patients attending our community heart failure clinic with left ventricular diastolic dysfunction (LVDD), rising or elevated LV end diastolic pressure, elevated brain natriuretic peptide (BNP), but with no clinical or radiographic evidence of heart failure; a group we hypothesised may be in the pre-HFPEF stage. METHODS: Those with LVEF >45% and LV diastolic dysfunction were included and divided into two groups: E/e' <15 and E/e' ≥15 corresponding with rising and raised LVEDP, respectively. Clinical events (deaths and hospital admissions) were compared at 1year and were grouped into all-cause events or cardiovascular events. The total numbers of all-cause and cardiovascular events of the individual groups and the entire cohort were assessed at 1year. RESULTS: Out of 584 screened, 80 patients were included. Thirty five patients had E/e' <15 and 45 had E/e' ≥15. At 1year follow-up the 1year all-cause events in the E/e' ≥15 group was higher compared to the E/e' <15 group (p=0.03). At 12months, in the entire cohort there were a total of 45 clinical events (39 hospital admissions and 6 deaths) out of which 20 events were cardiovascular. CONCLUSION: Patients in the pre-HFPEF stage had many events and those with elevated E/e' ≥15 had a poor 1year outcome. As this was strongly influenced by comorbidities we suggest close monitoring of these patients in dedicated HFPEF clinics along with vigorous management of comorbidities.