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In this large single-centre study, we report high prevalence (25%) of, small (<10%) and very small (<1%), paroxysmal nocturnal hemoglobinuria (PNH) clones by high-sensitive cytometry among 3085 patients tested. Given PNH association with bone marrow failures, we analyzed 869 myelodysplastic syndromes (MDS) and 531 aplastic anemia (AA) within the cohort. PNH clones were more frequent and larger in AA vs. MDS (p = 0.04). PNH clone, irrespective of size, was a good predictor of response to immunosuppressive therapy (IST) and to stem cell transplant (HSCT) (in MDS: 84% if PNH+ vs. 44.7% if PNH−, p = 0.01 for IST, and 71% if PNH+ vs. 56.6% if PNH− for HSCT; in AA: 78 vs. 50% for IST, p < 0.0001, and 97 vs. 77%, p = 0.01 for HSCT). PNH positivity had a favorable impact on disease progression (0.6% vs. 4.9% IPSS-progression in MDS, p < 0.005; and 2.1 vs. 6.9% progression to MDS in AA, p = 0.01), leukemic evolution (6.8 vs. 12.7%, p = 0.01 in MDS), and overall survival [73% (95% CI 68–77) vs. 51% (48–54), p < 0.0001], with a relative HR for mortality of 2.37 (95% CI 1.8–3.1; p < 0.0001) in PNH negative cases, both in univariate and multivariable analysis. Our data suggest systematic PNH testing in AA/MDS, as it might allow better prediction/prognostication and consequent clinical/laboratory follow-up timing.

Summary 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.

Purpose: Selenium is a trace element that is fundamental to human health. Research has mainly focussed on its role in cancer prevention, but recent evidence supports its role in established cancer, with high concentrations inducing tumour cell death and non-toxic concentrations sensitising cells to chemotherapy. However, the precise mechanism of selenium action is not clear. The effect of methylseleninic acid (MSA), an organic selenium compound, on HDAC activity in diffuse large B-cell lymphoma cell lines is reported here.Methods: Lymphoma cell lines were exposed to MSA under normoxic and hypoxic conditions. Protein expression was determined by western blotting, HDAC activity and VEGF concentration by fluorimetric and electrochemiluminescence assays respectively, and intracellular Se metabolites quantified by mass spectrometry. Results: MSA inhibited HDAC activity, which resulted in the acetylation of histone H3 and α-tubulin. However, cellular metabolism of MSA to methylselenol was required for this effect. Dimethylselenide, the methylation product of methylselenol, was found to be the major intracellular metabolite.MSA also inhibited hypoxia-induced HIF1α expression and VEGF secretion, a possible consequence of HDAC inhibition. Conclusion: The ability of methylselenol to inhibit HDAC activity has not been previously reported, thus providing a novel mechanism of selenium action.