British Journal of Haematology

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...

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We studied the efficacy and safety of humanized CAR-T therapy following intensive chemotherapy for refractory/relapsed (R/R) acute lymphoblastic leukaemia (B-ALL). Twenty-three patients with R/R B-ALL were pretreated with intensive chemotherapy (fludarabine combined with medium-dose cytarabine) 12 days before CAR-T therapy. Adverse events (AEs), curative effects, infection indicators and cytokine release syndrome (CRS) were monitored. Each of the 23 patients received a dose of 1·0 × 106 cells/kg CAR-T cell infusion on day 0...

Exomic rare variant polymorphisms (c. 300 000) were analysed in the Scripps Venous Thrombosis (VTE) registry (subjects aged <55 years). Besides coagulation factor V (F5) single nucleotide polymorphisms (SNPs), family with sequence similarity 134, member B (FAM134B; rs78314670, Arg127Cys) and myosin heavy chain 8 (MYH8; rs111567318, Glu1838Ala) SNPs were associated with recurrent VTE (n = 34 cases) (false discovery rate-adjusted P < 0·05). FAM134B (rs78314670) was associated with low plasma levels of anticoagulant glucosylceramide...

Future progress in the treatment of multiple myeloma (MM) requires both the characterisation of key drivers of the disease and novel, innovative approaches to tackle these vulnerabilities. The present study focussed on the pre-clinical evaluation of a novel drug class, BMI-1 modulators, in MM. We demonstrate potent activity of PTC-028 and PTC596 in a comprehensive set of in vitro and in vivo models, including models of drug resistance and stromal support. Treatment of MM cells with PTC-028 and PTC596 downregulated BMI-1 protein levels, which was found to correlate with drug activity...

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Despite the availability of guidelines for the management of chronic myeloid leukaemia (CML), various issues may prevent their successful implementation. The TARGET survey examined real-world management of CML patients compared with international recommendations. This online survey was completed in 2017. Results were discussed by a Steering Committee (SC) of eight international haematologists, challenges were identified and practical solutions developed. Of the 1008 haematologists invited (33 countries), 614 completed the survey...

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Late relapse [>3 years from complete remission (CR)] in acute lymphoblastic leukaemia (ALL), is unusual. Data from the MRC UKALLXII/ECOG E2993 trial are presented to evaluate the incidence and characteristics of late relapse in adult ALL. Of 1,909 patients, 1,752 (92%) achieved CR and among these 757 (43·2%) relapsed; 691 (91·3%) within three years and 66 (8·7%) beyond. Among these 66 patients, median time to relapse was 47 (37-144) months. Relapse beyond three years occurred in 3·8% of all who achieved CR...

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Inhibitor development is a major complication of treatment with factor VIII concentrates in nonsevere haemophilia A. It has been suggested that plasma-derived factor VIII (FVIII) concentrates elicit fewer inhibitors than recombinant FVIII concentrates, but studies in severe haemophilia A patients have shown conflicting results. We designed a case-control study to investigate the clinical and genetic risk factors for inhibitor development in nonsevere haemophilia A patients. We investigated whether the type of FVIII concentrate was associated with inhibitor development in nonsevere haemophilia A patients...

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Myelofibrosis is an enigmatic myeloproliferative neoplasm, despite noteworthy strides in understanding its genetic underpinnings. Driver mutations involving JAK2, CALR or MPL in 90% of patients mediate constitutive JAK-STAT signaling which, in concert with epigenetic alterations (ASXL1, DNMT3A, SRSF2, EZH2, IDH1/2 mutations), play a fundamental role in disease pathogenesis. Aberrant immature megakaryocytes are a quintessential feature, exhibiting reduced GATA1 protein expression and secreting a plethora of pro-inflammatory cytokines (IL-1 ß, TGF-ß), growth factors (b-FGF, PDGF, VEGF) in addition to extra cellular matrix components (fibronectin, laminin, collagens)...

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