Clinicopathological characterisation of myeloproliferative neoplasm-unclassifiable (MPN-U): a retrospective analysis from a large UK tertiary referral centre.

Myeloproliferative neoplasm-unclassifiable (MPN-U) presents an MPN-type phenotype that fails to meet diagnostic criteria for other MPN variants. Variability in the clinicopathological phenotypes presents many challenges. Amongst a registry cohort of 1512 patients with MPN, 82 with MPN-U were included, with a median (range) age of 49·7 (13-79) years. Albeit heterogeneous, common presentation features included raised lactate dehydrogenase, thrombocytosis and clustered/pleomorphic megakaryocytes on trephine biopsy. Thrombosis was common (21%), necessitating vigilance. The median event-free survival was 11·25 years (95% confidence interval 9·3-not reached), significantly shortened in cases with lower platelet counts (<500 × 109 /l) and a leucocytosis (≥12 × 109 /l) at presentation. Generation of potential MPN-U prognostic scores is required.

Patients with triple-negative, JAK2V617F- and CALR-mutated essential thrombocythemia share a unique gene expression signature.

Approximately 10% to 15% of patients with essential thrombocythemia (ET) lack the common driver mutations, so-called "triple-negative" (TN) disease. We undertook a systematic approach to investigate for somatic mutations and delineate gene expression signatures in 46 TN patients and compared the results to those with known driver mutations and healthy volunteers. Deep, error-corrected, next-generation sequencing of peripheral blood mononuclear cells using the HaloPlexHS platform and whole-exome sequencing was performed. Using this platform, 10 (22%) of 46 patients had detectable mutations (MPL, n = 6; JAK2V617F, n = 4) with 3 of 10 cases harboring germline MPL mutations. RNA-sequencing and DNA methylation analysis were also performed by using peripheral blood mononuclear cells. Pathway analysis comparing healthy volunteers and ET patients (regardless of mutational status) identified significant enrichment for genes in the tumor necrosis factor, NFκB, and MAPK pathways and upregulation of platelet proliferative drivers such as ITGA2B and ITGB3. Correlation with DNA methylation showed a consistent pattern of hypomethylation at upregulated gene promoters. Interrogation of these promoter regions highlighted enrichment of transcriptional regulators, which were significantly upregulated in patients with ET regardless of mutation status, including CEBPß and NFκB. For "true" TN ET, patterns of gene expression and DNA methylation were similar to those in ET patients with known driver mutations. These observations suggest that the resultant ET phenotype may, at least in part and regardless of mutation type, be driven by transcriptional misregulation and may propagate downstream via the MAPK, tumor necrosis factor, and NFκB pathways with resultant JAK-STAT activation. These findings identify potential novel mechanisms of disease initiation that require further evaluation.

Altered immune response to the annual influenza A vaccine in patients with myeloproliferative neoplasms.

The seasonal influenza A vaccine is recommended for patients with myeloproliferative neoplasms (MPNs). We hypothesised that immune deregulation associated with MPNs may affect the immune response gained following vaccinations when compared to healthy controls. Using deep immunophenotyping with high-dimensional single-cell analysis and mass cytometry we could demonstrate an altered immune response in MPN patients following vaccination. We found that prior to vaccination, MPN patients had reduced numbers of naive CD4 T cells. Furthermore, at 3-weeks and 3-months post-vaccination there was evidence of both delayed and impaired B- and T-memory cells responses. Thus, although, the immune systems of MPN patients can 'recognise' the Influenza A vaccine, the response appears inferior compared to healthy controls.

Essential thrombocythaemia treated with recombinant interferon: 'real world' United Kingdom referral centre experience.

Standard first-line therapy choice for essential thrombocythaemia (ET) requiring cytoreduction, supported by randomized trials, is low-dose aspirin with hydroxycarbamide, but the role of recombinant interferon-alfa (IFNα)-2a/2b and pegylated (PEG)-IFN-α-2a/2b is increasingly highlighted. Longer-term outcome data, however, remains somewhat scarce, particularly in the 'real world'. We hereby report on a large, well-annotated cohort of ET patients from a single referral centre undergoing therapy with either IFNα or (PEG)-IFN-α-2a/2b and demonstrate high rates of complete haematological responses, good tolerability and safety, low rates of thromboembolic events in compliant patients and confirm feasibility of long-term therapy in a significant proportion of patients.

How We Treat Myeloproliferative Neoplasms.

The present report focuses on management strategies for the myeloproliferative neoplasm according to the structure and processes we use within our center, a large tertiary unit in central London. The standard procedures for achieving an accurate diagnosis and risk stratification and therapeutic strategies for these diseases with a detailed focus on contentious areas are discussed. In the 9 years after the description of the Janus kinase 2 mutation, this field has altered quite radically in several aspects. For example, a new therapeutic paradigm exists, especially for myelofibrosis. We share how our unit has adapted to these changes.

Anemia management: development of a rapidaccess anemia and intravenous iron service.

This article describes the initiation and evolution of the Rapid-Access Anemia Clinic (RAAC) at Guy's and St Thomas' Hospitals, London, UK. This clinic was set up to provide diagnosis and treatment, and to coordinate investigative procedures, where necessary, into the underlying causes of anemia. Initially piloted with anemic preoperative orthopedic patients, the clinic now treats a wide range of conditions, deriving from both internal and external referrals. Treatment includes dietary advice, supplementation with iron, vitamin B12 and folate, and blood transfusion. Most patients at the RAAC need iron replacement, the majority of which require intravenous (IV) iron. Therefore the first-line IV iron-administration protocol is carefully considered to ensure viability of the service and patient satisfaction. Four IV irons available in the UK are discussed, with explanation of the benefits and drawbacks of each product and the reasoning behind the IV iron choice at different stages of the RAAC's development. Costs to the service, affected by IV iron price and administration regimen, are considered, as well as the product's contraindications. Finally, the authors reflect on the success of the RAAC and how it has improved patients' quality-of-treatment experience, in addition to benefiting the hospital and National Health Service in achieving specific health-care mandates and directives. Drawing from the authors' experiences, recommendations are given to assist others in setting up and providing a successful rapid-access anemia service or similar facility.

Myeloproliferative neoplasms: diagnosis, management and treatment.

This article provides an overview of myeloproliferative neoplasms for nurses who do not specialise in haematology. Diagnosis, management and treatment of patients with these conditions is discussed, as well as long-term nursing implications.

Comparative efficacy of three forms of parenteral iron.

Intravenous iron therapy is a useful treatment for the rapid correction of iron deficiency anaemia and can be used to avoid or reduce the requirement for allogeneic blood transfusion. Several intravenous iron preparations are available commercially which differ in cost, mode of administration and side effect profile. There are few data directly comparing the efficacy of these preparations. In this retrospective single-centre study, we present the results from two hundred and eight patients treated using three different iron preparations (iron dextran, iron sucrose and ferric carboxymaltose) and compare the effect on haemoglobin levels and other measures of iron deficiency six weeks after treatment. Within the limitations of our study design, we show a statistically and clinically significant difference in efficacy between these preparations.