Search

Summary: 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. [ABSTRACT FROM AUTHOR]

Myeloproliferative neoplasms (MPNs) are a group of disorders of clonal haemopoiesis associated with an inherent risk of arterial and venous thrombotic complications. The prevalence of thrombotic complications and the impact of cardiovascular risk factors (CVRFs) in contemporary patient cohorts within the current era of MPN treatments have not been completely defined. We aim to characterise the cardiovascular risk of patients with MPN by identifying the prevalence of CVRFs and describing the pattern of thrombotic events. We also aim to utilise the QRISK3 algorithm, which is a validated model used to estimate an individual's risk of developing cardiovascular disease, to further phenotype this cohort of patients. We perform a retrospective analysis on a single-centre cohort of 438 patients with MPN. MPN patients continue to carry a high burden of vascular morbidity with a prevalence of arterial thrombotic events in 15.8 % (69/438) and venous thrombotic events in 13.2 % (58/438) of the cohort. The novel use of the QRISK3 algorithm, which showed a mean score of 13.7 % across the MPN population, provides further evidence to suggest an increased cardiovascular risk in MPN patients. With an increased risk of cardiovascular disease in patients with MPN, we propose an integrated approach between primary and specialised healthcare services using risk stratification tools such as QRISK3, which will allow aggressive optimisation of CVRFs to prevent thrombosis and reduce the overall morbidity and mortality in patients with MPN. [ABSTRACT FROM AUTHOR]

Myelofibrosis ( MF) is a rare haematopoietic disorder, commonly diagnosed in the 6th decade: less than 20% are diagnosed before the age of 50 years. In this retrospective study we included all patients given a diagnosis of World Health Organization-defined primary or secondary MF when aged ≤50 years. Forty-three patients with a median age of 43 years were included. Median follow up was 44 months. Twenty-two (51%) harboured the JAK2 V617F mutation, 18/43 (42%) CALR, 0/43 (0%) MPL mutations and 3/43 (7%) were 'Triple Negative' ( TN). At the time of diagnosis, no significant differences existed in haematological and clinical phenotypes between JAK2, CALR and TN patients. The frequency of splenomegaly was greater ( P = 0·047) in the JAK2-mutated group compared to CALR-mutated patients. In the whole cohort, the 5-year probability of developing anaemia, thrombocytopenia and marked leucocytosis was 24%, 10% and 13% respectively. Finally, the cumulative incidence of thrombotic events and progression to acute myeloid leukaemia was 1% and 0·5% patient-year respectively. No death was reported during the follow-up. These findings suggest that MF in younger patients may have a more indolent course when compared to older patients. [ABSTRACT FROM AUTHOR]

The reported higher risk of maternal and fetal complications in women with myeloproliferative neoplasms ( MPN) poses challenge during pregnancy. A national prospective study of maternal and fetal outcomes of pregnant women with a diagnosis of MPN was undertaken via the United Kingdom Obstetric Surveillance System between January 2010 and December 2012. Fifty-eight women with a diagnosis of MPN were identified; 47 (81%) essential thrombocythaemia, five (9%) polycythaemia vera, five (9%) myelofibrosis and one (2%) MPN-unclassified. There were 58 live births. The incidence of miscarriage was 1·7/100 (95% confidence interval [CI]: 0·04-9·24) and the perinatal mortality rate was 17/1000 (95% CI: 0·44-92·36) live and stillbirths. Incidence of maternal complications was 9% (5/57) pre-eclampsia, 9% (5/57) post-partum haemorrhage and 3·5% (2/57) post-partum haematoma. There were no maternal deaths or thrombotic events. Delivery was induced in 45% (24/53) of women and the Caesarean section rate was 45% (24/53). The majority (85%, 45/53) delivered at term (>37 weeks gestation). Twenty-two percent (12/54) of neonates were below the 10% centile for growth and 13% (7/54) required admission to a neonatal care-unit; there were no neonatal deaths. The findings of this large, UK prospective study suggests women with MPN appear to have successful pregnancies with better outcomes than would be anticipated from the literature. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive review of the use of machine learning (ML) in transfusion medicine. It discusses the potential benefits of ML in improving patient outcomes and clinical practice in patient blood management. The review covers various studies that have developed prediction models for blood transfusion requirements in different surgical procedures, as well as studies on predicting transfusion needs in trauma patients, identifying risk factors for adverse outcomes, assessing transfusion appropriateness, and investigating transfusion safety. The studies utilize different ML models and report varying levels of accuracy in their predictions. The article highlights the potential of ML in improving transfusion practices and optimizing inventory management in hospital settings, but also emphasizes the need for further research, validation, and standardization in this field. [Extracted from the article]

The approach to the diagnosis and management of essential thrombocythaemia ( ET) is steadily changing, influenced by advances in molecular biology, data from clinical trials and retrospective analyses of patient cohorts. In the past decade options for clinical management largely remain unchanged, but who we treat, and with what target in mind, is evolving. A further area of change is recognition of symptoms that may be associated with ET, as well as other myeloproliferative neoplasms, and that potential options for their management are becoming available. Judicious and careful diagnosis is increasingly a fundamental key to successful management followed by cytoreductive therapy in a subset of patients. In this review we demonstrate our management strategies for ET using a case-based format. [ABSTRACT FROM AUTHOR]

The article presents a case study of a young adult male with a 3-day history of ataxia and bilateral deafness who demonstrated leucostasis-induced bilateral intracerebral haemorrhages and chronic myeloid leukaemia.

Summary: 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. [ABSTRACT FROM AUTHOR]

Treatments for high-risk essential thrombocythemia (ET) address thrombocytosis, disease-related symptoms, as well as risks of thrombosis, hemorrhage, transformation to myelofibrosis and leukemia. Patients resistant/intolerant to hydroxycarbamide (HC) have a poor outlook. MAJIC (ISRCTN61925716) is a randomized phase II trial of ruxolitinib (JAK1/2 inhibitor) vs Best Available Therapy (BAT) in ET and polycythemia vera (PV) patients resistant or intolerant to HC. Here findings of MAJIC-ET are reported, where the modified intention-to-treat population included 58 & 52 patients randomized to receive ruxolitinib or BAT respectively. There was no evidence of improvement in complete response within 1 year reported in 27 (46.6%) patients treated with ruxolitinib vs 23 (44.2%) with BAT (P=.40). At 2 years rates of thrombosis, hemorrhage and transformation were not significantly different, however some disease-related symptoms improved in patients receiving ruxolitinib relative to BAT. Molecular responses were uncommon; there were two complete molecular responses (CMR) and one partial molecular response (PMR) in CALR positive ruxolitinib-treated patients. Transformation to myelofibrosis occurred in one CMR patient, presumably due to the emergence of a different clone raising questions about the relevance of CMR in ET patients. Grade 3&4 anemia occurred in 19% & 0% of ruxolitinib vs 0% (both grades) BAT arm, grade 3&4 thrombocytopenia in 5.2% & 1.7% of ruxolitinib vs 0% (both grades) of BAT treated patients. Rates of discontinuation or treatment switching did not differ between the two trial arms. The MAJIC-ET trial suggests that ruxolitinib is not superior to current second-line treatments for ET. [ABSTRACT FROM AUTHOR]

We performed a meta-analysis to evaluate the risk of venous thromboembolism (VTE) in pregnant women with essential thrombocythemia. Twenty-one trials and 756 pregnancies met inclusion criteria. The absolute VTE risk in the antepartum period is not above a threshold where lowmolecular- weight heparin (LMWH) prophylaxis is clearly indicated or below a threshold where LMWH should be withheld (2.5%; 95% CI, 1.3-4.3). Postpartum, the absolute VTE risk is above a threshold where postpartum LMWH prophylaxis should be considered (4.4%;95% CI, 1.2-9.5). [ABSTRACT FROM AUTHOR]