British Society For Haematology Research Articles

Guideline for laboratory diagnosis and monitoring of von Willebrand disease: A joint guideline from the United Kingdom Haemophilia Centre Doctors' Organisation and the British Society for Haematology.

Guideline for laboratory diagnosis and monitoring of von Willebrand disease: A joint guideline from the United Kingdom Haemophilia Centre Doctors' Organisation and the British Society for Haematology.

Evidence creation for myelofibrosis: Challenges and opportunities.

Evidence-based guidelines for rare diseases, such as myelofibrosis (MF), continue to prove challenging to develop, and decision-making for MF is complex. The British Society for Haematology (BSH) has created a pragmatic symptom-guided risk-adapted framework on all aspects of management of MF and shared best practices on the use of JAK inhibitors, transplantation and other conventional therapies in the management of myelofibrosis. Commentary on: McLornan etal. The management of myelofibrosis: A British Society for Haematology Guideline. Br J Haematol 2024;204:136-150.

Battle of the (Chat)Bots: Comparing Large Language Models to Practice Guidelines for Transfusion-Associated Graft-Versus-Host Disease Prevention.

Published guidelines and clinical practices vary when defining indications for irradiation of blood components for the prevention of transfusion-associated graft-versus-host disease (TA-GVHD). This study assessed irradiation indication lists generated by multiple artificial intelligence (AI) programs, or chatbots, and compared them to 2020 British Society for Haematology (BSH) practice guidelines. Four chatbots (ChatGPT-3.5, ChatGPT-4, Bard, and Bing Chat) were prompted to list the indications for irradiation to prevent TA-GVHD. Responses were graded for concordance with BSH guidelines. Chatbot response length, discrepancies, and omissions were noted. Chatbot responses differed, but all were relevant, short in length, generally more concordant than discordant with BSH guidelines, and roughly complete. They lacked several indications listed in BSH guidelines and notably differed in their irradiation eligibility criteria for fetuses and neonates. The chatbots variably listed erroneous indications for TA-GVHD prevention, such as patients receiving blood from a donor who is of a different race or ethnicity. This study demonstrates the potential use of generative AI for transfusion medicine and hematology topics but underscores the risk of chatbot medical misinformation. Further study of risk factors for TA-GVHD, as well as the applications of chatbots in transfusion medicine and hematology, is warranted.

Predicting COVID‐19 infection risk in lymphoma by immune monitoring

Introduction: Patients with B-cell lymphoma have poorer antibody responses to COVID-19 vaccines compared to patients with other malignancies. However, the immune responses are heterogeneous and its association with clinical outcomes are poorly understood. Here, we study the association between antibody and cellular responses with the outcomes from COVID-19 infection from the PROSECO study. Methods: THE UK PROSECO study is a prospective observational cohort study evaluating COVID-19 vaccine response in people with lymphoma. Peripheral blood antibody titres (anti-spike (S) IgG by Mesoscale Discovery), antibody avidity (surface plasmon resonance) and IFNγ T-cell responses (ELISpot) against spike protein after two to four COVID-19 vaccines, and clinical outcomes data were collected. Results: 524 patients (92 Hodgkin lymphoma, 180 aggressive B non-Hodgkin lymphoma (B-NHL), 234 indolent B-NHL and 18 peripheral T-cell lymphoma) were included: 334 (84·3%), 315 (79·5%) and 266 (67·1%) participants were eligible for post-two, three and four vaccine dose analysis, respectively. Breakthrough infections (BTI) occurred in 20 (5.9%), 40 (12.7%) and 36 (13.5%) participants after two, three and four vaccine doses. Of 96 participants with BTI, 12 (12.5%) needed hospitalisation. No deaths were observed due to COVID-19 infection. No differences were observed in T-cell responses between BTI and non-BTI groups, but 4/9 (44.5%) hospitalised BTI cases had undetectable cellular and antibody responses. There was no association between antibody titres and infection episodes after two vaccine doses, but antibody titres were associated with lower BTI risk after three or four vaccine doses on multivariable analysis. Intriguingly, the antibody threshold associated with infection risk was lower after four than three vaccine doses (41 vs. 820 BAU/mL). We also observed stronger antibody binding avidity to SARS-CoV-2 spike receptor-binding domain (RBD) proteins from Wuhan and Omicron BQ.1 variants, with increasing vaccine doses, i.e., fourth versus third dose: 10-fold increase (p: <0.01); fourth versus second dose:100-fold-increase than the second dose (p: <0.0001) (see Figure). The research was funded by: the Blood Cancer UK Vaccine Research Collaborative, which is led by Blood Cancer UK in partnership with Myeloma UK, Anthony Nolan and the British Society for Haematology; a Cancer Research UK Advanced Clinician Scientist Fellowship to SH Lim; Cancer Research UK/National Institute for Health Research (NIHR) Southampton Experimental Cancer Medicine Center; NIHR Southampton Clinical Research Facility (Southampton Research Biorepository) and NIHR Southampton Biomedical Research Center; NIHR Great Ormond Street Biomedical Research Center and the NIHR Oxford Biomedical Research Center and CRUK Experimental Cancer Medicines Center. Keywords: Lymphoid Cancers, Other: Covid-19, Therapeutics and Clinical Trials in Lymphoma, vaccination Conflicts of interests pertinent to the abstract. M. Ahearne Research funding: Pfizer C. P. Fox Consultant or advisory role: Astra Zeneca G. P. Collins Consultant or advisory role: Astra Zeneca and Pfizer Research funding: Pfizer A. J. Davies Honoraria: Astra Zeneca and Janssen Research funding: Astra Zeneca and Janssen S. H. Lim Honoraria: Astra Zeneca

Guideline on the investigation and management of acute transfusion reactions.

Guideline on the investigation and management of acute transfusion reactions.

Recommendations for laboratory testing of UK patients with acute myeloid leukaemia.

Recommendations for laboratory testing of UK patients with acute myeloid leukaemia.

The Use of Next-generation Sequencing in the Diagnosis of Rare Inherited Anaemias: A Joint BSH/EHA Good Practice Paper.

The Use of Next-generation Sequencing in the Diagnosis of Rare Inherited Anaemias: A Joint BSH/EHA Good Practice Paper.

Oral Abstracts

Oral Abstracts

Guideline for the first-line management of Classical Hodgkin Lymphoma - A British Society for Haematology guideline.

This guideline was compiled according to the British Society for Haematology (BSH) process at BSH Guidelines Process 2016 (b-s-h.org.uk). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org. Recommendations are based on a review of the literature using Medline, PubMed/Medline and Cochrane searches beginning from 2013 up to January 2021. The following search terms were used: [Hodgkin lymphoma OR Hodgkin disease] NOT non-Hodgkin; AND [chemotherapy OR radiotherapy]; AND [elderly]; AND [teenage OR adolescent OR young adult]; AND [pregnancy]. Filters were applied to include only publications written in English, studies carried out in humans, clinical conferences, congresses, clinical trials, clinical studies, meta-analyses, multicentre studies and randomised controlled trials. References pre-2013 were taken from the previous version of this guideline.1 Review of the manuscript was performed by the British Society for Haematology (BSH) Guidelines Committee Haematology Oncology Taskforce, the BSH Guidelines Committee and the Haematology Oncology sounding board of BSH.

Diagnosis and management of Waldenström macroglobulinaemia-A British Society for Haematology guideline.

The objective of this guideline is to provide healthcare professionals with clear guidance on the management of patients with Waldenström macroglobulinaemia. In individual patients, circumstances may dictate an alternative approach. This guideline was compiled according to the British Society for Haematology (BSH) process at http://www.b-s-h.org.uk/guidelines/proposing-and-writing-a-new-bsh-guideline/. Recommendations are based on a review of the literature using Medline, Pubmed, Embase, Central, Web of Science searches from beginning of 2013 (since the publication of the previous guidelines) up to November 2021. The following search terms were used: Waldenström('s) macroglobulin(a)emia OR lymphoplasmacytic lymphoma, IgM(-related) neuropathy OR cold h(a)emagglutinin disease OR cold agglutinin disease OR cryoglobulin(a)emia AND (for group a only) cytogenetic OR molecular OR mutation OR MYD88 OR CXCR4, management OR treatment OR transfusion OR supportive care OR plasma exchange OR plasmapheresis OR chemotherapy OR bendamustine OR bortezomib OR ibrutinib OR fludarabine OR dexamethasone OR cyclophosphamide OR rituximab OR everolimus,bone marrow transplantation OR stem cell transplantation. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org. Review of the manuscript was performed by the British Society for Haematology (BSH) Guidelines Committee Haemato-Oncology Task Force, the BSH Guidelines Committee and the Haemato-Oncology sounding board of BSH. It was also on the members section of the BSH website for comment. It has also been reviewed by UK Charity WMUK; these organisations do not necessarily approve or endorse the contents.

Obituary: Samuel J. Machin MB ChB FRCP FRCPath, 26 March 1949 – 2 October 2021

On Saturday 2 October, we were saddened to learn of the death of Professor Samuel (Sam) Machin after a short, final illness. Sam was a larger than life character who had a certain vision about how haematology should be and strived to achieve modernization. Through his distinguished career, he was involved with many of the National and International societies and committees involved in haematology and standardization. Sam studied medicine at Sheffield University from 1966 to 1971. He received his haematology training at Manchester Royal Infirmary before taking a Senior Registrar post at the Middlesex Hospital Medical School. In 1979, he joined Jos Vermylen and others at the Department of Vascular and Haemostasis Research, KU, Leuven. It was here where he commenced his career in haemostasis and thrombosis, researching on platelets, prostacyclin and haemolytic uraemic syndrome. Returning to London, he was appointed Consultant Haematologist (the youngest at the time to achieve that post in the UK) and worked with Professor Jimmie Stewart. Sam’s career progressed with his achievements leading to his appointment as Professor of Haematology at The Middlesex and later University College London (UCL). A large number of scientists and junior doctors received expert training in the Department, many obtaining MD and/or PhD. Almost without exception, trainees whom Sam mentored and supported have gone on to become consultants, professors, heads of department and divisions in hospitals, universities, the National Blood Service and industry. He took an active role in organizing the UCL Haemostasis Training Course, which helped haematologists from many parts of the world to obtain Fellowship of the Royal College of Pathologists. In 1981, Sam founded what was to become the Haemostasis Research Unit at UCL and directed research in many aspects of haemostasis and thrombosis. His primary areas were platelet function, thrombotic thrombocytopaenia, antiphospholipid syndrome and the prothrombotic effects of combined oral contraceptives. He was also interested in laboratory automation and set up an analyser and reagent evaluations unit that studied most new haematology and coagulation systems. He understood the need to communicate and encouraged staff to present their data at conferences, and he co-authored over 400 peer-reviewed publications. Sam worked tirelessly in supporting the interests of many societies and organizations. He was President of the British Society for Haemostasis and Thrombosis (2001-03) and British Society for Haematology (2005-07), serving as treasurer from 1994 to 2000. He chaired the British Committee for Standardisation in Haematology, UK NEQAS Haematology Steering Committee (2006-11) and the International Council for Standardization in Haematology (2007-20). He was Treasurer of the International Society for Thrombosis and Haemostasis (ISTH) for the 2003 congress in Birmingham and Vice Chairman of the ISTH Scientific Standards Committee. In 2007, Sam led the reorganization and modernization of the International Council for Standardization in Haematology and remained as Chair of this body until 2020. His enthusiasm and energy resulted in the publication of more than 30 peer-review publications on standardization in haematology, including many guidance and recommendation documents. He was a supporter of laboratory haematology as a discipline. He encouraged the late Berend Houwen to develop further meetings on “Technical Innovations in Laboratory Hematology,” which later led to the formation of the International Society for Laboratory Hematology, of which Sam became a board member. He served on the Editorial Board of this journal (International Journal of Laboratory Hematology) and remained an active reviewer (even saying just 2 weeks prior to his death that he would like to receive more manuscripts). Sam enjoyed playing and watching sport, being passionate about cricket, hockey and rugby league. A kind and generous man, although sometimes controversial because he liked to speak his mind. He had a way of cutting through bureaucracy, side stepping obstacles and getting things done. He is survived by his wife Jean, son Robert and daughters Clare and Rowena as well as 5 grandchildren.

Guidelines for the monitoring and management of iron overload in patients with haemoglobinopathies and rare anaemias.

Guidelines for the monitoring and management of iron overload in patients with haemoglobinopathies and rare anaemias.

Richter transformation of chronic lymphocytic leukaemia: a British Society for Haematology Good Practice Paper.

Richter transformation of chronic lymphocytic leukaemia: a British Society for Haematology Good Practice Paper.

Guidelines: the same evidence but different conclusions - relaxation of indications for irradiation of cellular blood components?

Guidelines: the same evidence but different conclusions - relaxation of indications for irradiation of cellular blood components?

Management of cardiovascular complications of bruton tyrosine kinase inhibitors.

Management of cardiovascular complications of bruton tyrosine kinase inhibitors.

Use of Direct Oral Anticoagulants in Patients With Antiphospholipid Syndrome: A Systematic Review and Comparison of the International Guidelines.

Antiphospholipid antibody syndrome (APS) requires long-term anticoagulation to prevent recurrent thrombosis. Direct oral anticoagulants (DOACs) have been increasingly used in APS patients, but contradictory guidelines recommendations on their use do exist. We performed a systematic review of literature including studies investigating the role of DOACs in APS patients. At this aim, PubMed and Cochrane databases were searched according to PRISMA guidelines. We identified 14 studies which investigated the use of DOACs in patients with APS, of which 3 randomized clinical trials (RCTs), 1 post-hoc analysis of 3 RCTs, 7 case series and 3 cohort studies (2 prospective and 1 retrospective). Among DOACs, rivaroxaban was the most used (n = 531), followed by dabigatran (n = 90) and apixaban (n = 46). Regarding guidelines indications, the 2019 European Society of Cardiology (ESC) and American Society of Hematology (ASH) guidelines recommend against the use of DOACs in all APS patients. The European League Against Rheumatism (EULAR), British Society for Haematology (BSH), and International Society on Thrombosis and Haemostasis (ISTH) guidance provided more detailed indications stating that warfarin should be the first-choice treatment but DOACs may be considered in patients (1) already on a stable anticoagulation with a DOAC, (2) with low-quality anticoagulation by warfarin, (3) unwilling/unable to undergo INR monitoring, (4) with contraindications or serious adverse events under warfarin. Patients with arterial APS or triple positivity should be treated with warfarin while venous APS with single or double positivity may be candidate to DOACs, but high-quality studies are needed.

2021 BSH guidelines for the management of adult myelodysplastic syndromes: a practical approach to a challenging disease.

Myelodysplastic syndromes (MDS) are a group of haematological malignancies with extremely variable biologic, genetic and clinical characteristics.1 The outcome of MDS patients is very heterogeneous, some having a near-normal life expectancy while others die within a few months of their diagnosis. The median age of patients at diagnosis is advanced, ranging between 70 and 75 years, thus further complicating the management of these complex syndromes, since non-haematological comorbidities frequently coexist in the elderly and tolerability of treatments is limited.2 Given the heterogeneity of the disease pathobiology and the highly variable disease course, prognostic risk stratification is of crucial importance in clinical decision-making.3 To drive appropriate counselling and individualisation of treatment decisions, several prognostic scoring systems based on clinical and haematological parameters have been developed. Principal scoring systems currently used in Europe are the International Prognostic Scoring System (IPSS), and the revised IPSS (R-IPSS), which are based on the evaluation of peripheral blood cytopenias, bone marrow blast count and cytogenetic features.4 In daily practice, reliability of these scores is limited by the variability of morphological evaluation and, less frequently, by non-informative cytogenetic findings in a proportion of patients. Moreover, other factors including the clonal mutational status have been reported to influence the prognosis of MDS patients, and to affect the clinical outcome.5, 6 In any case, diagnostic procedures and evaluation of prognosis are not covered by these guidelines as they will be published in a separate British Society for Haematology (BSH) document. Unlike the previous edition, the 2021 BSH guidelines also do not include recommendations for CMML, for which dedicated guidelines will follow. The 2021 updated BSH guidelines for the Management of Adult Myelodysplastic Syndromes provide clear, simple and practical recommendations to approach patients with such a challenging diagnosis.7 Given the heterogeneity of the disease, the importance of establishing an individual risk-adapted treatment strategy is crucial; nonetheless, transfusion requirements and infectious complications are common to almost all patients, sooner or later. The guidelines first exhaustively describe the supportive measures that should be adopted with most patients; in particular, recommendations are reported the for prevention of fungal infection, a common complication in neutropenic patients, and for transfusion thresholds and policies to be adopted to improve patient quality of life (QoL) on the one hand, saving blood products on the other. Then, individual planning of therapeutic options is described extensively, also by means of simplified algorithms. Although standard care for MDS is constantly changing, recommendations for the initial treatment choice are still based on IPSS and R-IPSS risk evaluation, and, importantly, on patient’s preference. Therapeutic measures for most lower risk patients aim to decrease the transfusion burden and improve QoL, whereas recommendations for higher risk patients aim to prolong their life. This distinction is clearly represented in these guidelines; for each group updated treatment strategies are reported, some reflecting the 2014 BSH document. Still relevant is the recommendation that the initial MDS diagnosis should be discussed by a multidisciplinary team, including a transplantation expert, as allogeneic transplantation remains the only potentially curative option. Worthy of note, in this setting recommendations for cytoreduction in advanced MDS with hypomethylating agents (HMA) or chemotherapy before transplant are still debated, although inferior survival outcomes for patients with excess BM blasts (> 5%) at the time of transplant have been reported. Moreover, it is important that clinicians review MDS cases regularly in multidisciplinary meetings to determine if a patient can become a possible transplant candidate and/or can possibly take part in a clinical trial. Patients’ details should also be made available to national and international dedicated registries, ‘to maximize information about the patient’s history and treatment of MDS in order to benefit future patients’. In general, the guidelines are proposed to improve the quality of care of patients as well as to help physicians in their daily practice. The BSH guidelines for the management of MDS represent a timely update and make a valid contribution for the diagnosis and treatment of this heterogeneous group of blood disorders.

British Society for Haematology guidelines for the management of adult myelodysplastic syndromes.

British Society for Haematology guidelines for the management of adult myelodysplastic syndromes.

An audit of platelet transfusion indications in acute leukaemia patients: six-year experience at an Academic Centre.

Platelet transfusion plays a critical role in the supportive treatment of acute leukaemia patients who receive chemotherapy and haematopoietic stem cell transplantation (HSCT). There are few studies assessing appropriateness of platelet transfusion in this population. An audit was conducted to determine how appropriately platelets are transfused in acute leukaemia patients at a tertiary care health institution. A six-year retrospective audit was conducted in acute lymphoblastic (ALL) and acute myeloid leukaemia (AML) patients in an Academic Centre. Episodes were assessed as either appropriate or inappropriate based on guidelines from the British Society for Haematology (BSH). Pre-transfusion platelet count, transfusion indication, World Health Organization (WHO) bleeding score, and antibiotic use were all documented. Overall, 745 platelet transfusion episodes in 154 patients were audited. The proportion of episodes appropriately indicated according to BSH guidelines was 75.3%. Paediatrics and Internal Medicine had the lowest and highest proportion of appropriateness by department at 63.9% and 86.8%, respectively. The best alignment to guidelines was found on the wards (82.3%). Inpatient cases were significantly better indicated (p=0.002), whereas therapeutic and HSCT-related transfusions were not. The majority of inappropriate transfusions had a pre-transfusion count >20×109/L without a valid justification (45.1%), whereas appropriate episodes were mainly accounted for by a pre-transfusion count <10×109/L (69%). The 25% rate of inappropriate platelet transfusion in acute leukaemia patients underscores the learning needs of physicians, particularly those in training, regarding adequate use of platelets in haematologic malignancies to optimise its utilisation and patient outcome.

British Society for Haematology Guidelines on transfusion for fetuses, neonates and older children (Br J Haematol. 2016;175:784-828). Addendum August 2020.

Following publication of the British Society for Haematology (BSH) transfusion guidelines for fetuses, neonates and older children,1 there have been a number of changes requiring this addendum, prior to full revision of the guideline. For each update in the addendum, the relevant section number in the main guideline is given. The PlaNeT-2/MATISSE study was a multicentre randomised controlled trial of prophylactic platelet transfusions in preterm neonates (660 babies, <34 weeks’ gestation). The results showed that babies with severe thrombocytopenia randomised to receive platelet transfusions to maintain a platelet count threshold of 50 × 109/l had a significantly higher rate of mortality or major bleeding within 28 days of randomisation than those transfused to maintain a platelet count threshold of 25 × 109/l.2 The possible reasons for this evidence of harm of platelet transfusions are not clear and are the subject of further investigation.3 The PlaNeT-2/MATISSE results support strengthening the current BSH guideline restrictive recommendation on prophylactic platelet transfusion thresholds. New additional wording is shown in italics: For preterm neonates with very severe thrombocytopenia (platelet count below 25 × 109/l) platelet transfusions should be administered in addition to treating the underlying cause of the thrombocytopenia (2C). For non-bleeding neonates platelet transfusions should not be routinely administered if platelet count is ≥25 × 109/l (1B). Suggested threshold counts for platelet transfusions in different situations are given in Table 2 (2C). The requirement to import plasma for treatment of individuals born on or after 1 January 1996 or with TTP was introduced in 2004 in the UK, as part of variant Creuzfeldt–Jacob disease (vCJD) risk reduction measures. In September 2019, the Department of Health and Social Care withdrew this requirement and approved the use of UK-sourced plasma and pooled platelets for these individuals (https://www.parliament.uk/business/publications/written-questions-answers-statements/written-statement/Commons/2019-09-09/HCWS1821/). This followed publication of advice and a comprehensive updated assessment of the vCJD risk by the Advisory Committee for the Safety of Blood, Tissues and Organs (SaBTO) (https://www.gov.uk/government/publications/risk-reduction-measures-for-variant-creutzfeldt-jakob-disease-pcwg-report). For details on the use of plasma for treatment of patients with TTP also refer to the relevant BSH guideline.4 The Joint UK Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee (JPAC) subsequently agreed that UK plasma for those born on or after 1 January 1996 does not need to be pathogen inactivated, similar to UK plasma for all other age groups (Oct 2019, https://www.transfusionguidelines.org/about/minutes-of-jpac-meetings). Helen V. New and Simon J. Stanworth wrote the initial manuscript, all authors critically reviewed it and approved the final version. We gratefully acknowledge the comments of the BSH Transfusion Task Force and review by paediatric haematology and neonatology expert colleagues.