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Patients transfused with at least two CCP units (patients nos 1-4 and patients nos 7 and 8) cleared the virus faster (median 21 days vs 32 days) than patients receiving only one CCP unit (patients nos 5 and 6). Keywords: COVID-19 convalescent plasma; immunocompromised; neutralizing antibodies; rituximab EN COVID-19 convalescent plasma immunocompromised neutralizing antibodies rituximab e22 e24 3 01/16/23 20230115 NES 230115 We read with interest the recent paper by Gachoud et al., shedding light on plasma anti-spike immunoglobulin G (IgG) level kinetics in 36 immunocompromised COVID-19 patients (mostly unvaccinated and seronegative) transfused with plasma at the time of the alpha variant of concern (VOC).[1] Seventeen patients received four 200-ml units of convalescent plasma (CP) over 48 h, while 19 patients received two 200-ml units of two-dose mRNA vaccine plasma [either putatively COVID-19-naïve (VP) or COVID-19-experienced (CP/VP, a.k.a. "hybrid" plasma or VaxCCP)] over 24 h. The authors show that, in 17 patients previously treated with anti-CD20 monoclonal antibodies within the last 12 months, who represent a difficult-to-treat COVID-19 patient population, post-transfusion plasma anti-spike IgG levels are lower than in 19 untreated immunocompromised patients. [Extracted from the article]

Treatment advances have greatly improved survival, but myeloma is among the worst of all cancers for delayed diagnosis, causing serious morbidities and early deaths. This delay is largely because the symptom profile of myeloma has very low specificity, and in primary care, myeloma is rare. However, initiating the journey to diagnosis simply requires considering myeloma and sending blood to test for monoclonal immunoglobulin. Laboratory tests reliably detect monoclonal immunoglobulin, which is present in 99% of myeloma cases, so why do health care systems have such a problem with delayed diagnosis? The Myeloma UK early diagnosis programme has brought together diverse expertise to investigate this problem, and this article was prepared by the programme's working group for laboratory best practice. It reviews evidence for test requesting, analysis and reporting, for which there is large variation in practice across the United Kingdom. It presents a 'GP Myeloma diagnostic tool' and how it can be integrated into laboratory practice alongside a laboratory best practice tool. It proposes improved requesting and integration with haematology services for reporting and interpretation. Here the laboratory has a central role in creating efficient and cost-effective pathways for appropriate and timely bone marrow examination for myeloma diagnosis., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

If AF rate control is not possible pharmacologically, then atrioventricular node (AVN) ablation and cardiac resynchronisation therapy (CRT) pacemaker implantation may be considered for symptomatic fast AF when CLL-related prognosis is more than one year.66,67 Recent studies have shown that the leading cause of death for AF patients already treated with appropriate anticoagulation is heart failure. Second, there are multiple drug interactions between ibrutinib and antiarrhythmic agents used for rate and rhythm control (amiodarone, digoxin, verapamil and diltiazem) via CYP3A4 hepatic metabolism.63-65 Atrial fibrillation ablation targeting the pulmonary veins is not recommended as it rarely offers long term AF-free survival. Keywords: ibrutinib; bruton tyrosine kinase inhibitor; atrial fibrillation; hypertension; sudden cardiac death; cardiovascular complication EN ibrutinib bruton tyrosine kinase inhibitor atrial fibrillation hypertension sudden cardiac death cardiovascular complication 70 78 9 12/27/21 20220101 NES 220101 Methodology This Good Practice Paper was compiled according to the British Society for Haematology (BSH) process at BSH Guidelines Development Process (PDF). GRAPH Footnotes 1 A recent alert from an unpublished clinical trial (FLAIR: a phase III, randomised controlled trial comparing the use of ibrutinib and rituximab [IR] versus FCR versus ibrutinib and venetoclax in treatment naïve CLL patients) reported that patients in the ibrutinib and rituximab (IR) arm have an elevated risk of sudden cardiac death if they were on ACE inhibitor treatment at study entry versus patients not on ACE inhibitors at study entry. [Extracted from the article]

Serial evaluation of CD19 surface expression in pediatric B-cell malignancies following CD19-targeted therapy. In contrast to the CD19-negative precursors, the level of CD19-positives increased significantly during the first three months of maintenance therapy, although the continued presence of B-lineage regeneration remained more or less stable (Fig. Keywords: CD19 targeting; minimal residual disease; ALL; flow cytometry; CD19-negative precursors EN CD19 targeting minimal residual disease ALL flow cytometry CD19-negative precursors e6 e9 4 12/27/21 20220101 NES 220101 Targeting the pan-B-lymphocyte antigen CD19 with the bispecific T-cell engager blinatumomab is one of the modern ways of treating acute lymphocytic B-cell precursor leukaemia (BCP-ALL).1,2 This drug has been very successful in treating patients with relapsed/refractory (R/R) disease,3,4 but it has recently been shown that blinatumomab is also effective in eradicating minimal residual disease (MRD) in patients with relapsed or primary BCP-ALL.5,6 Loss of the target molecule is one of the key mechanisms for leukaemia cells to escape the selective pressure of blinatumomab.7,8 The resulting possible CD19 negativity interferes with MRD monitoring by multicolour flow cytometry (MFC), which is usually based on analysis of the CD19-positive compartment.9 On the other hand, the use of other early B-line antigens [CD22, CD24, CD10, intracellular (i) CD79a] instead of CD19 for primary B-cell gating, such as to improve the MFC-MRD technique in the case of CD19-targeted treatment,7,10,11 could lead to errors in the interpretation of the immunophenotype of normal haematopoietic cells. CD19-negative B-cell precursors were gated as described previously.12 All BM samples obtained after completion of blinatumomab were MFC-MRD-negative, including those from patients who were MFC-MRD-positive at EOI ( I n i = 7, median MFC-MRD 0-030%, range 0-001-0-166%). [Extracted from the article]

Summary: This paper concerns an alleged event in the history of haematology that disrupts the otherwise positive narrative of papal encouragement for blood transfusion. It is frequently stated, in popular websites and in the scholarly literature, that when blood transfusion was first developed it was banned by the Pope. However, careful analysis of the sources cited shows this claim to be without historical foundation. There was never any papal prohibition of blood transfusion. It is a myth that needs to be dispelled if the full extent of the Catholic Church's support for blood and organ donation is to be appreciated. [ABSTRACT FROM AUTHOR]

Keywords: Castleman disease; interleukins; POEMS; KSHV/HHV8; HIV; TAFRO EN Castleman disease interleukins POEMS KSHV/HHV8 HIV TAFRO 328 337 10 11/01/21 20211101 NES 211101 Methodology This "Good Practice Paper" was compiled according to the British Society for Haematology (BSH) process at (http://www.b-s-h.org.uk/guidelines). Despite the success of IL-6-signalling blockade, there remains a significant unmet clinical need not only for patients who are intolerant of anti-IL-6 therapy, but also for a reliable disease-modifying therapy.50 Tocilizumab is a monoclonal antibody that antagonises the IL-6 receptor (IL-6R) to block signal transduction.57 Tocilizumab is licensed in Japan, but not in the UK, for the treatment of iMCD-TAFRO. Survival rates for MCD are not clear given changes in in diagnostic criteria, reporting and therapy.7 Nevertheless, the 5-year OS rate for MCD have been estimated at ˜65%.4 Human herpesvirus 8-associated MCD (HHV8-MCD) A proportion of cases of MCD have been attributed to infection with HHV8. The choice of therapy in MCD depends on the presentation of the patient as well as identification of drivers of disease: HHV8-MCD, POEMS-MCD, iMCD (NOS and TAFRO). [Extracted from the article]

The article focuses on a research which aims to evaluate the efficacy of bendamustine, dexamethasone and thalidomide in relapsed or refractory multiple myeloma patients following lenalidomide and bortezomib therapy or who were ineligible to receive such drugs as measured by the rate of response in terms of overall response rate. It also aims to assess the tolerability and toxicity and evaluate the time to treatment failure, overall survival, and disease-free survival.

The first sentence should read as follows: The BSH Haematology Oncology task force members at the time of writing this good practice paper were Professor Barbara Bain, Dr Robert Sellers, Dr Gail Jones, Dr David Bloxham, Dr Mamta Garg, Dr Simon Stern, Dr Nilima Parry-Jones, Dr Guy Pratt, Dr Tracey Chan. In the Acknowledgements section of the published article,[1] Professor Barbara Bain was incorrectly mentioned as a Dame. [Extracted from the article]

Patient-specific primers from 10 children/adolescents with Burkitt leukaemia (BL) ± central nervous system disease who were treated with French-British-American/Lymphome Malins de Burkitt 96 C1 plus rituximab were developed from diagnostic blood/bone marrow. Minimal residual disease ( MRD) was assessed by real-time polymerase chain reaction at the end of induction ( EOI) and consolidation ( EOC). Seventy per cent (7/10) and 71% (5/7) were MRD-positive at EOI and EOC, respectively, with no disease recurrences. MRD after induction and consolidation did not predict relapse and subsequent therapy appeared to eliminate MRD. Thus, assessing MRD at a later time point is warranted in future trials to determine its clinical significance. [ABSTRACT FROM AUTHOR]

Summary: Immunocompromised patients, such as those with a haematological malignancy, are at higher risk of SARS‐CoV‐2 infection, severe outcomes and mortality. Tixagevimab/cilgavimab is a monoclonal antibody combination which binds to the SARS‐CoV‐2 spike protein. The PROVENT phase III clinical trial reported that tixagevimab/cilgavimab prophylaxis significantly reduced the risk of COVID‐19 infection in immunocompromised participants. However, the trial was conducted before the Omicron variant became prevalent. This systematic review and meta‐analysis provide an up‐to‐date summary of the real‐world effectiveness of tixagevimab/cilgavimab in immunocompromised patients, including patients with haematological malignancies. Clinical studies from 1 January 2021 to 1 October 2022, which reported breakthrough COVID‐19 infections after tixagevimab/cilgavimab, were included. COVID‐19‐related hospitalisations, intensive care admissions and mortality were also assessed. A meta‐analysis was performed to ascertain overall clinical effectiveness. Eighteen studies, with 25 345 immunocompromised participants, including 5438 patients with haematological pathologies, were included in the review. The overall clinical effectiveness of tixagevimab/cilgavimab against COVID‐19 breakthrough infection, hospitalisation, intensive care admission and COVID‐19‐specific mortality was 40.54%, 66.19%, 82.13% and 92.39%, respectively. This review highlights the clinical effectiveness of tixagevimab/cilgavimab at reducing COVID‐19 infection and severe outcomes for immunosuppressed individuals, including patients with a haematological malignancy, during the Omicron‐predominant era. Real‐world studies are important to provide ongoing certainty of the clinical benefit for immunocompromised patients against new SARS‐CoV‐2 variants. [ABSTRACT FROM AUTHOR]

In their paper, the authors quantified liver iron concentration (LIC) and hepatic steatosis (HS) using MRI‐T2* technology in transfusion‐dependent thalassaemia (TDT) patients and healthy controls and found that the prevalence of HS among patients with TDT was 36.4%. In comparison with healthy controls, the hepatic fat fraction (FF) was significantly higher in the TDT population (p = 0.013). Active hepatitis C virus infection, body mass index (BMI) and LIC were independent predictors of HS. An inverse correlation between hepatic FF and high‐density lipoprotein cholesterol (p = 0.042) and a significant association of high glycaemia level (p = 0.037) with higher hepatic FF and a significant relationship (p = 0.026) between HS and higher BMI (though in a 'lean' group of patients) in TDT patients indicated that 'metabolic syndrome' was present in this subset with TDT. The impact of metabolic syndrome on TDT, including cardiac disease unrelated to iron overload, needs further study. Commentary on: Ricchi et al. Liver steatosis in patients with transfusion‐dependent thalassaemia. Br J Haematol 2024;204:2458–2467. [ABSTRACT FROM AUTHOR]

In their paper, the authors present their experience with the use of chimeric antigen receptor T cells targeting CD7 as a bridge to allogeneic haematopoietic cell transplantation in patients with relapsed/refractory T‐cell acute lymphoblastic leukaemia/lymphoblastic lymphoma. Commentary on: Cao et al. A safety and efficacy study of allogeneic haematopoietic stem cell transplantation for refractory and relapsed T‐cell acute lymphoblastic leukaemia/lymphoblastic lymphoma patients who achieved complete remission after autologous CD7 chimeric antigen receptor T‐cell therapy. Br J Haematol 2024;204:2351‐2364. [ABSTRACT FROM AUTHOR]

The rich history surrounding Diamond–Blackfan anaemia (DBA), originally described in 1938 as congenital hypoplastic anaemia2 reflects the evolution of paediatric haematology. In their paper, the authors1 present the results of a clinical trial using the thrombopoietin‐mimetic agent eltrombopag to treat red cell failure in DBA. A low response rate belies the importance of this work. Commentary on: Duncan et al. Treatment of refractory/relapsed Diamond–Blackfan anaemia with eltrombopag. Br J Haematol 2024;204:2077‐2085. [ABSTRACT FROM AUTHOR]

Summary: Based on promising results in older adults with acute myeloid leukaemia (AML), we treated patients with NPM1mut measurable residual disease (MRD) using off‐label venetoclax in combination with low‐dose cytarabine or azacitidine. Twelve consecutive patients were retrospectively identified, including five with molecular persistence and seven with molecular relapse/progression. All patients with molecular persistence achieved durable molecular complete remission (CRMRD‐) without transplantation. Six of seven patients with molecular relapse/progression achieved CRMRD‐ after 1–2 cycles of venetoclax. This paper highlights the promising efficacy of venetoclax‐based therapy to reduce the relapse risk in patients with persistent or rising NPM1mut MRD. [ABSTRACT FROM AUTHOR]

Up‐front allogeneic haematopoietic stem cell transplantation (allo‐HSCT) after a reduced intensity conditioning regimen is the standard treatment in children with acquired severe aplastic anaemia (aSAA) and inherited bone marrow failure syndromes (iBMFs) in the presence of a healthy matched related donor (MRD). The paper by Alsultan et al. report the safety and efficacy of MRD HSCT conditioned with low‐dose cyclophosphamide, fludarabine and thymoglobulin in both aSAA and non‐Fanconi iBMFs, strengthening the concept of the pivotal role of immunosuppressive approach in allo‐HSCT for specific subgroups of non‐malignant diseases requiring a reduced risk of toxicities, offering the opportunity to discuss the essential points for achieving patients' long‐term survival after MRD HSCT in BMF. Commentary on: Alsultan et al. Human leucocyte antigen‐matched related haematopoietic stem cell transplantation using low‐dose cyclophosphamide, fludarabine and thymoglobulin in children with severe aplastic anaemia. Br J Haematol 2023;203:255‐263. [ABSTRACT FROM AUTHOR]

Also, a therapy decision requires comparing multiple alternative interventions and accounting for patient socio-demographic, cytogenetic and molecular covariates and prior therapy response(s). In their paper several biostatisticians and haematology colleagues propose a new algorithmic approach to developing consensus guidelines for treating acute myeloid leukaemia (AML).1 The problem they want to address is that conventional consensus guidelines development cannot keep pace with the rapid evolution of AML therapies. Evidence from clinical trials including randomized controlled trials (RCTs) is often insufficient to guide patient-level therapy decision-making for several reasons. [Extracted from the article]

(A) C3d binding to PNH red cells in a PNH patient naïve to anti-C5 therapy who started ravulizumab. C3d binding to PNH red cells in a PNH patient naïve to anti-C5 therapy (left panel), during eculizumab treatment (middle panel) and after the switch to ravulizumab (right panel). [Extracted from the article]

Summary: Non‐alcoholic fatty liver disease (NAFLD) is a global health problem. Iron is the leading cause of liver damage in patients with transfusion‐dependent thalassaemia (TDT), and data on the contribution of NAFLD to liver damage in TDT is lacking. Forty‐five heavily transfused TDT patients who did not have biochemical or ultrasonic evidence of liver cirrhosis were evaluated for effects of iron overload, including the presence of diabetes mellitus, hypogonadism, serum ferritin, R2‐MRI‐liver, and liver enzymes alanine aminotransferase and aspartate aminotransferase. Liver fibrosis and steatosis were estimated using transient elastography (TE). Nine (20%) patients had significant steatosis (S1), and their body mass index (BMI) and liver fibrosis scores were higher than in patients without significant steatosis (S0) (p = 0.03 and p = 0.004, respectively). On regression analysis, the controlled attenuation parameter (CAP) score (i.e., degree of liver steatosis) was associated only with increasing BMI. The TE score (i.e., degree of liver fibrosis) was associated with increasing age, CAP score, male gender, and presence of diabetes. Neither liver steatosis nor fibrosis showed significant association with the liver iron concentration or iron‐related organ damage (hypogonadism). In this cohort of TDT patients, steatosis of the liver, which is associated with increasing BMI, appeared to increase the risk of liver fibrosis. [ABSTRACT FROM AUTHOR]

Summary: The British Journal of Haematology has now been in existence for 65 years. In this time it has served the international community as well as British haematology and has become increasingly international in its outlook. Its changing content has mirrored the changes in haematology over more than six decades, particularly with an increasing emphasis on haematological neoplasms and their treatment. [ABSTRACT FROM AUTHOR]

Summary: Prolonged cytopenia after CAR‐T cell therapy is an acknowledged problem. At present, the causes and implications of prolonged cytopenia are unclear. The paper by Kitamura et al identified that prolonged cytopenia is associated with alterations in the bone marrow niche identified before CAR‐T therapy, indicating a potential predictor of this serious side‐effect of treatment. Commentary on: Kitamura et al. Bone marrow microenvironment disruption and sustained inflammation with prolonged haematologic toxicity after CAR T‐cell therapy? Br J Haematol 2023;202:294‐307. [ABSTRACT FROM AUTHOR]

The article offers information on frequency and impact of bowel perforation in aggressive non-Hodgkin lymphoma with gastrointestinal involvement. Topics include Non-Hodgkin lymphoma (NHL) which involves the gastrointestinal (GI) tract in patients at diagnosis and were treated with curative intent chemoimmunotherapy and GI involvement by either direct tissue biopsy or positron emission tomography through perforation rates and concluded overall survival according to bowel set.

Therefore, this included all patients undergoing a BMA for investigation of potential aleukaemic leukaemia: patients who may have initially presented to rheumatology but been diagnosed with leukaemia prior to classification as JIA. No patient in our JIA cohort had clear non-arthritis bone pain, and on the occasion an MRI was performed 2/7 had a bone marrow signal abnormality but did not have leukaemia. [Extracted from the article]

Observation is recommended for patients without immunoglobulin M (IgM)-related complications and/or symptoms related to bone marrow or extramedullary lymphoplasmacytic involvement.2 Asymptomatic IgM monoclonal gammopathy encompasses two clinicopathological entities with a distinct risk of progression to symptomatic WM: IgM monoclonal gammopathy of undetermined significance (IgM MGUS) and smouldering WM (SWM). In their paper, Zanwar I et al i .11 focussed on patients with SWM with the aim of identifying risk factors for early progression to symptomatic WM. Interestingly, they were able to identify a subset of patients (30% of patients with the two variables available) with a high risk of progression to symptomatic WM (median TTP 2-4 years). Zanwar I et al i .11 report that patients with SWM represent one-fifth of patients with WM. [Extracted from the article]

Pre-eclampsia affects 4-5% of pregnancies worldwide and leads to increased maternal and fetal morbidity and mortality.2 Although the exact mechanisms for developing pre-eclampsia are unclear, placental ischaemia is central in its pathogenesis. Furthermore, those patients with SCD who developed pre-eclampsia had a higher proportion with >=1 VOC/year during their pregnancy compared those that did not have pre-eclampsia (78% vs. 48%). In their paper Boudhabhay I et al i . investigate risk factors and consequences of pre-eclampsia on pregnancy outcomes and kidney function in patients with sickle cell disease (SCD).1 They report that pre-eclampsia: (i) was independently associated with higher body mass index, increased haemolysis and >=1 vaso-occlusive crisis (VOC) requiring hospitalisation; (ii) led to poor maternal and neonatal outcomes and (iii) predicted a more rapid decline in kidney function and greater risk of developing chronic kidney disease (CKD) on longitudinal follow-up. [Extracted from the article]

Nineteen of these 33 patients had reached CR after three to six cycles of treatment, while 14 patients had failed to achieve CR (nCR). Keywords: TP53; MDS; AML; treatment; prognosis EN TP53 MDS AML treatment prognosis e77 e79 3 08/18/21 20210815 NES 210815 I TP53 i mutations, which abrogate normal p53 protein functions and may also induce deleterious "gain of function" of the protein, are a poor prognostic factor in myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), especially when mutations are biallelic.1 Restoration of mutant p53 normal functions in those cases, especially by protein "reconformation", has been considered a relevant strategy and many drugs have been tested.2 APR-246 (Eprenetapopt) is a pro-drug that induces structural changes to mutant p53 and restores the active conformation of the protein.3 We recently reported the I in vitro i and I in vivo i synergy of azacitidine (AZA) in combination with APR-246. In vitro assessment of the sensitivity to APR-246 + azacitidine combination predicts response to this combination in myelodysplastic/acute myeloid leukaemia patients. [Extracted from the article]

Keywords: intracranial haemorrhage; neonatal haematology; children; haemophilia; \sequelae EN intracranial haemorrhage neonatal haematology children haemophilia \sequelae e101 e104 4 07/20/20 20200715 NES 200715 Intracranial haemorrhage (ICH) in neonates with severe haemophilia is a potentially life-threatening complication and has been reported to occur in about 2-4% of boys with severe haemophilia; around 44-60 times higher than that expected in a non-haemophilia population.1,2 ICH requires intensive replacement therapy with factor concentrates, which has been identified as a risk factor for inhibitor development in patients with haemophilia A (HA).3 Death and neurological sequelae (motor function problems, seizures and developmental delay) are the most feared complications and have been reported to affect 50-60% of children with ICH.4 The aim of this paper was to study the incidence and symptoms of ICH in neonates with severe haemophilia and the impact of early diagnosis and treatment of ICH on long-term outcomes. The case report form registered patients' type of haemophilia, mode of delivery, ICH, and in cases of ICH, neurological signs and symptoms at presentation, treatment and sequelae. To be able to compare neonatal ICH incidences to ICH incidences later in life, the 450 neonatal months were added up to 34-52 patient years, resulting in an incidence of 0-26 ICH/patient year. The neonate might not be diagnosed as having haemophilia if there is no family history of haemophilia, symptoms like lethargy and vomiting are non-specific and not all cases of ICH are detected. [Extracted from the article]

Summary: Frailty assessment in older patients with haematological malignancies is extremely beneficial in order to optimize treatment decisions and supportive interventions. A comprehensive geriatric assessment can provide a better understanding of the functional age than clinical judgement by evaluating several skills domains such as physical function, autonomy, comorbidities, nutrition, cognition, psychological status and social support. However, the use of a multidisciplinary geriatric assessment may fail to detect unsuspected vulnerability such as mild cognitive impairment among so‐called "clinically fit" patients. The objective of this paper is to update the current knowledge about predictive factors for toxicity and "frailty scoring" in older patients with haematological malignancies. The unsuspected major role of cognitive impairment and how to detect it will be emphasized. [ABSTRACT FROM AUTHOR]

Summary: Diamond–Blackfan anaemia (DBA) is a rare and heterogeneous disease characterised by hypoplastic anaemia, congenital anomalies and a predisposition for malignancies. The aim of this paper is to report the findings from the Italian DBA Registry, and to discuss the Registry's future challenges in tackling this disease. Our 20‐year long work allowed the connection of 50 Italian Association of Paediatric Haematology and Oncology (AIEOP) centres and the recruitment of 283 cases. Almost all patients have been characterised at a molecular level (96%, 271/283), finding a causative mutation in 68% (184/271). We confirm the importance of determination of erythrocyte adenosine deaminase activity (eADA) and of ribosomal RNA assay in the diagnostic pipeline and characterisation of a remission state. Patients with mutations in large ribosomal subunit protein (RPL) genes had a significant correlation with the incidence of malformations, higher eADA levels and more severe outcomes, compared to patients with mutations in small ribosomal subunit protein (RPS) genes. Furthermore, as a consequence of our findings, particularly the incidence of malignancies and the high percentage of patients aged >18 years, we stress the importance of collaboration with adult clinicians to guarantee regular multi‐specialist follow‐up. In conclusion, this study highlights the importance of national registries to increase our understanding and improve management of this complex disease. [ABSTRACT FROM AUTHOR]

Summary: The combined incidence of classical Philadelphia‐negative myeloproliferative neoplasm (MPN) is 6–9/100 000 with a peak frequency between 50 and 70 years. MPN is less frequent in women of reproductive age. However, for essential thrombocythaemia (ET) in particular there is a second peak in women of reproductive age and 15% of polycythaemia vera (PV) patients are less than 40 years of age at the time of diagnosis. Thus these diseases are encountered in women of reproductive potential and may be diagnosed in pregnancy or in women being investigated for recurrent pregnancy loss. The incidence of MPN pregnancies is 3·2/100 000 maternities per year in the UK. The majority of data regarding Philadelphia‐negative MPNs relates to patients with ET, for which the literature suggests significant maternal morbidity and poor fetal outcome; specifically maternal thrombosis and haemorrhage, miscarriage, pre‐eclampsia, intrauterine growth restriction (IUGR), stillbirth and premature delivery as summarised in the recent systematic review and meta‐analysis in Blood, 2018, 132, 3046. The literature for PV is more sparse but increasing and is concordant with ET pregnancy outcomes. The literature regarding primary myelofibrosis (PMF) is even more scarce. Treatment options include aspirin, venesection, low molecular weight heparin (LMWH) and cytoreductive therapy. Data and management recommendations are often extrapolated from other pro‐thrombotic conditions or from ET to PV and PMF. Women of reproductive age with a diagnosis of MPN should receive information and assurance regarding management and outcome of future pregnancies. From pre‐conceptual planning to the post‐partum period, women should have access to joint care from an obstetrician with experience of high‐risk pregnancies and a haematologist in a multidisciplinary setting. This paper provides an update with regards to Philadelphia‐negative MPN in pregnancy, details local practise in an internationally recognised centre for patients with MPN and outlines a future research strategy. [ABSTRACT FROM AUTHOR]

Summary: Mastocytosis is a rare disease with varied presentation, myriad symptomatology and variable prognosis. Most patients present with cutaneous disease and mediator‐related symptomatology with a small subset having systemic disease (systemic mastocytosis, SM). A subset of the latter develops synchronous or metachronous haematologic neoplasms (SM‐AHN), most commonly chronic myelomonocytic leukaemia (CMML). Advanced systemic mastocytosis (ASM) is seen in a relatively small number of patients and is usually associated with organ dysfunction, and may present with hepatosplenomegaly, lymphadenopathy and ascites with progression to leukaemic transformation (mast cell leukaemia/acute myeloid leukaemia) occurring in a few patients. This paper discusses the clinical and pathologic features of the entire spectrum of SM in adults. [ABSTRACT FROM AUTHOR]

Summary: There is a large therapeutic gap in the treatment of sickle cell disease (SCD). Recent studies demonstrated the presence of pathophysiological and microbial changes in the intestine of patients with SCD. The intestinal microbes have also been found to regulate neutrophil ageing and possible basal activation of circulating neutrophils. Both aged and activated neutrophils are pivotal for the pathogenesis of vaso‐occlusive crisis in SCD. In this paper, we will provide an overview of the intestinal pathophysiological and microbial changes in SCD. Based on these changes, we will propose therapeutic approaches that could be investigated for treating SCD. [ABSTRACT FROM AUTHOR]

Point of care testing (POCT) refers to any testing performed outside the hospital laboratory, near or at the site of the patient where the result influences patient management (ISO 15189:2012; ISO 22870:2016). At the same time, the accreditation requirements for clinical laboratories, specified in the International Organization for Standardization (ISO) 15189:2012 and ISO 22870:2016 standards (ISO, [31], [32]), have driven the development of comprehensive clinical, financial and quality governance. Patient results should be filed permanently in the patient electronic patient record if available, or paper records, and clearly identified as a POCT result along with the operator who performed the test. Where there is a large number of the same model/make of POCT devices on one site, a minimum of one POCT device should be chosen for an extensive verification as per ISO minimum verification requirements for ISO 17025 and ISO 15189 testing laboratories. [Extracted from the article]

In this issue, the British Society for Haematology presents guidelines for the diagnosis and management of patients with smouldering multiple myeloma (SMM). The authors provide a practical, evidence‐based approach to managing these patients. Key questions remain yet unsolved. Commentary on: Hughes et al. Diagnosis and management of smouldering myeloma: A British Society for Haematology Good Practice Paper. Br J Haematol 2024;204:1193‐1206. [ABSTRACT FROM AUTHOR]

In their paper, Hannan et al. suggest that new approaches to the management of the acute and remission phases of thrombotic thrombocytopenic purpura should be considered to address white matter changes seen in patients undergoing magnetic resonance imaging. Timely intervention may have significant implications for the long‐term physical and mental health of patients. Commentary on: Hannan et al. Cognitive decline in thrombotic thrombocytopenic purpura survivors: The role of white matter health as assessed by MRI. Br J Haematol 2024;204:1005‐1016. [ABSTRACT FROM AUTHOR]

Transplantation from haploidentical donors is widely used, with progressive reduction of cord blood (CB) as alternative donor. The paper by Matsuda and colleagues, the largest analysing the outcome in non‐remission acute myeloid leukaemia (AML) transplanted with haploidentical donor or CB, suggests that CB is still a viable option when considering allogeneic transplantation for advanced AML. Commentary on: Matsuda et al. Comparison of transplant outcomes between haploidentical transplantation and single cord blood transplantation in non‐remission acute myeloid leukaemia: A nationwide retrospective study. Br J Haematol. 2023;201:106–113. [ABSTRACT FROM AUTHOR]

Summary: We describe the clinical/haematological characteristics of 446 patients with hereditary spherocytosis diagnosed in the last 40 years in a reference centre. The frequency of splenectomy decreased over time (44% before 1990 to 7% in 2011–2020), notwithstanding a confirmed good efficacy. Age at splenectomy progressively increased (63% in children before 1990 to 88% in patients aged ≥20 years in 2011–2020). Our real‐life experience showed that even a fraction of patients in the trait/mild categories (19/92, 21%) were splenectomised, whilst 30/78 (38%) in the moderate/severe groups were not. Overall, these data pinpoint to the increasing awareness about post‐splenectomy thromboses and infections. [ABSTRACT FROM AUTHOR]

The article presents a study of chronic lymphocytic leukaemia patients treated with ibrutinib below the U.S. Food and Drug Administration-recommended starting dose to compare efficacy between the various dosing schedules. Topics discussed include the lack of significant differences in baseline characteristics between the standard-dose and reduced dose cohorts and reasons for ibrutinib dose reduction including gastrointestinal toxicity, bleeding and pharmacokinetic considerations.

Parasitised red blood cells misclassified as giant platelets by an automated digital morphology analyser (Sysmex DI-60/CellaVision): a case report and a retrospective EQA analysis Next, all the leucocyte and non-leucocyte boxes were evaluated to investigate the cause of the thrombocytopenia and, as shown in Fig 1, many elements which could have been referenced as malaria parasites were found to be incorrectly placed in the giant platelet subtype box. This data not only highlights the usefulness of the remote observation of haematological digital morphology, but also underlines the importance of carefully evaluating all the CellaVision boxes ("leucocytes" and "non-leucocytes"), since useful information could be provided by misclassification. [Extracted from the article]

Multigene testing for inherited thrombocytopenia can detect an unexpected diagnosis as demonstrated in the case report from Ming-Ping et al., where the mode of inheritance and clinical phenotype did not point towards dominant Schlafen family member 14 (SLFN14) moderate thrombocytopenia. In their paper Ming-Ping et al. describe two siblings with severe thrombocytopenia (platelets counts <15 × 10 SP 9 sp /l) and bleeding symptoms, born from healthy non-consanguineous parents.1 The first child died at the age of 5 months due to intracranial haemorrhage. In addition, SLFN14-related thrombocytopenia is an ultrarare disorder and clinical and laboratory data have only been described for four unrelated pedigrees.4 All patients with pathogenic SLFN14 variants have platelet counts >65 × 10 SP 9 sp /l (moderate thrombocytopenia) and highly variable degrees of bleeding symptoms and International Society of Thrombosis and Haemostasis (ISTH) bleeding scores ranging between 2 and 20. [Extracted from the article]

Prior reports evaluating SARS‐CoV‐2 vaccine efficacy in chronic lymphocytic leukaemia (CLL) used semiquantitative measurements of anti‐S to evaluate immunity; however, neutralization assays were used to assess functional immunity in the trials leading to vaccine approval. Here, we identified decreased rates of seroconversion in vaccinated CLL patients and lower anti‐S levels compared to healthy controls. Notably, we demonstrated similar results with the Roche anti‐S assay and neutralization activity. Durable responses were seen at six months; augmentation with boosters was possible in responding patients. Absence of normal B cells, frequently seen in patients receiving Bruton tyrosine kinase and B‐cell lymphoma 2 inhibitors, was a strong predictor of lack of seroconversion. [ABSTRACT FROM AUTHOR]

The article discusses the mantle cell lymphoma (MCL) which is an incurable subtype of non-Hodgkin lymphoma that can be treated with ONC201. It states that Bruton tyrosine kinase (BTK) inhibitor ibrutinib ahieves 68% overall response rate in relapsed/refractory MCL patients following an ONC201 treatment.

The article discusses the effectiveness of the oral metronomic chemotherapy (MC), DEVEC (Deltacortene, etoposide, vinorelbine, cyclophosphamide), as treatment for aggressive lymphomas in elderly patients. Also cited are the study conducted on patients with aggressive B- and T-cell lymphomas, as well as the results like estimated median overall survival (OS), progression-free survival (PFS), and the estimated direct cost of drugs.

Summary: Sickle Cell Disease (SCD) is an increasing global health problem and presents significant challenges to European health care systems. Newborn screening (NBS) for SCD enables early initiation of preventive measures and has contributed to a reduction in childhood mortality from SCD. Policies and methodologies for NBS vary in different countries, and this might have consequences for the quality of care and clinical outcomes for SCD across Europe. A two‐day Pan‐European consensus conference was held in Berlin in April 2017 in order to appraise the current status of NBS for SCD and to develop consensus‐based statements on indications and methodology for NBS for SCD in Europe. More than 50 SCD experts from 13 European countries participated in the conference. This paper aims to summarise the discussions and present consensus recommendations which can be used to support the development of NBS programmes in European countries where they do not yet exist, and to review existing programmes. [ABSTRACT FROM AUTHOR]

Summary: Increasing use of direct oral anticoagulants (DOACs) has made management of non‐valvular atrial fibrillation and venous thromboembolism easier in most patients. But the presence of co‐existing renal impairment could render the use of DOACs problematic because all of these drugs have varying degrees of renal excretion. In this paper we address misconceptions about the safety and efficacy of DOACs in moderate‐severe renal impairment by presenting a summary of the literature from phase III trials and real‐world studies. It also addresses the important consideration of correct estimate of renal function for DOAC dosing. It is hoped that the review will serve as a valuable resource for clinicians involved in anticoagulation decision‐making in patients with renal impairment to guide the choice of most suitable agent. Accurate dosing is of particular relevance as registry data suggests it is done inconsistently and may be resulting in avoidable thromboembolic and bleeding events. [ABSTRACT FROM AUTHOR]

Summary: The post‐transplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of neoplasms that are one of the most serious complications of bone marrow and solid organ transplants. Because these disorders are rare, there are no randomized trials from which to derive optimal treatment. Management can be challenging and must balance the goal of PTLD eradication with the risks of graft rejection, graft‐versus‐host disease, further delays in immune reconstitution and life‐threatening infections, among others. This paper will provide a comprehensive review of PTLD following solid organ transplant and haematopoietic stem cell transplant with a focus on management. Included is a discussion of novel agents that are being studied in clinical trials and, when combined or sequenced with conventional therapy, have the potential to improve outcomes. [ABSTRACT FROM AUTHOR]

In transfusional iron overload, extra-hepatic iron distribution differs, depending on the underlying condition. Relative mechanisms of plasma non-transferrin bound iron ( NTBI) generation may account for these differences. Markers of iron metabolism (plasma NTBI, labile iron, hepcidin, transferrin, monocyte SLC40A1 [ferroportin]), erythropoiesis (growth differentiation factor 15, soluble transferrin receptor) and tissue hypoxia (erythropoietin) were compared in patients with Thalassaemia Major ( TM), Sickle Cell Disease and Diamond-Blackfan Anaemia ( DBA), with matched transfusion histories. The most striking differences between these conditions were relationships of NTBI to erythropoietic markers, leading us to propose three mechanisms of NTBI generation: iron overload (all), ineffective erythropoiesis (predominantly TM) and low transferrin-iron utilization ( DBA). [ABSTRACT FROM AUTHOR]

The paper by Noor et al. in this issue provides important and interesting data on the incidence and outcomes of patients with acute myeloid leukaemia in Afghanistan. The age of patients is much lower than we are used to seeing in the West, reflecting in part the particular demographics of the country; these data provide an important first step to identifying areas for improvement. Commentary on: Noor et al. Demographic and clinical characteristics of acute myeloid leukaemia diagnosed and treated at tertiary level in Afghanistan. Br J Haematol 2023;203:404–410. [ABSTRACT FROM AUTHOR]

Treatment of post-transfusion hyperhaemolysis syndrome in Sickle Cell Disease with the anti-IL6R humanised monoclonal antibody Tocilizumab It is characterised by brisk haemolysis of both transfused and recipient red cells, also known as "By-stander" haemolysis, with a haemoglobin (Hb) drop below pre-transfusion levels, marked increase in serum ferritin (SF) and a fall in reticulocyte count. 1 Hb, haemoglobin, LDH, lactate dehydrogenase; PTHS, post-transfusion hyperhaemolysis syndrome; RTC, reticulocytes; SF, serum ferritin. [Extracted from the article]