Autologous chimeric antigen receptor (CAR) T-cell therapy has transformed the management of B-cell leukaemia and lymphoma. However, current manufacturing processes present logistical hurdles, restricting broader application. As clinical outcomes can be heavily influenced by the quality of autologous starting materials and production processes, strategies to improve product phenotype are crucial. Short manufacturing processes have the advantage of bringing products to patients more quickly and, in parallel, avoiding the highly differentiated and exhausted CAR T-cell phenotypes associated with prolonged ex vivo manufacture. This Review examines advances in our understanding of what constitutes an effective CAR T-cell product and approaches to improve product quality. Historically, strategies have relied on adjustments in medium composition and selection of less differentiated cell subtypes. Since 2020, the field has been shifting towards reduced-expansion protocols, no-activation protocols, and point-of-care manufacturing. These approaches have the advantage of a rapid turnaround while maintaining a less differentiated and exhausted phenotype. These efforts are leading to ultrarapid production methods and even elimination of ex vivo manipulation with the use of in vivo manufacturing approaches. In this Review, we focus on the advances needed to accelerate CAR T-cell manufacture (including near-patient methods), with an emphasis on improved therapeutic efficacy and rapid turnaround time, and simplified quality control procedures required to fully realise the clinical potential of CAR T-cell therapies.

Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody in development as a once-daily, subcutaneous prophylaxis for patients with haemophilia A or haemophilia B with or without inhibitors. We aimed to assess the efficacy and safety of concizumab in patients with haemophilia A or B without inhibitors. Here we report the results from the confirmatory analysis cutoff.

Advances in haemolytic disease of the fetus and newborn have led to numerous treatment options. We report practice variations in the management and outcomes of haemolytic disease of the fetus and newborn in at-risk pregnancies.

The WHO and International Consensus Classification 2022 classifications of myelodysplastic syndromes enhance diagnostic precision and refine decision-making processes in these diseases. However, some discrepancies still exist and potentially cause inconsistency in their adoption in a clinical setting. We adopted a data-driven approach to provide a harmonisation between these two classification systems. We investigated the importance of genomic features and their effect on the cluster assignment process to define harmonised entity labels. A panel of expert haematologists, haematopathologists, and data scientists who are members of the International Consortium for Myelodysplastic Syndromes was formed and a modified Delphi consensus process was adopted to harmonise morphologically defined categories without a distinct genomic profile. The panel held regular online meetings and participated in a two-round survey using an online voting tool. We identified nine clusters with distinct genomic features. The cluster of highest hierarchical importance was characterised by biallelic TP53 inactivation. Cluster assignment was irrespective of blast count. Individuals with monoallelic TP53 inactivation were assigned to other clusters. Hierarchically, the second most important group included myelodysplastic syndromes with del(5q). Isolated del(5q) and less than 5% of blast cells in the bone marrow were the most relevant label-defining features. The third most important cluster included myelodysplastic syndromes with mutated SF3B1. The absence of isolated del(5q), del(7q)/-7, abn3q26.2, complex karyotype, RUNX1 mutations, or biallelic TP53 were the basis for a harmonised label of this category. Morphologically defined myelodysplastic syndrome entities showed large genomic heterogeneity that was not efficiently captured by single-lineage versus multilineage dysplasia, marrow blasts, hypocellularity, or fibrosis. We investigated the biological continuum between myelodysplastic syndromes with more than 10% bone marrow blasts and acute myeloid leukaemia, and found only a partial overlap in genetic features. After the survey, myelodysplastic syndromes with low blasts (ie, less than 5%) and myelodysplastic syndromes with increased blasts (ie, 5% or more) were recognised as disease entities. Our data-driven approach can efficiently harmonise current classifications of myelodysplastic syndromes and provide a reference for patient management in a real-world setting.

Pregnancy-associated haematological malignancy is a rare event; therefore, data available to guide the treatment are scarce. We aimed to evaluate the incidence, overall survival, and maternal morbidity and mortality of women with pregnancy-associated haematological malignancies.

Over the last decade, the advent of direct oral anticoagulants (DOACs) has rapidly changed the landscape of anticoagulation. In the early 2010s, DOACs became widely available for stroke prevention in atrial fibrillation and the treatment of venous thromboembolism. About 10 years later, approximately two-thirds of patients requiring oral anticoagulant treatment were receiving a DOAC. The results of several post-marketing studies consistently confirmed the findings of phase 3 clinical trials, and research has focused on new areas of development, with heterogeneous results. A role for DOACs has emerged for patients with peripheral artery disease and other challenging conditions, such as cancer-associated thrombosis, unusual-site venous thromboembolism, and end-stage renal disease. Conversely, clinical trials showed that DOACs were not efficacious in patients with valvular atrial fibrillation, mechanical heart valves, embolic strokes of undetermined source, or antiphospholipid syndrome. In this Review, we discuss the impact of DOACs in clinical practice over the last decade, new areas under development, and practical issues in the management of these drugs.