British Journal of Haematology最新文献

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by antiplatelet autoantibodies, with many patients refractory or relapsing on conventional treatments. GPIbα, an important autoantigen in ITP, is notably linked to refractoriness, highlighting the need for novel treatments. We assessed CD19 chimeric antigen receptor (CAR)-T cell therapy's potential in a modified murine model targeting GPIbα. CD19 CAR-T cell infusion accelerated platelet count recovery compared to the control group, effectively depleted CD19⁺ B cells and CD138⁺ plasma cells, and markedly reduced anti-GPIbα autoantibodies in vivo. In vitro CD19 CAR-T cells reduced both plasma cells and B cells in the spleens of mice and ITP patients. CD19 CAR-T cell therapy significantly altered T-cell subsets, increasing regulatory T cells, T helper 1 and T helper 17 populations, suggesting a role in modulating the immune response for sustained ITP remission. Monitoring of body/spleen weights and temperature showed no significant cytokine release syndrome, indicating a favourable safety profile. These promising results support the potential of CD19 CAR-T cell therapy as a novel treatment option for refractory ITP, particularly in GPIbα-positive autoantibody patients. Further clinical studies are warranted to assess the safety and efficacy of this approach in human patients.

Unconventional genetic subtypes of B-cell precursor acute lymphoblastic leukaemia (B-ALL) were analysed to compare their frequency and their impact on outcomes between children and young adults in Taiwan. Unconventional subtypes were found in 23.0% of 456 paediatric B-ALL and 24.5% of 139 young adult B-ALL. The most frequently unconventional subtype both in children and young adults was BCR::ABL1-like, which could be subdivided into different kinase-altering aberrations in 67.3% of children and 78.6% of young adults. CRLF2-R was more frequent in children, while IL7R mutations were more common in young adults. In children, favourable outcomes were observed in patients with DUX4-R and PAX5alt, whereas those with BCR::ABL1-like and MEF2D-R had inferior outcomes. BCR::ABL1-like and MEF2D-R were also the independent predictors of inferior event-free survival in children. Conversely, most unconventional subtypes in young adults were associated with adverse outcomes except for DUX4-R. We found a lower incidence of BCR::ABL1-like and a better prognosis for paediatric PAX5alt in Taiwan compared to the West. Additionally, genetic differences were identified between paediatric and young adult BCR::ABL1-like subtypes. The extremely poor prognosis for unclassified young adults highlights the potential use of further subdivision of unfavourable genetic subtypes in refining risk classification and treatment optimization.

Identifying aberrant T lymphocytes in peripheral blood is essential for diagnosing Sezary syndrome (SS) and is a prognostic indicator in mycosis fungoides (MF). Flow cytometry using a T-cell receptor constant beta-1 chain (TRBC1)-targeting antibody provides a refined approach for detecting T-cell clonality. We evaluated the performance of the TRBC1 antibody assay (TRBC1-aa) in 164 patients, compared to standard flow cytometry methods for assessing T-cell aberrancy, demonstrating 92.3% sensitivity and 83.5% specificity. TRBC1-aa accurately excluded clonality in 100% of benign inflammatory dermatoses and improved the detection of residual blood involvement earlier than standard flow cytometry in 66.7% of SS and 25.0% of advanced-stage MF patients on systemic therapy.

There are clear sex-based differences in the incidence, risk factors and mortality of most haematologic malignancies (HM). Despite known differences in physiology, haematopoiesis, molecular profiles, drug pharmacokinetics, treatment-related toxicities and treatment experience, males and females receive standardized and identical treatment for most HMs. Previous published work has demonstrated disparities in female representation in cancer clinical trials and highlighted a paucity of information on differential treatment outcomes and toxicities by sex. We analysed references of 182 clinical trials which form the basis of recent treatment guidelines from the National Comprehensive Cancer Network and found a minority (17/9.3%) did not report the sex distribution of trial participants. However, a majority (165/90.6%) did not report sex-disaggregated outcomes. Of those that did, 36.5% showed outcome differences by sex. Academic leadership by women in the assessed trials as well as in guidelines committees was disproportionately lower than their representation in the profession. We call on all clinical trials leaders, consortia and guideline builders to include sex-disaggregated data in their analyses, reporting these in a transparent manner (as per regulations mandating such reporting), and for investigators to assess whether aetiological factors differ by sex. These actions will enhance personalized prevention, therapy and follow-up.

Glofitamab is a CD3-CD20 bispecific antibody used to treat B-cell non-Hodgkin lymphoma. We describe three cases of enterocolitis occurring with glofitamab at a single institution. Similarities between cases include onset post cycle 4-5, moderately elevated faecal calprotectin, abnormal bowel avidity on positron emission tomography scan (2/3), absence of CD20-positive B cells on gut histology and steroid responsiveness. There was variability in the area of gastrointestinal inflammation, severity of symptoms, histological findings and impact on subsequent therapy. The mechanism for this phenomenon is unknown. Possible explanations include B-regulatory cell depletion and T-cell recruitment to the gastrointestinal tract because of CD20 antigen density. Clinicians should consider this toxicity in glofitamab-treated patients presenting with sustained diarrhoea or abdominal pain when infectious colitis has been comprehensively excluded.

This study examined mortality rates among 2475 patients with thalassaemia and sickle cell disease (SCD) per year over 12 years in Greece, recording 335 deaths (27.92/year), with an overall mortality rate of 1.13% per year. The primary aim was to identify causes of death, comorbidities, treatment efficacy and iron overload prevalence. Of the deaths, 239 were attributed to thalassaemia and 96 to SCD. For thalassaemia patients, cardiac failure, hepatocellular carcinoma and sepsis were the leading causes of death, with no neoplasms observed in β+/β+ genotypes. In SCD, sepsis, liver failure and stroke were the predominant causes, with sepsis-related deaths higher in frequently transfused patients. The median age of death was significantly lower in thalassaemia (50 years) compared to SCD (58.49 years, p < 0.001). Differences in comorbidities and treatment effectiveness highlight the need for improved management strategies. Addressing iron overload, optimizing chelation therapy and expanding hydroxyurea use in SCD patients could enhance survival and quality of life. Strengthening treatment protocols and monitoring may reduce mortality, emphasizing the importance of targeted interventions in haemoglobinopathies.

Despite the development of novel treatments, multiple myeloma (MM) and light-chain (AL) amyloidosis remain incurable diseases. BCL2 inhibitors are a class of drugs under development for plasma cell disorders, with strong data supporting their use, particularly in patients with MM and AL amyloidosis harbouring the t(11;14). Venetoclax, the most extensively studied BCL2-specific inhibitor, was initially designed and evaluated for other malignant blood disorders. However, it has since shown promising efficacy in both randomized and real-world studies for MM and AL amyloidosis, either as a monotherapy or in combination with other agents. Nonetheless, toxicity concerns have been raised, underscoring the need for careful patient selection and precise dose optimization. Additionally, other BCL2-targeting drugs are under investigation in preclinical and clinical studies. This review focuses on the current role of BCL2 inhibitors in the treatment landscape of MM and AL amyloidosis.

This study evaluated the kinetics of KMT2A-r during chemotherapy and its impact on allogeneic haematopoietic stem cell transplantation (allo-HSCT) outcomes. KMT2A-r was assessed post-induction (MRD1), after the first (MRD2) and second (MRD3) consolidations and pre-transplant (MRD4) in 52 patients with acute myeloid leukaemia (AML). KMT2A-r significantly decreased from diagnosis to MRD2 (p < 0.001 for diagnosis vs. MRD1; p = 0.019 for MRD1 vs. MRD2). The incidence of KMT2A-r negativity (57.5%) peaked at MRD2. KMT2A-r status at each time point significantly affected post-transplant outcomes. Cluster analysis identified four KMT2A-r kinetic profiles: persistently negative (-/-), turned negative at transplant (+/-), turned positive at transplant (-/+) and persistently positive (+/+). The (-/-) group had the best outcomes, with a cumulative incidence of relapse (CIR) of 13.0%, overall survival (OS) of 82.0% and leukaemia-free survival (LFS) of 81.7%. The (+/+) group had the worst prognosis, with a CIR of 58.8%, OS of 29.4% and LFS of 23.5%. KMT2A dynamics were an independent risk factor for CIR (Hazard ratio [HR] = 11.070, 95%CI 2.395-51.165, p = 0.002), LFS (HR = 9.316, 95%CI 2.656-32.668, p < 0.001) and OS (HR = 7.172, 95%CI 1.999-25.730, p = 0.003). In conclusion, KMT2A-r status after chemotherapy and its kinetics are significant HSCT prognostic indicators.