British Journal of Haematology最新文献

CPX-351 is a standard front-line induction regimen for newly diagnosed acute myeloid leukaemia (AML) with myelodysplasia-related changes (AML-MRC). The 2022 International Consensus Classification (ICC) and World Health Organization (WHO) classifications redefine AML with myelodysplasia-related (AML-MR) to include myelodysplasia-related mutations as well as cytogenetic abnormalities. Clinical outcomes of patients treated with CPX-351 within these refined AML-MR classifications remain unclear. We conducted a retrospective, multicentre study of 235 adults with newly diagnosed AML-MR treated with CPX-351 across seven US academic centres. Patients were stratified by age (younger: <60 vs. older: ≥60 years) and AML-MR subgroup: cytogenetics (AML-MRc), molecular (AML-MRm) and antecedent haematological disorder (AML-AHD). Outcomes included complete remission (CR) and CR with incomplete recovery (CR/CRi), rates of allogeneic haematopoietic stem cell transplant (alloHSCT) and overall survival (OS). The overall CR/CRi rate of CPX-351 was 52%, with no difference by age. AML-MRm had the highest CR/CRi rate (57%). Among CR/CRi responders, 55% underwent alloHSCT (<60 years: 53% vs. ≥60 years: 57%). Median OS was 13.8 months with no significant difference by age. Younger AML-MRm patients had longer median OS compared with older AML-MRm patients (38.0 vs. 19.5 months; p = 0.05). Favourable outcomes in AML-MRm, particularly in younger patients, support molecular classification in guiding therapy and selectively extending CPX-351 use beyond older adults.

This study aimed to investigate the distinct clinical characteristics and molecular features of TP53-mutant acute myeloid leukaemia (AML) patients. We retrospectively analysed 193 TP53-mutant AML patients. Better responses were observed in patients treated with the venetoclax in combination with hypomethylating agent (VEN + HMA) regimen compared to those receiving the '3 + 7' regimens (composite complete remission [CRc], 53.8% vs. 30.2%; p = 0.018). TP53 V272 mutation was associated with a lower relapse rate (0% vs. 35.2%; p = 0.041). The single hit group exhibited superior OS compared to the multi-hit group (the median overall survival [OS]: 14.3 months vs. 10.8 months; p = 0.029). TP53-mutant AML patients with CEBPA bZIP in-frame mutations showed prolonged OS (the median OS: 25.2 months vs. 13.8 months; p = 0.036). Better prognoses were also shown in patients with RUNX1-RUNX1T1 fusion gene (the median OS: 31.1 months vs. 13.7 months; p = 0.002). Multivariate analysis identified three significant prognostic factors for OS: RUNX1-RUNX1T1 fusion gene (hazard ratio [HR] = 0.23, 95% confidence interval [CI], 0.08-0.63; p = 0.005), RUNX1 mutation (HR = 1.84; 95% CI, 1.14-2.96; p = 0.012) and FLT3-ITD mutation (HR = 3.14; 95% CI, 1.80-5.47; p = 0.001). In conclusion, molecular factors matter in influencing the prognosis of TP53-mutant AML patients. Among them, TP53 mutation sites merit particular attention.

Waldenström's macroglobulinaemia (WM) has heterogeneous clinical features and limited standard therapeutic options. Although rituximab-based combinations and Bruton's tyrosine kinase inhibitors have improved outcomes, challenges like incomplete responses and toxicity remain. This prospective, multicentre, phase II study evaluated the efficacy and safety of rituximab, bortezomib, lenalidomide and dexamethasone (R-VRD) induction therapy, followed by lenalidomide maintenance in patients with symptomatic WM. Two-year progression-free survival (PFS) was the primary end-point, and the secondary end-points included overall response rate (ORR), overall survival (OS) and safety. Thirty-eight patients (median age: 66 years) were enrolled. The ORR was 81.6%, and 18.4% of the patients achieved a complete response (CR). The estimated 2-year PFS and OS rates were 57.9% and 94.7%, respectively, after a median follow-up of 38.5 months. Notably, responses deepened during lenalidomide maintenance, and 16 experienced further response improvement during the maintenance phase. The most common adverse events were Grade 3-4 haematological toxicities, particularly neutropenia, but they were manageable. Peripheral neuropathy and rash were generally mild. Patients achieving a CR showed no disease progression within 2 years, emphasizing the deep responses' prognostic value. R-VRD induction, followed by lenalidomide maintenance, demonstrated high efficacy and an acceptable safety profile against symptomatic WM.

The upper panel illustrates the study design, including recruitment, randomisation, intervention and oral glucose tolerance tests (OGTTs) conducted 2 weeks before and after. The lower panel shows reductions in serum ferritin associated with lower 2-h OGTT glucose and lower glucose area under the curve (AUC). Data from donation (DON) and simulated donation (SIM) groups are shown in red and grey respectively.

This study provides a comprehensive assessment of haematological malignancies among children, adolescents and young adults aged 0-24 years, using data from the Global Burden of Disease 2021 across 204 countries from 1990 to 2021. We found that global incidence and prevalence remained relatively stable, with approximately 150 000 new cases and over one million prevalent cases in 2021, while mortality and disability-adjusted life year (DALY) rates declined markedly. Leukaemia was the leading contributor to incidence, deaths, and DALYs, although decreases were observed across most subtypes. Age- and sex-specific analyses revealed higher burdens in males and a pronounced peak in the <5-year group, with a secondary rise in late adolescence. High-income regions bore higher incidence and DALY burdens but exhibited lower mortality, whereas low-high social-demographic index regions suffered disproportionate lethality and disability. These findings highlight both progress and persisting inequities, underscoring the urgent need for subtype-specific interventions, earlier diagnosis and equitable treatment access to improve outcomes for young patients globally.