British Journal of Haematology最新文献

Zandelisib, a selective, potent PI3Kδ inhibitor, demonstrated favourable outcomes in patients with relapsed or refractory follicular lymphoma in a global phase II study. This phase II study evaluated the efficacy and safety of zandelisib for relapsed or refractory follicular lymphoma or marginal zone lymphoma. Sixty-one patients received zandelisib orally at 60 mg daily continuously in the first two 28-day cycles, followed by intermittent dosing on Days 1–7 following each cycle until progressive disease or unacceptable toxicity. Objective and complete response rates were 75.4% (95% confidence interval [CI], 62.7%–85.5%) and 24.6% (95% CI, 14.5%–37.3%) respectively. Median time to response was 58 days; 70.5% (43/61) of patients achieved their first response by Week 8. At least one Grade ≥ 3 treatment-emergent adverse event (TEAE) occurred in 55.7% of patients: transaminase elevation (8.2%); cutaneous reactions (3.3%); and diarrhoea, enterocolitis and lung infection (1.6% each), defined as adverse events of special interest. The discontinuation rate due to any TEAE was 14.8%. No zandelisib-related death occurred. Zandelisib showed favourable efficacy and tolerability in Japanese patients with relapsed or refractory indolent non-Hodgkin B-cell lymphoma. This unique dosing schedule may maintain efficacy while mitigating the safety issues observed with other PI3Kδ inhibitors (ClinicalTrials.gov number, NCT04533581).

There is no diagnostic test for primary immune thrombocytopenia (ITP). Certain microRNAs have shown to have diagnostic potential in ITP. We validated 12 microRNAs identified from two previous studies to find a diagnostic biomarker. The study included two ITP cohorts (n = 61) and healthy controls (n = 28). The first ITP cohort involved 24 patients from the Prolong study, patients with newly diagnosed/persistent ITP (<1 year) treated with corticosteroids ± IVIG but relapsed/failed to respond. The second cohort comprised 37 patients from ITP biobank, Østfold Hospital, Norway, patients had different disease stages and therapies. Twelve microRNAs were measured: miR-199a-5p, miR-33a-5p, miR-195-5p, miR-130a-3p, miR-144-3p, miR-146a-5p, miR-222-3p, miR-374b-5p, miR-486-5p, miR-1341-5p, miR-766-3p and miR-409-3p. miR-199a-5p, miR-33a-5p, miR-374b-5p, miR-146a-5p and miR-409-3p were expressed differentially in the entire ITP cohort compared to controls; of those only miR-199a-5p showed good discriminative ability between ITP and controls with area under the curve (AUC) of 0.718 (95% CI: 0.599-0.836). In the Prolong cohort (ITP < 1 year), miR-199a-5p and miR-374b-5p showed very good discriminative ability between ITP and controls with AUC of 0.824 (0.708-0.940) and 0.806 (0.688-0.924) respectively. This study confirmed that miR-199a-5p has good discriminative ability between primary ITP and healthy controls, thus may be a diagnostic biomarker of ITP.

This guideline provides consensus opinion on the investigations required for people presenting with suspected monoclonal gammopathy of renal significance to both nephrology and haematology physicians. The guideline discusses the principles of treating a patient with MGRS and provides recommendations for both supportive management and haematological therapy. It details the recommended on-going monitoring required for both specialty areas.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains an option for young and fit chronic lymphocytic leukaemia (CLL) patients with high-risk disease features. However, allotransplanted patients are generally excluded from clinical trials, making data regarding the use of venetoclax after alloHSCT extremely rare. We report data from 7 CLL patients who received venetoclax after alloHSCT among 53 Italian centers. These patients underwent alloHSCT between 2006 and 2021 after failing chemoimmunotherapy (7/7), ibrutinib (5/7) and/or idelalisib (1/7). Of note, 3/7 patients had already received venetoclax-based therapy before alloHSCT. Post-allo HSCT venetoclax treatment resulted safe, with adverse events not different from what reported in clinical trials. Importantly, no meaningful impact on graft versus host disease (GvHD) course was observed: 4/7 patients with pre-existing chronic GvHD had no exacerbation after venetoclax start, and only one patient developed GvHD during venetoclax therapy, that was managed as per standard clinical practice. Concerning efficacy, 5/7 patients presented a clinical response to venetoclax, with two patients achieving an undetectable minimal residual disease. To our knowledge, this is the largest reported series of CLL patients treated with venetoclax after alloHSCT. In these heavily pretreated and high-risk patients, previous alloHSCT did not compromise the feasibility of venetoclax therapy, that lacked unexpected toxicities and did not exacerbate GvHD.

Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease characterised by the uncontrolled proliferation of mature lymphocytes. A subset of CLL patients harbouring complex karyotype (CK) presents with poor prognosis and limited treatment options. This review aims to discuss the current understanding of such patient subset, including its molecular landscape, diagnostic approaches, treatment modalities and emerging therapies. Furthermore, it outlines strategies for personalised management to improve clinical outcomes in this challenging patient population.

Approximately 1.92 billion people worldwide are anaemic, and iron deficiency is the most common cause. Iron deficiency anaemia (IDA) disproportionately affects women of reproductive age and remains under-addressed in low- to middle-income countries (LMICs). The primary objective of our scoping review is to evaluate the barriers and facilitators to IDA management in LMICs by using an intersectionality-enhanced implementation science lens adapted from the consolidated framework for implementation research and the theoretical domains framework. A total of 53 studies were identified. Contextual barriers included the deprioritization of IDA risk, unequal gender norms and stigma from the HIV/AIDS epidemic. Regional poverty, conflict and natural disasters led to supply chain barriers. Individual-level facilitators included partner support and antenatal care access while barriers included forgetfulness and having medical comorbidities. Successful interventions also utilized education initiatives to empower women in community decision-making. Moreover, community mobilization and the degree of community ownership determined the sustainability of IDA reduction strategies. IDA is not only a medical problem, but one that is rooted in the sociocultural and political context. Future approaches must recognize the resilience of LMIC communities and acknowledge the importance of knowledge translation rooted in community ownership and empowerment.

Chimeric antigen receptor T-cell (CAR-T) therapy has shown transformative potential in treating malignant tumours, with increasing global approval of CAR-T products. However, high-production costs and risks associated with viral vector-based CAR-T cells—such as insertional mutagenesis and secondary tumour formation—remain challenges. Our study introduces an innovative CAR-T engineering approach using mRNA delivered via lipid nanoparticles (LNPs), aiming to reduce costs and enhance safety while maintaining strong anti-tumour efficacy. We developed an LNP-based transfection protocol for efficient delivery of mRNA encoding full-human CAR constructs, achieving high CAR expression and significant cytotoxicity against leukaemic cells in vitro. Co-culture with Raji cells showed increased cytokine secretion and tumour cell killing by mRNA-LNP CAR-T cells. Therapeutic efficacy was further demonstrated in an NOD-scid-IL2Rγnull (NSG) mouse model with Raji engraftment, where treated mice exhibited marked tumour regression and extended survival. These findings underscore the potential of mRNA-LNPs as a non-viral, effective CAR-T engineering platform, offering a promising alternative to traditional methods that could improve CAR-T safety, efficacy and accessibility in clinical cancer immunotherapy.