British Journal of Haematology最新文献

Mycosis fungoides and Sézary syndrome represent the most common types of cutaneous T-cell lymphoma. This series provides an updated perspective on their management, integrating new evidence on pathophysiology and therapeutic advances. Prompt recognition of early blood involvement and new prognostic models incorporating large-cell transformation have shown their importance in complementing the current staging. New monoclonal antibodies have represented a breakthrough in the management, though allogeneic transplantation remains the only potentially curative option, with growing evidence on its indications. Despite this therapeutic progress, the optimal sequencing of treatments, the selection of patients for transplantation and maintenance strategies remain unmet needs.

Immune thrombocytopenia (ITP) is an autoimmune disorder that occurs in children and adults, and it is characterized by a reduced platelet count. Hetrombopag, a novel thrombopoietin receptor agonist (TPO-RA) for second-line ITP treatment, lacks thorough efficacy and safety evaluation in paediatric patients. In this study, we assessed complete response (CR), response (R), overall response (OR), no response (NR), durable response (DR), relapse and treatment-free response (TFR) rates in 93 paediatric ITP patients who were treated with hetrombopag. The results demonstrated that the CR rate, R rate, OR rate, NR rate, DR rate, relapse rate and TFR rate were 61.3%, 15.1%, 76.3%, 23.7%, 76.1%, 26.8% and 52.1% respectively. Patients with newly diagnosed ITP exhibited a higher TFR rate than those with persistent or chronic ITP. Furthermore, among the nine patients who switched from other TPO-RAs, seven patients achieved OR during initial treatment, including three patients who achieved CR and four patients who achieved R. The overall incidence of adverse events was 37.6%, with no serious adverse events reported. Our findings highlight that hetrombopag is both safe and effective in paediatric patients and may serve as a viable option for patients for whom first-line therapy fails.

Small nucleolar ribonucleic acids (snoRNAs) are a class of small non-coding RNAs involved in the post-transcriptional modification of ribosomal RNAs (rRNA) and small nuclear RNAs (snRNA). Mounting evidence indicates that specific snoRNAs are drivers of oncogenesis, but their role in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is unknown. We found that a small subset of 30 snoRNAs is commonly deregulated in BCP-ALL. Small Cajal body-specific RNA 12 (scaRNA12) was the strongest downregulated snoRNAs in BCP-ALL. Forced expression of scaRNA12 in BCP-ALL cells largely recovered the level of uridine-46 pseudouridylation of U5 snRNA (U5:Ψ46), an important RNA modification for proper splicing and gene expression regulation. We found that scaRNA12 controls a set of genes that belong to pathways that are frequently affected in BCP-ALL samples. We show that scaRNA12 activates p53, which is commonly affected in BCP-ALL even in the absence of p53 mutations. We show that scaRNA12 expression decreased the expression of upstream p53 regulators and provide novel evidence for a role of scaRNA12 in p53 regulation. We found that forced expression of scaRNA12 in BCP-ALL increased p53 activity and significantly enhanced the sensitivity of BCP-ALL to chemotherapeutic reagents. Together, our results suggest a tumour-suppressing role for scaRNA12 in BCP-ALL.

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an X-linked, systemic, haemato-inflammatory syndrome caused by somatic mutations in the UBA1 gene. No standardized treatment guidelines exist, but evidence is emerging that treatment with hypomethylating agents (HMAs) can induce improvement of the inflammatory symptoms, reverse cytopenia, enable weaning of the corticosteroids and, in some cases, induce molecular remission. We systematically reviewed the literature to evaluate the experience with HMA in the management of VEXAS, following 2020 PRISMA guidelines across three databases. A total of 30 citations reporting 166 patients with genetically confirmed VEXAS syndrome treated with HMA were included. All but three patients were males (98%), and the median age was 71 years (range, 29-86). Inflammatory symptoms (96% of patients), constitutional symptoms (84%) and cytopenia (89%) were most frequently reported, and 81% had a concomitant diagnosis of myelodysplastic syndromes (MDS). Most mutations were substitutions of p.Met41 (81%). Overall inflammatory response was achieved in 59% of treated patients with most complete response (52%). Responses were documented in patients with and without concomitant MDS. Any haematological response was achieved in 74% of the patients, and eradication of the UBA1 clone (to a variant allele fraction of <2%) was detected in 51% of cases in whom mutation testing was performed (n = 32/63). Toxicity was the most frequent reason for discontinuation of therapy. This review highlights HMAs as a feasible option in the management of VEXAS syndrome. Prospective studies are needed to identify predictors for response or resistance and optimal regimens.

In adults with classic Hodgkin lymphoma (cHL), metabolic tumour volume (MTV) is valuable for risk stratification. This systematic review explored the role of volumetric parameters in children, adolescents and young adults (CAYA) with cHL. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. Five databases were searched on 16 October 2024. Eligible studies were peer-reviewed manuscripts, written in English, published since database inception that included patients ≤21 years of age with a diagnosis of cHL treated with chemotherapy ± radiotherapy with a baseline ¹⁸F-Fluorodeoxyglucose (F-FDG) PET/CT scan for MTV quantification. The search strategy identified 3669 studies, of which 35 were eligible for inclusion. Fifteen studies (43%) evaluated a cohort exclusively ≤21 years of age. All eight studies that explored the association of baseline PET parameters with known risk factors identified a significant correlation. Nine of 12 papers (75%) demonstrated a statistically significant correlation with disease response to therapy on PET/CT. Fifteen of 20 papers (75%) demonstrated an independent statistically significant correlation with clinical outcomes. In the CAYAHL population, volumetric PET parameters are valuable for risk stratification despite heterogeneity in results. Future harmonization of the segmentation approach will facilitate incorporation of MTV into clinical practice.