British Journal of Haematology最新文献

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is an uncommon aggressive large B-cell lymphoma variant which can develop synchronously or following a diagnosis of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). There is morphological, immunophenotypic and molecular overlap between THRLBCL and NLPHL suggesting that these two entities may lie on the same spectrum. Due to the rarity of THRLBCL, accurate diagnosis can be challenging and there is a paucity of data on which to base treatment decisions. The management has largely followed diffuse large B-cell lymphoma (DLBCL) with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone established as the standard of care in the first line, with outcomes comparable to international prognostic index matched DLBCL. In the relapsed/refractory (R/R) setting, there is no standard of care. There is a move towards inclusion of THRLBCL patients in clinical trials evaluating novel agents, although historically they were commonly excluded. Due to the small numbers included in clinical trials, it has been difficult to discern the effect of novel agents in this cohort. Thus, we are reliant on larger real-world datasets to inform our understanding. This review will examine the data available in the first line and R/R setting with a focus on immunotherapeutic approaches.

This is a new British Society of Haematology (BSH) guideline which focuses on the management of hepatitis B and C (HBV and HCV) infection affecting people with bleeding disorders (PwBD), including those who cleared the infection many years previously. It is based on the European Association for the Study of the Liver (EASL) guidance and is a succinct practical guide for haematologists to support joint care with hepatology. It is compatible with the joint international guidance from the European Association for Haemophilia and Allied Disorders, European Haemophilia Consortium, International Society on Thrombosis and Haemostasis (ISTH) and World Federation of Hemophilia 2024. However, it provides more specific guidance on investigations for fibrosis/cirrhosis and thresholds for onwards referral to hepatology in those who cleared HCV historically (either through spontaneous clearance or following effective treatment). The aim of this guideline is to improve the management of this group of patients nationally as well as potentially supporting the management of this group of patients internationally. It also contributes to the delivery of recommendations made by the UK Infected Blood Inquiry 2024.

We evaluated the tolerability and efficacy of pegylated interferon alfa-2B (peg-IFNα; PegIntron, MSD) combined with nilotinib in the Australasian Leukaemia and Lymphoma Group CML11 (Pinnacle) study. This phase II study started patients on nilotinib 300 mg twice daily. Subcutaneous peg-IFNα was added at 30-50 50 μg/week from 3 months until 24 months as tolerated. Sixty patients were enrolled with a median age of 48.5 years (range 19-72); 45% were female. With a median follow-up of 60 months, 40 patients (67%) remain on study. The proportion of patients who received ≥50% and ≥85% of their assigned peg-IFNα doses were 58% and 35% respectively. Common reasons for peg-IFNα discontinuation were mood disturbance (5), thyroid disease (4) and myalgia (4). The cumulative incidence of Major Molecular Response (MMR, BCR::ABL1≤0.1%) was 87% by 12 months; Molecular Response 4.5 (MR4.5, BCR::ABL1≤0.0032%) incidence at 24 and 60 months was 55% and 82% respectively. Thirty-seven patients (62%) had MR4.5 for >24 months, 14 of whom attempted treatment-free remission (TFR); 13 remained in TFR at a median follow-up of 32 months. CML11 demonstrated that peg-IFNα with nilotinib leads to high rates of molecular response, with tolerability similar to prior studies. Trial registration ANZCTRN12612000851864.

Allogeneic haematopoietic stem cell transplantation (ASCT) is a curative treatment for acute myeloid leukaemia (AML) but carries a high risk of gonadotoxicity. Ovarian tissue cryopreservation (OTC) offers a fertility preservation option, yet its safety in AML remains uncertain due to the risk of leukaemic cell reintroduction. The FERTILAM pilot study evaluated measurable residual disease (MRD) in ovarian tissue collected at complete remission (CR) from nine AML patients undergoing OTC before ASCT. MRD was assessed using patient-specific clonal markers via droplet digital polymerase chain reaction on DNA and RNA from bone marrow (BM), ovarian cortex and medulla. At CR, MRD-DNA was detected in ovarian cortex of four of nine patients, all with concurrent MRD positivity in BM. Three patients were negative in both BM and ovarian tissue. Paired cortex/medulla analyses showed concordant MRD-DNA results in five of six patients. BM MRD-RNA and MRD-DNA were fully concordant, whereas two discrepancies were observed between MRD-DNA and MRD-RNA in ovarian tissue. These findings suggest potential leukaemic cell persistence in ovarian tissue despite CR and highlight the need for sensitive molecular assays to assess safety prior to ovarian tissue transplantation.

Girls and women with bleeding disorders (GWBD) comprise more than half of all registered patients with bleeding disorders in the UK National Haemophilia Database. The gynaecological care of GWBD, until recently, has not been prioritised despite high health burdens, where four of every five patients experience heavy menstrual bleeding (HMB). We report the results of a national survey exploring gynaecological health-care services offered across haemophilia centres in the United Kingdom, with a focus on HMB. We combine these results with a retrospective cohort analysis of individual patient care records, across a 3-year period. Of 65 haemophilia centres, 41 responded, covering 90% of the UK GWBD population. Six hundred and ninety-seven individual patient care records were included, from 13 centres. Our results show that immediate clinical care offered to GWBD experiencing HMB is adequate, despite infrastructure deficiencies (such as lack of joint-gynaecology input and few centres having named clinical leads for GWBD). We recommend several areas for immediate prioritisation within haemophilia centres which will improve the equity of care for GWBD. These include direct access to gynaecological services; universal testing of iron status; and more broadly, a shift towards clinical practices that recognise and address the impact HMB has on patients' psycho-social, sexual and overall quality of life.

The British Osteonecrosis Study (BONES) is the first multicentre prospective study assessing bone health and vertebral fractures in patients aged 10-24 in the United Kingdom undergoing treatment for acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma (LBL). Sixty-one patients were recruited from three tertiary centres in the United Kingdom. Dual-energy X-ray absorptiometry (DXA) scans with vertebral fracture analysis were performed within 4 weeks of diagnosis and annually for 3 years. Subjective pain assessments were performed at the same time points. Bone mineral density (assessing total body less head (TBLH)) significantly reduced after 2 years, compared to baseline (estimate = -0.964, 95% CI [-1.357, -0.572]), with the greatest decrease occurring within the first year. Vertebral fracture prevalence was 4.9%, with two further patients experiencing incident vertebral fractures. All vertebral fractures occurred in male patients, 75% of whom were British Asian. Back pain was not a predictor of low bone mineral density (BMD) or vertebral fractures. We report a lower vertebral fracture prevalence in patients aged 10-24 with ALL than has been previously reported in a cohort of younger patients. Male British Asian patients appeared to be at higher risk of vertebral fractures in our study. BMD and pain were not predictors of vertebral fractures.

The response to salvage chemotherapy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor, and data on circulating tumour deoxyribonucleic acid (ctDNA) in this setting are limited. We evaluated ctDNA dynamics in 29 patients with relapsed or refractory DLBCL who received platinum-based salvage chemotherapy at the University Medical Center Groningen. In total, 124 plasma samples were analysed using low-coverage whole-genome sequencing to detect copy number alterations (CNAs) and targeted sequencing with a 115-gene panel for single- and multi-nucleotide variants (SNVs/MNVs). The complete response rate at the end of treatment was 55%, with a 1-year progression-free survival of 31%. At the R/R baseline, defined as the time after confirmation of relapse or refractory status and prior to initiation of salvage chemotherapy, CNAs were detected in 15 patients, SNVs in 27 and MNVs in 21. Patients with treatment failure had higher fraction of genome altered (FGA) and ctDNA levels at baseline. Low FGA combined with low metabolic tumour volume (MTV) at baseline was associated with favourable outcome. Clearance of all baseline SNVs at interim evaluation correlated with improved response, while persistence predicted failure (p < 0.05). Two of three patients with complete metabolic response at the end of treatment and detectable ctDNA relapsed, indicating ctDNA as a sensitive marker of minimal residual disease. These findings indicate the value of ctDNA profiling as a prognostic biomarker and as a tool for response-adapted treatment strategies in R/R DLBCL.