British Journal of Haematology最新文献

Warm autoimmune haemolytic anaemia (wAIHA) is an acquired autoimmune disorder caused by autoantibodies-primarily immunoglobulin G (IgG)-that bind to red blood cells and trigger haemolysis. It can be primary or secondary to associated conditions. This nutshell review summarizes pathophysiology, diagnostic workup, prognosis and treatment options.

Hepatitis-associated aplastic anaemia is a rare entity that can sometimes be life-threatening due to its rapid progression to liver failure, necessitating an urgent liver transplantation (LT). Treating severe aplastic anaemia following an LT can be very challenging. While immunosuppressive therapy (IST) has been reported to have some success, the vulnerable state of these patients in addition to the time taken for IST to work makes this a less suitable option for the majority of patients. Haematopoietic stem cell transplantation (HSCT) with matched related donors has been reported as a curative option; there has been less success using alternate donors. Here, we present our experience of predominantly alternate donor HSCT following liver transplantation in an extremely high-risk group of 10 children. Overall survival was 90% at a median of 38 months post-LT. Surviving children have normal blood counts, normal liver function and performance status. No liver-related complications or significant graft versus host disease were encountered. Multiple infective and non-infective post-HSCT complications were successfully treated with excellent multidisciplinary input. Upfront HSCT, even with alternate donors, can be lifesaving if performed in a timely manner, following close liaison between liver transplantation and HSCT teams and with the appropriate multidisciplinary support.

Identifying chronic myeloid leukaemia (CML) patients at risk of therapeutic switch remains debated. We analysed the cumulative risk of treatment change in the CML Italian network prospective cohort based on first-line tyrosine kinase inhibitors and patient characteristics. Sub-hazard ratios (sHRs) were estimated using Fine and Gray multivariable models. Among 1662 patients, initial treatment consisted of imatinib for 840 (50.5%), nilotinib for 490 (29.5%) and dasatinib for 332 (20.0%). Subsequently, 492 patients (29.6%) required second-line therapy, with 232 (47.1%) switching due to resistance and 176 (35.8%) due to intolerance. At 2 years, the risk of resistance was 18.3% for imatinib, 8.4% for dasatinib (sHR = 0.32; 95% confidence interval 0.21-0.49) and 6.8% for nilotinib (0.29; 0.19-0.42). The risk of switching increased in intermediate (1.95; 1.40-2.72) and high Eutos long term survival (ELTS) risk (3.19; 2.10-4.83) but was reduced with older age (0.97 per year; p < 0.0001). Intolerance at 2 years was 8.5% for imatinib, 12.4% for dasatinib (2.55; 1.73-3.75) and 5.2% for nilotinib (1.04; 0.65-1.65). Switching to a third-line therapy at 3 years was 8% for imatinib, 5% for dasatinib and 4% for nilotinib. The results showed that the time to first treatment switch for resistance is shorter for younger patients, for imatinib and for intermediate/high ELTS risks. The risk of switching for intolerance is higher for patients initially treated with dasatinib.

Sickle cell disease (SCD) and its treatments may lead to gonadal dysfunction. Limited research has examined how these effects translate into actual fertility outcomes and family-building perspectives. We aimed to determine the frequency of infertility and to examine family-building goals, knowledge and concerns among 91 adults with SCD from The Ohio State University Wexner Medical Center SCD clinic. Participants completed surveys capturing their demographic and medical information. Fertility status and family-building perspectives were measured using modified versions of surveys used in fertility-related literature in other populations. Descriptive statistics summarized demographics, frequency of infertility and family-building perspectives. Most participants expressed a desire for children. Approximately half met the clinical definition of infertility at some point, but only a few who met this definition had knowledge of it. Lastly, most reported low to moderate fertility and reproductive concerns potentially due to lack of awareness about their infertility status. These findings underscore the need to increase infertility education and counselling for individuals with SCD.

Excisional lymph node biopsy remains the gold standard for lymphoma diagnosis, yet the optimal timing is often overlooked. In this study, two cases illustrating delays caused by reliance on imaging and fine-needle aspiration, emphasizing histopathology and clinical suspicion for timely diagnosis, were reported.

More than half of patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL) experience progression after chimeric antigen receptor (CAR) T-cell therapy, and subsequent treatment options remain limited with poor outcomes. Despite the need for effective therapies in this setting, post-CAR T clinical trial enrolment is low. We conducted a single-centre study of patients with r/r LBCL who progressed after CAR T-cell therapy between January 2018 and September 2023 to describe the practice patterns and identify factors associated with clinical trial participation. Patient, disease and clinical characteristics were analysed across screening, enrolment and treatment phases. Among 166 patients who progressed after CAR T-cell therapy, 39% were screened, 23% enrolled and 22% ultimately received trial treatment. High-risk clinical features, including eastern cooperative oncology group (ECOG) performance status ≥2, stage IV disease, high-risk International Prognostic Index, incomplete response to CAR T-cell therapy and severe cytokine release syndrome, were associated with non-participation. Using the eligibility criteria of pivotal trials that led to FDA approval of novel agents, only 14%-36% of patients who had relapsed disease after CAR T-cell therapy were eligible for these trials. The study highlights the unmet need to develop trials that accommodate high-risk populations to reduce barriers to trial participation following CAR T-cell therapy failure.

Microvascular, inflammatory and myelin pathologies may contribute to chemotherapy-related cognitive impairment (CRCI). This study applied a novel three-compartment intravoxel incoherent motion-free water imaging (IVIM-FWI) technique that estimates the perfusion fraction (PF), free water fraction (FW) and anisotropic diffusion of tissue (FAt) to study microvascular and microstructural changes in grey and white matter regions in 16 cancer survivor (CS) participants compared to 15 matched healthy controls (HCs). We found significantly decreased PF and increased FW in grey and white matter regions and significantly decreased FAt in white matter regions in the CS versus HC group. These changes were located in key regions involved in emotion, cognition and sensory processing. Furthermore, in both groups, decreased FAt and varying changes in PF and FW were significantly associated with poor performance on cognitive tests assessing general cognitive ability, fluid intelligence, inhibition and processing speed. Overall, the three-compartment IVIM-FWI model provides neuroinflammation, myelination and microvascular metrics that may be related to CRCI pathologies and are associated with cognition. This approach may facilitate targeted interventions aimed at preserving cognitive function and improving overall quality of life for paediatric haematological cancer survivors.

Alemtuzumab in vivo T-cell depletion is safe and effective at a single dose of 30 mg in reduced-intensity matched unrelated donor transplants.