British Journal of Haematology最新文献

Left panel: Scheme of the XPAG-immune thrombocytopenia trial. The dexamethasone (DEX) arm consisted of DEX 40 mg/day for days 1-4 for one to three cycles every 28 days to a maximum of 12 weeks, cycles 2 + 3 were optional. Patients randomised to eltrombopag (ETB) + DEX received eltrombopag in combination with a short course of high-dose DEX beginning on day 1 (40 mg/day during days 1-4). The starting dose of ETB was 50 mg/day for 2 weeks; thereafter, the ETB dose was increased by 25 mg for all patients who did not achieve the target platelet count of ≥50 × 10⁹/L. The ETB tapering was performed by decreasing the dose by 25 mg every 2 weeks to a minimum dose of 25 mg every other day for all patients. Right upper panel: Clinical outcomes in patients treated with first-line ETB + DEX. Patients displayed a qualitatively longer response duration and qualitatively reduced usage of rescue medication. Right lower panel: The immunological T-cell response was different in treatment responders and non-responders. Patients with sustained response (responders) displayed a high T-cell clonality at baseline. Clones are depicted as bubbles (right side).

The efficacy of a triple combination of rabbit anti-human thymocyte immunoglobulin (rATG), ciclosporin and eltrombopag (EPAG) was prospectively evaluated in patients with severe or transfusion-dependent non-severe aplastic anaemia (SAA) across 29 institutions in Japan. Sixty patients were enrolled, of whom 48 had SAA. The primary end-point, the haematological overall response rate at 12 weeks, was 52.6% (95% confidence interval, 39.0%-66.0%), increasing to 67.9% at 26 weeks. The most frequent grade 3/4 adverse event was febrile neutropenia (20.0%). One elderly patient with severe neutropenia died of sepsis. Progression to myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) was observed in one patient each. There was no association between the haematological response and high thrombopoietin levels, presence of paroxysmal nocturnal haemoglobinuria-type cells or Human Leukocyte Antigen (HLA) class I allele-lacking cells. Five patients (8.5%) had chromosomal abnormalities at baseline with no subsequent progression to MDS or AML. By 26 weeks, chromosomal abnormalities had emerged or expanded in eight patients (17.4%), although abnormalities of chromosome 7 were not observed within 52 weeks. These results suggest that triple therapy with rATG may be as effective as that with horse anti-human thymocyte immunoglobulin. Notably, the addition of EPAG did not induce chromosomal abnormalities associated with poor prognosis.

This review emphasises how studies on animal red cells have enriched our understanding of the behaviour of those from humans. For example, the pump-leak model for long-term volume stability is indebted to work on high potassium (HK)- and low potassium (LK)-containing sheep red cells. Studies in several species including trout have been useful for detailing how the co-ordinated behaviour of red cell transport proteins is involved in shorter term volume homeostasis and other functions. Our understanding of how protein phosphorylation pathways control the activity of the cation-chloride cotransporters has been given impetus by work in rabbit, sheep, trout and other species. Red cells from dogs and cats were historically important for developing theories on macromolecular crowding and cation permeability. Cattle red cells have helped substantiate that band 3 is not essential for red cell integrity. Work in many other species has informed our understanding of red cell physiology and a discussion of these areas illustrates how a comparative perspective has resoundingly enhanced and enriched our knowledge of human red cell physiology. A similar comparative approach to red cell pathophysiology is much less comprehensive although it has the potential to be invaluable for a better understanding of problems in humans.

Plasma direct oral anticoagulant (DOAC) levels are not routinely required for the majority of patients; however, they may provide valuable information in urgent clinical situations, including perioperative management, life- or limb-threatening bleeding and patients requiring thrombolysis, when measurement mostly aims to determine whether a clinically significant concentration of DOAC is present in plasma. In non-urgent indications, including investigation of DOAC failure and in patients with extremes of body weight or drug-drug interactions, levels may assist clinical decision-making by determining whether the plasma DOAC level is within expected therapeutic ranges. 'In a nut-shell' review, we summarise the current recommendations and limitations regarding testing DOAC levels.

Multirefractory immune thrombocytopenia (ITP) is difficult to manage. The simultaneous administration of an immunosuppressive/immunomodulatory drug (IS/IM) and a thrombopoietin receptor agonist (TPO-RA) is increasingly used. We present the experience of the Spanish ITP Group in this retrospective, observational study. Ninety-seven patients with ≥3 failed treatment lines were administered combination therapy (CT) with an IS/IM and a TPO-RA between January 2021 and December 2023. The IS/IMs were steroids, purine synthesis inhibitors and fostamatinib. The TPO-RAs were romiplostim, eltrombopag and avatrombopag. Seventy-five (77.3%) patients responded to treatment in a median (interquartile range [IQR]) time of 14 (7-52) days. An inverse correlation between previous failures and response was observed (Rho = -0.290, p = 0.009). After 840 (448-1054) days, relapse was reported in 35 (46.7%) of 75 responders (time to relapse: 197 [47-402] days). Relapse was more frequent in chronic ITP patients. Twenty-one patients received a second CT after failure of the first one. Eleven were administered a third CT for the same reason. Response and relapse were similar to those observed with the first CT. Three thromboembolic events and 14 infections that required hospitalization were reported, none fatal. The combination of IS/IMs and TPO-RAs arises as an alternative option of treatment in multirefractory ITP.

High-dose melphalan followed by autologous stem cell transplantation (ASCT) is the standard of care for eligible patients with newly diagnosed multiple myeloma (NDMM). A substantial proportion of patients are deemed ineligible for ASCT due to age, comorbidities, performance status and/or frailty. Criteria defining transplant ineligibility remain inconsistent and poorly characterized. We conducted a systematic review that assessed phase II, III and IV randomized controlled trials (RCTs) through March 2025. We included a total of 55 studies that enrolled transplant-ineligible/deferred NDMM patients. Among 55 transplant-ineligible trials, only 47% explicitly defined ineligibility criteria. Of these, 44% of trials used age as a cut-off with/without other criteria. Only two studies explicitly specified which comorbidities constituted transplant ineligibility. When age was utilized as a cut-off, age ≥65 was the most commonly used cut-off. The median age of participants in these trials ranged from 62 years to 78.5 years and showed a trend upwards over time (p = 0.1388). Performance status of enrolled patients was reported inconsistently. Frailty tools were reported in 22% of studies. RCTs enrolling transplant-ineligible patients with NDMM demonstrated considerable heterogeneity in defining ineligibility. While the decision to pursue ASCT remains individualized, the absence of evidence-based definitions of transplant ineligibility complicates research interpretation and clinical decision-making.

In this retrospective, multicentre cohort study, we compared the real-world efficacy of polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin and prednisone (Pola-R-CHP) versus the conventional rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in 370 patients in the propensity score matching cohort from 1096 patients with previously untreated diffuse large B-cell lymphoma (DLBCL) (pola; n = 185 in the matched and 356 in the full cohort). The analysis focused on clinical efficacy, the prognostic performance of established risk models and the relapse profiles with the chemotherapies. The Pola-R-CHP group showed superior 1-year progression-free survival (PFS) compared to the R-CHOP group (86.7% vs. 73.5%, p = 0.027); however, the 1-year overall survival (OS) was similar (92.8% vs. 89.6%, p = 0.24). Within the Pola-R-CHP group, the Central Nervous System International Prognostic Index (CNS-IPI) effectively stratified the cumulative incidence of CNS relapse of 0%, 2.1% and 4.5% in the low, intermediate and high-risk groups respectively (p = 0.023). Additionally, the 1-year incidence of nodal relapse was significantly lower in the Pola-R-CHP group than in the R-CHOP group (2.1% vs. 10.9%, p = 0.013), whereas the incidence of extra-nodal relapse remained similar (3.8% vs. 5.2%, p = 0.57). These findings underscore the clinical efficacy of Pola-R-CHP over R-CHOP in first-line DLBCL treatment. However, early extra-nodal relapse and CNS relapse remained a therapeutic challenge.

Despite evidence-based guidelines to inform platelet transfusion practice, unnecessary platelet transfusion persists. We performed a multicentre retrospective analysis of adults admitted to general medicine, subspecialty medicine and critical care from 1 January 2017 to 30 June 2022. Platelet transfusion guideline compliance was defined as platelet transfusion below 100 × 10⁹/L for neurosurgical, cardiac surgery or extracorporeal membrane oxygenation indications, below 50 × 10⁹/L for invasive procedures, bleeding or therapeutic anticoagulation, and below 10 × 10⁹/L if the patient did not have an immune-mediated thrombocytopenia. We analysed 821 950 patient admissions at 22 hospital sites, identifying 56 825 platelet transfusion events. Overall, 13 199 (23.2%) platelet transfusion events were guideline-non-compliant. High rates of non-compliant transfusions were observed in the context of anti-platelet therapy (n = 1515, 48.5% non-compliant), cardiac surgery (n = 1935, 49.7%), invasive procedures (n = 4648, 29.2%), immune-mediated thrombocytopenia (n = 596, 32.9%) and primary prophylaxis (n = 7370, 47.2%). After adjusting for physician characteristics, there was a lower risk of guideline-non-compliant platelet transfusions at academic than at community hospitals (odds ratio [OR] 0.768, 95% confidence interval [CI] 0.678-0.871, p < 0.001). Physician specialty, but not physician gender or years in practice, influenced guideline compliance. These findings underscore the need for targeted intervention to optimize platelet transfusion practices, minimize avoidable transfusion reactions, reduce costs and mitigate platelet shortages.