Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra rare haematological disorder. This study aimed to estimate the clinical burden, healthcare resource use (HCRU) and associated costs of cTTP in England usi...Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra rare haematological disorder. This study aimed to estimate the clinical burden, healthcare resource use (HCRU) and associated costs of cTTP in England using primary and secondary care data. A retrospective cohort study was undertaken using the Clinical Practice Research Datalink (Aurum) linked to Hospital Episode Statistics data. The study period was from 01 January 2000 to 31 December 2019. Patients with cTTP were identified using an algorithm and matched 1:2 to patients without thrombotic thrombocytopenic purpura (TTP) (non-TTP cohort) to contextualise the findings. A total of 36 cTTP patients were identified. The mean follow-up for cTTP patients was 4.4 and 5.7 years in primary and secondary care, respectively, and 4.9 and 5.8 years for the non-TTP cohort. Of the 36 patients, 38.9% experienced an acute episode and 19.4% experienced an organ damage event during follow-up. HCRU (including inpatient admission, outpatient appointments and primary care appointments) was higher in the cTTP cohort relative to the non-TTP cohort. The average yearly cost of healthcare for a cTTP patient was £6155, relative to £858 in the non-TTP cohort. This study demonstrates the high clinical and economic burden of cTTP and provides evidence to inform healthcare planning.
AL amyloidosis is caused by a plasma cell clone that produces abnormal light chains that misfold and deposit as amyloid fibrils in tissues and thus affect organ function. The survival of patients with systemic amyloid li...AL amyloidosis is caused by a plasma cell clone that produces abnormal light chains that misfold and deposit as amyloid fibrils in tissues and thus affect organ function. The survival of patients with systemic amyloid light-chain (AL) amyloidosis largely depends on the extent of end-organ damage. Patients with early-stage disease can expect approximately 80% survival at 5 years with contemporary treatment, compared to less than 30% for those with advanced disease. The aim of this guideline is to facilitate recognition and raise suspicion of amyloidosis. It is important to recognise that amyloidosis can present in any clinic, including general medicine/care of the elderly and general practice.
Bobin A, Macro M, Touzeau C
… +13 more, Mariette C, Manier S, Brechignac S, Vincent L, Hebraud B, Decaux O, Schulman S, Lenoir C, Godmer P, Parienti JJ, Paul LPS, Briant A, Leleu X
The combination of CD38 immunotherapy and proteasome inhibition has shown synergistic activity. Elderly relapsed or refractory multiple myeloma (RRMM) experience worse outcomes due to variabilities in fitness and higher...The combination of CD38 immunotherapy and proteasome inhibition has shown synergistic activity. Elderly relapsed or refractory multiple myeloma (RRMM) experience worse outcomes due to variabilities in fitness and higher rates of adverse events (AEs) and treatment discontinuations. The Intergroupe Francophone du Myélome (IFM) 2018-02 trial (NCT03757221) evaluated a dexamethasone-free regimen of daratumumab and ixazomib (I-Dara) in elderly frail RRMM. This prospective, phase 2 trial was conducted at 14 IFM centres. Patients aged ≥65 years with International Myeloma Working Group frailty score ≥2 and an Eastern Cooperative Oncology Group 0-2 in first or second relapse received daratumumab 16 mg/kg; ixazomib 4 mg weekly d1, d8, d15 in a 28-day cycle; and methylprednisolone. The primary end-point was ≥ very good partial response (VGPR) rate. Of 55 patients included, the median age was 82 years, with 90% aged over 75. VGPR or better was 32%. With a median follow-up of 35.3 months, the median progression-free survival time was 19.5 months. The median OS was not reached: 75% at 33.6 months. Grade ≥3 AEs occurred in 36 (67%) patients: cytopenias in 18 and infection in 8 (6 pneumonia). The IFM 2018-02 shows that I-Dara demonstrated an acceptable safety profile for this elderly frail RRMM patients' population. The response rates and survival outcomes were acceptable given the studied population.
Vazquez R, Deredec N, Boussaid I
… +16 more, Boncoeur P, Knosp C, Houvert A, Zalmai L, Friedrich C, Almire C, Dussiau C, Willems L, Birsen R, Decroocq J, Bouscary D, Kosmider O, Kordasti S, Fontenay M, Simoni Y, Chapuis N
Br J Haematol
· 2026 Jun · PMID 42080308
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Dynamic interactions between mutated haematopoietic cells and immune cells are key drivers of myelodysplastic neoplasms (MDS) initiation and progression. Regulatory T cells (Tregs) are central mediators of immunosuppress...Dynamic interactions between mutated haematopoietic cells and immune cells are key drivers of myelodysplastic neoplasms (MDS) initiation and progression. Regulatory T cells (Tregs) are central mediators of immunosuppression in MDS. We thus aimed to characterize Treg subpopulations in the bone marrow (BM) of MDS patients and to explore their clinical significance. Using mass cytometry and an unbiased multidimensional analytical approach, we first confirmed the presence in MDS BM of two Treg subsets, including the highly activated CD95/CD45RA subpopulation previously reported in aplastic anaemia. We then prospectively analysed Tregs distribution in BM of 113 MDS patients at diagnosis and during follow-up. While Treg proportions among CD4 T cells were unchanged, CD95/CD45RA Tregs were significantly expanded in the BM of both low- and high-risk MDS patients. CD95/CD45RA Tregs accumulated during disease evolution but remained stable in patients responding to hypomethylating agents. At diagnosis, CD95/CD45RA Tregs levels correlated with specific clinical features: low CD95/CD45RA Tregs with TET2/IDH mutations and autoimmune manifestations; high CD95/CD45RA Tregs with an increased risk of disease progression independently of the IPSS-R and the IPSS-M. Our findings suggest that profiling Treg subpopulations at diagnosis could improve MDS risk stratification and guide immunosuppressive therapeutic decisions.
Sickle cell disease (SCD), a prevalent inherited non-communicable disease, remains a neglected public health priority, especially children and adolescents in many low- and middle-income countries. The global burden of SC...Sickle cell disease (SCD), a prevalent inherited non-communicable disease, remains a neglected public health priority, especially children and adolescents in many low- and middle-income countries. The global burden of SCD in youth remains under-characterized given fragmented data and disparities in diagnostics. This study aims to conduct a systematic review and meta-analysis quantifying the global prevalence and cause-specific mortality of SCD in individuals aged under-5 and under-20. A search was conducted to identify studies reporting SCD prevalence or mortality published between 2017 and 2023. Eligible studies were assessed for quality and random-effects meta-analyses generated pooled estimates, stratified by age group, study design and United Nations country group classification. Fifty-seven studies were included, encompassing data from over 3.6 million individuals and 56 593 recorded deaths. Among children under-5, the prevalence was 0.008 (95% confidence interval [CI]: 0.004-0.016). The global under-20 population-based prevalence of SCD was 0.009 (95% CI: 0.005-0.017). The global under-20 cause-specific mortality proportion was 0.029 (95% CI: 0.001-0.621), with under-5 and 5-19 years of age mortality proportions estimated at 0.021 and 0.017, respectively. This first global synthesis of under-5s and under-20s demonstrates substantial paediatric burden but is constrained by extreme heterogeneity, wide uncertainty and incomplete geographic coverage, underscoring the urgency for improved screening, surveillance and cause-of-death attribution to support accurate global burden estimation of SCD.
Rampotas A, Naylor-Layland G, Brown C
… +33 more, Alabdulkarim A, Ryan J, Wadelin F, Alimam S, Tun PWW, Lambert J, O'Sullivan J, Wilson AJ, Tafesh L, McGregor A, Claudiani S, Innes A, Booth E, Leveson J, Knapper S, Garg M, Dubey M, Vatopoulou T, Brierley C, Leung WKN, Greenfield G, McMullin MF, Khan A, Milne K, Brian D, Godfrey A, Harrison CN, Psaila B, Harrington P, Kirkwood A, Somervaille TCP, McLornan DP, UK Blood Cancer Research Network MPN Clinical Study Group
This UK-based retrospective analysis describes real-world treatment patterns and outcomes in 175 patients with accelerated (AP, n = 69) or blast-phase (BP, n = 106) 'Philadelphia-negative' myeloproliferative neoplasms (M...This UK-based retrospective analysis describes real-world treatment patterns and outcomes in 175 patients with accelerated (AP, n = 69) or blast-phase (BP, n = 106) 'Philadelphia-negative' myeloproliferative neoplasms (MPN-AP/BP) diagnosed between 2013 and 2025. Median age at transformation was 71 years. With a median follow-up of 45.2 months, median overall survival (OS) was 14.9 months, significantly worse for MPN-BP (6.7 months) versus MPN-AP (25.3 months). Treatment selection was heterogeneous across centres. Intensive chemotherapy (IC) improved outcomes only when followed by allogeneic haematopoietic stem cell transplant (allo-HSCT) (median OS 24.7 months). Ruxolitinib-based regimens, particularly combined with azacitidine, showed acceptable activity in AP (median OS 27.2 months). Venetoclax-based regimens achieved a median OS of 14.9 months across the cohort. Multivariable analysis identified IC and venetoclax-based therapy as independently associated with better outcomes, reflecting patient selection, while TP53 mutations predicted inferior survival. IC carried high rates of febrile neutropenia and sepsis; venetoclax was associated with prolonged cytopenias. This study confirms the poor prognosis of MPN-AP/BP, the absence of a unified UK consensus approach and the need for improved therapies and prospective studies to determine optimal treatment approaches for this challenging cohort.
Xue Y, Zhang R, Liang D
… +8 more, Xu Y, Tian Z, Dai X, Xu W, Cao Q, Zhu H, Wang Y, Yuan Y
Br J Haematol
· 2026 Jun · PMID 42070774
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This study aimed to develop prediction models for chronic immune thrombocytopenia (ITP) using a sex-stratified proteomic and metabolomic approach, providing a framework for individualized prognosis evaluation and timely...This study aimed to develop prediction models for chronic immune thrombocytopenia (ITP) using a sex-stratified proteomic and metabolomic approach, providing a framework for individualized prognosis evaluation and timely clinical management. This investigation was designed as a non-interventional, prospective observational cohort. Plasma samples were collected from 67 children initially diagnosed with ITP along with 40 healthy controls. After a minimum of 1 year of regular follow-up, participants were classified according to sex and disease progression. The male and female cohorts each comprised individuals with chronic ITP, non-chronic ITP and healthy controls. From each subgroup, three peripheral blood samples were randomly chosen for proteomic and metabolomic profiling. Integrative omics were analysed for correlations using Pearson's coefficient (threshold: |r| > 0.8, p < 0.05). Predictive models were constructed using sex-specific biomarkers associated with chronic progression. The analysis identified intercellular adhesion molecule-1 (ICAM-1) and biopterin in males and actin, alpha 2, smooth muscle, aorta (ACTA-2) and N6-acetyl-L-lysine in females as associated factors. Cross-sex applications of these biomarkers revealed limited predictive value. Furthermore, the receiver operating characteristics curves, calibration curves and clinical decision curve analysis demonstrated good predictive efficacy of these predictive models. The underlying mechanisms of interaction between these biomarkers, sex differences and ITP chronicity progression warrant further investigation.
Cornago J, Baile M, Acera M
… +28 more, Fox L, Del Mar Pérez-Artigas M, Santamaría A, Del Carmen Quintela M, Sánchez-Salinas A, Salmerón JM, Illana V, Abdallahi-Lefdil Z, Pardo L, Solán L, López-Lorenzo JL, Fernández-Luis S, Vega LP, Villar S, Beorlegui-Murillo P, Molina M, Esquirol A, Izquierdo I, Ribes J, Mussetti A, Lavilla E, Alda O, López-Marín J, Bento L, Filaferro S, Balsalobre P, Sureda A, Salas MQ
This prospective study evaluated the incidence and dynamics of frailty in 156 adults with lymphoproliferative syndromes undergoing autologous haematopoietic stem cell transplantation (HSCT). Frailty was assessed using th...This prospective study evaluated the incidence and dynamics of frailty in 156 adults with lymphoproliferative syndromes undergoing autologous haematopoietic stem cell transplantation (HSCT). Frailty was assessed using the haematopoietic cell transplantation (HCT) frailty scale in patients from 15 Spanish institutions at initial consultation, transplant admission and day +100. Quality of life (QoL) was measured using the EuroQoL. At first consultation, 45 patients (28.8%) were classified as fit, 93 (59.6%) as pre-frail and 18 (11.6%) as frail. Frailty was more frequent among older patients, those with Karnofsky performance status (KPS) below 90%, and abnormal Mini-Cog scores (<3). Rates of relapse, death, readmission and median hospital stay were similar across frailty groups. However, frail patients reported significantly worse QoL. One-year non-relapse mortality was higher in frail patients than in pre-frail and fit patients, although differences were not statistically significant (p = 0.19). At day +100, 33.6% of patients were fit, 57.9% pre-frail and 8.5% frail, demonstrating significant transitions in frailty over time (p = 0.001). Moreover, frail patients showed lower relapse-free [53.3% (17.7-79.6) vs. 85.3% (68.3-93.6), p = 0.05] and overall survival [77.8% (36.5-93.9) vs. 100%, p = 0.16], and worse perceived QoL than fit ones. Overall, frailty was dynamic and clinically relevant, supporting routine assessment and targeted interventions to mitigate adverse outcomes.
Zhang X, Shah BN, Han J
… +6 more, Nouraie M, Zhang Y, Machado RF, Gladwin MT, Saraf SL, Gordeuk VR
Br J Haematol
· 2026 Apr · PMID 42052798
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Elevated erythropoietin (EPO) concentration associates with thrombotic risk in hypoxic conditions, hereditary erythrocytosis and treatment of anaemia with recombinant EPO. We evaluated sickle cell disease (SCD) patients...Elevated erythropoietin (EPO) concentration associates with thrombotic risk in hypoxic conditions, hereditary erythrocytosis and treatment of anaemia with recombinant EPO. We evaluated sickle cell disease (SCD) patients from the University of Illinois at Chicago (UIC) and the Treatment of Pulmonary Hypertension and SCD with Sildenafil Therapy (Walk-PHaSST) study and found that higher serum EPO concentration associated with increased thromboembolic risk (combined odds ratio [OR] = 1.9, p = 0.0029, N = 557). Percent haemoglobin F and haemoglobin concentration strongly correlated with EPO concentration in SCD, and the haemoglobin F locus BCL11A affected EPO concentration through percent haemoglobin F. In peripheral blood mononuclear cells from 159 UIC patients, we identified an expression quantitative trait locus for EPOR encoding EPO receptor, in which the G allele of rs322139 associated with higher EPOR expression (β = 0.055, p = 2.0 × 10). This G allele associated with lower EPO concentration in Walk-PHaSST (β = -0.23, p = 6.4 × 10, N = 327) and UIC (β = -0.18, p = 0.017, N = 179), but not in normal populations. The G allele of rs322139 also associated with a trend to decreased thromboembolism (combined OR = 0.64, p = 0.054, N = 665). In summary, our study indicates that higher serum EPO concentration associates with thromboembolic risk in SCD and reveals a novel role of EPOR expression variation in modulating EPO concentration and, possibly, thromboembolic risk in this condition.
González de Pablo J, Molina YL, Vicario JL
… +10 more, Moreno Hidalgo MÁ, de la Cruz A, Galán A, Zubicaray J, López de Hontanar G, Sanz A, Marín L, Verdejo de Antonio J, Sevilla J, Sebastián E
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated low platelet counts. Although several studies have explored the relationship between the human leucocyte antigen (HLA) system and ITP, fin...Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated low platelet counts. Although several studies have explored the relationship between the human leucocyte antigen (HLA) system and ITP, findings have been inconsistent. We compared HLA typing between paediatric ITP patients and healthy controls to assess its role in ITP susceptibility. We also evaluated the association between HLA alleles and clinical outcomes in our paediatric ITP cohort. This retrospective observational study included 135 patients with primary ITP and a control group of 929 healthy individuals. The median age of ITP patients was 5.71 years (Interquartile range 2.71-10.21). The HLA-DRB1*07 and HLA-DRB1*13 alleles were more prevalent in healthy controls than in ITP patients, suggesting a potential protective role (p < 0.05). In contrast, HLA-A*68, HLA-B*40 and HLA-DRB1*14 alleles were associated with an increased risk of ITP (p < 0.05). Regarding prognosis, HLA-A*26 allele correlated with lower recovery rates, while HLA-C*03 allele was associated with a higher recovery likelihood (p < 0.05). In addition, HLA-A*02 and HLA-C*04 alleles and the HLA-A02 supertype showed a significant association with a higher probability of chronicity (p < 0.05). Our results highlight the potential role of HLA typing as a diagnostic and prognostic tool for ITP. However, larger studies are required to validate these associations.