Marchisio S, Yakymiv Y, Lin L
… +12 more, Ortolan E, Pullano V, Ponti R, de Bie FJ, van der Sluijs-Gelling AJ, Zoutman WH, Pala V, Scheeren FA, Vermeer MH, Funaro A, Quaglino P, Roccuzzo G
Sézary syndrome (SS) is an aggressive cutaneous T-cell lymphoma, characterized by erythroderma, lymphadenopathy and circulating malignant CD4 T cells. Despite therapeutic advances, SS remains an incurable disease. Early...Sézary syndrome (SS) is an aggressive cutaneous T-cell lymphoma, characterized by erythroderma, lymphadenopathy and circulating malignant CD4 T cells. Despite therapeutic advances, SS remains an incurable disease. Early diagnosis is therefore essential for timely therapeutic intervention; however, reliable biomarkers to identify circulating SS cells are still lacking. Recent studies highlighted dysregulation of the ectoenzymes CD39, CD73 and CD38 in SS, suggesting a potential role for these molecules in the disease. Thirty-three patients were enrolled in this study, and CD39/CD73/CD38 expression was analysed on circulating CD4 T cells by multiparametric flow cytometry, enabling discrimination between malignant and non-malignant T-cell subsets. SS cells exhibited marked CD39 or CD73 overexpression together with consistent CD38 downregulation, a pattern also confirmed in paired skin biopsy, whereas non-malignant CD4 T cells largely maintained expression profiles comparable to healthy controls. Genotyping further identified ENTPD1 single nucleotide polymorphism rs10748643 as a contributor to CD39 dysregulation, defining a CD39-permissive subgroup characterized by CD39 SS cells. In conclusion, the combined overexpression of CD39 or CD73 and loss of CD38 defines a distinct tumour-restricted immunophenotypic signature in SS. Integrating these ectoenzymes into flow cytometry panels may improve detection of malignant CD4 T cells across blood and skin, eventually strengthening diagnostic accuracy.
Ishida H, Okamoto Y, Sakaguchi H
… +22 more, Arai Y, Ueda T, Yamamoto S, Yano M, Yokosuka T, Okada K, Sato M, Karakawa S, Kobayashi R, Kato K, Koh K, Fujiki T, Goi K, Saito S, Takita J, Miyamura T, Koga Y, Yoshida N, Sato A, Hino M, Tabuchi K, Arakawa Y
Down syndrome-associated acute lymphoblastic leukaemia (DS-ALL) is associated with inferior outcomes compared with non-DS-ALL; however, data on haematopoietic stem cell transplantation (HSCT) in DS-ALL remain limited. We...Down syndrome-associated acute lymphoblastic leukaemia (DS-ALL) is associated with inferior outcomes compared with non-DS-ALL; however, data on haematopoietic stem cell transplantation (HSCT) in DS-ALL remain limited. We analysed nationwide data of patients aged <30 years with B-cell precursor ALL who underwent first allogeneic HSCT between 2000 and 2022 in Japan. In total, 56 patients with DS-ALL and 3873 with non-DS-ALL were identified. The incidences of neutrophil engraftment, grade II-IV acute graft-versus-host disease and chronic graft-versus-host disease were comparable between groups. The 4-year event-free survival (EFS) was lower in DS-ALL than in non-DS-ALL (40.3% vs. 55.2%), but was similar when stratified by disease status at HSCT. The 4-year EFS rates in first and second complete remission (CR) were 62.7% and 48.2% in DS-ALL and 69.5% and 56.0% in non-DS-ALL respectively. Relapse, rather than non-relapse mortality (NRM), was the leading cause of treatment failure in DS-ALL. Among patients with DS-ALL undergoing HSCT in CR1/2, myeloablative conditioning (MAC) showed a trend towards superior EFS compared with reduced-intensity conditioning (RIC), which was associated with a higher incidence of NRM. Accordingly, patients in CR1/2 who are unable to tolerate MAC are considered good candidates for emerging novel therapies rather than RIC-HSCT.
Standard first-line therapy with dexamethasone requires further optimization due to unsatisfying long-term outcomes in patients with primary immune thrombocytopenia (ITP). Previous research suggested that glycyrrhizinate...Standard first-line therapy with dexamethasone requires further optimization due to unsatisfying long-term outcomes in patients with primary immune thrombocytopenia (ITP). Previous research suggested that glycyrrhizinate induces platelet responses in ITP murine models. This study aimed to compare the efficacy and safety of dexamethasone plus glycyrrhizinate with dexamethasone in patients with newly diagnosed ITP. Eligible patients aged ≥18 years with newly diagnosed, treatment-naïve ITP who had baseline platelet count of <30 × 10/L were enrolled during routine outpatient visits. Recruited patients were randomly assigned 1:1 to receive either dexamethasone plus glycyrrhizinate (n = 55) or dexamethasone (n = 56). The modified intention-to-treat analysis included 96 patients (48 vs. 48) who received at least one dose of allocated treatments. The primary end-point overall response, defined as a platelet count of ≥30 × 10/L, at least doubling of baseline platelet count and no bleeding, was reached in more patients in combination group [56.25% (27/48)] than that in the monotherapy group [31.25% (15/48)] at month 6 (*p = 0.0231), with a longer duration of response, but not at day 14. The most common treatment-emergent adverse events were gastrointestinal reactions and anxiety. No grade 3-5 adverse events or deaths occurred. Dexamethasone plus glycyrrhizinate was an optimized initial therapy in ITP (NCT05023915).
Classical cytogenetics (CC) encompassing fluorescence in situ hybridisation (FISH) and karyotype remains central to the diagnostic work-up of non-Hodgkin lymphoma (NHL). However, karyotype is limited by restricted access...Classical cytogenetics (CC) encompassing fluorescence in situ hybridisation (FISH) and karyotype remains central to the diagnostic work-up of non-Hodgkin lymphoma (NHL). However, karyotype is limited by restricted access to fresh tumour tissue and low resolution, while FISH provides targeted information. Optical genome mapping (OGM) has emerged as a genome-wide, high-resolution approach capable of detecting both translocations and copy number variations in a single assay. To assess its feasibility and diagnostic performance in routine practice, we prospectively compared OGM to CC in 105 patients with NHL. OGM was technically feasible in both fresh and frozen tissue specimens. Among 511 cytogenetic abnormalities (CAs) directly compared, 91.1% were concordant between the two methods. Using the low allele fraction guided assembly pipeline, OGM identified all 77 immunoglobulin loci rearrangements, with a sensitivity threshold of 5%. Overall, OGM detected diagnostically relevant CAs in 99/105 patients (94.2%). OGM outperformed CC in 10/105 patients (9.5%), revealing cryptic rearrangements involving major target genes (MYC, BCL2 and BCL6) as well as diagnostically relevant CAs in cases with uncertain diagnoses or non-informative karyotypes. In conclusion, OGM demonstrated feasibility in routine practice and superior diagnostic performance compared with CC, supporting its integration into the standard genetic work-up of NHL.
Frutos Díaz-Alejo J, Díaz de la Pinta FJ, Pavía Pascual L
… +9 more, Manso R, Morillo D, Moreno-Delgado M, García-Cosío M, García-Hernández S, García Fernández E, Rebollo-González M, Rodríguez M, Rodríguez Pinilla SM
T-lymphoblastic lymphoma (T-LBL) is an aggressive malignancy with a high relapse risk despite intensive therapy. The optimal transplant strategy remains uncertain. We retrospectively analysed 81 patients with T-LBL under...T-lymphoblastic lymphoma (T-LBL) is an aggressive malignancy with a high relapse risk despite intensive therapy. The optimal transplant strategy remains uncertain. We retrospectively analysed 81 patients with T-LBL undergoing haematopoietic stem cell transplantation (HSCT) (59 allogeneic [allo-HSCT] and 22 autologous [auto-HSCT]). Survival outcomes were evaluated using Kaplan-Meier and competing-risk methods. Multivariable Cox regression, propensity score matching and landmark analyses at 12 months were performed. At 3 years, overall survival (OS) was comparable between allo-HSCT and auto-HSCT (76.0% vs. 77.0%; p = 0.890), while progression-free survival (PFS) was numerically higher following allo-HSCT (77.0% vs. 58.7%; p = 0.141). The cumulative incidence of relapse tended to be lower after allo-HSCT (18.6% vs. 30.5%; p = 0.129), with similar non-relapse mortality. Landmark analyses suggested a time-dependent pattern, with divergence in PFS beyond 12 months. In multivariable analyses, allo-HSCT (hazard ratio [HR] 0.34; p = 0.037) and complete remission at transplantation (HR 0.23; p = 0.001) were independently associated with improved PFS, highlighting disease status as a key determinant. Allo-HSCT showed a trend towards improved disease control without increased non-relapse mortality. This effect may be influenced by disease status at transplantation. Findings should be interpreted cautiously and require prospective validation.
Mo A, Haysom H, Carrandi A
… +13 more, de Albornoz SC, Guglielmino J, Rushford K, Ellison A, Andrew D, Jesurajah A, Hu E, Banahene P, Hoo LS, Higgins AM, Shortt J, Wood EM, McQuilten ZK
Patients with myelodysplastic syndromes (MDS) often require red blood cell (RBC) transfusion. However, the true cost of RBC transfusion, beyond the acquisition cost of the unit, is poorly defined. We conducted a prospect...Patients with myelodysplastic syndromes (MDS) often require red blood cell (RBC) transfusion. However, the true cost of RBC transfusion, beyond the acquisition cost of the unit, is poorly defined. We conducted a prospective time-driven activity-based costing study at a large Australian university teaching hospital. Every activity relating to RBC transfusion in patients with MDS was observed and process-mapped, ranging from patient pre-transfusion phlebotomy through to laboratory processes, clinical transfusion in inpatient and outpatient wards, clinical follow-up and transfusion governance and oversight. For each activity, detailed data collection was undertaken, including timing of individual steps and recording all consumables, equipment and personnel involved. The total per-unit cost was US$440.47, with an annual per-patient estimated cost of US$6607.12. Hospital-related costs contributed 41% of the total cost, with the largest contributor being equipment (16%) followed by staffing (14%). Alloimmunisation increased process costs by 24%. These findings demonstrate that hospital process costs need to be included when considering and budgeting for the total cost of the transfusion process. Our findings will inform future transfusion-related resourcing and cost-effectiveness evaluations of treatments which aim to reduce RBC transfusion burden and improve quality of life in MDS.
Delia et al. How unfitness criteria can make a difference in treating AML patients with hypomethylating agents and venetoclax. Br J Haematol 2026 (Online ahead of print). doi: 10.1111/bjh.70569.Delia et al. How unfitness criteria can make a difference in treating AML patients with hypomethylating agents and venetoclax. Br J Haematol 2026 (Online ahead of print). doi: 10.1111/bjh.70569.
Haslam A, Iqbal G, Drayson M
… +7 more, Pratt G, Yong K, Dunn J, Atkin C, Bunce C, Howe D, Bowcock S
Br J Haematol
· 2026 Jun · PMID 42162568
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The Tackling Early Morbidity and Mortality in Myeloma trial (TEAMM) trial recruited 977 newly diagnosed myeloma patients from 93 UK hospitals to assess the advantages and disadvantages of prophylactic antibiotics for the...The Tackling Early Morbidity and Mortality in Myeloma trial (TEAMM) trial recruited 977 newly diagnosed myeloma patients from 93 UK hospitals to assess the advantages and disadvantages of prophylactic antibiotics for the first 12 weeks. This paper analyses the 133 (14%) patients who had previously known precursor disease including monoclonal gammopathy of undetermined significance (MGUS) and smouldering myeloma (SMM), reporting the relative importance of blood-based biomarkers, imaging findings and symptoms in their management. Prior to progression with active myeloma, patients with precursor conditions had symptoms for five times longer than patients with no diagnosed precursor phase. Although only 29% of patients reported new myeloma-related symptoms developing after their first haematology appointment, 70% had a significant rise in paraprotein levels prior to progression. Likewise, risk scores for both MGUS and SMM increased prior to progression. Fractures occurred in 25% of patients despite being monitored for precursor disease. These fractures were difficult to predict as biomarkers lacked specificity and only 40% of patients reported back pain in combination with vertebral fractures. This study highlights the ongoing challenge of promptly recognising disease progression when using patient-reported symptoms and monoclonal immunoglobulin monitoring.
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition associated with severe fetal thrombocytopenia and intracerebral haemorrhage. Antenatal management of subsequent pregnancies relies on intravenous...Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition associated with severe fetal thrombocytopenia and intracerebral haemorrhage. Antenatal management of subsequent pregnancies relies on intravenous immunoglobulin (IVIg); yet, practice varies internationally and UK data are limited. We conducted a national survey to characterise the current antenatal management of FNAIT across UK regional fetal medicine centres using an electronic, scenario-based design. Responses were analysed descriptively, with ≥75% concordance considered strong agreement. Sixteen of 22 regional fetal medicine centres (73%) responded; all respondents were fetal medicine specialists or haematologists. There was strong consensus to treat standard- and high-risk pregnancies associated with anti-human platelet antigen (HPA)1a or anti-HPA5b antibodies using weekly IVIg, most commonly at a dose of 1 g/kg/week. Earlier initiation of IVIg was favoured for high-risk pregnancies, while timing was more variable for standard-risk cases. Corticosteroids were not routinely used in standard-risk pregnancies but were considered in high-risk scenarios. Fetal blood sampling and intrauterine platelet transfusion were generally avoided. Considerable variation was observed in delivery planning and in the management of pregnancies at risk without a prior confirmed diagnosis. This survey demonstrates the areas of both consistency and variation in UK practice, highlighting gaps in the evidence base and priorities for future research and guidelines development.
Germline gain-of-function variants in sterile alpha motif domain-containing 9-like (SAMD9L), located on chromosome 7q, cause a multisystem disorder characterized by bone marrow failure, immunodeficiency and variable neur...Germline gain-of-function variants in sterile alpha motif domain-containing 9-like (SAMD9L), located on chromosome 7q, cause a multisystem disorder characterized by bone marrow failure, immunodeficiency and variable neurological involvement. Disease evolution is frequently shaped by somatic genetic rescue (SGR), most commonly through monosomy 7, somatic loss-of-function (LOF) variants in cis or uniparental disomy of 7q (UPD7q). We report a 6-month-old girl presenting with pancytopenia and severe infections, in whom we identified a novel heterozygous SAMD9L variant. Trio-based whole-genome sequencing demonstrated maternal transmission and revealed distinct SGR mechanisms in both the proband and her asymptomatic mother, including UPD7q and an additional somatic LOF variant. Longitudinal molecular follow-up showed dynamic clonal evolution associated with haematological improvement. To assess the broader relevance of SAMD9/SAMD9L variants, we also performed a gene-centred analysis of the 2025 French Genomic Medicine Initiative (PFMG2025), enabling the identification and classification of additional candidate variants. These findings support systematic screening for SGR, including mosaic UPD7q, even in cases with apparently normal variant allele frequency, and highlight the importance of integrating haematopoietic and non-haematopoietic tissues in diagnostic workflows for inherited bone marrow failure syndromes.
Haploidentical haematopoietic stem cell transplantation (haplo-HSCT) expands donor availability for cerebral adrenoleukodystrophy (cALD). However, conventional graft-versus-host disease (GVHD) prophylaxis based on calcin...Haploidentical haematopoietic stem cell transplantation (haplo-HSCT) expands donor availability for cerebral adrenoleukodystrophy (cALD). However, conventional graft-versus-host disease (GVHD) prophylaxis based on calcineurin inhibitors like ciclosporin (CsA) poses a potential neurotoxicity risk that may exacerbate neurological injury. We retrospectively analysed 26 cALD patients who underwent haplo-HSCT with an optimized ciclosporin-free GVHD prophylaxis regimen consisting of anti-thymocyte globulin (ATG; 4 mg/kg), post-transplant cyclophosphamide (PTCy) and mycophenolate mofetil. Neutrophil and platelet engraftment each occurred at a median of 15 days (ranges, 13-26 and 9-33 days respectively). The cumulative incidence (CI) of grades II-IV acute GVHD by day 100 was 18.49% ± 8.37%, and the 3-year CI of moderate-to-severe chronic GVHD was 9.32% ± 6.28%. After a median follow-up of 29 months, overall survival was 90.4% ± 6.6% and major functional disability-free survival was 69.0% ± 9.1%. Post-transplantation, plasma C26:0 levels and the C24:0/C22:0 and C26:0/C22:0 ratios were markedly reduced. Magnetic resonance imaging (MRI) at a mean of 7.3 ± 5.9 months post-HSCT showed largely preserved LOES scores without significant progression. Our experience supports the safety and efficacy of this optimized ciclosporin-free haplo-HSCT approach for patients with cALD, warranting further validation in prospective studies.
This study aimed to assess whether routine nephrology examinations could predict renal amyloidosis in kidney disease patients with monoclonal gammopathy. A total of 356 consecutive hospitalized patients in the nephrology...This study aimed to assess whether routine nephrology examinations could predict renal amyloidosis in kidney disease patients with monoclonal gammopathy. A total of 356 consecutive hospitalized patients in the nephrology department with monoclonal gammopathy performed renal biopsies, including 50 renal amyloidosis patients and 306 non-renal amyloidosis patients, were included after strict filtering. Laboratory and imaging data were collected for each patient. Renal amyloidosis patients exhibited significantly higher 24-h proteinuria and estimated glomerular filtration rate and decreased serum creatinine (SCr), albumin and immunoglobin M, with lower κ light chain and κ/λ ratio in urine and serum. Higher 24-h proteinuria and 24-h microalbuminuria and lower random urine κ/λ ratio, serum κ light chain, serum κ/λ ratio and SCr were significant risk factors for renal amyloidosis. Nomogram model identified albumin, 24-h urinary microalbumin excretion rate, 24-h urine κ light chain, 24-h urine κ/λ ratio and serum IgM as combined predictors of renal amyloidosis (area under the curve 0.781, 95% CI 0.718-0.854). Combined biomarkers (albumin, 24-h urinary microalbumin excretion rate, 24 h urine κ light chain, 24-h urine κ/λ ratio and serum IgM) effectively predicted renal amyloidosis in kidney disease patients with monoclonal gammopathy.