Cold agglutinin disease is an autoimmune haemolytic anaemia related to a clonal B-cell disorder of the bone marrow. Haemolysis is complement-dependent, while acrocyanosis is monoclonal agglutinin-dependent. Established t...Cold agglutinin disease is an autoimmune haemolytic anaemia related to a clonal B-cell disorder of the bone marrow. Haemolysis is complement-dependent, while acrocyanosis is monoclonal agglutinin-dependent. Established therapies target the clonal B cells or the classical complement pathway. Treatment can be tailored based on clinical phenotypes.
Therapeutic options for relapsed or refractory diffuse large B-cell lymphoma (rDLBCL) have expanded following accelerated approvals based largely on surrogate end-points, yet confirmatory studies have not consistently re...Therapeutic options for relapsed or refractory diffuse large B-cell lymphoma (rDLBCL) have expanded following accelerated approvals based largely on surrogate end-points, yet confirmatory studies have not consistently reproduced these benefits across all agents, and outcomes for many patients remain poor. Restrictive and heterogeneous eligibility criteria further limit generalisability of trial findings to routine populations. We examined eligibility criteria across seven registrational rDLBCL trials and applied them hypothetically to a real-world cohort of 180 patients treated in Australia with standard-of-care therapies. The trials required a median of 39 criteria (range 31-45), with marked variability across patient and disease domains. The greatest discordance related to prior lines of therapy, definitions of measurable disease and organ function parameters. Among 320 patient relapses (median 1, range 1-8), 52% were ineligible for any trial and no patient met criteria for all seven. Eligibility ranged from 4% (SADAL) to 22% (ZUMA-1). Common reasons for exclusion were limits on prior therapy, washout requirements and organ dysfunction. Overall survival did not differ between patients ineligible for all trials and those eligible for at least one (p = 0.97). Median progression-free survival (PFS) was comparable to registrational studies in both groups. Substantial eligibility heterogeneity excludes most real-world patients, limiting trial generalisability and supporting the need for more inclusive, standardised frameworks.
Hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HPP) are red blood cell (RBC) membrane disorders caused by defects in spectrin interactions, leading to variable degrees of haemolysis. This study aimed t...Hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HPP) are red blood cell (RBC) membrane disorders caused by defects in spectrin interactions, leading to variable degrees of haemolysis. This study aimed to compare RBC fragility, oxidative stress and antioxidant capacity among individuals with HE, HPP and healthy controls. Blood samples from 15 subjects (n = 5 per group) were analysed. Chemical-induced haemolysis assays revealed significantly increased haemolysis in HPP RBCs, whereas haemolysis did not differ between HE and healthy controls. Intracellular reactive oxygen species (ROS) were highest in HPP RBCs under basal and 0.5 mM HO-induced conditions. Lipid peroxidation was increased in HPP RBC ghosts under basal conditions and was significantly elevated in plasma compared with both normal and HE groups. Antioxidant enzyme activities (superoxide dismutase [SOD] and glutathione peroxidase [GPx]) were largely comparable among groups, except for increased RBC SOD activity in HPP compared with normal controls. These findings indicate that HPP is characterized by marked membrane instability, elevated oxidative stress and increased lipid peroxidation, while antioxidant capacity remains relatively preserved. Collectively, these abnormalities are likely to contribute to the severe haemolytic phenotype observed in HPP compared with HE and healthy individuals.
Piatek C, Oladapo A, Kolodny S
… +6 more, Vredenburg M, Lucht S, Bland E, Pathak P, Feinberg B, Maitland H
Br J Haematol
· 2026 Jun · PMID 42136034
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Real-world data on treatment response after switching between thrombopoietin receptor agonists are limited for patients with immune thrombocytopenia (ITP). The objective of this study is to describe treatment patterns an...Real-world data on treatment response after switching between thrombopoietin receptor agonists are limited for patients with immune thrombocytopenia (ITP). The objective of this study is to describe treatment patterns and outcomes in patients with primary ITP who switched from eltrombopag (ELT) or romiplostim (ROMI) to avatrombopag (AVA). We conducted a retrospective chart review study of adults with primary ITP who initiated ELT or ROMI on or after 1 July 2019, switched to AVA within 30 days of ELT/ROMI discontinuation and had ≥6 months follow-up after AVA initiation. Patients were followed from AVA initiation until last contact, death or study end (21 March 2025), whichever occurred earliest. Response was defined as achieving ≥1 platelet count (PC) of ≥30 × 10/L, ≥50 × 10/L or ≥100 × 10/L in the absence of rescue therapy. Response durability was the percentage of time on AVA with PCs above the response threshold among responders. Patients (N = 201) most commonly discontinued ELT/ROMI due to lack of efficacy (59.2%). Among patients with baseline PCs <30 × 10/L (n = 79), 98.7% and 94.9% achieved PCs ≥30 × 10/L and ≥50 × 10/L on AVA respectively. Median response durability was 93.8%, 89.6% and 67.4% for ≥30 × 10/L, ≥50 × 10/L and ≥100 × 10/L respectively. Most patients who switched to AVA from ELT or ROMI achieved or maintained a clinically meaningful and durable platelet response throughout the study period.
Bastos-Boente M, Medina-Herrera A, Navarro-Bailón A
… +24 more, Ferrero S, Sarasquete ME, Jiménez C, García-Álvarez M, Antón A, Balanzategui A, Moia R, Re A, Boccomini C, Balzarotti M, Zilioli VR, da Silva MG, Díaz-Gálvez FJ, González-Mena B, Peñarrubia MJ, Fernández-Ferrero S, de Ramón C, Blanco Ó, Cabero A, Ladetto M, García-Sanz R, Gutiérrez NC, Martín García-Sancho A, Alcoceba M
Mantle cell lymphoma (MCL) is a clinically heterogeneous disease with varying treatment responses and outcomes. Despite the utility of the Mantle Cell Lymphoma International Prognostic Index (MIPI), its predictive capaci...Mantle cell lymphoma (MCL) is a clinically heterogeneous disease with varying treatment responses and outcomes. Despite the utility of the Mantle Cell Lymphoma International Prognostic Index (MIPI), its predictive capacity can be enhanced by integrating genetic markers such as TP53 mutations. We analysed 143 newly diagnosed MCL patients from a real-world cohort, assessing TP53 mutational status, clinical and biological markers. We developed the MIPI53 index by incorporating TP53 mutations, lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group (ECOG) status and age. Internal validation was performed via bootstrapping, and external validation was conducted with data from the fondazione Italiana Linfomi (FIL) MCL0208 trial. Patients were stratified into low-, intermediate- and high-risk groups, showing significant differences in 5-year progression-free survival (PFS) (83.1%, 35.4% and 12.0%, respectively; p < 0.0001) and 5-year overall survival (OS) (92.1%, 80.5% and 33.8%, respectively; p < 0.0001). External validation confirmed the robustness of the model (c-index: 0.732; akaike information criterion, AIC: 296.2 according to OS). A simplified version (sMIPI53) was developed, maintaining high predictive accuracy in both training (c-index: 0.819; AIC: 404.5) and external cohort (c-index: 0.730; AIC: 296.7). The MIPI53 index effectively stratifies MCL patients into prognostic groups by integrating genetic and clinical variables to enhance outcome prediction.
A better understanding of factors influencing red blood cell (RBC) alloimmunization is desirable, given the dangers of this non-infectious serious hazard of transfusion. In a case-control retrospective study utilizing th...A better understanding of factors influencing red blood cell (RBC) alloimmunization is desirable, given the dangers of this non-infectious serious hazard of transfusion. In a case-control retrospective study utilizing the Recipient Epidemiology and Donor Evaluation study (REDS)-III Biological Specimen and Data Repository Information Coordinating Center (BioLINCC) dataset, we investigated blood donor, component and recipient variables associated with RBC alloantibody specificities. 19 697 controls with no new alloantibody detected 2-16 weeks post-transfusion and 861 cases (with antibodies including anti-E, -K, -Jka, -C and -c) were studied. Univariate comparison revealed multiple factors are found more frequently in alloimmunized cases than controls, including use of ABO non-identical units, recipient female gender and shorter RBC unit storage duration. Multivariate donor/component odds ratio for each antibody specificity revealed myelodysplastic syndrome (MDS), sickle cell disease, rheumatoid arthritis and lupus as being associated with higher odds of antibody formation, with MDS being associated with the most antibody specificities. ABO non-identical recipient-donor pairs were associated with higher odds of alloimmunization for all antibody specificities evaluated. RBC storage duration showed significance only for anti-E after multivariable analysis, with units stored for a longer duration (>12 days) associated with reduced odds of alloimmunization. In sum, blood donor, recipient and component elements variably impacted alloantibody formation in transfusion recipients, with differences observed by antibody specificity.
Scott AP, Lo A, Xia Y
… +15 more, Thompson K, Bodimeade H, Fazlollahi A, Weber N, Curley C, Hunt S, Morris K, McNamara C, Perera N, Subramoniapillai E, Lane SW, Kennedy GA, Salvado O, Urriola J, McMahon KL
Multiple myeloma (MM) is a highly heterogeneous plasma cell malignancy whose progression and relapse are influenced by clonal heterogeneity. Although serum free light chains (sFLCs) are key biomarkers for tumour burden a...Multiple myeloma (MM) is a highly heterogeneous plasma cell malignancy whose progression and relapse are influenced by clonal heterogeneity. Although serum free light chains (sFLCs) are key biomarkers for tumour burden assessment, the clinical value of λ, κ and their ratio remains controversial. This study investigated the associations of sFLC κ, λ and the κ/λ ratio with clinical features, cytogenetic abnormalities, prognosis and response to the VRd regimen (bortezomib, lenalidomide, dexamethasone) in newly diagnosed MM (NDMM) patients, aiming to optimize risk stratification. A retrospective analysis of 113 NDMM patients was conducted. Baseline clinical data, cytogenetic markers (RB1/D13S319/IGH/1q21/P53/1p32) and treatment responses were collected, with stratification by renal function. Tumour proliferation, apoptosis and angiogenesis were assessed by immunohistochemistry. Prognostic factors were evaluated using Kaplan-Meier and Cox regression analyses. A modified revised International Staging System (R-ISS) (MR-ISS) model incorporating sFLC κ was then developed and temporally externally validated. Abnormal sFLC κ indicated poor prognosis. Among NDMM patients with normal renal function, abnormal sFLC κ was significantly associated with adverse clinical features, high tumour burden, an anti-apoptotic and angiogenic tumour microenvironment, D13S319 deletion and a lower rate of deep remission after VRd induction. Moreover, the MR-ISS model demonstrated superior risk discrimination compared with the R-ISS. In conclusion, abnormal sFLC κ is a potential marker of poor prognosis and suboptimal response to VRd therapy in NDMM. Integrating sFLC κ with the R-ISS improves risk stratification, providing new evidence for clinical application of this biomarker.
Fuseya A, Yamamoto M, Nishio M
… +13 more, Kitabayashi R, Hirakawa A, Yasui H, Umezawa Y, Tanaka K, Tamai H, Uemura Y, Oshima K, Sano F, Mori T, Koike R, Ohga S, Arai A
Systemic chronic active Epstein-Barr virus disease (sCAEBV) is a life-threatening disorder characterized by Epstein-Barr virus (EBV) infection in T cells and/or natural killer (NK) cells leading to systemic inflammation....Systemic chronic active Epstein-Barr virus disease (sCAEBV) is a life-threatening disorder characterized by Epstein-Barr virus (EBV) infection in T cells and/or natural killer (NK) cells leading to systemic inflammation. We retrospectively analysed 46 adult patients diagnosed with sCAEBV at two high-volume centres in Japan. Patients with active disease received immunosuppressive therapy, chemotherapy-based regimens and/or ruxolitinib. Allogeneic haematopoietic stem cell transplantation (allo-HSCT) was pursued whenever feasible. Of 46 patients, 41 (89.1%) ultimately underwent allo-HSCT. Five patients progressed from hydroa vacciniforme lymphoproliferative disorder (HV-LPD); all showed EBV-infected CD4+ cells. The 3-year overall survival (OS) was 43.1% (95% confidence interval [CI], 27.7-57.5), and all patients who did not undergo allo-HSCT died within 8 months from diagnosis. Five patients (10.9%) developed lymphoma or leukaemia. Leading causes of death included haemophagocytic lymphohistiocytosis and infections. Multivariable analysis identified high alanine aminotransferase (ALT) and ferritin as independent predictors of poor outcome. Based on these findings, we developed a risk model stratifying patients into three groups with distinct 3-year OS rates: 69.9% (95% CI, 44.6-85.3) in patients with neither factor, 24.8% (95% CI, 7.0-48.2) in those with one factor and 0% in those with both factors (p < 0.001). ALT and ferritin are practical biomarkers for risk stratification and treatment.
Clinical decision support (CDS) can potentially improve the rate of heparin-induced thrombocytopenia (HIT) diagnostic testing for patients who are at increased risk. We implemented and evaluated CDS utilizing the HIT com...Clinical decision support (CDS) can potentially improve the rate of heparin-induced thrombocytopenia (HIT) diagnostic testing for patients who are at increased risk. We implemented and evaluated CDS utilizing the HIT computerized risk (HIT-CR) score in a large healthcare system. The CDS was triggered by a HIT-CR score of 4 and provided clinicians with a temporal graph of platelet counts and prompts to help further assess the risk of HIT. The primary outcome of this study was the percentage of patients at intermediate to high risk for HIT (4Ts scores ≥4) who underwent recommended diagnostic testing for HIT. Among those with 4Ts scores ≥4, the diagnostic testing rate increased from 28/237 (11.8%) to 98/288 (34.0%) (p < 0.0001) after implementation of the CDS advisory. The rate of patients determined to have HIT was 6/332 (1.8%) pre-intervention and 13/412 (3.2%) post-intervention (p = 0.25). Fourteen of the 26 patients with 4Ts scores ≥6 did not undergo diagnostic testing for HIT despite the CDS advisory, and eight had possible complications from undiagnosed HIT. A CDS tool using the HIT-CR score for assessment of risk of HIT can increase the rate of diagnostic testing in patients with elevated risk of HIT, but there is potential for further improvement.
Nakamura T, Okamoto H, Maekura C
… +24 more, Niiyama-Uchibori Y, Inoue Y, Fujino T, Tsukamoto T, Shimura Y, Mizutani S, Shimura K, Kaneko H, Nakao M, Ide D, Okano A, Takahashi R, Kuwahara-Ota S, Fuchida SI, Hayata H, Nishiyama D, Murao T, Kamitsuji Y, Uchiyama H, Sasaki N, Yamaguchi J, Kawata E, Uoshima N, Kuroda J
Renal response (RenR) in light-chain (AL) amyloidosis is associated with a lower risk of end-stage kidney disease and improved survival. However, substantial variation exists in the time to and depth of RenR. We investig...Renal response (RenR) in light-chain (AL) amyloidosis is associated with a lower risk of end-stage kidney disease and improved survival. However, substantial variation exists in the time to and depth of RenR. We investigated variables associated with RenR in a retrospective study of newly diagnosed AL amyloidosis patients (n = 350) assessable for RenR between 2010 and 2022. RenRs were recorded at 6, 12 and 24 months and best response. Deep RenR was defined as a ≥renal very good partial response (RenVGPR, >60% reduction in 24-h proteinuria or ≤200 mg). Logistic regression and competing risk methods were used to examine variables associated with RenR. The median age was 64 years, and median follow-up was 5.5 years. On multivariable logistic regression, obtaining ≥HemVGPR within 6 months, kappa isotype, high baseline difference between involved and uninvolved free light chains (dFLC ≥40 mg/dL), renal stage and autologous haematopoietic stem cell transplant (AHSCT) were significantly associated with deep RenR. Cumulative incidence rates for deep RenR, treating death or renal progression as a competing event, demonstrated that early HemR, first-line AHSCT, lower renal stage and dFLC ≥40 mg/dL significantly increased the likelihood of deep RenR. Specific clonal plasma cell features, namely light-chain isotype and baseline dFLC levels, independently influence the timing and depth of RenRs in AL amyloidosis following treatment, in addition to renal stage and HemR.