Graft-versus-host disease, involving from 20%-80% of patients, is one of the main complications of allogeneic hematopoietic cell transplantation contributing significantly to mortality and morbidity. The methodological basis of these graft-versus-host disease prophylaxis guidelines for allogeneic hematopoietic cell transplantation, developed by the Brazilian Association of Hematology, Hemotherapy, and Cell Therapy (ABHH) and the Brazilian Society of Cellular Therapy and Bone Marrow Transplantation (SBTMO), is a review which applied the GRADE process to eleven PICO (population, intervention, comparator, and outcome) questions. These questions address graft-versus-host disease prophylaxis in allogeneic hematopoietic cell transplantation across various settings, including myeloablative and non-myeloablative/reduced-intensity conditioning. The scope encompasses related matched, unrelated matched or mismatched, and haploidentical donors, utilizing both bone marrow and peripheral blood as stem-cell sources. The combination of a calcineurin inhibitor (e.g., cyclosporine or tacrolimus) plus methotrexate or mycophenolate mofetil (MMF) has been the standard graft-versus-host disease prophylaxis regimen for allogeneic hematopoietic cell transplantation. The excellent results of post-transplant cyclophosphamide in haploidentical related donor hematopoietic cell transplantation have led to broader use in human leukocyte antigen-(mis)matched related and unrelated donor grafts. Sirolimus, low-dose antithymocyte globulin (4-6 mg/kg) and more recently abatacept are other drugs used. Hence, this review is meant to be a useful reference tool for clinicians who are dealing with this complex complication.
Immunotherapy, particularly natural killer cell therapy, is garnering attention for treating lymphoma, due to the unique properties of natural killer cells, most importantly rapid and potent antitumor responses without prior sensitization. However, the tumor microenvironment and immune escape mechanisms can impair natural killer cell function in lymphoma. To address these challenges, researchers are exploring therapeutic interventions to restore or enhance their activity. Of the various approaches of cell therapy, such as allogeneic- or autologous-natural killer cell infusions, chimeric antigen receptor natural killer cells, and combination therapies, allogeneic natural killer cell transplantation has shown promise in specific subtypes of lymphoma, offering a reduced risk of graft-versus-host disease, improved response rates, prolonged remissions, and increased overall survival. Combining natural killer cell therapy with standard treatments such as chemotherapy or immune checkpoint inhibitors holds potential for synergistic effects. Nevertheless, addressing challenges such as cell persistence, the immunosuppressive tumor microenvironment, and optimal delivery methods is crucial to improve efficacy. Further investigations are required to gain a better understanding of natural killer cell-mediated responses, refine genetic engineering approaches, identify predictive biomarkers, and optimize combination strategies. Continued research and clinical trials will play a vital role in optimizing cell therapy and expanding treatment options for lymphoma patients.
Hematologic disorders, including sickle cell disease, anemias, hemoglobinopathies, leukemias, lymphomas, and bleeding disorders, constitute a substantial and growing burden of morbidity and mortality across Africa. Structural health system constraints-limited diagnostic capacity, shortages of trained hematology specialists, fragmented blood transfusion services, and inequitable access to essential medicines-continue to drive delayed diagnosis, suboptimal treatment, and poor outcomes. Despite these challenges, recent years have witnessed important advances in laboratory strengthening, point-of-care diagnostics, access to targeted therapies, and innovative service delivery models. This narrative review synthesizes current evidence on diagnostic and therapeutic gaps in hematology care in Africa and examines emerging strategies aimed at strengthening equitable, sustainable, and context-appropriate care. Recent initiatives demonstrate measurable progress in several domains. Expansion of point-of-care testing and regional laboratory networks has improved early diagnosis of sickle cell disease and hematologic malignancies in countries such as Kenya, Uganda, and Rwanda. Access to essential therapies, including hydroxyurea for sickle cell disease and tyrosine kinase inhibitors for chronic myeloid leukemia, has improved through national insurance schemes and international partnerships in settings such as Ghana and Nigeria, although coverage remains uneven. Innovations in blood transfusion services, including drone-assisted delivery in Rwanda and strengthened voluntary donation programs in Kenya and Nigeria, have reduced delays in emergency transfusion for severe anemia. Capacity-building initiatives supported by international collaborations and professional societies have expanded continuing medical education, teleconsultation, and subspecialty training; however, workforce shortages, supply chain vulnerabilities, and financial barriers persist. Transforming hematology care in Africa requires coordinated, system-level strategies that integrate diagnostic strengthening, equitable access to essential therapies, resilient blood transfusion services, workforce development, and digital health innovations. While country-level experiences demonstrate that targeted investments and international collaborations can yield tangible improvements, sustainable progress will depend on stronger health system financing, regional manufacturing and procurement mechanisms, regulatory support, and context-sensitive implementation research. A deliberate shift from fragmented, disease-specific interventions toward integrated, patient-centered hematology care frameworks is essential to reduce preventable morbidity and mortality and to advance equitable cancer and blood disorder outcomes across the continent.
To examine differences in perceptions between hematologists (HOs) and palliative care physicians (PCs) regarding red blood cell transfusion at the end of life. This cross-sectional questionnaire survey, conducted from August to September 2020, included responses from 1000 hematologists (HOs) and 759 palliative care physicians (PCs). The questionnaire assessed cutoff indications and opinions regarding red blood cell transfusion for anemia due to hematologic malignancy progression in patients with no indication for anticancer therapy. We defined a consensus Hb threshold as the highest level at which ≥ 70% of respondents would transfuse. Of 659 responses, 596 were valid (269 HOs and 327 PCs). For symptomatic cases, > 70% of HOs and PCs considered Hb cutoffs of 8.0 and 7.0 g/dL, respectively. For asymptomatic cases, < 70% of PCs recommended transfusion even at Hb ≤ 6.0 g/dL; therefore, an Hb cutoff for PCs could not be determined. Most HOs and PCs agreed to reduce transfusion frequency, while PCs were more likely than HOs to agree to discontinue transfusion. In contrast, HOs were more likely than PCs to agree to continue transfusion upon patient and/or family request and to consider patients with performance status 4 eligible for transfusion. Among adult patients with hematological malignancies who have no indication for anticancer therapy, hematologists tend to view transfusion more favorably and to transfuse more actively than palliative care physicians. Greater mutual understanding and consensus-building regarding transfusion indications at the end of life may facilitate appropriate palliative care referral for these patients.
Sickle cell disease (SCD) care includes pharmacologic disease-modifying therapies (pDMTs) and chronic blood transfusion therapy (CBT). Using Optum Labs Data Warehouse (2014-2021), we identified individuals with SCD and classified yearly treatment as pDMT only, CBT only, combined pDMT + CBT, or no disease-modifying therapy. Among 4,100 patients, 26% used pDMT only, 3% received CBT only, 1% received both, and 70% received no DMT in a given year. pDMT uptake rose steadily while CBT remained low (3%-4%). In multinomial models (reference: no DMT), older age was associated with lower odds of pDMT and CBT, while prior vaso-occlusive crises and severe organ complications were associated with higher odds across categories. Men had higher odds of pDMT and combined therapy. These findings suggest treatment intensification in routine practice follows accumulating morbidity rather than preceding it, and that substantial implementation gaps persist, particularly among older adults and for CBT, which depends on specialized capacity. Expanding CBT capacity and improving pDMT uptake may narrow gaps and better align real-world care with guideline intent.
Palliative care is, according to the World Health Organization (WHO), "a global ethical responsibility" and crucial to person-centered healthcare, for the relief of physical and psychological symptoms and social and spiritual suffering, impacting the improvement of the quality of life not only of pediatric and adult patients dealing with life-threatening illnesses, but also of their families. Despite the growing recognition of palliative care in the hematological setting and the increase in the number of publications on the subject, the available data are still scarce and limited. The objective of this consensus is to establish recommendations for the referral of pediatric and adult hematological patients to specialized palliative care teams and the possible integration of these two specialties.
Derived hematological indices reflect immune activation, but their dynamics during the plerixafor era and their predictive value for stem cell yield remain unclear. To assess changes in derived hematological inflammatory markers during peripheral blood stem cell mobilization in autologous patients and allogeneic donors, and to evaluate their correlation with CD34+ stem cell yield. These markers include ratios (neutrophil-to-lymphocyte, platelet-to-lymphocyte and lymphocyte-to-monocyte), and composite indices (systemic immune-inflammation and systemic inflammation response indices). A retrospective analysis was conducted of 127 autologous and 53 allogeneic mobilization events between January 2019 and March 2024. Blood counts and derived indices were analyzed before and after granulocyte colony-stimulating factor administration with and without plerixafor. CD34+ cell enumeration was performed after mobilization. Dynamic changes in inflammatory indices and their correlation with CD34+ counts were assessed. After mobilization, there was a significant increase in the neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, and systemic inflammation response index, and a decrease in the platelet-to-lymphocyte and lymphocyte-to-monocyte ratios in both groups. While allogeneic donors had higher CD34+ counts (median 110 cells/µL versus 48 cells/µL in autologous), no consistent correlation was found between dynamic inflammatory marker changes and CD34+ yield. Plerixafor use in autologous patients significantly influenced the platelet-to-lymphocyte ratio and systemic immune-inflammation index dynamics, highlighting its role in modulating the acute inflammatory response in the plerixafor era. Inflammatory markers change significantly during mobilization with granulocyte colony-stimulating factor, reflecting acute immune activation. However, the studied markers do not predict CD34+ yield and should not replace direct enumeration. Their role may be better suited to complement biological understanding rather than clinical decision-making.
Blood transfusion is a critical component of modern medicine, yet the risk of transfusion-transmitted infections remains a significant challenge. Despite stringent screening protocols, infections such as hepatitis B, hepatitis C, human immunodeficiency virus, and syphilis continue to pose risks. Understanding the seroprevalence of transfusion-transmitted infections in blood donors is essential for improving transfusion safety and shaping public health strategies. The objective of this study is to evaluate transfusion-transmitted infection seroprevalence, analyze trends, and assess seropositivity by age, donation type, and co-infections over five years. A five-year cross-sectional study (2020-2024) was conducted at three blood centers: Jagjivan Ram Hospital Blood Bank (Mumbai), Bloodline Charitable Blood Bank (Thane), and Sadguru Charitable Blood Centre (Navi Mumbai). The study assessed the prevalence of transfusion-transmitted infections by screening 87,878 donor samples for human immunodeficiency virus, hepatitis B, hepatitis C, syphilis, and malaria using standardized diagnostic methods. Donor demographics, infection patterns, and regional variations were analyzed statistically. The overall seroprevalence of transfusion-transmitted infections was 0.78%, with Hepatitis B being the most common infection (0.48%), followed by syphilis (0.144%), human immunodeficiency virus (0.078%), and hepatitis C (0.075%). No malaria cases were detected. Seropositivity was highest among younger donors (18-30 years) and predominant among males (97%). Mumbai recorded the highest seroprevalence, followed by Navi Mumbai and Thane. Co-infections were rare, with human immunodeficiency virus with syphilis being the most frequently observed combination. This study identifies Hepatitis B as the most common transfusion-transmitted infection, followed by syphilis, human immunodeficiency virus, and hepatitis C. This study emphasizes the need for better detection strategies, specifically the use of enzyme-linked immunosorbent assay, electrochemiluminescence Immunoassay, and individual donor nucleic acid testing to improve blood safety. Transfusion-transmitted infection screening plays a vital role as a quality indicator for blood banks, driving method evaluation and improvements. Mumbai's structured referral system ensures seropositive donors receive counseling and treatment, reinforcing blood safety protocols.
Systemic immunoglobulin light chain amyloidosis is characterized by the extracellular deposition of misfolded light chains, leading to progressive dysfunction of multiple organs. Diagnosis remains a significant clinical challenge and is frequently delayed due to the presence of nonspecific symptoms, coupled with limited access to specialized diagnostic tools and expertise. Currently, no established national recommendations for the diagnosis and management of this condition exist in Brazil. These expert recommendations were developed following a structured advisory meeting in May 2025. The guidelines were formulated after a national survey of 96 Brazilian institutions (50 private and 46 public). Key diagnostic and therapeutic challenges were identified, including delayed diagnosis, limited access to biopsy techniques and biomarker testing, and uneven availability of treatment options. Recommendations focused on areas where consensus would benefit healthcare professionals in establishing best practices. The recommendations included: 1) Early detection: Educational initiatives for patients and healthcare professionals and the establishment of multidisciplinary specialized centers are needed to improve time to diagnosis and subsequent prognosis. 2) Accurate diagnosis: Clear, standardized procedures for tissue biopsy and timing are necessary to ensure accurate diagnosis and efficient testing. Improved access to Congo red staining and polarized light microscopy is critical. 3) Evaluation and classification: Biomarker testing should be used at all stages. Validated biomarker cut-offs and scoring systems should be implemented to standardize patient evaluation and risk stratification. 4) Optimal management and treatment: A multidisciplinary approach is crucial. Daratumumab should be added, if available, to bortezomib, cyclophosphamide and dexamethasone. Bortezomib and melphalan based regimens are an alternative. These expert-guided recommendations aim to support earlier diagnosis, standardized evaluation, and optimized treatment of light chain amyloidosis in Brazil.
Sickle cell disease, a genetic blood disorder marked by vaso-occlusive crises and severe pain, presents a major global health challenge. Haptoglobin, a glycoprotein that binds free hemoglobin in the blood, protects tissues from oxidative damage. This study aims to explore the link between variations in the haptoglobin (HP) gene and susceptibility to more severe sickle cell disease. A comprehensive literature search was performed across Scopus, Embase, Google Scholar, Web of Science, and PubMed. Methodological quality was evaluated using the RoB 2 tool. Statistical analyses employed MetaGenyo software with significance being set at a p-value <0.05. Functional enrichment, gene ontologies, and protein-protein interaction networks were mapped using the Enrichr and STRING web platforms. Eight studies were evaluated to determine the association between HP gene polymorphisms and susceptibility to sickle cell disease complications. The results indicate a significant association between HP gene polymorphisms and sickle cell disease severity under the dominant model (odds ratio = 0.76; 95% confidence interval: 0.61-0.94; p-value = 0.01). Additionally, a subgroup analysis based on ethnicity demonstrated associations in the African and South American populations (p-value <0.05) but the Asian population showed no correlation between HP gene polymorphisms and sickle cell disease severity (p-value >0.05). This meta-analysis demonstrates a significant association between HP gene polymorphisms and increased severity of sickle cell disease, suggesting that the HP genotype may serve as a valuable predictive biomarker for clinical outcomes.
Plasma transfusion is commonly used in intensive care units, often for non-bleeding indications despite limited evidence. This study aimed to evaluate the association between plasma transfusions and in-hospital mortality among critically ill patients. A retrospective cohort study was conducted using data from 282 adult intensive care unit patients who received transfusion therapy between January and December 2020. Patients were grouped by their exposure to plasma transfusion and further by the transfusion volume. First, multivariable Cox regression coupled with propensity score matching was used to control for baseline confounders and quantify the independent association of plasma transfusion with in-hospital mortality. Subsequently, Cox models and Kaplan-Meier survival curves were employed to elucidate the dose-response relationship between transfusion volume and mortality risk, with additional subgroup analyses. In the unadjusted analysis, plasma transfusion was significantly associated with increased in-hospital mortality (Hazard ratio = 4.199; 95% confidence interval: 2.53-6.97; p-value <0.001). This association persisted after propensity score matching adjusted for key confounders (Hazard ratio = 3.271; 95% confidence interval: 1.30-8.21; p-value = 0.012). Kaplan-Meier survival analysis demonstrated significantly lower survival probabilities in the transfusion group (log-rank p-value <0.05). Furthermore, a dose-dependent relationship was revealed: mortality risk increased at higher volumes, reaching statistical significance at >800 mL (Hazard ratio = 4.09; 95% confidence interval: 1.19-14.04; p-value = 0.025). Subgroup analysis indicated that the elevated risk was particularly pronounced among patients who concurrently received red blood cell transfusions. Plasma transfusion is independently and dose-dependently associated with increased mortality in critically ill patients, particularly when used without clear indications. These findings support a restrictive, evidence-based approach, emphasizing correction of underlying coagulopathy over prophylactic transfusion. Strict adherence to guidelines and an individualized risk-benefit assessment are essential to improve patient safety.
Neutrophils and platelets are key elements of the host immune response to sepsis, participating in both pathogen clearance and in sepsis-related tissue damage. Although it is widely recognized that patients with hematological malignancies and chemotherapy-induced febrile neutropenia are at increased risk of severe sepsis complications, the prognostic impact of neutrophil and platelet counts on sepsis-related outcomes remains controversial, with conflicting results regarding the magnitude of neutropenia. Moreover, to our knowledge, no studies have addressed the association of thrombocytopenia with outcomes in febrile neutropenia in patients with hematological malignancies. This study investigated the association of neutropenia and thrombocytopenia in a consecutive cohort of 113 patients with underlying hematological malignancies who were admitted to an academic tertiary hospital with chemotherapy-induced neutropenia. Neutrophil and platelet counts were obtained at fever onset and 24, 48 and 72 hours thereafter. Neutrophil counts at the time of febrile neutropenia were not associated with sepsis-related mortality or other negative outcomes. However, a lower platelet count at fever onset was associated with non-bleeding sepsis-related mortality and the need of organ support. Moreover, the trajectories of both neutrophil and platelet counts in the first 72 hours after the onset of febrile neutropenia were also associated with negative outcomes. These results highlight the heterogeneous role of platelets in the immune response and pave the way for studies exploring to what extent severe thrombocytopenia modulates the molecular and cellular mechanisms of post-febrile neutropenia sepsis in these patients.
Acquired pure red cell aplasia (aPRCA) is rare and challenging to treat. We investigated the efficacy and safety of sirolimus plus roxadustat in patients with aPRCA (Chinese Clinical Trial Register number, ChiCTR2200065107). We enrolled 82 patients with aPRCA in this prospective single-arm, open-label, multicenter trial between October 2022 and January 2024. Treatment response and safety files were evaluated. The median age was 63 years. Seven patients withdrew during the trial period. Sirolimus plus roxadustat produced an overall response (OR) in 65 patients (90.3%) 3 months after initiation, which included a complete response (CR) in 39 (54.2%) and a partial response in 26 (36.1%). The 3-month CR rate was significantly higher in the newly diagnosed group (65.9% vs. 38.7%; P = 0.022). The 6-month OR rate in the entire cohort was 93.0% (CR, 77.5%; PR, 15.5%). The mean hemoglobin concentration increased from 5.5 ± 1.6 g/dL at baseline to 11.6 ± 2.5 g/dL after 6 months of treatment. The proportions of patients who achieved transfusion independence within 1, 2, and 3 months of treatment were 57.4%, 76.6%, and 89.5%, respectively. The Functional Assessment of Chronic Illness Therapy-Fatigue Scale score and SF-36 survey score significantly improved after treatment. Treatment-related adverse events occurred in 24 patients (29.2%), and four events (4.9%) were grade ≥3. Sirolimus plus roxadustat is a promising treatment for aPRCA and has an acceptable safety profile, which warrants further investigation in a randomized setting.
Covalent Bruton tyrosine kinase (BTK) inhibitors have advanced the treatment of Waldenström macroglobulinaemia; however, the occurrence of progression, intolerance, and acquired resistance are not fully understood. We aim to report on the safety and activity of pirtobrutinib (a highly selective, non-covalent BTK inhibitor) in patients with relapsed or refractory Waldenström macroglobulinaemia, including those who received previous covalent BTK inhibitors as part of the phase 1/2 BRUIN trial. The BRUIN study was an open-label, multicentre, phase 1/2 trial that enrolled patients with relapsed or refractory B-cell malignancies from 29 sites across eight countries. Patients aged 18 years or older who previously received BTK inhibitor-containing regimens, had an Eastern Cooperative Oncology Group performance status of 0-2, and histologically confirmed Waldenström macroglobulinaemia were eligible. In phase 1, patients received 100-300 mg oral pirtobrutinib once a day in 28-day cycles and the recommended phase 2 dose (RP2D) of 200 mg pirtobrutinib once a day was determined. The phase 2 primary endpoint was antitumour activity of pirtobrutinib based on objective response rate as assessed by an investigator in patients with chronic lymphocytic leukaemia, small lymphocytic leukaemia, or mantle cell lymphoma. In patients with Waldenström macroglobulinaemia, response was evaluated using the Sixth International Workshop on Waldenström Macroglobulinemia (IWWM-6) criteria. BRUIN is registered with ClinicalTrials.gov, NCT03740529 (completed). BRUIN recruited patients from Aug 12, 2019, to March 14, 2022, and 778 patients received pirtobrutinib. 80 patients had relapsed or refractory Waldenström macroglobulinaemia (n=18 in phase 1 and n=62 in phase 2), with a median age of 68·5 years (IQR 61·0-75·0). 52 (65%) patients were male and 28 (35%) were female. The median number of previous lines of systemic therapy was 3·0 (2·0-5·0). 63 (79%) patients received previous covalent BTK inhibitors. 73 (91%) received 200 mg pirtobrutinib once per day (the RP2D). Using IWWM-6 criteria, the objective response rate was 82·5% (95% CI 72·4-90·1), with one (1·3%) patient reaching complete response, eight (10·0%) reaching very good partial response, 49 (61·3%) reaching partial response, and eight (10·0%) reaching minor response. The median study follow-up was 35·0 months (17·7-47·7). The objective response rate was 81·0% (69·1-89·8) for those who received previous covalent BTK inhibitors and 88·2% (63·6-98·5) for covalent BTK inhibitor-naive patients. Grade 3 or higher treatment-emergent adverse events occurred in 57 (71%) patients, with the most common being neutropenia or neutrophil count decreased (15 [19%]) and anaemia (19 [24%]). Treatment-emergent deaths were reported in five (6%) patients (bacterial sepsis, intracranial haemorrhage, COVID-19 pneumonia, hypertensive cardiomegaly and pneumonia [n=1 each unrelated to treatment], and treatment-related necrotising pneumonia [n=1]). Treatment-emergent adverse events leading to dose reductions occurred in four (5%) patients and pirtobrutinib discontinuation in 12 (15%). Pirtobrutinib was highly active and well tolerated, regardless of previous exposure to covalent BTK inhibitors, and might be a promising new therapeutic option for patients with relapsed or refractory Waldenström macroglobulinaemia, particularly in those previously exposed to covalent BTK inhibitors, for whom durable and effective treatments are needed. Eli Lilly and Company.
Despite evidence supporting the clinical equivalence of whole blood-derived platelets (WBDP) and apheresis platelets (AP), AP remains the dominant choice for platelet transfusions in many countries. This study aimed to assess Chinese healthcare professionals' preferences, barriers, and conditional acceptance of WBDP as an alternative to AP, especially in the context of platelet shortages and rising clinical demand. A nationwide survey targeting physicians, transfusionists, and blood center staff was conducted via the WeChat Mini Program. The survey included 35 questions focusing on attitudes toward AP and WBDP, particularly regarding safety, efficacy, and barriers to WBDP adoption. A total of 781 participants from various healthcare institutions across China completed the survey. A substantial majority of physicians (78.41%) and transfusionists (93.88%) exhibited a preference for AP compared to WBDP, safety (77.54% and 86.12%) and clinical efficacy (63.77% and 84.9%) as primary factors. Surprisingly, 94.32% of physicians and 89.59% of transfusionists expressed willingness to use WBDP when AP is unavailable, primarily due to blood resource shortages. One of the key findings of this task was that merely 31% of blood center staff and 27% of their hospital customers acknowledged the clinical equivalence between AP and WBDP, with 47% and 53% expressing no opinion. Key barriers to WBDP adoption included concerns over transfusion reactions (92%), efficacy (72%), and safety (68%). To improve the current situation, the following strategies were identified to enhance WBDP adoption: increasing clinical research (60.87%) and physician education (46.96%). This survey highlights significant reservations among healthcare professionals regarding the clinical equivalence and safety of WBDP. Future efforts should focus on bridging the knowledge gap, optimizing WBDP collection and distribution, and promoting the rational use of both platelet products to address shortages and ensure high-quality patient care.
Immunocompromised individuals were identified early in the pandemic as being at increased risk of severe COVID-19 and have demonstrated variable immune responses to SARS-CoV-2 vaccination. Although coordinated vaccination programmes are now well established, their long-term effects on sustained immunity in the present patient populations remain insufficiently understood. The prospective SARS-CoV-2 mRNA vaccine trial COVAXID was conducted in a well-characterised, real-world cohort of 539 immunocompromised and healthy individuals across 21 subgroups, organised into six main categories. At the 36-month time point, 218 participants remained. Participants provided blood samples for assessment of binding antibody titres and pseudo-neutralisation activity against ancestral SARS-CoV-2 and 21 variants, including Omicron sub-lineages. T cell responses were evaluated in a defined subset of participants. Immunogenicity outcomes were analysed over a three-year period in relation to SARS-CoV-2 vaccination, SARS-CoV-2 infection, and immunoglobulin replacement therapy (IGRT). Between years two and three, antibody titres and neutralisation capacity showed a consistent pattern of maintenance or increase across most study groups and subgroups. These increases were driven by cumulative exposure to vaccine booster doses, SARS-CoV-2 infection, and, in some cases, passive immunisation through IGRT. CD4+ and CD8+ T cell responses were detected across all study groups. Early immune responses were primarily vaccine-driven, whereas later immune profiles reflected substantial contributions from natural infection and anti-SARS-CoV-2 antibodies in IGRT products. The findings support continued, tailored vaccination strategies for elderly and immunocompromised individuals. Integrating immune monitoring with infection history and adjunctive therapies may help refine booster policies, optimise protection, and strengthen future vaccination programmes for high-risk populations. The present studies were supported by the European Research Council, Karolinska Institutet, Knut and Alice Wallenberg Foundation, Nordstjernan AB, Region Stockholm, and the Swedish Research Council.
Toxoplasma gondii affects one-third-of the global population and may alter hematological parameters and CD4+ T cell counts, especially during pregnancy. This study evaluated the association of T. gondii with alterations in hematological values in pregnant women attending a public antenatal care hospital in Northwest Ethiopia. An analytic cross-sectional study of 554 pregnant women (301 seropositive, 253 seronegative) attending antenatal care at a public hospital from 2022 to 2023 assessed T. gondii exposure using ELISA IgG/IgM kits (Human Diagnostics, Germany). Blood samples collected in EDTA tubes were analyzed for hematological profiles using a Coulter Hematology analyzer, and the CD4+ cell count with a BD FACSPresto™. Data were analyzed with SPSS 21.0. Descriptive statistics and independent sample t tests were performed: normality was confirmed using the Kolmogorov-Smirnov test RESULTS: Significant differences were observed in hematological values (white blood cell count, hemoglobin, hematocrit, red blood cell count, lymphocytes, neutrophils, and mean corpuscular volume) between seropositive and seronegative women (p-value < 0.001). Platelet counts showed no significant variation (p-value = 0.811). However, CD4+ cell counts were significantly lower in toxoplasmosis-infected women (p-value < 0.001). Toxoplasma gondii infection is associated with alterations in hematological parameters and immunological profiles in pregnant women. Routine screening during antenatal care and preventive education are recommended.
The clinical need for treating anemia in aplastic anemia (AA) patients remains unmet. Luspatercept has been shown to be effective in myelodysplastic neoplasms (MDS). Patients who were newly diagnosed with non-transfusion-dependent non-severe AA (NTD-NSAA) were randomly assigned to receive either cyclosporine (CsA) combined with luspatercept or CsA monotherapy at a 1:1 ratio. This study (ClinicalTrials.gov NCT05399732) aimed to compare their treatment responses, safety, disease progression, and outcomes. In total, 58 patients participated in the final analysis, with 29 receiving CsA+luspatercept and 29 receiving CsA monotherapy. With a median follow-up of 12 months (range: 6-25) and 12 months (range: 7-25), respectively, the overall response rates (ORRs) were 69.0% vs. 37.9% (p = 0.018) at the 3rd month, 79.3% vs. 51.7% (p = 0.027) at the 6th month, and 72.4% vs. 51.7% (p = 0.104) at the end of follow-up. Patients receiving CsA+luspatercept had a shorter time to achieve a positive response than those receiving CsA alone (p = 0.004). A post hoc subgroup analysis based on age (< 60 vs. ≥60 years) showed no significant difference in ORRs for those < 60 years old. However, for patients ≥ 60 years old receiving CsA+luspatercept, a significantly greater ORR was demonstrated at both the 3rd month (p = 0.032) and 6th month (p = 0.046) compared with CsA monotherapy. Compared with CsA monotherapy, the combination of CsA and luspatercept resulted in a higher response rate and a shorter time to response for patients with NTD-NSAA, with an acceptable safety profile. The benefit of CsA+luspatercept was most pronounced in older patients.
A woman in her 30s presented with irregular vaginal bleeding and abdominal distension. Initial imaging suggested a uterine fibroid; however, intraoperative findings during planned laparotomy were atypical, prompting an excisional biopsy. The initial pathological diagnosis was endometrial stromal sarcoma, and staging imaging suggested liver metastases, prompting chemotherapy initiation. One month later, she developed urinary retention, oedema and dyspnoea. Imaging revealed a large pelvic mass causing bilateral hydronephrosis, extensive lymphadenopathy and tumour lysis syndrome, managed with stents and supportive care. Re-evaluation of the biopsy established the diagnosis of primary endometrial diffuse large B-cell lymphoma (DLBCL). Hepatitis B positivity delayed chemotherapy; interim dexamethasone provided relief. Intensive chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and methotrexate/ifosfamide, etoposide and cytarabine resulted in a rapid response but was complicated by neutropenic sepsis, leading to death. This case highlights the diagnostic challenge of endometrial DLBCL, the critical importance of pathological re-evaluation and the need for careful toxicity monitoring during intensive chemotherapy.
Postoperative atrial fibrillation is the most common complication following cardiac surgical procedures. The objective of this study was to assess a possible association of postoperative atrial fibrillation, intraoperative autologous blood salvage, and blood transfusion. A total of 357 adult patients undergoing cardiac surgery with the use of intraoperative autologous blood salvage were included. They were divided into two groups: one with 161 patients (45%) who only received their recovered autologous blood, and another with 196 patients (55%) who additionally required the transfusion of homologous blood components. Demographic data, pre- and post-operative laboratory parameters, transfusion profiles, and clinical outcomes (mortality) were compared. The number of recovered autologous blood units was not associated with an increased risk of postoperative arrhythmia (Odds ratio: 0.75; 95% CI: 0.45-1.11). Intraoperative homologous blood transfusion was associated with a significantly increased risk of death (Hazard ratio: 5.17; 95% CI 1.44-18.56). When autologous salvaged blood volume and homologous components were evaluated together, homologous transfusion was associated with higher risk of postoperative atrial fibrillation (Odds ratio: 2.51, 95% CI 1.18-5.65), whereas number of autologous units was not (OR 0.66, 95% CI 0.39-1.01). Transfusion at any time point (intraoperative, intensive care unit [ICU], or ward) was also associated with an increased risk of death (Hazard ratio: 5.15, 95% CI 1.16-22.94). While advanced age was significantly associated with postoperative atrial fibrillation, no association was found with intraoperative autologous blood salvage and blood transfusion.