Hasil untuk "Diseases of the blood and blood-forming organs"

Cristina Banella

Introduction: Acute myeloid leukemia (AML) in pediatric patients is a biologically heterogeneous malignancy, with particularly poor prognosis in relapsed or refractory cases. Evidence from adult AML suggests that metabolic rewiring and dependence on oxidative phosphorylation (OXPHOS) contribute to disease progression and therapeutic resistance. In contrast, the metabolic and genomic landscape of pediatric AML remains largely uncharacterized. This study aims to explore metabolic heterogeneity and genomic alterations in pediatric AML and to compare these preliminary findings with adult data, ultimately improving diagnostic and prognostic precision. Methods: We employed two complementary approaches: real-time bioenergetic profiling using the Seahorse XF Analyzer to assess OXPHOS and glycolytic activity in AML blasts, and Oxford Nanopore long-read sequencing for comprehensive genomic characterization. Nanopore sequencing enables simultaneous detection of single nucleotide variants, structural rearrangements, copy number alterations, and methylation profiles. Samples were collected at diagnosis and at relapse or from non-responder patients. Although pediatric sample numbers were limited, this approach allows initial comparison of metabolic and genetic features between pediatric and adult AML. Results: Preliminary analysis revealed distinct metabolic patterns associated with therapeutic resistance in the few pediatric cases studied, showing trends similar to adult AML, with higher OXPHOS activity correlating with adverse outcomes. Nanopore sequencing accurately reconstructed both the conventional mutational panel and karyotype of these patients. Furthermore, novel genomic “hotspots” were identified, including an expanded region within the FLT3 promoter in a representative case, potentially contributing to an “FLT3-like” phenotype and intrinsic therapy resistance. These findings illustrate the potential of long-read sequencing to uncover cryptic structural variants not detected by conventional diagnostics. Conclusions: This study provides an initial integrated metabolic–genomic overview of pediatric AML and suggests functional links between OXPHOS activity and specific genomic features, consistent with adult AML observations. The combined use of Seahorse profiling and Nanopore sequencing establishes a framework for high-resolution, unified diagnostics. Future work will expand pediatric sample numbers and integrate RNA sequencing and metabolomics to refine molecular classification, identify predictive biomarkers, and develop metabolism-informed therapeutic strategies.

Jiaqi Wei, Zhen Yang, Xiaojin Wu et al.

Abstract Background Coagulation defects, including purpura and other haemorrhagic conditions, are a critical area of medical research because of their significant health effects worldwide. Understanding the metabolic basis of these conditions may improve therapeutic strategies. Methods A two-sample Mendelian randomization (MR) approach was employed to evaluate the causal relationships between the levels of 1,400 metabolites and coagulation defects. Colocalization analysis confirmed significant shared genetic influences. Pathway and protein‒protein interaction (PPI) analyses identified rate-limiting enzymes and drug targets. The impacts of lifestyle factors on metabolite levels were also explored through MR. Results MR analysis revealed four metabolites whose abundance was significantly associated with coagulation defects: docosapentaenoate n3 DPA 22:5n3 (DPA) (OR: 1.594, 95% CI: 1.263–2.011, P < 0.001), 1-palmitoyl-2-stearoyl-gpc (PSPC) (16:0/18:0) (OR: 1.294, 95% CI: 1.134–1.477, P < 0.001), 1-stearoyl-2-docosahexaenoyl-gpc (SDPC) (18:0/22:6) (OR: 1.232, 95% CI: 1.101–1.380, P < 0.001) and hydroxypalmitoyl sphingomyelin (HPSM) (d18:1/16:0 (OH)) (OR: 0.803, 95% CI: 0.719–0.896, P < 0.001). Colocalization analysis provided robust evidence for shared genetic loci. Pathway analysis highlighted the importance of lipid metabolism, identifying key enzymes such as FADS1, FADS2 and TCP1. PPI analysis revealed an interaction between TCP1 and plasminogen, indicating potential therapeutic synergy. Further analysis revealed that lifestyle factors, including dried fruit and oily fish intake, were linked to the abundance of metabolites associated with coagulation risk. Conclusions This study identifies specific metabolites and metabolic pathways involved in coagulation defects, proposes novel therapeutic targets and highlights the roles of dietary and lifestyle interventions in the management of these conditions. These findings pave the way for personalized strategies to manage coagulation-related conditions.

Jesús Duque-Afonso, Julian List, Michael Lübbert

Not available.

Xin-xin Yang, Guo-li Yao, Yu-jing Yang et al.

Background Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet count (PLT). Bruton tyrosine kinase (BTK) is a therapeutic target in immune-mediated diseases. This study aimed to evaluate the effects of a BTK inhibitor, zanubrutinib (Zan), on refractory ITP.Methods Peripheral blood was collected from healthy controls (HC) and refractory ITP patients (n = 15), and peripheral blood mononuclear cell (PBMC) extraction was performed. The proportion of myeloid-derived suppressor cells (MDSCs) in PBMCs and Arg-1, iNOS, Fc gamma receptor (FcγR), GPIIb/IIIa, and GPIb/IX autoantibody levels were measured. ITP monocytes were separated into control (Con), Zan (Zan), dexamethasone (DXM), and combination (Zan + DXM) groups. Detection ophagocytosis and platelet activation by flow cytometry; FcγR expression by qRT-PCR and western blot; and IFN-γ, IL-4, IL-2, and IL-10 levels were determined by ELISA.Results PBMCs from the ITP group demonstrated lower MDSCs proportions and Arg-1 levels, but higher iNOS, FcγRIII, FcγRIIb, FcγRI, GPIIb/IIIa, and GPIb/IX autoantibody levels than those in the HC group. Following Zan intervention, ITP monocytes exhibited decreased phagocytosis, FcγRIIa, FcγRI protein, IFN-γ, IL-2, p-mTOR/mTOR levels, and increased FcγRIIb, PLTs, IL-4, PAC-1, and CD62p levels.Conclusion Zan may modulate FcγR toward FcγRIIb to inhibit platelet destruction, thereby improving refractory ITP.

HUANG Xiulan, YUE Shuhan, CAI Qun et al.

[Objective] To validate and optimize the platelet transfusion refractoriness (PTR) prediction model for patients with hematological disorders established by our center. [Methods] The data of patients with hematological diseases who received platelet transfusions from December 2021 to December 2022 were used as the training set, and data from January 2023 to December 2023 as the validation set. The validation set data was used to validate the predictive model constructed on the training set. Relevant risk factors for PTR were collected through literature review and preliminary studies。 The patients were divided into effective and ineffective groups according to the corrected count increment (CCI) of platelet counts. Predictive factors were screened using univariate and multivariate logistic regression. The calibration of the model were assessed via calibration curves, while discrimination, accuracy, sensitivity, and specificity were evaluated using receiver operating characteristic (ROC) curves Clinical utility was further analyzed with decision curve analysis (DCA). [Results] The Hosmer-Lemeshow (H-L) goodness-of-fit test for the validation set yielded S: P=0.000, indicating that the original model needs optimization. Baseline comparisons and logistic regression identified the number of red blood cell units (RBCU) and platelet units (PLT-U) transfused as key predictors for the optimized model. The H-L goodness-of-fit test S: P values for the training and validation sets were 0.930 and 0.056, respectively; the ROC areas were 0.793 5 and 0.809 4, specificities 90.95% and 84.21%, sensitivities 59.26% and 70.04%, and accuracies 78.14% and 74.10%, respectively. DCA demonstrated clinical net benefit within a prediction probability threshold range of 0.2-0.8. [Conclusion] Transfusion volumes of RBC-U and PLT-U were inversely associated with PTR in hematological patients. The resulting PTR prediction model exhibits moderate predictive efficacy and clinical benefit.

Rashmi Parashar, Sunita Bundas, Amit Sharma

Autoimmune myasthenia gravis (MG) is sometimes associated with thymic abnormalities. Thymectomy is performed in cases of MG with a thymoma or general MG that is resistant to medical therapy. The aims and objectives of the study are to assess the survivability and response to plasma exchange in patients planned for thymectomy in unstable disease activity status of MG. Plasma exchange is indicated before and after thymectomy in unstable disease activity status. Here, we are presenting case summary of five patients undergoing plasma exchange for unstable disease activity status. The outcome was poor in patients having Masoka staging III and Iva, respectively. The survival rate was 60% during an unstable state of MG with thymoma in our study.

Bengisu Ece Duman, Büşra Akdoğan, Birol Güvenç

Objective: Multiple myeloma is a plasma cell malignancy that mainly affects the bones and skeletal system. The involvement of the brain as a site is very rare; it usually takes place via calvarial lesions with intracranial extension and is considered resistant to treatment. This report presents the case of a patient presenting with refractory MM and discusses in detail the efficiency of bendamustine-pomalidomide therapy and daratumumab-based maintenance after ASCT. Case Report: A 62-year-old female was diagnosed with kappa-positive MM in 2015, when plasma cell infiltration in the bone marrow was 20%. The patient underwent chemotherapy followed by ASCT in 2016. This patient attained remission after the transplant. Three years later, she presented with brain involvement, and MRI confirmed lesions of the parietal calvarium along with soft tissue expansion into the brain.The patient received radiotherapy to the affected area of the brain and initiated bendamustine-pomalidomide therapy; indeed, remarkable improvements were made in lesions of the brain and skeleton. Following that response, daratumumab, lenalidomide, and dexamethasone maintenance therapy was initiated to ensure ongoing disease control. Currently, the patient is clinically stable, with no evidence of further progression on follow-up imaging. Discussion: This case underlines the rarity of brain involvement in MM, as well as the role of ASCT as part of first-line treatment. The late appearance of extramedullary brain involvement three years post-transplantation truly epitomizes the whim of MM. Bendamustine-pomalidomide therapy was effective for refractory disease management, whereas daratumumab-based maintenance has helped maintain stability.

CR Cohen, RE Boehm, F Bonacina et al.

Introdução: A malária é uma doença parasitária infecciosa, de alta morbimortalidade. No Brasil é endêmica nos estados da Amazônia Legal e em outras regiões mais de 80% dos casos são importados. Apesar disso, existe transmissão residual de malária em estados não-endêmicos, principalmente em áreas de Mata Atlântica. A malária é transmitida através da picada da fêmea do mosquito do gênero Anopheles infectada pelo protozoário do gênero Plasmodium (P. vivax , P. falciparum , P. malariae e P. ovale ), sendo as três primeiras espécies as mais frequentes no Brasil. A transmissão da doença não ocorre diretamente entre pessoas, mas é possível haver transmissão por transfusão sanguínea. Desta forma, a testagem de malária é obrigatória em regiões endêmicas e em março de 2023 foi incluída entre as patologias pesquisadas pelo teste de amplificação de ácidos nucléico (NAT) de Bio-Manguinhos (Fiocruz). O Rio Grande do Sul (RS) não está na região endêmica de Malária, mas preserva uma parte pequena de Mata Atlântica e o principal vetor, o Anopheles darlingi não está presente no estado. Apesar de não ser frequente no RS, no período de 2010 a 2021 foram notificados 191 casos de Malária. Objetivo: Relatar dois casos de Malária assintomática diagnosticados a partir do teste NAT em Porto Alegre. Descrição: Doador masculino realizou a doação de sangue no Serviço de Hemoterapia do Hospital da Santa Casa de Misericórdia de Porto Alegre. Dentre os exames de triagem sorológica o NAT Malária (Bio-Manguinhos) foi detectável, apresentando cycle threshold (CT) 34,82. O doador coletou nova amostra após 10 dias, e nesta, o NAT foi repetido e se manteve detectável (CT 30,49), amostras também foram encaminhadas para o Laboratório Central de Saúde Pública do Rio Grande do Sul (LACEN), que realizou o teste de gota espessa e imunocromatografia [Bioline Malaria Ag (Abbott)], ambos negativos. Uma amostra foi encaminhada à Bio-Manguinhos para confirmação por RT-PCR, sendo identificado P. vivax na amostra deste doador. De modo similar, um doador masculino realizou a doação de sangue no Serviço de Hemoterapia do Hospital de Clínicas de Porto Alegre. Apresentou NAT Malária detectável, com CT 32,91. O doador coletou nova amostra após 7 dias, e nesta, o NAT se manteve detectável (CT 34,63) e os teste de gota espessa e imunocromatografia (LACEN) foram ambos negativos. A amostra encaminhada à Bio-Manguinhos identificou P. malariae na amostra deste doador. Ambos os doadores são residentes em Porto Alegre (RS) e não tem histórico de viagem à região endêmica ou atividade laboral de risco para Malária. Um ponto em comum é que ambos frequentaram em momentos de lazer a região de Mata Atlântica no RS próxima ao litoral de Santa Catarina. Os dois doadores se apresentavam assintomáticos no momento da doação e na recoleta. Discussão e conclusão: A incorporação do NAT Malária na qualificação de doadores no RS está evidenciando casos assintomáticos. Desta forma, os serviços de Hemoterapia e a Vigilância Epidemiológicas devem estar preparados para orientar esses doadores. A transmissão de malária dos dois casos parece ter sido autóctone, provavelmente na região de Mata Atlântica. Esses casos inesperados servem de alerta para a transmissão de Malária em regiões não endêmicas e para a importância na incorporação desta patologia na triagem de doadores de sangue em todo o Brasil.

PEM Flores, JN Cavalcante, TAS Pereira et al.

Introdução: As síndromes mielodisplásicas (SMD) são um grupo heterogêneo de doenças mieloides caracterizadas por hematopoiese clonal e insuficiência medular que causam citopenias periféricas, anormalidades citogenéticas recorrentes e um risco variável de progressão para leucemia mieloide aguda (LMA). Dada a heterogeneidade da doença e o comportamento clínico variável em termos de evolução para leucemia, muitas análises citogenéticas e molecular têm surgido como ferramentas para identificar pacientes com características biológicas, clínicas e prognósticas semelhantes. Nesse contexto, a alteração citogenética de del20q isolada denota um bom prognóstico, de acordo com a estratificação de risco vigente (IPSS-R e IPSS-M). Objetivo: Relatar um caso de SMD com del 20q isolada, em seguimento clínico há sete anos, sem progressão de doença. Relato de caso: Paciente masculino, 85 anos, evoluiu com bicitopenia – anemia leve com Hb 11,0 e plaquetopenia grave – 20.000, desde 2017. Na ocasião do diagnóstico, realizou estudo medular que mostrou displasia moderada nas três séries, associada a 20% de sideroblastos em anel e cariótipo com del 20q11.2 em 14 das 20 metáfases analisadas. Na ocasião, estratificado como risco baixo (IPSS-R: 2), no entanto, devido à plaquetopenia importante, optado por tratamento com hipometilante. Recebeu 3 ciclos de Azacitidina, com suspensão por sangramento com hemorragia subaracnóidea e infecções bacterianas graves de repetição. Desde então, manteve apenas seguimento clínico, sempre com plaquetopenia entre 20-30mil. Em Abril/24, quando teve piora da anemia – Hb 7,0, porém mantendo hemograma sem neutropenia e sem piora da plaquetopenia de base, optado por repetir estudo medular. Novo mielograma hipercelular, com displasia das três séries e 1,6% de blastos. Coloração para ferro mostrando 8% de sideroblastos em anel. Citogenética mantendo del 20q11.2 isolada em 19 das 20 metáfases analisadas. Não foi realizado estudo molecular por indisponibilidade pela operadora. Novo IPSS-R: 3 – baixo risco. Optado por iniciar tratamento com Alfapoetina 30.000 unidades semanais. Conclusão: Estudo retrospectivos demonstram que a entidade acima descrita é mais comum em homens, idosos, apresentando plaquetopenia como citopenia mais exuberante no diagnóstico e durante o acompanhamento. O caso do paciente acima vai de acordo ao encontrado na literatura disponível, e o tempo de seguimento do paciente está acima da média para a estratificação inicial, sem indícios atuais de evolução para LMA. Apesar de não termos estudo molecular disponível, a evolução do doente fala contra presença de mutação clonal de risco adicional em associação ao achado citogenético da del20q.

Oliver M, Patriquin CJ

Monika Oliver,1 Christopher J Patriquin2 1Department of Medicine, University of Alberta; Division of Hematology, University of Alberta Hospital, Edmonton, Alberta, Canada; 2Department of Medicine (Hematology), University of Toronto, Division of Medical Oncology & Hematology, University Health Network, Toronto, Ontario, CanadaCorrespondence: Christopher J Patriquin, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, M5G2C4, Canada, Tel + 1-416-340-5233, Fax + 1-416-340-3799, Email christopher.patriquin@uhn.caAbstract: Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare, acquired clonal abnormality, which renders hematopoietic cells exquisitely sensitive to complement-mediated destruction. Classical features of PNH include intravascular hemolytic anemia, increased thrombotic risk, and manifestations related to end-organ damage (eg fatigue, chest pain, dyspnea, renal failure, and pulmonary hypertension). With supportive care alone, mortality rate of patients with PNH is approximately 35%. The anti-C5 monoclonal antibody, eculizumab, was the first targeted therapy approved for PNH, and led to improved hemoglobin, quality of life, reduced transfusion need, reduced thrombosis, and greater overall survival. More recently, therapeutics such as longer acting anti-C5 (ravulizumab) and anti-C3 (pegcetacoplan) medications have been approved, along with other novel therapeutics in late-stage clinical trials. Biosimilars of eculizumab are also now available. Proximal inhibitors (against C3, factor B, and factor D) have shown significant improvements in hemoglobin and transfusion-avoidance in patients who remain anemic despite C5 inhibition. Despite these novel therapies, some unmet challenges remain, including management of breakthrough hemolysis, clinically significant iatrogenic extravascular hemolysis, optimal management in pregnancy, and infection risk mitigation as new targets in the complement system are blocked. In addition, the use of self-administered subcutaneous and oral therapies raises concerns around treatment adherence and the risks of uncontrolled terminal complement. Given the ultra-rare nature of PNH, development is underway of a centralized international registry to capture and analyze the data as they mature for various new therapies and characterize the clinical challenges related to PNH management.Keywords: complement, hemolysis, hemolytic anemia, PNH, thrombosis

Lijian TAO, Zhongxiu WU, Fuxian KONG et al.

Objective To understand the structural characteristics of lapsed apheresis donors in our blood center and provide guidance for further improving recruitment and retention strategies by retrospectively analyzing the characteristics of lapsed apheresis donors in our center in recent years. Methods The apheresis donation and lapsed apheresis donors in Zhejiang Blood Center from 2016 to 2020 were statistically analyzed, and the general information of lapsed donors, including gender, blood type, age, education level and occupation composition, were compared and analyzed. The lapse of novel and long-term donors with different frequency were retrospectively analyzed. The SPSS 19.0 statistical software package was used for data analysis. Results In 2020, the total lapse of apheresis donors decreased by 16.6% as compared with 2016(P<0.05). The lapse rate of donors with blood groups A, B, O and AB was 1∶1∶1∶1, higher in female donors(59.0%) than males(50.0%), and dominated by age group of 18-35(66.3%). With the increase of age, the lapse rate decreased. Donors lapsed were mainly with college or above educational background(60.8%), with high proportion in students and the staff. In 2020, the lapse of novel apheresis donors decreased by 34.1% as compared with 2016, but the average lapse rate of novel apheresis donors was still as high as 70.5%. The average lapse rate of blood donors with different frequency was 52.5%, and the lapse rate decreased significantly with the increase of apheresis donation frequency. The average lapse rate of novel blood donors with whole blood donation experience was lower than those without (56.1% vs 82.9%). Conclusion Multiple measures for recruitment and retention have effectively reduced the lapse of apheresis donors. However, apheresis donors who are 18-35 years old, with college degree or above, students and staff were the main groups from lapsing. In addition, low-frequency and novel apheresis donors without whole blood donation experience were more likely to be lapsing. Targeted and personalized blood donation services should be further provided, and the management of " full cycle of blood donation" should be strengthened to reduce the lapsing, so as to retain more blood donors.

N. L. Bartlett, C. A. Yasenchak, K. K. Ashraf et al.

Jodi V. Mones, Michael B. Streiff, Alok A. Khorana et al.

Abstract Background Prophylactic anticoagulation with rivaroxaban significantly reduced the risk of cancer‐associated thrombosis during the intervention period in the CASSINI trial. Direct oral anticoagulants may increase the risk of gastrointestinal (GI) tract bleeding in patients with an in situ GI tract cancer or lesion. Objective This post hoc analysis characterized the efficacy and safety of rivaroxaban in patients with and without gastric/gastroesophageal junction (G/GEJ) tumors. Methods Primary and secondary efficacy end points and adjudicated bleeding events, including bleeding sites, were analyzed for the intent‐to‐treat population by cancer type (G/GEJ vs non‐G/GEJ) for the 180‐day observation period. Results In patients with G/GEJ tumors, the rates for the primary efficacy end point were 3.4% for rivaroxaban versus 6.9% for placebo (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.11‐1.80). In patients with non‐G/GEJ tumors, the rivaroxaban group had a lower risk of the primary end point (6.6% vs 9.3%; HR, 0.70; 95% CI, 0.40–1.21). Rates of major bleeding in patients with G/GEJ tumors were 4.6% (4/88) versus 1.2% (1/85) for rivaroxaban and placebo; rates in patients with non‐G/GEJ tumors were 1.3% (4/317) versus 0.9% (3/319), respectively. Conclusions Excluding patients with G/GEJ tumors resulted in a definable population of cancer patients who achieved an improved benefit‐risk balance from rivaroxaban prophylaxis.

Tuba Oskay, Mehmet Özen

Hyo Kee Kim, Ahram Han, Sanghyun Ahn et al.

Intravascular fasciitis (IVF) is a very rare disease that is difficult to diagnose preoperatively. Frequently, it can be misdiagnosed as a malignancy or deep vein thrombosis. A 26-year-old man presented with a 6-month history of intermittent cramping pain in the right calf. Duplex ultrasonography, computed tomography, magnetic resonance imaging, and positron emission tomography were performed in various hospitals. The work-up revealed a hypermetabolic mass in the femoral vein, suggestive of a malignancy, such as leiomyosarcoma. The tumor was located inside the femoral vein with no invasion, and the mass was resected en bloc with the vein wall. Intraoperative frozen section biopsy revealed no malignancy, and the final pathological diagnosis was IVF. Herein, we report a case of IVF and discuss the role of imaging studies in its preoperative diagnosis, with an extensive literature review.