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

Huijian Zheng, Huajian Xian, Wenjie Zhang et al.

Abstract B-cell maturation antigen (BCMA) is currently the most extensively explored target for multiple myeloma (MM). BCMA-targeted therapies such as antibody-drug conjugate (ADC), bispecific antibodies (BsAbs), chimeric antigen receptor T(CAR-T) cell have shown promising therapeutic prospects in MM. We have summarized the latest reports on the three types of drugs for MM at the 2024 ASH Annual Meeting.

WANG Tianju, QI Jun, WANG Manni et al.

[Objective] To screen the frequency of CD36 antigen expression in platelet donor database in Shaanxi province and analyze the molecular genetic characteristics of samples with CD36 antigen deficiency and low expression. [Methods] A total of 525 platelet donors samples were randomly collected during May 2023. CD36-FITC monoclonal antibody was used for immunofluorescence labeling, and flow cytometry was applied to detect the expression of CD36 antigen on platelets. For samples with CD36 antigen deficiency on platelets, the expression of CD36 on monocytes was further detected. Samples with CD36 antigen deficiency and low expression were sequenced and analyzed. [Results] Among the 525 blood samples, 99.24% (521/525) showed positive expression of CD36 antigen. There were differences in the expression intensity of CD36 antigen, with low expression accounting for 3.43% (18/525) and CD36 antigen deficiency accounting for 0.76% (4/525), all of which were type Ⅱ deficiency. The exon mutation frequency of CD36 type Ⅱ deficiency and low expression samples was 31.82% (7/22), and the exon mutation types were 121-1_126delGCAAGTT, 329-330delAC, 1142T>G, 1204-1246dupl 43bp, 1221G>A, and 1228-1239delATTGTGCCTATT. All four cases of CD36 type Ⅱ deficiency had a 121-6 T>C mutation in intron 3. All CD36 low expression samples had a mutation of 282-10A>G, and 121-6T>C mutation rate was 61.1%(11/18). [Conclusion] There were differences in the expression of CD36 antigen in the platelet donor database in Shaanxi province, which may be caused by multiple molecular genetic variations. The frequency of CD36 antigen deficiency in Shaanxi was lower than that of Han, Zhuang and Yao populations in southern China. This study provides references for solving the CD36 antibody mediated transfusion reaction and auxiliary treatment of diseases caused by CD36 antigen deficiency in the future. It also provides a basis for investigating the molecular mechanisms of CD36 deficiency and low expression.

Cristina A. Tentori, Lin P. Zhao, Benedetta Tinterri et al.

Abstract Advancements in comprehending myelodysplastic neoplasms (MDS) have unfolded significantly in recent years, elucidating a myriad of cellular and molecular underpinnings integral to disease progression. While molecular inclusions into prognostic models have substantively advanced risk stratification, recent revelations have emphasized the pivotal role of immune dysregulation within the bone marrow milieu during MDS evolution. Nonetheless, immunotherapy for MDS has not experienced breakthroughs seen in other malignancies, partly attributable to the absence of an immune classification that could stratify patients toward optimally targeted immunotherapeutic approaches. A pivotal obstacle to establishing “immune classes” among MDS patients is the absence of validated accepted immune panels suitable for routine application in clinical laboratories. In response, we formed International Integrative Innovative Immunology for MDS (i4MDS), a consortium of multidisciplinary experts, and created the following recommendations for standardized methodologies to monitor immune responses in MDS. A central goal of i4MDS is the development of an immune score that could be incorporated into current clinical risk stratification models. This position paper first consolidates current knowledge on MDS immunology. Subsequently, in collaboration with clinical and laboratory specialists, we introduce flow cytometry panels and cytokine assays, meticulously devised for clinical laboratories, aiming to monitor the immune status of MDS patients, evaluating both immune fitness and identifying potential immune “risk factors.” By amalgamating this immunological characterization data and molecular data, we aim to enhance patient stratification, identify predictive markers for treatment responsiveness, and accelerate the development of systems immunology tools and innovative immunotherapies.

JL Teodoro, RM Correa, CAR Silva et al.

Objetivos: Relatar a experiência do serviço quanto às estratégias de identificação e manejo de sintomas após a infusão de células CAR-T. Material e métodos: Estudo descritivo e observacional, baseado na descrição das principais estratégias de identificação e manejo de sintomas após a infusão de células CAR-T implementadas em um serviço de referência em terapia celular, entre fevereiro de 2023 e julho de 2024. Durante a internação, aplicamos rotinas de cuidados e escalas de classificação (CRS, ICE, ICANS) e outras de risco (Braden, Johns Hopkins, broncoaspiração). Resultados: Desde o início do programa, em fevereiro de 2023 até julho de 2024, foram realizadas 6 infusões de células CAR-T. Dos pacientes tratados, 100% eram do sexo masculino, com uma média de idade de 59 anos (24 a 83 anos). Diagnósticos incluíram 83% linfoma difuso de grandes células B e 17% leucemia linfoide aguda pré B. Os sintomas mais frequentes foram febre (100%), citopenias (83%), astenia (67%), confusão mental (33%), diarreia (33%), hiperglicemia (33%) e fadiga (33%). Discussão: A terapia com células CAR-T tem revolucionado o tratamento das doenças onco-hematológicas, proporcionando melhores taxas de sobrevida e remissões duradouras. No entanto, está associada a graves toxicidades, como síndrome de liberação de citocinas (CRS) e síndrome neurotóxica associada a células imunoefetoras (ICANS), além de toxicidades decorrentes do tratamento quimioterápico. A expertise no reconhecimento e manejo dessas complicações é essencial. Durante o período de 17 meses, foram observadas toxicidades compatíveis com as descritas na literatura, incluindo febre, citopenias, astenia, confusão mental, diarreia, hiperglicemia e fadiga. Para a classificação e manejo da CRS e ICANS, utilizamos o sistema da Sociedade Americana de Transplante e Terapia Celular (ASTCT). Desenvolvemos protocolos assistenciais que permitem o reconhecimento precoce e o manejo ágil desses sintomas, iniciando na avaliação multidisciplinar pré-internação para identificar fatores de risco de complicações baseados no histórico de tratamento, evolução da doença e comorbidades do paciente. Durante a internação, aplicamos rotinas de cuidados e escalas recomendadas. É crucial que os profissionais realizem a aplicação dessas escalas antes da administração do CAR-T, visando estabelecer parâmetros basais. Garantimos a disponibilidade de Tocilizumabe, quando indicado, e protocolos estruturados para o atendimento de urgência, como neutropenia febril, sepse e código amarelo. Mantemos acordos de nível de serviço (SLA) com fornecedores críticos (banco de sangue, laboratório) e uma interface eficiente com essas áreas, assegurando comunicação, segurança e agilidade nos processos assistenciais e no manejo das complicações. Envolvemos pacientes e famílias em todas as etapas (pré, intra e pós-tratamento), fortalecendo a educação, comunicação e protagonismo nas decisões. Conclusão: A terapia com CAR-T representa um importante avanço no tratamento de doenças onco-hematológicas, mas traz novos efeitos adversos que exigem preparação da equipe. A construção de protocolos assistenciais e o treinamento da equipe multiprofissional são essenciais para garantir o cuidado adequado em todas as fases do tratamento, desde a identificação precoce até o manejo e seguimento. O envolvimento de pacientes e famílias e a interface com a equipe multiprofissional são fundamentais para o sucesso do programa.

Xianlin YE, Tong LI, Ruonan WANG et al.

Objective To investigate asymptomatic infection of hepatitis B virus(HBV) among hepatitis B vaccinated donors in Shenzhen, and analyze its serological and molecular characteristics. Methods The HBsAg ELISA positive blood samples of blood donors born after 1992 were collected. HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc were further detected by Roche electrochemiluminescence immunoassay (ECL). BCP/PC and S regions were amplified by Nested-PCRs, HBV DNA quantification were adopted by qPCR simultaneously, and the sequences were also analyzed. Results A total of 46 632 blood samples of donors(31 612 males and 15 020 females) from December 2020 to January 2022 collected, and 99 samples with HBsAg ELISA positive were screened out. After tested by ECL, Nested-PCRs, and real-time fluorescence PCR, 61 were confirmed HBsAg positive, with the positive rate at 0.13% (61/46 632), including 49 males (0.16%, 49/31 612) and 12 females (0.08%, 12/15 020). The HBsAg positive rate of males was higher than that of females (P<0.05). 50 out of 61 sequences for S region were obtained. By phylogenetic analysis, there were 46 cases of type B (92%, 46/50, 38 males and 8 females), 4 cases of type C (8%, 4/50, 3 males and 1 female). The high frequency mutations observed in S region were N40S (8/46,17.39%), G44E (7/46,15.22%), Q129H/R(6/46,13.04%), Y161F/S(7/46, 15.22%), V179A(4/46,8.70%), S53L(2/4,50%), C69T(2/4,50%) and I126S/T(2/4,50%), including the immune escape mutations Q129R and T/I126A/N/S/T. Conclusion Hepatitis B vaccination can significantly reduce the positive rate of HBsAg and increase the safety of blood transfusion. The high frequency immune escape mutations have become a potential risk of blood safety, and need to be further explored.

Ayesha Sinha, Najla Haneefa Basheela, Durba Biswas et al.

A 39-year-old female with breast carcinoma presented with complaints of menorrhagia and weakness. At current admission, her hemoglobin was 6.2 g/dL, and a requisition for packed red blood cells (PRBCs) was sent to the blood center. There was no previous history of transfusions, and the last pregnancy was 11 years ago. During the immunohematological (IH) workup, she was typed as O, ccdee, with an extra reaction in reverse grouping. Her antibody screening was positive, followed by the antibody identification, which was suggestive of anti-D and anti-C antibodies. The “Rhesus G” is an immunogenic antigen that is present on red cells that are D- and/or C-positive. Therefore, it is essential to determine the possibility of the presence of an anti-G antibody in the patient since anti-G appears as anti-D + anti-C serologically. In our case, a series of IH tests were performed, which ultimately led to the detection of all three antibodies: anti-D, anti-C, and anti-G. The patient’s husband and both children were typed as A, CcDee. Hence, her alloantibodies were most probably pregnancy induced, and since antibodies to the Rhesus system have a poor evanescence phenomenon, they are persisting to date. She was safely transfused with two units of O, ccdee PRBCs, and a special blood group card was provided to ensure that she always receives transfusions with phenotype-matched red cells in the future to avoid further alloimmunization.

Amit I. Bery, Hailey M. Shepherd, Wenjun Li et al.

Mingot-Castellano ME, Rodríguez-Martorell FJ, Nuñez-Vázquez RJ et al.

María Eva Mingot-Castellano,1 Francisco Javier Rodríguez-Martorell,1 Ramiro José Nuñez-Vázquez,1 Pascual Marco2 1Hematology Department, Hospital Universitario Virgen del Rocío. Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain; 2General Medicine Department, Universidad Miguel Hernández, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, SpainCorrespondence: María Eva Mingot-Castellano, Hematology Department, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain, Email mariae.mingot.sspa@juntadeandalucia.esAbstract: Autoantibodies against plasma coagulation factors could be developed by some individuals inducing severe and sometimes fatal bleedings. This clinical entity is called acquired haemophilia. It should be suspected in subjects with acute abnormal bleedings, without personal or familiar history of congenital bleeding disorders with an unexplained prolonged aPTT. It is rare disease, although its incidence may be underestimated due to the low knowledge about it by many specialists, the frequent use of anticoagulant or antiplatelet therapies in the affected population that can mask the diagnosis and, sometimes, a so withering effect that avoid its confirmation. Mortality ranges between 9% and 33% depending on the series in the first 2 months after diagnosis. This mortality is attributed in up to 40% of the cases to infections in the context of immunosuppressive treatments used to eliminate the inhibitor. Factor VIII levels below 1% and high inhibitor titers are conditions of worse response rates. Advanced age, patient’s ECOG, and underlying conditions are key prognostic factors for response to treatment and patient survival. To reduce morbidity and mortality in these patients, it is important to have clinical knowledge and access to guidelines to achieve an early diagnosis and to optimize the haemostatic and immunosuppressive treatment. This review aims to contribute to the dissemination of basic concepts on the epidemiology etiopathogenesis, diagnosis, treatment and management of these patients, as well as risk factors to get remission and the longest overall survival to allow individualized care. Especial awareness will be proposed in patients with some underlying conditions like cancer, autoimmune diseases, children, pregnancy or drugs.Keywords: acquired haemophilia, inhibitors, coagulopathy, autoimmune, bleeding

MBIYA-MUKINAYI B., KALOMBO-KALENDA D., MUKENDI-NKESU Y. et al.

MG Cliquet, VD Poggetto

Objetivos: O sistema hemostático é um balanço bioquímico que mantem o sangue líquido e fluido. Quando a resposta hemostática está desregulada podemos ter a formação de trombos. Trombos são massas sólidas formadas a partir do processo de coagulação compostas por plaquetas e fibrina. A associaçãoclínica entre neoplasias e trombos é conhecida há mais de um século, e os eventos tromboembólicos são mais frequentes em pacientes oncológicos. Esse trabalho visou avaliar a presença e frequência de eventos trombóticos em pacientes com Linfoma Hodgkin (LH) e Não-Hodgkin (LNH) do ambulatório de hematologia do Conjunto Hospitalar de Sorocaba e analisar estatisticamente as principais causas de trombose nesse grupo, com o objetivo de determinar se a frequência de eventos trombóticos acompanha o valor de 6% a 12% descrito na literatura. Material e métodos: A obtenção dos dados foi realizada através da avaliação dos prontuários de 77 pacientes após autorização obtida via Termo de Consentimento Livre Esclarecido. As informações foram obtidas por meio de um formulário e transferidas para um computador onde foram avaliadas estatisticamente. Resultados: Dos 77 pacientes, nove (11.68%) desenvolveram algum tipo de evento trombótico. Destes, sete (77.78%) tiveram o sistema venoso acometido e dois (22.22%) o sistema arterial. Dos 50 pacientes com LNH, sete (14.00%) e dos 27 pacientes com LH, dois (7.40%) desenvolveram eventos trombóticos. Dos nove pacientes que apresentaram eventos trombóticos, três (33.33%) estavam no estadiamento II, dois (22.22%) no estadiamento III e três (33.34%) no estadiamento IV. Destes nove pacientes, seis (66.67%) apresentaram sintomas B, seis (66.67%) foram tratados com quimioterapia R-CHOP e dois (22.22%) com ABVD. Foram realizadas as análises dos seguintes desfechos utilizando o teste de Qui-quadrado: Eventos trombóticos e Faixa etária, Eventos trombóticos e Linfomas, Eventos trombóticos e Estadiamento, Eventos trombóticos e Ocorrência de recidiva, Eventos trombóticos e Presença de sintomas B. Todos obtiveram p maior que 0.05. Discussão: Os resultados que relacionam os linfomas com os eventos trombóticos estão dentro do esperado uma vez que tais eventos, em pacientes com linfomas, variam de 6% a 12% dependendo, também, dos subtipos de linfomas avaliados. Existe uma maior frequência de eventos trombóticos venosos em comparação aos arteriais, corroborando com o que é encontrado na literatura atual. Grande parte dos eventos trombóticos possui associação direta com o tratamento, intensidade do tratamento, estadiamento da doença e idade. Em uma meta-análise incluindo 18.018 pacientes com linfoma de 29 independentes coortes, a taxa de eventos trombóticos foi de 6,4%, sendo significativamente maior no LNH (6,5%) em comparação com LH (4,7%). No entanto, a partir de diferentes estudos clínicos, pode-se observar que a incidência de eventos trombóticos nos linfomas não depende apenas do subtipo e local do tumor, mas, também, do estágio da doença. Conclusão: A frequência de eventos trombóticos nos Linfomas de Hodgkin e Não-Hodgkin no Conjunto Hospitalar de Sorocaba foi de 11,68% e encontra-se dentro do valor estabelecido na literatura médica. Os eventos trombóticos ocorreram, em sua maioria, em pacientes com Linfoma Não-Hodgkin, estadiamento III e IV e com presença de sintoma B conforme indicado pela literatura, apesar do valor de p indicar ausência de relevância estatística.

Archana Solanki, Ashutosh Singh, Abhishek Chauhan et al.

We report a case of Wegener's granulomatosis (WG) who very well responded to the combination strategy of therapeutic plasma exchange (TPE) and immunosuppression. The patient was a 38-year-old female, diagnosed with severe form of WG. A total of seven cycles was performed with 1.3 total plasma volumes (TPVs) on every alternate day. Standard induction therapy was also started that comprised of a combination of 500 mg intravenous (i.v.) cyclophosphamide and methylprednisolone 1 g slow i.v. daily for 3 days followed by oral prednisolone 60 mg daily for 4 weeks. After seven cycles of TPE, the patient improved and hence TPE was stopped.

Dre'Von A. Dobson, Alisa S. Wolberg

Abstract Accounts of the numerous negative effects caused by COVID‐19 are pervasive, but few perspectives have identified any positive impacts of this massive societal shift. This forum examines potentially positive changes that have occurred within the scientific community amid the chaotic pandemic. Among these positives are the formation of virtual supergroups and an interdisciplinary brain trust. In forcing scientists away from their lab benches, COVID‐19 has created time and space for more conversations about science and experimental design. Being away from the lab in this time of social unrest has also given scientists time to directly address institutional racism and its suppression of diversity in science. Although COVID‐19 has been an unforeseen disaster of epic proportions, some of the resulting changes in our scientific community should remain in place after the pandemic is over. By leveraging these small wins, we will undoubtedly return to our laboratories stronger, smarter, and more efficient.

Nataly Apollonsky, Norma B. Lerner, Fengqing Zhang et al.

Objective. The aim of this preliminary study was to describe putative markers of cerebral vasculopathy and investigate relationships among these markers, demographic factors, and cognitive function in a young sample of neurologically normal children with SCD. Study Design. Thirty-eight children with homozygous HbS, aged 4–11 years, were included. Estimated IQ and markers of coagulation and endothelial activation, hemolysis, and inflammation, as well as transcranial Doppler velocities, hydroxyurea use, and demographic information were obtained. Results. Using multiple regression analyses, there were few significant independent associations between biomarkers or blood flow velocity and estimated IQ. Lactic dehydrogenase (LDH) independently predicted cognitive function, but blood flow velocity did not mediate this relationship. Maternal education, patient age, and hydroxyurea status were independent predictors of cognition. Given the small sample size, a LASSO statistical model was employed to further identify potential predictors of IQ, which identified LDH, absolute neutrophil count (ANC), platelet count, thrombin-antithrombin (TAT), tissue factor (TF), maternal education, age, and hydroxyurea as potential predictors of cognition. Conclusions. In addition to effects of age and maternal education, some vasculopathic markers are associated with cognitive function in young children with SCD, and these relationships do not appear to be mediated through blood flow velocity. Although the lack of association among certain variables was not as predicted, results provide support for further research regarding the influence of vasculopathic markers on cognitive function in children with SCD without stroke, especially intravascular hemolysis and coagulation/endothelial activation, and a possible role for HU treatment in preventing or reversing cognitive decline.

Peter Valent, Attilio Orazi, Michael R. Savona et al.

Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm characterized by dysplasia, abnormal production and accumulation of monocytic cells and an elevated risk of transforming into acute leukemia. Over the past two decades, our knowledge about the pathogenesis and molecular mechanisms in CMML has increased substantially. In parallel, better diagnostic criteria and therapeutic strategies have been developed. However, many questions remain regarding prognostication and optimal therapy. In addition, there is a need to define potential pre-phases of CMML and special CMML variants, and to separate these entities from each other and from conditions mimicking CMML. To address these unmet needs, an international consensus group met in a Working Conference in August 2018 and discussed open questions and issues around CMML, its variants, and pre-CMML conditions. The outcomes of this meeting are summarized herein and include diag nostic criteria and a proposed classification of pre-CMML conditions as well as refined minimal diagnostic criteria for classical CMML and special CMML variants, including oligomonocytic CMML and CMML associated with systemic mastocytosis. Moreover, we propose diagnostic standards and tools to distinguish between ‘normal’, pre-CMML and CMML entities. These criteria and standards should facilitate diagnostic and prognostic evaluations in daily practice and clinical studies in applied hematology.

Alexander T. Cohen, Cihan Ay, Philippe Hainaut et al.

Correction to: Thrombosis Journal (2018) 16:9 DOI 10.1186/s12959-018-0163-7

Saartje Bloemen, Hilde Kelchtermans, H. Coenraad Hemker

Abstract Accurate thrombin generation determination by calibrated automated thrombinography can be sustained when reducing the plasma and reagent volumes up to half, but not for higher reductions or plasma dilutions.

İbrahim Kulaç, Çetin Demir, Yahya Büyükaşık et al.

Objective: Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disease in adults. The aim of this study is to find out if the extent of proliferation centers or the immunohistochemical expression of p53 is related to disease prognosis. Materials and Methods: In the scope of this study, 54 biopsy specimens from 51 patients (50 of lymph nodes; the others of spleen, tonsil, orbit, and liver) diagnosed with CLL at the Hacettepe University Department of Pathology in 2000-2013 were reevaluated. The clinical and demographic data of the patients were obtained from our patient database. Biopsy samples were assessed semi-quantitatively for the percentage of proliferation center/total biopsy area (PC/TBA) and an immunohistochemical study was performed on representative blocks of tissues for p53 expression. Results: When the patients were divided into two categories according to Rai stage as high and low (stages 0, 1, and 2 vs. stages 3 and 4), it was seen that patients with low Rai stage had a better prognosis than those with high stages (p=0.030). However, there was no statistically significant correlation between overall survival and PC/TBA ratio or p53 expression levels. Conclusion: In our cohort, PC/TBA ratio and immunopositivity of p53 did not show correlations with overall survival.

Janice P. Dutcher

Christopher P. Venner, Joanna Wegrzyn Woltosz, Thomas J. Nevill et al.

We examined whether lenalidomide exposure up-regulates miRNAs and mRNAs, previously shown to play a role in the disease phenotype of del(5q) myelodysplastic syndrome, in pre-treatment CD34+ marrow cells. We hypothesized that increased expression would predict for clinical response. Changes in miR-143, miR-145, miR-146a, miR-146b, miR-378, miR-584, SPARC and RPS14 were examined in del(5q) (n=10) and non-del(5q) (n=18) myelodysplastic syndrome patient samples. Significantly increased expression of miR-143 (1.8-fold and 1.5-fold in del(5q) and non-del(5q), respectively), and miR-145 (1.9-fold and 1.6-fold in del(5q) and non-del(5q), respectively) was observed. In the del(5q) myelodysplastic syndrome cohort, transfusion independence correlated with a 1.3-fold or more increase in miR-145 expression and response over 12 months correlated with a 1.5-fold or more increase. Knockdown of miR-143 and miR-145 in cord blood CD34+ cells resulted in increased erythroid progenitor activity. Lenalidomide selectively abrogated progenitor activity in cells depleted of miR-143 and miR-145 supporting a key role for miR-143/145 in the sensitivity to lenalidomide of del(5q) myelodysplastic syndrome patients.

Fatih Kardas, Aysun Cetin, Musa Solmaz et al.

OBJECTIVE: The aim of our study is to discuss the efficacy of low-density lipoprotein-cholesterol (LDL-C) apheresis procedure using the cascade filtration system for pediatric patients with homozygous familial hypercholesterolemia (FH), and to clarify the adverse effects and difficulties. METHODS: LDL apheresis using the cascade filtration system was performed in 3 pediatric patients with homozygous FH. In total, 120 apheresis sessions were performed for all patients. RESULTS: Cascade filtration therapy significantly reduced the mean LDL-C values from 418 +- 62 mg/dl to 145 +- 43 mg/dl (p<0.05). We determined an acute mean reduction in the plasma levels of total cholesterol (57.9%), LDL cholesterol (70.8%), and high-density lipoprotein (HDL) cholesterol (40.7%). Treatments were well tolerated. The most frequent clinical adverse effects were hypotension in 3 sessions (2.5%), chills/feeling cold (1.7%) in 2 sessions, and nausea and vomiting in 3 sessions (2.5%). CONCLUSION: Our experience with three patients using the cascade filtration system were, good clinical outcomes, laboratory findings, safety of usage, minor adverse effects and technical problems.