Blood最新文献

{"title":"How I treat infant acute lymphoblastic leukemia.","authors":"Jack Bartram, Philip Ancliff, Ajay Vora","doi":"10.1182/blood.2023023154","DOIUrl":"10.1182/blood.2023023154","url":null,"abstract":"<p><strong>Abstract: </strong>Infant acute lymphoblastic leukemia (ALL) is an aggressive malignancy that has historically been associated with a very poor prognosis. Despite large cooperative international trials and incremental increases in intensity of therapy, there has been no significant improvement in outcome over the last 3 decades. Using representative cases, we highlight the key differences between KMT2A-rearranged and KMT2A-germ line infant ALL, and how advances in molecular diagnostics are unpicking KMT2A-germ line genetics and guiding treatment reduction. We focus on KM2TA-rearranged infant B-cell ALL for which the last few years have seen the emergence of novel therapies that both are more effective and less toxic than conventional chemotherapy. Of these, there is promising early data on the efficacy and tolerability of the bispecific T-cell engager monoclonal antibody, blinatumomab, as well as the use of autologous and allogeneic chimeric antigen receptor T-cell therapy. We discuss how we can improve risk stratification and incorporate these new agents to replace the most toxic elements of currently deployed intensive chemotherapy schedules with their associated unacceptable toxicity.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"35-42"},"PeriodicalIF":21.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How I use noninvasive prenatal testing for red blood cell and platelet antigens","authors":"Renske M. van ’t Oever, E. J. T. Verweij, Masja de Haas","doi":"10.1182/blood.2023022893","DOIUrl":"https://doi.org/10.1182/blood.2023022893","url":null,"abstract":"Alloimmunization during pregnancy occurs when a mother produces antibodies against fetal antigens, leading to complications like hemolytic disease of the fetus and newborn (HDFN) and fetal and neonatal alloimmune thrombocytopenia (FNAIT). HDFN involves destruction of fetal red blood cells, potentially causing severe anemia, hydrops fetalis, and fetal death. FNAIT affects fetal platelets and possibly endothelial cells, resulting in risk of intracranial hemorrhage and brain damage. Traditional invasive methods for fetal antigen genotyping, like amniocentesis, carried miscarriage risks. The discovery of cell-free fetal DNA (cff-DNA) in maternal plasma enabled safe, noninvasive prenatal testing (NIPT). Initially used for Rhesus antigen D blood group typing, NIPT now covers various blood group antigens. Advances in technology have further enhanced the accuracy of NIPT. Despite challenges such as low cff-DNA fractions and complex genetic variations, NIPT has become essential in managing alloimmunized pregnancies. In NIPT it is important to prevent both false-positive results and false-negative results. Particularly in the coming decades, more possibilities for personalized antenatal treatment for HDFN and FNAIT cases will become apparent and accurate NIPT blood group antigen typing results are crucial for guiding clinical decisions. In this paper we describe this journey and provide practical tools for the clinic.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"39 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding cost-effectiveness of PNH therapies.","authors":"Amar H Kelkar, Gregory A Abel","doi":"10.1182/blood.2024027053","DOIUrl":"https://doi.org/10.1182/blood.2024027053","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 1","pages":"8-10"},"PeriodicalIF":21.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of standard-of-care ciltacabtagene autoleucel for relapsed/refractory multiple myeloma.","authors":"Surbhi Sidana, Krina K Patel, Lauren C Peres, Radhika Bansal, Mehmet H Kocoglu, Leyla Shune, Shebli Atrash, Kinaya Smith, Shonali Midha, Christopher Ferreri, Binod Dhakal, Danai Dima, Patrick Costello, Charlotte Wagner, Ran Reshef, Hitomi Hosoya, Lekha Mikkilineni, Djordje Atanackovic, Saurabh Chhabra, Ricardo Parrondo, Omar Nadeem, Hashim Mann, Nilesh Kalariya, Vanna Hovanky, Gabriel De Avila, Ciara L Freeman, Frederick L Locke, Melissa Alsina, Sandy Wong, Megan Herr, Myo Htut, Joseph McGuirk, Douglas W Sborov, Jack Khouri, Thomas Martin, Murali Janakiram, Yi Lin, Doris K Hansen","doi":"10.1182/blood.2024025945","DOIUrl":"10.1182/blood.2024025945","url":null,"abstract":"<p><strong>Abstract: </strong>Ciltacabtagene autoleucel (cilta-cel) was approved in 2022 for patients with relapsed/refractory multiple myeloma (RRMM). We report outcomes with cilta-cel in the standard-of-care setting. Patients with RRMM who underwent leukapheresis for cilta-cel manufacturing between 1 March 2022 and 31 December 2022 at 16 US academic medical centers were included. Overall, 255 patients underwent leukapheresis and 236 (92.5%) received cilta-cel, of which 54% would not have met CARTITUDE-1 eligibility criteria. In treated patients (N = 236), cytokine release syndrome was seen in 75% (grade ≥3, 5%), immune effector cell-associated neurotoxicity syndrome in 14% (grade ≥3, 4%), and delayed neurotoxicity in 10%. Overall and complete response rates were as follows: all patients who received cilta-cel (N = 236), 89% and 70%; patients receiving conforming cilta-cel (n = 191), 94% and 74%; and conforming cilta-cel with fludarabine/cyclophosphamide lymphodepletion (n = 152), 95% and 76%, respectively. Nonrelapse mortality was 10%, most commonly from infection. After a median follow-up of 13 months from cilta-cel, the median progression-free survival (PFS) was not reached, with 12-month estimate being 68% (95% confidence interval, 62-74). High ferritin levels, high-risk cytogenetics, and extramedullary disease were independently associated with inferior PFS, with a signal for prior B-cell maturation antigen-targeted therapy (P = .08). Second primary malignancies excluding nonmelanoma skin cancers were seen in 5.5% and myeloid malignancies/acute leukemia in 1.7%. We observed a favorable efficacy profile of standard-of-care cilta-cel in RRMM, despite more than half the patients not meeting the CARTITUDE-1 eligibility criteria.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"85-97"},"PeriodicalIF":21.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How I treat postimmunotherapy relapsed B-ALL.","authors":"Adam J Lamble, Alexandra E Kovach, Nirali N Shah","doi":"10.1182/blood.2024024517","DOIUrl":"10.1182/blood.2024024517","url":null,"abstract":"<p><strong>Abstract: </strong>Despite significant advancements in single-antigen targeted therapies for B-cell acute lymphoblastic leukemia (B-ALL), nonresponse and relapse persist as major challenges. Antigen escape after blinatumomab or CD19-directed chimeric antigen receptor (CAR) T cells (CD19-CAR), as CD19-negative B-ALL or lineage switch (LS) to acute myeloid leukemia, present diagnostic and treatment complexities. Given the poor outcomes for patients experiencing a postinfusion relapse, particularly those with loss of the target antigen, a strategic approach to diagnosis and treatment is imperative. In this discussion, we outline a systematic approach to managing postimmunotherapy events, categorized by CD19-positive relapse, CD19-negative relapse, and LS. We explore treatment modalities including CD19-CAR reinfusions, humanized CAR constructs, combinatorial strategies, and alternative antigen-targeted therapies, such as blinatumomab and inotuzumab. Challenges in diagnosis, particularly with antigen-escape, are addressed, highlighting the role of next-generation sequencing and multiparameter flow cytometry for myeloid marker monitoring.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"64-74"},"PeriodicalIF":21.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parvovirus B19-induced autoimmune hemolytic anemia in hereditary elliptocytosis.","authors":"Supapitch Chanthong, Pimlak Charoenkwan","doi":"10.1182/blood.2024026797","DOIUrl":"https://doi.org/10.1182/blood.2024026797","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 1","pages":"141"},"PeriodicalIF":21.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solvitur ambulando.","authors":"Jonathan L Kaufman","doi":"10.1182/blood.2024026813","DOIUrl":"https://doi.org/10.1182/blood.2024026813","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 1","pages":"4-5"},"PeriodicalIF":21.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin C deprivation puts stem cells to sleep.","authors":"Juan Carlos Balandrán, Iannis Aifantis","doi":"10.1182/blood.2024026887","DOIUrl":"https://doi.org/10.1182/blood.2024026887","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 1","pages":"7-8"},"PeriodicalIF":21.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How I treat adult Ph+ ALL.","authors":"Sabina Chiaretti, Robin Foà","doi":"10.1182/blood.2023023152","DOIUrl":"10.1182/blood.2023023152","url":null,"abstract":"<p><strong>Abstract: </strong>The Philadelphia (Ph) chromosome is one of the few genetic aberrations in which a casualty has been proven and, as such, represents a success in the history of medicine. This is also evident in the setting of Ph+ acute lymphoblastic leukemia (ALL), the most frequent genetic subgroup in adult ALL, whose incidence increases with age and whose prognosis, before the advent of tyrosine kinase inhibitors (TKIs), was particularly poor. The outcome and management of patients with Ph+ ALL have greatly improved since the incorporation of first-, second-, and third-generation TKIs in the therapeutic backbone and is further changing with the more recent introduction of immunotherapy. This allows for long-term survival rates currently ranging between 75% and 80%. The clinical scenario of adult Ph+ ALL has thus changed profoundly, and new challenges are emerging. In this article, illustrative clinical cases are used to discuss the current role of systemic chemotherapy and allogeneic stem cell transplant, the difficulty in treating central nervous system relapses and, more in general, relapses in the current therapeutic era, and the possibility of stopping TKIs. Finally, the challenges related to an optimal management of these patients are discussed.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"11-19"},"PeriodicalIF":21.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How I manage patients with unexplained cytopenia","authors":"Luca Malcovati, Mario Cazzola","doi":"10.1182/blood.2024025771","DOIUrl":"https://doi.org/10.1182/blood.2024025771","url":null,"abstract":"The term “unexplained cytopenia” is used to describe a condition characterized by peripheral blood cytopenia that cannot be attributed to identifiable causes using conventional tests or to any concomitant diseases. Unexplained cytopenia requires clinical attention and further investigation to identify individuals at risk of developing a hematologic neoplasm. The available evidence suggests that somatic mutation analysis may effectively complement the diagnostic workup and clinical management of unexplained cytopenia. Indeed, the presence or absence of somatic mutation(s) in myeloid genes shows high positive and negative predictive values for myeloid neoplasms (MNs). Mutation analysis is also crucial for identifying patients with clonal cytopenia of undetermined significance (CCUS), a condition at increased risk of developing a MN. Recently, clinical/molecular prognostic models have been developed, providing valuable tools for the personalization of clinical and molecular surveillance. Most patients with CCUS show mild cytopenia and do not require therapeutic intervention. Currently, there is no treatment approved for CCUS, and transfusion therapy is the sole therapeutic option for patients with severe symptomatic cytopenia. However, this field has been emerging as a domain of active clinical investigation. This article presents 4 case studies of patients with unexplained cytopenia, which hematologists may encounter in their clinical practice.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"48 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}