Hematology. American Society of Hematology. Education Program最新文献

{"title":"Choosing the optimal maintenance strategy in multiple myeloma.","authors":"Benjamin Puliafito, Diana Cirstea, Noopur Raje","doi":"10.1182/hematology.2025000732","DOIUrl":"10.1182/hematology.2025000732","url":null,"abstract":"<p><p>While lenalidomide has been the established standard of care for maintenance after autologous stem cell transplantation in newly diagnosed multiple myeloma, risk-adapted maintenance strategies with the addition of proteasome inhibitors can provide additional benefit in high-risk disease. The widespread use of anti-CD38 monoclonal antibodies (mAbs) in induction and consolidation has further disrupted this paradigm, offering the use of anti-CD38 mAbs in maintenance. Novel immunotherapeutic approaches and minimal residual disease-guided maintenance strategies are being actively investigated. The evolution of maintenance strategies provides a window to a future where maintenance therapy is not only more effective at sustaining deep and durable responses but also more dynamic with careful de-escalation strategies.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"412-423"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proactive management to improve outcomes of high-risk pregnancy in people with sickle cell disease.","authors":"Mofiyin A Obadina, Lydia H Pecker","doi":"10.1182/hematology.2025000744","DOIUrl":"10.1182/hematology.2025000744","url":null,"abstract":"<p><p>Pregnancy is high risk for individuals with sickle cell disease (SCD), and maternal morbidity and mortality are unchanged in middle- and high-income settings. As many as 30% of SCD pregnancies may be uncomplicated, but most are associated with complications. The odds of severe maternal morbidity are much higher in Black women with SCD than in Black women without SCD or non-Black women. Prophylactic red cell transfusions are considered low risk according to American Society of Hematology guidelines and are the only disease-modifying therapy available for use in pregnancy. When initiated in the preconception and/or prenatal period, treatment is associated with reduced maternal and fetal mortality, painful crises, and pulmonary complications in pregnancy. Furthermore, pain occurs in as many as 75% of SCD pregnancies; in meta-analyses and randomized controlled data, transfusions reduce pain events during SCD pregnancy. British, American, and French guidelines make recommendations regarding transfusion indications in SCD pregnancy. Many people with SCD, and most with hemoglobin SS or hemoglobin Sβ0-thalassemia, have an indication for prophylactic transfusion during pregnancy. Transfusion may meaningfully improve outcomes for pregnant people with SCD. We discuss our approach to managing SCD pregnancy using the case of a patient cared for in the mid-Atlantic region of the United States.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"511-522"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The challenge of deintensifying chemotherapy for children and adolescents with B-ALL in the immunotherapy era.","authors":"Sumit Gupta, Jennifer McNeer, Maureen O'Brien, Rachel Rau, David Teachey","doi":"10.1182/hematology.2025000709","DOIUrl":"10.1182/hematology.2025000709","url":null,"abstract":"<p><p>Recent clinical trials have shown that the addition of immunotherapy has substantially improved cure rates for children and adolescents newly diagnosed with B-acute lymphoblastic leukemia. Most of these patients now have outcomes similar to those previously seen in only the most favorable subgroups. As such, efforts are underway to study whether the incorporation of immunotherapy can allow for elements of traditional toxic chemotherapy to be removed while maintaining excellent outcomes. In this article, we discuss important considerations for such studies, including those related to which patients are appropriate targets of deintensification efforts and which elements of therapy are or are not appropriate candidates for omission.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"229-235"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updates in antithrombotic therapy in coronary and peripheral artery disease.","authors":"Amy West Pollak","doi":"10.1182/hematology.2025000684","DOIUrl":"10.1182/hematology.2025000684","url":null,"abstract":"<p><p>Atherosclerotic cardiovascular disease (ASCVD) encompasses a spectrum of vascular conditions, including coronary artery disease (CAD) and lower extremity peripheral artery disease (PAD), which frequently coexist. In the setting of ASCVD, there is a common underlying pathophysiology for acute ischemic events related to platelet activation and thrombin generation. The scope of this review focuses on the role of dual-pathway inhibition, the approach combining antiplatelet and antithrombotic therapy, for improvement in cardiovascular outcomes in patients with ASCVD. To determine which patients with CAD and PAD may benefit from dual-pathway inhibition, a brief overview of clinical presentations for both stable CAD and the spectrum of lower extremity PAD is outlined.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"34-38"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No shots needed: direct oral anticoagulants in cancer-associated thrombosis-10-year follow-up.","authors":"Ruchi Desai, Michael Jaglal","doi":"10.1182/hematology.2025000690","DOIUrl":"10.1182/hematology.2025000690","url":null,"abstract":"<p><p>Active malignancy is a known prothrombotic state, first described by Armand Trousseau as thrombophlebitis occurring in a patient with metastatic gastric cancer. The most common presentation of cancer-associated thrombosis (CAT) is venous thromboembolism, inclusive of deep venous thrombosis and pulmonary embolism. With advances in survival of many cancers, the incidence of CAT is increasing, and an estimated 15% to 20% of all patients with cancer will experience venous thromboembolism during their treatment. Consequently, management and prevention strategies for CAT are paramount for comprehensive clinical care of patients with active malignancy. Direct oral anticoagulants, which have fixed drug dosing, few drug-drug interactions, lack of monitoring requirements, and ease of oral administration, have emerged as the preferred option for CAT, with significant clinical trial data supporting their use. Here, we review the current treatment and prevention paradigms for patients with CAT, the specific role of direct oral anticoagulants for CAT, and ongoing challenges in CAT treatment.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"80-86"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cryptogenic stroke: definitions and management.","authors":"William J Powers","doi":"10.1182/hematology.2025000682","DOIUrl":"10.1182/hematology.2025000682","url":null,"abstract":"<p><p>The term cryptogenic strokes refers to ischemic strokes that, after thorough evaluation, do not meet criteria for any of 4 designated major subtypes: stenosis due to large or medium artery atherosclerosis, cardiac pathology that could lead to embolism, presumed intracranial small artery disease (lacunar stroke), and other less common specific conditions. The term embolic strokes of undetermined source (ESUS) was introduced to further refine this classification by specifying the necessary diagnostic evaluation and exclusionary conditions. In patients with cryptogenic stroke/ESUS, nonstenotic atherosclerosis and its attendant risk factors are common. Randomized controlled trials have demonstrated no benefit of oral anticoagulants over aspirin in preventing recurrent stroke in these patients. Patients with cryptogenic stroke/ESUS should be treated with aspirin and aggressive atherosclerosis risk factor management.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"15-21"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deconstructing gene therapy in hemophilia for the clinician.","authors":"Guy Young","doi":"10.1182/hematology.2025000763","DOIUrl":"10.1182/hematology.2025000763","url":null,"abstract":"<p><p>After decades of research, gene therapy for hemophilia is now commercially available for both hemophilia A and B. Currently, two products, valoctocogene roxaparvovec (for hemophilia A) and etranacogene dezaparvovec (for hemophilia B), have been licensed following approval in the United States and several other countries. Therefore, clinicians must familiarize themselves with these novel treatment options just as they do with other newly available products in order to provide their patients the opportunity to consider which treatment may suit them best. Undoubtedly, gene therapy is a novel platform for treating human disease, and unlike other hemophilia treatments, its biology, mechanisms, and administration logistics are quite complex. Furthermore, additional products using different approaches have entered clinical trials, with more in the preclinical stages of development. This review's aims are (1) to deconstruct gene therapy in hemophilia and provide a basic framework for understanding its components and processes, including the transgene, the vector, and the delivery systems, in order to help clinicians present gene therapy as a treatment option in a shared decision-making model, better understand the clinical data, and explain gene therapy to their patients; (2) to gain knowledge of the currently approved gene therapies for hemophilia A and B, including their eligibility and exclusion criteria and the range of expected outcomes; and (3) to comprehend the shared decision-making process for these therapies and their implementation in clinical practice. In addition, a brief review of the currently approved products and those in clinical trials is presented, followed by a discussion of practical considerations for implementing gene therapy in practice.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"659-667"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endless possibilities and how to exploit them? What is the optimal treatment sequence?","authors":"Rajshekhar Chakraborty, Divaya Bhutani, Suzanne Lentzsch","doi":"10.1182/hematology.2025000760","DOIUrl":"10.1182/hematology.2025000760","url":null,"abstract":"<p><p>The therapeutic landscape of multiple myeloma has undergone a profound transformation with the incorporation of anti-CD38 monoclonal antibody (mAb)-based quadruplet regimens in the frontline setting and T-cell redirecting immunotherapies in the relapsed setting. In this article, we synthesize evidence from pivotal trials to guide treatment decisions and sequencing across the disease trajectory. For transplant-eligible, transplant-deferred, and fit transplant-ineligible patients who are younger than 80 years old, we use anti-CD38 mAb-, lenalidomide-, and bortezomib/carfilzomib-based quadruplets as an induction regimen. For early relapse (1-3 prior lines), chimeric antigen receptor T-cell therapies targeting B-cell maturation antigen (BCMA) have demonstrated superiority over standard regimens, with ciltacabtagene autoleucel (cilta-cel) being the most efficacious product currently, albeit with some unique toxicities such as parkinsomism. Belantamab mafadotin-based triplets have shown impressive efficacy in lenalidomide and anti-CD38 mAb-refractory patients, although ocular toxicity remains a concern. Anti-CD38 mAb and carfilzomib-based triplets remain an essential therapeutic option in patients not refractory to anti-CD38 mAb. In late relapse (≥4 prior lines), bispecific antibodies (BsAbs) targeting BCMA (teclistamab, elranatamab, and linvoseltamab) and GPRC5D (talquetamab) have demonstrated impressive single-agent activity with distinct toxicity profiles. Emerging evidence supports prioritizing chimeric antigen receptor T-cell therapy before BsAbs when clinically feasible, as sequential efficacy appears compromised in the reverse sequence. For patients with BCMA- and GPRC5D-refractory disease, FcRH5-targeting BsAb (cevostamab), BCL2 inhibitors for t(11;14)-positive disease, and novel trispecific antibodies (BCMAXCD38; BCMAXGPRC5D) offer promising options. Strategic sequencing trials represent a critical unmet need, with PFS (progression-free survival)-2 potentially serving as a valuable intermediate end point to guide clinical decision-making while waiting for mature survival data.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"636-644"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune targeting in Ph-negative and Ph-positive B-ALL: improving outcomes and minimizing chemotherapy in adult B-ALL.","authors":"Kristen M O'Dwyer","doi":"10.1182/hematology.2025000710","DOIUrl":"10.1182/hematology.2025000710","url":null,"abstract":"<p><p>With the addition of antibody-based immunotherapy to frontline treatment regimens for B-lineage acute lymphoblastic leukemia (B-ALL), patients across the age spectrum now experience superior long-term survival. The pressing question for the field is whether immunotherapy may replace some of the intensive elements of the standard chemotherapy backbone to reduce overall toxicity and duration while maintaining superior outcomes. For young adults with B-ALL, most clinical trials have added immunotherapy to the intensive, pediatric-inspired regimens to achieve deeper remissions, while necessarily increasing duration, complexity, and possible toxicities. In contrast, clinical trials for older adults have used immunotherapy as a substitute to eliminate or reduce cytotoxic chemotherapy. And although survival outcomes for older adults remain distinctly inferior to those in the pediatric age group, it is hoped that the potential simplification of the chemoimmunotherapy backbone for all patients may be guided by the successes and shortcomings discovered in the treatment of older adults. In this article, I discuss the treatment of older adult patients with B-ALL in the immunotherapy era and how this approach may pave the way for implementing a deescalation strategy for younger adult patients with B-ALL, while maintaining the significant survival benefits that have been achieved during the past 20 years.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"236-244"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using genomics to refine pediatric AML risk stratification.","authors":"Martina Pigazzi, Soheil Meshinchi, Franco Locatelli","doi":"10.1182/hematology.2025000714","DOIUrl":"10.1182/hematology.2025000714","url":null,"abstract":"<p><p>In the past 20 years, advances in genomic technologies have greatly improved our understanding of pediatric acute myeloid leukemia (AML). Today, cytogenetic tests can detect structural changes in approximately 75% of cases and remain a main tool for assessing risk. Recent technologies, such as next-generation sequencing, are revealing additional structural alterations (cryptic fusions) and mutations that often cooperate to influence disease biology and treatment response. This evolving genetic landscape has identified unique childhood subtypes of AML defined by specific fusions, such as NUP98::NSD1, CBFA2T3::GLIS2, and varied KMT2A rearrangements, which are linked to distinct clinical outcomes. Emerging data also point to the poor prognosis associated with certain subtypes of NPM1, like the NPM1-D isoform. Additionally, mutations in genes like WT1, DNMT3A, and TP53, the latter of which are rare in childhood AML, may influence patients' outcomes, particularly when occurring in combination. Targeted therapies, including FLT3, BCL2, and menin inhibitors, are beginning to reshape treatment, offering more personalized approaches. However, integrating these drugs effectively into the patient's treatment strategy remains challenging due to the genetic complexity and rarity of pediatric AML. Key issues ahead include identifying which genetic features truly affect outcomes, using this information to personalize therapy, predicting who will benefit from targeted drugs, and choosing the best markers to track disease response over time. Looking forward, collaborative efforts are urgently needed to validate pediatric-specific biomarkers, test novel drug combinations, and link genetic data to clinical outcomes to design trials and future treatment strategies.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"270-278"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}