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

{"title":"New age GVHD prophylaxis regimens: what works for what donor and why.","authors":"Mahasweta Gooptu, John Koreth","doi":"10.1182/hematology.2025000737","DOIUrl":"10.1182/hematology.2025000737","url":null,"abstract":"<p><p>Allogeneic hematopoietic stem-cell transplantation is a curative modality for hematologic malignancies, bone marrow failure syndromes, hemoglobinopathies, and other nonmalignant disorders. Graft-versus-host disease (GVHD)-in its acute or chronic form-is an important transplant complication. The effective prevention of GVHD is crucial to the success of allotransplantation. Acute GVHD is mediated by the recognition of recipient antigens by donor T lymphocytes, with the subsequent activation and proliferation of T cells and establishment of an inflammatory cytokine cascade. Chronic GVHD is mediated by T-cell, B-cell, and macrophage activation with eventual inflammation and fibrosis. Standard approaches for GVHD prevention have been calcineurin-inhibitor (CNI) based, while newer approaches have focused on adding in-vivo T-cell modulation to a CNI backbone with antimetabolites such as posttransplant cyclophosphamide (PTCy), checkpoint blocking agents such as abatacept, or mammalian target of rapamycin (mTOR) inhibition with sirolimus. Still other approaches focus on blocking T-cell trafficking to target organs via integrin blockade (vedolizumab), cytokine blockade (JAK inhibitors), and B-cell blockade for chronic GVHD prevention. The use of PTCy and abatacept have improved allotransplantation safety and efficacy with human leukocyte antigen (HLA)-mismatched as well as HLA-matched donors, thus expanding the donor pool greatly for patients of all ancestries, and ushering in a new era in transplantation where donors are available for almost every patient.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"458-464"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677507","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":"Predictors for future bleeding in bleeding disorder of unknown cause.","authors":"Tim Dreier, Dino Mehic, Cihan Ay, Johanna Gebhart, Ingrid Pabinger","doi":"10.1182/hematology.2025000696","DOIUrl":"10.1182/hematology.2025000696","url":null,"abstract":"<p><p>Bleeding disorder of unknown cause (BDUC) is increasingly recognized as a common diagnosis among adult patients with mild to moderate bleeding symptoms and is reflective of unremarkable hemostatic tests despite a clinically relevant bleeding tendency. While extensive clinical and basic research has been conducted on the bleeding phenotype and underlying mechanisms of BDUC, great uncertainty remains regarding the long-term risk for spontaneous bleeding and the bleeding risk after hemostatic challenges. Currently available data suggest that a substantial portion of BDUC patients continue to experience spontaneous bleeding symptoms, such as easy bruising, epistaxis, and heavy menstrual bleeding. Risk factors associated with the persistence of these symptoms include the presence of the respective symptom prior to the BDUC diagnosis and a higher baseline bleeding score. Furthermore, a large proportion of BDUC patients report bleeding complications after surgery or child delivery prior to initial investigations. Patients with prior bleeding complications after such events, patients with blood group O, and patients who did not receive hemostatic prophylaxis demonstrate an increased risk for postinterventional bleeding during follow-up. Although BDUC remains a diagnosis of exclusion, accumulating data underscore the need to recognize it as a potentially persistent clinically relevant condition. Future studies should focus on refining diagnostic algorithms, investigating underlying mechanisms, and developing predictive tools for bleeding risk to improve individualized management strategies.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"120-126"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677515","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":"When it's not Glanzmann thrombasthenia or Bernard-Soulier syndrome: diagnosing other qualitative platelet disorders.","authors":"Catherine P M Hayward, Subia Tasneem","doi":"10.1182/hematology.2025000699","DOIUrl":"10.1182/hematology.2025000699","url":null,"abstract":"<p><p>Inherited and acquired disorders that qualitatively impair platelet function represent important and commonly encountered conditions. While some rare, well-characterized conditions (eg, Glanzmann thrombasthenia and Bernard-Soulier syndrome) have pathognomonic findings and glycoprotein deficiencies, the more commonly encountered platelet function disorders are much more heterogeneous and challenging to diagnose. Qualitative platelet disorders typically present with mild to moderate, mucocutaneous, and challenge-related bleeding, particularly for hemostatic challenges prior to diagnosis. Diagnostic tests should assess platelet counts and size; platelet morphology by light microscopy; platelet function in aggregation assays (a \"gold standard\" test for qualitative platelet disorders); platelet-dense granule numbers, granule contents, and/or release; and, less commonly, platelet glycoproteins, procoagulant function, α-granule release, or ultrastructure. Genetic tests can be helpful, but the chances of finding a diagnostic, disease-causing, pathogenic mutation with a platelet disorder genetic test panel is much lower if there is not an a priori suspected cause and/or inherited thrombocytopenia. Commonly, the diagnosis of a qualitative platelet disorder is made after confirming impaired platelet aggregation responses to multiple agonists, with a pattern that excludes rare disorders (eg, Glanzmann thrombasthenia and Bernard-Soulier syndrome), and/or platelet-dense granule deficiency; both findings are highly predictive of a bleeding disorder. To communicate and discuss diagnostic test findings with patients and optimize care, it is also important to have knowledge of the bleeding risks for qualitative platelet disorders and their typical responses to therapies.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"137-146"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677366","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":"Advances in the diagnosis and management of pediatric Langerhans cell histiocytosis and Rosai-Dorfman disease: therapies, biomarkers, and response assessment.","authors":"Olive S Eckstein, Nitya Gulati","doi":"10.1182/hematology.2025000708","DOIUrl":"10.1182/hematology.2025000708","url":null,"abstract":"<p><p>Histiocytic disorders are characterized by abnormal accumulation of myeloid-derived histiocytes and a shared biology marked by RAS/MAPK/ERK pathway activation, yet the rarity and heterogeneity of these conditions have limited the availability of robust, well-controlled clinical trials to guide therapy. This review highlights Langerhans cell histiocytosis, the most common subtype, and Rosai-Dorfman disease, a less common non-Langerhans cell histiocytosis entity, using them as key examples to illustrate how advancements in molecular diagnostics and targeted MAPK inhibitors are reshaping clinical management in histiocytic disorders. In both disorders, treatment approaches range from active observation in mild cases to more aggressive interventions in high-risk or progressive disease, emphasizing the spectrum of clinical presentations and the need for individualized, biology-driven strategies.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"215-228"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677545","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 low/intermediate-risk MDS.","authors":"Hetty E Carraway","doi":"10.1182/hematology.2025000768","DOIUrl":"10.1182/hematology.2025000768","url":null,"abstract":"<p><p>Low- and intermediate-risk myelodysplastic syndromes (LR-MDS and Int-MDS, respectively) are characterized by ineffective hematopoiesis, along with the presence of at least 10% dysplasia in one cell line, accompanied by a low number and depth of peripheral blood cytopenias, a low bone marrow blast percentage, and a score of ≤0 on the Molecular International Prognostic Scoring System (IPSS-M). The information gleaned from mutational profiles at the time of myelodysplastic syndrome (MDS) diagnosis and over subsequent time points help with classification and prognosis, guiding therapeutic decisions. In LR-MDS, these decisions are initially focused on improving symptom control and optimizing hematologic parameters. New therapeutic options to reduce the red blood cell (RBC) transfusion burden have emerged since 2020 and include luspatercept and imetelstat. Erythropoiesis-stimulating agents and lenalidomide also address anemia and are generally recommended to start at the time of transfusion dependency, although emerging data suggest that an earlier start of these interventions might offer clinical benefits. Patients can derive years of benefit from these approaches in LR-MDS, but despite these therapies, ultimately MDS will evolve into higher-risk MDS (HR-MDS)/acute myeloid leukemia. Even though most LR-MDS patients present with anemia, patients can have isolated thrombocytopenia for which thrombopoietin receptor analogues can be used if blasts are low. Immunosuppressive therapy such as antithymocyte globulin is favored in the hypocellular MDS setting. Dose-modified hypomethylating agent use can be considered for LR-MDS, although neither overall survival (OS) nor progression-free survival (PFS) has been shown to improve with this approach. Targeted therapy directed to the presence of an IDH1 mutation is U.S. Food and Drug Administration (FDA) approved for the rare IDH1 mutated MDS (<10% of the time) and consideration to use an IDH2 inhibitor for IDH2 mutated MDS (<5% of the time) is reasonable. Interestingly, IDH mutations seem to appear with increased frequency in older patients and in patients with underlying autoimmune/rheumatological disorders.1.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"699-708"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677331","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":"Targeted triplet therapies incorporating FLT3 or IDH inhibitors: ready for prime time?","authors":"Himachandana Atluri, Yasmin Abaza, Jessica K Altman","doi":"10.1182/hematology.2025000754","DOIUrl":"10.1182/hematology.2025000754","url":null,"abstract":"<p><p>Combination therapies in acute myeloid leukemia (AML) are an area of current investigation due to the potential of overcoming resistance by targeting multiple pathways simultaneously. Triplet therapies combining hypomethylating agents, venetoclax, and targeted inhibitors are emerging as a promising therapy for older patients with AML unfit for intensive chemotherapy. These regimens have predominantly been studied in FLT3- and IDH1/2-mutated AML with attainment of high rates of measurable residual disease-negative composite remissions. Notably, patients with FLT3-internal tandem duplication and IDH1-mutated AML appear to garner a significant benefit from combination treatment due to poor duration of response to hypomethylating agents/venetoclax alone. While effective, the need to remain on indefinite therapy for individuals who are not stem cell transplant candidates and dose optimization/de-escalation strategies remain critical concerns. Herein, we aim to review the current treatment landscape of newly diagnosed and relapsed/refractory FLT3- and IDH1/2-mutated AML and the role of triplet regimens in these molecular subgroups.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"592-598"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677508","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":"Donor selection, graft engineering, and dosing oh my!","authors":"Amy Moskop, Julie-An Talano","doi":"10.1182/hematology.2025000736","DOIUrl":"10.1182/hematology.2025000736","url":null,"abstract":"<p><p>Allogeneic hematopoietic cell transplantation is a potentially curative therapy for patients with both malignant and nonmalignant disorders. To select the optimal donor for allogeneic hematopoietic cell transplantation, the first step is to search for a matched sibling donor or a matched unrelated donor, both of which yield comparable outcomes in the current clinical landscape. Additional donor options include haploidentical donors, mismatched unrelated donors, and umbilical cord blood donors. Newer transplant approaches have refined the use of these donor sources to improve outcomes. Beyond human leukocyte antigen compatibility, several non-human leukocyte antigen factors influence optimal donor selection. These include donor age, the presence of donor-specific antibodies, cytomegalovirus status, and ABO blood type compatibility. Various graft engineering strategies have been developed. These include posttransplant cyclophosphamide, T-cell depletion techniques such as CD34+ selection, CD45RA depletion, and αβ T-cell depletion, T regulatory purification, and umbilical cord blood expansion. Optimizing the cell dose used in transplantation is also critical to improving outcomes. All of these strategies combined allow nearly every patient to find a donor with continued improvements in outcomes.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"450-457"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677616","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":"Management of iron overload in adult myelodysplastic syndrome.","authors":"Heather A Leitch, Rena Buckstein","doi":"10.1182/hematology.2025000691","DOIUrl":"10.1182/hematology.2025000691","url":null,"abstract":"<p><p>The clinical benefits of iron overload (IOL) management in hereditary anemias, including organ preservation and dramatically improved overall survival (OS), are widely accepted. Adult myelodysplastic syndrome (MDS) patients are older and may have comorbidities, treatments to extend OS are limited, and the clinical benefits of IOL management have been more challenging to demonstrate due to little prospective data in this population. However, current prognostic systems identify MDS patients with reasonable life expectancy who may benefit from IOL management. Half of MDS patients ultimately become dependent on red blood cell transfusion and develop transfusional IOL. Considerable preclinical and clinical data have accumulated indicating the adverse impact of IOL on multiple cellular and clinical end points and a clinical benefit to IOL management in MDS, which should be considered in some patients. Here we provide an overview of salient data in the usual (nonhematopoietic stem cell transplant) clinical MDS setting, summarize mechanisms of iron toxicity including increased radiologically detectable organ stores and redox-active iron-mediated tissue damage, furnish strategies for the identification of IOL, and suggest a framework for IOL severity and IOL reduction. We review which patients are appropriate for IOL management, recommend an appropriate time to intervene, discuss evidence supporting a clinical benefit to IOL management, and recommend how to off-load iron. We identify data gaps for future study and forecast future tools that may become available to minimize IOL toxicity in MDS.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"87-95"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677385","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":"Gene transfer and genome editing of T cells for cancer immunotherapy: from allogeneic HSCT to TCR gene editing.","authors":"Chiara Bonini","doi":"10.1182/hematology.2025000681","DOIUrl":"10.1182/hematology.2025000681","url":null,"abstract":"<p><p>Adoptive T-cell therapy has emerged as a transformative modality in cancer immunotherapy, building upon foundational principles established in allogeneic hematopoietic stem cell transplantation. In this setting, while donor T cells mediate curative graft-versus-leukemia and graft-versus-infection effects, their alloreactivity poses significant risks. Gene transfer strategies-such as suicide gene insertion-have enabled the safer use of donor lymphocytes by allowing the selective elimination of T cells in case of adverse events. With this initial gene therapy approach, several lessons on the function, persistence, safety, and efficacy of engineered T cells were learned. More recently, advances in genome editing technologies have enabled precise manipulation of T-cell genomes and function, including disruption of endogenous T-cell receptors (TCRs) and insertion of tumor-specific receptors, such as chimeric antigen receptors and tumor-specific TCRs. Integration of T-cell manufacturing protocols optimized for persistence and resistance to immune suppression-largely facilitated by the possibility to simultaneously edit multiple genes (multiplex genome editing) in the same cells-has positioned engineered T cells as programmable and persistent therapeutics. Here, we briefly review key milestones, challenges, and innovations in T-cell gene engineering, from allogeneic hematopoietic stem cell transplantation to next-generation TCR-edited immunotherapies.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"1-14"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677263","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":"From treatment to biology and back: managing iron overload in transfused hemoglobinopathies.","authors":"Thomas D Coates","doi":"10.1182/hematology.2025000693","DOIUrl":"10.1182/hematology.2025000693","url":null,"abstract":"<p><p>Before effective iron chelation became available, patients with transfusion-dependent thalassemia often died from iron-induced cardiomyopathy and endocrine failure in their second decade of life. This experience shaped long-standing expectations of poor outcomes and continues to fuel provider and patient anxiety in all conditions associated with iron overload. While severe iron overload and toxicity still cause considerable morbidity and mortality globally, advances in the understanding of iron metabolism, noninvasive organ-specific iron monitoring, and chelation therapy have significantly reduced their impact. Clinical insights from hemoglobinopathies have reinforced iron biology findings from animal models and highlighted shared mechanisms of iron toxicity across disorders, guiding broader management approaches that address the prevention of iron toxicity independently of the removal of organ iron burden. The resulting significant improvement in survival now presents new challenges tied to prolonged exposure to both anemia and iron overload, which must be addressed in long-term treatment planning.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"103-110"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677130","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}