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

{"title":"Monoclonal gammopathy of renal significance from a hematologic perspective.","authors":"Eugene Brailovski, Insara S Jaffer, Heather J Landau","doi":"10.1182/hematology.2025000727","DOIUrl":"10.1182/hematology.2025000727","url":null,"abstract":"<p><p>Monoclonal gammopathy of renal significance (MGRS) represents a clinical entity where clonal plasma or B-cell proliferative disorders secrete a monoclonal protein that leads to renal damage without meeting the diagnostic criteria for overt hematologic malignancies such as multiple myeloma or lymphoma. The diagnosis typically requires a kidney biopsy. MGRS subtypes are divided into 3 groups based on their pathologic findings: organized deposits, nonorganized deposits, and absence of immune deposits. Identifying the underlying clonal population of plasma cells or B cells is important to guide therapy. The standard of care for upfront treatment of light chain amyloidosis is daratumumab, cyclophosphamide, bortezomib, and dexamethasone. For other types of MGRS, the treatment depends on the underlying clone or the identified monoclonal protein. While light chain amyloidosis has validated response criteria, there are no uniform response criteria for other MGRS subtypes. Renal transplantation has been historically underutilized and represents a potentially transformative intervention in carefully selected patients who achieve good disease control using clone-directed therapy.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"377-384"},"PeriodicalIF":3.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677488","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 promise of menin inhibitors: from approval to triplet regimens.","authors":"Rahul K Thakur, Eunice S Wang","doi":"10.1182/hematology.2025000755","DOIUrl":"10.1182/hematology.2025000755","url":null,"abstract":"<p><p>Pharmacologic targeting of the menin-KMT2A protein-protein interaction has emerged as a therapeutic breakthrough for acute leukemias harboring KMT2A rearrangements or NPM1 mutations. The first-in-class menin inhibitor (revumenib) achieved accelerated regulatory approval in November 2024 for monotherapy of relapsed/refractory KMT2A rearranged leukemia. Next-generation agents (ziftomenib, bleximenib, enzomenib, BMF-219) have displayed similar composite complete remission rates (20-35%) and overall response rates (45-65%) in heavily pretreated KMT2Ar and NPM1m acute myeloid leukemia (AML) with measurable residual disease (MRD) negativity and prolonged overall survival (5-7 months). While all menin inhibitors result in on-target blast differentiation with clinical sequelae (\"differentiation syndrome\") in 10% to 20% of patients, not all menin inhibitors are the same, with differing safety, toxicity (heartrate corrected QT interval (QTc) prolongation, cytopenias), and pharmacokinetic profiles. Acquired mutations in the menin gene described in 39% of post-revumenib relapses have not been identified following other inhibitors (ziftomenib, bleximenib), prompting new questions about resistance mechanisms. These promising results swiftly led to the launch of multiple trials of menin inhibitors combined with intensive (cytarabine and anthracycline) and nonintensive (venetoclax and hypomethylating) chemotherapy backbones. To date, these triplets have yielded high response rates (ie, ≥80% in de novo, 50-70% in relapsed) with most patients achieving MRD negativity and prolonged one-year survival. Ongoing/pending phase 3 trials will clarify whether menin blockade should be incorporated into frontline and maintenance regimens for all patients with KMT2A rearranged or NPM1 mutant disease. In the current era, menin inhibition remains a key pillar of the success of precision medicine for AML therapy.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"599-606"},"PeriodicalIF":3.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677479","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 sickle cell trait is not just trait: risk of VTE.","authors":"Rakhi P Naik, Rafal Pawlinski, Nigel S Key","doi":"10.1182/hematology.2025000717","DOIUrl":"10.1182/hematology.2025000717","url":null,"abstract":"<p><p>The pathophysiology of venous thromboembolism (VTE) is complex. While perturbations in the coagulation system have generally been considered the primary driver of VTE risk, there is increasing recognition that additional whole-blood components also play a crucial role in clot formation. The erythrocyte is a particularly important-and often overlooked-contributor to venous thrombi (\"red clots\"). Sickle cell trait (SCT), the most common hemoglobin variant worldwide, has been consistently shown to confer a modestly increased risk of VTE, and pathophysiologic studies indicate that subclinical erythrocyte changes in SCT interact both with the coagulation system and with clot composition. In this review, we characterize SCT (\"HbAS\" or \"heterozygous HbS\") as a low-risk inherited thrombophilia and compare it to the most well-known thrombophilias: heterozygous factor V Leiden and prothrombin 20210A mutation.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"291-294"},"PeriodicalIF":3.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677417","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 the management of newly diagnosed chronic lymphocytic leukemia.","authors":"Kristen McClellan, Andrea Sitlinger","doi":"10.1182/hematology.2025000686","DOIUrl":"10.1182/hematology.2025000686","url":null,"abstract":"<p><p>The options for frontline chronic lymphocytic leukemia (CLL) treatment continue to expand. Therapies include monotherapy with a Bruton's tyrosine kinase inhibitor (BTKi), doublet therapies such as venetoclax with intravenous obinutuzmab or an oral BTKi, and triplet therapy combining BTKi, venetoclax, and CD20 antibody. Treatment duration also is increasingly variable, from fixed duration to utilization of undetectable minimal residual disease (uMRD) to determine optimal treatment completion. Currently, the best option for an individual patient requires a multifaceted approach considering the individual's cytogenetics, comorbidities, and personal preferences, including time-limited therapy vs continuous treatment. In this article, we outline the current state of frontline CLL including ongoing questions and future directions.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"45-51"},"PeriodicalIF":3.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677275","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 xanthogranuloma family of histiocytic neoplasms in the molecular era: Erdheim-Chester disease and beyond.","authors":"Gaurav Goyal, Ronald S Go","doi":"10.1182/hematology.2025000706","DOIUrl":"10.1182/hematology.2025000706","url":null,"abstract":"<p><p>Histiocytic neoplasms with xanthogranulomatous morphology encompass a continuum of disorders-from isolated cutaneous juvenile xanthogranuloma (JXG) or adult xanthogranuloma (AXG) to the multisystem Erdheim-Chester disease (ECD)-that share overlapping histopathologic and molecular features. In this article, we (1) define the spectrum of xanthogranuloma lesions, highlighting morphologic and immunohistochemical commonalities; (2) examine the clinical and radiographic criteria that distinguish localized juvenile xanthogranuloma/adult xanthogranuloma from classical Erdheim-Chester disease and related entities; (3) review the latest insights into MAPK pathway alterations that blur traditional diagnostic boundaries; and (4) outline contemporary management strategies, including approaches to staging \"occult\" disease, patient selection for BRAF and MEK inhibitors, and the role of other targeted and nontargeted agents. Readers will gain practical frameworks for recognizing early or atypical presentations, integrating molecular testing into routine practice, and optimizing personalized therapy across the xanthogranuloma family.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"199-205"},"PeriodicalIF":3.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677613","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":"JAK2 wild-type erythrocytosis: concept, differential diagnosis, diagnostic steps, and treatment approaches.","authors":"Natasha Szuber, Ayalew Tefferi, Naseema Gangat","doi":"10.1182/hematology.2025000704","DOIUrl":"10.1182/hematology.2025000704","url":null,"abstract":"<p><p>JAK2 unmutated/wild-type erythrocytosis is a prevalent condition encompassing a wide spectrum of hereditary and acquired entities. It is conventionally defined by the same hemoglobin/hematocrit thresholds as for polycythemia vera. Incidence has been reported to be between 0.13% and 4.1%. The most clinically relevant step in the workup of erythrocytosis is the exclusion of polycythemia vera through JAK2 mutation screening. Consideration of relative polycythemia, normal outliers, and the influence of erythropoietic drugs and comorbidities is also imperative. Distinguishing long-standing from newly acquired erythrocytosis further streamlines the diagnostic process. Hereditary erythrocytosis (HE) is lifelong and typically associated with a positive family history. Subnormal serum erythropoietin (EPO) suggests an EPO receptor mutation. Otherwise, oxygen tension at 50% hemoglobin saturation (p50) discerns between high oxygen-affinity hemoglobin variants, 3-bisphosphoglycerate deficiency, methemoglobinemia, and PIEZO1 mutations (low p50) and germline oxygen-sensing pathway/other rare mutations (normal p50). Acquired erythrocytosis results from hypoxia-driven factors (eg, cardiopulmonary, altitude, renal artery stenosis) and other mechanisms of EPO overproduction (eg, EPO-secreting tumors) or hypersensitivity, as well as EPO-independent mechanisms. Drugs (eg, sodium glucose co-transporter-2 inhibitors, testosterone) are also common causes. Idiopathic erythrocytosis is a diagnosis of exclusion, increasingly attributed to underlying genetic mutations/polymorphisms. There are currently no evidence-based treatment guidelines. Low-dose aspirin and/or phlebotomy (with frequency determined by symptom relief) might be considered on an individualized basis in the presence of hyperviscosity symptoms, cardiovascular comorbidities, and/or a history of thrombosis. Aggressive control of cardiovascular risk factors is recommended in all. A graphic abstract representation is provided in Figure 1.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"183-190"},"PeriodicalIF":3.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677384","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":"Anticoagulants in hematologic malignancies: what is the data?","authors":"Ruah Alyamany, Damon E Houghton","doi":"10.1182/hematology.2025000688","DOIUrl":"10.1182/hematology.2025000688","url":null,"abstract":"<p><p>Hematologic malignancies are associated with an increased risk of venous thromboembolism (VTE) with aggressive lymphomas and multiple myeloma exhibiting the highest VTE incidence. The performance of VTE risk scores in hematologic malignancies remains suboptimal. Concomitant thrombocytopenia and coagulopathies complicate thrombosis prevention and management. This review synthesizes current evidence on anticoagulation in hematologic malignancies (excluding myeloproliferative neoplasms), outlines key clinical challenges, and proposes practical strategies to guide decision-making.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"61-71"},"PeriodicalIF":3.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677462","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":"Sanctuary sites and extramedullary relapses in the chemo-free world: insights from immunotherapies in B-ALL.","authors":"Ryan D Cassaday","doi":"10.1182/hematology.2025000711","DOIUrl":"10.1182/hematology.2025000711","url":null,"abstract":"<p><p>When acute lymphoblastic leukemia (ALL) involves extramedullary sites, the appropriate pathologic term for this is lymphoblastic lymphoma. The biological mechanisms underpinning this process are not clear, but they are presumed to involve a multifactorial interplay between tumor cells and the microenvironment of the tissue in which they develop (eg, lymph nodes, thymus, leptomeninges). Importantly for clinicians, these factors may impair the efficacy of systemic therapy given to treat ALL. This gives rise to \"sanctuary sites,\" so named because of the relative protection they provide to malignant blasts that may possess these characteristics. This has become increasingly relevant in the era of \"chemotherapy-free\" approaches for B-cell ALL, where the potency of antigen-targeted immunotherapies (eg, blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor-modified T cells) has been leveraged to reduce or eliminate the reliance on cytotoxic chemotherapy. Such approaches are appealing for their high response rates and favorable toxicity profiles compared to chemotherapy. However, extramedullary relapses have been observed with increased frequency: an outcome historically seen in around 10% of such cases, this can represent over 50% of relapses in some series. This review provides an overview of this emerging issue and what clinicians and investigators can do to address it.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"245-251"},"PeriodicalIF":3.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677469","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":"Can I stop my treatment, doctor? Is MRD-guided therapy ready for prime time?","authors":"Benjamin A Derman","doi":"10.1182/hematology.2025000761","DOIUrl":"10.1182/hematology.2025000761","url":null,"abstract":"<p><p>Indefinite maintenance therapy, typically with lenalidomide, remains a standard of care for patients with multiple myeloma, largely based on studies that demonstrated improved progression-free and overall survival compared to observation or placebo. However, these early trials often did not incorporate modern induction regimens or measurable residual disease (MRD) assessments. Despite newer induction regimens leading to high rates of MRD negativity, further intensification of maintenance remains the focus rather than de-escalation. As treatment paradigms have evolved to include quadruplet induction regimens and sensitive MRD assays, clinicians and patients increasingly question whether maintenance therapy can be safely stopped in selected individuals. This review examines the rationale for maintenance therapy, the historical data supporting its use, and emerging evidence from prospective studies suggesting that maintenance may be safely discontinued in patients with sustained multimodal MRD negativity. Patient-centered considerations, such as treatment-related toxicity, quality of life, and financial burden, underscore the importance of individualized decision-making regarding maintenance cessation. Also explored are future directions in MRD-guided treatment strategies, including de-escalation in the context of deep and sustained response. As the evidence base evolves, the challenge remains to balance the risks of indefinite therapy with the potential benefits of personalized, response-adaptive care in multiple myeloma.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"645-651"},"PeriodicalIF":3.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677471","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":"Optimizing the right time to start sickle cell therapies.","authors":"Olufunke Y Martin, Seethal A Jacob","doi":"10.1182/hematology.2025000752","DOIUrl":"10.1182/hematology.2025000752","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is a genetically and clinically heterogeneous disorder marked by hemolysis and vaso-occlusion, leading to a wide range of acute and chronic complications. While newborn screening enables early identification, the optimal timing for initiating disease-modifying therapies (DMTs) remains a critical and evolving question. This review explores how genetic and clinical risk factors, along with phenotypic variability, influence treatment timing, emphasizing a shift toward earlier and more personalized interventions. Hydroxyurea, the most widely used DMT, demonstrates strong evidence for early initiation in severe genotypes yet is underutilized due to concerns around long-term effects and adherence challenges. Additional therapies, such as L-glutamine, crizanlizumab, and formerly voxelotor, highlight the growing yet complex therapeutic landscape. Curative and transformative options, such as hematopoietic stem cell transplantation and newly approved gene therapies, underscore the need for individualized decision-making based on risk, disease trajectory, and patient goals. Rethinking treatment paradigms to incorporate multiagent approaches, biomarker-driven strategies, and earlier intervention may yield improved outcomes. Ultimately, optimizing the timing of therapy initiation requires moving from reactive to proactive care models that consider risk, clinical severity, and evolving therapeutic options, with the goal of improving quality of life and long-term survival for individuals living with SCD.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"577-584"},"PeriodicalIF":3.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677483","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}