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

{"title":"Posttransplant cells for the win? DLI and adoptive cell therapy to eradicate MRD.","authors":"Pleun Schonewille, Anna van Rhenen, Renske Mt Ten Ham, Moniek de Witte, Jürgen Kuball","doi":"10.1182/hematology.2025000747","DOIUrl":"10.1182/hematology.2025000747","url":null,"abstract":"<p><p>Relapse remains the leading cause of failure after allogeneic stem cell transplantation (allo-SCT) for hematologic malignancies. Donor lymphocyte infusion (DLI), the infusion of lymphocytes from the original stem cell donor, was introduced in the late 1980s as a strategy to prevent or treat relapse by augmenting the graft-versus-leukemia (GvL) effect. Over time, DLI has been used in various settings: initially as therapeutic DLI for overt relapse and later as preemptive DLI, administered in response to early signs of relapse, such as persistent or recurrent measurable residual disease (MRD), or as prophylactic DLI to mitigate high relapse risk before clinical relapse occurs (see Visual Abstract). However, questions remain regarding how, when, and in whom DLI is best deployed, reflecting ongoing controversy and heterogeneity in clinical practice. A recent survey of 165 European Society for Blood and Marrow Transplantation centers across 43 countries reported that DLI was used prophylactically for high-risk hematologic diseases in 43.8% of these centers. DLI was used preemptively for MRD positivity in 86.9% of centers and for mixed chimerism in 73.1%. Therapeutic DLI was administered for hematologic relapse in 73.1% of centers. Active graft-versus-host disease and active infections were considered absolute contraindications by 85.6% and 57.5% of the centers, respectively. This observed variability in center practices underscores the need to clarify the \"who, when, and why\" of posttransplant cellular interventions. In this review, we explore DLI strategies and the potential sequencing with novel targeted therapies across prophylactic, preemptive, and therapeutic applications, illustrated through case examples in patients with acute myeloid leukemia. We highlight findings from retrospective, as well as the scarce prospective studies and extend considerations to other indications, including chronic myeloid leukemia, myelofibrosis, and acute lymphoblastic leukemia. Additionally, we review emerging combination strategies with targeted therapies across different hematologic malignancies and adoptive cell therapies beyond conventional DLI.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"537-546"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677497","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 right patient, the right treatment: tailoring sickle cell disease care.","authors":"Sheinei Alan, Payal Desai","doi":"10.1182/hematology.2025000753","DOIUrl":"10.1182/hematology.2025000753","url":null,"abstract":"<p><p>Sickle cell disease (SCD) remains the most common monogenic disorder worldwide, yet more than a century after its formal discovery, our treatment options and approach to care remain underdeveloped. Despite scientific progress, care for SCD continues to lag behind other chronic conditions, in part due to a lack of consensus on straightforward medical decision-making-driven by a persistent paucity of data and compounded by historical neglect, systemic inequities, and clinical heterogeneity. To truly serve this vulnerable population, we must move toward a more comprehensive, personalized approach to adult care-one that mirrors the individualized pain management plans routinely used in acute care settings. While much of the foundational work in SCD has been in pediatrics, this manuscript focuses on the adult population, where the burden of disease increases and access to specialized care declines. We emphasize the importance of considering genotype, hematologic profile, comorbid conditions, psychosocial context, and health literacy when developing treatment plans in shared decision-making with our patients. Ultimately, we hope this manuscript provides practical insights to help clinicians answer the daily complex questions surrounding sickle cell care: whom to treat and which interventions offer the most meaningful benefit for that particular patient.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"585-591"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677526","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":"A practical approach to immune thrombocytopenia in pregnancy.","authors":"Kristine Matusiak, A Kinga Malinowski, Donald M Arnold","doi":"10.1182/hematology.2025000743","DOIUrl":"10.1182/hematology.2025000743","url":null,"abstract":"<p><p>Immune thrombocytopenia (ITP) often presents for the first time in pregnancy, or, in patients with a history of ITP, pregnancy can trigger a relapse. ITP in pregnancy is often mild, leading to minimal or no symptoms; however, treatment may be needed if thrombocytopenia becomes severe, if bleeding occurs, or in anticipation of delivery and neuraxial analgesia. To facilitate the diagnosis of ITP in pregnancy, we present a systematic approach that allows clinicians to first consider urgent pregnancy-related thrombocytopenic conditions such as hypertensive disorders of pregnancy or thrombotic thrombocytopenic purpura; exclude other causes of thrombocytopenia; and determine the need for treatment. We review options for first-line therapies for ITP in pregnancy, including corticosteroids (prednisone or methylprednisolone) and intravenous immune globulin, which has a favorable safety profile in pregnancy, and second-line therapy options that have been used in pregnancy including thrombopoietin receptor agonists, rituximab, and certain immunosuppressant medications such as azathioprine. We summarize the recommendations for platelet targets for delivery, recognizing that the evidence is limited, including a platelet count of 50  ×  109/L or higher for caesarean delivery and 70  ×  109/L or higher for neuraxial anesthesia. Treatment decisions for ITP in pregnancy should be informed by patients' values and preferences along with a multidisciplinary team that includes hematologists, obstetricians, and anesthesiologists.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"503-510"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677533","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":3.7,"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":"What to know about rare B-cell malignancies in 2025.","authors":"Salman Fazal, Yazan Samhouri, Cyrus Khan, Haifaa Abdulhaq","doi":"10.1182/hematology.2025000687","DOIUrl":"10.1182/hematology.2025000687","url":null,"abstract":"<p><p>Rare B-cell malignancies pose a unique management challenge because of their rarity and aggressiveness. Given their low incidence, they require a high index of suspicion for diagnosis and necessitate specialized therapeutic approaches. Herein, we discuss 3 of those rare lymphomas: plasmablastic lymphoma, lymphomatoid granulomatosis, and intravascular lymphoma. Plasmablastic lymphoma is aggressive and often linked to immunosuppression, particularly in HIV- infected individuals. It is characterized by plasmablastic morphology lacking CD20 expression, extranodal disease, MYC rearrangement, and frequent Epstein-Barr virus infection. Recent advancements in treatment involve using novel agents like bortezomib, daratumumab, and B-cell maturation antigen-targeted therapy, which are improving outcomes; however, the prognosis for relapsed disease remains poor. Lymphomatoid granulomatosis is a rare, Epstein-Barr virus-driven B-cell disorder defined by angiocentric and angiodestructive infiltrates. It primarily affects the lungs but can also involve skin and the central nervous system, causing systemic symptoms. Treatment and prognosis vary by histologic grade; low-grade cases may be treated with immunomodulation, while high-grade cases generally require chemoimmunotherapy. Intravascular lymphoma involves malignant B cells proliferating in small blood vessels, leading to nonspecific clinical symptoms. Early diagnosis through tissue biopsy is crucial. The best remission chances come from rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy combined with central nervous system-directed treatment. New research is ongoing for relapsed cases.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"52-60"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677402","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":"High-grade B-cell lymphomas: high difficulties to diagnose and treat?","authors":"Andrew J Davies","doi":"10.1182/hematology.2025000749","DOIUrl":"10.1182/hematology.2025000749","url":null,"abstract":"<p><p>The high-grade B-cell lymphomas represent a pathologically and clinically heterogeneous group of mature B-cell malignancies. With modern molecular diagnostics and genomic studies, they are becoming increasingly resolved as we understand more of their shared oncogenic mechanisms. The result has been a realignment of the classification of these tumors, which may initially appear baffling. These tumors are most commonly of large cell morphology but can be of variable high-grade morphology. The double-hit high-grade B-cell lymphomas (HGBLs) that harbor dual translocations of MYC and BCL2 are of a germinal center phenotype and have a homogeneous biology. By contrast, those with dual MYC and BCL6 translocations do not appear to have such a unifying biology. The group of HGBLs not otherwise specified is poorly resolved and not characterized by distinct oncogenic aberrations. Together, the HGBLs may present with aggressive features; respond poorly to R-CHOP, ie, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; and may benefit from intensified induction regimens. However, clinical interpretation is hampered by a paucity of prospective studies. In the relapsed and refractory setting, chimeric antigen receptor T-cell therapy has demonstrated significant efficacy, and there is much expectation for other novel therapeutic approaches, including bispecific antibodies. By understanding the biology and a commitment to collaborative prospective evaluation, their high diagnostic and treatment challenges may be resolved.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"555-563"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677351","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":"Revisiting novel genomic classifiers in the era of immunotherapy for pediatric B-ALL.","authors":"Ruth W Wang'ondu, Mignon L Loh","doi":"10.1182/hematology.2025000712","DOIUrl":"10.1182/hematology.2025000712","url":null,"abstract":"<p><p>While recent improvements in survival for pediatric patients with newly diagnosed B-cell precursor acute lymphoblastic leukemia (B-ALL) have been attributed to risk stratification algorithms incorporating somatic genetics and early response dictating therapeutic intensity, recent antibody-based immunotherapeutic agents are changing the therapeutic landscape. Blinatumomab, inotuzumab ozogamicin, and chimeric antigen T-cell receptor therapies are approved by the US Food and Drug Administration for the treatment of relapsed and refractory B-ALL in children, and some have been incorporated into frontline therapies. Studies in both pediatric and adult patients have recently demonstrated superiority of adding blinatumomab to the consolidation phase of treatment in the frontline setting. Revisiting genomic classifiers of B-ALL in the era of antibody-based immunotherapeutic agents may be necessary to maximize the benefits of current risk stratification algorithms in combination with immunotherapy. Available data suggest the efficacy of these agents across genomic subtypes. Here we consider the impact of immunotherapeutic agents within the context of minimal residual disease and molecular classification-based risk stratification.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"252-261"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677539","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":"Could treatment modification based on early response assessment improve results in DLBCL?","authors":"Hari S Raman, Jennifer L Crombie","doi":"10.1182/hematology.2025000739","DOIUrl":"10.1182/hematology.2025000739","url":null,"abstract":"<p><p>Despite the curative potential of frontline therapy in diffuse large B-cell lymphoma (DLBCL), nearly a third of patients will have relapsed or refractory disease and thus have a poor prognosis. While potentially curative options exist in the relapsed setting, these treatments are intensive, are not available to all patients, and are associated with high rates of relapse. As such, there is considerable interest in preemptively identifying high-risk patients who could benefit from modifications to initial treatment strategies. Alternatively, there may also be a subset of patients with favorable disease who could benefit from de-escalation strategies and reduction in toxicity. Personalized treatment approaches, including those that incorporate modification of therapy based on early response assessments, have the potential to improve outcomes in DLBCL, though these approaches require further evaluation in clinical practice. Here we review the prognostic role of interim positron emission tomography and the primarily unsuccessful efforts to use this tool to guide response-adaptive treatment strategies thus far. We subsequently review the potential role of evaluating minimal residual disease (MRD) in this context, discussing the available tools, the data to support its role in interim response assessment, and the future directions of MRD use in DLBCL clinical trials.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"476-481"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677553","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":"Emerging immunotherapy advances for non-Hodgkin lymphomas: engaging T cells in the fight.","authors":"Alexandra E Rojek, Sonali M Smith","doi":"10.1182/hematology.2025000722","DOIUrl":"10.1182/hematology.2025000722","url":null,"abstract":"<p><p>The treatment landscape of B-cell non-Hodgkin lymphoma (B-NHL) has been rapidly transformed by the emergence of T-cell engaging (TCE) therapies. Within the past decade, anti-CD19 chimeric antigen receptor (CAR) T-cell therapies have moved from relapsed/refractory to second-line settings in aggressive large B-cell lymphomas and are now also approved for R/R follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia. More recently, bispecific antibodies with dual engagement of CD20 × CD3 have emerged as an alternative TCE option with regulatory approval as monotherapies in several relapsed/refractory B-cell lymphomas. Common investigational themes for TCE therapies include earlier integration in the treatment paradigm, testing combination approaches, and considering optimal sequencing approaches. Despite major progress, there remains opportunity for technical innovations that may improve efficacy, attenuate toxicity, and ease the sometimes complex logistics around treatment delivery. Alternative and multiantigen targets are being explored in CAR T-cell constructs as well as bispecific antibodies, with some of these approaches now in early-phase clinical trials. Strategies to improve CAR T manufacturing, optimize T-cell fitness, and design novel \"armored\" CAR T-cells designs are actively being tested in preclinical and early-phase clinical data. From a safety perspective, much progress has been made in reducing the burden of side effects and broadening access; however, barriers remain before TCE therapies can be widely available to all patients. This brief review addresses some of the latest strategies being tested to elevate TCE therapies as pillars of immunotherapy for B-NHL.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"334-341"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677610","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 role of MRD monitoring and options for CLL management in relapsed/refractory disease.","authors":"Brian Sworder, Tanya Siddiqi","doi":"10.1182/hematology.2025000685","DOIUrl":"10.1182/hematology.2025000685","url":null,"abstract":"<p><p>The role of minimal residual disease (MRD) testing is well defined in curable hematological malignancies like acute lymphoblastic leukemia. However, in chronic lymphocytic leukemia (CLL), which is an incurable low-grade lymphoma, MRD is mostly investigational, especially in the relapsed setting. Newer techniques are trying to get to even deeper levels than before-for instance, 10-6 with sequencing. Here we describe the current techniques of MRD testing in CLL and explore the applications of these modalities in relapsed/refractory CLL in novel targeted therapies, cellular therapy, and other immunotherapies that can lead to deep and durable remissions, especially when used in combinations. More and more prospective interventional trials are now using MRD testing to inform decisions, and the data from these trials will further elucidate the best use of MRD testing in CLL patients. For now, MRD testing is not used for treatment decisions in the real world, although it can be done for monitoring in patients with high-risk genetics.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":"2025 1","pages":"39-44"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677498","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}