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Measurable/Minimal Residual Disease: What Method and What Cut-Off? 可测量/最小残留疾病：什么方法和什么截止？
IF 2.7 3区 医学
Hematology-Oncology Clinics of North America Pub Date : 2025-07-30 DOI: 10.1016/j.hoc.2025.05.012
Andrew Rawstron
{"title":"Measurable/Minimal Residual Disease: What Method and What Cut-Off?","authors":"Andrew Rawstron","doi":"10.1016/j.hoc.2025.05.012","DOIUrl":"https://doi.org/10.1016/j.hoc.2025.05.012","url":null,"abstract":"<p><p>Minimal residual disease (MRD) testing has become a central response biomarker in clinical trials of time-limited treatment, with MRD-guided strategies under increasing evaluation. This article compares key technical and practical features of available MRD approaches and provides guidance on selecting the appropriate method and threshold for varied clinical applications.</p>","PeriodicalId":55060,"journal":{"name":"Hematology-Oncology Clinics of North America","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Understanding and Managing Infectious Complications in Chronic Lymphocytic Leukemia. 了解和处理慢性淋巴细胞白血病的感染并发症。
IF 2.5 3区 医学
Hematology-Oncology Clinics of North America Pub Date : 2025-07-25 DOI: 10.1016/j.hoc.2025.05.003
Noomi Vainer, Andreas Katsimigas, Emelie Curovic Rotbain, Carsten Utoft Niemann
{"title":"Understanding and Managing Infectious Complications in Chronic Lymphocytic Leukemia.","authors":"Noomi Vainer, Andreas Katsimigas, Emelie Curovic Rotbain, Carsten Utoft Niemann","doi":"10.1016/j.hoc.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.hoc.2025.05.003","url":null,"abstract":"<p><p>Despite major improvements in the treatment landscape of chronic lymphocytic leukemia (CLL), infections remain the major cause of death for patients with CLL. Management of infections in patients with CLL includes antimicrobial therapy, prophylactic vaccinations, and immunoglobulin replacement. Prognostic tools to identify patients with CLL at high risk of infections are warranted. Comorbidities, history of infections, and patient preferences should be considered in addition to molecular prognostic markers when choosing treatment strategy for patients with CLL. Targeted, sequential doublet therapy may provide similar efficacy with less immunosuppression as compared to triplet targeted therapy and indefinite monotherapy.</p>","PeriodicalId":55060,"journal":{"name":"Hematology-Oncology Clinics of North America","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Triplet Therapies in Chronic Lymphocytic Leukemia. 慢性淋巴细胞白血病的三联疗法。
IF 2.5 3区 医学
Hematology-Oncology Clinics of North America Pub Date : 2025-07-23 DOI: 10.1016/j.hoc.2025.05.001
Jacob D Soumerai, Matthew S Davids
{"title":"Triplet Therapies in Chronic Lymphocytic Leukemia.","authors":"Jacob D Soumerai, Matthew S Davids","doi":"10.1016/j.hoc.2025.05.001","DOIUrl":"https://doi.org/10.1016/j.hoc.2025.05.001","url":null,"abstract":"<p><p>Triplet therapy regimens, which we define as the combination of a BTK inhibitor (ibrutinib, acalabrutinib, zanubrutinib, or pirtobrutinib), BCL2 inhibitor (venetoclax or sonrotoclax), and a CD20 antibody (obinutuzumab), have been developed in chronic lymphocytic leukemia (CLL). Herein, we comprehensively review the available clinical data for triplet regimens in treatment-naïve CLL, including an evidence-based discussion of the role of TP53 aberrancy in patients receiving triplet therapies, and of retreatment options after frontline triplet therapy. We also review ongoing trials with potential to further define the role of triplet therapies in treatment-naïve CLL.</p>","PeriodicalId":55060,"journal":{"name":"Hematology-Oncology Clinics of North America","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Understanding and Targeting BCL2-inhibitor Resistance in Chronic Lymphocytic Leukemia. 慢性淋巴细胞白血病bcl2抑制剂耐药的认识与靶向
IF 2.5 3区 医学
Hematology-Oncology Clinics of North America Pub Date : 2025-07-22 DOI: 10.1016/j.hoc.2025.06.001
Alexander F Vom Stein, Lukas P Frenzel
{"title":"Understanding and Targeting BCL2-inhibitor Resistance in Chronic Lymphocytic Leukemia.","authors":"Alexander F Vom Stein, Lukas P Frenzel","doi":"10.1016/j.hoc.2025.06.001","DOIUrl":"https://doi.org/10.1016/j.hoc.2025.06.001","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia (CLL) treatment has evolved with the introduction of venetoclax, a selective BCL-2 inhibitor capable of inducing apoptosis in CLL cells. However, resistance has emerged as a significant clinical obstacle. Here, we delineate the multifactorial basis of venetoclax resistance in CLL by exploring genetic mutations, epigenetic alterations, microenvironmental protection, metabolic rewiring, and downstream signaling adaptations. Furthermore, we examine strategies to overcome resistance, including drug combinations, next-generation BCL-2 inhibitors, and novel immunotherapeutic approaches. Finally, we consider the clinical implications of emerging resistance patterns and discuss future directions in a personalized therapy.</p>","PeriodicalId":55060,"journal":{"name":"Hematology-Oncology Clinics of North America","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Autonomous B-cell Receptor Signaling in Chronic Lymphocytic Leukemia. 慢性淋巴细胞白血病的自主b细胞受体信号传导。
IF 2.5 3区 医学
Hematology-Oncology Clinics of North America Pub Date : 2025-07-16 DOI: 10.1016/j.hoc.2025.05.004
Anastasia Iatrou, Andreas Agathangelidis, Jessica Bordini, Kostas Stamatopoulos, Paolo Ghia
{"title":"Autonomous B-cell Receptor Signaling in Chronic Lymphocytic Leukemia.","authors":"Anastasia Iatrou, Andreas Agathangelidis, Jessica Bordini, Kostas Stamatopoulos, Paolo Ghia","doi":"10.1016/j.hoc.2025.05.004","DOIUrl":"https://doi.org/10.1016/j.hoc.2025.05.004","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia (CLL) is driven by both antigen-dependent and antigen-independent cell-autonomous B-cell receptor (BcR) signaling. The latter has been documented in CLL cases in different disease subgroups and correlates with disease progression. Autonomous signaling is also relevant in monoclonal B-cell lymphocytosis and other B-cell malignancies, including diffuse large B-cell lymphoma and splenic marginal zone lymphoma. This article examines its molecular basis, prognostic significance, and potential therapeutic relevance, highlighting the need for novel strategies to overcome resistance and improve outcomes.</p>","PeriodicalId":55060,"journal":{"name":"Hematology-Oncology Clinics of North America","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Management of Relapsed and/or Refractory Chronic Lymphocytic Leukemia. 复发和/或难治性慢性淋巴细胞白血病的治疗。
IF 2.5 3区 医学
Hematology-Oncology Clinics of North America Pub Date : 2025-07-16 DOI: 10.1016/j.hoc.2025.05.008
Allison Kagerer, Meghan C Thompson
{"title":"Management of Relapsed and/or Refractory Chronic Lymphocytic Leukemia.","authors":"Allison Kagerer, Meghan C Thompson","doi":"10.1016/j.hoc.2025.05.008","DOIUrl":"https://doi.org/10.1016/j.hoc.2025.05.008","url":null,"abstract":"<p><p>Covalent Bruton's tyrosine kinase inhibitors (cBTKis), including acalabrutinib and zanubrutinib, and the BCL2 inhibitor venetoclax are currently sequenced in both front-line and relapsed and/or refractory (R/R) chronic lymphocytic leukemia (CLL). A newer challenge is the management of patients with R/R CLL after exposure to both a cBTKi and BCL2 inhibitor. Herein, we review the management of R/R CLL following prior treatment with chemoimmunotherapy, cBTKi, and venetoclax-based therapy. We review treatment options for \"double exposed\" CLL including venetoclax retreatment, pirtobrutinib, and CAR T-cell therapy with lisocabtagene maraleucel. Emerging treatment options include agents in clinical trials such as BTK degraders and bispecific antibodies.</p>","PeriodicalId":55060,"journal":{"name":"Hematology-Oncology Clinics of North America","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Rapidly Evolving Landscape of the Biology and Therapy of Chronic Lymphocytic Leukemia. 慢性淋巴细胞白血病的生物学和治疗的快速发展景观。
IF 2.5 3区 医学
Hematology-Oncology Clinics of North America Pub Date : 2025-07-16 DOI: 10.1016/j.hoc.2025.06.002
Jennifer R Brown, Matthew S Davids
{"title":"The Rapidly Evolving Landscape of the Biology and Therapy of Chronic Lymphocytic Leukemia.","authors":"Jennifer R Brown, Matthew S Davids","doi":"10.1016/j.hoc.2025.06.002","DOIUrl":"https://doi.org/10.1016/j.hoc.2025.06.002","url":null,"abstract":"","PeriodicalId":55060,"journal":{"name":"Hematology-Oncology Clinics of North America","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Resistance to Bruton Tyrosine Kinase Inhibitors. 对布鲁顿酪氨酸激酶抑制剂的耐药性。
IF 2.5 3区 医学
Hematology-Oncology Clinics of North America Pub Date : 2025-07-11 DOI: 10.1016/j.hoc.2025.05.009
Jennifer R Brown
{"title":"Resistance to Bruton Tyrosine Kinase Inhibitors.","authors":"Jennifer R Brown","doi":"10.1016/j.hoc.2025.05.009","DOIUrl":"https://doi.org/10.1016/j.hoc.2025.05.009","url":null,"abstract":"<p><p>Targeting Bruton tyrosine kinase (BTK) has revolutionized the therapy for chronic lymphocytic leukemia. As patients remain on therapy, however, resistance develops progressively over time. The most common mechanism of resistance to covalent BTK inhibitors is mutation of the C481 target residue to serine, abrogating covalent binding. Other less common mutations are C481Y/R/F after ibrutinib, T474I after acalabrutinib, and L528W after zanubrutinib. The first-in-class noncovalent inhibitor pirtobrutinib has activity against C481 mutations, but resistance develops through alternative site BTK mutations. About one-third of BTK inhibitor resistance, both covalent and noncovalent, is not related to BTK mutations and remains poorly understood.</p>","PeriodicalId":55060,"journal":{"name":"Hematology-Oncology Clinics of North America","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
First-line Therapy: Time-Limited Venetoclax Doublet Therapy. 一线治疗：有时间限制的Venetoclax双重治疗。
IF 2.5 3区 医学
Hematology-Oncology Clinics of North America Pub Date : 2025-07-11 DOI: 10.1016/j.hoc.2025.05.007
Jennifer Huang, Mazyar Shadman
{"title":"First-line Therapy: Time-Limited Venetoclax Doublet Therapy.","authors":"Jennifer Huang, Mazyar Shadman","doi":"10.1016/j.hoc.2025.05.007","DOIUrl":"https://doi.org/10.1016/j.hoc.2025.05.007","url":null,"abstract":"<p><p>Studies examining venetoclax in combination with anti-CD20 monoclonal antibodies and covalent Bruton tyrosine kinase inhibitors (BTKi) demonstrated a progression-free survival and in some cases overall survival benefit over chemoimmunotherapy. It is currently unclear what is the most optimal combination partner for a B-cell leukemia/lymphoma 2 inhibitor (BCL2i). We are eagerly awaiting results from studies to determine the most effective BCL2i and BTKi combination for the first-line treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma given the development of second-generation drugs.</p>","PeriodicalId":55060,"journal":{"name":"Hematology-Oncology Clinics of North America","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunotherapy in Chronic Lymphocytic Leukemia. 慢性淋巴细胞白血病的免疫治疗。
IF 2.5 3区 医学
Hematology-Oncology Clinics of North America Pub Date : 2025-07-08 DOI: 10.1016/j.hoc.2025.05.010
Brian Sworder, Tanya Siddiqi
{"title":"Immunotherapy in Chronic Lymphocytic Leukemia.","authors":"Brian Sworder, Tanya Siddiqi","doi":"10.1016/j.hoc.2025.05.010","DOIUrl":"https://doi.org/10.1016/j.hoc.2025.05.010","url":null,"abstract":"<p><p>Immune-based therapies have redefined treatment strategies for a number of lymphomas including chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). This review highlights the evolution and efficacy of immune-based therapies in CLL/SLL, especially the novel monoclonal antibodies, bispecific antibodies, and chimeric antigen receptor T-cell therapy.</p>","PeriodicalId":55060,"journal":{"name":"Hematology-Oncology Clinics of North America","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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