Jeffrey Lantz, Natalie Pham, Caroline Jones, Daniel Reed, Firas El Chaer, Michael Keng
{"title":"Blinatumomab in Practice.","authors":"Jeffrey Lantz, Natalie Pham, Caroline Jones, Daniel Reed, Firas El Chaer, Michael Keng","doi":"10.1007/s11899-023-00714-7","DOIUrl":"10.1007/s11899-023-00714-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>Acute lymphoblastic leukemia (ALL) is a rare hematologic neoplasm in adults, with most cases defined by pathology related to abnormal B cell proliferation known as B-cell ALL. The course is challenging, with less-than-optimal survival outcomes, even with aggressive multiagent chemotherapy and consideration for stem cell transplantation. Novel therapies focused on targetable pathways are being investigated to improve outcomes while simultaneously decreasing toxicity. In our review, we aim to evaluate the utilization of blinatumomab in B-cell ALL and provide insight on how this guides our management.</p><p><strong>Recent findings: </strong>Blinatumomab is a bispecific T-cell engager (BiTE) immunotherapy that neutralizes malignant cells by instigating CD3-positive T cells to target CD19-positive B cells. However, this therapy targets both malignant and non-malignant lymphocytes with potentially severe side effects such as cytokine release syndrome or neurotoxicity. Evidence evaluating utilization in the relapsed or refractory setting has been most supported; however, newer trials have also indicated improved survival in the frontline treatment of B-cell ALL. As this therapy is relatively new, the treatment team may include members who are less experienced with the typical treatment course and drug mechanics. This review synthesized available data investigating the effectiveness of blinatumomab effectiveness and its adverse events in addition to providing guidance on safe administration methods utilizing a multidisciplinary healthcare team. When care is coordinated in these settings, serious side effects can be recognized early, allowing for necessary intervention leading to improved quality of life and overall survival. Future research will continue to evaluate blinatumomab in different lines of therapy and expand its way into community settings.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498040","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}
{"title":"Novel Biomarkers and Molecular Targets in ALL.","authors":"Hong De Sa, Jessica Leonard","doi":"10.1007/s11899-023-00718-3","DOIUrl":"10.1007/s11899-023-00718-3","url":null,"abstract":"<p><strong>Purpose of review: </strong>Acute lymphoblastic leukemia (ALL) is a widely heterogeneous disease in terms of genomic alterations, treatment options, and prognosis. While ALL is considered largely curable in children, adults tend to have higher risk disease subtypes and do not respond as favorably to conventional chemotherapy. Identifying genomic drivers of leukemogenesis and applying targeted therapies in an effort to improve disease outcomes is an exciting focus of current ALL research. Here, we review recent updates in ALL targeted therapy and present promising opportunities for future research.</p><p><strong>Recent findings: </strong>With the utilization of next-generation sequencing techniques, the genomic landscape of ALL has greatly expanded to encompass novel subtypes characterized by recurrent chromosomal rearrangements, gene fusions, sequence mutations, and distinct gene expression profiles. The evolution of small molecule inhibitors and immunotherapies, and the exploration of unique therapy combinations are some examples of recent advancements in the field. Targeted therapies are becoming increasingly important in the treatment landscape of ALL to improve outcomes and minimize toxicity. Significant recent advancements have been made in the detection of susceptible genomic drivers and the use of novel therapies to target them.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138476962","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}
{"title":"Unlocking the Potential of Artificial Intelligence in Acute Myeloid Leukemia and Myelodysplastic Syndromes.","authors":"Abdulrahman Alhajahjeh, Aziz Nazha","doi":"10.1007/s11899-023-00716-5","DOIUrl":"10.1007/s11899-023-00716-5","url":null,"abstract":"<p><strong>Purpose of the review: </strong>This review aims to elucidate the transformative impact and potential of machine learning (ML) in the diagnosis, prognosis, and clinical management of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). It further aims to bridge the gap between current advances of ML and their practical application in these diseases.</p><p><strong>Recent findings: </strong>Recent advances in ML have revolutionized prognostication, diagnosis, and treatment of MDS and AML. ML algorithms have proven effective in predicting disease progression, optimizing treatment responses, and in the stratification of patient groups. Particularly, the use of ML in genomic and epigenomic data analysis has unveiled novel insights into the molecular heterogeneity of MDS and AML, leading to better-informed therapeutic strategies. Furthermore, deep learning techniques have shown promise in analyzing complex patterns in bone marrow biopsy images, providing a potential pathway towards early and accurate diagnosis. While still in the nascent stages, ML applications in MDS and AML signify a paradigm shift towards precision medicine. The integration of ML with traditional clinical practices could potentially enhance diagnostic accuracy, refine risk stratification, and improve therapeutic approaches. However, challenges related to data privacy, standardization, and algorithm interpretability must be addressed to realize the full potential of ML in this field. Future research should focus on the development of robust, transparent ML models and their ethical implementation in clinical settings.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298611","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}
{"title":"Diagnosis and Management of Pulmonary Manifestations of Telomere Biology Disorders","authors":"Kathryn T. del Valle, Eva M. Carmona","doi":"10.1007/s11899-023-00720-9","DOIUrl":"https://doi.org/10.1007/s11899-023-00720-9","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose of Review</h3><p>Telomere biology disorders (TBD) are a group of genetic disorders characterized by premature shortening of telomeres, resulting in accelerated aging of somatic cells. This often leads to major multisystem organ dysfunction, and TBDs have become increasingly recognized as a significant contributor to numerous disease processes within the past 10–15 years. Both research and clinical practice in this field are rapidly evolving.</p><h3 data-test=\"abstract-sub-heading\">Recent Findings</h3><p>A subset of patients with TBD suffers from interstitial lung disease, most commonly pulmonary fibrosis. Often, the clinical presentation is indistinguishable from other forms of lung fibrosis. There are no pathognomonic radiographic or histological features, and a high level of suspicion is therefore required. Telomere evaluation is thus crucial to establishing the diagnosis.</p><h3 data-test=\"abstract-sub-heading\">Summary</h3><p>This review details the clinical presentation, objective evaluation, indicated genetic testing, and recommended management strategies for patients affected by interstitial lung disease associated with TBDs. Our goal is to empower pulmonologists and other healthcare professionals who care for these patients to provide appropriate and personalized care for this population.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139070758","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}
{"title":"Adaptive and Maladaptive Clonal Hematopoiesis in Telomere Biology Disorders","authors":"Terra Lasho, Mrinal M. Patnaik","doi":"10.1007/s11899-023-00719-2","DOIUrl":"https://doi.org/10.1007/s11899-023-00719-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose of Review</h3><p>Telomere biology disorders (TBDs) are germline-inherited conditions characterized by reduction in telomerase function, accelerated shortening of telomeres, predisposition to organ-failure syndromes, and increased risk of neoplasms, especially myeloid malignancies. In normal cells, critically short telomeres trigger apoptosis and/or cellular senescence. However, the evolutionary mechanism by which TBD-related telomerase-deficient cells can overcome this fitness constraint remains elusive.</p><h3 data-test=\"abstract-sub-heading\">Recent Findings</h3><p>Preliminary data suggests the existence of adaptive somatic mosaic states characterized by variants in TBD-related genes and maladaptive somatic mosaic states that attempt to overcome hematopoietic fitness constraints by alternative methods leading to clonal hematopoiesis.</p><h3 data-test=\"abstract-sub-heading\">Summary</h3><p>TBDs are both rare and highly heterogeneous in presentation, and the association of TBD with malignant transformation is unclear. Understanding the clonal complexity and mechanisms behind TBD-associated molecular signatures that lead to somatic adaptation in the setting of defective hematopoiesis will help inform therapy and treatment for this set of diseases.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629780","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}
Stephanie L Fetzko, Leander D Timothy, Robin Parihar
{"title":"NK Cell Therapeutics for Hematologic Malignancies: from Potential to Fruition.","authors":"Stephanie L Fetzko, Leander D Timothy, Robin Parihar","doi":"10.1007/s11899-023-00711-w","DOIUrl":"10.1007/s11899-023-00711-w","url":null,"abstract":"<p><strong>Purpose of review: </strong>The current review focuses on the preclinical development and clinical advances of natural killer (NK) cell therapeutics for hematologic malignancies and offers perspective on the unmet challenges that will direct future discovery in the field.</p><p><strong>Recent findings: </strong>Approaches to improve or re-direct NK cell anti-tumor functions against hematologic malignancies have included transgenic expression of chimeric antigen receptors (CARs), administration of NK cell engagers including BiKEs and TriKEs that enhance antibody-dependent cellular cytotoxicity (ADCC) by co-engaging NK cell CD16 and antigens on tumors, incorporation of a non-cleavable CD16 that results in enhanced ADCC, use of induced memory-like NK cells alone or in combination with CARs, and blockade of NK immune checkpoints to enhance NK cytotoxicity. Recently reported and ongoing clinical trials support the feasibility and safety of these approaches. NK cell-based therapeutic strategies hold great promise as cost-effective, off-the-shelf cell therapies for patients with relapsed and refractory hematologic diseases.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41110633","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}
{"title":"Updates in the Classification of T-cell Lymphomas and Lymphoproliferative Disorders.","authors":"Naoki Oishi, Reham Ahmed, Andrew L Feldman","doi":"10.1007/s11899-023-00712-9","DOIUrl":"10.1007/s11899-023-00712-9","url":null,"abstract":"<p><strong>Purpose of review: </strong>Mature T/NK-cell neoplasms comprise a heterogeneous group of diseases with diverse clinical, histopathologic, immunophenotypic, and molecular features. A clinically relevant, comprehensive, and reproducible classification system for T/NK-cell neoplasms is essential for optimal management, risk stratification, and advancing understanding of these diseases. Two classification systems for lymphoid neoplasms were recently introduced: the 5th edition of World Health Organization classification (WHO-HAEM5) and the 2022 International Consensus Classification (ICC). In this review, we summarize the basic framework and updates in the classification of mature T/NK-cell neoplasms.</p><p><strong>Recent findings: </strong>WHO-HAEM5 and ICC share basic concepts in classification of T/NK-cell neoplasms, emphasizing integration of clinical presentation, pathology, immunophenotype, and genetics. Major updates in both classifications include unifying nodal T-follicular helper-cell lymphomas into a single entity and establishing EBV-positive nodal T/NK-cell lymphoma as a distinct entity. However, some differences exist in taxonomy, terminology, and disease definitions. The recent classifications of mature T/NK-cell neoplasms are largely similar and provide new insights into taxonomy based on integrated clinicopathologic features.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10834031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49689167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetic Counseling and Family Screening Recommendations in Patients with Telomere Biology Disorders.","authors":"Laura Ongie, Hannah A Raj, Katie Barrett Stevens","doi":"10.1007/s11899-023-00713-8","DOIUrl":"10.1007/s11899-023-00713-8","url":null,"abstract":"<p><strong>Purpose of review: </strong>Telomere biology disorders (TBDs) encompass a spectrum of genetic diseases with a common pathogenesis of defects in telomerase function and telomere maintenance causing extremely short telomere lengths. Here, we review the current literature surrounding genetic testing strategies, cascade testing, reproductive implications, and the role of genetic counseling.</p><p><strong>Recent findings: </strong>The understanding of the genetic causes and clinical symptoms of TBDs continues to expand while genetic testing and telomere length testing are nuanced tools utilized in the diagnosis of this condition. Access to genetic counseling is becoming more abundant and is valuable in supporting patients and their families in making informed decisions. Patient resources and support groups are valuable to this community. Defining which populations should be offered genetic counseling and testing is imperative to provide proper diagnoses and medical management for not only the primary patient, but also their biological relatives.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41178269","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}
Eleanor P Taranto, Stefan K Barta, Rahul S Bhansali
{"title":"Central Nervous System Relapse in T and NK cell Lymphomas.","authors":"Eleanor P Taranto, Stefan K Barta, Rahul S Bhansali","doi":"10.1007/s11899-023-00710-x","DOIUrl":"10.1007/s11899-023-00710-x","url":null,"abstract":"<p><strong>Purpose of review: </strong>T and NK cell lymphomas are relatively rare and heterogeneous forms of non-Hodgkin lymphoma that are associated with high rates of mortality. Central nervous system relapse carries significant morbidity, though management is largely extrapolated from literature in B cell neoplasms. As such, outcomes for central nervous system involvement in T/NK cell lymphomas are dismal with no standard of care. In this review, we discuss the epidemiology of central nervous system relapse in T/NK cell lymphomas and critically analyze available literature regarding prophylaxis and treatment.</p><p><strong>Recent findings: </strong>Retrospective studies of central nervous system involvement in T/NK cell lymphomas have been limited by small sample sizes and heterogeneity of subtypes, though sites of extranodal involvement and disease subtypes are consistently reported as risk factors. Compelling evidence for the use of central nervous system-directed prophylactic therapy has not yet been established, though recent reports of central nervous system activity with novel agents may suggest promising therapeutic options. The overall rarity of T and NK cell lymphomas has precluded adequate study of prophylaxis and treatment of central nervous system relapse. Collaborative efforts are needed to better define strategies to address CNS disease in T/NK cell lymphomas. These should involve the use of targeted agents, which may hold an advantage over traditional cytotoxic drugs.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10058085","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}
{"title":"Measurable Residual Disease Monitoring in Lymphoma.","authors":"Brian Cuzzo, Andrew Lipsky, Hua-Jay J Cherng","doi":"10.1007/s11899-023-00715-6","DOIUrl":"10.1007/s11899-023-00715-6","url":null,"abstract":"<p><strong>Purpose of review: </strong>The utility of analyzing circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and disease in the bone marrow as an adjunctive tool in caring for hematologic cancer patients is expanding. This holds true for lymphoma where these biomarkers are being explored as a means of genotyping and quantifying disease. Regarding the latter, they can be used to monitor measurable residual disease (MRD) during and after treatment. This holds potential for aiding clinical decisions amidst treatment, detecting earlier relapse, and improving prognostication. Here, we review the evidence to support these applications in a variety of lymphoma subtypes.</p><p><strong>Recent findings: </strong>Numerous clinical trials across a variety of lymphomas have demonstrated value in MRD monitoring. MRD monitoring is often prognostic for progression free survival (PFS) and even overall survival (OS) at several time points in a disease course, particularly when utilizing serial measurements. With regards to tailoring treatment, there are a growing number of trials examining MRD-adaptive treatment strategies to intensify or de-escalate treatment to individualize care. Lastly, MRD monitoring has been utilized successfully in detecting earlier relapse when compared to more standard methods of clinical surveillance such as radiographic assessment. Although not routinely implemented into clinical practice, MRD monitoring in lymphoma is helping shape the future landscape of this disease by aiding in prognostication, guiding therapy, and detecting earlier relapse. Steps to standardize and further examine this technology prospectively are being taken to bring MRD monitoring to the forefront of the field.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479172","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}