Current Hematologic Malignancy Reports最新文献_第8页

CML Resistant to 2nd-Generation TKIs: Mechanisms, Next Steps, and New Directions. CML抵抗第二代tki:机制，下一步和新方向。

IF 2.9 3区医学

Current Hematologic Malignancy Reports Pub Date : 2022-12-01 DOI: 10.1007/s11899-022-00683-3

Emilia Scalzulli, Ida Carmosino, Maria Laura Bisegna, Maurizio Martelli, Massimo Breccia

{"title":"CML Resistant to 2nd-Generation TKIs: Mechanisms, Next Steps, and New Directions.","authors":"Emilia Scalzulli, Ida Carmosino, Maria Laura Bisegna, Maurizio Martelli, Massimo Breccia","doi":"10.1007/s11899-022-00683-3","DOIUrl":"https://doi.org/10.1007/s11899-022-00683-3","url":null,"abstract":"Purpose of review: The clinical scenario for chronic myeloid leukemia patients rapidly changed after the introduction of tyrosine kinase inhibitors (TKIs). Second-generation TKIs as frontline treatment increased the rate of deep molecular responses without increasing the rate of overall survival. About 20% of patients experience resistance to these agents, needing alternative treatments. Here, we reviewed the possible mechanisms of resistance, available treatment, and new drugs developed to counteract and overcome resistance.Recent findings: Results of novel TKIs have been recently reported, especially for the setting of T315I mutated patients, such as olverembatinib and asciminib, or for patients who developed resistance due to other mutations, such as vodobatinib. Most of new TKIs are selected among compounds tested selective on ABL, therefore without possible off-target effects in the long term. New potential treatments are on the horizon in the field of CML, able to rescue patients treated firstly with one or more second-generation TKIs. Results of ongoing trials and real-world evidence dataset will help us to identify the appropriate timing of intervention and to select appropriate candidate to these drugs.","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10621385","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: 3

Towards a Personalized Definition of Prognosis in Philadelphia-Negative Myeloproliferative Neoplasms. 费城阴性骨髓增生性肿瘤预后个性化定义的探讨。

IF 2.9 3区医学

Current Hematologic Malignancy Reports Pub Date : 2022-10-01 Epub Date: 2022-09-01 DOI: 10.1007/s11899-022-00672-6

Barbara Mora, Francesco Passamonti

{"title":"Towards a Personalized Definition of Prognosis in Philadelphia-Negative Myeloproliferative Neoplasms.","authors":"Barbara Mora, Francesco Passamonti","doi":"10.1007/s11899-022-00672-6","DOIUrl":"https://doi.org/10.1007/s11899-022-00672-6","url":null,"abstract":"Purpose of review: Philadelphia-negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), prefibrotic (pre-), and overt-primary myelofibrosis (primary MF, PMF). PV and ET could evolve into secondary MF (SMF), whose early diagnosis relies on monitoring signs of possible progression. All MPNs have a risk of blast phase (BP), that is associated with a very dismal outcome. Overall survival (OS) is different among MPNs, and disease-specific prognostic scores should be applied for a correct clinical management. In this review, an overview of current prognostic scores in MPNs will be provided.Recent findings: The biological complexity of MPNs and its role on the trajectory of disease outcome have led to the design of integrated prognostic models that are nowadays of common use in PMF patients. As for PV and ET, splicing gene mutations could have a detrimental role, but with the limit of the not routinary recommended application of extensive molecular analysis in these diseases. SMF is recognized as a distinct entity compared to PMF, and OS estimates should be calculated by the MYSEC-PM (Myelofibrosis SECondary-prognostic model). Both in PMF and SMF, decisions as selection of patients potentially candidates to allogenic stem cell transplant or that could benefit from an early shift from standard treatment are based not only on conventional prognostic scores, but also on multivariable algorithms. The expanding landscape of risk prediction for OS, evolution to BP, and SMF progression from PV/ET informs personalized approach to the management of patients affected by MPNs.","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40336063","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}

引用次数: 5

Novel Therapies in Myelofibrosis: Beyond JAK Inhibitors. 骨髓纤维化的新疗法:超越JAK抑制剂。

IF 2.9 3区医学

Current Hematologic Malignancy Reports Pub Date : 2022-10-01 Epub Date: 2022-08-19 DOI: 10.1007/s11899-022-00671-7

Julian A Waksal, John Mascarenhas

{"title":"Novel Therapies in Myelofibrosis: Beyond JAK Inhibitors.","authors":"Julian A Waksal, John Mascarenhas","doi":"10.1007/s11899-022-00671-7","DOIUrl":"https://doi.org/10.1007/s11899-022-00671-7","url":null,"abstract":"Purpose of review: To discuss the current treatment paradigm, review novel targets, and summarize completed and ongoing clinical trials that may lead to a paradigm shifts in the management of myelofibrosis (MF).Recent findings: In addition to the recent approval and ongoing late-stage development of multiple novel JAK inhibitors, recent clinical studies demonstrate therapeutic potential of targeting multiple alternate proteins and pathways including BET, MDM2, telomerase, BCL2, LSD1, PI3K, SMAC, and PTX2 in patients with MF. MF is a myeloproliferative neoplasm characterized by clonal proliferation of myeloid cells and bone marrow fibrosis often causing cytopenias, extramedullary hematopoiesis resulting in hepatosplenomegaly, and increased pro-inflammatory cytokine production driving systemic symptoms. A significant proportion of morbidity and mortality is related to the propensity to transform to acute leukemia. Allogeneic hematopoietic stem cell transplantation is the only curative therapy; however, due to the high associated mortality, this treatment is not an option for the majority of patients with MF. Currently, there are three targeted Food and Drug Administration (FDA)-approved therapies for MF which include ruxolitinib, fedratinib, and pacritinib, all part of the JAK inhibitor class. Many patients are unable to tolerate, do not respond, or develop resistance to existing therapies, leaving a large unmet medical need. In this review, we discuss the current treatment paradigm and novel therapies in development for the treatment of MF. We review the scientific rationale of each targeted pathway. We summarize updated clinical data and ongoing trials that may lead to FDA approval of these agents.","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40625246","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: 5

Management of Chronic Myeloid Leukemia in Children and Young Adults. 儿童和青年慢性髓性白血病的治疗。

IF 2.9 3区医学

Current Hematologic Malignancy Reports Pub Date : 2022-10-01 Epub Date: 2022-08-03 DOI: 10.1007/s11899-022-00673-5

Maegan Ford, Michael Mauro, Catherine Aftandilian, Kathleen M Sakamoto, Nobuko Hijiya

{"title":"Management of Chronic Myeloid Leukemia in Children and Young Adults.","authors":"Maegan Ford, Michael Mauro, Catherine Aftandilian, Kathleen M Sakamoto, Nobuko Hijiya","doi":"10.1007/s11899-022-00673-5","DOIUrl":"https://doi.org/10.1007/s11899-022-00673-5","url":null,"abstract":"Purpose of review: Due to lack of pediatric-specific data, the management of chronic myeloid leukemia (CML) in pediatric, adolescents, and young adults is guided by adult CML evidence-based recommendations. Pediatric CML presents differently than adult CML and is often a more aggressive disease with different biological and host factors, yet there is sparse literature on how to address those differences.Recent findings: Over the past two decades, tyrosine kinase inhibitors (TKIs) have changed the way CML is treated. There are currently three FDA-approved TKIs (imatinib, dasatinib, and nilotinib) for pediatric patients. When choosing which TKI to begin treatment with, there are many factors that should be considered on a case-to-case basis to obtain optimal outcomes. The safety profiles for long-term TKI use in pediatrics require further study. Unlike adults, children are still actively growing during TKI use, and the effect on development can be detrimental. TKI therapy is not recommended during pregnancy with variable but significant risk of fetal abnormalities and miscarriage, warranting counseling for young female patients prior to beginning TKIs. Attempts for treatment-free remission (TFR) by planned TKI cessation in eligible adult patients in deep and sustained molecular remission are now done as a standard of practice. However, data is sparse in the pediatric population. There is currently an ongoing Children's Oncology Group (COG) study to determine the feasibility of TFR as a treatment goal. Further research and additional pediatric trials are needed to characterize the unique aspects of CML in children and adolescents and optimize outcomes.","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40578076","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}

引用次数: 5

IF 2.9 3区医学

Current Hematologic Malignancy Reports Pub Date : 2022-10-01 Epub Date: 2022-06-25 DOI: 10.1007/s11899-022-00666-4

Mia J Sullivan, Elizabeth L Palmer, Juliana Perez Botero

{"title":"ANKRD26-Related Thrombocytopenia and Predisposition to Myeloid Neoplasms.","authors":"Mia J Sullivan, Elizabeth L Palmer, Juliana Perez Botero","doi":"10.1007/s11899-022-00666-4","DOIUrl":"https://doi.org/10.1007/s11899-022-00666-4","url":null,"abstract":"Purpose of review: This review describes ANKRD26-related thrombocytopenia (RT) from a molecular, clinical, and laboratory perspective, with a focus on the clinical decision-making that takes place in the diagnosis and management of families with ANKRD26-RT.Recent findings: ANKRD26-related thrombocytopenia (ANKRD26-RT) is a non-syndromic autosomal dominant thrombocytopenia with predisposition to hematologic neoplasm. The clinical presentation is variable with moderate thrombocytopenia with normal platelet size and absent to mild bleeding being the hallmark which makes it difficult to distinguish from other inherited thrombocytopenias. The pathophysiology involves overexpression of ANKRD26 through loss of inhibitory control by transcription factors RUNX1 and FLI1. The great majority of disease-causing variants are in the 5' untranslated region. Acute myeloid leukemia, myelodysplastic syndrome, and chronic myelomonocytic leukemia have been reported to occur in the context of germline variants in ANKRD26, with the development of somatic driver mutations in hematopoietic regulators playing an important role in malignant transformation. In the absence of clear risk estimates of development of malignancy, optimal surveillance strategies and interventions to reduce risk of evolution to a myeloid disorder, multidisciplinary evaluation, with a strong genetic counseling framework is essential in the approach to these patients and their families. Gene-specific expertise and a multidisciplinary approach are important in the diagnosis and treatment of patients and families with ANKRD26-RT. These strategies help overcome the challenges faced by clinicians in the evaluation of individuals with a rare, non-syndromic, inherited disorder with predisposition to hematologic malignancy for which large data to guide decision-making is not available.","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40398657","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: 3

Advances in Risk Stratification and Treatment of Polycythemia Vera and Essential Thrombocythemia. 真性红细胞增多症和原发性血小板增多症的危险分层及治疗进展。

IF 2.9 3区医学

Current Hematologic Malignancy Reports Pub Date : 2022-10-01 Epub Date: 2022-08-06 DOI: 10.1007/s11899-022-00670-8

Ivan Krecak, Marko Lucijanic, Srdan Verstovsek

{"title":"Advances in Risk Stratification and Treatment of Polycythemia Vera and Essential Thrombocythemia.","authors":"Ivan Krecak, Marko Lucijanic, Srdan Verstovsek","doi":"10.1007/s11899-022-00670-8","DOIUrl":"https://doi.org/10.1007/s11899-022-00670-8","url":null,"abstract":"Purpose of review: Estimating and modifying thrombotic risk is currently the mainstay of care for patients with polycythemia vera (PV) and essential thrombocythemia (ET). In recent years, however, increased attention has shifted towards quality of life and disease modification. In this review, we discuss recent advances in risk stratification, present updated results for ruxolitinib and interferon randomized clinical trials, discuss new approaches in antiplatelet and anticoagulant treatment, and summarize early phase trials of novel agents and emerging therapeutic concepts for the treatment of PV and ET.Recent findings: International collaborations and novel technologies, i.e., next-generation sequencing and machine learning techniques, have demonstrated excellent abilities to improve thrombotic risk stratification in PV and ET. Updated results from ruxolitinib and interferon randomized clinical trials have confirmed excellent efficacy and safety of these agents, both as first- and second-line treatments. Early trials of novel agents (histone deacetylase inhibitors, telomerase inhibitors, lysine-specific demethylase-1 inhibitors, human double-minute 2 inhibitors, and hepcidin mimetics) have shown encouraging efficacy and safety in blood count control, reduction of splenomegaly, and alleviation of disease-related symptoms. Finally, accumulating evidence suggested that direct oral anticoagulants may be a valid therapeutic alternative to warfarin for prolonged thromboprophylaxis. International collaborations (\"big data\") with the help of new technologies represent an exciting new approach to analyze rare outcomes in rare diseases, especially for identifying novel prognostic biomarkers in PV and ET. Randomized clinical trials are also needed to fully elucidate whether novel agents may establish new standards of care.","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40585867","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: 10

Germline and Somatic Defects in DDX41 and its Impact on Myeloid Neoplasms. DDX41的种系和体细胞缺陷及其对髓系肿瘤的影响。

IF 2.9 3区医学

Current Hematologic Malignancy Reports Pub Date : 2022-10-01 DOI: 10.1007/s11899-022-00667-3

Talha Badar, Timothy Chlon

{"title":"Germline and Somatic Defects in DDX41 and its Impact on Myeloid Neoplasms.","authors":"Talha Badar, Timothy Chlon","doi":"10.1007/s11899-022-00667-3","DOIUrl":"https://doi.org/10.1007/s11899-022-00667-3","url":null,"abstract":"Purpose of review: While DDX41 mutation (m) is one of the most prevalent predisposition genes in adult myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), most patients do not always present with a family history of MDS/AML. In this review, we will be highlighting epidemiological data on DDX41m, roles of DDX41 in oncogenesis, mechanisms of clonal evolution with somatic DDX41m, and clinical phenotypes and management of MDS/AML in patients harboring DDX41m.Recent findings: DDX41 encodes a DEAD-box helicase protein that is considered essential for cell growth and viability. High incidence of myeloid malignancies and other cancers in patients bearing DDX41m suggests that defects in DDX41 lead to loss of a tumor suppressor function, likely related to activities in RNA splicing and processing pathways. Seventy percent of cancer cases with DDX41m are associated with MDS/AML alone. More than 65% of familial cases harbor heterozygous germline frameshift mutations, of which p.D140Gfs*2 is the most common. A somatic DDX41m of the second allele is acquired in 70% of cases, leading to hematological malignancy. Myeloid neoplasms with DDX41m are typically characterized by long latency, high-risk disease at presentation with normal cytogenetics and without any additional molecular markers. Recent reports suggests that a subgroup of these patients have an indolent clinical course and have a better long-term survival compared to favorable or intermediate risk AML. Distinct clinical/pathologic features and favorable outcomes in MDS/AML highlight the need for standardized classification and gene specific guidelines that could assist in management decisions in patients with DDX41m.","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324161/pdf/nihms-1906846.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10133935","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}

引用次数: 7

Germline CHEK2 and ATM Variants in Myeloid and Other Hematopoietic Malignancies 骨髓和其他造血系统恶性肿瘤的种系CHEK2和ATM变体

IF 2.9 3区医学

Current Hematologic Malignancy Reports Pub Date : 2022-06-08 DOI: 10.1007/s11899-022-00663-7

Ryan J. Stubbins, S. Korotev, L. Godley

引用次数: 15

Germline Abnormalities in DNA Methylation and Histone Modification and Associated Cancer Risk DNA甲基化和组蛋白修饰与相关癌症风险的种系异常

IF 2.9 3区医学

Current Hematologic Malignancy Reports Pub Date : 2022-06-02 DOI: 10.1007/s11899-022-00665-5

Jenna A. Fernandez, M. Patnaik

引用次数: 0

MRD in ALL: Optimization and Innovations ALL中的MRD：优化与创新

IF 2.9 3区医学

Current Hematologic Malignancy Reports Pub Date : 2022-05-26 DOI: 10.1007/s11899-022-00664-6

E. Pierce, B. Mautner, J. Mort, Anastassia Blewett, A. Morris, M. Keng, F. El Chaer

引用次数: 3