Barbara Mora, Cristina Bucelli, Daniele Cattaneo, Valentina Bellani, Francesco Versino, Kordelia Barbullushi, Nicola Fracchiolla, Alessandra Iurlo, Francesco Passamonti
{"title":"Prognostic and Predictive Models in Myelofibrosis.","authors":"Barbara Mora, Cristina Bucelli, Daniele Cattaneo, Valentina Bellani, Francesco Versino, Kordelia Barbullushi, Nicola Fracchiolla, Alessandra Iurlo, Francesco Passamonti","doi":"10.1007/s11899-024-00739-6","DOIUrl":"10.1007/s11899-024-00739-6","url":null,"abstract":"<p><strong>Purpose of review: </strong>Myelofibrosis (MF) includes prefibrotic primary MF (pre-PMF), overt-PMF and secondary MF (SMF). Median overall survival (OS) of pre-PMF, overt-PMF and SMF patients is around 14 years, seven and nine years, respectively. Main causes of mortality are non-clonal progression and transformation into blast phase.</p><p><strong>Recent findings: </strong>Discoveries on the impact of the biological architecture on OS have led to the design of integrated scores to predict survival in PMF. For SMF, OS estimates should be calculated by the specific MYSEC-PM (MYelofibrosis SECondary-prognostic model). Information on the prognostic role of the molecular landscape in SMF is accumulating. Crucial treatment decisions for MF patients could be now supported by multivariable predictive algorithms. OS should become a relevant endpoint of clinical trials. Prognostic models guide prediction of OS and treatment planning in MF, therefore, their timely application is critical in the personalized approach of MF patients.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"223-235"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046390","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}
Valerie Tran, Kiarash Salafian, Kenan Michaels, Caroline Jones, Daniel Reed, Michael Keng, Firas El Chaer
{"title":"MRD in Philadelphia Chromosome-Positive ALL: Methodologies and Clinical Implications.","authors":"Valerie Tran, Kiarash Salafian, Kenan Michaels, Caroline Jones, Daniel Reed, Michael Keng, Firas El Chaer","doi":"10.1007/s11899-024-00736-9","DOIUrl":"10.1007/s11899-024-00736-9","url":null,"abstract":"<p><strong>Purpose of review: </strong>Measurable residual disease (MRD) is integral in the management of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). This review discusses the current methods used to evaluate MRD as well as the interpretation, significance, and incorporation of MRD in current practice.</p><p><strong>Recent findings: </strong>New molecular technologies have allowed the detection of MRD to levels as low as 10<sup>- 6</sup>. The most used techniques to evaluate MRD are multiparametric flow cytometry (MFC), quantitative reverse transcription polymerase chain reaction (RT-qPCR), and high-throughput next-generation sequencing (NGS). Each method varies in terms of advantages, disadvantages, and MRD sensitivity. MRD negativity after induction treatment and after allogeneic hematopoietic cell transplantation (HCT) is an important prognostic marker that has consistently been shown to be associated with improved outcomes. Blinatumomab, a new targeted therapy for Ph + ALL, demonstrates high efficacy in eradicating MRD and improving patient outcomes. In the relapsed/refractory setting, the use of inotuzumab ozogamicin and tisagenlecleucel has shown promise in eradicating MRD. The presence of MRD has become an important predictive measure in Ph + ALL. Current studies evaluate the use of MRD in treatment decisions, especially in expanding therapeutic options for Ph + ALL, including tyrosine kinase inhibitors, targeted antibody therapies, chimeric antigen receptor cell therapy, and HCT.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"186-196"},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418291","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}
Rachel S Werk, Mallorie B Heneghan, Sherif M Badawy
{"title":"Use of Patient-Centered Technology and Digital Interventions in Pediatric and Adult Patients with Hematologic Malignancies.","authors":"Rachel S Werk, Mallorie B Heneghan, Sherif M Badawy","doi":"10.1007/s11899-024-00732-z","DOIUrl":"10.1007/s11899-024-00732-z","url":null,"abstract":"<p><strong>Purpose of review: </strong>As society continues to advance in technology, it is important to address how this advancement can impact and enhance patient care. The purpose of this review is to identify patient-centered technology currently available for adult and pediatric patients with and those having survived hematologic malignancies. Given that patients with hematologic malignancies often have to adhere to strenuous medication regimens, coordinate care with many different providers, manage symptoms associated with treatment, and manage late effects associated with survivorship, they would benefit greatly from patient-centered technology aimed at decreasing these burdens.</p><p><strong>Recent findings: </strong>This review found various available digital interventions for this patient population and focuses on an overview of commercially available smartphone applications, patient portals, and technology for remote monitoring. In summary, many digital interventions exist for use in the medical care of oncology patients. The incorporation of these interventions can allow for more personalized medical care, better organization of treatment plans by caregivers at home, and easy delivery of accurate medical information.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"153-162"},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160565","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":"Glucocorticoid Therapy in Acute Lymphoblastic Leukemia: Navigating Short-Term and Long-Term Effects and Optimal Regimen Selection.","authors":"Hoda Pourhassan, Lindsey Murphy, Ibrahim Aldoss","doi":"10.1007/s11899-024-00735-w","DOIUrl":"10.1007/s11899-024-00735-w","url":null,"abstract":"<p><strong>Purpose of review: </strong>Glucocorticoids are a mainstay in acute lymphoblastic leukemia treatment and lack of early response is predictive for overall disease prognosis. Given the vital position of glucocorticoids and well known long and short-term side effects associated with differing glucocorticoids, we aim to highlight the wide breadth of historical and more contemporary data to describe the current landscape of glucocorticoid use in this arena.</p><p><strong>Recent findings: </strong>Emerging studies aim to overcome issues such as steroid resistance and to optimize the antileukemic effects of glucocorticoids while aiming to mitigate the risks and side effects associated with their exposure. Glucocorticoids have and likely always will be a fundamental component of acute lymphoblastic leukemia treatment and understanding how to navigate short- and long-term effects and how to optimize regimens is at the heart of continued treatment success.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"175-185"},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310319","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":"Novel Approaches to Managing Patients with Relapsed and Refractory Waldenström Macroglobulinemia.","authors":"Karan L Chohan, Prashant Kapoor","doi":"10.1007/s11899-024-00730-1","DOIUrl":"10.1007/s11899-024-00730-1","url":null,"abstract":"<p><strong>Purpose of review: </strong>Waldenström macroglobulinemia is a rare non-Hodgkin lymphoma (NHL) characterized by lymphoplasmacytic bone marrow infiltration associated with an immunoglobulin M (IgM) monoclonal gammopathy. Over the past two decades, a number of important novel therapies have emerged for the treatment of relapsed and refractory (R/R) WM. The purpose of this review is to discuss these novel agents.</p><p><strong>Recent findings: </strong>Chemoimmunotherapy which formed the basis treatment for R/R WM is slowly being replaced by novel targeted agents. These therapies, including Bruton's tyrosine kinase inhibitors, proteasome inhibitors, and B-cell lymphoma 2 inhibitors, have widened the landscape of management. Emerging therapies currently under investigation, such as bispecific T-cell engagers, chimeric antigen T-cell receptor therapy, and novel small molecule inhibitors, have additionally shown the potential to improve response and survival. The treatment of R/R WM has greatly evolved, in large part due to a greater understanding of the biology of WM, and the evaluation of novel targeted agents in the basket trials of NHL, showing early activity in the small WM cohorts. Combination regimens with these established and emerging novel therapies have the potential to further improve disease control and induce higher rates of deep responses. Strategies aimed at altering the disease trajectory would require randomized controlled trials to provide relevant data on optimal integration and sequencing of more effective and tolerable regimens earlier in the disease course.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"163-174"},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544685","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":"Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia: Strategies to Optimize Success and New Directions.","authors":"Delphine Rea, Sofiane Fodil, Etienne Lengline, Emmanuel Raffoux, Jean-Michel Cayuela","doi":"10.1007/s11899-024-00728-9","DOIUrl":"10.1007/s11899-024-00728-9","url":null,"abstract":"<p><strong>Purpose of review: </strong>The discovery that patients suffering from chronic myeloid leukemia who obtain deep and long-lasting molecular responses upon treatment with tyrosine kinase inhibitors may maintain their disease silent for many years after therapy discontinuation launched the era of treatment-free remission as a key management goal in clinical practice. The purpose of this review on treatment-free remission is to discuss clinical advances, highlight knowledge gaps, and describe areas of research.</p><p><strong>Recent findings: </strong>Patients in treatment-free remission are a minority, and it is believed that some may still retain a reservoir of leukemic stem cells; thus, whether they can be considered as truly cured is uncertain. Strengthening BCR::ABL1 inhibition increases deep molecular responses but is not sufficient to improve treatment-free remission, and we lack biomarkers to identify and specifically target residual cells with aggressive potential. Another level of complexity resides in the intra- and inter-patient clonal heterogeneity of minimal residual disease and characteristics of the bone marrow environment. Finding determinants of deep molecular responses achievement and elucidating varying biological mechanisms enabling either post-tyrosine kinase inhibitor chronic myeloid leukemia control or relapse may help develop innovative and safe therapies. In the light of the increasing prevalence of CML, targeting the residual leukemic stem cell pool is thought to be the key.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"104-110"},"PeriodicalIF":2.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139930452","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}
Reema K Tawfiq, Jithma P Abeykoon, Prashant Kapoor
{"title":"Bruton Tyrosine Kinase Inhibition: an Effective Strategy to Manage Waldenström Macroglobulinemia.","authors":"Reema K Tawfiq, Jithma P Abeykoon, Prashant Kapoor","doi":"10.1007/s11899-024-00731-0","DOIUrl":"10.1007/s11899-024-00731-0","url":null,"abstract":"<p><strong>Purpose of review: </strong>The treatment of Waldenström macroglobulinemia (WM) has evolved over the past decade. With the seminal discoveries of MYD88 and CXCR warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) mutations in WM cells, our understanding of the disease biology and treatment has improved. The development of a new class of agents, Bruton tyrosine kinase inhibitors (BTKi), has substantially impacted the treatment paradigm of WM. Herein, we review the current and emerging BTKi and the evidence for their use in WM.</p><p><strong>Recent findings: </strong>Clinical trials have established the role of covalent BTKi in the treatment of WM. Their efficacy is compromised among patients who harbor CXCR4<sup>WHIM</sup> mutation or MYD88<sup>WT</sup> genotype. The development of BTK<sup>C481</sup> mutation-mediated resistance to covalent BTKi may lead to disease refractoriness. Novel, non-covalent, next-generation BTKi are emerging, and preliminary results of the early phase clinical trials show promising activity in WM, even among patients refractory to a covalent BTKi. Covalent BTK inhibitors have demonstrated meaningful outcomes in treatment-naïve (TN) and relapsed refractory (R/R) WM, particularly among those harboring the MYD88<sup>L265P</sup> mutation. The next-generation BTKi demonstrate improved selectivity, resulting in a more favorable toxicity profile. In WM, BTKi are administered until progression or the development of intolerable toxicity. Consequently, the potential for acquired resistance, the emergence of cumulative toxicities, and treatment-related financial burden are critical challenges associated with the continuous therapy approach. By circumventing BTK C481 mutations that alter the binding site to covalent BTKi, the non-covalent BTKi serve as alternative agents in the event of acquired resistance. Head-to-head comparative trials with the conventional chemoimmunotherapies are lacking. The findings of the RAINBOW trial (NCT046152), comparing the dexamethasone, rituximab, and cyclophosphamide (DRC) regimen to the first-generation, ibrutinib are awaited, but more studies are needed to draw definitive conclusions on the comparative efficacy of chemoimmunotherapy and BTKi. Complete response is elusive with BTKi, and combination regimens to improve upon the efficacy and limit the treatment duration are also under evaluation in WM.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"120-137"},"PeriodicalIF":2.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305179","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}
Jane J Chen, Franco Castillo Tokumori, Christina Del Guzzo, Jeanyoung Kim, Jia Ruan
{"title":"Update on T-Cell Lymphoma Epidemiology.","authors":"Jane J Chen, Franco Castillo Tokumori, Christina Del Guzzo, Jeanyoung Kim, Jia Ruan","doi":"10.1007/s11899-024-00727-w","DOIUrl":"10.1007/s11899-024-00727-w","url":null,"abstract":"<p><strong>Purpose of review: </strong>T-cell lymphomas (TCLs) are a group of rare subtypes of non-Hodgkin lymphoma derived from mature T-lymphocytes. Recent updates in lymphoma classification based on the cell-of-origin pathogenesis have shed new light on TCL epidemiology and outcomes. Contemporary regional consortia and international studies, including those conducted recently in Asia and South America, have provided an updated delineation of the major subtypes across various global regions.</p><p><strong>Recent findings: </strong>Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), remains the most common subtype globally except in Asia, where extra-nodal NK-T cell lymphoma (ENKTL) has emerged as the most prevalent. Angioimmunoblastic T-cell lymphoma (AITL) is the second most common subtype globally except in South America where its incidence falls behind adult T-cell leukemia/lymphoma (ATLL) and ENKTL. ALK-negative anaplastic large cell lymphoma (ALCL) has been recognized as the second most common subtype in some parts of South America. Studies on the newly classified breast implant-associated ALCL (BIA-ALCL) are beginning to reveal its distribution and risk factors. Deciphering the epidemiology of TCLs is a challenging endeavor due to the rarity of these entities and ongoing refinement in classification. Collaborative efforts on prospective registries based on the most current WHO classifications will help capture the true epidemiology of TCL subtypes to better focus resources for diagnostic, prognostic, and therapeutic efforts.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"93-103"},"PeriodicalIF":2.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048998","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":"Management of Patients with Early Myelofibrosis: A Discussion of Best Practices.","authors":"Prithviraj Bose","doi":"10.1007/s11899-024-00729-8","DOIUrl":"10.1007/s11899-024-00729-8","url":null,"abstract":"<p><strong>Purpose of review: </strong>Summarize best practices for management of patients with early myelofibrosis (MF).</p><p><strong>Recent findings: </strong>Myelofibrosis is a progressive myeloproliferative neoplasm (MPN) that generally produces burdensome symptoms and ultimately leads to worse overall survival than that observed in healthy controls or patients with other MPNs. Several Janus kinase inhibitors and various interferon formulations are now available for treatment of MF, with ruxolitinib notable for extending overall survival in addition to improving MF signs and symptoms. The chronic nature of the disease can lead some patients to avoid immediate treatment in favor of a watch-and-wait approach. This review summarizes the patient management approach taken in my practice, providing guidance and a discussion of best practices with an emphasis on the importance and clinical benefits of active treatment in early MF. In particular, a case is made to consider treatment with ruxolitinib for patients with intermediate-1 risk disease and to minimize delay between diagnosis and treatment initiation for patients with intermediate or high-risk disease.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":" ","pages":"111-119"},"PeriodicalIF":2.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027611","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}
Tariq Kewan, Maximillian Stahl, Jan Philipp Bewersdorf, Amer M. Zeidan
{"title":"Treatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities","authors":"Tariq Kewan, Maximillian Stahl, Jan Philipp Bewersdorf, Amer M. Zeidan","doi":"10.1007/s11899-024-00733-y","DOIUrl":"https://doi.org/10.1007/s11899-024-00733-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose of Review</h3><p>Myelodysplastic syndromes/neoplasms (MDS) represent a diverse group of pathologically distinct diseases with varying prognoses and risks of leukemia progression. This review aims to discuss current treatment options for elderly patients with MDS, focusing on patients ineligible for intensive chemotherapy or allogenic hematopoietic stem cell transplantation (HSCT). The challenges associated with treatment in this population and emerging therapeutic prospects are also explored.</p><h3 data-test=\"abstract-sub-heading\">Recent Findings</h3><p>Recent advancements in molecular diagnostics have enhanced risk stratification by incorporating genetic mutations, notably through the molecular International Prognostic Scoring System (IPSS-M). Lower-risk MDS (LR-MDS) treatment ranges from observation to supportive measures and erythropoiesis-stimulating agents (ESAs), with emerging therapies like luspatercept showing promise. High-risk MDS (HR-MDS) is treated with hypomethylating agents (HMAs) or allogenic HSCT, but outcomes remain poor.</p><h3 data-test=\"abstract-sub-heading\">Summary</h3><p>Elderly MDS patients, often diagnosed after 70, pose challenges in treatment decision-making. The IPSS-M aids risk stratification, guiding therapeutic choices. For LR-MDS, supportive care, ESAs, and novel agents like luspatercept are considered. Treatment of HR-MDS involves HMAs or allogenic HSCT. Emerging treatments, including oral HMAs and novel agents targeting FLT3, and IDH 1/2 mutations, show promise. Future research should refine treatment strategies for this elderly population focusing on quality-of-life improvement.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":"75 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630989","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}