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Current Hematologic Malignancy Reports

Roberta Zappasodi, Jedd D Wolchok, Taha Merghoub
PURPOSE OF REVIEW: Despite the clinical successes of immune checkpoint blockade across multiple tumor types, many patients do not respond to these therapies or become resistant after an initial response. This underscores the need to improve our understanding of the molecular determinants of response to guide more personalized and rational utilization of these therapies. Here, we describe available biomarkers of checkpoint blockade activity by classifying them into four major categories: tumor-intrinsic, immune microenvironmental, host-related, and dynamic factors...
August 29, 2018: Current Hematologic Malignancy Reports
John H Baird, Jason Gotlib
PURPOSE OF REVIEW: We discuss recent developments in the treatment of advanced systemic mastocytosis (advSM) with inhibitors of the KIT receptor tyrosine kinase. RECENT FINDINGS: advSM is a heterogeneous group of neoplasms of poor prognosis characterized by the accumulation of neoplastic mast cells. The canonical KIT D816V mutation is present in approximately 90% of SM patients, and its detection is critical for both diagnosis and therapeutic decision-making. The multikinase/KIT inhibitor midostaurin was recently approved for advSM...
August 28, 2018: Current Hematologic Malignancy Reports
Justin M Darrah, Alex F Herrera
PURPOSE OF REVIEW: The use of circulating tumor DNA (ctDNA) for the purposes of diagnosis, prognosis, assessment of treatment response, and monitoring for relapse is a new and developing field in lymphoma. This review aims to summarize many of the most recent advances in ctDNA applications. RECENT FINDINGS: Recent studies have demonstrated the use of ctDNA assessment across many lymphoma subtypes including diffuse large B-cell lymphoma, follicular lymphoma, Hodgkin lymphoma, and T-cell lymphoma...
August 23, 2018: Current Hematologic Malignancy Reports
Katherine C Pehlivan, Brynn B Duncan, Daniel W Lee
PURPOSE OF REVIEW: Genetically engineered T cells expressing a chimeric antigen receptor (CAR-T) targeting specific antigens present on acute lymphoblastic leukemia (ALL) blasts have generated promising results in children and adults with relapsed and refractory disease. We review the current evidence for CAR-T cell therapy in ALL, associated toxicities, and efforts to improve durable response to therapy. RECENT FINDINGS: CD19-directed CAR-T cells have recently been approved by the FDA for use in children and young adults with ALL and in adults with diffuse large B cell lymphoma (DLBCL) in the relapsed/refractory setting...
August 17, 2018: Current Hematologic Malignancy Reports
Joanna Rhodes, Daniel J Landsburg
PURPOSE OF REVIEW: Diffuse large B cell lymphoma (DLBCL) remains the most common non-Hodgkin lymphoma (NHL) in developed countries. Up to 30-40% of patients experience either refractory or relapsed disease following receipt of front-line chemoimmunotherapy, and the majority of these patients will not be cured following receipt of subsequent therapy. RECENT FINDINGS: Small-molecule inhibitors (SMIs) are an attractive class of therapeutics for patients with chemorefractory DLBCL, and early-phase studies with these agents have typically demonstrated prolonged periods of disease control in responding patients without significant toxicity...
August 15, 2018: Current Hematologic Malignancy Reports
Jennifer K Lue, Jennifer E Amengual
PURPOSE OF REVIEW: Enhancer of Zeste Homolog 2 (EZH2) is histone methyltransferase and catalyzes the methylation of histone 3 lysine 27, a mark of transcriptional repression. Various studies have elucidated the complex role of EZH2 in both normal biology and tumorigenesis. Here, we critically review the emerging role of EZH2 in malignancies, the development of small molecule inhibitors of EZH2, and their application in lymphoma. RECENT FINDINGS: Activating mutations and overexpression of EZH2 are found in non-Hodgkin lymphoma (NHL)...
August 15, 2018: Current Hematologic Malignancy Reports
Aziz Nazha, Mrinal M Patnaik
PURPOSE OF REVIEW: To evaluate established prognostic models in chronic myelomonocytic leukemia (CMML) and describe the challenges associated with their application in clinical practice. RECENT FINDINGS: CMML is a clonal hematopoietic stem cell disorder with heterogeneous clinical and molecular features. Outcomes of CMML patients can vary from indolent disease with expected survival measured in years versus proliferative subtypes with rapid progression to acute myeloid leukemia and survival measured in months...
July 31, 2018: Current Hematologic Malignancy Reports
Jessica T Leonard, Brandon Hayes-Lattin
PURPOSE OF REVIEW: Outcomes for older adults with acute lymphoblastic leukemia (ALL) remain poor, and allogeneic hematopoietic stem cell transplant (HSCT) remains a potentially curative modality. However, benefits are offset by high rates of non-relapse mortality (NRM) in patients undergoing myeloablative conditioning (MAC) regimens. Reduced intensity conditioning (RIC) regimens can extend this therapy to adults who are unfit for MAC, although at the cost of higher relapse rates. In this review, we discuss evidence to support the usage of RIC regimens, controversies, and potential strategies to improve transplant outcomes going forward...
July 14, 2018: Current Hematologic Malignancy Reports
Kathleen W Phelan, Anjali S Advani
PURPOSE OF REVIEW: Treatment options for patients with acute lymphoblastic leukemia (ALL) beyond standard chemotherapy have grown significantly in recent years. In this review, we highlight new targeted therapies in ALL, with an emphasis on immunotherapy. RECENT FINDINGS: Major advances include antibody-based therapies, such as naked monoclonal antibodies, antibody-drug conjugates and bispecific T cell engaging (BiTE) antibodies, as well as adoptive cellular therapies such as chimeric antigen receptor (CAR) T cells...
August 2018: Current Hematologic Malignancy Reports
Adrienne A Phillips, Janine C K Harewood
PURPOSE OF REVIEW: ATL is a rare and highly aggressive T cell malignancy caused by HTLV-1. We will review the state of the art of ATL epidemiology, pathogenesis, diagnosis, and treatment. RECENT FINDINGS: Because of population migration, cases of ATL in non-HTLV-1 endemic countries including North America and Europe are increasingly recognized. ATL has diverse clinical manifestations, limited treatment options not widely available globally, and poor prognosis despite therapy...
August 2018: Current Hematologic Malignancy Reports
Talal Hilal, Jeffrey A Betcher, Jose F Leis
PURPOSE OF REVIEW: Small molecule tyrosine kinase inhibitors (TKIs) and BCL2 inhibitors are oral targeted therapies that have changed the treatment approach to patients with chronic lymphocytic leukemia (CLL). The aim of this review is to summarize the relevant literature on the economic impact of oral novel therapies for the treatment of CLL and discuss the underlying factors and suggested solutions for high drug prices. RECENT FINDINGS: The cost of therapy for CLL has increased substantially since the introduction of oral therapies...
August 2018: Current Hematologic Malignancy Reports
Prashant Sharma, Daniel A Pollyea
PURPOSE OF REVIEW: Apoptosis results from the interaction between pro- and anti-apoptotic proteins, mediated by BCL-2 homology 3 (BH3) proteins. B cell lymphoma-2 (BCL-2) is an inhibitor of apoptosis which stabilizes the mitochondria, resulting in the prevention of activation of the pro-apoptotic proteins. In addition, BCL-2 is overexpressed in the leukemic stem cell (LSC) population, and its inhibition may lead to selective LSC eradication. Herein, we will discuss the mechanism and rationale of BCL-2 inhibition in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) with an overview of the selective BCL-2 inhibitor venetoclax...
August 2018: Current Hematologic Malignancy Reports
Waseem Lone, Aisha Alkhiniji, Jayadev Manikkam Umakanthan, Javeed Iqbal
PURPOSE OF REVIEW: Peripheral T cell lymphoma (PTCL) is a heterogeneous group of lymphoproliferative neoplasms, with at least 29 distinct entities described in current WHO classification. Using present diagnostic approaches, more than a third of PTCL cases cannot be classified, hence designated as PTCL-not otherwise specified (PTCL-NOS). Herein, we summarize the current genomic findings and their role in the molecular pathogenesis in different PTCL entities. RECENT FINDINGS: Gene expression profiling (GEP) studies have identified distinct molecular signatures for accurate diagnosis and elucidated oncogenic pathways enriched in major PTCL entities...
August 2018: Current Hematologic Malignancy Reports
Christopher Wenzinger, Eli Williams, Alejandro A Gru
PURPOSE OF REVIEW: Acute lymphoblastic leukemias (ALL) are malignant disorders of immature B or T cells that occur characteristically in children, usually under the age of 6 (75%). Approximately 6000 new cases of ALL are diagnosed each year in the USA, 80-85% of which represent B-ALL forms. Most presentations of B-ALL are leukemic, whereas T-ALL presents with a mediastinal mass, with or without leukemic involvement. The revised fourth edition of the World Health Organization (WHO) classification (2017) has introduced some changes in both B and T-ALL...
August 2018: Current Hematologic Malignancy Reports
Mehrdad Hefazi, Mark R Litzow
PURPOSE OF REVIEW: This article provides an overview of the current knowledge regarding the biology and treatment of T cell acute lymphoblastic leukemia (T-ALL) and highlights the most recent findings in this field over the past 5 years. RECENT FINDINGS: Remarkable progress has been made in the genomic landscape of T-ALL over the past few years. The discovery of activating mutations of NOTCH1 and FBXW7 in a majority of patients has been a seminal observation, with several early phase clinical trials currently exploring these as potential therapeutic targets...
August 2018: Current Hematologic Malignancy Reports
Udit Chander, Rebecca J Leeman-Neill, Govind Bhagat
PURPOSE OF REVIEW: To provide an update on the pathogenesis of enteropathy-associated T cell lymphoma (EATL) and its relationship with refractory celiac disease (RCD), in light of current knowledge of immune, genetic, and environmental factors that promote neoplastic transformation of intraepithelial lymphocytes (IELs). RECENT FINDINGS: EATL frequently evolves from RCD type II (RCD II) but can occur "de novo" in individuals with celiac disease. Recurrent activating mutations in members of the JAK/STAT pathway have been recently described in EATL and RCD II, which suggests deregulation of cytokine signaling to be an early event in lymphomagenesis...
August 2018: Current Hematologic Malignancy Reports
Kathryn S Ivy, P Brent Ferrell
PURPOSE OF REVIEW: Immune dysregulation is a defining feature of myelodysplastic syndromes (MDS). Recently, several studies have further defined the complex role of immune alterations within MDS. Herein, we will summarize some of these findings and discuss the therapeutic strategies currently in development. RECENT FINDINGS: Immune alterations in MDS are complex, heterogeneous, and intertwined with clonal hematopoiesis and stromal cell dysfunction. Inflammation in MDS proceeds as a vicious cycle, mediated in large part by secreted factors, which induce cell death and activate innate immune signaling...
June 22, 2018: Current Hematologic Malignancy Reports
Nisha S Joseph, Jonathan L Kaufman
PURPOSE OF REVIEW: Light-chain-associated (AL) amyloidosis is a rare disease with a poor prognosis. However, we have made recent strides in more accurate diagnosis and effective treatment. Here, we discuss the most recent updates and advancements during the past year in the diagnosis, prognostication, and management of AL amyloidosis both in the upfront and relapsed setting. RECENT FINDINGS: New imaging modalities, such as cardiac magnetic resonance (CMR) and use of fluorine-labeled radiotracers, are emerging as an important diagnostic tool in conjunction with biomarkers in the diagnosis, prognosis, and monitoring of the effects of therapy...
June 2018: Current Hematologic Malignancy Reports
Prithviraj Bose, Srdan Verstovsek
PURPOSE OF REVIEW: Cytopenias, particularly anemia, are frequently encountered in patients with myelofibrosis. Management of cytopenias in myelofibrosis can be very challenging because current therapeutic interventions are only of modest efficacy and ruxolitinib, the only approved drug for myelofibrosis, is myelosuppressive. Yet, dose optimization of ruxolitinib is important for its survival benefit in patients with advanced disease. We sought to summarize the data on treatments for cytopenias available at present and review promising agents in development and emerging strategies...
June 2018: Current Hematologic Malignancy Reports
Thuy T Koll, Ashley E Rosko
PURPOSE OF REVIEW: Older adults with hematologic malignancy are a growing demographic. Estimating risk of chemotherapy toxicity based on age alone is an unreliable estimate of quality of life, functional capacity, or risk of treatment complications. RECENT FINDINGS: Dedicated geriatric assessment tools can aid the clinician in identifying geriatric syndromes such as frailty, resulting in improved prognostication to decrease morbidity and mortality. Frailty is not synonymous with individual performance status and is dynamic...
June 2018: Current Hematologic Malignancy Reports
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