The Evolving Landscape of Frontline Therapy in Chronic Phase Chronic Myeloid Leukemia (CML)
AbstractPurpose of ReviewChronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by uncontrolled proliferation of mature and maturing granulocytes. The disease is characterized by the presence of translocation t(9;22) leading to the abnormal BCR-ABL fusion. Historically, treatment options included hydroxyurea, busulfan, and interferon- α (IFN-α), with allogeneic stem cell transplant being the only potential curative therapy. More recently, the development of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of CML and turned a once fatal disease into a chronic and manageab...
Source: Current Hematologic Malignancy Reports - October 18, 2021 Category: Hematology Source Type: research

Challenges in Chronic Myeloid Leukemia Management in South America
AbstractPurpose of ReviewChronic myeloid leukemia (CML) management in developing countries has improved in the last years, but the availability of therapeutic resources, monitoring, reimbursement, and financial issues may be a challenge and interfere with the best practices and results of CML treatment. This review points out the main challenges in CML management in South America.Recent Findings.In this review, we describe the access to tyrosine kinase inhibitors and monitoring in different countries of South America. We also address the ongoing discontinuation trials, the progress, and limitations of hematopoietic stem ce...
Source: Current Hematologic Malignancy Reports - October 15, 2021 Category: Hematology Source Type: research

Health-Related Quality of Life of Patients with Chronic Myeloid Leukemia as Measured by Patient-Reported Outcomes: Current State and Future Directions
AbstractPurpose of ReviewTyrosine kinase inhibitors (TKIs) allow many patients with chronic myeloid leukemia (CML) to live normal life spans but have the potential to impact patients ’ health-related quality of life (HRQOL). Patient-reported outcome (PRO) measures can provide valuable information to inform treatment decision-making. Here, we review pivotal studies that used PRO measures to evaluate HRQOL of patients with CML in the first-line and treatment-free remission (TFR) , and identify areas for future research.Recent FindingsPRO measures commonly studied in patients with CML include the SF-36, FACT-Leu, EORTC ...
Source: Current Hematologic Malignancy Reports - October 14, 2021 Category: Hematology Source Type: research

Future Directions in Chronic Phase CML Treatment
AbstractPurpose of ReviewThis review will focus on recent and emerging treatment paradigms in chronic phase CML. The discussion of each novel treatment or drug combination will include a brief overview of scientific rational and pre-clinical data, followed by recently published or ongoing clinical trial efforts. The review will be divided into three focus areas in CML treatment: new frontline approaches and approaches to deepen remission, second treatment-free remission studies, and the treatment of refractory disease.Recent FindingsThe section on new frontline approaches will highlight several strategies of combination th...
Source: Current Hematologic Malignancy Reports - October 14, 2021 Category: Hematology Source Type: research

A Multi-disciplinary Approach to Managing Chronic Myelogenous Leukemia Patients on Oral Anticancer Therapy at a Large Academic Medical Center
AbstractPurpose of ReviewSince the discovery of imatinib, an oral breakpoint cluster region —Abelson murine leukemia tyrosine kinase inhibitor, chronic myelogenous leukemia transformed from a hematologic malignancy primarily treated with intravenous chemotherapy to a disease almost solely managed with oral agents. While certainly there are benefits to taking a medication at home, this ch ange in treatment modality also came with unique challenges, including patient adherence, medication acquisition and cost, and toxicity management.Recent FindingsPharmacists are uniquely equipped to assist with educating patients, sa...
Source: Current Hematologic Malignancy Reports - October 7, 2021 Category: Hematology Source Type: research

Treatment-Free Remission: the New Goal in CML Therapy
AbstractPurpose of ReviewTreatment-free remission (TFR) is considered one of the main goals of therapy in patients with CML. Our goal in this paper is to review the current data on TFR, and discuss future directions.Recent FindingsMultiple studies have demonstrated that attempting a treatment-free remission is safe and effective in a select group of patients. More recent data suggested that undetectable BCR-ABL1 by digital PCR prior to discontinuation is highly predictive of successful TFR. However, some patients have a successful TFR with no evidence of clinical disease despite persistent detectable BCR-ABL1. Some recent ...
Source: Current Hematologic Malignancy Reports - October 7, 2021 Category: Hematology Source Type: research

Application of Next-Generation Sequencing-Based Mutational Profiling in Acute Lymphoblastic Leukemia
This article identifies avenues within the landscape of adult acute lymphoblastic leukemia (ALL) where mutational data hold the opportunity to enhance understanding of disease biology and patient care.Recent FindingsNGS-based assessment of measurable residual disease (MRD) after ALL treatment allows for a sensitive and specific molecular survey that is at least comparable, if not superior, to existing techniques. Mutational assessment by NGS has unraveled complex signaling networks that drive pathogenesis of T-cell ALL. Sequencing of patients with familial clustering of ALL has also identified novel germline mutations whos...
Source: Current Hematologic Malignancy Reports - October 6, 2021 Category: Hematology Source Type: research

BTK Inhibitors in Chronic Lymphocytic Leukemia
AbstractPurpose of ReviewThe treatment landscape of chronic lymphocytic leukemia (CLL) has dramatically changed over the last few years with the introduction of novel targeted agents. Physicians are now faced with several equally effective therapy options when treating patients with CLL. Here, we review the role of Bruton tyrosine kinase (BTK) inhibitors in treating patients with treatment-na ïve and relapsed or refractory CLL. We review recent approvals of BTK inhibitors as well as reported and ongoing clinical trial data.Recent FindingsThe approval of ibrutinib rapidly led to a paradigm shift in the management of CL...
Source: Current Hematologic Malignancy Reports - October 2, 2021 Category: Hematology Source Type: research

Philadelphia-Negative Myeloproliferative Neoplasms Around the COVID-19 Pandemic
AbstractPurpose of ReviewCoronavirus disease 2019 (COVID-19) is associated with a high rate of respiratory failure, thromboembolism, bleeding, and death. Patients with myeloproliferative neoplasms (MPNs) are prone to both thrombosis and bleeding, calling for special care during COVID-19. We reviewed the clinical features of MPN patients with COVID-19, suggesting guidance for treatment.Recent FindingsOne study by the European LeukemiaNet collected 175 MPN patients with COVID-19 during the first wave of the pandemic, from February to May 2020. Patients with primary myelofibrosis (PMF) were at higher risk of mortality (48%) i...
Source: Current Hematologic Malignancy Reports - September 29, 2021 Category: Hematology Source Type: research

Elevating Twitter-Based Journal Club Discussions by Leveraging a Voice-Based Platform: #HemepathJC Meets Clubhouse
AbstractPurpose of ReviewSocial media-based scientific journal clubs provide an opportunity to promote published literature to a broader audience and allow robust multi-disciplinary and inter-professional discussion. Hematopathology Journal Club (#HemepathJC) on Twitter has successfully conducted monthly sessions since November 2019, covering topics related to lymphoma and leukemia.Recent FindingsTo enhance connectivity, multitasking, and productivity, we present our experience of leveraging the voice-based platform Clubhouse concurrent with Twitter.SummaryThe Twitter and Clubhouse partnership for #hemepathJC holds the pot...
Source: Current Hematologic Malignancy Reports - September 29, 2021 Category: Hematology Source Type: research

Philadelphia-Negative Myeloproliferative Neoplasms Around the COVID-19 Pandemic
AbstractPurpose of ReviewCoronavirus disease 2019 (COVID-19) is associated with a high rate of respiratory failure, thromboembolism, bleeding, and death. Patients with myeloproliferative neoplasms (MPNs) are prone to both thrombosis and bleeding, calling for special care during COVID-19. We reviewed the clinical features of MPN patients with COVID-19, suggesting guidance for treatment.Recent FindingsOne study by the European LeukemiaNet collected 175 MPN patients with COVID-19 during the first wave of the pandemic, from February to May 2020. Patients with primary myelofibrosis (PMF) were at higher risk of mortality (48%) i...
Source: Current Hematologic Malignancy Reports - September 29, 2021 Category: Hematology Source Type: research

Elevating Twitter-Based Journal Club Discussions by Leveraging a Voice-Based Platform: #HemepathJC Meets Clubhouse
AbstractPurpose of ReviewSocial media-based scientific journal clubs provide an opportunity to promote published literature to a broader audience and allow robust multi-disciplinary and inter-professional discussion. Hematopathology Journal Club (#HemepathJC) on Twitter has successfully conducted monthly sessions since November 2019, covering topics related to lymphoma and leukemia.Recent FindingsTo enhance connectivity, multitasking, and productivity, we present our experience of leveraging the voice-based platform Clubhouse concurrent with Twitter.SummaryThe Twitter and Clubhouse partnership for #hemepathJC holds the pot...
Source: Current Hematologic Malignancy Reports - September 29, 2021 Category: Hematology Source Type: research

Avapritinib in the Treatment of Systemic Mastocytosis: an Update
AbstractPurpose of ReviewPatients with systemic mastocytosis, a dangerous and rare myeloid neoplasm, have long had few therapies available to them and, historically, rarely achieved from significant disease control. However, research and translational developments over the last decade have led to promising new options for disease management. In this review, we briefly outline the history of treatment for systemic mastocytosis and subsequently focus on the clinical development and potential applications of avapritinib (previously known as BLU-285), a potent and selective oral inhibitor of the tyrosine kinase most commonly m...
Source: Current Hematologic Malignancy Reports - September 27, 2021 Category: Hematology Source Type: research

Management of Myelofibrosis-Associated Anemia: Focus on Standard Agents and Novel Therapeutics in Phase 3 Clinical Trials
AbstractPurpose of ReviewThe management of myelofibrosis is risk-adapted when considering transplant eligibility and symptom-directed, prioritizing the most burdensome symptoms for the patient. Unfortunately, myelofibrosis-anemia is common, multifactorial in its origin, and impactful regarding prognosis. While clinical trials are advised, not all patients have convenient access, and therefore, hematologists should be aware of the data supporting the use of conventional agents such as erythropoietin-stimulating agents, steroid treatments (danazol and prednisone), and immunomodulatory drugs (thalidomide and lenalidomide). Th...
Source: Current Hematologic Malignancy Reports - September 9, 2021 Category: Hematology Source Type: research

Management and Outcomes of Blast Transformed Chronic Myelomonocytic Leukemia
AbstractPurpose of ReviewDespite recent advances in the treatment of de novo acute myeloid leukemia (AML), AML arising from antecedent chronic myelomonocytic leukemia (CMML) continues to have dismal outcomes. While the unique biological drivers of CMML and subsequent leukemic transformation (LT) have been revealed with advances in molecular characterization, this has not yet translated to the bedside. Here, we review these biologic drivers, outcomes with current therapies, and rationale avenues of future investigation specifically in blast phase CMML (CMML-BP).Recent FindingsCMML-BP outcomes are studied as an aggregate wit...
Source: Current Hematologic Malignancy Reports - September 9, 2021 Category: Hematology Source Type: research

Management of Myelofibrosis-Associated Anemia: Focus on Standard Agents and Novel Therapeutics in Phase 3 Clinical Trials
AbstractPurpose of ReviewThe management of myelofibrosis is risk-adapted when considering transplant eligibility and symptom-directed, prioritizing the most burdensome symptoms for the patient. Unfortunately, myelofibrosis-anemia is common, multifactorial in its origin, and impactful regarding prognosis. While clinical trials are advised, not all patients have convenient access, and therefore, hematologists should be aware of the data supporting the use of conventional agents such as erythropoietin-stimulating agents, steroid treatments (danazol and prednisone), and immunomodulatory drugs (thalidomide and lenalidomide). Th...
Source: Current Hematologic Malignancy Reports - September 9, 2021 Category: Hematology Source Type: research

Management and Outcomes of Blast Transformed Chronic Myelomonocytic Leukemia
AbstractPurpose of ReviewDespite recent advances in the treatment of de novo acute myeloid leukemia (AML), AML arising from antecedent chronic myelomonocytic leukemia (CMML) continues to have dismal outcomes. While the unique biological drivers of CMML and subsequent leukemic transformation (LT) have been revealed with advances in molecular characterization, this has not yet translated to the bedside. Here, we review these biologic drivers, outcomes with current therapies, and rationale avenues of future investigation specifically in blast phase CMML (CMML-BP).Recent FindingsCMML-BP outcomes are studied as an aggregate wit...
Source: Current Hematologic Malignancy Reports - September 9, 2021 Category: Hematology Source Type: research

Management Issues and Controversies in Low-Risk Patients with Essential Thrombocythemia and Polycythemia Vera
AbstractPurpose of ReviewEssential thrombocythemia (ET) and polycythemia vera (PV) are the most common myeloproliferative neoplasms (MPNs). Treatment of ET and PV is based on the risk for subsequent thrombosis. High-risk patients, defined as older than 60,JAK2 V617F–positive patients, or patients with a history of prior thrombosis, merit cytoreduction to control blood counts, whereas a watchful waiting paradigm is utilized in low-risk patients. However, low-risk patients have a host of other specific management issues that arise during their disease course. This review will discuss the most common management issues s...
Source: Current Hematologic Malignancy Reports - September 3, 2021 Category: Hematology Source Type: research

Targeting BCMA in Multiple Myeloma
AbstractPurpose of ReviewDespite considerable advances in the treatment of multiple myeloma (MM) in the last decade, a significant number of patients still progress on current available therapies. Here, we review treatment modalities used to target BCMA in the treatment of MM, specifically antibody-drug conjugates (ADC), bispecific antibody constructs, and chimeric antibody receptor (CAR) modified T-cell therapies. We will provide an overview of therapies from these classes that have presented or published clinical data, as well as data on mechanisms of resistance to these novel agents.Recent FindingsClinical trials explor...
Source: Current Hematologic Malignancy Reports - August 25, 2021 Category: Hematology Source Type: research

Acute Lymphoblastic Leukemia and Acute Lymphoblastic Lymphoma: Same Disease Spectrum but Two Distinct Diagnoses
AbstractPurpose of ReviewRare malignancies developing from lymphocyte precursor cells, lymphoblastic leukemia (LBL), and acute lymphoblastic lymphoma (ALL) have historically been viewed as different manifestations of the same disease process. This review examines data on their epidemiology, genetics, clinical presentation, and response to treatment while highlighting areas of similarity and divergence between these two clinical entities.Recent FindingsPediatric-type ALL chemotherapy regimens, compared to both lymphoma-type chemotherapy and adult-type ALL regimens, have led to improved outcomes for children, adolescents, an...
Source: Current Hematologic Malignancy Reports - August 21, 2021 Category: Hematology Source Type: research

Amyloidosis with Cardiac Involvement: Identification, Characterization, and Management
AbstractPurpose of ReviewAmyloidosis is a protein deposition disease whereby a variety of precursor proteins form insoluble fibrils that deposit in tissues, causing organ dysfunction and, many times, death. Accurate characterization of the disease based on the nature of the precursor protein, organ involvement, and extent of disease is paramount to guide management. Cardiac amyloidosis is critical to understand because of its impact on prognosis and new treatment options available.Recent FindingsNew imaging methods have proven to be considerably valuable in the identification of cardiac amyloid infiltration. For treating c...
Source: Current Hematologic Malignancy Reports - August 1, 2021 Category: Hematology Source Type: research

Balancing Quality, Cost, and Access During Delivery of Newer Cellular and Immunotherapy Treatments
We describe various novel approaches to manage challenges in improving access and improving widescale implementation of cellular therapies. (Source: Current Hematologic Malignancy Reports)
Source: Current Hematologic Malignancy Reports - August 1, 2021 Category: Hematology Source Type: research

Frontline Treatment for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Targeted Therapy vs. Chemoimmunotherapy
AbstractPurpose of ReviewThe treatment options for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have expanded significantly in the last few years, including the use of new classes of oral small molecular inhibitors targeting the B cell receptor signaling pathway or the apoptosis machinery. Targeted therapy with or without immunotherapy has quickly emerged as a new standard for frontline treatment of CLL/SLL, though the previous standard chemoimmunotherapy (CIT) remains a treatment option. In this review, we present data from key clinical trials to evaluate the benefits and risks associated with differe...
Source: Current Hematologic Malignancy Reports - August 1, 2021 Category: Hematology Source Type: research

The Emerging Role of Hematopathologists and Molecular Pathologists in Detection, Monitoring, and Management of Myeloid Neoplasms with Germline Predisposition
AbstractPurpose of ReviewAwareness, widespread availability, and routine use of sequencing techniques in work-up of myelodysplastic syndromes and acute myeloid leukemia have facilitated increased recognition of these entities arising in a background of germline predisposition disorders (GPD).Recent FindingsThe latest revisions to the WHO classification of myeloid neoplasms incorporate “myeloid neoplasms with germline predisposition” as a separate entity due to the therapeutic implications of this diagnosis. It has become apparent that some of these entities have unique recognizable morphologic findings that can...
Source: Current Hematologic Malignancy Reports - August 1, 2021 Category: Hematology Source Type: research

Amyloidosis with Cardiac Involvement: Identification, Characterization, and Management
AbstractPurpose of ReviewAmyloidosis is a protein deposition disease whereby a variety of precursor proteins form insoluble fibrils that deposit in tissues, causing organ dysfunction and, many times, death. Accurate characterization of the disease based on the nature of the precursor protein, organ involvement, and extent of disease is paramount to guide management. Cardiac amyloidosis is critical to understand because of its impact on prognosis and new treatment options available.Recent FindingsNew imaging methods have proven to be considerably valuable in the identification of cardiac amyloid infiltration. For treating c...
Source: Current Hematologic Malignancy Reports - June 9, 2021 Category: Hematology Source Type: research

Balancing Quality, Cost, and Access During Delivery of Newer Cellular and Immunotherapy Treatments
We describe various novel approaches to manage challenges in improving access and improving widescale implementation of cellular therapies. (Source: Current Hematologic Malignancy Reports)
Source: Current Hematologic Malignancy Reports - June 5, 2021 Category: Hematology Source Type: research

Pegaspargase in Practice: Minimizing Toxicity, Maximizing Benefit
AbstractPurpose of ReviewThe incorporation of pegaspargase in chemotherapy regimens has significantly improved the prognosis of ALL in adults. However, pegaspargase use poses many challenges due to its unique toxicity profile. Here, we review pegaspargase ’s most clinically significant toxicities, and provide guidance for their prevention and management in order to avoid unnecessary drug discontinuation and achieve maximum clinical benefit.Recent FindingsClinically significant toxicities of pegaspargase include thrombosis, hypersensitivity and inactivation, hepatotoxicity, pancreatitis, and hypertriglyceridemia. The ...
Source: Current Hematologic Malignancy Reports - June 1, 2021 Category: Hematology Source Type: research

Novel Pathophysiological Mechanisms of Thrombosis in Myeloproliferative Neoplasms
AbstractPurpose of ReviewThrombosis remains a leading cause of morbidity and mortality in BCR/ABL negative myeloproliferative neoplasms (MPN). Circulating blood cells are both increased in quantity and qualitatively abnormal in MPN, resulting in an increased thrombotic risk. Herein, we review recently elucidated mechanisms of MPN thrombosis and discuss implications of drugs currently under investigation for MPN.Recent FindingsRecent studies highlight that inJAK2V617F granulocytes and platelets, thrombo-inflammatory genes are upregulated. Furthermore, inJAK2V617F granulocytes, protein expression of integrin CD11b, tissue fa...
Source: Current Hematologic Malignancy Reports - June 1, 2021 Category: Hematology Source Type: research

Pediatric Neoplasms Presenting with Monocytosis
AbstractPurpose of ReviewJuvenile myelomonocytic leukemia (JMML) is a rare but severe pediatric neoplasm with hematopoietic stem cell transplant as its only established curative option. The development of targeted therapeutics for JMML is being guided by an understanding of the pathobiology of this condition. Here, we review JMML with an emphasis on genetics in order to (i) demonstrate the relationship between JMML genotype and clinical phenotype and (ii) explore potential genetic targets of novel JMML therapies.Recent FindingsDNA hypermethylation studies have demonstrated consistently that methylation is related to diseas...
Source: Current Hematologic Malignancy Reports - June 1, 2021 Category: Hematology Source Type: research

Clinical and Molecular Approach to Adult-Onset, Neoplastic Monocytosis
AbstractPurpose of ReviewIn this review, we provide a comprehensive and contemporary understanding of malignant monocytosis and provide a framework by which the appropriate diagnosis with malignant monocytosis can be rendered.Recent FindingsIncreasing data support the use of molecular data to refine the diagnostic approach to persistent monocytosis. The absence of aTET2,SRSF2, orASXL1 mutation has ≥ 90% negative predictive value for a diagnosis of CMML. These data may also reliably differentiate chronic myelomonocytic leukemia, the malignancy that is most associated with mature monocytosis, from several other diseases t...
Source: Current Hematologic Malignancy Reports - June 1, 2021 Category: Hematology Source Type: research

Genomic Landscape and Risk Stratification in Chronic Myelomonocytic Leukemia
AbstractPurposeThe advent of next-generation sequencing has allowed for the annotation of a vast array of recurrent somatic mutations across human malignancies, ushering in a new era of precision oncology. Chronic myelomonocytic leukemia is recognized as a myelodysplastic/myeloproliferative neoplasm and displays heterogenous clinical and genetic features. Herein, we review what is currently understood regarding the genomic landscape of this disease and discuss how somatic mutations have impacted current risk stratification methods.Recent FindingsGenomic studies in chronic myelomonocytic leukemia have identified a character...
Source: Current Hematologic Malignancy Reports - June 1, 2021 Category: Hematology Source Type: research

Laboratory Evaluation and Pathological Workup of Neoplastic Monocytosis — Chronic Myelomonocytic Leukemia and Beyond
AbstractPurpose of ReviewMonocytosis is a distinct but non-specific manifestation of various physiologic and pathologic conditions. Among hematopoietic stem cell neoplasms, depending on the criteria used for disease classification, monocytosis may be a consistent and integral component of diseases such as chronic myelomonocytic leukemia or acute myeloid leukemia with monocytic differentiation, or it may represent an inconsistent finding that often provides a clue to the underlying genetic changes driving the neoplasm. The purpose of this review is to provide the readers with a laboratory-based approach to neoplastic monocy...
Source: Current Hematologic Malignancy Reports - June 1, 2021 Category: Hematology Source Type: research

Differential Diagnosis and Workup of Monocytosis: A Systematic Approach to a Common Hematologic Finding
AbstractPurpose of ReviewMonocytosis is a frequently encountered clinical condition that needs appropriate investigation due to a broad range of differential diagnoses. This review is meant to summarize the latest literature in the diagnostic testing and interpretation and offer a stepwise diagnostic approach for a patient presenting with monocytosis.Recent FindingsBasic studies have highlighted the phenotypic and functional heterogeneity in the monocyte compartment. Studies, both translational and clinical, have provided insights into why monocytosis occurs and how to distinguish the different etiologies. Flow cytometry s...
Source: Current Hematologic Malignancy Reports - June 1, 2021 Category: Hematology Source Type: research

Treatment advances for pediatric and adult onset neoplasms with monocytosis
AbstractPurpose of reviewFor decades, the management of chronic myelomonocytic leukemia (CMML) or juvenile myelomonocytic leukemia (JMML) has been largely inextricable from myelodysplastic syndromes (MDS), myeloproliferative neoplasms, and acute myeloid leukemia. Hallmarks of these diseases have been the emergence of unique genomic signatures and discouraging responses to available therapies. Here, we will critically examine the current options for management and review the rapidly developing opportunities based on advances in CMML and JMML disease biology.Recent findingsFew clinical trials have exclusively been done in CM...
Source: Current Hematologic Malignancy Reports - June 1, 2021 Category: Hematology Source Type: research

The Emerging Role of Hematopathologists and Molecular Pathologists in Detection, Monitoring, and Management of Myeloid Neoplasms with Germline Predisposition
AbstractPurpose of ReviewAwareness, widespread availability, and routine use of sequencing techniques in work-up of myelodysplastic syndromes and acute myeloid leukemia have facilitated increased recognition of these entities arising in a background of germline predisposition disorders (GPD).Recent FindingsThe latest revisions to the WHO classification of myeloid neoplasms incorporate “myeloid neoplasms with germline predisposition” as a separate entity due to the therapeutic implications of this diagnosis. It has become apparent that some of these entities have unique recognizable morphologic findings that can...
Source: Current Hematologic Malignancy Reports - May 24, 2021 Category: Hematology Source Type: research

Frontline Treatment for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Targeted Therapy vs. Chemoimmunotherapy
AbstractPurpose of ReviewThe treatment options for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have expanded significantly in the last few years, including the use of new classes of oral small molecular inhibitors targeting the B cell receptor signaling pathway or the apoptosis machinery. Targeted therapy with or without immunotherapy has quickly emerged as a new standard for frontline treatment of CLL/SLL, though the previous standard chemoimmunotherapy (CIT) remains a treatment option. In this review, we present data from key clinical trials to evaluate the benefits and risks associated with differe...
Source: Current Hematologic Malignancy Reports - May 22, 2021 Category: Hematology Source Type: research

Enteropathy-Associated T cell Lymphoma
This article provides a summary and review of the available literature addressing this entity in terms of risk factors, pathogenesis, diagnostic, and therapeutic options.Recent FindingsEATL has two distinct subtypes. Type I EATL, now known as EATL, is closely, but not exclusively linked to celiac disease (CD), and it is primarily a disease of Northern European origin. It accounts for
Source: Current Hematologic Malignancy Reports - May 19, 2021 Category: Hematology Source Type: research

Progress in the Management of Smoldering Multiple Myeloma
AbstractPurpose of ReviewSmoldering multiple myeloma (SMM) is defined as an asymptomatic clonal proliferation of pre-malignant plasma cells and an increased risk of progression to multiple myeloma (MM) relative to monoclonal gammopathy of undetermined significance. Whether patients with SMM should be treated prior to development of symptomatic disease is fiercely debated and is a highly active area of research.Recent FindingsThe ECOG E3A06 study demonstrated that early treatment with lenalidomide significantly reduced the risk of progression to MM compared to observation in patients with high risk SMM. The IMWG recently va...
Source: Current Hematologic Malignancy Reports - May 13, 2021 Category: Hematology Source Type: research

Pegaspargase in Practice: Minimizing Toxicity, Maximizing Benefit
AbstractPurpose of ReviewThe incorporation of pegaspargase in chemotherapy regimens has significantly improved the prognosis of ALL in adults. However, pegaspargase use poses many challenges due to its unique toxicity profile. Here, we review pegaspargase ’s most clinically significant toxicities, and provide guidance for their prevention and management in order to avoid unnecessary drug discontinuation and achieve maximum clinical benefit.Recent FindingsClinically significant toxicities of pegaspargase include thrombosis, hypersensitivity and inactivation, hepatotoxicity, pancreatitis, and hypertriglyceridemia. The ...
Source: Current Hematologic Malignancy Reports - May 12, 2021 Category: Hematology Source Type: research

MRD Assessment in Multiple Myeloma: Progress and Challenges
AbstractPurpose of ReviewOver the last decade, the development of effective treatment approaches for multiple myeloma (MM) has been associated with higher response rates and longer survival. In patients who achieve complete response, several high sensitivity techniques have been studied to assess minimal residual disease (MRD) and detect residual neoplastic cells within the bone marrow (by flow cytometry or molecular biology techniques) or outside the bone marrow (by imaging or circulating disease markers in the peripheral blood). This is of utmost importance, since residual disease can drive clinical relapse. This review ...
Source: Current Hematologic Malignancy Reports - May 5, 2021 Category: Hematology Source Type: research

Laboratory Evaluation and Pathological Workup of Neoplastic Monocytosis — Chronic Myelomonocytic Leukemia and Beyond
AbstractPurpose of ReviewMonocytosis is a distinct but non-specific manifestation of various physiologic and pathologic conditions. Among hematopoietic stem cell neoplasms, depending on the criteria used for disease classification, monocytosis may be a consistent and integral component of diseases such as chronic myelomonocytic leukemia or acute myeloid leukemia with monocytic differentiation, or it may represent an inconsistent finding that often provides a clue to the underlying genetic changes driving the neoplasm. The purpose of this review is to provide the readers with a laboratory-based approach to neoplastic monocy...
Source: Current Hematologic Malignancy Reports - May 4, 2021 Category: Hematology Source Type: research

IDH Inhibitors in AML —Promise and Pitfalls
AbstractPurpose of ReviewMutations in isocitrate dehydrogenase genes (IDH1 and IDH2) are common in acute myeloid leukemia (AML), occurring in up to 30% of AML cases. Mutations in IDH leads to abnormal epigenetic regulation in AML cells and blocks differentiation. Inhibitors of mutated IDH1 and IDH2, ivosidenib and enasidenib, respectively, were recently approved by the FDA for relapsed/refractory AML; ivosidenib is also approved for newly diagnosed AML patients not fit for standard chemotherapy. Here, we discuss the clinical development of IDH inhibitors, their unique side effects, and outline future combination approaches...
Source: Current Hematologic Malignancy Reports - April 30, 2021 Category: Hematology Source Type: research

Chimeric Antigen Receptor –Modified T Cells and T Cell–Engaging Bispecific Antibodies: Different Tools for the Same Job
AbstractPurpose of ReviewBoth chimeric antigen receptor (CAR) T cells and T cell –engaging antibodies (BiAb) have been approved for the treatment of hematological malignancies. However, despite targeting the same antigen, they represent very different classes of therapeutics, each with its distinct advantages and drawbacks. In this review, we compare BiAb and CAR T cells with regard to their mechanism of action, manufacturing, and clinical application. In addition, we present novel strategies to overcome limitations of either approach and to combine the best of both worlds.Recent FindingsBy now there are multiple app...
Source: Current Hematologic Malignancy Reports - April 30, 2021 Category: Hematology Source Type: research

Clinical and Molecular Approach to Adult-Onset, Neoplastic Monocytosis
AbstractPurpose of ReviewIn this review, we provide a comprehensive and contemporary understanding of malignant monocytosis and provide a framework by which the appropriate diagnosis with malignant monocytosis can be rendered.Recent FindingsIncreasing data support the use of molecular data to refine the diagnostic approach to persistent monocytosis. The absence of aTET2,SRSF2, orASXL1 mutation has ≥ 90% negative predictive value for a diagnosis of CMML. These data may also reliably differentiate chronic myelomonocytic leukemia, the malignancy that is most associated with mature monocytosis, from several other diseases t...
Source: Current Hematologic Malignancy Reports - April 22, 2021 Category: Hematology Source Type: research

Differential Diagnosis and Workup of Monocytosis: A Systematic Approach to a Common Hematologic Finding
AbstractPurpose of ReviewMonocytosis is a frequently encountered clinical condition that needs appropriate investigation due to a broad range of differential diagnoses. This review is meant to summarize the latest literature in the diagnostic testing and interpretation and offer a stepwise diagnostic approach for a patient presenting with monocytosis.Recent FindingsBasic studies have highlighted the phenotypic and functional heterogeneity in the monocyte compartment. Studies, both translational and clinical, have provided insights into why monocytosis occurs and how to distinguish the different etiologies. Flow cytometry s...
Source: Current Hematologic Malignancy Reports - April 20, 2021 Category: Hematology Source Type: research