Preparing Trainees to Deliver High-Value and Cost-Conscious Care in Hematology
AbstractPurpose of ReviewDespite national-level directives to reduce healthcare waste and promote high-value care (HVC), clinical educators struggle to equip trainees with the knowledge and skills needed to practice value-based care. In this review, we analyze ongoing efforts in graduate medical education (GME) to enhance trainee competence in delivery of high-value and cost-conscious care.Recent FindingsSurveys of residents and program directors have shown that while many training programs want to offer formal training in high-value care delivery, few succeed. Although several studies suggest that trainees model stewardsh...
Source: Current Hematologic Malignancy Reports - July 6, 2020 Category: Hematology Source Type: research

Advances in Supportive Care for Acute Lymphoblastic Leukemia
This article will review the novel therapies in acute leukemias and highlight the clinically relevant supportive care advances.Recent FindingsThe American Society for Transplantation and Cellular Therapy (ASTCT) has put forth the most recent recommendations in managing the cytokine release syndrome and neurotoxicity after chimeric antigen receptor T cells (CAR-T) and blinatumomab. The hepatic injury incurred by inotuzumab, and the vascular toxicity of tyrosine kinase inhibitors, other relatively novel agents, require subspecialist intervention and multidisciplinary care. Asparaginase, a long-established and key element of ...
Source: Current Hematologic Malignancy Reports - June 30, 2020 Category: Hematology Source Type: research

Frontline Therapy of Chronic Lymphocytic Leukemia: Changing Treatment Paradigm
AbstractPurpose of ReviewThe treatment landscape of treatment-naive chronic lymphocytic leukemia (TN-CLL) is rapidly evolving. As more and more new drugs and combinations are becoming part of therapeutic armamentarium, it becomes highly pertinent to understand the evidence for each of the treatment options to select the right drug for the right patient. We summarize the recent data of the available frontline treatment options.Recent FindingsThe novel agents can overcome adverse biological attributes and provide long-term disease control. MRD may become a reliable surrogate for survival in the evaluation of future therapies...
Source: Current Hematologic Malignancy Reports - June 15, 2020 Category: Hematology Source Type: research

Immunodeficiency-Related Lymphoid Proliferations: New Insights With Relevance to Practice
AbstractPurpose of ReviewOur understanding of risk factors and mechanisms underlying immunosuppression-related lymphoproliferative disorders continues to evolve. An increasing number of patients are living with altered immune status due to HIV, solid organ or hematopoietic stem cell transplant, treatment of autoimmune disease, or advanced age. This review covers advances in understanding, emerging trends, and revisions to diagnostic guidelines.Recent FindingsThe tumor microenvironment, including interactions between the host immune system and tumor cells, is of increasing interest in the setting of immunosuppression. While...
Source: Current Hematologic Malignancy Reports - June 13, 2020 Category: Hematology Source Type: research

Choosing Wisely ® in Hematology: Have We Made a Difference?
AbstractPurpose of ReviewThe Choosing Wisely® initiative, led by the American Board of Internal Medicine Foundation in collaboration with national professional medical societies, aims to help patients choose care that is essential, free from harm, and evidence-based. The American Society of Hematology has advocated practices specific to hematology for physicians and patients to examine carefully. Here, we summarize various barriers to adopting these practices, interventions used to improve adoption, and challenges in measuring the effectiveness of these interventions.Recent FindingsThe Choosing Wisely ® campaign ha...
Source: Current Hematologic Malignancy Reports - June 12, 2020 Category: Hematology Source Type: research

Hematopoietic Cell Transplantation and Adoptive Cell Therapy in Peripheral T Cell Lymphoma
AbstractPurpose of ReviewPeripheral T cell lymphomas (PTCLs) are a heterogeneous group of diseases and represent approximately 10 –15% of all non-Hodgkin lymphomas. Multiagent chemotherapy with a CHOP (cyclophosphamide, adriamycin, vincristine, prednisone)-like regimen is the current standard of care in the frontline setting, but outcomes for PTCL patients generally remain poor. Strategies used to improve survival and reduce the risk of relapse in PTCL patients include autologous hematopoietic cell transplant (autoHCT) and allogeneic HCT (alloHCT). Due to the relative rarity of these diseases, the evidence supporting...
Source: Current Hematologic Malignancy Reports - June 11, 2020 Category: Hematology Source Type: research

The Evolution of Targeted Therapies in Chronic Lymphocytic Leukaemia
AbstractPurpose of ReviewThe treatment landscape for chronic lymphocytic leukaemia (CLL) is rapidly evolving, with several targeted agents recently approved. These compounds have dramatically changed the natural history of the disease.Recent FindingsHowever, with the array of effective therapies commercially available, the challenge is to define tailored treatment strategies able to realize a balance between treatment efficacy and toxicity or tolerance. New algorithms of treatment are being developed, and it appears that minimal residual disease (MRD) directed therapy will become the norm in the future.SummaryClinical tria...
Source: Current Hematologic Malignancy Reports - June 4, 2020 Category: Hematology Source Type: research

NPM1 Biology in Myeloid Neoplasia
AbstractPurpose of ReviewNucleophosmin (NPM1) mutations are encountered in myeloid neoplasia and are present in ~  30% of de novo acute myeloid leukemia cases. This review summarizes features of mutantNPM1-related disease, with a particular emphasis on recent discoveries relevant to disease monitoring, prognostication, and therapeutic intervention.Recent FindingsRecent studies have shown thatHOX/MEIS gene overexpression is central to the survival ofNPM1-mutated cells. Two distinct classes of small molecule drugs, BH3 mimetics and menin-MLL interaction inhibitors, have demonstrated exquisite leukemic cell toxicity in...
Source: Current Hematologic Malignancy Reports - June 3, 2020 Category: Hematology Source Type: research

Novel Therapies in the Treatment of Adult Acute Lymphoblastic Leukemia
AbstractPurpose of ReviewAcute lymphoblastic leukemia (ALL) is a rare hematologic malignancy. Advances in multi-agent chemotherapy have resulted in dramatic improvements in the number of pediatric cases that result in a cure; however, until recently, treatment options for older adults or patients with relapsed and refractory disease were extremely limited. This review seeks to describe in greater detail a number of emerging novel treatment modalities recently approved for this cancer.Recent FindingsIn this review, we discuss a number of recently approved novel therapies for ALL, including new approaches with targeted tyros...
Source: Current Hematologic Malignancy Reports - May 22, 2020 Category: Hematology Source Type: research

Primary Cutaneous CD30+ Lymphoproliferative Disorders: a Comprehensive Review
AbstractPurpose of ReviewPrimary cutaneous CD30+ T-cell lymphoproliferative disorders (CD30+ LPDs) are the second most common cutaneous lymphomas after mycosis fungoides and Sezary syndrome. They include primary cutaneous anaplastic large cell lymphoma (pcALCL), lymphomatoid papulosis (LyP), and borderline lesions. The purpose of this literature review is to consolidate the available evidence on the primary cutaneous CD30+ LPD in order to define the tools for correct diagnosis and appropriate treatment.Recent FindingsThe current body of knowledge regarding the clinical features, histopathologic changes, recently described ...
Source: Current Hematologic Malignancy Reports - May 20, 2020 Category: Hematology Source Type: research

Radiogenomics and Its Role in Lymphoma
AbstractPurpose of ReviewImaging features of lymphoma vary regionally. Awareness of site-specific key imaging characteristics of lymphoma can aid in rapid staging and assist in prompt treatment. FDG PET/CT and conventional MRI are readily available diagnostic modalities with excellent sensitivity and good specificity. Diagnostic specificity can be enhanced using emerging PET radiotracers, e.g., FLT and FET.Recent FindingsEmerging research has shown higher dimensional analysis (radiomics and radiogenomics) of imaging data can yield information of the underlying genetic aberrations in lymphoma, which can aid in assessing rea...
Source: Current Hematologic Malignancy Reports - May 20, 2020 Category: Hematology Source Type: research

Management of Ibrutinib Toxicities: a Practical Guide
AbstractPurpose of ReviewIbrutinib is a first-in-class, highly potent Bruton tyrosine kinase inhibitor which has become standard of care for patients with chronic lymphocytic leukaemia and other lymphoproliferative disorders. It requires indefinite administration which places emphasis on toxicity and long-term tolerance.Recent FindingsExtensive use of ibrutinib in studies and clinical practice has better defined its full toxicity profile which has made its use more challenging than initially foreseen. In particular, dysrhythmias, bleeding, infections and constitutional symptoms have been reported and can result in dose red...
Source: Current Hematologic Malignancy Reports - May 15, 2020 Category: Hematology Source Type: research

Editing of Endogenous Genes in Cellular Immunotherapies
AbstractPurpose of ReviewT cell-based cellular and antibody immunotherapies have dramatically altered the landscape of cancer treatment over the past decade. Over the same time span, gene editing technologies have enabled unprecedented degrees of genetic control.Recent FindingsKnock-outs of endogenous genes, especially based on electroporation of targetable nucleases such as CRISPR/Cas9, have rapidly proliferated. Simultaneous introduction of large DNA sequences can integrate new synthetic genetic instructions with specific endogenous loci to alter T cell function and specificity. Recently developed discovery technologies ...
Source: Current Hematologic Malignancy Reports - May 15, 2020 Category: Hematology Source Type: research

Thrombocytosis and Thrombosis: Is There Really a Correlation?
AbstractPurpose of ReviewThrombocytosis is common to all myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis. Despite the traditionally held belief amongst many clinicians that thrombocytosis correlates with thrombosis risk, there is little evidence in the literature to support that claim. Herein we critically analyze the literature to better understand the relationship between thrombocytosis and risk of thrombosis in MPN.Recent FindingsBoth retrospective and prospective studies argue against associations between thrombocytosis and risk of thrombosis in pa...
Source: Current Hematologic Malignancy Reports - May 12, 2020 Category: Hematology Source Type: research

PD-1/PD-L1 Pathway and Its Blockade in Patients with Classic Hodgkin Lymphoma and Non-Hodgkin Large-Cell Lymphomas
AbstractPurpose of ReviewProgrammed cell death protein-1 (PD-1) is currently the most extensively studied inhibitory checkpoint molecule. Many malignant neoplasms express the PD-1 ligands, PD-L1, and/or PD-L2, which bind to PD-1 on T cells and induce T cell “exhaustion.” By doing so, the malignant cells escape from an antitumor immune response (immune evasion). Blockade of the PD-1/PD-L1 pathway releases T cells from the inhibitory effects exerted by tumor cells and restores a T cell-mediated antitumor immune response. Here, we focus on understandi ng the immune biology of the PD-1/PD-L1 pathway in large-cell l...
Source: Current Hematologic Malignancy Reports - May 11, 2020 Category: Hematology Source Type: research

Updates in the Diagnosis and Management of AL Amyloidosis
AbstractPurpose of ReviewLight chain (AL) amyloidosis is an insidious progressive disease which results in significant morbidity and inevitable mortality if not diagnosed and treated promptly. This review will highlight recent developments and summarize critical clinical points and updated practice changes for the clinician in 2020.Recent FindingsComparative analyses of staging systems, updated prognostic tools, and treatment response criteria now allow for improved patient stratification and treatment decisions; the role of minimal residual disease in response assessment is still being assessed. Clinical and genetic predi...
Source: Current Hematologic Malignancy Reports - May 11, 2020 Category: Hematology Source Type: research

Clinical Applications of Chromosomal Microarray Testing in Myeloid Malignancies
AbstractPurpose of ReviewKnowledge of both somatic mutations and copy number aberrations are important for the understanding of cancer pathogenesis and management of myeloid neoplasms. The currently available standard of care technologies for copy number assessment such as conventional karyotype and FISH are either limited by low resolution or restriction to targeted assessment.Recent FindingsChromosomal microarray (CMA) is effective in characterization of chromosomal and gene aberrations of diagnostic, prognostic, and therapeutic significance at a higher resolution than conventional karyotyping. These results are compleme...
Source: Current Hematologic Malignancy Reports - May 7, 2020 Category: Hematology Source Type: research

Utilizing Real-World Evidence (RWE) to Improve Care in Chronic Lymphocytic Leukemia: Challenges and Opportunities
AbstractPurpose of ReviewThis review discusses important findings from real-world evidence (RWE) studies impacting the field of chronic lymphocytic leukemia (CLL), from prognostication to long-term management and sequencing of novel agents.Recent FindingsRWE data, which represents a heterogeneous cohort of patients treated at non-academic centers and off-clinical trial, demonstrate several key differences between findings in randomized controlled trials (RCT) of novel agents in CLL. While toxicity and discontinuation rates are higher, survival outcomes are encouraging in clinical practice, with often equivalent outcomes fr...
Source: Current Hematologic Malignancy Reports - May 7, 2020 Category: Hematology Source Type: research

Treatment of Aggressive B Cell Lymphomas: Updates in 2019
AbstractPurpose of ReviewRecent years have seen the development of gene expression profiling and next-generation sequencing in diffuse large B cell lymphoma (DLBCL), leading to a more defined characterization of this disease into distinct subentities. The genomic era has ushered in the possibility of using precision guided therapy, in part based on targeting genes with somatic mutations. Such precision-targeted therapies will ultimately reduce the need for chemotherapy, induce fewer adverse events, and likely enhance the cure rate for these patients. Here, we discuss emerging therapeutic strategies that have been recently ...
Source: Current Hematologic Malignancy Reports - May 5, 2020 Category: Hematology Source Type: research

Hematopoietic Cell Transplantation for Philadelphia Chromosome Negative Adult Acute Lymphoblastic Leukemia in the Modern Era of Immune Therapy
AbstractPurpose of ReviewThis review will discuss the data and controversies related to HCT in the front-line and relapsed/refractory setting in the context of newly available targeted immunotherapies.Recent FindingsRecent studies in adult Ph-negative ALL support the use of measurable residual disease (MRD) response to front-line therapy to guide consolidation. As such, most MRD-negative patients do not require front-line HCT. Blinatumomab benefits patients with B-ALL with MRD+ complete response (CR) and can be used as a bridge to HCT; whether HCT is still required in this setting is an area of ongoing inquiry. Blinatumoma...
Source: Current Hematologic Malignancy Reports - May 2, 2020 Category: Hematology Source Type: research

MLL -Rearranged Acute Lymphoblastic Leukemia
AbstractPurpose of ReviewRearrangements of the histonelysine [K]-MethylTransferase 2A gene (KMT2A) gene on chromosome 11q23, formerly known as the mixed-lineage leukemia (MLL) gene, are found in 10% and 5% of adult and children ALL cases, respectively. The most common translocated genes areAFF1 (formerlyAF4),MLLT3 (formerlyAF9), andMLLT1 (formerlyENL). The bimodal incidence ofMLL-r-ALL usually peaks in infants in their first 2  years of life and then declines thereafter during the pediatric/young adult phase until it increases again with age.MLL-rearranged ALL (MLL-r-ALL) is characterized by hyperleukocytosis, aggress...
Source: Current Hematologic Malignancy Reports - April 30, 2020 Category: Hematology Source Type: research

Artificial Intelligence in Hematology: Current Challenges and Opportunities
AbstractPurpose of ReviewArtificial intelligence (AI), and in particular its subcategory machine learning, is finding an increasing number of applications in medicine, driven in large part by an abundance of data and powerful, accessible tools that have made AI accessible to a larger circle of investigators.Recent FindingsAI has been employed in the analysis of hematopathological, radiographic, laboratory, genomic, pharmacological, and chemical data to better inform diagnosis, prognosis, treatment planning, and foundational knowledge related to benign and malignant hematology. As more widespread implementation of clinical ...
Source: Current Hematologic Malignancy Reports - April 1, 2020 Category: Hematology Source Type: research

Monoclonal Gammopathy of Undetermined Significance: Current Concepts and Future Prospects
AbstractPurpose of the ReviewMonoclonal gammopathy of undetermined significance (MGUS) is a highly prevalent precursor condition in the general population, with an approximate 1% annual risk of progression to multiple myeloma (MM) or a related disorder. Our understanding of MGUS and its association with myriad clinical disorders, its progression to MM, and the genomic alterations in the setting of a conducive or permissive microenvironment has deepened considerably.Recent FindingsData from gene expression profiling studies have underscored the heterogeneity in the risk of progression of MGUS to MM. Ongoing efforts are bein...
Source: Current Hematologic Malignancy Reports - March 28, 2020 Category: Hematology Source Type: research

Decision Analysis of Transplantation for Patients with Myelodysplasia: “Who Should We Transplant Today?”
AbstractPurpose of ReviewMyelodysplastic syndrome (MDS) is a heterogeneous hematological disorder characterized by a spectrum of clinical presentation, cytogenetic, and somatic gene mutations and the risk of transformation to acute leukemia. Management options include observation, supportive care, blood transfusion, administration of growth factors and/or hypomethylating agents, and hematopoietic cell transplant (HCT) either upfront or after disease progression.Recent FindingsCurrently, HCT is the only curative therapy available for patients with MDS, with multiple factors such as donor availability, patient, and disease c...
Source: Current Hematologic Malignancy Reports - March 28, 2020 Category: Hematology Source Type: research

Extramedullary Disease in Multiple Myeloma
AbstractPurpose of ReviewExtramedullary disease (EMD) is a rare but recognized manifestation of multiple myeloma (MM), characterized by involvement of several organs including skin, liver, lymphatic system, pleura, and central nervous system. The incidence is about 3 –5% in newly diagnosed MM patients, but has been reported in up to 20% patients in the relapsed MM setting.Recent FindingsPresence of EMD has been associated with more aggressive phenotype of MM, elevated serum lactate dehydrogenase (LDH) enzyme, and high-risk cytogenetics [deletion 17p, translocation (4;14), translocation (14;16)]. There are several hyp...
Source: Current Hematologic Malignancy Reports - March 20, 2020 Category: Hematology Source Type: research

Supportive Care in Multiple Myeloma
AbstractPurpose of ReviewAs novel therapies are expanding the life expectancy of patients with multiple myeloma, appropriate supportive care has become critical in the management of these patients. This review aims to outline the key principles of supportive care of patients with myeloma, including management of bone disease, renal disease, anemia, peripheral neuropathy, infections, and venous thromboembolism.Recent FindingsThe results from large randomized, controlled trials on the use of high-cutoff hemodialysis in the removal of free light chains in renal disease and the use of levofloxacin in the prevention of infectio...
Source: Current Hematologic Malignancy Reports - March 14, 2020 Category: Hematology Source Type: research

Polatuzumab Vedotin: a New Target for B Cell Malignancies
AbstractPurpose of ReviewAntibody-drug conjugates are a new class of therapeutic agents in the treatment of B cell malignancies. In this review, we summarize the recent developments of polatuzumab vedotin in the treatment of relapsed or refractory diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL).Recent FindingsPolatuzumab vedotin recently received its first FDA approval in combination with bendamustine and rituximab for the treatment of patients with relapsed or refractory DLBCL. Polatuzumab vedotin has been evaluated and is being studied in combinations with chemoimmunotherapy, immunomodulating agents, b...
Source: Current Hematologic Malignancy Reports - March 14, 2020 Category: Hematology Source Type: research

Myeloproliferative Neoplasms in Children, Adolescents, and Young Adults
AbstractPurpose of ReviewMyeloproliferative neoplasms are traditionally seen in older adults, making them poorly understood in younger patients. Clinical presentation, genetic landscape, outcomes, and best management practices are inadequately described in this group. Over the past decade, more research has focused on younger patients, and this paper seeks to review and describe the current status of the field.Recent FindingsA recent review analyzed the available pediatric MPN literature and highlighted the paucity of published data. Pediatric patients showed lower rates of the common mutations found in adults, thrombotic ...
Source: Current Hematologic Malignancy Reports - March 14, 2020 Category: Hematology Source Type: research

Indications for Allogeneic Hematopoietic Cell Transplantation in Myelodysplastic Syndrome
AbstractPurpose of ReviewMyelodysplastic syndromes (MDS) are heterogeneous diseases that principally affect older adults. Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy; however, non-relapse mortality (NRM) accounts for as many as 40% of deaths after HCT and underscores the need for careful patient selection. We review the common indications and causes of failure after HCT in MDS.Recent FindingsAppropriate patient selection is necessary to optimize HCT outcomes and maximize the life-expectancies of MDS patients. The international prognostic scoring systems (IPSS) and revised IP...
Source: Current Hematologic Malignancy Reports - March 3, 2020 Category: Hematology Source Type: research

Is There a Role for Chemotherapy in the Era of Targeted Therapies?
AbstractPurpose of ReviewThe treatment landscape of chronic lymphocytic leukemia has been rapidly evolving over the past few years. The prior standard of care, chemoimmunotherapy, is being replaced by targeted agents, and the utility of chemotherapy has come under question. In this review, we examine recent data comparing chemoimmunotherapy to targeted agents, how these data impact clinical management, and whether there are potential future roles for cytotoxic chemotherapy.Recent FindingsClinical trials have shown improved clinical outcomes with targeted agents compared to traditional chemoimmunotherapy. Based on these dat...
Source: Current Hematologic Malignancy Reports - February 27, 2020 Category: Hematology Source Type: research

Mechanisms of Cardiovascular Toxicity of BCR-ABL1 Tyrosine Kinase Inhibitors in Chronic Myelogenous Leukemia
AbstractPurpose of ReviewOral tyrosine kinase inhibitors have revolutionized the treatment of chronic myelogenous leukemia, with many patients achieving major clinical and molecular responses without complications. While typically well-tolerated, clinical experience with tyrosine kinase inhibitors (particularly those of the second and third generations) has highlighted unanticipated associations with serious non-cancer adverse effects on various organs, particularly the cardiovascular system.Recent FindingsHerein, we review the current literature surrounding the major cardiovascular toxicities of BCR-ABL1 tyrosine kinase i...
Source: Current Hematologic Malignancy Reports - February 20, 2020 Category: Hematology Source Type: research

Advances in the Diagnosis and Treatment of Large Granular Lymphocytic Leukemia
AbstractPurpose of ReviewThe past decade in LGL leukemia research has seen increased pairing of clinical data with molecular markers, shedding new insights on LGL leukemia pathogenesis and heterogeneity. This review summarizes the current standard of care of LGL leukemia, updates from clinical trials, and our congruent improved understanding of LGL pathogenesis.Recent FindingsVarious clinical reports have identified associations between stem, bone marrow, and solid organ transplants and incidence of LGL leukemia. There is also a potential for underdiagnosis of LGL leukemia within the rheumatoid arthritis patient population...
Source: Current Hematologic Malignancy Reports - February 15, 2020 Category: Hematology Source Type: research

Patient-Reported Outcomes in Myelodysplastic Syndromes: the Move from Life Span to Health Span
AbstractPurpose of ReviewThe lack of fully effective therapies to alter the natural course of myelodysplastic syndromes (MDS) leads to chronic morbidity, mortality and affects quality of life (QoL). Since existing therapies outside of hematopoietic cell transplantation (HCT) are not curative, there is a growing interest in incorporating patient-reported outcomes (PROs) as meaningful endpoints for these patients in research and clinical practice.Recent FindingsCurrently, there are limited numbers of studies reporting the impact of MDS therapeutics on PROs to guide clinical decision-making and increase patient satisfaction. ...
Source: Current Hematologic Malignancy Reports - February 11, 2020 Category: Hematology Source Type: research

Novel Therapies in Polycythemia Vera
AbstractPurpose of ReviewPolycythemia vera is a myeloproliferative neoplasm characterized by increased erythrocyte count, thrombotic potential, and transformation to myelofibrosis. Older patients and those who have a history of thrombosis require cytoreductive therapy, most commonly with hydroxyurea. Other currently available therapies include pegylated interferon alfa-2a and the JAK1/2 inhibitor ruxolitinib. However, there are limitations to these agents, including potential detrimental adverse effects. In this review, we will describe current therapeutic options for the treatment of PV and then detail new agents with ava...
Source: Current Hematologic Malignancy Reports - February 7, 2020 Category: Hematology Source Type: research

Advances and Perspectives in the Treatment of T-PLL
AbstractPurpose of ReviewT cell prolymphocytic leukemia (T-PLL) is a rare mature T cell tumor. Available treatment options in this aggressive disease are largely inefficient and patient outcomes are highly dissatisfactory. Current therapeutic strategies mainly employ the CD52-antibody alemtuzumab as the most active single agent. However, sustained remissions after sole alemtuzumab-based induction are exceptions. Responses after available second-line strategies are even less durable. More profound disease control or rare curative outcomes can currently only be expected after a consolidating allogeneic hematopoietic stem cel...
Source: Current Hematologic Malignancy Reports - February 7, 2020 Category: Hematology Source Type: research

Current Approaches to Transplantation for FLT3-ITD AML
AbstractPurpose of ReviewThis review discusses the current standard of care for incorporation of FLT3 TKIs and HCT into the treatment of FLT3-ITD AML. Additionally, this review provides an approach to the patient with relapsed/refractory disease.Recent FindingsOver the last decade, the routine use of HCT as consolidative therapy and the development of FLT3 TKIs have significantly improved remission rates and overall survival. The value and challenges of MRD assessment in FLT3 disease are discussed and current mechanisms of relapse are explored, as are the ongoing questions in the field that current clinical trials are seek...
Source: Current Hematologic Malignancy Reports - February 7, 2020 Category: Hematology Source Type: research

Brentuximab Vedotin in the Treatment of Peripheral T Cell Lymphoma and Cutaneous T Cell Lymphoma
AbstractPurpose of ReviewThe recent development of brentuximab vedotin (BV), an antibody-drug conjugate targeting CD30-positive cells, has led to therapeutic advances in the treatment of T cell lymphomas. In this review, we discuss key studies of BV in peripheral T cell lymphoma (PTCL) and cutaneous T cell lymphoma (CTCL) and highlight important questions for further investigation.Recent FindingsMonotherapy with BV has proven to be effective and well tolerated in patients with relapsed/refractory (R/R) CD30-positive CTCL. BV has shown significant activity in R/R PTCL as well, with particularly durable responses in patients...
Source: Current Hematologic Malignancy Reports - February 3, 2020 Category: Hematology Source Type: research

The Cardiovascular Complications of Chimeric Antigen Receptor T Cell Therapy
AbstractPurpose of ReviewChimeric antigen receptor T cell therapy is gaining clinical use in the management of B cell lymphomas. As the use of this unique treatment option increases, its associated toxicities will require recognition and treatment. In this review, we aim to discuss the cardiovascular toxicities of chimeric antigen receptor T cell therapy and our approach to their clinical management.Recent FindingsCardiotoxicity may be due to direct or indirect effects of infused chimeric antigen receptor T cells. The cytokine release syndrome has been described extensively in the literature. Studies have also reported car...
Source: Current Hematologic Malignancy Reports - February 3, 2020 Category: Hematology Source Type: research

Novel Treatment Strategies in the Management of Waldenstr öm Macroglobulinemia
AbstractPurpose of ReviewRecent advances the genomic profiling of patients with Waldenstr öm macroglobulinemia (WM) have led to the identification of novel therapeutic targets in these patients. In this review, we cover the current standard of care and the recently evaluated novel approaches with high potential to be incorporated in the therapeutic armamentarium against WM.Recent FindingsTheMYD88L265P mutation is the most common genomic abnormality in WM, and is encountered in 80 –95% of patients, making it an important target for drug development. The success of the first-generation Bruton tyrosine kinase (BTK)...
Source: Current Hematologic Malignancy Reports - January 31, 2020 Category: Hematology Source Type: research

Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy
AbstractPurpose of ReviewCMV DNA polymerase inhibitors such as ganciclovir and foscarnet have dramatically reduced the burden of CMV infection in the HCT recipient. However, their use is often limited by toxicities and resistance. Agents with novel mechanisms and favorable toxicity profiles are critically needed. We review recent developments in CMV antivirals and immune-based approaches to mitigating CMV infection.Recent FindingsLetermovir, an inhibitor of the CMV terminase complex, was approved in 2017 for primary CMV prophylaxis in adult seropositive allogeneic HCT recipients. Maribavir, an inhibitor of the CMV UL97 kin...
Source: Current Hematologic Malignancy Reports - January 24, 2020 Category: Hematology Source Type: research

What Does Chronic Myeloid Leukaemia Tell Us About Other Leukaemias?
AbstractPurpose of ReviewDetermine if therapy of chronic myeloid leukaemia (CML) is a model for treating other cancers.Recent FindingsCML has a relatively homogeneous phenotype and genotype and is caused by one mutation,BCRABL1, in every instance. In contrast, most other leukaemias, haematologic cancers and solid cancer have more heterogeneous phenotypes and extraordinarily greater genotypic diversity and mutational complexity.SummaryLesions learned from treating CML have little applicability to other leukaemias, haematologic cancers or solid cancer. (Source: Current Hematologic Malignancy Reports)
Source: Current Hematologic Malignancy Reports - December 19, 2019 Category: Hematology Source Type: research

Updates in Novel Therapies for Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
AbstractPurpose of ReviewBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, clinically aggressive hematologic malignancy that has heterogeneous presentation and can involve the skin, lymph nodes, and bone marrow. Recent advancements in our patho-biologic understanding of the disease have led to the development of new targeted therapies for BPDCN. In this review, we aimed to describe some of the novel treatments that are being put forward for the management of BPDCN.Recent FindingsTagraxofusp is the first CD123-targeted therapy approved as the first ever targeted treatment of BPDCN in patients aged 2  year...
Source: Current Hematologic Malignancy Reports - December 18, 2019 Category: Hematology Source Type: research

Health-Related Quality of Life and Treatment of Older Adults with Acute Myeloid Leukemia: a Young International Society of Geriatric Oncology Review Paper
AbstractPurpose of ReviewThe treatment landscape for older patients with acute myeloid leukemia (AML) is evolving. Many treatments have comparable efficacy making their impact on quality of life (QoL) an important differentiating factor. In this review, we discuss QoL in older adults with AML, focusing on therapeutic and observational trials that have incorporated QoL assessments.Recent FindingsHealth-related quality of life (HRQoL) is a multi-dimensional concept incorporating physical, mental, emotional, and social functioning domains. HRQoL components overlap with components of geriatric assessment, a multidisciplinary d...
Source: Current Hematologic Malignancy Reports - November 27, 2019 Category: Hematology Source Type: research

Treatment of MDS/MPN and the MDS/MPN IWG International Trial: ABNL MARRO
AbstractPurpose of ReviewMDS/MPNs comprise a group of rare hematologic malignancies that balance features of myeloproliferation and bone marrow failure. Given overlapping clinical features and rarity of incidence, MDS/MPNs have long posed a diagnostic and therapeutic challenge. Herein, we sought to review recent advances in diagnosis and emerging therapeutic strategies and highlight the upcoming ABNL MARRO study which aims to individualize therapy for patients with MDS/MPN.Recent FindingsFocused study of molecular mutations in MDS/MPNs has provided improved diagnostic clarity. Specific gene mutation or patterns of mutation...
Source: Current Hematologic Malignancy Reports - November 27, 2019 Category: Hematology Source Type: research

Mutation-Driven Therapy in MDS
AbstractPurpose of ReviewGenetic sequencing in myelodysplastic syndrome (MDS) has provided an improved understanding of the complexity and heterozygosity of the disease. More importantly, our molecular understanding of MDS is leading to rapid advancements and personalized therapy for our patients. Herein, we review the current mutation-driven treatment landscape in MDS, first focusing on individual mutations. We then discuss the effect of specific gene mutations on response and outcomes to standard therapies as well as to cutting edge investigational therapies.Recent FindingsMolecular annotation of MDS can predict response...
Source: Current Hematologic Malignancy Reports - November 23, 2019 Category: Hematology Source Type: research

Towards a Personalized Treatment of Patients with Chronic Myeloid Leukemia
AbstractPurpose of ReviewTreatment goals and ambitions have even been upwardly revised since demonstration was made that under certain conditions, treatment-free remission was possible. Herein, we will discuss on how to try tailoring treatment choices to the unique characteristics of each patient.Recent FindingsSince the first-generation ATP-competitive TKI imatinib was made available in the clinic in 2001, second-generation drugs such as dasatinib, nilotinib and bosutinib and the third-generation TKI ponatinib have broadened the therapeutic armamentarium, providing effective salvage against intolerance and different types...
Source: Current Hematologic Malignancy Reports - November 23, 2019 Category: Hematology Source Type: research

Targeting the JAK/STAT Pathway in T Cell Lymphoproliferative Disorders
AbstractPurpose of ReviewT cell lymphoproliferative disorders represent a diverse group of hematologic malignancies with poor prognosis underscoring the need for novel therapeutic approaches. Disruption of the JAK/STAT signaling pathway has been described in this group of blood cancers and may represent an approach for targeted therapy. Here, we summarize the current data describing the disruptions of JAK/STAT signaling in T cell malignancies and focus on the existing evidence for exploitation of this pathway with targeted therapies.Recent FindingsTo date, preclinical studies have demonstrated the efficacy of JAK/STAT inhi...
Source: Current Hematologic Malignancy Reports - November 18, 2019 Category: Hematology Source Type: research

The Clinical Challenge of Idiopathic Cytopenias of Undetermined Significance (ICUS) and Clonal Cytopenias of Undetermined Significance (CCUS)
AbstractPurpose of ReviewTo review terminology, diagnostic algorithms, and clinical outcomes for patients with unexplained blood cytopenias.Recent FindingsPatients with cytopenias that remain unexplained after organized diagnostic testing can be described as having “idiopathic cytopenias of undetermined significance” (ICUS). Patients with unexplained cytopenias have a risk of progression to clonal myeloid neoplasms, including myelodysplastic syndromes (MDS). If a somatic mutation in a gene associated with leukemia is detectable in hematopoietic tissue, esp ecially if multiple mutations with a high (> &thinsp...
Source: Current Hematologic Malignancy Reports - November 7, 2019 Category: Hematology Source Type: research

The Hidden Pathogenesis of CML: Is BCR-ABL1 the First Event?
AbstractPurpose of ReviewIdentification of theBCR-ABL1 fusion oncogene in patients diagnosed with chronic myeloid leukemia (CML) led to the development of targeted therapy responsible for the dramatic survival benefits observed in the past two decades. However, despite these revolutionary findings, there remains marked disparity in patient outcomes. Why do some patients present de novo while others evolve to the more aggressive stages of CML? Why can select patients successfully discontinue therapy as part of a treatment-free remission attempt whereas others fail to meet specific molecular milestones?Recent FindingsBCR-ABL...
Source: Current Hematologic Malignancy Reports - November 7, 2019 Category: Hematology Source Type: research

Early Management of CML
AbstractPurpose of ReviewThe marked improvement in clinical outcomes for patients with chronic myeloid leukaemia (CML) can be solely attributed to the introduction of targeted therapies against the fusion oncoprotein,BCR-ABL1. However, patient responses, although generally positive, remain heterogenous. Careful drug selection, ensuring the optimal TKI, is chosen for each patient and involves a complex decision process which incorporates consideration of numerous factors.Recent FindingsFor some patients, with disease characteristics that indicate adverse intrinsic disease biology, more potentBCR-ABL1 inhibition is often app...
Source: Current Hematologic Malignancy Reports - November 7, 2019 Category: Hematology Source Type: research