Current Hematologic Malignancy Reports

PURPOSE OF REVIEW: Telomere biology disorders (TBDs) encompass a spectrum of genetic diseases with a common pathogenesis of defects in telomerase function and telomere maintenance causing extremely short telomere lengths. Here, we review the current literature surrounding genetic testing strategies, cascade testing, reproductive implications, and the role of genetic counseling. RECENT FINDINGS: The understanding of the genetic causes and clinical symptoms of TBDs continues to expand while genetic testing and telomere length testing are nuanced tools utilized in the diagnosis of this condition...

PURPOSE OF REVIEW: The treatment landscape of multiple myeloma (MM) has evolved resulting in MM becoming a chronic condition. The costs of MM therapies are substantial and compound as patients remain on long-term maintenance therapies and progress through multiple lines of high-cost therapies. MM predominantly impacts the elderly population insured by Medicare; here, we analyze how these costs impact patients and the Medicare trust fund. RECENT FINDINGS: With the recent passing of the Inflation Reduction Act (IRA), we postulate how costs may be impacted and debate future policy initiatives that may result in sustainability...

PURPOSE OF REVIEW: The development of potent novel agents has improved outcomes for patients with multiple myeloma (MM). Heterogeneity of response to therapy, an expanding arsenal of treatment options, and cost are however major challenges for physicians making treatment decisions. Response-adapted therapy is hence an attractive strategy for sequencing of therapy in MM. Despite its successful application in other haematologic malignancies, response-adapted therapy is yet to become a standard of care for MM...

PURPOSE OF REVIEW: Chronic myeloid leukemia (CML) is a disease that previously signified a poor prognosis, but treatment options and outcomes have improved over the last several decades. Despite this, challenges remain in optimal management in clinical practice, as the characteristics in trial populations differ from patients who are treated in a real-world setting. This review describes recent updates in real-world treatment patterns and outcomes in patients with CML. RECENT FINDINGS: Several analyses describing real-world practice patterns show that tyrosine kinase inhibitors (TKIs) are the most commonly prescribed agents in multiple lines of therapy...

PURPOSE OF REVIEW: Chronic myeloproliferative neoplasms (MPN) represent a group of diseases characterised by constitutive activation of the JAK/STAT pathway in a clonal myeloid precursor. The therapeutic approach aims to treat the symptom burden (headache, itching, debilitation), splenomegaly, slow down the fibrotic proliferation in the bone marrow and reduce the risk of thrombosis/bleeding whilst avoiding leukaemic transformation. RECENT FINDINGS: In recent years, the advent of JAK inhibitors (JAKi) has significantly broadened treatment options for these patients...

PURPOSE OF REVIEW: The treatment paradigm of chronic lymphocytic leukemia (CLL) has dramatically changed with the advent of novel targeted agents over the past decade. Richter transformation (RT), or the development of an aggressive lymphoma from a background of CLL, is a well-recognized complication of CLL and carries significantly poor clinical outcomes. Here, we provide an update on current diagnostics, prognostication, and contemporary treatment of RT. RECENT FINDINGS: Several genetic, biologic, and laboratory markers have been proposed as candidate risk factors for the development of RT...

PURPOSE OF REVIEW: There have been significant advances in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) over the past two decades. However, the intention of treatment remains control of the disease and delay of progression rather than a cure which remains largely elusive. Considering that CLL is mostly seen in older patients, there are multiple factors that play a role in the selection of CLL beyond the frontline treatment. Here, we review the concept of relapsed CLL, factors that predispose to relapse, and therapeutic options available to this patient population...

PURPOSE OF REVIEW: While most patients with chronic myeloid leukemia (CML) present in a chronic phase and are expected to have a normal life expectancy, some patients present with or progress to a more aggressive accelerated phase (AP) or blast phase (BP) of CML. Herein, we discuss the diagnostic considerations of advanced phase CML and review its contemporary management. RECENT FINDINGS: Later-generation, more potent BCR::ABL1 tyrosine kinase inhibitors (TKIs) such as ponatinib may result in superior outcomes in patients with advanced phase CML...

PURPOSE OF REVIEW: T and NK cell lymphomas are relatively rare and heterogeneous forms of non-Hodgkin lymphoma that are associated with high rates of mortality. Central nervous system relapse carries significant morbidity, though management is largely extrapolated from literature in B cell neoplasms. As such, outcomes for central nervous system involvement in T/NK cell lymphomas are dismal with no standard of care. In this review, we discuss the epidemiology of central nervous system relapse in T/NK cell lymphomas and critically analyze available literature regarding prophylaxis and treatment...

PURPOSE OF REVIEW: Epstein-Barr Virus (EBV) is a ubiquitous herpesvirus that affects almost all humans and establishes lifelong infections by infecting B-lymphocytes leading to their immortalization. EBV has a discrete life cycle with latency and lytic reactivation phases. EBV can reactivate and cause lymphoproliferation in both immunocompetent and immunocompromised individuals. There is sparse literature on monitoring protocols for EBV reactivation and no standardized treatment protocols to treat EBV-driven lymphoproliferation...

PURPOSE OF REVIEW: This review focuses on vascular complications associated with chronic myeloproliferative neoplasms (MPN) and more specifically aims to discuss the clinical and biological evidence supporting the existence of a link between clonal hematopoiesis, cardiovascular events (CVE), and solid cancer (SC). RECENT FINDINGS: The MPN natural history is driven by uncontrolled clonal myeloproliferation sustained by acquired somatic mutations in driver (JAK2, CALR, and MPL) and non-driver genes, involving epigenetic (e...

PURPOSE OF REVIEW: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by bone marrow fibrosis, megakaryocyte atypia, and inflammatory cytokine overproduction, resulting in progressive cytopenias, splenomegaly, and high symptom burden. Current backbone of care includes JAK inhibitor (JAKi) therapy, which offers limited benefits and significant discontinuation rates. Targeting the epigenetic modifiers bromodomain and extra-terminal domain (BET) proteins is a novel approach for harnessing the expression of genes involved in critical oncogenic signalling pathways implicated in MF and other malignancies...

PURPOSE OF REVIEW: Largely, treatment advances in relapsed and/or refractory acute lymphoblastic leukemia (ALL) have been made in B cell disease leaving T cell ALL reliant upon high-intensity chemotherapy. Recent advances in the understanding of the biology of T-ALL and the improvement in immunotherapies have led to new therapeutic pathways to target and exploit. Here, we review the more promising pathways that are able to be targeted and other therapeutic possibilities for T-ALL. RECENT FINDINGS: Preclinical models and early-phase clinical trials have shown promising results in some case in the treatment of T-ALL...

INTRODUCTION: Financial toxicity is a developing research area to quantify the financial stress experienced by patients and caregivers, as well as the mechanisms by which they manage the costs associated with treatment and the very real harms that this stress can inflict upon cancer care. Patients with blood malignancies experience increased costs associated with their diagnosis due to possible inpatient admissions for treatment, frequent office visits, and even more frequent lab evaluations and testing...

PURPOSE OF REVIEW: CCAAT enhancer binding protein A (CEBPA) gene mutation is one of the common genetic alterations in acute myeloid leukemia (AML), which can be associated with sporadic and familial AML. RECENT FINDINGS: Due to the recent advances in molecular testing and the prognostic role of CEBPA mutation in AML, the definition for AML with CEBPA mutation (AML-CEBPA) has significantly changed. This review provides the rationale for the updates on classifications, and the impacts on laboratory evaluation and clinical management for sporadic and familial AML-CEBPA patients...

PURPOSE OF REVIEW: To discuss novel targeted therapies under investigation for treatment of myelodysplastic neoplasms (MDS). RECENT FINDINGS: Over the last few years, results of phase 3 trials assessing novel therapies for high-risk MDS have been largely disappointing. Pevonedistat (NEDD-8 inhibitor) and APR-246 (TP53 reactivator) both did not meet trial endpoints. However, early phase trials of BCL-2, TIM3, and CD47 inhibitors have shown exciting data and are currently under phase 3 investigation...

PURPOSE OF REVIEW: Cutaneous T cell lymphomas (CTCLs) exhibit a wide variety of clinical features, histologic characteristics, and genetic drivers. We review novel molecular findings that inform our understanding of the pathogenesis of CTCL, with a focus on the tumor microenvironment (TME). RECENT FINDINGS: There is increasing evidence challenging the model of TCM :mycosis fungoides (MF) and TEM :Sézary syndrome (SS) phenotype. Phylogenetic analysis performed using whole-exome sequencing (WES) raises the possibility that MF can arise without a common ancestral T cell clone...

PURPOSE OF REVIEW: Despite progress in the treatment of pediatric B-cell acute lymphoblastic leukemia (ALL) and PH + ALL, fewer advancements have been for older adults with PH-negative B-cell ALL. Treatment of this population is mired by higher incidence of poor risk biologic features, increased incidence of medical comorbidities, and higher rates of treatment-related mortality (TRM). Here, we review the difficulties in managing elderly patients with PH-negative ALL. RECENT FINDINGS: The development of novel agents has brought additional tools to the armamentarium of drugs and has changed the landscape of treatment...

PURPOSE OF REVIEW: GATA2 deficiency is a haploinsufficiency syndrome associated with a wide spectrum of disease, including severe monocytopenia and B and NK lymphopenia, predisposition to myeloid malignancies, human papillomavirus infections, and infections with opportunistic organisms, particularly nontuberculous mycobacteria, herpes virus, and certain fungi. GATA2 mutations have variable penetrance and expressivity with imperfect genotype-phenotype correlations. However, approximately 75% of patients will develop a myeloid neoplasm at some point...

PURPOSE OF REVIEW: Long-term outcomes have significantly improved with treatment of chronic myeloid leukemia. With proper treatment, most patients will achieve similar survival rates compared to an age-matched population. Treatment-free remission is not attainable for over half of patients and chronic treatment carries with it unique challenges. We provide a pragmatic approach to the monitoring and management of chronic adverse effects (AEs). RECENT FINDINGS: In the presence of severe or intolerable AEs, switching tyrosine kinase inhibitors (TKIs) is reasonable but is not without risk...