Expert Review of Hematology

INTRODUCTION: The combined use of the BCL-2 inhibitor venetoclax with azacitidine now is the standard of care for patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy with outcomes exceeding those achieved with hypomethylating agents alone. Venetoclax in combination with intensive chemotherapy is also increasingly used both as frontline as well as salvage therapy. However, resistance to and relapse after venetoclax-based therapies are of major concern and outcomes after treatment failure remain poor...

INTRODUCTION: Hemophilia A is managed with coagulation clotting factor VIII (FVIII) therapy that poses significant challenges, such as a high treatment burden, immunogenicity, inconsistent hemostatic cover, poor treatment outcomes, and musculoskeletal progression despite adequate prophylactic treatment. Various non-factor therapies, such as several natural anticoagulant inhibitors and factor FVIII mimetics, have been developed to address these unmet needs. However, the role of emicizumab in addressing these unmet needs remains underexplored...

INTRODUCTION: The improved quality of care and increased drug availability have shifted the goal of treating people with hemophilia from life-threatening bleeding prevention to joint health preservation and quality of life amelioration. Many tools are now available to the clinician in order to optimize the management of hemophilic arthropathy. AREAS COVERED: This paper reviews the pivotal role of ultrasound evaluation in early detection of joint bleeding and differential diagnosis of joint pain, with a focus on the feasibility of a long-term monitoring of joint health through the use of artificial intelligence and telemedicine...

INTRODUCTION: Bruton's tyrosine kinaseinhibitors (BTKis) changed the trajectory of upfront and relapsed/refractory chronic lymphocytic leukemia (CLL) treatment. However, BTKis are plagued by a spectrum of toxicities. Zanubrutinib was developed to circumvent challenges with prolonged tolerability by increasing BTK selectivity and maximizing efficacy through pharmacokinetic/pharmacodynamic optimization. However, with the availability of ibrutinib, acalabrutinib, and zanubrutinib, limited data exists to guide sequencing of BTKi therapy in the relapsed/refractory setting...

INTRODUCTION: Light chain (AL) amyloidosis is a rare and complex disease which can affect various systems of the body. In common with many rare and multisystemic diseases, the breadth of diagnostic, clinical and supportive expertise required to care for such patients is best met by a multidisciplinary team. AREAS COVERED: We outline different phases of the patients' journey, including diagnosis, staging, treatment, and response assessment, to highlight common clinical issues best resolved by a multidisciplinary approach...

INTRODUCTION: Endogenous DNA damage is a significant factor in the damage of hematopoietic cells. Megakaryopoiesis is one of the pathways of hematopoiesis that ends with the production of platelets and plays the most crucial role in hemostasis. Despite the presence of efficient DNA repair mechanisms, some endogenous lesions can lead to mutagenic alterations, disruption of pathways of hematopoiesis including megakaryopoiesis and potentially result in human diseases. AREAS COVERED: The complex regulation of DNA repair mechanisms plays a central role in maintaining genomic integrity during megakaryopoiesis and influences platelet production efficiency and quality...

INTRODUCTION: Artificial intelligence (AI) is a rapidly growing field of computational research with the potential to extract nuanced biomarkers for the prediction of outcomes of interest. AI implementations for the prediction for clinical outcomes for myeloproliferative neoplasms (MPNs) are currently under investigation. AREAS COVERED: In this narrative review, we discuss AI investigations for the improvement of MPN clinical care utilizing either clinically available data or experimental laboratory findings...

INTRODUCTION: Acute promyelocytic leukemia (APL) is a distinct form of acute myeloid leukemia characterized by the presence of t(15;17)(q24;21) and the PML:RARA gene fusion. Frontline use of intravenous arsenic trioxide (i.v.-ATO) and all-trans retinoic acid (ATRA) has vastly improved cure rates in APL. Researchers in Hong Kong invented the oral formulation of ATO (oral-ATO) and have confirmed a bioavailability comparable to i.v.-ATO. A plethora of studies have confirmed the safety and efficacy of oral-ATO-based regimens in the frontline and relapsed setting...

INTRODUCTION: Mantle cell lymphoma (MCL) is an uncommon non-Hodgkin lymphoma that is generally considered incurable. Covalent BTK inhibitors (cBTKi) are the cornerstone of treatment for relapsed or refractory (R/R) MCL, but treatment options are limited and prognosis is poor after cBTKi failure. Pirtobrutinib is a non-covalent BTK inhibitor that has demonstrated excellent efficacy and safety and represents an important new treatment in the evolving treatment landscape of R/R MCL. AREAS COVERED: This review will provide an overview of the therapeutic landscape of R/R MCL, characteristics of pirtobrutinib, and efficacy and safety data of pirtobrutinib in R/R MCL from pivotal clinical trials...

INTRODUCTION: Children receiving treatment for acute myeloid leukemia (AML) are at high risk of invasive fungal disease (IFD). Evidence from pediatric studies support the efficacy of antifungal prophylaxis in reducing the burden of IFD in children receiving therapy for AML, yet existing antifungal agents have specific limitations and comparative data to inform the optimal prophylactic approach are lacking. AREAS COVERED: This review summarizes the epidemiology of invasive fungal disease (IFD) and current antifungal prophylaxis recommendations for children with acute myeloid leukemia (AML)...

No abstract text is available yet for this article.

INTRODUCTION: Immunethrombocytopenia (ITP) affecting pregnancy is a diagnostic and often atherapeutic challenge. AREAS COVERED: We review thecurrent diagnostic criteria for ITP in pregnancy and the potential utility oflaboratory tests. We discuss the impact of ITP on pregnancy outcomes and theeffects of pregnancy on patients living with chronic ITP.  We describe the criteria for intervention,the evidence supporting first-line treatment approaches and the therapeuticdecisions and challenges in cases refractory to steroids and IVIG...

BACKGROUND: Multiple myeloma (MM) is a plasma cell neoplasm which accounts for 1-2% of cancers and approximately 17% of hematological malignancies in the United States each year. Fifty percent of patients with symptomatic MM have three or more primary care visits before being referred to a specialist, which is greater than any other cancer. A delay in the diagnosis of multiple myeloma has been shown to negatively impact the clinical course of the disease; patients with longer diagnostic intervals have been shown to experience shorter disease-free survival and higher rates of treatment-related complications...

INTRODUCTION: Sickle cell disease (SCD) is a monogenic disorder that exerts several detrimental health effects on those affected, ultimately resulting in significant morbidity and early mortality. There are millions of individuals globally impacted by this disease. Research in gene therapy has been growing significantly over the past decade, now with two FDA approved products, aiming to find another cure for this complex disease. AREAS COVERED: This perspective article aims to provide a clinician's insight into the current landscape of gene therapies, exploring the novel approaches, clinical advances, and potential impact on the management and prognosis of SCD...

BACKGROUND: Due to the numerous complications associated with sickle cell disease (SCD), patients often receive a variety of medications alongside their SCD treatment. However, a notable gap exists in the current literature regarding medication use patterns among them. This study aimed to investigate medication usage patterns in patients with SCD. RESEARCH DESIGN AND METHODS: This cross-sectional study, conducted in Bushehr Province, employed a stratified random sampling method to select eligible participants with SCD...

INTRODUCTION: Gelatinous transformation of the bone marrow (GTBM) represents a clinically significant but often underdiagnosed condition, emphasizing the pivotal role of accurate diagnosis in facilitating appropriate treatment strategies. AREAS COVERED: This special report synthesizes insights gathered from a comprehensive appraisal of clinical and pathology publications on GTBM available on PubMed. By employing search terms such as 'gelatinous,' 'gelatinous transformation,' and 'bone marrow,' this report aims to provide a nuanced understanding of GTBM, elucidating distinctive pathological features while distinguishing it from similar pathologies...

INTRODUCTION: The treatment of multiple myeloma (MM) is evolving rapidly. We have seen quadruplet regimens incorporating proteasome inhibitors, immunomodulatory drugs (IMiDs), and CD38 monoclonal antibodies emerge as standard-of-care options for newly diagnosed MM, and numerous novel therapies approved for relapsed/refractory MM. However, there remains an ongoing need for novel treatment options in multiple treatment settings, including refractoriness to frontline standards of care. AREAS COVERED: Targeting degradation of the lymphoid transcription factors IKZF1 and IKZF3 - Ikaros and Aiolos - through modulation of cereblon, an E3 ligase substrate recruiter/receptor, is a key mechanism of action of the IMiDs and the more recent class of compounds known as the CELMoD agents...

INTRODUCTION: Comorbidities play an important role in the management of chronic lymphocytic leukemia (CLL) and may influence survival and treatment outcomes. Considering the aging general population and increasing incidence of type 2 diabetes (T2D), a comprehensive understanding of the interplay between CLL and T2D is essential for optimizing care and outcomes. AREAS COVERED: We present current knowledge on co-existing CLL and T2D including prevalence, shared etiology and risk factors and how the conditions and treatment hereof may influence the outcome of one another...

INTRODUCTION: The global need for antifungal stewardship is driven by spreading antimicrobial and antifungal resistance. Triazoles are the only oral and relatively well-tolerated class of antifungal medications, and usage is associated with acquired resistance and species replacement with intrinsically resistant organisms. On a per-patient basis, hematology patients are the largest inpatient consumers of antifungal drugs, but are also the most vulnerable to invasive fungal disease. AREAS COVERED: In this review we discuss available and forthcoming antifungal drugs, antifungal prophylaxis and empiric antifungal therapy, and how a screening based and diagnostic-driven approach may be used to reduce antifungal consumption...

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