Hematology. American Society of Hematology. Education Program最新文献

Thrombocytopenia will occur in 10% of pregnancies-ranging from the clinically benign to processes that can threaten both mother and fetus. Accurately identifying the specific etiology and appropriate clinical management is challenging due to the breadth of possible diagnoses and the potential of shared features among them. Further complicating diagnostic certainty is the lack of confirmatory testing for most possible pathophysiologies. Immune thrombocytopenia (ITP) is recognized in less than 0.1% of pregnancies but is the most common cause of thrombocytopenia in early trimesters. ITP is an autoimmune disease of IgG-mediated enhanced platelet clearance and reduced platelet production. While there is an increasing number of drugs approved to treat ITP and more being examined in clinical trials, few have been sufficiently studied in pregnancy, representing a major unmet need in clinical practice. As such, treatment options for ITP in pregnancy are limited to corticosteroids and immunoglobulin therapy, which will not be effective in all cases. Maternal ITP also may have fetal impact, and any proposed therapeutic intervention must account for this possibility. Optimal care requires multidisciplinary collaboration between hematology, obstetrics, and anesthesia to enhance diagnostic clarity, develop an optimized treatment regimen, and shepherd mother and neonate to delivery safely.

Historically considered a lymphoma with limited treatment options and poor outcomes, the treatment landscape in mantle cell lymphoma (MCL) has evolved remarkably in the last decade. Chemoimmunotherapy (CIT) remains the primary frontline treatment for most patients with MCL, typically with an intensive approach in younger and fit patients. The role of consolidative autologous stem cell transplantation remains controversial, with recent data further questioning its benefit. Novel agents have shown promising results in recent frontline clinical trials and challenge the current paradigm in MCL, particularly in high-risk patients who generally have poor outcomes with CIT. Risk stratification is key to incorporating novel agents in the frontline treatment of MCL, identifying patients who do not benefit from or could be spared CIT, guiding treatment intensity and duration, and improving overall outcomes, including safety and quality of life. The MCL International Prognostic Index and Ki-67 play an important role in identifying patients with high-risk MCL. TP53 aberrations, particularly mutations, currently identify patients with the highest risk, limited benefit from CIT, and greatest need for novel therapies. Other genetic aberrations and biological clusters are being identified but currently have limited clinical utility.

A 64-year-old woman with hereditary hemorrhagic telangiectasia (HHT) characterized by a pathological variant in ACVRL1 presents to the clinic for follow-up. Manifestations of HHT include frequent epistaxis and gastrointestinal bleeding, leading to iron-deficiency anemia. Bevacizumab is initiated, with resolution of the anemia. While maintained on a regimen of bevacizumab every 6 weeks, she continues to report frequent epistaxis and has ongoing iron-deficiency requiring periodic iron infusions. She also finds the bevacizumab infusions inconvenient. She is interested in discussing other options for managing her disease.

Heparin-induced thrombocytopenia (HIT) is an immune reaction to heparin associated with thrombocytopenia, thrombotic risk, and a high risk of morbidity and mortality. Given the frequent use of heparin and the common occurrence of thrombocytopenia in hospitalized patients, the diagnosis and management of HIT is a recurrent challenge in everyday inpatient care. This article presents practical guidance and tools to support the individual clinician providing evidence-based care to patients with suspected or confirmed HIT. The optimal diagnostic evaluation requires the stepwise use of risk-stratification tools and laboratory assays. Management requires the selection and use of nonheparin anticoagulation in these complex patients with both increased thrombotic risk and possible concurrent increased bleeding risk due to thrombocytopenia. Each step in the diagnostic and management process has important nuances and complexities, many of which vary based on patient characteristics and institutional resources. Given the many challenges of HIT care, truly practical management is best achieved when tools are implemented to support the delivery of consistent, high quality, and cost-effective care across health systems.

Although heparin-induced thrombocytopenia (HIT) presents management challenges for any population, it adds complexity to the management of certain patient populations, including those undergoing cardiac surgery and those with refractory HIT and/or acute bleeding. For each of these scenarios, we review alternative management strategies when standard therapies-heparin cessation and the initiation of a nonheparin anticoagulant-are either insufficient or not practicable. In patients with HIT undergoing cardiac surgery, we review the clinical experience for heparin reexposure using therapeutic plasma exchange (TPE) or antiplatelet therapy. In patients with refractory HIT despite adequate nonheparin anticoagulation, we address the use of intravenous immune globulin, TPE, and rituximab. Finally, in patients with active bleeding, we discuss bleeding management and the risks associated with platelet transfusion. Although they may facilitate a patient-centered approach, most of these strategies are supported by limited evidence.

In patients receiving allogeneic hematopoietic cell transplantation to cure acute myeloid leukemia (AML), recurrence of the underlying disease, or relapse, represents a crucial unanswered issue and prominent cause of mortality. Still, over recent years, advancements in omic technologies have allowed us to gain new insights into the dynamic changes occurring in cancer and the host over the course of treatments, providing a novel evolutionary perspective on the issue of disease relapse. In this review, we summarize current knowledge on the molecular features of relapsing AML, with a specific focus on changes in the mutational asset of the disease and in the interplay between the tumor and the donor-derived immune system. In particular, we discuss how this information can be translated into relevant indications for monitoring transplanted patients and selecting the most appropriate therapeutic options to prevent and treat relapse.

The emergence of blastic plasmacytoid dendritic cell neoplasm (BPDCN) as its own distinct entity within the pantheon of hematologic malignancies is due to the growing understanding of its unique multiorgan clinical presentation and characteristic skin lesions. The occurrence of BPDCN is generally heralded by a multicompartmental presentation of violaceous cutaneous lesions, involvement by bone marrow and/or blood, lymph node invasion, and an inclination toward extramedullary organ involvement, including, most remarkably, central nervous system (CNS)/cerebrospinal fluid positivity. With a median age historically of ≥ 70 years and up to 5:1 male predominance in most of the field's earlier studies, the most notable development in the modern era is the recognition of emerging important groups with BPDCN, such as female, pediatric, and adolescent/young adult patients; CNS + BPDCN patients; and an increasing number of cases being diagnosed worldwide. These trends are in line with the increased educational and research efforts, greater international collaboration, and markedly improved diagnostic tools and clinical approaches among hematology/oncology, hematopathology, dermatology, and dermatopathology teams around the world. Now, with over 5 years since the first commercially approved targeted agent specifically dedicated for BPDCN, the CD123-targeted agent tagraxofusp, improvements have been demonstrated particularly in the frontline setting for patients with BPDCN. The field is abundant with hope, as it has experienced advancements including greater molecular characterization, expanded identification of potential targets for therapy beyond CD123, advent of combination therapies, improving parameters for stem cell transplantation, and novel clinical trials specifically available for patients with BPDCN.

Racial, ethnic, and socioeconomic survival disparities have been well-demonstrated across population-based and clinical trial datasets in pediatric hematologic malignancies. To date, these analyses have relied on trial-collected data such as race, ethnicity, insurance, and zip code. These exposures serve as proxies for factors such as structural racism, genetic ancestry, and adverse social determinants of health (SDOH). Systematic measurement of SDOH and social needs-and interventions targeting these needs-are feasible in pediatric oncology. We use these data to present a roadmap for the next decade of health equity research to identify actionable mechanisms and develop a portfolio of interventions to advance equitable outcomes across pediatric hematologic malignancies.