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

Research regarding the hematologic sequelae of estrogen and testosterone therapy for transgender people is an emerging area. While estrogen therapy has been widely studied in cisgender women, studies in transgender individuals are limited, revealing variable adverse effects influenced by the dose and formulation of estrogen used. Thrombotic risk factors in transgender and gender-diverse individuals are multifactorial, involving both modifiable and nonmodifiable factors. Management of venous thromboembolism (VTE) in individuals receiving gender-affirming estrogen entails standard anticoagulation therapy alongside shared decision-making regarding hormone continuation and risk factor modification. While data and guidance from cisgender women can offer a reference for managing thrombotic risk in transgender individuals on hormone therapy, fully applying these insights can be challenging. The benefits of gender-affirming hormone therapy include significantly reducing the risk of suicide and depression, highlighting the importance of a contemplative approach to the management of hormonal therapy after a VTE event. Although limited, the available data in the literature indicate a low thrombotic risk for transgender individuals undergoing gender-affirming testosterone therapy. However, polycythemia is a common adverse effect necessitating monitoring and, occasionally, adjustments to hormonal therapy. Additionally, iron deficiency may arise due to the physiological effects of testosterone or health care providers' use of phlebotomy, an aspect that remains unstudied in this population. In conclusion, while the set of clinical data is expanding, further research remains vital to refine management strategies and improve hematologic outcomes for transgender individuals undergoing gender-affirming hormone therapy.

Chimeric antigen receptor T-cell therapy (CAR-T) has transformed the treatment paradigm of relapsed/refractory B-cell malignancies. Yet, this therapy is not without toxicities. While the early inflammation-mediated toxicities are now better understood, delayed hematopoietic recovery and infections result in morbidity and mortality risks that persist for months following CAR-T. The predisposition to infections is a consequence of immunosuppression from the underlying disease, prior therapies, lymphodepletion chemotherapy, delayed hematopoietic recovery, B-cell aplasia, and delayed T-cell immune reconstitution. These risks and epidemiology can vary over a post-CAR-T timeline of early (<30 days), prolonged (30-90 days), or late (>90 days) follow-up. Antibacterial, antiviral, and antifungal prophylaxis; growth factors and stem cell boost to expedite count recovery; immunoglobulin replacement therapy; and possibly revaccination programs are important prevention strategies to consider for infection mitigation. Assessment of risk factors, evaluation, and treatment for pathogen(s) prevalent in a particular time frame post-CAR-T are important clinical considerations in patients presenting with clinical features suggestive of infectious pathology. As more data emerge on the topic, personalized risk assessments to inform the type and duration of prophylaxis use and planning interventions will continue to emerge. Herein, we review our current approach toward infection mitigation while recognizing that this continues to evolve and that there are differences among practices stemming from data availability limitations.

Kidney disease is a common complication of monoclonal immunoglobulin (MIg)-secreting B-cell disorders and predominantly occurs in patients who do not meet the criteria for an overt hematological disease. To distinguish this situation from monoclonal gammopathy of undetermined significance, which lacks organ damage, the term monoclonal gammopathy of renal significance (MGRS) was introduced to depict the association of a small, otherwise indolent B-cell clone, with renal disease induced by the secreted MIg. The spectrum of renal disorders in MGRS is wide, encompassing both tubular and glomerular disorders, classified according to the composition of deposits and their ultrastructural pattern of organization. Renal lesions, independent of the tumor burden, are mostly governed by the molecular characteristics of the MIg variable domain and involve either direct (deposition or precipitation) or indirect (autoantibody activity, complement activation) mechanisms. The diagnosis, often suggested by careful analysis of renal and extrarenal symptoms, almost always requires histological confirmation by a kidney biopsy with light, immunofluorescence, and electron microscopy studies. Most patients do not have a known monoclonal gammopathy at presentation. Hematologic investigations should include serum and urine protein electrophoresis and immunofixation, serum-free light chain measurements, and bone marrow studies with flow cytometry and cytogenetics to determine the nature of the pathogenic clone (most commonly plasmocytic). Early diagnosis before the development of severe chronic kidney disease and rapid achievement of deep hematological response through clone-targeted chemotherapy (currently based on proteasome inhibitor and monoclonal anti-CD38 antibody-based combinations for plasma cell clones) are the main factors influencing long-term renal and patient outcomes.

Despite promising advances leading to improved survival, many patients with hematologic malignancies end up dying from their underlying disease. Their end-of-life (EOL) care experience is often marked by worsening symptoms, late conversations about patient values, increased healthcare utilization, and infrequent involvement of palliative care and hospice services. There are several challenges to the delivery of high-quality EOL care that span across disease, patient, clinician, and system levels. These barriers include an unpredictable prognosis, the patient's prognostic misunderstandings and preference to focus on the immediate future, and the oncologist's hesitancy to initiate EOL conversations. Additionally, many patients with hematologic malignancies have increasing transfusion requirements at the end of life. The hospice model often does not support ongoing blood transfusions for patients, creating an additional and substantial hurdle to hospice utilization. Ultimately, patients who are transfusion-dependent and elect to enroll in hospice do so often within a limited time frame to benefit from hospice services. Strategies to overcome challenges in EOL care include encouraging repeated patient-clinician conversations that set expectations and incorporate the patient's goals and preferences and promoting multidisciplinary team collaboration in patient care. Ultimately, policy-level changes are required to improve EOL care for patients who are transfusion-dependent. Many research efforts to improve the care of patients with hematologic malignancies at the end of life are underway, including studies directed toward patients dependent on transfusions.

Direct oral anticoagulants (DOACs) do not require routine monitoring of anticoagulant effect, but measuring DOAC activity may be desirable in specific circumstances to detect whether clinically significant DOAC levels are present (eg, prior to urgent surgery) or to assess whether drug levels are excessively high or excessively low in at-risk patients (eg, after malabsorptive gastrointestinal surgery). Routine coagulation tests, including the international normalized ratio (INR) or activated partial thromboplastin time (aPTT), cannot accurately quantify drug levels but may provide a qualitative assessment of DOAC activity when considering the estimated time to drug clearance based on timing of last drug ingestion and renal and hepatic function. Drug-specific chromogenic and clot-based assays can quantify drug levels but they are not universally available and do not have established therapeutic ranges. In this review, we discuss our approach to measuring DOAC drug levels, including patient selection, interpretation of coagulation testing, and how measurement may inform clinical decision-making in specific scenarios.

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated disease with many important manifestations in hematopoietic and lymphoid tissue. IgG4 is the least naturally abundant IgG subclass, and the hallmark feature of IgG4-RD is markedly increased IgG4-positive plasma cells (with an IgG4 to IgG ratio >40%) in affected tissue, along with elevated polyclonal serum IgG and IgG4 in most patients. Histological diagnosis is essential, and other key features include storiform fibrosis, lymphoplasmacytic infiltrate, tissue eosinophilia, and obliterative phlebitis. The disease can present with predominantly proliferative features, such as swollen lacrimal and salivary glands, orbital pseudotumor, autoimmune pancreatitis, polyclonal hypergammaglobulinemia (PHGG), eosinophilia, and tubulointerstitial nephritis of the kidneys, or predominantly fibrotic disease, including mediastinal and retroperitoneal fibrosis, sclerosing mesenteritis, and hypertrophic pachymeningitis. This review focuses on 4 key hematological manifestations: PHGG, IgG4-positive plasma cell enriched lymphadenopathy (LAD), eosinophilia, and retroperitoneal fibrosis (RPF). These features are found in 70%, 60%, 40%, and 25% of IgG4-RD patients, respectively, but can also represent key hematological "mimickers" of IgG4-RD, including Castleman disease (PHGG, LAD), eosinophilic vasculitis (eosinophilia, PHGG, LAD), hypereosinophilic syndromes (eosinophilia, LAD, PHGG), and histiocyte disorders (PHGG, LAD, RPF). An organized approach to these 4 manifestations, and how to distinguish IgG4-RD from its mimickers, is explained. Proliferative manifestations typically respond very well to treatment corticosteroids, rituximab, and other immunosuppressives, whereas chronic fibrotic disease may not be reversible with current treatment modalities.

Peripheral T-cell lymphomas (PTCLs) are a heterogenous yet aggressive group of lymphomas that arise from mature T- or NK-cell precursors. Nodal PTCLs include anaplastic large-cell lymphoma, PTCL not otherwise specified, and follicular helper T-cell lymphomas. Recent advances in understanding these heterogenous diseases have prompted investigation of novel agents to improve on treatment. Brentuximab vedotin, a CD30 antibody-drug conjugate, has been incorporated into frontline treatment regimens of CD30-expressing PTCLs based on the ECHELON-2 trial. Multiple ongoing trials are evaluating the addition of other targeted agents in the frontline and relapsed/refractory setting. These include single-agent brentuximab vedotin, histone deacetylase inhibitors, duvelisib, ruxolitinib, EZH2 inhibitors, and azacitidine, among others. Follicular helper T-cell lymphomas, given frequent mutations in epigenetic regulator genes, may preferentially respond to agents such as histone deacetylase inhibitors, EZH2 inhibitors, and hypomethylating agents. As these therapies evolve in their use for both relapsed/refractory disease and then into frontline treatment, subtype-specific therapy will likely help personalize care for patients with PTCL.

Leukemia and lymphoma are 2 common hematologic cancers in adolescents and young adults (AYAs, age 15-39 years at diagnosis); however, this population has historically had lower clinical trial enrollment and less dramatic improvements in overall survival compared to other age populations. Several unique challenges to delivering care to this population have affected drug development, clinical trial availability, accessibility, and acceptance, all of which impact clinical trial enrollment. Recently, several national and institutional collaborative approaches have been utilized to improve trial availability and accessibility for AYAs with hematologic malignancies. In this review, we discuss the known barriers to cancer clinical trial enrollment and potential approaches and solutions to improve enrollment for AYAs with leukemia and lymphoma on clinical trials.