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

The overall survival in patients with multiple myeloma has increased over recent decades. This trend is anticipated to further advance with the emergence of T-cell-redirecting therapies, including chimeric antigen receptor T-cell (CAR T) therapy and T-cell-engaging bispecific antibodies. Despite these therapeutic improvements, treatment-related adverse events impede quality of life. This underscores the imperative of optimizing supportive care strategies to maximize treatment outcomes. Such optimization is crucial not only for patient well-being but also for treatment adherence, which may translate into long-term disease control. We here describe a) how to prevent bone disease, b) a risk-adapted thrombosis prophylaxis approach, c) the management of on-target, off-tumor toxicity of G-protein-coupled receptor class C group 5 member D-targeting T-cell-redirecting therapies, and d) infectious prophylaxis, with a focus on infections during T-cell-redirecting therapies.

Antibodies to platelet factor 4 (PF4) have been primarily linked to classical heparin-induced thrombocytopenia (cHIT). However, during the rollout of the COVID-19 vaccine program a new condition, vaccine-induced thrombocytopenia and thrombosis (VITT), was identified, related to adenoviral-based COVID-19 vaccines. The differences between these 2 conditions, both clinically and in laboratory testing, set the scene for the development of a new rapid anti-PF4 assay that is not linked with heparin (as relevant for cHIT). Concurrently, there has been a reassessment of those cases described as autoimmune HIT. Such scenarios do not follow cHIT, but there is now a clearer differentiation of heparin-dependent and heparin-independent anti-PF4 conditions. The importance of this distinction is the identification of heparin-independent anti-PF4 antibodies in a new subgroup termed VITT-like disorder. Cases appear to be rare, precipitated by infection and in a proportion of cases, orthopaedic surgery, but are associated with high mortality and the need for a different treatment pathway, which includes immunomodulation therapy.

End-of-life (EOL) care is a critical part of sickle cell disease (SCD) management. However, barriers to high-quality EOL care remain, including (1) disease-related barriers (prior opioid exposure, risk of vaso-occlusive crises, chronic conditions with conflicting needs, and limitations of receiving disease-directed therapy on hospice); (2) communication-related barriers (challenges of identifying and responding to religious and spiritual concerns, limited health literacy, and previous health care system experience); (3) systemic issues (social determinants of health, structural racism, and mistrust of the medical system). However, palliative care and interdisciplinary collaboration can overcome many of these barriers. In addition, we can improve EOL care by accounting for opioid exposures, multimodal symptom management, and exploring (1) who people want involved in decision-making, (2) the role of religion and spirituality in decision-making, and (3) previous experiences with EOL. Systemic barriers can be addressed through the social determinants of health screening, minimizing financial burdens of care, and building longitudinal relationships with people with SCD. This requires the continued education of SCD providers about primary palliative care and palliative care providers about SCD. With such strategies, high-quality EOL care is possible for this vulnerable population.

The success of chimeric antigen receptor (CAR) T-cell therapy in adult patients with hematologic malignancies has resulted in a large number of long-term survivors who may experience late complications distinct from those in the early CAR T-cell treatment period. These late complications, defined as occurring more than 90 days after CAR T-cell infusion, include cytopenias, infections, secondary malignancies, and delayed neurotoxicities. Late cytopenias may be from prolonged recovery after lymphodepleting (LD) chemotherapy or arise anew, raising concerns for recurrent primary disease or a secondary malignancy. Cytopenias are treated with supportive care, hematopoietic cytokines, and, occasionally, hematopoietic stem cell support. LD chemotherapy profoundly affects B, T, and natural killer cells. CD19 and B-cell maturation antigen are expressed on normal B cells and plasma cells, respectively, and the targeting of these structures by CAR T-cell products can result in prolonged lymphopenias and hypogammaglobulinemia, making infection an ongoing risk. Late infections are predominantly due to respiratory viruses, reactivation of herpes viruses, and Pneumocystis jirovecii. Patients may require ongoing prophylaxis and immunoglobulin replacement therapy. Although responses may be blunted, vaccinations are generally recommended for most adult CAR T-cell patients. Both hematologic and solid secondary malignancies are a known risk of CAR T-cell therapy; retroviruses used to produce CAR T-cell products have resulted in T-cell cancers secondary to insertional oncogenesis. It is essential to monitor for late complications in adult patients receiving CAR T-cells by using a multidisciplinary approach between referring hematologist oncologists and cell therapy centers to improve the outcomes and quality of life for these patients.

Posttransplant relapse is the most significant challenge in allogeneic stem cell transplantation (alloSCT). Posttransplant interventions, in conjunction with optimal conditioning regimens and donor selection, are increasingly supported by evidence for their potential to prolong patient survival by promoting antileukemia or graft-versus-leukemia effects. Our review begins by highlighting the current evidence supporting maintenance therapy for relapse prevention in acute myeloid leukemia and acute lymphocytic leukemia. This includes a broad spectrum of strategies, such as targeted therapies, hypomethylating agents, venetoclax, and immunotherapies. We then shift our focus to the role of disease monitoring after alloSCT, emphasizing the potential importance of early detection of measurable residual disease and a drop in donor chimerism. We also provide an overview of salvage therapies for overt relapse, including targeted therapies, chemotherapies, immunotherapies, donor lymphocyte infusion, and selected agents under investigation in ongoing clinical trials. Finally, we review the evidence for a second alloSCT (HSCT2) and discuss factors that impact donor selection for HSCT2.

Chronic neutrophilic leukemia (CNL) is a very rare myeloid neoplasm characterized by peripheral blood neutrophilia and a hypercellular marrow with increased granulopoiesis. An activating mutation in CSF3R is present in 80% to 90% of cases. CNL displays some biological overlap in terms of clinical presentation and behavior, as well as genetic profile, with several other myeloid neoplasms, particularly myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and other MPN. Distinguishing these related entities can be challenging, requires close attention to peripheral blood and bone marrow morphology, and can be informed by the mutation pattern: CNL is strongly associated with CSF3R mutation, usually lacks JAK2, MPL, or CALR mutations, and, by definition, lacks BCR::ABL1 rearrangement. Pitfalls in diagnosis include subjectivity in assessing neutrophil dysplasia and distinguishing true neoplastic neutrophilia from reactive neutrophilias that may be superimposed upon or occur as a manifestation of the progression of other myeloid neoplasms. Accurate distinction between neutrophilic myeloid neoplasms is important, as it helps guide patient management and may disclose specific genetic lesions amenable to targeted therapy.

Idiopathic multicentric Castleman disease (iMCD) is a rare, life-threatening subtype of Castleman disease (CD), which describes a group of rare, polyclonal lymphoproliferative disorders that demonstrate characteristic histopathology and variable symptomatology. iMCD involves a cytokine storm that occurs due to an unknown cause. Rapid diagnosis is required to initiate appropriate, potentially life-saving therapy, but diagnosis is challenging and impeded by clinical overlap with a wide spectrum of inflammatory, neoplastic, and infectious causes of generalized lymphadenopathy. Diagnosis, which requires both consistent histopathologic and clinical criteria, can be further delayed in the absence of close collaboration between clinicians and pathologists. A multimodal assessment is necessary to effectively discriminate iMCD from overlapping diseases. In this review, we discuss a pragmatic approach to generalized lymphadenopathy and clinical, laboratory, and histopathological features that can aid with identifying iMCD. We discuss diagnostic barriers that impede appropriate recognition of disease features, diagnostic criteria, and evidence-based treatment recommendations that should be initiated immediately following diagnosis.

Hodgkin lymphoma (HL) is a rare hematologic malignancy with a bimodal distribution of incidence, with most patients diagnosed between the ages of 15 and 30 years and another peak in patients older than 55 years. It is estimated that in 2023, almost 9000 people were diagnosed with HL in the United States. Most patients will be cured using conventional chemotherapy and radiotherapy. The treatment of HL has changed significantly over the past decade following the approval of highly effective novel therapies, including brentuximab vedotin and the checkpoint inhibitors (CPIs) nivolumab and pembrolizumab. The increasing use of these novel therapies has resulted in decreased utilization of both autologous and allogeneic hematopoietic cell transplantation (HCT) in patients with HL. In this review, we discuss the role of stem cell transplantation in patients with HL, with a particular focus on recent data supporting allogeneic HCT as a curative option in patients who progress on or are intolerant to CPI treatment.

Measurable residual disease (MRD) is a strong but imprecise predictor of relapse in acute myeloid leukemia. Many patients fall into the outlier categories of MRD positivity without relapse or MRD negativity with relapse. Why? We will discuss these states in the context of "clonal ontogeny" examining how mutations, clonal structure, and Darwinian rules impact response, resistance, and relapse.

Philadelphia chromosome-positive (Ph+) ALL is the most common genetic subtype of ALL and primarily affects adults. Ph+ ALL is characterized by the constitutively active ABL1 kinase and is resistant to conventional chemotherapy. Thus, Ph+ ALL was historically associated with a dismal prognosis, particularly among patients who did not undergo allogeneic hematopoietic stem cell transplantation (alloHCT) in first complete remission (CR). Imatinib, the first tyrosine kinase inhibitor (TKI) effective against ABL1, transformed the treatment and prognosis of Ph+ ALL, allowing more patients to achieve CR and become eligible for alloHCT, thereby improving outcomes. In recent years, there has been an improved understanding of the biology of Ph+ ALL, including recognition of distinct subtypes (multilineage and lymphoblast-only Ph+ ALL). There has also been a dramatic expansion of effective therapeutic and diagnostic tools for management of Ph+ ALL, including more potent TKIs, which have activity against ABL kinase-resistance mutations; refinement of the chemotherapy and alloHCT regimens that accompany TKI therapy; introduction of immunotherapy (blinatumomab); and better assays for measurable residual disease monitoring. This article reviews recent advancements and future directions for the initial treatment of Ph+ ALL in adults.