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

India, the most populous nation in the world, also has a high frequency of the sickle hemoglobin (HbS) allele globally. The Arab Indian HbS haplotype in India is characterized by a relatively high percentage of fetal Hb, with widely varying frequencies of α-thalassemia. Hence, sickle cell disease (SCD) in India was perceived to be mild. Advances in the past decade in screening and SCD management have revealed that the severity of SCD in India is comparable to many other parts of the world. Clinical features in India include vaso-occlusive crisis, acute chest syndrome, avascular necrosis, renal involvement, stroke, etc, at a relatively young age. Once a fatal disease of childhood, the majority of patients born with SCD are expected to survive into adulthood, largely because of improvements in comprehensive care programs including newborn screening, penicillin prophylaxis, transcranial Doppler, and hydroxyurea therapy. Several centers are performing hematopoietic stem cell transplants successfully for SCD. To address the urgent need to control and manage SCD in India's population, the Government of India launched the National Sickle Cell Anaemia Elimination Mission, with significant funding for large-scale measures to screen, treat, counsel, educate, and develop technologies and novel therapies and gene therapies.

The last 2 decades of genetic discovery in the field of vascular anomalies have brought targeted medical therapies to the forefront of care patients with vascular anomalies and have broadened the role of hematologists/oncologists in this field. Many vascular anomalies have now been identified to be driven by somatic gain-of-function variants in the PI3K/AKT/ mTOR and Ras/MAPK intracellular signaling pathways. This has led to the introduction of various antiangiogenic agents that inhibit these pathways. Knowledge of the indications for and the safe administration of these agents in patients with vascular anomalies is now a crucial part of training for hematologists/oncologists.

Frontline therapy for chronic lymphocytic leukemia (CLL) has substantially advanced in the previous decade. While monotherapy with a Bruton's tyrosine kinase (BTK) inhibitor is an excellent option for many patients, combination therapies are of high clinical interest as they can induce deep responses and durable remissions, and in many cases allow discontinuation of therapy. There are several doublet therapies that are currently in clinical use. These include combinations of BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib) or BCL2 inhibitors (venetoclax) with anti-CD20 monoclonal antibodies, and combinations of BTK and BCL2 inhibitors. While BTK inhibitors with anti-CD20 monoclonal antibodies still typically require indefinite therapy, combinations involving the BCL2 inhibitor venetoclax have allowed for successful therapy discontinuation. Triplets, which combine all 3 of these paradigms, are of interest especially for patients with higher-risk disease. While triplets have been mainly studied in single-arm trials with excellent outcomes, comparative data to doublets are limited. In this article, we outline the doublet and triplet regimens that have been evaluated in CLL as well as the data from trials comparing doublets and triplets.

Significant progress has been made in the treatment of multiple myeloma (MM), with the introduction of several new drugs with different mechanisms of action. The treatment of newly diagnosed MM has evolved dramatically with the development of highly effective combinations that include 1 or more of the new drugs. Despite the continuing improvement in the overall survival of patients with MM, nearly a quarter of the patients have significantly inferior survival, often driven by a combination of factors, including tumor genetics and host frailty. The focus of initial therapy remains rapid control of the disease with reversal of the symptoms and complications related to the disease with minimal toxicity and a reduction in early mortality. The selection of the specific regimen, to some extent, depends on the ability of the patient to tolerate the treatment and the underlying disease risk. It is typically guided by results of randomized clinical trials demonstrating improvements in progression-free and/or overall survival. While increasing risk calls for escalating the intensity of therapy by using quadruplet combinations that can provide the deepest possible response and the use of autologous stem cell transplant, increasing frailty calls for a reduction in the intensity and selective use of triplet or doublet regimens. The choice of subsequent consolidation treatments and maintenance approaches, including duration of treatment, also depends on these factors, particularly the underlying disease risk. The treatment approaches for newly diagnosed myeloma continue to evolve, with ongoing trials exploring bispecific antibodies as part of initial therapy and CAR T cells for consolidation.

Vascular malformations, which result from anomalies in angiogenesis, include capillary, lymphatic, venous, arteriovenous, and mixed malformations and affect specific vessel types. Historically, treatments such as sclerotherapy and surgery have shown limited efficacy in complicated cases. Most vascular malformations occur sporadically, but some can be inherited. They result from mutations similar to oncogenic alterations, activating pathways such as PI3K-AKT-mTOR or Ras-MAPK-ERK. Recognizing these parallels, we highlight the potential of targeted molecular inhibitors, repurposing anticancer drugs for the treatment of vascular malformations. This case-based review explores recent developments in precision medicine for slow-flow and fast-flow vascular malformation.

The last 20 years witnessed relevant clinical advancements in the field of hematopoietic cell transplantation (HCT) for leukemia patients. The introduction of novel conditioning regimens, a better prophylaxis and management of graft- versus-host disease, and an ameliorated posttransplant support system improved safety and, therefore, outcomes. On the other hand, leukemia relapse remains the major cause of allogeneic HCT failure. Efforts have been made to understand the mechanisms of leukemia relapse, and new insights that clarify how donor immunity exerts graft-versus- leukemia (GVL) activity are available. Such studies set the base to design novel transplant strategies that can improve disease control. In our review we begin by discussing the most relevant criteria to choose a donor that provides a strong GVL effect. We also report some of the novel conditioning regimens that aim to deliver and extend myeloablation in order to reduce the disease burden at time of graft infusion. Finally, we discuss how the graft can be manipulated to limit the use of immune suppression and ensure potent antileukemic activity.

The remarkable improvement in survival among individuals with hematological malignancies receiving chimeric antigen receptor (CAR) T-cell therapy has highlighted the growing unmet need to incorporate patient-centered assessments in management guidelines for these patients. That CAR T-cell therapy is associated with unique toxicities and relatively high symptom burden in the first few weeks after cell infusion is well known. Magnifying the patient's voice by using patient-reported outcomes (PROs) might support personalized intervention in the acute-care setting, optimize the use of medical resources, improve satisfaction with therapy, and enhance survival benefit. However, various factors impede PRO use in routine patient care: (1) the feasibility of PRO assessment during the acute phase of treatment, especially in patients experiencing neurological toxicities, is not well established; (2) although PROs are widely used in drug- development trials, the assessment tools used in clinical trials primarily inform quality-of-life or safety comparisons among study arms and are rarely the proper tools for assessing and capturing clinically meaningful adverse events that should be monitored in routine patient care; (3) PRO data that could guide how best to monitor and capture the delayed effects of CAR T-cell therapy in long-term survivors are limited. There is a pressing need to overcome these barriers to integrating evidence-based PROs into standard-of-care guidelines for patients receiving CAR T-cell therapy. In this review, we present the current state of PRO utilization in CAR T-cell therapy. We also discuss practical approaches and future directions for successful implementation of PROs in the care of patients receiving CAR T-cell therapy.

The cutaneous T-cell lymphomas (CTCLs) comprise a diverse set of diseases with equally diverse presentations ranging from asymptomatic solitary lesions to highly aggressive diseases with propensity for visceral spread. The more aggressive CTCLs, which herein we consider as certain cases of advanced-stage mycosis fungoides/Sézary syndrome (MF/SS), primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (PCAETCL), and primary cutaneous gamma delta T-cell lymphoma (PCGDTCL), require systemic therapy. Over the last 5 years, treatment options for MF/SS have expanded with biological insights leading to new therapeutic options and increasingly unique management strategies. An enhanced appreciation of the compartmental efficacy of these agents (skin, blood, lymph nodes, visceral organs) is incorporated in current management strategies in MF/SS. In addition, approaches that combine modalities in attempts to increase depth and durability of responses across multiple compartments are being trialed. In contrast to MF/SS, PCAETCL and PCGDTCL remain diseases with few prospective studies to guide treatment. However, recent genomic insights on these diseases, such as the presence of JAK2 fusions in PCAETCL and cell of origin findings in PCGDTCL, have created options for new biomarker-driven strategies.

Managing recurrent and refractory venous thromboembolism (VTE) in patients with cancer presents unique challenges. This review outlines the complexities and therapeutic strategies for recurrent VTE in cancer patients, which includes distinguishing thrombus acuity, differentiating between tumor and bland thrombi, and evaluating potential contributing factors including anticoagulant adherence, extrinsic tumor compression, drug interactions, and anticoagulant-specific considerations such as heparin-induced thrombocytopenia or antithrombin deficiency. Different anticoagulation strategies are discussed, including the administration of escalated-dose low molecular weight heparin (LMWH) as well as the indications and rationale for switching between direct oral anticoagulants or LMWH.