Blood Reviews最新文献

Diffuse large B-cell lymphoma (DLBCL) remains a therapeutic challenge, as a substantial proportion of patients experience relapsed or refractory (R/R) disease. Antibody-drug conjugates (ADCs) have emerged as a transformative class of targeted therapy, designed to deliver potent cytotoxic payloads directly to malignant cells via specific surface antigens. This approach enhances antitumor efficacy while minimizing toxicity. Recently, ADCs have expanded the DLBCL therapeutic landscape, with the approvals of CD79b-targeted polatuzumab vedotin and CD19-directed loncastuximab tesirine for R/R and even frontline disease. Additionally, numerous other ADCs targeting antigens such as CD22, CD30, and CD37 are under clinical investigation. However, the clinical application of ADCs is accompanied by challenges, including the management of characteristic toxicities, understanding and overcoming mechanisms of resistance. This review systematically synthesizes the mechanisms of action, updated clinical evidence, toxicity profiles, and resistance mechanisms of ADCs in DLBCL, while also discusses management strategies and provides perspectives on future directions.

Monoclonal gammopathy of undetermined significance (MGUS) represents a premalignant clinical state with an evolving footprint beyond its established role as a precursor to multiple myeloma. This review is intended for hematologists, oncologists, and translational investigators involved in MGUS risk stratification and prevention research and confronts four unresolved controversies shaping modern MGUS management: (1) The debate surrounding population screening-weighing potential benefits against economic/psychological burdens; (2) Limitations of current risk-stratification models and the promise of dynamic genomic tools; (3) The contentious pathogenic role of MGUS in non-malignant conditions versus its frequent bystander status; and (4) The paradigm-shifting question of early intervention to prevent malignancy. We synthesize emerging evidence suggesting that while MGUS presents unique opportunities for myeloma prevention, significant knowledge gaps persist in risk prediction, disease biology, and therapeutic strategy. Future progress hinges on defining the right patient, right time, and right intervention through advanced biomarker discovery and carefully designed clinical trials.

Immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by reduced platelet counts, increased bleeding risk, and impaired quality of life. Thrombopoietin receptor agonists are established second-line therapies; among these, avatrombopag is an oral agent supported by its phase 3 clinical evidence base. In adults with ITP, avatrombopag has demonstrated a rapid onset of action, durable platelet response, and favorable safety profile. A subsequent trial in pediatric populations confirmed the efficacy and safety of avatrombopag was consistent with the adult data. Real-world studies further reinforce these findings, supporting avatrombopag's profile in routine clinical practice. Beyond ITP, emerging evidence suggests potential roles for avatrombopag in other thrombocytopenic settings, including chemotherapy-induced thrombocytopenia, aplastic anemia, and post-hematopoietic stem-cell transplantation, where early data appear promising.

Metabolic reprogramming is a hallmark of cancer, actively contributing to tumour growth and therapeutic resistance. Multiple myeloma (MM) is a common haematological malignancy that exhibits distinct metabolic features, while Extramedullary Myeloma Disease (EMD) is a rare but highly aggressive manifestation of MM with increasing incidence, and an elusive metabolic landscape. Shifts in the population dietary habits have reshaped the gut microbiome, potentially altering the host metabolism and driving cancer progression, including MM and EMD. In this review, we examine the three major metabolic pathways in MM and explore emerging evidence linking gut microbiome dynamics to MM and EMD disease progression. Furthermore, we consider recent studies identifying obesity as a MM risk factor and we explore emerging metabolic targets of MM and EMD. By integrating perspectives from metabolic reprogramming, microbiome dynamics, and obesity-related risk, we aim to provide novel perspectives on MM progression from its asymptomatic precursor stage to high-risk EMD.

This review synthesizes the current evidence to assess the efficacy and safety of caplacizumab in the treatment of iTTP, focusing on its impact on TPE requirements, time to platelet normalization, relapse prevention, and treatment-related adverse events. Thirteen studies (11 observational and 2 RCTs), involving 2956 patients with iTTP were included. The majority of included studies were of high methodological quality, indicating a low risk of bias based on the assessment tools. The analysis found that caplacizumab was associated with significant clinical benefits. It marked a reduction in daily TPE sessions (MD = -3.92, p < 0.001) and time to platelet normalization (MD = -2.44, p = 0.03). Caplacizumab also significantly reduced mortality (RR = 0.29, p < 0.001) and iTTP exacerbations (RR = 0.27, p < 0.001), leading to shorter hospital stays (MD = -5.13, p = 0.001). Caplacizumab demonstrated notable clinical benefits in managing iTTP, with significant reductions in daily TPE sessions, time to platelet normalization, mortality, and iTTP exacerbations. Promising results were also noticed for early initiation compared to delayed initiation.

Chimeric antigen receptor T-cell (CAR-T) immunotherapy has revolutionized the treatment of hematologic malignancies, especially in B-cell acute lymphoblastic leukemia, B-cell non-Hodgkin lymphoma, and multiple myeloma. However, inequitable access to CAR T-cell immunotherapy has been demonstrated among racial and ethnic minority populations. This scoping review examined 37 works of published literature on barriers and facilitators to accessing commercial CAR-T therapy, as well as interventions to mitigate access inequities. The results are organized using the socio-ecological model across patient, provider, institutional, and policy levels, and highlight how these barriers and facilitators can disproportionately affect racial and ethnic minority populations. Barriers are complex and present at all socio-ecological levels, and only two published interventions that target minority access disparities to CAR-T therapy were identified. Key research gaps, including the limited number of barriers supported by objective, primary data and the absence of patient-identified barriers, are discussed. Collectively, the barriers, facilitators, and interventions identified in this scoping review can inform comprehensive, multilevel strategies to eliminate access inequities to commercial CAR T-cell immunotherapy.

The gut microbiome (GMB) describes the commensal bacteria which reside in the gastrointestinal tract. Mounting evidence suggests a major role of the GMB in several key aspects of lymphoma development and care. The GMB is implicated in lymphomagenesis, response to therapy and lymphoma-specific outcomes. Moreover, certain gut bacteria can also specifically influence the course of the disease and therapeutic response. In this review we provide an overview of sampling techniques and analytical methodologies for characterising the GMB, a brief outline pertaining to the "healthy" GMB and detailed description of existing literature regarding differences in GMB composition in lymphoma patients, prognostic indicators and the impact of different treatment modalities on the GMB in different lymphoma histologies. Additionally, we describe the relationship of the GMB and treatment of infections in lymphoma patients as well as early-stage research results in GMB manipulation to improve outcomes in patients with B cell lymphomas.

Hemophilia B, an X-linked recessive bleeding disorder caused by mutations in the gene encoding coagulation factor IX (FIX). Gene therapy using adeno-associated viral (AAV) vectors targeting hepatocytes has emerged as a promising treatment, enabling sustained FIX expression. However, AAV vectors exhibit strong liver tropism, often triggering immune responses that lead to hepatotoxicity. Clinical trials involving Etranacogene Dezaparvovec, Fidanacogene Elaparvovec, and BBM-H901 (Dalnacogene Ponparvovec) reported transient elevations in liver enzymes, typically occurring 2-6 weeks post-infusion. These elevations are usually mild to moderate and respond well to corticosteroid-based immunosuppression. The hepatic complications, while manageable, pose a risk to therapeutic efficacy and highlight the need for careful monitoring, early detection, and personalized immunosuppressive strategies. This review explores the mechanisms of AAV-induced liver dysfunction in gene therapy for Hemophilia B, with a focus on clinical manifestations, immune-mediated pathogenesis, and emerging approaches for mitigating liver-related adverse effects and providing clinical guidance.

Background: Primary myelofibrosis (PMF), the most aggressive of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), is characterized by progressive marrow fibrosis, ineffective hematopoiesis, and a pro-inflammatory milieu. These pathobiologic features drive extramedullary hematopoiesis (EMH) and confer heightened risks for hepatic, pulmonary, and thrombotic complications, particularly in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT).

Objective: Drawing on our institutional transplant experience in PMF, we review the pathophysiology, clinical manifestations, and management of EMH-related complications to optimize outcomes in this complex patient population.

Methods: We synthesized current literature on EMH in MPNs and integrated contemporary data on hepatic portal hypertension, pulmonary hypertension, splanchnic vein thrombosis, and transplant-related complications. Key insights from recent European Society for Blood and Marrow Transplantation (EBMT) registry data are highlighted.

Results: Portal hypertension affects 3-18 % of patients with myeloproliferative neoplasms (MPNs), driven by intrahepatic sinusoidal infiltration, splenic hyperdynamic circulation, and splanchnic thrombosis. Splanchnic vein thrombosis often precedes overt MPN diagnosis, with JAK2V617F detected in a substantial proportion of affected patients. Pulmonary complications-including extramedullary hematopoiesis (EMH), pulmonary hypertension, and peri-engraftment respiratory failure-contribute meaningfully to non-relapse mortality in the transplant setting. Ruxolitinib, reduced-intensity conditioning, and spleen-directed strategies have improved engraftment kinetics and mitigated graft-related complications in myelofibrosis patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). Institutional observations are incorporated throughout to contextualize hepatic, pulmonary, and vascular manifestations of EMH in contemporary practice.

Conclusion: These institutional observations complement published data and emphasize that EMH-related hepatic, pulmonary, and vascular complications are biologically active yet potentially reversible when clonal disease control is achieved. EMH-associated complications in PMF require a multidisciplinary management approach tailored to disease biology and transplant considerations. Advances in cytokine modulation, conditioning strategies, and emerging antifibrotic agents hold promise for improving patient outcomes.

Chimeric Antigen Receptor (CAR) T cell therapy, initially developed for hematologic malignancies, has recently emerged as a promising modality for treating autoimmune diseases. This review explores the evolving role of CAR T cells in reprogramming immune tolerance and achieving durable remission in autoimmune disorders. By engineering T cells to target pathogenic B cells or autoreactive T cells, CAR T therapy offers a targeted and potentially curative approach for diseases such as systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes. Early clinical trials and preclinical models have demonstrated the feasibility, safety, and efficacy of CD19-targeted CAR T cells in depleting autoreactive B cells and restoring immune homeostasis. Furthermore, next-generation CAR designs-including regulatory T cell-based CARs and antigen-specific constructs-highlight the growing precision and versatility of this platform. Despite these advances, challenges remain, including potential toxicity, antigen escape, and the need for long-term immune monitoring. This review summarizes current findings, delineates mechanistic insights, and discusses future directions for optimizing CAR T cell therapies in the context of autoimmunity.