Blood Reviews最新文献

In the recent few decades, outcomes in patients diagnosed with hematological malignancies have been steadily improving. However, the improved prognosis does not distribute equally among patients from different backgrounds. Besides cancer biology, demographic and geographic disparities have been found to impact overall survival significantly. Specifically, patients from underrepresented minorities including Black and Hispanics, and those with uninsured status, having low socioeconomic status, or from rural areas have had worse outcomes historically, which is uniformly true across all major subtypes of hematological malignancies. Similar discrepancy is also seen in the health care professional field, where a gender gap and a disproportionally low representation of health care providers from underrepresented minorities have been long existing. Thus, a comprehensive strategy to mitigate disparity in the health care system is needed to achieve equity in health care.

The available treatments for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have experienced a dramatic change since 2017. Incremental advances in basic and translational science over several decades have led to innovations in immune-oncology. These innovations have culminated in eight separate approvals by the US Food and Drug Administration for the treatment of patients with R/R DLBCL over the last 10 years. High-dose therapy and autologous stem cell transplant (HDT-ASCT) remains the standard of care for transplant-eligible patients who relapse after an initial remission. For transplant-ineligible patients or for those who relapse following HDT-ASCT, multiple options exist. Monoclonal antibodies targeting CD19, antibody-drug conjugates, bispecific antibodies, immune effector cell products, and other agents with novel mechanisms of action are now available for patients with R/R DLBCL. There is increasing use of chimeric antigen receptor (CAR) T-cells as second-line therapy for patients with early relapse of DLBCL or those who are refractory to initial chemoimmunotherapy. The clinical benefits of these strategies vary and are influenced by patient and disease characteristics, as well as the type of prior therapy administered. Therefore, there are multiple clinical scenarios that clinicians might encounter when treating R/R DLBCL. An optimal sequence of drugs has not been established, and there is no evidence-based consensus on how to best order these agents. This abundance of choices introduces a paradox: proliferating treatment options are initially a boon to patients and providers, but as choices grow further they no longer liberate. Rather, more choices make the management of R/R DLBCL more challenging due to lack of direct comparisons among agents and a desire to maximize patient outcomes. Here, we provide a review of recently-approved second- and subsequent-line agents, summarize real-world data detailing the use of these medicines, and provide a framework for sequencing therapy in R/R DLBCL.

β-Thalassemia is one of the most common monogenetic diseases worldwide, with a particularly high prevalence in the Middle East region. As such, we have developed long-standing experience with disease management and devising solutions to address challenges attributed to resource limitations. The region has also participated in the majority of clinical trials and development programs of iron chelators and more novel ineffective erythropoiesis-targeted therapy. In this review, we provide a practical overview of management for patients with transfusion-dependent β-thalassemia, primarily driven by such experiences, with the aim of transferring knowledge to colleagues in other regions facing similar challenges.

Chronic graft-versus-host-disease (cGvHD) remains the leading cause of morbidity among transplant recipients. The efficacy of second-line treatments varies widely based on many factors, including wide differences in the organ overall response-rate response and in the current era where multiple agents are approved, and optimal sequencing of drugs based on organ ORR is unknown. We aimed to evaluate outcomes based on ORRs to the most common agents for the treatment of steroid-refractory/steroid-dependent cGvHD by conducting a systematic literature review. A total of 387 studies were evaluated for the ORRs of 12 cGvHD treatments. The highest skin ORR was observed to be 77% though some agents had an acceptable ORR. Most agents had an ocular response ranging from 17 to 50% Some agents resulted in a GI ORR of ≥88%. Rituximab showed the best response for musculoskeletal-GvHD. In the case of lung-GvHD (bronchiolitis obliterans syndrome [BOS]), negligible response was observed in patients treated with various agents. No clinically meaningful responses to treatments were reported for genital-GvHD. Most GvHD trials are focused on the ORR and partial response rates (PRR). The evidence for optimal agents for each organ is limited, and therefore, our study results are striking for differences in organ-ORR yields for a clinically meaningful difference. Thus, a personalized organ-based approach to the selection of therapeutic agents in cGvHD could result in favorable outcomes.

Chimeric antigen receptor T-cell (CAR T-cell) therapy has revolutionized the treatment of hematologic malignancies in patients with relapsed or refractory disease without other treatment options. However, only a very small proportion of patients with an indication for CAR T-cell can access the treatment. The imbalance between supply and demand is magnified in minority and vulnerable populations. Limited access is multifactorial and in part a result of factors directly related to the cellular product such as cost, complex logistics and manufacturing limitations. On the other hand, the impact of diversity, equity, and inclusion (DEI) and their social and structural context are also key to understanding access barriers in cellular therapy and health care in general. CAR T-cell therapy provides us with a new opportunity to better understand and prioritize this gap, a key step towards proactively and strategically addressing access.

The aim of this review is to provide an analysis of the current state of access to CAR T therapy with a focus on the influence of DEI. We will cover aspects related to the cellular product and the inseparable context of social and structural determinants. Identifying and addressing barriers is necessary to ensure equitable access to this and all future novel therapies.

Chemotherapy-induced thrombocytopenia (CIT) is a common complication of antineoplastic therapy, resulting in antineoplastic therapy dose reductions, treatment delays, treatment discontinuation, and morbid bleeding events. Despite several decades of research into thrombopoietic growth factors in CIT, there are presently no available U.S. FDA- or EMA-approved agents to treat CIT. However, a respectable body of evidence has been published evaluating the thrombopoietin receptor agonists (TPO-RAs) for the management and prevention of CIT in patients with solid tumors, and critical studies are ongoing with the TPO-RAs romiplostim and avatrombopag. When employed in the appropriate patient population and used properly, TPO-RAs can successfully and safely manage CIT for extended periods of time with minimal apparent risks. This comprehensive review discusses the evidence for TPO-RAs in CIT in patients with solid tumors, provides detailed guidance for their use in the clinic, and discusses ongoing essential clinical trials in management of CIT.

Gene modification of haematopoietic stem cells (HSCs) is a potentially curative approach to sickle cell disease (SCD) and offers hope for patients who are not eligible for allogeneic HSC transplantation. Current approaches require in vitro manipulation of healthy autologous HSC prior to their transplantation. However, the health and integrity of HSCs may be compromised by a variety of disease processes in SCD, and challenges have emerged in the clinical trials of gene therapy. There is also concern about increased susceptibility to haematological malignancies during long-term follow up of patients, and this raises questions about genomic stability in the stem cell compartment. In this review, we evaluate the evidence for HSC deficits in SCD and then discuss their potential causation. Finally, we suggest several questions which need to be addressed in order to progress with successful HSC manipulation for gene therapy in SCD.

Immune thrombocytopenia (ITP) is a rare autoimmune condition, due to peripheral platelet destruction through antibody-dependent cellular phagocytosis, complement-dependent cytotoxicity, cytotoxic T lymphocyte-mediated cytotoxicity, and megakaryopoiesis alteration. This condition may be idiopathic or triggered by drugs, vaccines, infections, cancers, autoimmune disorders and systemic diseases. Recent advances in our understanding of ITP immunobiology support the idea that other forms of thrombocytopenia, for instance, occurring after immunotherapy or cellular therapies, may share a common pathophysiology with possible therapeutic implications. If a decent pipeline of old and new agents is currently deployed for classical ITP, in other more complex immune-mediated thrombocytopenic disorders, clinical management is less harmonized and would deserve further prospective investigations.

Here, we seek to provide a fresh overview of pathophysiology and current therapeutical algorithms for adult patients affected by this disorder with specific insights into poorly codified scenarios, including refractory ITP and post-immunotherapy/cellular therapy immune-mediated thrombocytopenia.

Chronic lymphocytic leukemia (CLL) is a B cell neoplasm characterized by the accumulation of aberrant monoclonal B lymphocytes. CLL is the predominant type of leukemia in Western countries, accounting for 25% of cases. Although many patients remain asymptomatic, a subset may exhibit typical lymphoma symptoms, acquired immunodeficiency disorders, or autoimmune complications. Diagnosis involves blood tests showing increased lymphocytes and further examination using peripheral blood smear and flow cytometry to confirm the disease. With the significant advancements in machine learning (ML) and artificial intelligence (AI) in recent years, numerous models and algorithms have been proposed to support the diagnosis and classification of CLL. In this review, we discuss the benefits and drawbacks of recent applications of ML algorithms in the diagnosis and evaluation of patients diagnosed with CLL.

We report 634 patients who underwent unmanipulated haploidentical (HAPLO) bone marrow transplantation (BMT) in two Centers. The diagnosis was acute myeloid leukemia (AML) (n = 251), acute lymphoblastic leukemia (ALL)(n = 107), myelodysplastic syndrome and myelofibrosis (MDS + MF) (n = 125) and chronic lymphoproliferative disorders (n = 151). Median age was 52 years (16–74). Graft versus host disease (GvHD) prophylaxis was intravenous cyclosporin (CSA) starting on day 0, oral mycophenolate on day +1, and post-transplant cyclophosphamide (PTCY) on days +3 + 5. Primary graft failure was seen in 23 patients (3,6%); 17 /23 (74%) were rescued with second HAPLO graft, and were alive at one year. The cumulative incidence of acute GvHD grade II-IV was 29% and 3% for grade III-IV; the cumulative incidence of moderate severe chronic GvHD was 23%: older donor and patients age were significant predictors of both acute and chronic GvHD. The overall non relapse mortality (NRM) at 2 years was 19%: 8%, 21% and 30% in patients aged <40, 41–60 > 60 years. Disease free survival (DFS) at 5 years was 64% for acute leukemia in first remission, 51% for acute leukemia CR2, 25% for acute leukemia advanced disease and 49% for MDS/MPN.

We confirm, on a relatively large number of patients, that unmanipulated HAPLO BMT with PTCY on days +3 + 5, mostly after a myeloablative conditioning regimen, is followed by a low incidence of graft failure and grade III-IV GvHD; moderate severe chronic GvHD is 23% and NRM at 2 years 19%; 5 year DFS is influenced by remission status of the underlying disease.