Expert Review of Hematology最新文献

Introduction: In chronic lymphocytic leukemia (CLL), progression-free survival (PFS) remains a fundamental efficacy endpoint; however, it does not fully capture patient-centric measures such as treatment discontinuation or adherence. Time to next treatment (TTNT) offers a pragmatic alternative, encompassing not only the interval until initiation of subsequent therapy but also reflecting treatment tolerability and compliance.

Areas covered: A comprehensive literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines identified 40 full-text articles reporting TTNT as an outcome measure. Among these, 30 were retrospective real-world studies, while 10 were prospective phase II or phase III clinical trials involving patients with either treatment-naïve or relapsed/refractory CLL. Meta-analytic evaluation of the prospective trials, each with a minimum follow-up of four years, revealed a strong trial-level correlation between PFS and TTNT, with an r² value of 0.7410 (p = 0.0003). Additionally, TTNT demonstrated a statistically significant, though more moderate, correlation with overall survival (OS), yielding an r² value of 0.5160 (p = 0.008).

Expert opinion: The analysis suggests that TTNT enriches the CLL endpoint repertoire by capturing patient-centered outcomes and informing pragmatic clinical decision-making. Nevertheless, regulatory and methodological standards advocate a two-tier validation approach that includes both individual patient-level analyses and trial-level validation. TTNT in CLL should complement, but not substitute for, PFS in evaluating therapeutic benefit and guiding clinical decision-making.

Introduction: Mucosal toxicities remain a longstanding and challenging concern in the treatment of hematopoietic malignancies (HM). In addition to the classic oral (OM) and gastrointestinal mucositis (GIM) induced by chemotherapy (CHT) and/or radiotherapy (RT), novel targeted treatments and immunotherapies may cause other forms of mucosal disorders.

Areas covered: This overview provides updated insights into the pathobiology and management strategies for mucosal toxicities induced by treatments for HMs. Additionally, it reappraises classic forms of mucositis and novel mucosal toxicities induced by new treatments for HMs.

Expert opinion: Although significant progress has been made in the pathophysiologic pathways of conventional CHT/RT-associated OM, much remains to be discovered. Indeed, OM and GIM have a multifactorial etiopathogenesis that includes direct effects, oxidative injury, upregulation of immunologic molecules, and changes in the microbiome. Preventive measures remain the cornerstone of management, mainly palliative in clinically established mucositis. However, new therapeutic insights, primarily related to mesenchymal cells and cytokine inhibitors, are emerging, and ongoing research is critical for translating these new findings into clinical practice.

Background: This study investigated the association between response to hydroxyurea (HU) treatment and fetal hemoglobin (HbF), and the prevalence of mutations that regulate HbF synthesis, drug transport and biotransformation in sickle cell disease (SCD) patients.

Research design and methods: Study included n = 390 Bahrainis with a history of sickle cell crises. Responders (n = 127; 68%) were patients achieving HbF ≥ 15% along with other improvements. Non-responders (n = 60; 32%) failed to achieve this threshold despite maximum tolerated dose treatment.

Results: Hydroxyurea treated patients had decreased frequency of painful crises and hospitalizations, increased Hb and HbF and decreased sickle cell hemoglobin (HbS), and white blood cells (WBCs). The minor allele frequency of ARG2 (rs10483801), HBS1L-MYB (rs4895441), CYP2C19 (rs4986893) CYP2C19 (rs4244285), and OATP1B3 (rs3711358) gene was significantly higher in non-responders compared to responders. A negative correlation was found between the number of pain crises and hospitalizations per year and HbF%. No significant correlation was reported between the dosage and the number of hospitalizations per year. No significant correlation was found between the duration of treatment and HbF%.

Conclusions: Findings highlight the importance of a personalized treatment approach to maximize the benefits and minimize the side effects of HU, thereby improving clinical outcomes.

Introduction: Sickle cell disease (SCD) is an inherited blood disorder affecting approximately 100,000 individuals in the United States and millions worldwide, characterized by acute vaso-occlusive pain episodes (VOEs) and other complications that frequently necessitate emergency department (ED) visits.

Areas covered: Despite therapeutic advancements, ED care remains a major concern, often cited by patients as the area of healthcare most in need of improvement. National guidelines have been established to ensure ideal emergency SCD care and management, however, these guidelines do not address barriers or facilitators that affect implementation in the complex ED setting. This review examines current diagnostic and management approaches for common SCD complications requiring ED utilization, particularly fever and pain in pediatric patients. It highlights the challenges children with SCD face in emergency care and the existing knowledge gaps. Despite guidelines recommending timely, individualized pain treatment, implementation remains inconsistent, resulting in prolonged suffering and increased hospitalizations.

Expert opinion: Future research should focus on enhancing guideline adherence, reducing disparities, and developing targeted therapies. Novel biomarkers could improve early diagnosis, while standardized severity scoring systems may optimize triage and treatment decisions. Advancing biomarker research and investigational therapies beyond traditional supportive care holds promise for improving SCD management and patient outcomes.

Introduction: The development of new lymphoma therapies in recent years has led to a significant increase in patient survival. However, in some cases, despite disease remission, the outcome of the applied therapy is diminished by the development of secondary cancers. These often have dismal outcomes and are unresponsive to standard therapies. Both therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML) are well-known side effects of cytotoxic chemotherapy and/or radiation therapy.

Areas covered: This review summarizes the key factors associated with an increased risk of therapy-related neoplasms in lymphoma patients, focusing on the various elements that may contribute to this susceptibility. The major factors described in detail include the impact of different anti-lymphoma therapies, disturbances in the bone marrow microenvironment, the presence of clonal hematopoiesis, and germline predispositions. The review is based on a PubMed database search for articles published up to 1 May 2025, covering the above mentioned topics, as well as the authors' clinical and research experience.

Expert opinion: Considering the progress in lymphoma therapy and the prospect of long-term survival, efforts should be made to identify patients at higher risk of developing therapy-related myeloid neoplasms. A better understanding of germline predispositions and the role of clonal hematopoiesis should support therapy tailored to individual risk profiles.

Introduction: One of the problems that remain unsolved in people with hemophilia (PwH) is how to regenerate articular cartilage.

Areas covered: In this article, we have reviewed the existing information on articular cartilage regeneration in the general population and in PwH. In the general population, it has been reported that the clinical results of different types of commercial products are better than those of microfractures and that the results of products that combined microfractures and allograft products are better than those of autologous chondrocyte products. In PwH iron chelators, anti-inflammatory drugs, and anti-fibrinolytics drugs have shown beneficial effects, predominantly in preclinical studies. Hemarthrosis models have shown that mesenchymal stem cells (MSCs) intraarticular injections have some beneficial effects on cartilage structure and function. An in vitro preliminary study has highlighted the opportunity of using hemophilic chondrocytes for autologous cartilage implants in PwH. In a clinical study, bone marrow-derived cells transplantation (BMDCT) seemed to be a promising regenerative treatment for osteochondral lesions in mild ankle hemophilic arthropathy in PwH.

Expert opinion: Today it is not possible to regenerate articular cartilage. It is essential to perform primary hematologic prophylaxis throughout the life of PwH to prevent the articular cartilage from degeneration.

Introduction: Leukocyte adhesion deficiency (LAD) is a rare genetic disorder that impairs leukocyte migration, leading to severe immune dysfunction and recurrent infections. Although allogeneic hematopoietic cell transplantation (HCT) remains the primary curative treatment for severe LAD, it is complicated by a high incidence of graft-versus-host-disease (GVHD).

Areas covered: This narrative review outlines the key factors influencing GVHD development in patients with LAD-I, the most common LAD subtype, undergoing HCT. It explores established and emerging strategies for preventing GVHD, focusing on their effectiveness and outcomes. The literature search was conducted using PubMed to identify studies reporting HCT for LAD published 1989-2025.

Expert opinion: Conventional GVHD prophylaxis regimens, primarily involving calcineurin inhibitors, have proven insufficient in preventing GVHD in high-risk populations. Among patients undergoing haploidentical HCT, post-transplantation cyclophosphamide has shown efficacy in preventing GVHD, although these results were based on limited cases. Graft manipulation techniques such as CD34⁺ selection have also been explored. However, these approaches are often associated with high graft failure rate and poor survival. Alemtuzumab, which is used in conditioning regimens, has shown promise in lowering GVHD incidence. Further studies are essential to optimize GVHD prophylaxis and improve survival outcomes in patients with LAD undergoing HCT.

Background: Polycythemia vera (PV) is characterized by erythrocytosis and an increased risk of thrombotic events (TEs). Currently, standard-of-care therapies for PV have limitations, which indicate the need to understand real-world treatment patterns and treatment burden in PV.

Research design and methods: This retrospective observational study analyzed real-world claims data in adult patients with PV using the Komodo Health claims database (2016-2022) in the United States. Burdensome treatment was classified as patients receiving ≥ 3 phlebotomies (PHLs) within a 6-month period and/or high-dose hydroxyurea (HU) ≥ 1,000 mg per day.

Results: Of 44,766 treated patients (mean age: 65 years; 64% male), 55% received burdensome treatment, which included frequent PHL (33%), high-dose HU (17%), or a combination of both (frequent PHL + high-dose HU, 5%). PHL and HU were the most common first-line treatments (PHL, 71%; HU, 27%), and 87% of patients initiating treatment with PHL monotherapy never advanced to another therapy regimen. TEs occurred in 16% of the treated patients.

Conclusions: These data suggest a substantial proportion of patients with PV receive burdensome treatments, with 55% of treated patients receiving frequent PHL and/or high-dose HU, highlighting need for therapy optimization. However, inherent limitations of using claims data should be taken into consideration.